UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 10-K

☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

For the fiscal year ended September 30, ~~2021~~2022

☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

For the transition period from ___________ to ___________

Commission file number 333-191083

RASNA THERAPEUTICS, INC.

(Exact name of registrant as specified in its charter)

Nevada		39-2080103
(State or other jurisdiction of incorporation or organization)		(I.R.S. Employer Identification Number)

420 Lexington Ave, Suite 2525, New York, NY 10170

(Address of principal executive offices) (Zip Code)

Telephone: (646) 396-4087

(Registrant’s telephone number)

Securities registered pursuant to Section 12(b) of the Act: None.

Securities registered pursuant to Section 12(g) of the Act: None.

Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act Yes ☐ No ☒

Indicate by check if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act. Yes ☐ No ☒

Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months and (2) has been subject to such filing requirements for the past 90 days. Yes ☒ No ☐

Indicate by check mark whether the registrant has submitted electronically and posted on its corporate Web site, if any, every Interactive Data File required to be submitted and posted pursuant to Rule 405 of Regulation S-T (§232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit and post such files). Yes ☒ No ☐

Indicate by check mark if disclosure of delinquent filers pursuant to Item 405 of Regulation S-K (§229.405 of this chapter) is not contained herein, and will not be contained, to the best of registrant’s knowledge, in definitive proxy or information statements incorporated by reference in Part III of this Form 10-K or any amendment to this Form 10-K. ☒

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, or a smaller reporting company. See the definition of “large accelerated filer”, “accelerated filer” and “smaller reporting company” in Rule 12b-2 of the Exchange Act. (Check one):

Large accelerated filer	☐	Accelerated filer	☐
Non-accelerated filer	☒	Smaller reporting company	☒
		Emerging growth company	☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

Indicate by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public accounting firm that prepared or issued its audit report. ☐

Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Act). Yes ☐ No ☒

The aggregate market value of the voting and non-voting common equity held by non-affiliates of the registrant was $21,~~632~~959,000 as of March 31, ~~2021~~ 2022, based upon the closing price on the OTCQB market reported for such date.

Indicate the number of shares outstanding of each of the issuer’s classes of common stock, as of the latest practicable date: 68771,~~908~~811,~~003~~360 shares of common stock were issued and outstanding as of February 287, ~~2022~~2023.

DOCUMENTS INCORPORATED BY REFERENCE: None

TABLE OF CONTENTS

		~~Page~~	Page
PART I		1	1
ITEM 1.	BUSINESS	1	1
ITEM 1A.	RISK FACTORS	19	19
ITEM 1B.	UNRESOLVED STAFF COMMENTS	46	46
ITEM 2.	PROPERTIES	46	46
ITEM 3.	LEGAL PROCEEDINGS	46	46
ITEM 4.	MINE SAFETY DISCLOSURES	46	46
PART II		47	47
ITEM 5.	MARKET FOR REGISTRANT’S COMMON EQUITY, RELATED STOCKHOLDER MATTERS, AND ISSUER PURCHASES OF EQUITY SECURITIES	47	47
ITEM 6.	~~SELECTED CONSOLIDATED FINANCIAL DATA~~[RESERVED]	47	47
ITEM 7.	MANAGEMENTS DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS	48	48
ITEM 7A.	QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK	58	56
ITEM 8.	FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA	58	56
ITEM 9.	CHANGES IN AND DISAGREEMENTS WITH ACCOUNTANTS ON ACCOUNTING AND FINANCIAL DISCLOSURE	59	57
ITEM 9A.	CONTROLS AND PROCEDURES	59	57
ITEM 9B.	OTHER INFORMATION	60	58
PART III		61
ITEM 9C.	DISCLOSURE REGARDING FOREIGN JURISDICTIONS THAT PREVENT INSPECTIONS		58
ITEM 10.	DIRECTORS, EXECUTIVE OFFICERS OF THE REGISTRANT, AND CORPORATE GOVERNANCE	61
PART III			59
ITEM 11.	EXECUTIVE COMPENSATION	64
ITEM 10.	DIRECTORS, EXECUTIVE OFFICERS OF THE REGISTRANT, AND CORPORATE GOVERNANCE		59
ITEM 12.	SECURITY OWNERSHIP OF CERTAIN BENEFICIAL OWNERS AND MANAGEMENT AND RELATED STOCKHOLDER MATTERS	65
ITEM 11.	EXECUTIVE COMPENSATION		62
ITEM 13.	CERTAIN RELATIONSHIPS AND RELATED TRANSACTIONS, AND DIRECTOR INDEPENDENCE	66
ITEM 12.	SECURITY OWNERSHIP OF CERTAIN BENEFICIAL OWNERS AND MANAGEMENT AND RELATED STOCKHOLDER MATTERS		63
ITEM 14.	PRINCIPAL ACCOUNTING FEES AND SERVICES	67
ITEM 13.	CERTAIN RELATIONSHIPS AND RELATED TRANSACTIONS, AND DIRECTOR INDEPENDENCE		64
PART IV		68
ITEM 14.	PRINCIPAL ACCOUNTING FEES AND SERVICES		66
ITEM 15.	EXHIBITS, FINANCIAL STATEMENT SCHEDULES	68
PART IV			67
SIGNATURES		69
ITEM 15.	EXHIBITS, FINANCIAL STATEMENT SCHEDULES		67
INDEX TO CONSOLIDATED FINANCIAL STATEMENTS		F-1
SIGNATURES			68
INDEX TO CONSOLIDATED FINANCIAL STATEMENTS			F-1

PART I

Forward Looking Statements.

This annual report contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These statements relate to future events or our future financial performance. In some cases, you can identify forward-looking statements by terminology such as “may”, “should”, “expects”, “plans”, “anticipates”, “believes”, “estimates”, “predicts”, “potential” or “continue” or the negative of these terms or other comparable terminology. These statements are only predictions and involve known and unknown risks, uncertainties and other factors, including the risks in the section entitled “Risk Factors”, any of which may cause our or our industry’s actual results, levels of activity, performance or achievements to be materially different from any future results, levels of activity, performance or achievements expressed or implied by these forward-looking statements. These risks include, by way of example and not in limitation:.

This list is not an exhaustive list of the factors that may affect any of our forward-looking statements. These and other factors should be considered carefully and readers should not place undue reliance on our forward-looking statements.

Forward looking statements are made based on management’s beliefs, estimates and opinions on the date the statements are made and we undertake no obligation to update forward-looking statements if these beliefs, estimates and opinions or other circumstances should change. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance or achievements. Except as required by applicable law, including the securities laws of the United States, we do not intend to update any of the forward-looking statements to conform these statements to actual results.

Our financial statements are stated in United States dollars (US$) and are prepared in accordance with United States Generally Accepted Accounting Principles.

In this annual report, unless otherwise specified, all dollar amounts are expressed in United States dollars and all references to “common stock” refer to the common shares in our capital stock.

As used in this annual report, the terms “we”, “us”, “our”, “Rasna” and the “Company” mean Rasna Therapeutics, Inc. unless the context clearly requires otherwise.

ITEM 1. BUSINESS

General.

We are a leukemia-focused biotechnology company that has been developing therapeutics to address the unmet need that exists for acute myeloid leukemia, or AML, and other forms of leukemia and lymphoma. AML is generally a disease of older adults, with onset typically after the age of 45 (average patient age approximately 68 years old). Our strategy is to develop small molecule drug candidates targeting ~~two~~the ~~genes: NPM1 and~~ LSD1 gene, which ~~are~~is considered to control major pathways underlying etiology of majority of AML sub-types.

RASP-201 is a novel, orally dosed, selective reversible inhibitor of lysine specific demethylase, or LSD1, a pathway that blocks differentiation and confers a poor prognosis to AML. We expect RASP-201 to display a safer metabolic profile than competitor irreversible inhibitors such as GSK2879552 (GlaxoSmithKline) and ORY-1001 (Oryzon/Roche). RASP-201 when dosed orally shows in vivo therapeutic utility in murine (mouse) models of AML.

RASP-301 is our innovative, first- in-class, oral, small molecule inhibitor that in preclinical studies has been shown to disrupt NPM1 oligomerization (aggregation of individual subunits) and has the potential to treat refractory AML with reduced toxicity at low dose levels. RASP-301 exhibits cytotoxic effects at nanomolar concentrations against AML cells in culture and was not cytotoxic to normal cells at the same concentrations. In vivo usefulness of these compounds in AML murine models has been evaluated confirming the druggability of the target and its potential to treat refractory AML. 1

1Our primary indication is AML which may be fatal within weeks to months, has a 5-year survival rate of only about 25% and very poor prospects for long-term survival of patients. Treatment options for AML comprise a variety of chemotherapy regimens, biologic agents, and stem cell transplantation. Current standard chemotherapy regimens cure only a minority of patients with AML. As a result, all patients should be evaluated for entry into well-designed clinical trials. If a clinical trial is not available, the patient can be treated with standard therapy. For consolidation chemotherapy or for the management of toxic effects of chemotherapy, readmission is required. Our strategy is to target master regulators of cancer through deep knowledge of highly conserved pathways that are common to leukemia sub-types. Employing a multi-pronged approach, our programs are focused on three druggable intervention points with a potential to improve safety and efficacy of current AML mono and/or combination therapies.

~~Our primary~~Leukemia ~~indication~~Overview ~~is AML which may be fatal within weeks to months, has a 5-year survival rate of only about 25%~~ and ~~very poor~~Market prospects for long-term survival of patients. Treatment options for AML comprise a variety of chemotherapy regimens, biologic agents, and stem cell transplantation. Current standard chemotherapy regimens cure only a minority of patients with AML. As a result, all patients should be evaluated for entry into well-designed clinical trials. If a clinical trial is not available, the patient can be treated with standard therapy. For consolidation chemotherapy or for the management of toxic effects of chemotherapy, readmission is required. Our strategy is to target master regulators of cancer through deep knowledge of highly conserved pathways that are common to leukemia sub-types. Employing a multi-pronged approach, our programs are focused on three druggable intervention points with a potential to improve safety and efficacy of current AML mono and/or combination therapies.Opportunity

Leukemia is a cancer of the blood or bone marrow ~~Overview~~involving abnormal proliferation of white blood cells, called WBCs or leukocytes. Leukemia is caused by a mutation of the DNA in bone marrow stem cells resulting in the abnormal multiplication of leukocytes. If untreated, surplus leukocytes will overwhelm the bone marrow, enter the bloodstream and ~~Market~~eventually ~~Opportunity~~invade other parts of the body, such as the lymph nodes, spleen, liver, and central nervous system. In this way, the behavior of leukemia is different from that of other cancers, which usually begin in major organs and ultimately spread to the bone marrow. Leukemia is an umbrella term covering a large group of blood cancers.

~~Leukemia is~~All aleukemia ~~cancer~~arises offrom ~~the~~mutations ~~blood~~ or ~~bone~~damage ~~marrow~~to the ~~involving~~DNA ~~abnormal~~within ~~proliferation~~the ~~of white~~ blood cells,. ~~called~~These ~~WBCs~~mutations ormay ~~leukocytes.~~occur ~~Leukemia~~spontaneously ~~is caused~~or byas a ~~mutation~~result of ~~the~~exposure ~~DNA~~to inradiation ~~bone~~or ~~marrow~~carcinogenic ~~stem~~substances. Ionizing ~~cells~~radiation, ~~resulting~~as inwell ~~the~~as ~~abnormal~~exposure ~~multiplication~~to ofchemicals ~~leukocytes.~~such Ifas ~~untreated~~benzene, ~~surplus leukocytes~~increases ~~will overwhelm~~ the ~~bone~~risk ~~marrow~~of AML, ~~enter~~while ~~the~~agricultural ~~bloodstream~~chemicals ~~and~~have ~~eventually~~been linked ~~invade~~to ~~other~~an ~~parts~~increased incidence of ~~the~~chronic ~~body,~~lymphocytic ~~such as the lymph nodes~~leukemia, ~~spleen,~~ ~~liver,~~or ~~and central nervous system~~CLL. InA ~~this~~weak ~~way~~immune system, ~~the~~some ~~behavior~~virus offorms ~~leukemia~~such isas ~~different~~human ~~from~~T-cell Leukemia ~~that~~virus ofI, ~~other~~or ~~cancers~~HTLV-1, ~~which~~genetic ~~usually begin~~predisposition, incigarette ~~major~~smoking, ~~organs~~ and ~~ultimately~~reactions ~~spread~~ to ~~the~~some ~~bone~~therapeutic ~~marrow.~~drugs ~~Leukemia~~are isalso animplicated ~~umbrella~~in the ~~term~~etiology ~~covering a large group~~ of ~~blood cancers~~leukemia.

All leukemia arises from mutations or damage to the DNA within the blood cells. These mutations may occur spontaneously or as a result of exposure to radiation or carcinogenic substances. Ionizing radiationDiagnosis, ~~as well as exposure to chemicals such as benzene~~ Treatment, increases the risk of AML, while agricultural chemicals have been linked to an increased incidence of chronic lymphocytic leukemia, or CLL. A weak immune system, some virus forms such as human T-cell Leukemia virus I, or HTLV-1, genetic predisposition, cigarette smoking, and ~~reactions to some therapeutic drugs are also implicated in the etiology of leukemia.~~ Management

~~Diagnosis~~The first symptoms of leukemia are often vague and are correlated with other disorders. Common symptoms include fatigue and malaise, ~~Treatment~~ excessive bruising, and ~~Management~~ abnormal bleeding due to low platelet count. Further symptoms can include weight loss, bone and joint pain, infection and fever, and an enlarged spleen, lymph nodes and liver. After a blood test, several blood abnormalities such as anemia, or leucopenia may be observed, and in most cases a bone marrow test is required to confirm the diagnosis.

The ~~first~~ ~~symptoms~~preliminary ofdiagnostic ~~leukemia~~test ~~are~~for ~~often~~leukemia ~~vague~~is a ~~and~~blood ~~are~~cell ~~correlated with other disorders. Common symptoms include fatigue and malaise~~count, ~~excessive bruising,~~which ~~and~~is ~~abnormal~~followed ~~bleeding~~by ~~due~~immune-phenotyping to ~~low~~assess ~~platelet~~whether ~~count.~~the ~~Further~~abnormal ~~symptoms~~lymphocyte ~~can~~levels ~~include~~are ~~weight~~caused ~~loss,~~by ~~bone and joint pain, infection and~~inflammation ~~fever,~~or ~~and an enlarged spleen, lymph nodes and liver~~cancer. ~~After~~The aphysician ~~blood~~may ~~test,~~also ~~several~~require ~~blood~~additional ~~abnormalities~~confirmatory tests such as ~~anemia,~~cytogenetic analysis or ~~leucopenia may be observed, and in most cases a~~ bone marrow ~~test is required to confirm the diagnosis~~sampling.

The specific variety and combination of anticancer ~~preliminary~~drugs ~~diagnostic~~prescribed ~~test~~depends on the form and stage of the disease. For example, treatment for ~~leukemia~~AML, isthe amost ~~blood~~common ~~cell~~form ~~count~~of leukemia, ~~which~~usually involves ischemotherapy ~~followed~~with bycytotoxic ~~immune-phenotyping~~cytarabine toin ~~assess~~conjunction ~~whether~~with ~~the~~an ~~abnormal~~anthracycline such as daunorubicin or idarubicin. Because of the ~~lymphocyte~~severity ~~levels~~of the cytotoxic treatment, bone marrow transplants, or BMTs are ~~caused~~sometimes necessary. By transplanting healthy bone marrow into the body, BMTs help rebuild tissue damaged by ~~inflammation~~the treatment. Interferon, or ~~cancer.~~INF, ~~The~~therapy, ~~physician~~particularly ~~may~~with ~~also~~INF-alpha, ~~require~~is an alternative or additional ~~confirmatory~~treatment ~~tests~~offered ~~such~~to asalmost ~~cytogenetic~~all newly diagnosed patients in these markets. However, it is very difficult to cure, even though ~~analysis~~early ortreatment ~~bone~~indicates ~~marrow~~it ~~sampling~~will help people to live longer.

The ~~specific~~ ~~variety~~standard ~~and~~first-line ~~combination~~treatment ofstrategy ~~anticancer~~for CLL ~~drugs~~for ~~prescribed~~patients ~~depends~~who onmight ~~the~~not ~~form~~be ~~and~~able ~~stage~~to oftolerate the ~~disease.~~side ~~For~~effects ~~example, treatment for AML, the most common form~~ of ~~leukemia,~~strong ~~usually involves~~ chemotherapy ~~with~~is ~~cytotoxic~~to ~~cytarabine~~be intreated ~~conjunction~~ with anchlorambucil ~~anthracycline such~~alone ~~as daunorubicin~~ or with ~~idarubicin.~~a ~~Because~~monoclonal ofantibody ~~the~~like ~~severity~~rituximab of(Rituxan) ~~the cytotoxic treatment, bone marrow transplants,~~ or ~~BMTs~~obinutuzumab ~~are sometimes necessary~~(Gazyva). ByOther ~~transplanting~~options ~~healthy~~include ~~bone~~ibrutinib ~~marrow into the body~~(Imbruvica), ~~BMTs~~rituximab ~~help rebuild tissue damaged by the treatment. Interferon~~alone, ~~or INF,~~ ~~therapy, particularly with INF-alpha, is an alternative~~ or ~~additional~~a ~~treatment~~corticosteroid ~~offered~~like ~~to almost all newly diagnosed patients in these markets~~prednisone. ~~However, it is very difficult to cure, even though early treatment indicates it will help people to live longer.~~

~~The standard~~Other ~~first-line~~drugs ~~treatment~~or ~~strategy~~combinations ~~for~~of ~~CLL~~drugs ~~for~~may ~~patients~~also be ~~who~~also ~~might~~used. ~~not~~If bethe ~~able~~only toproblem ~~tolerate~~is ~~the~~an ~~side~~enlarged ~~effects~~spleen ofor ~~strong~~swollen ~~chemotherapy is~~lymph tonodes bein ~~treated~~one ~~with~~region ~~chlorambucil~~of ~~alone~~the orbody, ~~with~~localized atreatment ~~monoclonal~~with ~~antibody~~low-dose radiation ~~like~~therapy ~~rituximab~~may ~~(Rituxan)~~be orused. ~~obinutuzumab~~Splenectomy (~~Gazyva).~~surgery ~~Other~~to ~~options include~~remove ~~ibrutinib~~the ~~(Imbruvica~~spleen), ~~rituximab~~is ~~alone,~~another oroption aif ~~corticosteroid~~the ~~like~~enlarged ~~prednisone~~spleen is causing symptoms.

~~Other drugs~~In oraddition, ~~combinations~~very high numbers of ~~drugs~~leukemia ~~may~~cells in ~~also~~the beblood ~~also~~causes ~~used.~~problems Ifwith ~~the~~normal ~~only~~circulation. ~~problem~~This is ancalled ~~enlarged~~leukostasis. ~~spleen~~Leukapheresis oris ~~swollen~~also ~~lymph~~sometimes ~~nodes~~used inbefore ~~one region~~chemotherapy ofif ~~the~~there ~~body,~~are ~~localized~~very ~~treatment~~high ~~with~~numbers ~~low-dose~~of ~~radiation~~leukemia ~~therapy~~cells ~~may be used. Splenectomy~~ (~~surgery~~even towhen ~~remove~~they ~~the~~aren’t ~~spleen~~causing problems) isto ~~another~~prevent ~~option if~~tumor ~~the~~lysis ~~enlarged spleen is causing symptoms~~syndrome.

In addition, very high numbers of leukemia cells in the blood causes problems with normal circulation. This is called leukostasis. Leukapheresis is also sometimes used before chemotherapy if there are very high numbers of leukemia cells (even when they aren’t causing problems) to prevent tumor lysis syndrome.2

Upon the failure of first line therapy, the standard therapy is usually to administer many of the drugs and combinations listed above as potential second-line treatments. For many people who have already had fludarabine, alemtuzumab seems to be helpful as second-line treatment, but it carries an increased risk of infections. Other purine analog drugs, such as pentostatin or cladribine (2-CdA), may also be tried. Newer drugs such as ofatumumab, ibrutinib, idelalisib (Zydelig), and venetoclax (Venclexta) may be other options. If these types of chemotherapy fail, the next option is usually a bone marrow transplant. A stem cell transplant is a third treatment option depending on leukemia response.

~~Upon the~~Our ~~failure~~business ofstrategy ~~first~~focuses ~~line~~on ~~therapy,~~differentiated targeted ~~the~~therapies ~~standard~~for ~~therapy~~genetic ispathways ~~usually~~which are known to ~~administer~~be ~~many~~involved in etiologies of ~~the~~number ~~drugs~~of leukemia and ~~combinations~~other ~~listed~~cancers. ~~above~~Our ~~as potential~~clinical ~~second-line~~program ~~treatments.~~is ~~For~~based ~~many~~around ~~people~~three druggable intervention ~~who~~points ~~have~~with ~~already~~potential ~~had~~to ~~fludarabine,~~improve ~~alemtuzumab~~safety ~~seems~~and toefficacy beof ~~helpful~~current asAML ~~second-line treatment~~therapies, ~~but~~ itnamely ~~carries~~“stemness” an(activation ~~increased risk~~ of ~~infections.~~stem ~~Other~~cell-like ~~purine~~growth ~~analog drugs~~patterns), ~~such~~cell assignaling ~~pentostatin~~(between ornucleus ~~cladribine~~and ~~(2-CdA~~cytoplasm), ~~may~~and ~~also be tried.~~stress-induced apoptosis (programmed ~~Newer~~cell ~~drugs such as ofatumumab, ibrutinib, idelalisib (Zydelig~~death),. ~~and~~Our ~~venetoclax~~focus ~~(Venclexta)~~is ~~may~~to betarget ~~other~~two ~~options.~~specific Ifgenetic ~~these~~pathways ~~types~~NPM1 ofand ~~chemotherapy fail~~LSD1, ~~the~~which ~~next~~are ~~option~~known isto ~~usually~~be aassociated ~~bone~~with ~~marrow~~etiologies ~~transplant.~~of ~~A stem cell transplant is~~ a number ~~third~~of ~~treatment~~cancers, ~~option~~including AML ~~depending~~(Figure ~~on leukemia response~~1).

~~Our business~~Figure ~~strategy~~1 ~~focuses~~Key onRegulators ~~differentiated targeted therapies~~ for ~~genetic~~Developing ~~pathways which are known to be involved in etiologies of number~~Targeted ~~of leukemia and other cancers. Our clinical program is based around three druggable intervention points with potential to improve safety and efficacy of current~~ AML therapies, namely “stemness” (activation of stem cell-like growth patterns), cell signaling (between nucleus and cytoplasm) and stress-induced apoptosis (programmed cell death). Our focus is to target two specific genetic pathways NPM1 and LSD1, which are known to be associated with etiologies of a number of cancers, including AML (Figure 1).Therapies

~~Figure 1~~Roles ~~Key~~of ~~Regulators~~LSD1 ~~for~~in ~~Developing Targeted AML Therapies~~Tumorigenesis

~~Roles~~Leukemia arises due to DNA damage or mutations. ofChromosomal ~~NPM1~~aberrations involving LSD1 have been found in patients with non-Hodgkin lymphoma, acute promyelocytic leukemia, myelodysplastic syndrome, and AML. Thus, targeting LSD1 is an appropriate approach for treatment of AML. In addition, combination of therapies targeting these two genes could also be effective in ~~Tumorigenesis~~treatment of relapse AML.

Leukemia arises due to DNA damage or mutations. Chromosomal aberrations involving NPM1 and LSD1 have been found in patients with non-Hodgkin lymphoma, acute promyelocytic leukemia, myelodysplastic syndrome, and AML. Thus, targeting NPM1 and LSD1 is an appropriate approach for treatment of AML. In addition, combination of therapies targeting these two genes could also be effective in treatment of relapse AML.3

The ~~NPM1~~ ~~gene~~histone isH3K4/K9 ~~up-regulated,~~demethylase ~~mutated~~LSD1 ~~and~~can ~~chromosomally~~regulate gene ~~translocated~~activation inand ~~many~~repression ~~tumor~~in ~~types.~~epigenetic ~~NPM1~~regulation ~~is transferred from nucleolus to nucleoplasm~~ and ~~cytoplasm~~is bya ~~anticancer~~key ~~drugs.~~effector ~~When~~of ~~expressed~~the atdifferentiation ~~high~~block ~~level, NPM1 could promote tumor growth by inactivation of tumor suppressor~~in MLL-rearranged ~~p53/ARF~~leukemia. ~~pathway;~~High ~~when~~LSD1 ~~expressed~~expression atblocks ~~low~~differentiation ~~level,~~and ~~NPM1~~is ~~could~~associated ~~suppress~~with ~~tumor~~a ~~growth~~poor byprognosis ~~inhibition of centrosome duplication. NPM1 is haplo insufficient~~ in ~~hemizygous mice that are vulnerable to tumor development~~AML. ~~NPM1c+~~LSD1 ~~(cytoplasm~~can ~~form)~~be ~~translocation~~targeted ~~into~~by ~~cytoplasm could~~tranylcypromine ~~serve~~analogs asor andownregulated ~~AML~~by ~~remission~~RNA ~~signal.~~interference ~~NPM1~~which ~~forms~~induces adifferentiation ~~pentamer~~of MLL-rearranged ~~that~~leukemic ~~could serve as a potential anticancer target~~cells. ~~Our~~A ~~technology~~number ~~(the~~of ~~process~~different ofsmall ~~targeting~~molecular ~~the~~inhibitors ~~mutation~~ of ~~the~~LSD1 ~~NPM1~~have ~~gene),~~been isin ~~believed~~clinical toevaluation. ~~inhibit~~While ~~the~~this ~~NPM1~~class ~~gene,~~of ~~reducing~~inhibitors ~~levels~~has ofshown ~~NPM1~~clinical ~~and~~activity ~~consequently~~in ~~reducing~~AML apatients, ~~tumor~~toxicities ~~cell’s~~associated ~~ability~~with toirreversible ~~duplicate.~~inhibitors ~~High~~prohibited ~~affinity,~~their ~~NPM1~~further ~~binding~~development. ~~molecules~~Reversible ~~exhibiting~~inhibitors ~~cytotoxic~~of ~~activity~~LSD1 ~~on AML cells and safe~~have onshown ~~normal~~good ~~cells~~potential ~~have~~for ~~been~~further ~~identified~~development.

3Other Leukemias

~~The histone~~Differences ~~H3K4/K9~~between ~~demethylase~~the ~~LSD1~~different ~~can~~leukemias ~~regulate~~are dependent ~~gene~~on ~~activation~~the ~~and~~types ~~repression~~of incells ~~epigenetic~~involved. ~~regulation~~Myeloid ~~and~~leukemias isoriginate ain ~~key effector of~~ the ~~differentiation block~~bone ~~in MLL-rearranged~~marrow ~~leukemia.~~and ~~High~~involve ~~LSD1~~granulocytes, ~~expression~~white ~~blocks differentiation~~ and isred ~~associated with a poor prognosis in~~blood ~~AML~~cells. ~~LSD1~~Lymphoid ~~can~~leukemias, beincluding ~~targeted~~lymphomas, byoriginate ~~tranylcypromine~~in ~~analogs~~the orlymph ~~downregulated~~nodes byand ~~RNA~~lymphoid ~~interference~~tissue ~~which~~but ~~induces~~involve ~~differentiation~~immune ~~of MLL-rearranged leukemic~~ cells. Aincluding ~~number~~lymphocytes, T ofcells ~~different~~and ~~small~~B ~~molecular inhibitors of LSD1 have been in clinical evaluation~~cells. ~~While~~MDS ~~this~~are ~~class~~group of ~~inhibitors has~~bone ~~shown~~marrow ~~clinical~~failure ~~activity~~disorders inthat ~~AML~~have ~~patients,~~various ~~toxicities~~subtypes ~~associated~~ with ~~irreversible~~variable ~~inhibitors~~onsets, ~~prohibited~~prognoses ~~their~~and ~~further development.~~risks ~~Reversible inhibitors~~ of ~~LSD1~~developing ~~have shown good potential for further development~~leukemia.

~~Other Leukemias~~RASP-201 (LSD1)

~~Differences between~~LSD1 ~~the~~is ~~different~~an ~~leukemias~~enzyme ~~are~~that ~~dependent~~demethylates on(remove ~~the~~methyl groups) ~~types~~lysine ofside ~~cells~~chain ~~involved~~of histones. ~~Myeloid~~The ~~leukemias~~levels ~~originate~~of inLSD1 ~~the~~are ~~bone~~elevated ~~marrow~~(overexpressed) ~~and~~in ~~involve granulocytes,~~several ~~white~~human ~~and~~cancers ~~red~~as ~~blood~~compared ~~cells~~to healthy normal adults. ~~Lymphoid~~In ~~leukemias~~AML, ~~including~~elevated ~~lymphomas,~~levels ~~originate~~of inLSD1 ~~the~~are ~~lymph~~observed ~~nodes~~in ~~and~~less ~~lymphoid~~differentiated ~~tissue~~blood ~~but involve~~cells ~~immune~~(immature cells). ~~including~~Inhibition ~~lymphocytes,~~of Tthe ~~cells~~enzyme activity ~~and~~was Bfound ~~cells.~~to ~~MDS~~promote ~~are~~differentiation. ~~group~~Hence, inhibitors of ~~bone~~LSD1 ~~marrow~~are ~~failure~~promising ~~disorders~~therapeutic candidates that ~~have~~can ~~various~~make ~~subtypes~~drug-insensitive forms of AML, due to reduced levels of methylated histones, responsive to treatment with ~~variable~~all-trans-retinoic ~~onsets~~acid, ~~prognoses~~or ATRA an agent that induces differentiation (maturation)and ~~risks~~used to treat a subtype of ~~developing~~AML called acute promyelocytic leukemia, or APL.

~~RASP-201~~Working from this premise, we executed a research (agreement with TES Pharma for screening of compounds and to conduct animal studies to identify lead compounds with suitable druggability properties. TES Pharma has screened ~34000 compounds across 4 chemical series for their ability to inhibit LSD1 in vitro. The hit rate was ~1%. The hits from this assay were expanded and IC50 (half maximal inhibitory concentration) values were determined for 115 compounds. One chemical class namely, Thienopyrrole series was prioritized for further expansion and in vitro characterization.

~~LSD1 is~~We anhave ~~enzyme~~filed ~~that~~patent ~~demethylates~~applications ~~(remove~~covering ~~methyl~~this novel ~~groups)~~potent ~~lysine~~inhibitor ~~side chain of histones~~class. The ~~levels~~current oflead ~~LSD1~~compound ~~are~~DDP_43242 ~~elevated~~inhibitory ~~(overexpressed) in~~effect ~~several~~on ~~human~~the ~~cancers as compared to healthy normal adults. In AML, elevated levels of~~ LSD1 ~~are observed~~ in less differentiated blood cells (immature cells). Inhibition of the enzyme activity was found to promote differentiation. Hence, inhibitors of LSD1 are promising therapeutic candidates that can make drugin-~~insensitive~~vitro ~~forms~~assay ofand ~~AML, due to reduced levels of methylated histones, responsive to treatment~~in-vivo ~~with~~efficacy ~~all-trans-retinoic~~in ~~acid,~~two ~~or ATRA an agent that induces differentiation (maturation)and used to treat a subtype of~~ AML ~~called~~animal ~~acute promyelocytic leukemia, or APL~~models.

~~Working from~~These ~~this~~studies ~~premise,~~have wefacilitated ~~executed~~the aselection ~~research~~of DDP_43242 ~~agreement~~as ~~with~~the ~~TES~~current ~~Pharma~~lead ~~for~~compound. ~~screening~~Additional ofabsorption, ~~compounds~~distribution, metabolism and toexcretion, ~~conduct~~or ~~animal~~ADME, ~~studies~~and toselectivity ~~identify~~characterization ~~lead~~is ~~compounds~~underway ~~with~~for ~~suitable~~drug ~~druggability~~candidate ~~properties.~~selection ~~TES~~for ~~Pharma~~clinical ~~has~~trials. ~~screened~~We ~~~34000~~anticipate ~~compounds~~filing ~~across~~an 4investigation ~~chemical~~new ~~series~~drug ~~for~~application, ~~their~~or ~~ability to~~IND, ~~inhibit LSD1~~ in ~~vitro~~the near future. ~~The~~We ~~hit~~believe ~~rate~~that ~~was~~this ~~~1%.~~breakthrough ~~The~~program ~~hits~~may ~~from~~have ~~this~~significant ~~assay~~benefits ~~were~~across ~~expanded~~all ~~and~~forms ~~IC50~~of ~~(half~~leukemia. ~~maximal~~We ~~inhibitory~~are ~~concentration)~~focusing on ~~values~~reversible ~~were~~small ~~determined~~molecular ~~for~~inhibitors ~~115~~of ~~compounds.~~LSD1 ~~One~~because ~~chemical~~these ~~class~~compounds ~~namely,~~are ~~Thienopyrrole~~expected ~~series~~to ~~was~~exhibit ~~prioritized~~less ~~for~~toxicity ~~further~~while ~~expansion~~retaining ~~and in~~desirable ~~vitro characterization~~efficacy.

We have filed patent applications covering this novel potent inhibitor class. The current lead compound DDP_43242 inhibitory effect on the LSD1 in in-vitro assay and in-vivo efficacy in two AML animal models.4

These studies have facilitated the selection of DDP_43242 as the current lead compound. Additional absorption, distribution, metabolism and excretion, or ADME, and selectivity characterization is underway for drug candidate selection for clinical trials. We anticipate filing an investigation new drug application, or IND, in the near future. We believe that this breakthrough program may have significant benefits across all forms of leukemia. We are focusing on reversible small molecular inhibitors of LSD1 because these compounds are expected to exhibit less toxicity while retaining desirable efficacy.Strategy

Our strategy is to target master regulators of cancer through deep knowledge of highly conserved pathways that are common to leukemia sub-types. Employing a multi-pronged approach, our programs are focused on two druggable intervention points with a potential to improve safety and efficacy of current AML mono and/or combination therapies. For the RASP-~~301~~201 program, the lead reversible LSD-1 candidate has been identified and manufacturing will be scaled for production of cGMP supplies for animal safety/toxicology studies, Phase 1, Phase 2 and Phase 3 clinical studies to support submission via the traditional 505(~~NPM1~~b)(1) regulatory pathway used for new chemical entities, or NCEs. We expect to use a similar pathway for the RASP-301 program, following identification of the lead drug candidate.

The NPM1 gene provides instructions for making a protein called nucleophosmin (NPM) which is found in a small region inside the nucleus of the cell called the nucleolus. Nucleophosmin shuttles back and forth between the nucleus and the fluid surrounding it (the cytoplasm). Nucleophosmin helps to transport other proteins from ribosomes (sites of protein synthesis) through the membrane surrounding the nucleus. The NPM-1 gene is mutated in approximately 35% of new cases of AML. However, mutations in the NPM1 gene, result in dislocation of NPM1 protein in the cytoplasm. NPM1 mutation may be an early event in development of leukemia. Given that NPM1 is thought to have a tumor-suppressor function, alterations in its localization in the cell (from the nucleus to the cytoplasm) may be crucial for the cell to change from normal to cancerous state. Our approach is to identify small molecule drugs that physically interfere with the aggregation of NPM1 which is important for normal function. RASP-301 is our innovative, first- in-class, oral, small molecule, potent inhibitor that disrupts NPM1-1 oligomerization (aggregation of individual subunits) and has the potential to treat refractory (resistant to treatment) AML with reduced toxicity at low dose levels The current lead candidate, TES-2169, exhibits cytotoxic (toxic to cancer cells) effects at nanomolar concentrations against AML cells in culture and was not cytotoxic to normal cells at the same concentrations. In vivo usefulness of these compounds in AML murine (mouse) models has been evaluated confirming the druggability of the target and its potential to treat refractory AML.

	●	Complete development of orally-available, small molecule, highly-selective, reversible inhibitor of LSD1 (RASP-201) and file IND in the near future. Manufacture of the lead RASP -201 candidate will be scaled to supply animal safety/toxicology studies and Phase 1, 2 and 3 clinical studies following the traditional 505(b)(1) pathway used for marketing approval of NCEs.

	●	Evaluate strategic opportunities to accelerate development timelines and maximize the commercial potential of the drug candidates. Such opportunities may include partnering to achieve business objectives and achieve maximum return on investment.

4Manufacturing

~~Strategy~~ We do not have any manufacturing facilities or personnel. We currently rely, and expect to continue to rely, on third parties for the manufacturing of our product candidates for preclinical as well as for commercial manufacturing if our product candidates receive marketing approval.

Our strategy is to target master regulators of cancer through deep knowledge of highly conserved pathways that are common to leukemia sub-types. Employing a multi-pronged approach, our programs are focused on two druggable intervention points with a potential to improve safety and efficacy of current AML mono and/or combination therapies. For the RASP-201 program, the lead reversible LSD-1 candidate has been identified and manufacturing will be scaled for production of cGMP supplies for animal safety/toxicology studies, Phase 1, Phase 2 and Phase 3 clinical studies to support submission via the traditional 505(b)(1) regulatory pathway used for new chemical entities, or NCEs. We expect to use a similar pathway for the RASP-301 program, following identification of the lead drug candidate.Commercialization

●We ~~Complete~~plan ~~development of orally-available, small molecule, highly-selective, reversible inhibitor of LSD1 (RASP-201) and file IND in the near future. Manufacture of the lead RASP -201 candidate will be scaled~~ to ~~supply~~retain ~~animal~~our ~~safety/toxicology~~worldwide ~~studies~~commercialization rights ~~and Phase 1, 2 and 3 clinical studies following the traditional 505(b)(1) pathway used~~ for ~~marketing~~some ~~approval~~ of ~~NCEs.~~our ●key ~~Selection~~product ofcandidates awhile ~~lead candidate~~ for ~~first~~other inproduct ~~class~~candidates ~~NPM1~~we ~~inhibitor~~might ~~(RASP-301).~~consider ●partnership ~~Evaluate strategic~~ opportunities to ~~accelerate development timelines and~~ maximize ~~the commercial potential of the drug candidates~~ returns. ~~Such opportunities may include partnering to achieve business objectives and achieve maximum return on investment.~~

~~Research~~While we currently have no sales, marketing or ~~Agreement~~commercial product distribution capabilities and have no experience as a company in commercializing products, we intend to build our own commercialization organization and capabilities over time. When appropriate, we will decide whether to build a specialty sales force to manage commercialization for these product candidates on our own or in combination with a larger pharmaceutical partner, to maximize patient coverage in the United States and to support global expansion especially as our programs have substantial opportunity for additional follow-up indications alone or in combinations.

~~On December~~As ~~17,~~product ~~2013~~candidates ~~TES~~advance ~~Pharma~~through ~~S.R.L. (“TES”) and~~ our ~~predecessor~~pipeline, ~~Arna Therapeutics Limited, entered into a research agreement~~ ~~pursuant~~our tocommercial ~~which~~plans ~~TES~~may ~~agreed~~change. toClinical ~~perform~~data, ~~research~~the ~~related~~size toof the development ofprograms, ~~products~~the ~~and~~size ~~services associated with NPM1 and AML. The initial term~~ of the ~~agreement~~target ~~was for two years and was extended by amendment on May 3~~market, ~~2016 for an additional year. On September 8, 2016,~~ the ~~agreement~~size ~~was~~of ~~assigned~~a ~~to our subsidiary, Rasna Research, Inc. The agreement was further extended on March 24, 2017 until August~~commercial ~~30,~~infrastructure ~~2017.~~and Wemanufacturing ~~are~~needs ~~currently~~may inall ~~discussions~~influence ~~with~~our ~~TES~~United ~~Pharma S.R.L~~States, ~~profiling~~European ~~the~~Union ~~next~~and ~~stage~~ rest-of-world ~~research activity to be included in a new research agreement.~~ strategies

~~Manufacturing~~Government Regulation

WeThe FDA and comparable regulatory authorities doin ~~not~~state ~~have~~and ~~any~~local ~~manufacturing~~jurisdictions ~~facilities~~and orin ~~personnel.~~other Wecountries ~~currently~~impose ~~rely~~substantial and burdensome requirements upon companies involved in the clinical development, manufacture, marketing and ~~expect~~distribution toof ~~continue~~drugs, tosuch ~~rely~~as those we are developing. These agencies and other federal, state onand ~~third~~local ~~parties~~entities ~~for~~regulate, among other things, the ~~manufacturing~~research and development, testing, manufacture, quality control, safety, effectiveness, oflabeling, ~~our~~storage, ~~product~~record ~~candidates~~keeping, ~~for~~approval, ~~preclinical~~advertising asand ~~well~~promotion, asdistribution, ~~for~~post-approval ~~commercial~~monitoring ~~manufacturing~~and ifreporting, ~~our~~sampling and ~~product~~export ~~candidates~~and ~~receive~~import ~~marketing~~of ~~approval~~our product candidates.

~~Commercialization~~5

~~We plan~~U.S. toGovernment ~~retain~~Regulation ~~our worldwide commercialization rights for some~~ of ~~our~~Drug ~~key product candidates while for other product candidates we might consider partnership opportunities to maximize returns.~~Products

~~While~~In the United States, the FDA regulates drugs weunder ~~currently~~the ~~have~~Federal noFood, ~~sales~~Drug, ~~marketing~~and orCosmetic ~~commercial~~Act, ~~product~~or ~~distribution~~FDCA, ~~capabilities~~ and ~~have~~its noimplementing ~~experience~~regulations. asThe aprocess ~~company~~of inobtaining ~~commercializing~~regulatory approvals ~~products,~~and wethe ~~intend~~subsequent tocompliance ~~build~~with ~~our~~applicable ~~own~~federal, ~~commercialization~~state, ~~organization~~local and ~~capabilities~~foreign ~~over~~statutes ~~time.~~and ~~When~~regulations ~~appropriate,~~requires wethe ~~will~~expenditure ~~decide~~of ~~whether~~substantial time and financial resources. Failure to ~~build~~comply awith ~~specialty~~the ~~sales~~applicable ~~force~~U.S. torequirements ~~manage~~at ~~commercialization~~any ~~for~~time ~~these~~during the product ~~candidates~~development onprocess, approval ~~our~~process ~~own~~ or inafter ~~combination~~approval, ~~with~~may subject an applicant to a ~~larger pharmaceutical~~variety ~~partner~~of administrative or judicial sanctions, such as the FDA’s refusal to ~~maximize~~approve ~~patient~~pending ~~coverage~~NDAs, withdrawal inof ~~the~~an ~~United~~approval, ~~States~~imposition ~~and~~of toa ~~support~~clinical ~~global~~hold, ~~expansion~~issuance ~~especially~~of aswarning ~~our~~letters, ~~programs~~product recalls, ~~have~~product ~~substantial~~seizures, ~~opportunity~~total ~~for~~or ~~additional~~partial ~~follow-up~~suspension ~~indications~~of ~~alone~~production or indistribution, ~~combinations~~injunctions, fines, refusals of government contracts, restitution, disgorgement or civil or criminal penalties.

~~As product~~The ~~candidates~~process ~~advance~~required ~~through~~by ~~our pipeline, our commercial plans may change. Clinical data,~~ the ~~size~~FDA ofbefore ~~the development programs,~~product ~~the~~candidates ~~size~~may ofbe ~~the~~marketed ~~target~~in ~~market,~~ the ~~size of a commercial infrastructure and manufacturing needs may all influence our~~ United States, ~~European Union~~generally ~~and~~involves ~~rest-of-world~~the ~~strategies~~following:

~~Government Regulation~~○ submission to the FDA of an IND application which must become effective before human clinical trials may begin and must be updated annually;

~~The FDA~~○ ~~and~~completion ~~comparable~~of ~~regulatory~~extensive ~~authorities~~preclinical inlaboratory ~~state~~tests and ~~local~~preclinical ~~jurisdictions~~animal ~~and~~studies, inall ~~other~~performed ~~countries~~in ~~impose~~accordance ~~substantial~~with ~~and~~the ~~burdensome~~FDA’s ~~requirements upon~~GLP ~~companies~~regulations. ~~involved~~Preclinical intesting ~~the~~generally ~~clinical~~includes ~~development,~~evaluation ~~manufacture, marketing and distribution~~ of ~~drugs,~~our ~~such~~products asin ~~those~~the welaboratory ~~are~~or ~~developing. These~~in ~~agencies~~animals ~~and~~to ~~other~~characterize ~~federal, state and local entities regulate, among other things,~~ the ~~research~~product and ~~development,~~determine ~~testing, manufacture, quality control,~~ safety, ~~effectiveness, labeling, storage, record keeping, approval, advertising~~ and ~~promotion, distribution, post-approval monitoring and reporting, sampling and export and import of our product candidates.~~efficacy;

5○ approval by an independent institutional review board, or IRB, at each clinical site before each trial may be initiated;

~~U.S. Government~~○ ~~Regulation~~performance of ~~Drug~~adequate ~~Products~~and well-controlled human clinical trials in accordance with good clinical practice, or GCP, requirements to establish the safety and efficacy of the product candidate for each proposed indication;

~~In the~~○ ~~United~~submission ~~States,~~to the FDA ~~regulates drugs under the Federal Food, Drug, and Cosmetic Act, or FDCA, and its implementing regulations. The process~~ of ~~obtaining~~a ~~regulatory~~NDA approvals and the subsequent compliance with applicable federal, state, local and foreign statutes and regulations requires the expenditure of substantial time and financial resources. Failure to comply with the applicable U.S. requirements at any time during the product development process, approval process or after ~~approval,~~completion ~~may subject an applicant to a variety~~ of ~~administrative or~~all ~~judicial~~pivotal ~~sanctions, such as the FDA’s refusal to approve pending NDAs, withdrawal of an approval, imposition of a~~ clinical ~~hold,~~ issuance of warning letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, refusals of government contracts, restitution, disgorgement or civil or criminal penalties.trials;

~~The process~~○ ~~required~~a determination by the FDA ~~before~~within ~~product~~60 ~~candidates~~days ~~may~~of beits ~~marketed~~receipt inof ~~the~~an ~~United~~NDA ~~States~~to ~~generally~~accept ~~involves~~ the ~~following:~~filing for review;

○ ~~submission~~satisfactory tocompletion ~~the FDA~~ of an ~~IND~~FDA ~~application~~advisory ~~which~~committee ~~must~~review, ~~become~~if ~~effective before human clinical trials may begin and must be updated annually~~applicable;

○ satisfactory completion of ~~extensive~~an ~~preclinical~~FDA ~~laboratory~~pre-approval ~~tests~~inspection ~~and~~of ~~preclinical~~the ~~animal~~manufacturing ~~studies~~facilities at which the active pharmaceutical ingredient, ~~all~~or ~~performed~~API, inand ~~accordance~~finished ~~with~~drug ~~the~~product ~~FDA’s~~are ~~GLP~~produced ~~regulations.~~and ~~Preclinical~~tested ~~testing~~to ~~generally~~assess ~~includes~~compliance ~~evaluation~~with ofcGMP ~~our~~regulations ~~products~~and into assure that the ~~laboratory~~facilities, ormethods inand ~~animals~~controls are adequate to ~~characterize~~preserve the ~~product~~drug’s ~~and~~identity, ~~determine~~strength, ~~safety~~quality and ~~efficacy~~purity;

○ ~~approval~~satisfactory bycompletion anof ~~independent~~FDA ~~institutional~~audits ~~review~~of ~~board,~~clinical ortrial ~~IRB,~~sites atto ~~each~~assure ~~clinical~~compliance ~~site~~with ~~before~~GCPs ~~each~~and ~~trial~~the ~~may~~integrity beof ~~initiated~~the clinical data;

○ ~~performance~~payment of ~~adequate~~user fees and ~~well-controlled~~securing ~~human~~FDA ~~clinical~~approval ~~trials in accordance with good clinical practice, or GCP, requirements to establish the safety and efficacy~~ of the ~~product candidate for each proposed indication~~NDA; and

○ ~~submission~~compliance towith any post-approval requirements, including the ~~FDA~~potential ofrequirement to implement a ~~NDA~~REMS ~~after~~and ~~completion~~the ofpotential ~~all~~requirement ~~pivotal~~to ~~clinical~~conduct ~~trials;~~post-approval studies.

○Preclinical studies include laboratory evaluation of product chemistry, toxicity and formulation, as well as animal studies to assess potential safety and efficacy. An IND is a ~~determination~~request for byauthorization from the FDA ~~within~~to 60administer ~~days~~an investigational drug product to humans. The central focus of ~~its~~an IND submission is on the general investigational plan and the protocol(s) for human studies. The IND also includes results of preclinical studies or other human studies, as appropriate, as well as manufacturing information, analytical data and any available clinical data or literature to support the use of the investigational new drug. An IND must become effective before human clinical trials may begin. An IND will automatically become effective 30 days after receipt by the FDA, unless before that time the FDA raises concerns or questions related to the proposed clinical trials. In such a case, the IND may be placed on clinical hold and the IND sponsor and the FDA must resolve any outstanding concerns or questions before clinical trials can begin. Accordingly, submission of an ~~NDA~~IND may or may not result in the FDA allowing clinical trials to ~~accept~~commence. As a result, submission of an IND may not result in the ~~filing~~FDA ~~for~~allowing ~~review;~~clinical trials to commence.

~~○ satisfactory completion of an FDA advisory committee review, if applicable;~~6

○Clinical ~~satisfactory~~trials ~~completion~~involve the administration of the annew ~~FDA~~investigational ~~pre-approval~~drug ~~inspection~~to ofhuman subjects under the ~~manufacturing~~supervision ~~facilities~~of atqualified investigators in accordance with GCPs, which include the ~~active~~requirement ~~pharmaceutical~~that ~~ingredient,~~all orresearch ~~API,~~subjects ~~and~~provide ~~finished~~their ~~drug~~informed ~~product~~consent ~~are~~for ~~produced~~their ~~and~~participation ~~tested~~in toany ~~assess~~clinical ~~compliance~~trial. ~~with~~Clinical ~~cGMP~~trials are ~~regulations~~conducted ~~and~~under toprotocols ~~assure~~detailing, ~~that~~among other things, the ~~facilities~~objectives of the study, ~~methods~~the parameters to be used in monitoring safety, and ~~controls~~the ~~are~~efficacy ~~adequate~~criteria to ~~preserve~~be ~~the~~evaluated. ~~drug’s~~A ~~identity,~~protocol ~~strength,~~for ~~quality~~each clinical trial and ~~purity;~~any subsequent protocol amendments must be submitted to the FDA as part of the IND.

○Additionally, ~~satisfactory~~approval ~~completion~~must ofalso ~~FDA~~be ~~audits~~obtained offrom each clinical trial ~~sites~~site’s toInstitutional ~~assure~~Review ~~compliance~~Board, ~~with~~or ~~GCPs~~IRB, before the trials may be initiated, and the ~~integrity~~IRB ofmust monitor the study until completed. There are also requirements governing the reporting of ongoing clinical ~~data;~~trials and clinical trial results to public registries.

○The ~~payment~~clinical investigation of ~~user~~a ~~fees~~drug ~~and~~is ~~securing~~generally divided ~~FDA~~into ~~approval~~three ofphases. Although the ~~NDA;~~phases ~~and~~are usually conducted sequentially, they may overlap or be combined. The three phases of an investigation are as follows:

○1. ~~compliance~~Phase 1. Phase 1 includes the initial introduction of an investigational new drug into humans. Phase 1 clinical trials are typically closely monitored and may be conducted in patients with ~~any~~the ~~post-approval~~target ~~requirements~~disease or condition or in healthy volunteers. These studies are designed to evaluate the safety, ~~including~~dosage tolerance, metabolism and pharmacologic actions of the ~~potential~~investigational ~~requirement~~drug toin ~~implement~~humans, athe ~~REMS~~side effects associated with increasing doses, and if possible, to gain early evidence on effectiveness. During Phase 1 clinical trials, sufficient information about the ~~potential~~investigational ~~requirement~~drug’s pharmacokinetics and pharmacological effects may be obtained to ~~conduct~~permit ~~post~~the design of well-~~approval~~controlled ~~studies~~and scientifically valid Phase 2 clinical trials.

~~Preclinical studies~~2. ~~include~~Phase ~~laboratory~~2. ~~evaluation~~Phase of2 ~~product~~includes ~~chemistry,~~controlled ~~toxicity~~clinical ~~and~~trials ~~formulation,~~conducted ~~as well as animal studies~~ to ~~assess~~preliminarily ~~potential~~or ~~safety and~~further ~~efficacy.~~evaluate ~~An IND is a request for authorization from~~ the ~~FDA~~effectiveness ~~to administer an investigational drug product to humans. The central focus~~ of ~~an IND submission is on~~ the ~~general~~ investigational ~~plan~~drug ~~and~~for ~~the~~a ~~protocol~~particular indication(s) ~~for~~in ~~human~~patients ~~studies.~~with ~~The~~the ~~IND~~disease ~~also includes results of preclinical studies~~ or ~~other~~condition ~~human~~under ~~studies~~study, asto ~~appropriate,~~determine asdosage ~~well~~tolerance asand ~~manufacturing~~optimal ~~information~~dosage, ~~analytical data~~ and ~~any~~to ~~available clinical~~identify ~~data~~possible oradverse ~~literature~~side toeffects ~~support~~and ~~the~~safety ~~use~~risks ofassociated with the ~~investigational new~~ drug. AnPhase ~~IND~~2 ~~must become effective before human~~ clinical trials ~~may~~ ~~begin.~~are Antypically ~~IND will automatically become effective 30 days after receipt by the FDA~~well-controlled, ~~unless~~closely ~~before that time the FDA raises concerns or questions related to the proposed clinical trials. In such a case~~monitored, ~~the IND may be placed on clinical hold~~ and ~~the~~conducted ~~IND sponsor and the FDA must resolve any outstanding concerns or questions before clinical trials can begin. Accordingly, submission of an IND may or may not result~~ in ~~the FDA allowing clinical trials to commence. As~~ a ~~result,~~limited ~~submission~~patient ~~of an IND may not result in the FDA allowing clinical trials to commence~~population.

63. Phase 3. Phase 3 clinical trials are generally controlled clinical trials conducted in an expanded patient population generally at geographically dispersed clinical trial sites. They are performed after preliminary evidence suggesting effectiveness of the drug has been obtained, and are intended to further evaluate dosage, clinical effectiveness and safety, to establish the overall benefit-risk relationship of the investigational drug product, and to provide an adequate basis for product approval.

~~Clinical trials~~A ~~involve~~pivotal ~~the~~study ~~administration~~is ofany ~~the~~clinical ~~new~~study, ~~investigational~~which ~~drug~~adequately meets toregulatory ~~human~~agency ~~subjects~~requirements ~~under~~for the ~~supervision~~evaluation of ~~qualified~~a ~~investigators in~~drug ~~accordance~~candidate’s ~~with~~efficacy ~~GCPs,~~and ~~which~~safety ~~include~~such ~~the requirement~~ that ~~all~~it ~~research~~can ~~subjects~~be ~~provide~~used ~~their~~to ~~informed consent for their participation~~justify inthe ~~any~~approval ~~clinical~~of ~~trial~~the product. ~~Clinical trials are conducted under protocols detailing~~Generally, ~~among~~pivotal ~~other~~studies ~~things,~~are ~~the~~Phase ~~objectives~~3 ofstudies ~~the~~but ~~study,~~may ~~the parameters~~also to be ~~used~~Phase in2 ~~monitoring~~studies ~~safety,~~if ~~and~~ the ~~efficacy~~trial ~~criteria~~design toprovides a bewell-controlled ~~evaluated.~~and Areliable ~~protocol~~assessment ~~for~~of ~~each~~ clinical ~~trial~~benefit, ~~and~~particularly ~~any~~in ~~subsequent protocol~~situations ~~amendments~~where ~~must~~there beis ~~submitted~~an tounmet ~~the~~medical ~~FDA as part of the IND~~need.

~~Additionally,~~Progress reports detailing the results of the ~~approval~~clinical trials must ~~also~~ be ~~obtained~~submitted ~~from~~at ~~each~~least annually to the FDA and more frequently if serious adverse events occur. Phase 1, Phase 2 and Phase 3 clinical ~~trial~~trials ~~site’s~~may ~~Institutional~~not ~~Review~~be ~~Board~~completed successfully within any specified period, or at all. The FDA, the IRB, ~~before~~or the ~~trials~~clinical trial sponsor may besuspend ~~initiated~~or terminate a clinical trial at any time on various grounds, ~~and~~ ~~the~~including ~~IRB~~a ~~must~~finding ~~monitor~~that the ~~study~~research ~~until~~subjects ~~completed~~are being exposed to an unacceptable health risk. ~~There~~Additionally, some clinical trials are ~~also~~overseen ~~requirements~~by ~~governing~~an ~~the~~independent ~~reporting~~group of ~~ongoing~~qualified experts organized by the clinical ~~trials~~trial ~~and~~sponsor, known as a data safety monitoring board or committee. This group provides authorization for whether or ~~clinical~~not a trial ~~results~~may move forward at designated check points based on access to ~~public~~certain ~~registries~~data from the study. We may also suspend or terminate a clinical trial based on evolving business objectives and/or competitive climate.

~~The clinical~~Assuming ~~investigation~~successful completion of aall ~~drug~~required testing isin ~~generally~~accordance ~~divided~~with ~~into~~all ~~three~~applicable ~~phases.~~regulatory ~~Although~~requirements, ~~the~~detailed ~~phases~~investigational ~~are~~drug ~~usually~~product ~~conducted~~information ~~sequentially,~~is ~~they~~submitted to the ~~may~~FDA ~~overlap~~in orthe beform ~~combined.~~of ~~The~~an ~~three~~NDA ~~phases~~requesting ofapproval anto ~~investigation~~market ~~are~~the asproduct ~~follows:~~for one or more indications.

1.The ~~Phase~~application 1.includes ~~Phase~~all 1relevant ~~includes~~data ~~the~~available from ~~initial~~pertinent ~~introduction~~preclinical ofand anclinical ~~investigational~~trials, ~~new~~including ~~drug~~negative ~~into~~or ~~humans.~~ambiguous ~~Phase~~results 1as ~~clinical~~well ~~trials~~as ~~are~~positive ~~typically~~findings, ~~closely~~together ~~monitored~~with ~~and~~detailed information ~~may~~relating beto ~~conducted~~the inproduct’s ~~patients~~chemistry, ~~with~~manufacturing, ~~the~~controls ~~target~~and ~~disease~~proposed orlabeling, ~~condition~~among orother inthings. ~~healthy~~Data ~~volunteers.~~can ~~These~~come from ~~studies~~company-sponsored ~~are~~clinical ~~designed~~trials intended to ~~evaluate~~test the safety, ~~dosage tolerance, metabolism~~ and ~~pharmacologic~~effectiveness ~~actions~~ of ~~the~~a ~~investigational~~use ~~drug~~of ina ~~humans~~product, ~~the~~or ~~side~~from ~~effects~~a ~~associated~~number ~~with~~of ~~increasing doses~~alternative sources, ~~and~~including ifstudies ~~possible,~~initiated toby ~~gain~~investigators. ~~early~~To ~~evidence~~support onmarketing ~~effectiveness.~~approval, ~~During~~the ~~Phase~~data 1submitted ~~clinical~~must ~~trials,~~be sufficient ~~information~~in ~~about~~quality and ~~the~~quantity ~~investigational~~to ~~drug’s~~establish ~~pharmacokinetics~~the safety and ~~pharmacological~~effectiveness ~~effects~~of ~~may~~the beinvestigational ~~obtained~~drug product to ~~permit~~ the ~~design~~satisfaction of ~~well-controlled~~the ~~and scientifically valid Phase 2 clinical trials~~FDA.

2. Phase 2. Phase 2 includes controlled clinical trials conducted to preliminarily or further evaluate the effectiveness of the investigational drug for a particular indication(s) in patients with the disease or condition under study, to determine dosage tolerance and optimal dosage, and to identify possible adverse side effects and safety risks associated with the drug. Phase 2 clinical trials are typically well-controlled, closely monitored, and conducted in a limited patient population.7

3.In ~~Phase~~most 3.cases, ~~Phase~~the 3submission ~~clinical~~of ~~trials~~an ~~are~~NDA ~~generally~~is ~~controlled~~subject to ~~clinical~~a ~~trials~~substantial ~~conducted~~application inuser anfee. ~~expanded~~Under ~~patient~~the ~~population~~Prescription ~~generally~~Drug atUser ~~geographically~~Fee ~~dispersed~~Act, ~~clinical~~or ~~trial~~PDUFA, ~~sites.~~guidelines ~~They~~that are ~~performed~~currently ~~after~~in ~~preliminary~~effect, ~~evidence~~the FDA ~~suggesting~~has ~~effectiveness~~a goal of ~~the~~ten ~~drug~~months ~~has~~from ~~been~~the ~~obtained,~~date ~~and~~of ~~are~~“filing” ~~intended~~of toa ~~further~~standard ~~evaluate~~NDA ~~dosage,~~for ~~clinical~~a ~~effectiveness~~new ~~and~~molecular ~~safety,~~entity to ~~establish~~review and act on the submission. ~~overall~~This ~~benefit-risk~~review ~~relationship~~typically oftakes twelve months from the ~~investigational~~date ~~drug~~the ~~product,~~NDA ~~and~~is submitted to ~~provide~~FDA anbecause ~~adequate~~the ~~basis~~FDA ~~for~~has ~~product~~approximately ~~approval~~two months to make a “filing” decision.

AIn addition, under the Pediatric Research Equity ~~pivotal~~Act ~~study~~of is2003, ~~any~~or ~~clinical~~PREA, ~~study~~as amended and reauthorized, ~~which~~certain ~~adequately~~NDAs ~~meets~~or ~~regulatory~~supplements ~~agency~~to ~~requirements~~an ~~for~~NDA must contain data that are adequate to assess the ~~evaluation~~safety and effectiveness of athe drug ~~candidate’s efficacy~~for ~~and~~the ~~safety~~claimed ~~such~~indications ~~that~~in itall ~~can~~relevant bepediatric ~~used~~subpopulations, and to ~~justify~~support ~~the~~dosing ~~approval~~and administration offor each pediatric subpopulation for which the product is safe and effective. ~~Generally,~~The ~~pivotal~~FDA ~~studies~~may, ~~are~~on ~~Phase~~its 3own ~~studies~~initiative ~~but~~or at ~~may~~the ~~also~~request beof ~~Phase~~the 2applicant, ~~studies~~grant ifdeferrals ~~the~~for ~~trial~~submission ~~design~~of ~~provides~~some aor ~~well-controlled~~all ~~and~~pediatric ~~reliable~~data ~~assessment~~until after approval of ~~clinical~~the ~~benefit,~~product ~~particularly~~for use in ~~situations~~adults, ~~where~~or ~~there~~full isor anpartial ~~unmet~~waivers ~~medical~~from ~~need~~the pediatric data requirements.

~~Progress reports~~The ~~detailing the results of the clinical trials must be submitted at least annually to the~~ FDA ~~and~~also ~~more frequently if serious adverse events occur. Phase 1, Phase 2 and Phase 3 clinical trials~~ may ~~not~~require besubmission ~~completed~~of ~~successfully~~a ~~within any specified period, or at all.~~risk ~~The~~evaluation ~~FDA,~~and ~~the~~mitigation ~~IRB~~strategy, or ~~the clinical trial sponsor may suspend or terminate a clinical trial at any time on various grounds~~REMS, ~~including~~plan ~~a finding~~to ensure that the ~~research~~benefits ~~subjects~~of ~~are~~the ~~being~~drug ~~exposed~~outweigh toits ~~an unacceptable health risk~~risks. ~~Additionally,~~The ~~some~~REMS ~~clinical~~plan ~~trials~~could ~~are overseen~~include bymedication anguides, ~~independent~~physician ~~group~~communication ofplans, ~~qualified~~assessment ~~experts~~plans, ~~organized~~and/or byelements ~~the~~to ~~clinical~~assure ~~trial~~safe ~~sponsor~~use, ~~known~~such as arestricted ~~data safety monitoring board or committee.~~distribution ~~This~~methods, ~~group~~patient ~~provides~~registries, ~~authorization for whether~~ or ~~not~~other arisk ~~trial~~minimization ~~may move forward at designated check points based on access to certain data from the study~~tools. ~~We may also suspend or terminate a clinical trial based on evolving business objectives and/or competitive climate.~~

~~Assuming successful~~The ~~completion~~FDA conducts a preliminary review of all ~~required~~NDAs within ~~testing~~the infirst ~~accordance~~60 ~~with~~days ~~all~~after ~~applicable~~submission, ~~regulatory~~before ~~requirements~~accepting them for filing, ~~detailed~~to ~~investigational~~determine ~~drug~~whether they are sufficiently complete to permit ~~product~~substantive review. The FDA may request additional information rather than accept an NDA for filing. In this event, the application must be resubmitted with the additional information. The resubmitted application is ~~submitted~~also subject to review before the FDA inaccepts ~~the~~it ~~form~~for offiling. Once anthe NDA ~~requesting~~submission ~~approval~~has been accepted for filing, the FDA’s goal is to ~~market~~review applications within ten months of submission or, if the ~~product~~application relates to an unmet medical need in a serious or life-threatening indication, six months from submission. The review process is often significantly extended by FDA requests for ~~one~~additional information or ~~more~~clarification. ~~indications~~The FDA may refer the application to an advisory committee for review, evaluation and recommendation as to whether the application should be approved. The FDA is not bound by the recommendation of an advisory committee but it typically follows such recommendations.

The ~~application~~ ~~includes~~FDA ~~all~~will ~~relevant~~not ~~data~~approve ~~available~~an ~~from~~application ~~pertinent~~unless it ~~preclinical~~determines ~~and~~that ~~clinical~~the ~~trials,~~manufacturing ~~including~~processes ~~negative~~and orfacilities ~~ambiguous~~are ~~results as~~in ~~well~~compliance aswith ~~positive~~cGMP ~~findings,~~requirements ~~together~~and ~~with~~adequate ~~detailed~~to ~~information~~assure ~~relating~~consistent production toof the product’s ~~chemistry,~~within ~~manufacturing~~required specifications. Additionally, ~~controls~~before ~~and proposed~~approving ~~labeling~~an NDA, ~~among~~the ~~other~~FDA ~~things.~~may ~~Data~~inspect ~~can~~one ~~come~~or ~~from~~more ~~company-sponsored~~ clinical trial ~~trials~~sites ~~intended~~ to ~~test~~assure ~~the~~compliance ~~safety~~with ~~and~~GCP ~~effectiveness of~~requirements. aThe ~~use~~FDA ofwill anot ~~product,~~approve oran ~~from~~application aunless ~~number~~it ofdetermines ~~alternative~~that ~~sources,~~the ~~including~~manufacturing processes ~~studies~~and ~~initiated~~facilities byare ~~investigators.~~in Tocompliance ~~support~~with ~~marketing~~cGMP ~~approval, the~~requirements ~~data~~and ~~submitted~~adequate ~~must~~to beassure ~~sufficient~~consistent inproduction ~~quality~~of ~~and~~the ~~quantity~~product towithin ~~establish~~required specifications. ~~the~~Additionally, ~~safety~~before ~~and~~approving ~~effectiveness~~an ofNDA, the ~~investigational~~FDA ~~drug~~may ~~product to~~inspect ~~the~~one ~~satisfaction~~or ofmore ~~the~~clinical ~~FDA~~trial sites to assure compliance with GCP requirements.

7After the FDA evaluates the NDA and conducts inspections of manufacturing facilities where the drug product and/or its active pharmaceutical ingredient, or API, will be produced, it may issue an approval letter or a Complete Response Letter. An approval letter authorizes commercial marketing of the drug with specific prescribing information for specific indications. A Complete Response Letter indicates that the review cycle of the application is complete and the application is not ready for approval. A Complete Response Letter may require additional clinical data and/or an additional pivotal Phase 3 clinical trial(s), and/or other significant, expensive and time-consuming requirements related to clinical trials, preclinical studies or manufacturing. Even if such additional information is submitted, the FDA may ultimately decide that the NDA does not satisfy the criteria for approval. The FDA could also approve the NDA with a Risk Evaluation and Mitigation Strategies, or REMS, plan to mitigate risks, which could include medication guides, physician communication plans, or elements to assure safe use, such as restricted distribution methods, patient registries and other risk minimization tools. The FDA also may condition approval on, among other things, changes to proposed labeling, development of adequate controls and specifications, or a commitment to conduct one or more post-market studies or clinical trials. Such post-market testing may include Phase 4 clinical trials and surveillance to further assess and monitor the product’s safety and effectiveness after commercialization. Regulatory approval of oncology products often requires that patients in clinical trials be followed for long periods to determine the overall survival benefit of the drug. The FDA may prevent or limit further marketing of a product based on the results of post-marketing studies or surveillance programs. After approval, some types of changes to the approved product, such as adding new indications, manufacturing changes, and additional labeling claims, are subject to further testing requirements and FDA review and approval.

In most cases, the submission of an NDA is subject to a substantial application user fee. Under the Prescription Drug User Fee Act, or PDUFA, guidelines that are currently in effect, the FDA has a goal of ten months from the date of “filing” of a standard NDA for a new molecular entity to review and act on the submission. This review typically takes twelve months from the date the NDA is submitted to FDA because the FDA has approximately two months to make a “filing” decision.8

InAfter regulatory approval of a drug product is ~~addition~~obtained, ~~under~~a ~~the~~company ~~Pediatric~~is ~~Research~~required ~~Equity~~to ~~Act~~comply with a number of ~~2003~~post-approval requirements. As a holder of an approved NDA, orwe ~~PREA~~would be required to report, asamong ~~amended~~other things, certain adverse reactions and ~~reauthorized~~production problems to the FDA, ~~certain~~to ~~NDAs~~provide orupdated ~~supplements~~safety and efficacy information, and to ancomply ~~NDA~~with requirements concerning advertising and promotional labeling for any of our products. Also, quality control and manufacturing procedures must ~~contain~~continue ~~data~~to ~~that~~conform ~~are~~to ~~adequate~~cGMP toafter ~~assess~~approval ~~the~~to ~~safety~~ensure and ~~effectiveness~~preserve the long-term stability of the drug ~~for~~product. ~~the~~In ~~claimed~~addition, drug ~~indications~~manufacturers and other entities involved in ~~all~~the ~~relevant~~manufacture ~~pediatric~~and distribution of approved drugs are required to register their establishments ~~subpopulations~~with the FDA and state agencies, and are subject to ~~support~~periodic ~~dosing~~unannounced inspections by the FDA and ~~administration~~these state agencies for ~~each~~compliance with ~~pediatric~~cGMP ~~subpopulation~~requirements. ~~for~~In ~~which~~addition, changes to the ~~product~~manufacturing isprocess ~~safe~~are strictly regulated, and, ~~effective.~~depending on the significance of ~~The~~the ~~FDA~~change, may, onrequire ~~its~~prior ~~own~~FDA ~~initiative~~approval orbefore atbeing ~~the~~implemented. ~~request~~FDA regulations also require investigation and correction of ~~the~~any deviations ~~applicant,~~from ~~grant~~cGMP ~~deferrals~~and ~~for~~impose ~~submission~~reporting ofand ~~some~~documentation orrequirements ~~all~~upon ~~pediatric~~us ~~data~~and ~~until after~~any ~~approval~~third-party ofmanufacturers ~~the~~that ~~product~~we ~~for~~may decide to use. ~~in adults~~Accordingly, ormanufacturers ~~full~~must orcontinue ~~partial~~to ~~waivers~~expend ~~from~~time, money and effort in the ~~pediatric~~area ~~data~~of ~~requirements~~production and quality control to maintain compliance with cGMP and other aspects of regulatory compliance.

~~The FDA~~We ~~also~~rely, ~~may~~and ~~require~~expect ~~submission~~to ofcontinue ato ~~risk~~rely, ~~evaluation~~on ~~and~~third parties ~~mitigation~~for ~~strategy,~~the orproduction ~~REMS,~~of ~~plan~~clinical toand ~~ensure~~commercial ~~that~~quantities ~~the~~of ~~benefits~~our ofproduct ~~the~~candidates. ~~drug~~Future ~~outweigh~~FDA and state inspections may identify ~~its~~compliance ~~risks.~~issues ~~The~~at ~~REMS~~our ~~plan~~facilities ~~could~~or ~~include~~at ~~medication~~the ~~guides,~~facilities ~~physician~~of ~~communication~~our ~~plans,~~contract ~~assessment~~manufacturers ~~plans~~that may disrupt production or distribution, ~~and/~~or require ~~elements~~substantial resources to ~~assure safe~~correct. ~~use~~In addition, ~~such~~discovery asof ~~restricted~~previously ~~distribution~~unknown ~~methods,~~problems ~~patient~~with ~~registries,~~a product or ~~other~~the ~~risk~~failure ~~minimization~~to ~~tools.~~comply with applicable requirements may result in, among other things,

~~The FDA~~● ~~conducts~~restrictions aon ~~preliminary~~the ~~review~~marketing ofor ~~all~~manufacturing ~~NDAs~~of ~~within~~ the ~~first 60 days after submission~~product, ~~before accepting them for filing, to determine whether they are sufficiently~~ complete towithdrawal permit substantive review. The FDA may request additional information rather than accept an NDA for filing. In this event, the application must be resubmitted with the additional information. The resubmitted application is also subject to review before the FDA accepts it for filing. Once the NDA submission has been accepted for filing, the FDA’s goal is to review applications within ten months of ~~submission or, if~~ the ~~application~~product ~~relates to an unmet medical need in a serious or life-threatening indication, six months~~ from ~~submission.~~the ~~The~~market ~~review process is often significantly extended by FDA requests for additional information~~ or ~~clarification.~~product The FDA may refer the application to an advisory committee for review, evaluation and recommendation as to whether the application should be approved. The FDA is not bound by the recommendation of an advisory committee but it typically follows such recommendations.recalls;

~~The FDA~~● will not approve an application unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications. Additionallyfines, ~~before~~warning ~~approving an~~letters ~~NDA, the FDA may inspect one~~ or ~~more~~holds ~~clinical~~on ~~trial~~post-approval sites to assure compliance with GCP requirements. The FDA will not approve an application unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications. Additionally, before approving an NDA, the FDA may inspect one or more clinical ~~trial sites to assure compliance with GCP requirements.~~trials;

~~After the~~● ~~FDA~~refusal ~~evaluates the NDA and conducts inspections~~ of ~~manufacturing facilities where~~ the ~~drug~~FDA product and/or its active pharmaceutical ingredient, or API, will be produced, it may issue an approval letter or a Complete Response Letter. An approval letter authorizes commercial marketing of the drug with specific prescribing information for specific indications. A Complete Response Letter indicates that the review cycle of the application is complete and the application is not ready for approval. A Complete Response Letter may require additional clinical data and/or an additional pivotal Phase 3 clinical trial(s), and/or other significant, expensive and time-consuming requirements related to clinical trials, preclinical studies or manufacturing. Even if such additional information is submitted, the FDA may ultimately decide that the NDA does not satisfy the criteria for approval. The FDA could also approve ~~the~~pending ~~NDA~~NDAs ~~with a Risk Evaluation and Mitigation Strategies,~~ or ~~REMS,~~supplements ~~plan~~ to ~~mitigate~~approved ~~risks~~NDAs, ~~which could include medication guides, physician communication plans,~~ or ~~elements~~suspension to assure safe use, such as restricted distribution methods, patient registries and other risk minimization tools. The FDA also may condition approval on, among other things, changes to proposed labeling, development of adequate controls and specifications, or arevocation commitment to conduct one or more post-market studies or clinical trials. Such post-market testing may include Phase 4 clinical trials and surveillance to further assess and monitor the product’s safety and effectiveness after commercialization. Regulatory approval of oncology products often requires that patients in clinical trials be followed for long periods to determine the overall survival benefit of the drug. The FDA may prevent or limit further marketing of a product based on the results of post-marketing studies or surveillance programs. After approval, some types of changes to the approved product, such as adding new indications, manufacturing changes, and additional labeling claims, are subject to further testing requirements and FDA review and approval.approvals;

8● product seizure or detention, or refusal to permit the import or export of products; or

~~After regulatory~~● ~~approval~~injunctions ofor a drug product is obtained, a company is required to comply with a number of post-approval requirements. As a holder of an approved NDA, we would be required to report, among other things, certain adverse reactions and production problems to the ~~FDA,~~ toimposition ~~provide updated safety and efficacy information, and to comply with requirements concerning advertising and promotional labeling for any~~ of ~~our~~civil ~~products.~~or ~~Also,~~criminal ~~quality control and manufacturing procedures must continue to conform to cGMP after approval to ensure and preserve the long-term stability of the drug product~~penalties. In addition, drug manufacturers and other entities involved in the manufacture and distribution of approved drugs are required to register their establishments with the FDA and state agencies, and are subject to periodic unannounced inspections by the FDA and these state agencies for compliance with cGMP requirements. In addition, changes to the manufacturing process are strictly regulated, and, depending on the significance of the change, may require prior FDA approval before being implemented. FDA regulations also require investigation and correction of any deviations from cGMP and impose reporting and documentation requirements upon us and any third-party manufacturers that we may decide to use. Accordingly, manufacturers must continue to expend time, money and effort in the area of production and quality control to maintain compliance with cGMP and other aspects of regulatory compliance.

~~We rely,~~Newly ~~and~~discovered ~~expect~~or todeveloped ~~continue~~safety or effectiveness data may require changes to ~~rely,~~a onproduct’s ~~third~~approved ~~parties~~labeling, ~~for~~including the ~~production~~addition of ~~clinical~~new warnings and ~~commercial~~contraindications, ~~quantities~~and also may require the implementation of ~~our~~other ~~product~~risk ~~candidates~~management measures. ~~Future~~ The FDA strictly regulates marketing, labeling, advertising and ~~state~~promotion of ~~inspections~~products ~~may~~that ~~identify~~are ~~compliance~~placed ~~issues~~on atthe ~~our~~market. ~~facilities~~Drugs or atdevices may be promoted only for the ~~facilities~~approved indications and in accordance with the provisions of ~~our~~the ~~contract~~approved ~~manufacturers~~label. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses, and a company that is found to have improperly promoted off-label uses may ~~disrupt~~be ~~production~~subject orto ~~distribution~~significant liability. Also, orfrom ~~require~~time to ~~substantial~~time, ~~resources~~legislation tois ~~correct~~drafted, introduced and passed in Congress that could significantly change the statutory provisions governing the approval, manufacturing and marketing of products regulated by the FDA. In addition, ~~discovery~~FDA ofregulations ~~previously~~and ~~unknown problems~~guidance ~~with~~are aoften ~~product~~ revised or reinterpreted by the ~~failure~~agency in ways that may significantly affect our business and our products. It is impossible to ~~comply~~predict ~~with~~whether legislative ~~applicable~~changes ~~requirements~~will ~~may~~be ~~result~~enacted, inor FDA regulations, ~~among~~guidance ~~other~~or ~~things~~interpretations changed or what the impact of such changes, if any, may be.

●Marketing ~~restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls;~~Exclusivity

●Market ~~fines~~exclusivity provisions under the FDCA also can delay the submission or the approval of certain applications. The FDCA provides a five-year period of non-patent marketing exclusivity within the United States to the first applicant to obtain approval of an NDA for a new chemical entity. A drug is a new chemical entity if the FDA has not previously approved any other new drug containing the same active moiety, ~~warning~~which ~~letters~~is the molecule or ~~holds~~ion onresponsible for ~~post~~the action of the drug substance. During the exclusivity period, the FDA may not accept for review an abbreviated new drug application, or ANDA, or a 505(b)(2) NDA submitted by another company for another version of such drug where the applicant does not own or have a legal right of reference to all the data required for approval. However, an application may be submitted after four years if it contains a certification of patent invalidity or non-infringement. The FDCA also provides three years of marketing exclusivity for an NDA, 505(b)(2) NDA or supplement to an approved NDA if new clinical investigations, other than bioavailability studies, that were conducted or sponsored by the applicant are deemed by the FDA to be essential to the approval of the application, for example, for new indications, dosages or strengths of an existing drug. This three-year exclusivity covers only the conditions associated with the new clinical ~~trials~~investigations and does not prohibit the FDA from approving ANDAs for drugs containing the original active pharmaceutical ingredient. Five-year and three-year exclusivity will not delay the submission or approval of a full NDA; however, an applicant submitting a full NDA would be required to conduct or obtain a right of reference to all of the preclinical studies and adequate and well-controlled clinical trials necessary to demonstrate safety and effectiveness.

~~● refusal of the FDA to approve pending NDAs or supplements to approved NDAs, or suspension or revocation of product approvals;~~9

●The ~~product~~Hatch-Waxman ~~seizure~~Amendments: or505(b)(2) ~~detention, or refusal to permit the import or export of products; or~~approval process

●Section ~~injunctions~~505(b)(2) of the FDCA provides an alternate regulatory pathway to FDA approval for new or improved formulations or new uses of previously approved drug products. Specifically, Section 505(b)(2) permits the ~~imposition~~filing of ~~civil~~an NDA where at least some of the information required for approval comes from studies not conducted by or ~~criminal~~for ~~penalties~~the applicant and for which the applicant has not obtained a right of reference. The applicant may rely upon the FDA’s findings of safety and effectiveness for an approved product that acts as the Reference Listed Drug, or RLD. If the 505(b)(2) applicant can establish that reliance on FDA’s previous findings of safety and effectiveness is scientifically appropriate, it may eliminate the need to conduct certain preclinical or clinical studies of the new product. The FDA may also require 505(b)(2) applicants to perform additional studies or measurements to support the change from the RLD. The FDA may then approve the new product candidate for all or some of the labeled indications for which the referenced product has been approved, as well as for any new indication sought by the Section 505(b)(2) applicant.

~~Newly discovered~~In orseeking ~~developed~~approval ~~safety~~for ora ~~effectiveness~~drug ~~data~~through ~~may~~an ~~require~~NDA, including ~~changes~~a 505(b)(2) NDA, applicants are required to alist ~~product’s~~with ~~approved~~the ~~labeling,~~FDA ~~including~~certain patents whose claims cover the ~~addition~~applicant’s product. ofUpon ~~new~~approval ~~warnings~~of ~~and~~an ~~contraindications~~NDA, ~~and~~each ~~also~~of ~~may~~the ~~require~~patents listed in the ~~implementation~~application offor ~~other~~the ~~risk~~drug ~~management~~is ~~measures.~~then ~~The~~published ~~FDA~~in ~~strictly~~the ~~regulates~~Orange Book. Any applicant ~~marketing,~~who ~~labeling,~~files ~~advertising~~an ~~and~~ANDA ~~promotion~~seeking approval of ~~products~~a ~~that~~generic ~~are~~equivalent ~~placed~~version onof a drug listed in the ~~market.~~Orange ~~Drugs~~Book or ~~devices~~a ~~may~~505(b)(2) beNDA ~~promoted~~referencing a ~~only~~drug ~~for~~listed in the ~~approved~~ ~~indications~~Orange ~~and~~Book inmust ~~accordance~~certify ~~with~~to the ~~provisions~~FDA that (1) no patent information on the drug product that is the subject of the application ~~approved~~has ~~label.~~been ~~The~~submitted to the FDA; ~~and~~(2) ~~other~~such ~~agencies~~patent ~~actively~~has ~~enforce~~expired; (3) the ~~laws~~date on which such patent expires; or (4) such patent ~~and~~is ~~regulations~~invalid ~~prohibiting~~or will not be infringed upon by the ~~promotion~~manufacture, use or sale of ~~off-label~~the ~~uses,~~drug ~~and~~product afor ~~company~~which ~~that~~the application is ~~found~~submitted. toThis last ~~have~~certification ~~improperly~~is ~~promoted~~known ~~off-label~~as ~~uses~~a ~~may~~ paragraph IV certification. A notice of the paragraph IV certification must be provided to each owner of the patent that is the subject of the certification and to ~~significant~~the ~~liability.~~holder ~~Also,~~of ~~from~~the ~~time~~approved NDA to ~~time,~~which ~~legislation~~the isANDA ~~drafted,~~or ~~introduced~~505(b)(2) ~~and~~application refers. ~~passed~~The inapplicant ~~Congress~~may also elect to submit a ‘‘section viii’’ statement certifying that ~~could~~its ~~significantly~~proposed label ~~change~~does not contain (or carves out) any language regarding the ~~statutory~~patented ~~provisions~~method-of-use ~~governing~~rather than certify to a listed method-of-use patent. If the ~~approval,~~reference ~~manufacturing~~NDA holder and ~~marketing~~patent owners assert a patent challenge directed to one of ~~products~~the ~~regulated~~Orange byBook listed patents within 45 days of the ~~FDA.~~receipt Inof ~~addition~~the paragraph IV certification notice, the FDA is prohibited from approving the application until the earlier of 30 ~~regulations~~months ~~and~~from ~~guidance~~the ~~are~~receipt ~~often~~of ~~revised~~the orparagraph ~~reinterpreted~~IV bycertification expiration of the ~~agency~~patent, insettlement ~~ways~~of ~~that~~the ~~may~~lawsuit ~~significantly~~or ~~affect~~a ~~our~~decision ~~business~~in ~~and~~the ~~our~~infringement ~~products.~~case Itthat is ~~impossible~~favorable to ~~predict~~the ~~whether~~applicant. ~~legislative~~The ~~changes~~ANDA ~~will~~or be505(b)(2) ~~enacted,~~application oralso ~~FDA~~will ~~regulations,~~not ~~guidance~~be orapproved ~~interpretations~~until ~~changed~~any applicable non-patent exclusivity orlisted ~~what~~in the ~~impact~~Orange ofBook ~~such~~for ~~changes,~~the ifbranded ~~any,~~reference ~~may~~drug behas expired.

~~Marketing~~Our current and anticipated product candidates ~~Exclusivity~~will be based on already approved active pharmaceutical ingredients, or APIs, rather than new chemical entities, and a formulation that has been through Phase 1 studies. Accordingly, we expect to be able to rely on information from previously conducted formulation studies involving our clinical development plans and our NDA submissions. For product candidates that involve novel fixed-dose combinations of existing drugs or for studies of an existing product or product candidate in a new indication, we believe we generally will be able to initiate Phase 2/3 studies without conducting any new non-clinical or Phase 1 studies, though the FDA may not agree with our conclusions and may require us to conduct additional clinical or preclinical studies prior to initiating Phase 3 or other pivotal clinical trials. In those instances where our product candidate is a pharmacokinetically enhanced version of an approved API, we will need to conduct certain non-clinical and Phase 1 studies to confirm the pharmacokinetic profile of the product candidate prior to conducting Phase 2/3 studies.

~~Market exclusivity provisions under the FDCA also can delay the submission or the approval of certain applications~~U. ~~The FDCA provides a five-year period of non-patent marketing exclusivity within the United States to the first applicant to obtain approval of an NDA for a new chemical entity~~S. AForeign ~~drug~~Corrupt isPractices aAct new chemical entity if the FDA has not previously approved any other new drug containing the same active moiety, which is the molecule or ion responsible for the action of the drug substance. During the exclusivity period, the FDA may not accept for review an abbreviated new drug application, or ANDA, or a 505(b)(2) NDA submitted by another company for another version of such drug where the applicant does not own or have a legal right of reference to all the data required for approval. However, an application may be submitted after four years if it contains a certification of patent invalidity or non-infringement. The FDCA also provides three years of marketing exclusivity for an NDA, 505(b)(2) NDA or supplement to an approved NDA if new clinical investigations, other than bioavailability studies, that were conducted or sponsored by the applicant are deemed by the FDA to be essential to the approval of the application, for example, for new indications, dosages or strengths of an existing drug. This three-year exclusivity covers only the conditions associated with the new clinical investigations and does not prohibit the FDA from approving ANDAs for drugs containing the original active pharmaceutical ingredient. Five-year and three-year exclusivity will not delay the submission or approval of a full NDA; however, an applicant submitting a full NDA would be required to conduct or obtain a right of reference to all of the preclinical studies and adequate and well-controlled clinical trials necessary to demonstrate safety and effectiveness.

9The U.S. Foreign Corrupt Practices Act, to which we are subject, prohibits corporations and individuals from engaging in certain activities to obtain or retain business or to influence a person working in an official capacity. It is illegal to pay, offer to pay or authorize the payment of anything of value to any foreign government official, government staff member, political party or political candidate to obtain or retain business or to otherwise influence a person working in an official capacity.

~~The Hatch-Waxman Amendments: 505(b)(2) approval process~~10

~~Section 505(b)(2)~~Federal of the FDCA provides an alternate regulatory pathway to FDA approval for new or improved formulations or new uses of previously approved drug products. Specifically, Section 505(b)(2) permits the filing of an NDA where at least some of the information required for approval comes from studies not conducted by or for the applicant and ~~for~~State ~~which~~Fraud ~~the applicant has not obtained a right of reference. The applicant may rely upon the FDA’s findings of safety~~ and ~~effectiveness~~Abuse ~~for~~Laws an approved product that acts as the Reference Listed Drug, or RLD. If the 505(b)(2) applicant can establish that reliance on FDA’s previous findings of safety and effectiveness is scientifically appropriate, it may eliminate the need to conduct certain preclinical or clinical studies of the new product. The FDA may also require 505(b)(2) applicants to perform additional studies or measurements to support the change from the RLD. The FDA may then approve the new product candidate for all or some of the labeled indications for which the referenced product has been approved, as well as for any new indication sought by the Section 505(b)(2) applicant.

~~In seeking~~Healthcare ~~approval for a drug through an NDA~~providers, ~~including~~physicians aand ~~505(b)(2) NDA, applicants are required to list with the FDA certain patents whose~~third-party ~~claims~~payors ~~cover~~play ~~the~~a ~~applicant’s~~primary ~~product.~~role ~~Upon approval of an NDA, each of the patents listed~~ in the ~~application~~recommendation ~~for~~and ~~the~~prescription ~~drug is then published in the Orange Book. Any applicant who files an ANDA seeking approval~~ of adrug ~~generic~~and ~~equivalent~~biologic ~~version~~product ofcandidates awhich ~~drug~~obtain ~~listed~~marketing ~~in the~~approval. ~~Orange~~In ~~Book~~addition ~~or a 505(b)(2) NDA referencing a drug listed in the Orange Book must certify~~ to ~~the~~ FDA ~~that~~restrictions ~~(1) no patent information~~ on ~~the~~ ~~drug~~marketing ~~product that is the subject~~ of ~~the~~pharmaceutical ~~application~~products, ~~has~~pharmaceutical ~~been~~manufacturers ~~submitted~~are toexposed, ~~the FDA; (2) such patent has expired; (3) the date on which such patent expires; or (4) such patent is invalid or will not be infringed upon by the manufacture~~directly, ~~use~~ or ~~sale of the drug product~~indirectly, ~~for~~through ~~which~~customers, ~~the application is submitted. This last certification is known as a paragraph IV certification. A notice of the paragraph IV certification must be provided~~ to ~~each~~broadly ~~owner~~applicable offraud ~~the~~and ~~patent~~abuse ~~that~~and isother ~~the~~healthcare ~~subject~~laws ~~of the certification~~ and toregulations ~~the~~that ~~holder~~may ofaffect the ~~approved NDA~~business ~~to which the ANDA~~ or ~~505(b)(2) application refers. The applicant may also elect to submit a ‘‘section viii’’~~financial ~~statement~~arrangements ~~certifying~~and ~~that~~relationships ~~its~~through ~~proposed~~which ~~label does not contain (or carves out) any language regarding the patented method-of-use rather than certify to~~ a ~~listed~~pharmaceutical ~~method-of-use~~manufacturer ~~patent.~~can Ifmarket, ~~the~~sell ~~reference~~and ~~NDA~~distribute ~~holder~~drug and ~~patent~~biologic ~~owners assert a patent challenge directed to one~~products. ofThese ~~the~~laws ~~Orange Book listed patents within 45 days of the receipt of the paragraph IV certification notice~~include, ~~the~~but ~~FDA~~are is prohibited from approving the application until the earlier of 30 months from the receipt of the paragraph IV certification expiration of the patent, settlement of the lawsuit or a decision in the infringement case that is favorable to the applicant. The ANDA or 505(b)(2) application also will not belimited ~~approved until any applicable non-patent exclusivity listed in the Orange Book for the branded reference drug has expired.~~to:

~~Our current~~The ~~and~~federal ~~anticipated~~Anti-Kickback ~~product~~Statute ~~candidates~~which ~~will~~prohibits, any beperson ~~based~~or onentity ~~already~~from, ~~approved~~among ~~active~~other ~~pharmaceutical ingredients~~things, orknowingly ~~APIs,~~and ~~rather~~willfully ~~than new~~offering, ~~chemical~~paying, ~~entities~~soliciting, ~~and~~or areceiving ~~formulation~~any ~~that~~remuneration, ~~has~~directly or ~~been~~indirectly, ~~through~~overtly ~~Phase~~or 1covertly, ~~studies.~~in ~~Accordingly,~~cash weor ~~expect~~in-kind, to beinduce ~~able~~or toreward ~~rely~~either onthe ~~information from~~referring ~~previously~~of ~~conducted~~an ~~formulation~~individual ~~studies~~for, ~~involving~~or ~~our~~the ~~clinical~~purchasing, leasing, ~~development~~ordering, ~~plans~~or ~~and~~arranging ~~our~~for ~~NDA~~the ~~submissions.~~purchase, ~~For~~lease, ~~product~~or ~~candidates that~~order ~~involve~~of ~~novel~~any ~~fixed-dose~~healthcare ~~combinations~~item ofor ~~existing~~service ~~drugs~~reimbursable, orin ~~for~~whole ~~studies~~or ofin anpart, under ~~existing~~Medicare, ~~product~~Medicaid, or ~~product~~any ~~candidate~~other infederally afinanced ~~new~~healthcare ~~indication, we~~program. ~~believe~~The weterm ~~generally~~“remuneration” ~~will~~has bebeen ~~able~~broadly interpreted to ~~initiate~~include ~~Phase~~anything ~~2/3~~of ~~studies~~value. ~~without~~This ~~conducting~~statute ~~any~~has ~~new~~been ~~non-clinical~~interpreted orto ~~Phase~~apply 1to ~~studies,~~arrangements ~~though the~~between ~~FDA~~pharmaceutical ~~may~~manufacturers ~~not~~on ~~agree~~one ~~with~~hand and ~~our~~prescribers, ~~conclusions~~purchasers, and ~~may~~formulary ~~require~~managers uson tothe ~~conduct~~other ~~additional~~hand. ~~clinical~~Although orthere ~~preclinical~~are ~~studies~~a ~~prior~~number toof ~~initiating Phase~~statutory 3exemptions orand ~~other~~regulatory safe ~~pivotal~~harbors ~~clinical~~protecting ~~trials.~~certain Incommon ~~those~~activities ~~instances~~from ~~where~~prosecution, ~~our~~the ~~product~~exemptions ~~candidate~~and issafe aharbors ~~pharmacokinetically~~are ~~enhanced~~drawn ~~version~~narrowly, ofand practices anthat ~~approved~~involve ~~API,~~remuneration weintended ~~will need~~ to ~~conduct~~induce ~~certain~~prescribing, ~~non-clinical~~purchases, ~~and~~or ~~Phase~~recommendations 1may ~~studies~~be subject to ~~confirm~~scrutiny ~~the~~if ~~pharmacokinetic~~they ~~profile~~do ofnot ~~the product~~qualify ~~candidate~~for ~~prior~~an toexemption ~~conducting~~or ~~Phase~~safe ~~2/3 studies~~harbor.

The federal false claims and civil monetary penalty laws, including the Federal False Claims Act, which imposes significant penalties and can be enforced by private citizens through civil qui tam actions, prohibits any person or entity from, among other things, knowingly presenting, or causing to be presented, a false, fictitious or fraudulent claim for payment to the federal government, or knowingly making, using or causing to be made, a false statement or record material to a false or fraudulent claim to avoid, decrease or conceal an obligation to pay money to the federal government. In addition, a claim including items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the False Claims Act. As a result of a modification made by the Fraud Enforcement and Recovery Act of 2009, a claim includes “any request or demand” for money or property presented to the U.S. government. In addition, manufacturers can be ~~Foreign~~held ~~Corrupt~~liable ~~Practices~~under the False Claims Act even when they do not submit claims directly to government payors if they are deemed to “cause” the submission of false or fraudulent claims. Criminal prosecution is also possible for making or presenting a false, fictitious or fraudulent claim to the federal government. Recently, several pharmaceutical and other healthcare companies have been prosecuted under these laws for allegedly providing free product to customers with the expectation that the customers would bill federal programs for the product. Other companies have been prosecuted for causing false claims to be submitted because of the company’s marketing of the product for unapproved, and thus non-reimbursable, uses.

The ~~U.S.~~ ~~Foreign~~federal ~~Corrupt~~Health ~~Practices~~Insurance Portability and Accountability Act of 1996, toor HIPAA, which, weamong ~~are~~other ~~subject~~things, ~~prohibits~~imposes ~~corporations~~criminal ~~and~~liability ~~individuals~~for ~~from~~executing ~~engaging~~or inattempting ~~certain~~to ~~activities~~ execute a scheme to ~~obtain~~defraud any orhealthcare ~~retain~~benefit ~~business~~program, including private third-party payors, knowingly and willfully embezzling or tostealing ~~influence~~from a ~~person~~healthcare benefit ~~working~~program, inwillfully anobstructing ~~official~~a ~~capacity.~~criminal Itinvestigation isof ~~illegal~~a tohealthcare ~~pay~~offense, ~~offer~~and tocreates ~~pay~~federal orcriminal ~~authorize~~laws that prohibit ~~the~~knowingly ~~payment~~and ofwillfully ~~anything~~falsifying, ofconcealing ~~value~~or tocovering ~~any~~up ~~foreign~~a ~~government~~material ~~official,~~fact ~~government~~or ~~staff~~making ~~member~~any materially false, ~~political~~fictitious ~~party~~or fraudulent statements or ~~political~~representations, ~~candidate to~~or ~~obtain~~making or ~~retain~~using ~~business~~any false writing or document knowing the same to ~~otherwise~~contain ~~influence~~any amaterially ~~person~~false, ~~working~~fictitious or fraudulent statement or entry in anconnection ~~official~~with ~~capacity~~the delivery of, or payment for, benefits, items or services.

10HIPAA, as amended by the Health Information Technology and Clinical Health Act of 2009, or HITECH, and its implementing regulations, which impose certain requirements relating to the privacy, security, transmission and breach reporting of individually identifiable health information upon entities subject to the law, such as health plans, healthcare clearinghouses and healthcare providers and their respective business associates that perform services for them that involve individually identifiable health information. HITECH also created new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates, and gave state attorneys general new authority to file civil actions for damages or injunctions in U.S. federal courts to enforce the federal HIPAA laws and seek attorneys’ fees and costs associated with pursuing federal civil actions.

~~Federal~~The federal physician payment transparency requirements, sometimes referred to as the “Physician Payments Sunshine Act,” and ~~State~~its ~~Fraud~~implementing regulations, which require certain manufacturers of drugs, devices, biologics and ~~Abuse~~medical ~~Laws~~supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions) to report annually to the United States Department of Health and Human Services, or HHS, information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors) and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members.

~~Healthcare providers,~~State ~~physicians~~ and ~~third-party~~foreign ~~payors~~law ~~play~~equivalents ~~a primary role in the recommendation and prescription~~ of ~~drug~~each ~~and biologic product candidates which obtain marketing approval. In addition to FDA restrictions on marketing~~ of ~~pharmaceutical products, pharmaceutical manufacturers~~the ~~are~~above ~~exposed,~~federal ~~directly~~laws, orsuch ~~indirectly,~~as ~~through~~anti-kickback ~~customers, to broadly applicable fraud~~ and ~~abuse~~false ~~and~~claims ~~other healthcare~~ laws, ~~and regulations~~ that may ~~affect~~impose ~~the~~similar ~~business~~ or ~~financial~~more ~~arrangements~~prohibitive restrictions, and ~~relationships~~may ~~through which a pharmaceutical manufacturer can market, sell~~apply ~~and~~to ~~distribute~~items ~~drug~~or ~~and~~services ~~biologic~~reimbursed ~~products.~~by ~~These~~non-governmental ~~laws~~third-party ~~include~~payors, ~~but~~including ~~are~~private ~~not limited to:~~insurers.

The federal Anti-Kickback Statute which prohibits, any person or entity from, among other things, knowingly and willfully offering, paying, soliciting, or receiving any remuneration, directly or indirectly, overtly or covertly, in cash or in-kind, to induce or reward either the referring of an individual for, or the purchasing, leasing, ordering, or arranging for the purchase, lease, or order of any healthcare item or service reimbursable, in whole or in part, under Medicare, Medicaid, or any other federally financed healthcare program. The term “remuneration” has been broadly interpreted to include anything of value. This statute has been interpreted to apply to arrangements between pharmaceutical manufacturers on one hand and prescribers, purchasers, and formulary managers on the other hand. Although there are a number of statutory exemptions and regulatory safe harbors protecting certain common activities from prosecution, the exemptions and safe harbors are drawn narrowly, and practices that involve remuneration intended to induce prescribing, purchases, or recommendations may be subject to scrutiny if they do not qualify for an exemption or safe harbor.11

~~The federal~~State ~~false claims~~ and ~~civil~~foreign ~~monetary penalty~~ laws, ~~including~~that ~~the~~require ~~Federal False Claims Act, which imposes significant penalties and~~pharmaceutical ~~can~~companies beto ~~enforced~~implement bycompliance ~~private citizens through civil qui tam actions~~programs, ~~prohibits~~comply ~~any~~with ~~person~~the orpharmaceutical ~~entity~~industry’s ~~from,~~voluntary ~~among~~compliance ~~other~~guidelines ~~things,~~and ~~knowingly~~the relevant ~~presenting,~~compliance orguidance ~~causing~~promulgated toby ~~be presented, a false, fictitious or fraudulent claim for payment to~~ the federal government, or ~~knowingly making, using or causing~~ to betrack ~~made,~~and areport ~~false statement or record material to a false or fraudulent claim to avoid~~gifts, ~~decrease~~compensation orand ~~conceal~~other anremuneration ~~obligation~~provided to ~~pay~~physicians ~~money~~and toother ~~the~~healthcare ~~federal government. In addition~~providers, aand ~~claim~~other ~~including items or services resulting from a violation of the~~ federal, ~~Anti-Kickback Statute~~state ~~constitutes~~and aforeign ~~false~~laws orthat ~~fraudulent~~govern ~~claim for purposes of~~ the ~~False~~privacy ~~Claims~~and ~~Act.~~security ~~As a result~~ of ~~a modification made by the Fraud~~health ~~Enforcement~~information ~~and Recovery Act of 2009, a claim includes “any request~~ or ~~demand”~~personally ~~for~~identifiable ~~money~~information orin ~~property~~certain ~~presented to the U.S. government. In addition~~circumstances, ~~manufacturers~~including ~~can~~state behealth ~~held~~information ~~liable~~privacy ~~under~~and ~~the~~data ~~False Claims Act even when they do not submit claims directly to~~breach ~~government~~notification ~~payors~~laws ifwhich ~~they~~govern ~~are deemed to “cause”~~ the ~~submission~~collection, ofuse, ~~false or fraudulent claims. Criminal prosecution is also possible for making or presenting a false~~disclosure, ~~fictitious~~and orprotection ~~fraudulent~~of ~~claim~~health-related ~~to the federal government. Recently, several pharmaceutical~~ and other ~~healthcare~~personal ~~companies~~information, ~~have been prosecuted under these laws for allegedly providing free product to customers with the expectation~~many ~~that~~of ~~the~~which ~~customers~~differ ~~would~~from ~~bill~~each ~~federal~~other ~~programs~~in ~~for~~significant ~~the~~ways ~~product.~~and ~~Other~~often ~~companies~~are ~~have~~not ~~been~~pre-empted ~~prosecuted~~by ~~for causing false claims to be submitted because of the company’s marketing of the product for unapproved~~HIPAA, ~~and~~ thus ~~non-reimbursable,~~requiring ~~uses~~additional compliance efforts.

~~The federal~~Because ~~Health~~of ~~Insurance~~the ~~Portability~~breadth ~~and Accountability Act~~ of ~~1996,~~these orlaws ~~HIPAA,~~and ~~which,~~the ~~among~~narrowness of ~~other~~the ~~things~~safe harbors, ~~imposes~~it ~~criminal~~is ~~liability for~~possible ~~executing~~that orsome ~~attempting~~business toactivities ~~execute~~can abe ~~scheme~~subject to ~~defraud~~challenge ~~any~~under ~~healthcare~~one ~~benefit~~or ~~program,~~more ~~including~~of ~~private~~such ~~third-party~~laws. ~~payors,~~The ~~knowingly~~scope and ~~willfully~~enforcement ~~embezzling~~of oreach ~~stealing~~of ~~from~~these alaws ~~healthcare~~is ~~benefit~~uncertain ~~program, willfully obstructing a criminal investigation of a healthcare offense,~~ and ~~creates~~subject ~~federal~~to ~~criminal~~rapid ~~laws~~change ~~that~~in ~~prohibit~~the ~~knowingly~~current ~~and~~environment ~~willfully~~of ~~falsifying~~healthcare reform, ~~concealing or covering up a material fact~~especially orin ~~making~~light ~~any~~of ~~materially~~the ~~false,~~lack ~~fictitious~~of orapplicable ~~fraudulent~~precedent ~~statements~~and orregulations. ~~representations,~~Federal orand ~~making~~state orenforcement ~~using~~bodies ~~any~~have ~~false~~recently ~~writing~~increased ortheir ~~document~~scrutiny ~~knowing~~of ~~the~~interactions ~~same~~between tohealthcare ~~contain~~companies ~~any~~and ~~materially~~healthcare ~~false~~providers, ~~fictitious~~which orhas ~~fraudulent~~led ~~statement~~to ora ~~entry~~number inof ~~connection~~investigations, ~~with the delivery of~~prosecutions, orconvictions ~~payment~~and ~~for,~~settlements ~~benefits,~~in ~~items~~the orhealthcare ~~services~~industry.

~~HIPAA, as~~Ensuring ~~amended~~that bybusiness ~~the~~arrangements ~~Health~~with ~~Information~~third parties ~~Technology~~comply ~~and~~with ~~Clinical~~applicable ~~Health~~healthcare ~~Act~~laws ofand ~~2009,~~regulations oris ~~HITECH,~~costly and ~~its~~time ~~implementing~~consuming. ~~regulations,~~If ~~which~~business ~~impose certain~~operations ~~requirements~~are ~~relating~~found to ~~the~~be ~~privacy,~~in violation ~~security,~~of ~~transmission~~any ~~and~~of ~~breach~~the ~~reporting~~laws ofdescribed ~~individually~~above ~~identifiable~~or ~~health~~any ~~information upon~~other ~~entities~~applicable ~~subject~~governmental toregulations ~~the~~a ~~law,~~pharmaceutical ~~such~~manufacturer asmay ~~health~~be ~~plans~~subject to penalties, ~~healthcare~~including ~~clearinghouses~~civil, criminal and ~~healthcare~~administrative ~~providers~~penalties, ~~and~~damages, ~~their~~fines, ~~respective~~disgorgement, ~~business associates~~individual ~~that~~imprisonment, ~~perform~~exclusion from ~~services~~governmental ~~for~~funded ~~them~~healthcare ~~that~~programs, ~~involve~~such ~~individually~~as ~~identifiable~~Medicare ~~health~~and ~~information.~~Medicaid, ~~HITECH~~contractual ~~also~~damages, ~~created~~reputational ~~new~~harm, ~~tiers~~diminished ofprofits ~~civil~~and ~~monetary~~future ~~penalties~~earnings, ~~amended~~additional ~~HIPAA~~reporting toobligations ~~make~~and ~~civil~~oversight ~~and~~if ~~criminal~~subject ~~penalties~~to ~~directly~~a ~~applicable~~corporate tointegrity ~~business~~agreement ~~associates,~~or ~~and~~other ~~gave~~agreement ~~state~~to ~~attorneys~~resolve ~~general~~allegations ~~new~~of ~~authority~~non-compliance towith ~~file~~these ~~civil~~laws, ~~actions~~and ~~for~~curtailment ~~damages~~ or ~~injunctions~~restructuring inof ~~U.S.~~operations, ~~federal~~any ~~courts~~of towhich ~~enforce~~could ~~the~~adversely ~~federal HIPAA~~affect ~~laws~~a ~~and~~pharmaceutical ~~seek attorneys~~manufacturer’s ~~fees~~ability ~~and~~to ~~costs~~operate ~~associated~~its ~~with~~business ~~pursuing~~and ~~federal~~the ~~civil~~results ~~actions~~of its operations.

~~The federal~~Healthcare ~~physician~~Reform ~~payment~~in ~~transparency requirements, sometimes referred to as~~ the “Physician Payments Sunshine Act,” and its implementing regulations, which require certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions) to report annually to the United States Department of Health and Human Services, or HHS, information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors) and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members.

~~State~~ In the United States, there have been, and ~~foreign~~continue to ~~law~~be, ~~equivalents~~a number of ~~each~~legislative ofand regulatory changes and proposed changes to the ~~above~~healthcare ~~federal~~system ~~laws~~that could affect the future results of pharmaceutical manufactures’ operations. In particular, ~~such~~there ashave ~~anti-kickback~~been and ~~false~~continue ~~claims~~to ~~laws,~~be a number of initiatives at the federal and state levels that ~~may~~seek ~~impose~~to ~~similar~~reduce healthcare costs. Most recently, the Patient Protection and Affordable Care Act, or PPACA, was enacted ~~more~~in ~~prohibitive~~March ~~restrictions~~2010, ~~and~~which ~~may~~includes ~~apply~~measures to ~~items~~significantly orchange ~~services~~the ~~reimbursed~~way byhealthcare ~~non-governmental~~is ~~third-party~~financed ~~payors,~~by ~~including~~both governmental and private insurers. Among the provisions of the PPACA of greatest importance to the pharmaceutical and biotechnology industry are the following:

11● an annual, nondeductible fee on any entity that manufactures or imports certain branded prescription drugs and biologic agents, apportioned among these entities according to their market share in certain government healthcare programs;

~~State and~~● ~~foreign~~implementation ~~laws~~of ~~that require pharmaceutical companies to implement compliance programs, comply with~~ the ~~pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the~~ federal ~~government,~~physician orpayment totransparency ~~track and report gifts~~requirements, ~~compensation~~ ~~and~~sometimes ~~other~~referred ~~remuneration provided~~ to ~~physicians~~as ~~and other healthcare providers, and other federal, state and foreign laws that govern~~ the ~~privacy~~“Physician ~~and~~Payments ~~security~~Sunshine of health information or personally identifiable information in certain circumstances, including state health information privacy and data breach notification laws which govern the collection, use, disclosure, and protection of health-related and other personal information, many of which differ from each other in significant ways and often are not pre-empted by HIPAA, thus requiring additional compliance efforts.Act”;

~~Because of~~● the breadth of these laws and the narrowness of the safe harbors, it is possible that some business activities can be subject to challenge under one or more of such laws. The scope and enforcement of each of these laws is uncertain and subject to rapid change in the current environment of healthcare reform, especially in light of the lack of applicable precedent and regulations. Federal and state enforcement bodies have recently increased their scrutiny of interactions between healthcare companies and healthcare providers, which has led to a ~~number~~licensure offramework ~~investigations,~~for ~~prosecutions,~~follow-on ~~convictions~~biologic ~~and settlements in the healthcare industry.~~products;

~~Ensuring that~~● business arrangements with third parties comply with applicable healthcare laws and regulations is costly and time consuming. If business operations are found to be in violation of any of the laws described above or any other applicable governmental regulations a ~~pharmaceutical~~new ~~manufacturer~~Patient-Centered ~~may~~Outcomes beResearch ~~subject~~Institute to ~~penalties~~oversee, ~~including~~identify ~~civil,~~priorities ~~criminal and administrative penalties~~in, ~~damages, fines, disgorgement, individual imprisonment, exclusion from governmental funded healthcare programs, such as Medicare~~ and ~~Medicaid,~~conduct ~~contractual~~comparative ~~damages, reputational~~clinical ~~harm,~~effectiveness ~~diminished profits and future earnings~~research, ~~additional~~along ~~reporting obligations and oversight if subject to a corporate integrity agreement or other agreement to resolve allegations of non-compliance~~ with ~~these~~funding ~~laws,~~for ~~and~~such ~~curtailment or restructuring of operations, any of which could adversely affect a pharmaceutical manufacturer’s ability to operate its business and the results of its operations.~~research;

~~Healthcare Reform~~● inestablishment of a Center for Medicare Innovation at the ~~United~~Centers ~~States~~for Medicare & Medicaid Services to test innovative payment and service delivery models to lower Medicare and Medicaid spending, potentially including prescription drug spending;

~~In the~~● ~~United~~an ~~States,~~increase ~~there~~in ~~have~~the ~~been,~~statutory ~~and~~minimum ~~continue~~rebates ~~to be,~~ a ~~number~~manufacturer ofmust ~~legislative~~pay ~~and~~under ~~regulatory~~the ~~changes~~Medicaid ~~and~~Drug ~~proposed~~Rebate ~~changes~~Program, to ~~the healthcare system that could affect the future results of pharmaceutical manufactures’ operations~~23.1% ~~In particular, there have been~~ and ~~continue to~~13% ~~be a number~~ of ~~initiatives at~~ the ~~federal~~average ~~and~~manufacturer ~~state~~price ~~levels~~for ~~that~~most ~~seek~~branded toand ~~reduce~~generic ~~healthcare costs. Most recently~~drugs, ~~the~~respectively ~~Patient Protection~~ and ~~Affordable~~capped ~~Care Act, or PPACA, was enacted in March 2010, which includes measures to significantly change~~ the ~~way~~total ~~healthcare~~rebate isamount ~~financed by~~for ~~both~~innovator ~~governmental~~drugs ~~and~~at ~~private~~100% ~~insurers. Among the provisions~~ of the ~~PPACA~~Average ofManufacturer ~~greatest~~Price, ~~importance~~or ~~to the pharmaceutical and biotechnology industry are the following:~~AMP;

● ana ~~annual,~~new ~~nondeductible~~methodology ~~fee~~by onwhich ~~any~~rebates ~~entity~~owed ~~that~~by ~~manufactures~~manufacturers orunder ~~imports~~the ~~certain~~Medicaid ~~branded~~Drug ~~prescription~~Rebate ~~drugs~~Program ~~and~~are ~~biologic~~calculated ~~agents,~~for ~~apportioned~~certain ~~among~~drugs ~~these~~and ~~entities~~biologics, ~~according~~including toour ~~their~~product ~~market~~candidates, ~~share~~that inare ~~certain~~inhaled, ~~government~~infused, ~~healthcare~~instilled, ~~programs~~implanted or injected;

~~● implementation of the federal physician payment transparency requirements, sometimes referred to as the “Physician Payments Sunshine Act”;~~12

● aextension ~~licensure~~of ~~framework~~manufacturers’ ~~for~~Medicaid ~~follow-on~~rebate ~~biologic~~liability ~~products~~to covered drugs dispensed to individuals who are enrolled in Medicaid managed care organizations;

● aexpansion ~~new~~of ~~Patient-Centered~~eligibility ~~Outcomes~~criteria ~~Research~~for ~~Institute~~Medicaid toprograms ~~oversee~~by, ~~identify~~among ~~priorities~~other inthings, allowing states to offer Medicaid coverage to additional individuals and ~~conduct~~by ~~comparative~~adding ~~clinical~~new ~~effectiveness~~mandatory ~~research,~~eligibility ~~along~~categories for individuals with ~~funding~~income ~~for~~at ~~such~~or ~~research~~below 133% of the federal poverty level, thereby potentially increasing manufacturers’ Medicaid rebate liability;

● ~~establishment of~~ a ~~Center~~new ~~for~~ Medicare ~~Innovation~~Part atD ~~the~~coverage ~~Centers~~gap ~~for~~discount ~~Medicare~~program, &in ~~Medicaid~~which ~~Services~~manufacturers must agree to ~~test~~offer ~~innovative~~50% ~~payment~~point-of-sale ~~and~~discounts ~~service~~off ~~delivery~~negotiated ~~models~~prices of applicable brand drugs to ~~lower~~eligible ~~Medicare~~beneficiaries ~~and~~during ~~Medicaid~~their ~~spending~~coverage gap period, ~~potentially~~as ~~including~~a ~~prescription~~condition ~~drug~~for ~~spending~~the manufacturer’s outpatient drugs to be covered under Medicare Part D; and

● anexpansion ~~increase in the statutory minimum rebates a manufacturer must pay under the Medicaid Drug Rebate Program, to 23.1% and 13%~~ of the ~~average~~entities ~~manufacturer~~eligible ~~price~~ for ~~most~~discounts ~~branded~~under ~~and generic drugs, respectively and capped~~ the ~~total~~Public ~~rebate~~Health ~~amount for innovator drugs at 100% of the Average Manufacturer Price, or AMP;~~program.

●Some aof ~~new~~the ~~methodology~~provisions byof ~~which~~the ~~rebates~~PPACA ~~owed~~have byyet ~~manufacturers~~to be ~~under~~implemented, ~~the~~and ~~Medicaid~~there ~~Drug~~have ~~Rebate~~been ~~Program~~legal ~~are~~and ~~calculated~~political ~~for~~challenges to certain ~~drugs~~aspects of the PPACA. Since January 2017, former President Trump has signed two executive orders and ~~biologics~~other directives designed to delay, ~~including~~circumvent, ~~our~~or ~~product~~loosen ~~candidates~~certain requirements mandated by the PPACA. Concurrently, Congress has considered legislation that ~~are~~would ~~inhaled~~repeal or repeal and replace all or part of the PPACA. While Congress has not passed repeal legislation, ~~infused~~the Tax Cuts and Jobs Act of 2017 includes a provision repealing, ~~instilled~~effective January 1, ~~implanted~~2019, the tax-based shared responsibility payment imposed by the PPACA on certain individuals who fail to maintain qualifying health coverage for all or ~~injected;~~part of a year that is commonly referred to as the “individual mandate”. Congress may consider other legislation to repeal or replace elements of the PPACA.

12Many of the details regarding the implementation of the PPACA are yet to be determined, and at this time, the full effect that the PPACA would have on a pharmaceutical manufacturer remains unclear. In particular, there is uncertainty surrounding the applicability of the biosimilars provisions under the PPACA. The FDA has issued several guidance documents, but no implementing regulations, on biosimilars. A number of biosimilar applications have been approved over the past few years. The regulations that are ultimately promulgated and their implementation are likely to have considerable impact on the way pharmaceutical manufacturers conduct their business and may require changes to current strategies. A biosimilar is a biological product that is highly similar to an approved drug notwithstanding minor differences in clinically inactive components, and for which there are no clinically meaningful differences between the biological product and the approved drug in terms of the safety, purity, and potency of the product.

●Individual ~~extension~~states ofhave ~~manufacturers’~~become ~~Medicaid~~increasingly ~~rebate~~aggressive in ~~liability~~passing legislation and implementing regulations designed to ~~covered~~control ~~drugs~~pharmaceutical ~~dispensed~~and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access, and marketing cost disclosure and transparency measures, and to ~~individuals~~encourage ~~who~~importation from other countries and bulk purchasing. Legally mandated price controls on payment amounts by third-party payors or other restrictions could harm a pharmaceutical manufacturer’s business, results of operations, financial condition and prospects. In addition, regional healthcare authorities and individual hospitals are ~~enrolled~~increasingly using bidding procedures to determine what pharmaceutical products and which suppliers will be included in ~~Medicaid~~their ~~managed~~prescription ~~care~~drug ~~organizations;~~and other healthcare programs. This could reduce ultimate demand for certain products or put pressure product pricing, which could negatively affect a pharmaceutical manufacturer’s business, results of operations, financial condition and prospects.

●In ~~expansion~~addition, given recent federal and state government initiatives directed at lowering the total cost of ~~eligibility~~healthcare, ~~criteria~~Congress ~~for~~and state legislatures will likely continue to focus on healthcare reform, the cost of prescription drugs and biologics and the reform of the Medicare and Medicaid programs. byWhile no one cannot predict the full outcome of any such legislation, ~~among~~it ~~other~~may ~~things~~result in decreased reimbursement for drugs and biologics, ~~allowing~~which ~~states~~may further exacerbate industry-wide pressure to ~~offer~~reduce ~~Medicaid~~prescription ~~coverage~~drug prices. This could harm a pharmaceutical manufacturer’s ability to ~~additional~~generate ~~individuals~~revenue. Increases in importation or re-importation of pharmaceutical products from foreign countries into the United States could put competitive pressure on a pharmaceutical manufacturer’s ability to profitably price products, which, in turn, could adversely affect business, results of operations, financial condition and byprospects. ~~adding~~A ~~new~~pharmaceutical ~~mandatory~~manufacturer ~~eligibility~~might ~~categories~~elect ~~for~~not ~~individuals~~to ~~with~~seek ~~income~~approval atfor or ~~below~~market products ~~133%~~in offoreign jurisdictions in order to minimize the ~~federal~~risk ~~poverty~~of ~~level~~re-importation, ~~thereby~~which ~~potentially~~could ~~increasing~~also ~~manufacturers’~~reduce ~~Medicaid~~the ~~rebate~~revenue ~~liability;~~generated from product sales. It is also possible that other legislative proposals having similar effects will be adopted.

●Furthermore, aregulatory ~~new~~authorities’ ~~Medicare~~assessment of ~~Part~~the Ddata ~~coverage~~and ~~gap~~results ~~discount~~required ~~program,~~to indemonstrate ~~which~~safety ~~manufacturers~~and ~~must~~efficacy ~~agree~~can tochange ~~offer~~over ~~50%~~time ~~point-of-sale~~and ~~discounts~~can ~~off~~be ~~negotiated~~affected ~~prices~~by many factors, such as the emergence of ~~applicable~~new ~~brand~~information, ~~drugs~~including toon ~~eligible~~other ~~beneficiaries~~products, ~~during~~changing ~~their~~policies ~~coverage~~and ~~gap~~agency ~~period~~funding, asstaffing aand ~~condition~~leadership. ~~for~~No one can be sure whether future changes to the ~~manufacturer’s~~regulatory ~~outpatient~~environment ~~drugs~~will be favorable or unfavorable to business prospects. For example, average review times at the FDA for marketing approval applications can be ~~covered~~affected ~~under~~by ~~Medicare~~a ~~Part~~variety D;of factors, including budget and funding levels and statutory, regulatory and policy changes.

~~● expansion of the entities eligible for discounts under the Public Health program.~~13

~~Some~~International of the provisions of the PPACA have yet to be implemented, and there have been legal and political challenges to certain aspects of the PPACA. Since January 2017, former President Trump has signed two executive orders and other directives designed to delay, circumvent, or loosen certain requirements mandated by the PPACA. Concurrently, Congress has considered legislation that would repeal or repeal and replace all or part of the PPACA. While Congress has not passed repeal legislation, the Tax Cuts and Jobs Act of 2017 includes a provision repealing, effective January 1, 2019, the tax-based shared responsibility payment imposed by the PPACA on certain individuals who fail to maintain qualifying health coverage for all or part of a year that is commonly referred to as the “individual mandate”. Congress may consider other legislation to repeal or replace elements of the PPACA.Regulations

~~Many of~~In ~~the~~addition ~~details~~to ~~regarding~~regulations in the ~~implementation~~United ofStates, we ~~the~~are ~~PPACA~~and ~~are~~will ~~yet~~be subject to bea ~~determined,~~variety ~~and~~of atforeign ~~this~~regulations ~~time~~regarding development, ~~the~~approval, ~~full~~commercial ~~effect~~sales ~~that~~and ~~the~~distribution ~~PPACA~~of ~~would~~our ~~have~~products. onWhether aor ~~pharmaceutical~~not ~~manufacturer~~we ~~remains~~obtain ~~unclear.~~FDA Inapproval ~~particular,~~for ~~there~~a isproduct, ~~uncertainty~~we ~~surrounding~~must obtain the ~~applicability~~necessary ofapprovals by the ~~biosimilars~~comparable regulatory authorities ~~provisions~~of ~~under~~foreign ~~the~~countries ~~PPACA.~~before ~~The~~we ~~FDA~~can ~~has~~commence ~~issued~~clinical ~~several~~trials ~~guidance~~or ~~documents,~~marketing ~~but~~of nothe ~~implementing~~product ~~regulations,~~in onthose ~~biosimilars~~countries. AThe ~~number~~approval process varies offrom ~~biosimilar~~country ~~applications~~to ~~have~~country ~~been~~and ~~approved~~can ~~over~~involve ~~the~~additional ~~past~~product ~~few~~testing ~~years.~~and ~~The~~additional ~~regulations~~review ~~that~~periods, ~~are~~and ~~ultimately~~the ~~promulgated~~time ~~and~~may ~~their~~be ~~implementation~~longer or shorter ~~are~~than ~~likely~~that required to ~~have~~obtain ~~considerable~~FDA ~~impact~~approval. onThe ~~the~~requirements ~~way~~governing, ~~pharmaceutical~~among ~~manufacturers~~other things, the conduct ~~their~~of ~~business~~clinical trials, product licensing, pricing and ~~may~~reimbursement ~~require~~vary ~~changes~~greatly from country to ~~current strategies~~country. ARegulatory ~~biosimilar~~approval isin one country does not ensure regulatory approval in another, but a ~~biological~~failure ~~product~~or ~~that~~delay isin ~~highly~~obtaining ~~similar~~regulatory toapproval anin ~~approved~~one ~~drug~~country ~~notwithstanding~~may ~~minor~~negatively ~~differences~~impact the regulatory process in ~~clinically~~others. ~~inactive~~If ~~components,~~we ~~and~~fail ~~for~~to ~~which~~comply ~~there~~with ~~are~~applicable noforeign ~~clinically~~regulatory ~~meaningful~~requirements, ~~differences~~we ~~between~~may ~~the~~be ~~biological~~subject ~~product~~to ~~and~~fines, ~~the~~suspension ~~approved~~or ~~drug in~~withdrawal ~~terms~~ of ~~the~~regulatory approvals, ~~safety~~product recalls, ~~purity~~seizure of products, ~~and~~operating ~~potency~~restrictions ofand ~~the~~criminal ~~product~~prosecution.

~~Individual states~~To ~~have~~obtain ~~become~~regulatory ~~increasingly~~approval ~~aggressive~~of inan ~~passing~~investigational drug ~~legislation~~under ~~and~~European ~~implementing~~Union ~~regulations~~regulatory ~~designed~~systems, towe ~~control~~must ~~pharmaceutical~~submit ~~and biological~~a ~~product~~marketing ~~pricing,~~authorization ~~including~~application. ~~price~~The orapplication ~~patient~~used ~~reimbursement~~to ~~constraints,~~file ~~discounts,~~the ~~restrictions~~NDA in onthe ~~certain~~United ~~product~~States ~~access, and~~is ~~marketing~~similar ~~cost~~to ~~disclosure~~that ~~and~~required ~~transparency~~in ~~measures~~Europe, ~~and~~with tothe ~~encourage~~exception ~~importation~~of, ~~from~~among other ~~countries~~things, ~~and~~country-specific ~~bulk~~document ~~purchasing~~requirements. ~~Legally~~ ~~mandated~~For ~~price~~other ~~controls~~countries onoutside ~~payment~~of ~~amounts~~the byEuropean ~~third-party~~Union, ~~payors~~such oras ~~other~~countries ~~restrictions~~in ~~could~~Eastern ~~harm~~Europe, aLatin ~~pharmaceutical~~America ~~manufacturer’s business~~or Asia, ~~results~~the ofrequirements ~~operations,~~governing the ~~financial~~conduct ~~condition~~of ~~and~~clinical ~~prospects.~~trials, Inproduct ~~addition~~licensing, ~~regional~~pricing ~~healthcare authorities~~ and ~~individual~~reimbursement ~~hospitals are~~vary ~~increasingly~~from ~~using~~country ~~bidding procedures~~ to ~~determine~~country. ~~what~~In ~~pharmaceutical~~all ~~products~~cases, ~~and~~again, ~~which~~the ~~suppliers~~clinical trials ~~will~~are beconducted ~~included~~ in ~~their~~accordance ~~prescription drug~~with GCP and ~~other~~the ~~healthcare~~applicable ~~programs.~~regulatory ~~This~~requirements ~~could~~and ~~reduce~~the ~~ultimate~~ethical ~~demand~~principles ~~for~~that ~~certain~~have ~~products~~their ~~or put pressure product pricing, which could~~origin ~~negatively~~in ~~affect~~the aDeclaration ~~pharmaceutical manufacturer’s business, results~~ of ~~operations, financial condition and prospects~~Helsinki.

~~In addition,~~If ~~given~~we ~~recent~~fail ~~federal~~to ~~and~~comply ~~state~~with ~~government~~applicable ~~initiatives~~foreign ~~directed at lowering the total cost of healthcare~~regulatory requirements, ~~Congress~~we ~~and~~may ~~state legislatures~~be ~~will~~subject ~~likely continue~~ to ~~focus on healthcare reform~~, ~~the~~among ~~cost~~other ~~of prescription drugs and biologics and the reform of the Medicare and Medicaid programs. While no one cannot predict the full outcome of any such legislation~~things, ~~it may result in decreased reimbursement for drugs and biologics~~fines, ~~which~~suspension ~~may further exacerbate industry-wide pressure to reduce prescription drug prices. This could harm a pharmaceutical manufacturer’s ability to generate revenue. Increases in importation~~ or ~~re-importation~~withdrawal of ~~pharmaceutical~~regulatory ~~products from foreign countries into the United States could put competitive pressure on a pharmaceutical manufacturer’s ability to profitably price products~~approvals, ~~which,~~product ~~in turn~~recalls, ~~could adversely affect business, results~~ seizure of ~~operations~~products, ~~financial~~operating ~~condition~~restrictions and ~~prospects.~~criminal A pharmaceutical manufacturer might elect not to seek approval for or market products in foreign jurisdictions in order to minimize the risk of re-importation, which could also reduce the revenue generated from product salesprosecution. ~~It is also possible that other legislative proposals having similar effects will be adopted.~~

~~Furthermore, regulatory~~Centralized authorities’ assessment of the data and results required to demonstrate safety and efficacy can change over time and can be affected by many factors, such as the emergence of new information, including on other products, changing policies and agency funding, staffing and leadership. No one can be sure whether future changes to the regulatory environment will be favorable or unfavorable to business prospects. For example, average review times at the FDA for marketing approval applications can be affected by a variety of factors, including budget and funding levels and statutory, regulatory and policy changes.Procedure

13The European Medicines Agency, or EMA, implemented the centralized procedure for the approval of human medicines to facilitate marketing authorizations that are valid throughout the EU. This procedure results in a single marketing authorization issued by the European Commission following a favorable opinion by the EMA that is valid across the European Union, as well as Iceland, Liechtenstein, and Norway. The centralized procedure is compulsory for human medicines that are: derived from biotechnology processes, such as genetic engineering, contain a new active substance indicated for the treatment of certain diseases, such as HIV/AIDS, cancer, diabetes, neurodegenerative disorders or autoimmune diseases and other immune dysfunctions, and officially designated orphan medicines. For medicines that do not fall within these categories, an applicant has the option of submitting an application for a centralized marketing authorization to the EMA, as long as the medicine concerned is a significant therapeutic, scientific or technical innovation, or if its authorization would be in the interest of public health.

~~International~~There are also two other possible routes to authorize ~~Regulations~~medicinal products in several European Union countries, which are available for investigational medicinal products that fall outside the scope of the centralized procedure: the decentralized procedure and the mutual recognition procedure. Under the decentralized procedure, an applicant may apply for simultaneous authorization in more than one EU country for medicinal products that have not yet been authorized in any EU country and that do not fall within the mandatory scope of the centralized procedure. Under the mutual recognition procedure, a medicine is first authorized in one EU Member State, in accordance with the national procedures of that country. Following a national authorization, the applicant may seek further marketing authorizations from other EU countries under a procedure whereby the countries concerned agree to recognize the validity of the original, national marketing authorization.

In ~~addition~~ ~~to regulations in~~ the ~~United States~~EU, wemedicinal ~~are~~products ~~and~~designated ~~will~~as ~~be subject to a variety of foreign regulations regarding development, approval,~~orphan ~~commercial~~drug ~~sales and distribution of our~~ products. ~~Whether~~benefit orfrom ~~not~~financial weincentives ~~obtain~~such ~~FDA~~as ~~approval~~reductions ~~for~~in amarketing ~~product,~~authorization weapplication ~~must~~fees ~~obtain~~or ~~the~~fee ~~necessary approvals~~waivers byand ~~the~~10 ~~comparable regulatory authorities~~ years of ~~foreign countries before we can commence clinical trials or~~ marketing ofexclusivity ~~the~~following medicinal product in ~~those countries~~approval. ~~The~~For ~~approval~~a ~~process~~medicinal ~~varies~~product ~~from country~~ to ~~country~~qualify ~~and~~as ~~can~~orphan ~~involve~~drugs: ~~additional~~(i) ~~product~~it ~~testing~~must ~~and~~be ~~additional review~~intended ~~periods,~~for ~~and~~ the ~~time~~treatment, ~~may~~prevention beor ~~longer~~diagnosis orof ~~shorter~~a ~~than~~disease that ~~required~~is tolife-threatening ~~obtain~~or ~~FDA~~chronically ~~approval.~~debilitating; ~~The~~(ii) ~~requirements governing, among other things,~~ the ~~conduct~~prevalence of ~~clinical trials, product licensing, pricing and reimbursement vary greatly from country to country. Regulatory approval~~the condition in ~~one~~the ~~country~~EU ~~does~~must not ~~ensure~~be ~~regulatory~~more ~~approval~~than five in ~~another~~10,000 ~~but~~or ait ~~failure~~must orbe ~~delay~~unlikely inthat ~~obtaining~~marketing ~~regulatory~~of ~~approval~~the inmedicine ~~one~~would ~~country~~generate sufficient ~~may~~returns ~~negatively~~to ~~impact~~justify the ~~regulatory~~investment ~~process~~needed infor ~~others.~~its Ifdevelopment; weand ~~fail~~(iii) tono ~~comply~~satisfactory ~~with~~method ~~applicable~~of ~~foreign~~diagnosis, ~~regulatory~~prevention ~~requirements,~~or wetreatment ~~may~~of bethe ~~subject~~condition toconcerned ~~fines,~~can ~~suspension~~be authorized, or, ~~withdrawal~~if ofsuch ~~regulatory~~a ~~approvals~~method exists, ~~product~~the ~~recalls,~~medicine ~~seizure~~must be of ~~products,~~significant ~~operating~~benefit ~~restrictions~~to ~~and~~those affected ~~criminal~~by ~~prosecution~~the condition.

To obtain regulatory approval of an investigational drug under European Union regulatory systems, we must submit a marketing authorization application. The application used to file the NDA in the United States is similar to that required in Europe, with the exception of, among other things, country-specific document requirements. For other countries outside of the European Union, such as countries in Eastern Europe, Latin America or Asia, the requirements governing the conduct of clinical trials, product licensing, pricing and reimbursement vary from country to country. In all cases, again, the clinical trials are conducted in accordance with GCP and the applicable regulatory requirements and the ethical principles that have their origin in the Declaration of Helsinki.14

~~If we~~Other ~~fail~~Regulations to comply with applicable foreign regulatory requirements, we may be subject to, among other things, fines, suspension or withdrawal of regulatory approvals, product recalls, seizure of products, operating restrictions and criminal prosecution.

~~Centralized~~We are also subject to numerous federal, state ~~Procedure~~and local laws relating to such matters as safe working conditions, manufacturing practices, environmental protection, fire hazard control, and disposal of hazardous or potentially hazardous substances and biological materials. We may incur significant costs to comply with such laws and regulations now or in the future.

The European Medicines Agency, or EMA, implemented the centralized procedure for the approval of human medicines to facilitate marketing authorizations that are valid throughout the EU. This procedure results in a single marketing authorization issued by the European Commission following a favorable opinion by the EMA that is valid across the European Union, as well as Iceland, Liechtenstein, and Norway. The centralized procedure is compulsory for human medicines that are: derived from biotechnology processes, such as genetic engineering, contain a new active substance indicated for the treatment of certain diseases, such as HIV/AIDS, cancer, diabetes, neurodegenerative disorders or autoimmune diseases and other immune dysfunctions, and officially designated orphan medicines. For medicines that do not fall within these categories, an applicant has the option of submitting an application for a centralized marketing authorization to the EMA, as long as the medicine concerned is a significant therapeutic, scientific or technical innovation, or if its authorization would be in the interest of public health.Reimbursement

~~There are~~Obtaining ~~also~~coverage ~~two~~and ~~other~~reimbursement ~~possible~~approval for ~~routes~~a toproduct ~~authorize~~from ~~medicinal~~a ~~products~~government inor ~~several~~other ~~European~~third-party ~~Union~~payor ~~countries,~~is ~~which~~a ~~are~~time-consuming ~~available~~and ~~for~~costly ~~investigational medicinal~~process ~~products~~ that ~~fall~~can ~~outside~~require the ~~scope~~provision of ~~the~~supporting scientific, ~~centralized~~clinical ~~procedure:~~and ~~the~~cost ~~decentralized~~effectiveness ~~procedure~~data ~~and~~for the ~~mutual~~use ~~recognition~~of ~~procedure. Under~~drug ~~the~~or ~~decentralized~~biologic ~~procedure,~~products anto ~~applicant~~the ~~may~~payor. ~~apply~~There ~~for~~may ~~simultaneous~~be ~~authorization~~significant delays in ~~more~~obtaining ~~than~~such ~~one~~coverage EUand ~~country~~reimbursement for ~~medicinal~~newly approved products ~~that~~, ~~have~~and ~~not~~coverage ~~yet~~may ~~been~~be ~~authorized~~more inlimited ~~any~~than EUthe ~~country~~purposes ~~and~~for ~~that~~which the doproduct ~~not~~is ~~fall~~approved ~~within~~by the ~~mandatory~~FDA ~~scope~~or similar regulatory authorities outside of the ~~centralized~~United ~~procedure~~States. ~~Under~~Moreover, eligibility for coverage ~~the~~and ~~mutual~~reimbursement ~~recognition~~does ~~procedure,~~not imply that a ~~medicine~~product iswill ~~first~~be ~~authorized~~paid for in ~~one~~all EUcases ~~Member~~or ~~State~~at a rate that covers operating costs, inincluding ~~accordance~~research, development, ~~with~~intellectual ~~the~~property, ~~national~~manufacture, ~~procedures~~sale and distribution expenses. Reimbursement rates may vary according to the use of ~~that~~the ~~country.~~product ~~Following~~and athe ~~national~~clinical ~~authorization~~setting in which it is used, ~~the~~may ~~applicant~~be based on reimbursement levels already set for lower cost products and may ~~seek~~be ~~further~~incorporated ~~marketing~~into ~~authorizations~~existing ~~from~~payments for other EUservices. ~~countries~~Net ~~under~~prices for products may be reduced by mandatory discounts or rebates arequired ~~procedure~~by ~~whereby~~government ~~the~~healthcare ~~countries~~programs ~~concerned~~or ~~agree~~private topayors ~~recognize~~and ~~the~~by ~~validity~~any future relaxation of ~~the~~laws ~~original,~~that ~~national~~presently ~~marketing~~restrict ~~authorization~~imports of product from countries where they may be sold at lower prices than in the United States.

~~In the~~There ~~EU,~~is ~~medicinal~~significant ~~products~~uncertainty ~~designated~~related asto ~~orphan drug products benefit from financial incentives such as reductions in marketing authorization~~the ~~application~~insurance ~~fees~~coverage ~~or fee waivers~~ and 10reimbursement ~~years~~ of ~~marketing~~newly ~~exclusivity~~approved ~~following medicinal product approval~~products. ~~For~~Third-party apayors ~~medicinal~~often ~~product~~rely ~~to qualify~~upon asMedicare ~~orphan~~coverage ~~drugs:~~policy ~~(i)~~and itpayment limitations ~~must~~in besetting ~~intended~~their ~~for~~own ~~the~~reimbursement ~~treatment~~policies, ~~prevention~~but oralso ~~diagnosis~~have oftheir aown ~~disease~~methods ~~that~~and isapproval ~~life-threatening~~process ~~or chronically~~apart ~~debilitating;~~from ~~(ii)~~Medicare ~~the~~coverage and ~~prevalence~~reimbursement ofdeterminations. ~~the~~It ~~condition~~is indifficult ~~the~~to EUpredict ~~must~~what ~~not~~third beparty ~~more~~payors ~~than~~will ~~five~~decide inwith ~~10,000~~respect orto itcoverage ~~must~~and ~~be unlikely~~reimbursement ~~that~~for ~~marketing~~new ofdrug ~~the~~and ~~medicine~~biologic ~~would~~product ~~generate~~candidates. ~~sufficient~~An ~~returns~~inability to ~~justify~~promptly ~~the~~obtain ~~investment~~coverage ~~needed~~and ~~for~~adequate ~~its~~reimbursement ~~development;~~rates ~~and~~from ~~(iii)~~both ~~no satisfactory~~government-funded ~~method~~and ofprivate ~~diagnosis,~~payors ~~prevention~~for orany ~~treatment~~approved ofproducts ~~the~~could ~~condition~~have ~~concerned~~a ~~can~~material beadverse ~~authorized,~~effect ~~or,~~on ~~if such~~ a ~~method~~pharmaceutical ~~exists,~~manufacturer’s ~~the~~operating ~~medicine~~results, ~~must~~ability beto ofraise ~~significant~~capital ~~benefit~~needed to ~~those~~commercialize ~~affected~~products byand ~~the~~overall financial condition.

14Reimbursement may impact the demand for, and/or the price of, any product which obtains marketing approval. Even if coverage is obtained for a given product by a third-party payor, the resulting reimbursement payment rates may not be adequate or may require co-payments that patients find unacceptably high. Patients who are prescribed medications for the treatment of their conditions, and their prescribing physicians, generally rely on third-party payors to reimburse all or part of the costs associated with those medications. Patients are unlikely to use products unless coverage is provided and reimbursement is adequate to cover all or a significant portion of the cost of the products. Therefore, coverage and adequate reimbursement is critical to new product acceptance. Coverage decisions may depend upon clinical and economic standards that disfavor new drug products when more established or lower cost therapeutic alternatives are already available or subsequently become available.

~~Other~~The U.S. government, state legislatures and foreign ~~Regulations~~governmental entities have shown significant interest in implementing cost containment programs to limit the growth of government-paid healthcare costs, including price controls, restrictions on reimbursement and coverage and requirements for substitution of generic products for branded prescription drugs. Adoption of government controls and measures, and tightening of restrictive policies in jurisdictions with existing controls and measures, could exclude or limit our products from coverage and limit payments for pharmaceuticals.

~~We are~~In ~~also~~addition, ~~subject~~it tois ~~numerous~~expected ~~federal,~~that ~~state~~the ~~and~~increased ~~local~~emphasis ~~laws~~on ~~relating~~managed care toand ~~such~~cost ~~matters~~containment asmeasures ~~safe~~in ~~working~~the ~~conditions,~~United ~~manufacturing~~States ~~practices, environmental~~by ~~protection,~~third-party ~~fire~~payors ~~hazard~~and ~~control,~~government authorities will continue and ~~disposal~~place offurther pressure ~~hazardous~~on orpharmaceutical ~~potentially~~pricing ~~hazardous~~and ~~substances~~coverage. Coverage policies and ~~biological~~third-party ~~materials~~reimbursement rates may change at any time. Even if Wefavorable ~~may~~coverage ~~incur~~and ~~significant~~reimbursement ~~costs~~status tois ~~comply~~attained ~~with~~for ~~such~~one ~~laws~~or more drug products that gain regulatory approval, less favorable coverage policies and ~~regulations~~reimbursement ~~now~~rates ormay be implemented in the future.

~~Reimbursement~~15

~~Obtaining coverage~~Intellectual and reimbursement approval for a product from a government or other third-party payor is a time-consuming and costly process that can require the provision of supporting scientific, clinical and cost effectiveness data for the use of drug or biologic products to the payor. There may be significant delays in obtaining such coverage and reimbursement for newly approved products, and coverage may be more limited than the purposes for which the product is approved by the FDA or similar regulatory authorities outside of the United States. Moreover, eligibility for coverage and reimbursement does not imply that a product will be paid for in all cases or at a rate that covers operating costs, including research, development, intellectual property, manufacture, sale and distribution expenses. Reimbursement rates may vary according to the use of the product and the clinical setting in which it is used, may be based on reimbursement levels already set for lower cost products and may be incorporated into existing payments for other services. Net prices for products may be reduced by mandatory discounts or rebates required by government healthcare programs or private payors and by any future relaxation of laws that presently restrict imports of product from countries where they may be sold at lower prices than in the United States.Property

~~There is~~Our ~~significant~~success ~~uncertainty~~depends, ~~related~~in topart, ~~the~~on ~~insurance~~our ~~coverage~~ability ~~and~~to obtain, ~~reimbursement~~maintain, ofand ~~newly~~enforce ~~approved~~patents ~~products.~~and ~~Third-party~~other ~~payors~~proprietary ~~often~~protections ~~rely upon~~of ~~Medicare~~our ~~coverage~~commercially ~~policy~~important technologies and ~~payment~~product ~~limitations~~candidates, to inoperate ~~setting~~without ~~their~~infringing ~~own~~the ~~reimbursement~~proprietary ~~policies~~rights of others, ~~but~~and ~~also~~to ~~have~~maintain ~~their~~trade ~~own~~secrets ~~methods~~or ~~and approval~~other ~~process~~proprietary ~~apart~~know-how, ~~from~~both ~~Medicare~~in ~~coverage~~the United States and ~~reimbursement~~other ~~determinations~~countries. ItOur isability ~~difficult~~ to ~~predict~~stop ~~what~~ third ~~party~~parties ~~payors~~from ~~will decide~~making, ~~with~~using, ~~respect~~selling, offering to ~~coverage~~sell ~~and~~or ~~reimbursement~~importing ~~for~~our ~~new~~products will ~~drug~~depend ~~and~~on ~~biologic~~the ~~product~~extent ~~candidates.~~to Anwhich ~~inability~~we tohave ~~promptly~~rights ~~obtain~~under ~~coverage~~ valid and ~~adequate~~enforceable ~~reimbursement~~patents ~~rates~~or ~~from~~trade ~~both~~secrets ~~government-funded~~that ~~and~~protect ~~private~~these ~~payors~~activities. We ~~for~~seek ~~any~~to ~~approved~~protect ~~products~~proprietary ~~could~~technology, ~~have~~inventions, aand ~~material~~improvements ~~adverse effect~~that onare acommercially ~~pharmaceutical~~important ~~manufacturer’s~~to ~~operating~~our ~~results~~business by seeking, ~~ability~~maintaining, and todefending ~~raise~~patent ~~capital~~rights, ~~needed~~whether todeveloped ~~commercialize~~internally ~~products~~or ~~and~~licensed ~~overall financial~~from ~~condition~~third parties.

~~Reimbursement may~~We ~~impact~~have ~~the~~two ~~demand~~active ~~for,~~patent ~~and/or~~families ~~the~~relating ~~price~~to our ~~of,~~dactinomycin ~~any product which obtains marketing approval~~program. ~~Even if coverage is obtained for a given product by a third-party payor~~Currently, ~~the~~we ~~resulting~~have ~~reimbursement~~one ~~payment~~granted ~~rates~~US ~~may~~patent ~~not~~and beten ~~adequate~~pending orpatent ~~may~~applications ~~require~~in ~~co-payments~~these ~~that~~families ~~patients find~~in ~~unacceptably high. Patients who are prescribed medications for~~ the ~~treatment of their conditions~~US, ~~and their prescribing physicians~~Australia, ~~generally~~Canada, rely on third-party payors to reimburse all or part of the costs associated with those medications. Patients are unlikely to use products unless coverage is provided and reimbursement is adequate to cover all or a significant portion of the cost of the products. ThereforeEurope, ~~coverage~~ and ~~adequate reimbursement is critical to new product acceptance~~Japan. Coverage decisions may depend upon clinical and economic standards that disfavor new drug products when more established or lower cost therapeutic alternatives are already available or subsequently become available.

~~The U.S.~~We ~~government,~~also ~~state~~have ~~legislatures~~an ~~and~~exclusive ~~foreign~~license ~~governmental~~to ~~entities~~patents ~~have~~and patent ~~shown~~applications ~~significant~~across ~~interest~~seven indifferent ~~implementing~~patent ~~cost~~families ~~containment programs~~relating to ~~limit~~our ~~the~~LSD1 ~~growth~~program. ofWe ~~government-paid~~currently ~~healthcare~~have ~~costs,~~four ~~including~~granted ~~price~~patents ~~controls, restrictions on reimbursement~~ and ~~coverage~~two ~~and~~pending ~~requirements~~application ~~for~~in ~~substitution~~the ~~of generic products for branded prescription drugs~~U.S. ~~Adoption~~We ofalso ~~government~~have ~~controls~~granted ~~and~~patents ~~measures,~~ and ~~tightening~~/or ofpending ~~restrictive~~applications ~~policies~~ in ~~jurisdictions~~these ~~with~~families ~~existing~~in ~~controls~~Europe, ~~and~~Australia, ~~measures~~Brazil, Canada, ~~could~~China, ~~exclude~~Eurasia, orIndia, ~~limit~~Israel, ~~our~~Japan, ~~products~~Mexico, ~~from coverage~~ and ~~limit~~South ~~payments for pharmaceuticals~~Africa.

InThe patent positions of biotechnology companies like ours are generally uncertain and involve complex legal, scientific and factual questions. In addition, itthe coverage claimed in a patent application can be significantly reduced before the patent is ~~expected~~issued. ~~that~~Consequently, we do not know whether the ~~increased~~product ~~emphasis~~candidates we onare ~~managed~~developing ~~care~~will ~~and~~gain ~~cost~~patent ~~containment~~protection ~~measures~~or, if patents are issued, whether they will provide significant proprietary protection or will be challenged, circumvented, invalidated, or found to be unenforceable. Because patent applications in the United States byand ~~third-party~~certain ~~payors~~other ~~and~~jurisdictions ~~government~~are ~~authorities~~maintained ~~will~~in ~~continue~~secrecy for 18 months, and ~~place~~since ~~further~~publication ~~pressure~~of ondiscoveries ~~pharmaceutical~~in ~~pricing~~the ~~and~~scientific ~~coverage.~~or ~~Coverage~~patent ~~policies~~literature ~~and~~often lags behind actual discoveries, we cannot be certain of the priority of inventions or filing dates covered by pending patent applications. Moreover, we may have to participate in post-grant proceedings, interference proceedings, or third-party ~~reimbursement~~ex ~~rates~~parte ~~may~~or ~~change~~inter atpartes reexamination ~~any~~proceedings ~~time~~before the U.S. ~~Even~~Patent ifand ~~favorable~~Trademark ~~coverage~~Office, ~~and~~or ~~reimbursement~~in ~~status~~opposition isproceedings ~~attained~~in ~~for~~a ~~one~~foreign orpatent office, any of ~~more~~which ~~drug~~could ~~products~~result ~~that~~in ~~gain~~substantial ~~regulatory~~cost ~~approval~~to us, ~~less~~even if the eventual outcome is favorable ~~coverage~~to ~~policies~~us. There can be no assurance that the patents, if issued, would be held valid and ~~reimbursement~~enforceable ~~rates~~by ~~may~~a court of competent jurisdiction. An adverse outcome could subject us to significant liabilities to third parties, require disputed rights to be ~~implemented~~licensed infrom third parties or require us to cease using specific compounds or technology. To the extent prudent, we intend to bring litigation against third parties that we believe are infringing one or more of ~~future~~our patents or other intellectual property rights.

15The term of individual patents depends upon the legal term of the patents in the countries in which they are obtained. In most countries in which we file, the patent term is 20 years from the earliest date of filing a non-provisional patent application. In the United States, a patent term may be lengthened by patent term adjustment, which compensates a patentee for administrative delays by the U.S. Patent and Trademark Office in granting a patent, or may be shortened if a patent is terminally disclaimed over another patent. Certain of our patents currently benefit from patent term adjustment and some of our patents issuing in the future may benefit from patent term adjustment.

~~Intellectual~~The patent term of a patent that covers an FDA-approved ~~Property~~product may also be eligible for patent term extension, which permits patent term restoration as compensation for the patent term lost during the FDA regulatory review process. The Drug Price Competition and Patent Term Restoration Act of 1984, or the Hatch-Waxman Act, permits a patent term extension of up to five years beyond the expiration of the patent. The length of the patent term extension is related to the length of time the product is under regulatory review. Patent term extension cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval and only one patent applicable to an approved product may be extended. Similar provisions are available in Europe and other non-U.S. jurisdictions to extend the term of a patent that covers an approved product. In the future, if and when our product candidates receive FDA approval, we expect to apply for patent-term extensions on patents covering those products.

~~Our success~~To ~~depends,~~protect inour ~~part,~~rights onto any of our ~~ability~~issued topatents and ~~obtain,~~proprietary ~~maintain~~information, ~~and~~we ~~enforce~~may ~~patents~~need ~~and~~to ~~other~~litigate ~~proprietary~~against ~~protections~~infringing third parties, or avail ourselves of ~~our~~the ~~commercially~~courts or participate ~~important~~in ~~technologies~~hearings ~~and~~to ~~product~~determine ~~candidates,~~the toscope ~~operate~~and ~~without~~validity ~~infringing~~of ~~the~~those patents or other proprietary rights. ofThese ~~others,~~types ~~and~~of toproceedings ~~maintain~~are ~~trade~~often costly ~~secrets~~and orcould ~~other~~be ~~proprietary~~very ~~know~~time-~~how~~consuming to us, ~~both~~and inthere ~~the~~can ~~United~~be ~~States~~no ~~and~~assurance ~~other~~that ~~countries.~~the ~~Our~~deciding ~~ability~~authorities towill ~~stop~~rule ~~third~~in ~~parties~~our ~~from~~favor. ~~making,~~An unfavorable ~~using,~~decision ~~selling,~~could ~~offering~~allow tothird ~~sell~~parties orto ~~importing~~use our ~~products~~technology ~~will~~without ~~depend~~being onrequired ~~the~~to ~~extent~~pay tous ~~which~~licensing wefees ~~have~~or ~~rights~~may ~~under~~compel ~~valid~~us ~~and~~to ~~enforceable~~license needed ~~patents~~technologies orto ~~trade~~avoid ~~secrets~~infringing ~~that~~third-party ~~protect~~patent ~~these~~and ~~activities~~proprietary rights. WeSuch ~~seek~~a todecision ~~protect~~could ~~proprietary~~even ~~technology,~~result ~~inventions,~~in ~~and~~the ~~improvements~~invalidation ~~that~~or a ~~are~~limitation ~~commercially~~in ~~important~~the toscope of our ~~business~~patents byor ~~seeking,~~forfeiture ~~maintaining,~~of ~~and~~the ~~defending patent~~ rights, ~~whether~~associated ~~developed~~with ~~internally~~our patents or ~~licensed from~~pending ~~third~~patent ~~parties~~applications.

We have two active patent families relating to our dactinomycin program. Currently, we have one granted US patent and ten pending patent applications in these families in the US, Australia, Canada, Europe, and Japan. 16

We intend to seek orphan drug status whenever ~~also~~it ~~have~~is available. If a product which has an ~~exclusive~~orphan ~~license~~drug todesignation ~~patents~~subsequently ~~and~~receives ~~patent~~the ~~applications~~first ~~across~~regulatory ~~seven~~approval ~~different~~for ~~patent~~the ~~families~~indication for ~~relating~~which it has such designation, the product is entitled to ~~our~~orphan ~~LSD1~~exclusivity, ~~program.~~meaning that the applicable regulatory authority may Wenot ~~currently~~approve ~~have~~any ~~four~~other ~~granted~~applications ~~patents~~to ~~and~~market ~~two~~the ~~pending~~same ~~application~~drug infor the ~~U.S.~~same Weindication, ~~also~~except ~~have~~in ~~granted~~certain ~~patents~~very ~~and/or~~limited ~~pending~~circumstances, ~~applications~~for a period of seven years in ~~these~~the ~~families~~United States and 10 years in ~~Europe,~~the ~~Australia,~~European ~~Brazil,~~Union. ~~Canada,~~Orphan ~~China,~~drug ~~Eurasia,~~designation ~~India,~~does ~~Israel,~~not ~~Japan,~~prevent ~~Mexico,~~competitors from ~~and~~developing ~~South~~or ~~Africa~~marketing different drugs for an indication.

~~The patent~~We ~~positions~~also ofrely ~~biotechnology~~on ~~companies~~trade ~~like~~secret ~~ours~~protection ~~are~~for ~~generally~~our confidential ~~uncertain~~ and ~~involve~~proprietary ~~complex legal, scientific and factual questions~~information. In ~~addition,~~No ~~the~~assurance ~~coverage claimed in a patent application~~ can be ~~significantly~~given ~~reduced~~that ~~before~~others ~~the~~will ~~patent is issued. Consequently, we do~~ not ~~know~~independently ~~whether~~develop ~~the~~substantially ~~product candidates we are developing will gain patent protection or, if patents are issued, whether they will~~equivalent ~~provide~~proprietary ~~significant~~information ~~proprietary~~and ~~protection~~techniques or ~~will~~otherwise begain ~~challenged,~~access ~~circumvented, invalidated, or found~~ to beour ~~unenforceable.~~trade ~~Because~~secrets ~~patent applications~~or indisclose ~~the~~such ~~United States and certain other jurisdictions are maintained in secrecy for 18 months~~technology, ~~and since publication of discoveries in the scientific~~ or ~~patent~~that ~~literature often lags behind actual discoveries,~~ we ~~cannot~~can ~~be certain of the priority of inventions or filing~~meaningfully ~~dates~~protect ~~covered~~our bytrade ~~pending patent applications~~secrets. ~~Moreover~~However, we ~~may~~believe ~~have~~that ~~to participate in post-grant proceedings, interference proceedings, or third-party ex parte or inter partes reexamination proceedings before~~ the ~~U.S. Patent and Trademark Office, or in opposition proceedings in a foreign patent office, any of which could result in~~ substantial ~~cost~~costs ~~to us, even if the eventual outcome is favorable to us. There can be no assurance that the patents, if issued, would be held valid~~ and ~~enforceable~~resources byrequired ~~a court of competent jurisdiction. An adverse outcome could subject us~~ to ~~significant~~develop ~~liabilities~~technological ~~to third parties, require disputed rights to be licensed from third parties~~innovations orwill ~~require~~help us to ~~cease~~protect ~~using specific compounds or technology. To~~ the ~~extent~~competitive ~~prudent,~~advantage ~~we intend to bring litigation against third parties that we believe are infringing one or more~~ of our ~~patents or other intellectual property rights~~products.

~~The term~~It ofis ~~individual~~our ~~patents~~policy ~~depends~~to ~~upon~~require ~~the~~our ~~legal~~employees, ~~term~~consultants, outside ofscientific ~~the~~collaborators, ~~patents~~sponsored inresearchers ~~the~~and ~~countries~~other inadvisors ~~which~~to ~~they~~execute ~~are~~confidentiality ~~obtained.~~agreements Inupon ~~most~~the ~~countries~~commencement inof ~~which~~employment weor ~~file,~~consulting ~~the~~or ~~patent~~collaborative ~~term~~relationships iswith 20us. ~~years~~These ~~from~~agreements ~~the~~provide ~~earliest~~that ~~date~~all ofconfidential ~~filing~~information adeveloped or ~~non-provisional~~made ~~patent~~known ~~application.~~to Inthe individual during the ~~United~~course ~~States, a~~of ~~patent~~the ~~term~~individual’s ~~may~~relationship bewith ~~lengthened~~us byis ~~patent~~to ~~term~~be ~~adjustment,~~kept ~~which~~confidential ~~compensates~~and anot ~~patentee~~disclosed to ~~for~~third ~~administrative~~parties ~~delays~~except byin ~~the~~specific Ucircumstances.S. ~~Patent and~~In ~~Trademark~~the ~~Office~~case inof ~~granting~~employees, athe ~~patent,~~agreements orprovide ~~may~~that beall ~~shortened~~inventions ifconceived aby ~~patent~~the individual isshall ~~terminally~~be ~~disclaimed~~and ~~over~~are ~~another~~our ~~patent~~exclusive property. ~~Certain~~There ofcan ~~our patents~~be ~~currently~~no ~~benefit~~assurance, ~~from~~however, ~~patent~~that ~~term~~these ~~adjustment~~agreements ~~and~~will ~~some~~provide ofmeaningful protection or adequate remedies for our ~~patents~~trade ~~issuing~~secrets in the ~~future~~event ~~may~~of ~~benefit~~unauthorized ~~from~~use ~~patent~~or ~~term~~disclosure ~~adjustment~~of such information.

The patent term of a patent that covers an FDA-approved product may also be eligible for patent term extension, which permits patent term restoration as compensation for the patent term lost during the FDA regulatory review process. The Drug Price Competition and Patent Term Restoration Act of 1984, or the Hatch-Waxman Act, permits a patent term extension of up to five years beyond the expiration of the patent. The length of the patent term extension is related to the length of time the product is under regulatory review. Patent term extension cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval and only one patent applicable to an approved product may be extended. Similar provisions are available in Europe and other non-U.S. jurisdictions to extend the term of a patent that covers an approved product. In the future, if and when our product candidates receive FDA approval, we expect to apply for patent-term extensions on patents covering those products.

~~To protect~~The ~~our~~biotechnology ~~rights to any of our issued patents~~ and ~~proprietary~~pharmaceutical ~~information,~~industries are wecharacterized ~~may~~by ~~need~~rapidly toadvancing ~~litigate against infringing third parties~~technologies, or ~~avail~~intense ~~ourselves~~competition ~~of the courts or participate in hearings to determine the scope~~ and ~~validity~~a ofstrong ~~those~~emphasis ~~patents~~on ~~or other~~ proprietary ~~rights~~ products. ~~These~~While ~~types~~we ofbelieve that ~~proceedings~~our ~~are~~technology, ~~often~~development ~~costly~~experience and ~~could~~scientific beknowledge ~~very~~provide ~~time-consuming to~~ us, ~~and~~with ~~there~~competitive ~~can~~advantages, bewe noface ~~assurance~~potential ~~that the deciding~~competition ~~authorities~~from ~~will~~many ~~rule~~different insources, ~~our~~including ~~favor.~~major Anpharmaceutical, ~~unfavorable~~specialty ~~decision~~pharmaceutical ~~could~~and ~~allow~~biotechnology ~~third~~companies, ~~parties~~academic ~~to use our technology without being required to~~institutions ~~pay~~and usgovernmental ~~licensing~~agencies ~~fees~~and orpublic ~~may~~and ~~compel~~private usresearch toinstitutions. ~~license~~Any ~~needed~~product ~~technologies~~candidates tothat ~~avoid~~we ~~infringing~~successfully ~~third-party~~develop ~~patent~~ and ~~proprietary rights.~~commercialize ~~Such~~will acompete ~~decision~~with ~~could~~existing ~~even~~therapies ~~result~~and innew ~~the~~therapies ~~invalidation~~that ormay abecome ~~limitation~~available in the ~~scope of our patents or forfeiture of the rights associated with our patents or pending patent applications~~future.

16Several types of existing treatments may be used for people with AML. The main treatments include chemotherapy, bone marrow transplants, stem cell transplants and/or interferon therapy. In most cases AML can progress rapidly, so it is important to start treatment as soon as possible after the diagnosis is made. In addition to currently marketed therapies, there are also a number of products in late stage clinical development to treat AML. These products in development may provide efficacy, safety, convenience and other benefits that are not provided by currently marketed therapies. As a result, they may provide significant competition for any of our product candidates for which we obtain market approval.

~~We intend~~There toare ~~seek~~other ~~orphan~~companies ~~drug~~and ~~status~~research ~~whenever~~institutions working itto isdevelop ~~available~~therapies that target AML. IfMany aof ~~product~~our ~~which~~competitors ~~has~~may anhave ~~orphan~~significantly ~~drug~~greater ~~designation~~financial ~~subsequently~~resources ~~receives~~and ~~the~~expertise ~~first~~in ~~regulatory~~research ~~approval~~and ~~for~~development, ~~the~~preclinical ~~indication~~testing, ~~for~~conducting ~~which~~clinical ittrials, ~~has~~obtaining ~~such~~regulatory ~~designation,~~approvals ~~the~~and ~~product~~marketing isapproved ~~entitled~~products than towe ~~orphan~~do. ~~exclusivity,~~Mergers ~~meaning that~~and acquisitions in the ~~applicable~~pharmaceutical, ~~regulatory~~biotechnology ~~authority~~and diagnostic industries may ~~not~~result ~~approve~~in ~~any~~even ~~other~~more ~~applications~~resources being toconcentrated ~~market~~among ~~the~~a ~~same~~smaller ~~drug~~number ~~for~~of ~~the~~our ~~same~~competitors. ~~indication,~~These ~~except in~~competitors ~~certain~~also ~~very~~compete ~~limited~~with ~~circumstances,~~us ~~for~~in arecruiting ~~period~~and ofretaining ~~seven~~qualified scientific ~~years~~and inmanagement ~~the~~personnel ~~United~~and ~~States~~establishing clinical trial sites and 10patient ~~years~~registration for clinical trials, as well as in acquiring ~~the~~technologies ~~European~~complementary ~~Union~~to, or necessary for, our programs. ~~Orphan~~Smaller ~~drug designation~~or ~~does~~early ~~not~~stage ~~prevent~~companies may also prove to be significant competitors, ~~from~~particularly ~~developing~~through orcollaborative ~~marketing~~arrangements ~~different~~with ~~drugs~~large ~~for~~and anestablished ~~indication~~companies.

~~We also~~A ~~rely~~listing onof ~~trade~~approved ~~secret~~products ~~protection~~currently used for ~~our~~treatment ~~confidential~~of ~~and~~AML ~~proprietary~~include ~~information.~~the Nofollowing: ~~assurance~~topoisomerase ~~can~~II beinhibitors, ~~given~~e.g., ~~that~~Cerubidine® ~~others~~(daunorubicin ~~will~~HCL, ~~not~~Bedford Labs), ~~independently~~Novantrone® ~~develop~~(mitoxantrone ~~substantially~~HCL, ~~equivalent~~Pfizer) ~~proprietary~~and ~~information~~Idamycin® ~~and~~(idarubicin ~~techniques~~HCl, orPfizer); ~~otherwise~~alkylating ~~gain~~agents, ~~access~~e.g., Cytoxan® to(cyclophosphamide, ~~our~~Baxter); ~~trade~~DNA ~~secrets~~polymerase orinhibitors, e.g,. Cytarabine® (cytarabine, Pfizer); ~~disclose~~DNA ~~such~~binding ~~technology~~agents, ore.g., ~~that~~Doxil® we(doxorubicin ~~can~~HCl ~~meaningfully~~liposome, ~~protect~~Alza); ~~our~~purine ~~trade~~analogs, ~~secrets~~e.g., ~~However~~Tabloid® (thioguanine, GlaxoSmithKline); wemitotic ~~believe~~spindle ~~that~~inhibitors, ~~the~~e.g., ~~substantial~~Vincasar ~~costs~~PFS® ~~and~~(vincristine ~~resources~~sulfate, Teva); DNA fragmentation agents, ~~required~~e.g,. toTrisenox® ~~develop~~(arsenic ~~technological~~trioxide, ~~innovations~~Cephalon); ~~will~~FLT3 ~~help~~inhibitors, use.g., toRydapt® ~~protect~~(midostaurin, ~~the~~Novartis); ~~competitive~~IDH2 inhibitors, ~~advantage~~e.g., ofIDHIFA® ~~our~~(enasidenib ~~products~~mesylate, Celgene).

It is our policy to require our employees, consultants, outside scientific collaborators, sponsored researchers and other advisors to execute confidentiality agreements upon the commencement of employment or consulting or collaborative relationships with us. These agreements provide that all confidential information developed or made known to the individual during the course of the individual’s relationship with us is to be kept confidential and not disclosed to third parties except in specific circumstances. In the case of employees, the agreements provide that all inventions conceived by the individual shall be and are our exclusive property. There can be no assurance, however, that these agreements will provide meaningful protection or adequate remedies for our trade secrets in the event of unauthorized use or disclosure of such information.17

~~Competition~~A listing of AML drugs in advanced clinical development by our competitors include the following: (irreversible) LSD-1 inhibitors, e.g. ORY-1001 (Oryzon); FLT3 inhibitors, e.g., quizartinib (Daiichi Sankyo), crenolanib (Arog Pharma) and gilteritinib (Astellas); topoisomerase inhibitors, e.g., Vosaroxin® (qinprezo, Sunesis Pharma), CPX-351 (vyxeos, Celator Pharma); DNA hypomethylating agents, e.g., guadecditabine (ASTX Pharma); PLK1 inhibitors, e.g., volasertib (Boehringer Ingelheim); IDH2 inhibitors, e.g., enasidenib (Agios Pharma); IDH1 inhibitors, e.g., ivosidenib (Agios Pharma); DOT1L ihibitors, e.g., pinometostat (Epizyme); BCL2 inhibitors, e.g., venetoclax (Roche); BET inhibitors, e.g., OTX-015 (OncoEthix) and HDAC inhibitors, e.g., pracinostat (MEI Pharma).

~~The biotechnology~~A ~~and~~large ~~pharmaceutical~~number ~~industries~~of ~~are~~irreversible ~~characterized~~inhibitors byof ~~rapidly~~LSD1 have ~~advancing~~been ~~technologies,~~developed ~~intense~~by ~~competition~~major ~~and~~pharmaceutical acompanies ~~strong~~and ~~emphasis on~~research ~~proprietary products~~institutes. ~~While~~Among ~~we believe that our technology~~them, ~~development~~ORY-1001 ~~experience~~ and ~~scientific~~GSK2879552, ~~knowledge~~two ~~provide~~TCP ~~us with competitive advantages~~derivatives, developed weby ~~face~~Oryzon ~~potential~~Genomics ~~competition~~and ~~from many different sources~~GSK, ~~including major pharmaceutical~~respectively, ~~specialty~~have ~~pharmaceutical~~been ~~and~~in ~~biotechnology companies,~~Phase ~~academic~~1 ~~institutions~~clinical ~~and~~trials ~~governmental~~for ~~agencies~~treatment ~~and~~of ~~public~~AML ~~and~~We ~~private~~have ~~research~~focused ~~institutions.~~on ~~Any product candidates that~~development weof ~~successfully~~reversible ~~develop~~inhibitors ~~and~~instead ~~commercialize~~of ~~will~~irreversible ~~compete~~inhibitors with ~~existing~~the ~~therapies~~expectation ~~and~~of ~~new~~better ~~therapies~~therapeutic ~~that~~effect, ~~may~~safety ~~become~~profiles ~~available~~and inlower toxicity compared to the ~~future.~~irreversible inhibitors

~~Several types of existing treatments may be used for people with AML.~~ The ~~main~~key ~~treatments~~competitive ~~include~~factors ~~chemotherapy,~~affecting ~~bone~~the ~~marrow transplants, stem~~success ~~cell~~of ~~transplants~~all ~~and/or~~our ~~interferon therapy. In most cases AML can progress rapidly~~targets, soif ~~it is important to start treatment as soon as possible after the diagnosis is made. In addition to currently marketed therapies~~approved, ~~there~~ are ~~also~~likely ~~a number of products in late stage clinical development~~ to ~~treat~~be ~~AML.~~their ~~These products in development may provide~~ efficacy, safety, convenience, ~~and other benefits that are not provided by currently marketed therapies. As a result~~price, ~~they~~the ~~may~~level ~~provide~~of ~~significant~~generic competition ~~for~~and ~~any~~the availability of ~~our~~reimbursement ~~product~~from ~~candidates for~~government ~~which~~and weother ~~obtain~~third-party ~~market approval~~payors.

~~There are~~Our ~~other~~commercial ~~companies~~opportunity ~~and~~could ~~research~~be ~~institutions~~reduced ~~working~~or eliminated toif our competitors develop ~~therapies~~and commercialize products that ~~target~~are ~~AML.~~safer, ~~Many~~more ofeffective, ~~our~~have ~~competitors~~fewer ~~may~~or ~~have~~less ~~significantly~~severe side effects, ~~greater~~are ~~financial~~more ~~resources~~convenient ~~and~~or ~~expertise~~are inless ~~research~~expensive ~~and~~than ~~development,~~any ~~preclinical~~products ~~testing,~~that ~~conducting~~we ~~clinical~~may ~~trials,~~develop. ~~obtaining~~Our competitors also may obtain FDA or other regulatory ~~approvals~~approval ~~and~~for ~~marketing~~their ~~approved~~ products more rapidly than we ~~do.~~may ~~Mergers~~obtain ~~and~~approval ~~acquisitions~~for ~~in the pharmaceutical~~ours, ~~biotechnology~~which ~~and~~could ~~diagnostic industries may~~ result in ~~even~~our ~~more~~competitors ~~resources~~establishing ~~being~~a ~~concentrated~~strong market ~~among~~position abefore ~~smaller~~we ~~number~~are ofable ~~our~~to ~~competitors~~enter the market. ~~These~~In ~~competitors~~addition, ~~also~~our ability to compete ~~with~~may us be affected in ~~recruiting~~many ~~and~~cases ~~retaining~~by ~~qualified~~insurers or ~~scientific~~other ~~and~~third-party ~~management~~payors ~~personnel~~seeking ~~and~~to ~~establishing~~encourage ~~clinical~~the ~~trial~~use ~~sites~~of ~~and~~generic ~~patient~~products. ~~registration~~There are many generic products currently on the market for ~~clinical~~the ~~trials,~~indications asthat ~~well~~we asare inpursuing, ~~acquiring~~and ~~technologies~~additional ~~complementary~~products ~~to,~~are orexpected ~~necessary~~to ~~for,~~become ~~our~~available ~~programs.~~on ~~Smaller~~a orgeneric ~~early~~basis ~~stage~~over ~~companies~~the coming ~~may~~years. ~~also~~If ~~prove~~our totherapeutic beproduct ~~significant~~candidates ~~competitors~~are approved, ~~particularly~~we ~~through~~expect ~~collaborative~~that ~~arrangements~~they ~~with~~will ~~large~~be ~~and~~priced ~~established~~at ~~companies~~a significant premium over competitive generic products.

~~A listing~~Shared ofServices approved products currently used for treatment of AML include the following: topoisomerase II inhibitors, e.g., Cerubidine® (daunorubicin HCL, Bedford Labs), Novantrone® (mitoxantrone HCL, Pfizer) and Idamycin® (idarubicin HCl, Pfizer); alkylating agents, e.g., Cytoxan® (cyclophosphamide, Baxter); DNA polymerase inhibitors, e.g,. Cytarabine® (cytarabine, Pfizer); DNA binding agents, e.g., Doxil® (doxorubicin HCl liposome, Alza); purine analogs, e.g., Tabloid® (thioguanine, GlaxoSmithKline); mitotic spindle inhibitors, e.g., Vincasar PFS® (vincristine sulfate, Teva); DNA fragmentation agents, e.g,. Trisenox® (arsenic trioxide, Cephalon); FLT3 inhibitors, e.g., Rydapt® (midostaurin, Novartis); IDH2 inhibitors, e.g., IDHIFA® (enasidenib mesylate, Celgene).Agreement

17On January 1, 2017, Tiziana Life Sciences plc, a company incorporated in England and Wales (“Tiziana”), entered into a Shared Services Agreement with us pursuant to which Tiziana agreed to provide certain services to us including various administrative, financial, legal, tax, insurance, facility and information technology services. The term of the agreement is until April 1, 2018 and is renewed automatically thereafter for successive three month terms with respect to any services still in effect unless either party elects not to renew the agreement or any specific service by notice in writing to the other party no later than 45 days prior to the end of any term. We may terminate any of the services provided under the agreement at any time upon 30 days prior written notice. Tiziana may terminate any of the services provided under the agreement if we shall have failed to perform any of our material obligations under the agreement and failed to cure any such failure within 30 days after receiving notice thereof.

A listing of AML drugs in advanced clinical development by our competitors include the following: (irreversible) LSD-1 inhibitors, e.g. ORY-1001 (Oryzon); FLT3 inhibitors, e.g., quizartinib (Daiichi Sankyo), crenolanib (Arog Pharma) and gilteritinib (Astellas); topoisomerase inhibitors, e.g., Vosaroxin® (qinprezo, Sunesis Pharma), CPX-351 (vyxeos, Celator Pharma); DNA hypomethylating agents, e.g., guadecditabine (ASTX Pharma); PLK1 inhibitors, e.g., volasertib (Boehringer Ingelheim); IDH2 inhibitors, e.g., enasidenib (Agios Pharma); IDH1 inhibitors, e.g., ivosidenib (Agios Pharma); DOT1L ihibitors, e.g., pinometostat (Epizyme); BCL2 inhibitors, e.g., venetoclax (Roche); BET inhibitors, e.g., OTX-015 (OncoEthix) and HDAC inhibitors, e.g., pracinostat (MEI Pharma).Employees

~~A large~~As ~~number~~ of ~~irreversible~~September ~~inhibitors of LSD1 have been developed by major pharmaceutical companies and research institutes. Among them~~30, ~~ORY-1001 and GSK2879552~~2022, ~~two TCP derivatives, developed by Oryzon Genomics~~ and ~~GSK,~~September ~~respectively~~30, ~~have been in Phase 1 clinical~~2021 ~~trials~~we ~~for~~had ~~treatment~~no of AML We have focused on development of reversible inhibitors instead of irreversible inhibitors with the expectation of better therapeutic effect, safety profiles and lower toxicity compared to the irreversible inhibitorsemployees.

The key competitive factors affecting the success of all our targets, if approved, are likely to be their efficacy, safety, convenience, price, the level of generic competition and the availability of reimbursement from government and other third-party payors.18

~~Our commercial~~ITEM opportunity could be reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, have fewer or less severe side effects, are more convenient or are less expensive than any products that we may develop1A. ~~Our~~RISK competitors also may obtain FDA or other regulatory approval for their products more rapidly than we may obtain approval for ours, which could result in our competitors establishing a strong market position before we are able to enter the market. In addition, our ability to compete may be affected in many cases by insurers or other third-party payors seeking to encourage the use of generic products. There are many generic products currently on the market for the indications that we are pursuing, and additional products are expected to become available on a generic basis over the coming years. If our therapeutic product candidates are approved, we expect that they will be priced at a significant premium over competitive generic products.FACTORS

~~Shared Services~~Risks ~~Agreement~~Relating to Our Business

~~On January~~We 1,are ~~2017, Tiziana Life Sciences plc,~~ a ~~company~~leukemia-focused ~~incorporated in England and Wales (“Tiziana”), entered into a Shared~~biotechnology ~~Services~~company ~~Agreement~~ with uslimited ~~pursuant~~operations to ~~which Tiziana agreed to provide certain services to us including various administrative, financial, legal, tax, insurance, facility and information technology services~~date. The term of the agreement is until April 1, 2018 and is renewed automatically thereafter for successive three month terms with respect to any services still in effect unless either party elects not to renew the agreement or any specific service by notice in writing to the other party no later than 45 days prior to the end of any term. We may terminate any of the services provided under the agreement at any time upon 30 days prior written notice. Tiziana may terminate any of the services provided under the agreement if we shall have failed to perform any of our material obligations under the agreement and failed to cure any such failure within 30 days after receiving notice thereof.

~~Employees~~We are a leukemia-focused biotechnology company with limited operations to date and no revenue. We have not yet commenced clinical trials, have no product candidates ready for commercialization, have not generated any revenue from operations and expect to incur substantial net losses for the foreseeable future to further develop and commercialize our product candidates. We are unable to predict the extent of these future net losses, or when we may attain profitability, if at all. We may never be able to generate any revenues or royalties from the sales of our therapeutics or become profitable even if we do generate revenues or royalties.

AsWe expect to continue to incur increasing ofnet ~~September~~losses ~~30,~~for ~~2021~~the foreseeable future, and ~~September~~we ~~30,~~may ~~2020~~never weachieve ~~had~~or nomaintain ~~employees~~profitability.

18Investment in biopharmaceutical product development is highly speculative because it entails substantial upfront capital expenditures and significant risk that any potential product candidate will fail to demonstrate adequate effect or an acceptable safety profile, gain regulatory approval and become commercially viable. We have no products approved for commercial sale and have not generated any revenue from product sales to date, and we continue to incur significant research and development and other expenses related to our ongoing operations. As a result, we are not profitable and have incurred losses in each period since our inception. For the year ended September 30, 2022 and 2021, we reported a net loss of $686,588 and $875,998, respectively. As of September 30, 2022, we had an accumulated deficit of $24,221,067.

~~ITEM~~To become and remain profitable, we or our partners 1Amust succeed in developing our product candidates, obtaining regulatory approval for them, and manufacturing, marketing and selling those products for which we or our partners may obtain regulatory approval. ~~RISK~~We ~~FACTORS~~or they may not succeed in these activities, and we may never generate revenue from product sales that is significant enough to achieve profitability. Because of the numerous risks and uncertainties associated with biopharmaceutical product development and commercialization, we are unable to accurately predict the timing or amount of future expenses or when, or if, we will be able to achieve or maintain profitability. Currently, we have no products approved for commercial sale, and to date we have not generated any product revenue. We have financed our operations primarily through the sale of equity securities. The size of our future net losses will depend, in part, on the rate of growth or contraction of our expenses and the level and rate of growth, if any, of our revenues. Our ability to achieve profitability is dependent on our ability, alone or with others, to complete the development of our products successfully, obtain the required regulatory approvals, manufacture and market our proposed products successfully or have such products manufactured and marketed by others, and gain market acceptance for such products. There can be no assurance as to whether or when we will achieve profitability.

~~Risks~~We will require substantial additional funding ~~Relating~~which may not be available to ~~Our~~us ~~Business~~on acceptable terms, or at all. If we fail to raise the necessary additional capital, we may be unable to complete the development and commercialization of our product candidates, or continue our development programs.

We expect to escalate moderately our spending ~~are~~to aadvance ~~leukemia~~the pre-~~focused~~clinical ~~biotechnology~~and ~~company~~clinical ~~with~~development ~~limited~~of ~~operations~~our toproduct ~~date~~candidates.

We ~~are~~ acannot ~~leukemia-focused~~be ~~biotechnology~~certain ~~company~~that ~~with~~additional ~~limited~~funding ~~operations~~will be toavailable ~~date~~on ~~and~~acceptable noterms, ~~revenue.~~or Weat ~~have~~all. ~~not~~If ~~yet~~we ~~commenced~~are ~~clinical~~unable ~~trials, have~~to noraise ~~product~~additional ~~candidates~~capital ~~ready~~in ~~for~~sufficient ~~commercialization,~~amounts ~~have~~or ~~not~~on ~~generated~~terms ~~any~~acceptable to ~~revenue~~us ~~from~~we ~~operations~~may ~~and~~have ~~expect~~ to ~~incur~~significantly ~~substantial net~~delay, ~~losses~~scale ~~for~~back ~~the~~or ~~foreseeable~~discontinue ~~future~~the todevelopment ~~further~~or ~~develop~~commercialization ~~and~~of ~~commercialize~~ our product ~~candidates~~candidate. We may ~~are~~also ~~unable~~seek tocollaborators ~~predict~~for ~~the~~one ~~extent of~~or ~~these~~more ~~future~~of ~~net~~our ~~losses,~~current or ~~when~~future weproduct ~~may~~candidates ~~attain~~at ~~profitability,~~an ifearlier atstage ~~all.~~than Weotherwise ~~may~~would ~~never~~ be ~~able~~desirable or toon ~~generate~~terms ~~any~~that ~~revenues~~are orless ~~royalties from~~favorable ~~the~~than ~~sales~~might ofotherwise ~~our~~be ~~therapeutics~~available. orAny ~~become~~of ~~profitable~~these ~~even~~events ifcould wesignificantly doharm ~~generate~~our ~~revenues~~business, orfinancial condition ~~royalties~~and prospects.

~~We expect~~Our tofuture ~~continue~~capital torequirements ~~incur~~will ~~increasing~~depend ~~net~~on many ~~losses for the foreseeable future~~factors, ~~and we may never achieve or maintain profitability.~~including:

~~Investment~~● in biopharmaceutical product development is highly speculative because it entails substantial upfront capital expenditures and significant risk that any potential product candidate will fail to demonstrate adequate effect or an acceptable safety profile, gain regulatory approval and become commercially viable. We have no products approved for commercial sale and have not generated any revenue from product sales to date, and we continue to incur significant research and development and other expenses related to our ongoing operations. As a result, we are not profitable and have incurred losses in each period since our inception. For the ~~year~~progress ~~ended September 30, 2021 and 2020, we reported a net loss~~ of ~~$785,082 and $5,346,672,~~the ~~respectively.~~development As of ~~September~~our ~~30,~~product ~~2021, we had an accumulated deficit of $23,443,563.~~candidates;

~~To become~~● and remain profitable, we or our partners must succeed in developing our product candidates, obtaining regulatory approval for them, and manufacturing, marketing and selling those products for which we or our partners may obtain regulatory approval. We or they may not succeed in these activities, and we may never generate revenue from product sales that is significant enough to achieve profitability. Because of the ~~numerous~~number ~~risks and uncertainties associated with biopharmaceutical product development and commercialization, we are unable to accurately predict the timing or amount~~ of ~~future expenses or when, or if, we will be able to achieve or maintain profitability. Currently, we have no products approved for commercial sale, and to date we have not generated any~~ product ~~revenue.~~candidates We have financed our operations primarily through the sale of equity securities. The size of our future net losses will depend, in part, on the rate of growth or contraction of our expenses and the level and rate of growth, if any, of our revenues. Our ability to achieve profitability is dependent on our ability, alone or with others, to complete the development of our products successfully, obtain the required regulatory approvals, manufacture and market our proposed products successfully or have such products manufactured and marketed by others, and gain market acceptance for such products. There can be no assurance as to whether or when we ~~will achieve profitability.~~pursue;

We will require substantial additional funding which may not be available to us on acceptable terms, or at all. If we fail to raise the necessary additional capital, we may be unable to complete the development and commercialization of our product candidates, or continue our development programs.19

~~We expect~~● ~~to escalate moderately our spending to advance~~ the ~~pre-clinical~~time and ~~clinical~~costs ~~development~~involved ofin ~~our~~obtaining ~~product~~regulatory ~~candidates.~~approvals;

~~We cannot~~● bethe ~~certain~~costs ~~that~~involved ~~additional funding will be available on acceptable terms, or at all. If we are unable to raise additional capital~~ in ~~sufficient~~filing ~~amounts~~and orprosecuting onpatent ~~terms~~applications ~~acceptable~~and toenforcing ~~us we may have to significantly delay, scale back~~ or ~~discontinue~~defending ~~the~~patent development or commercialization of our product candidate. We may also seek collaborators for one or more of our current or future product candidates at an earlier stage than otherwise would be desirable or on terms that are less favorable than might otherwise be available. Any of these events could significantly harm our business, financial condition and prospects.claims;

~~Our future~~● ~~capital~~our ~~requirements~~plans ~~will~~to ~~depend~~establish onsales, ~~many~~marketing ~~factors,~~and/or ~~including:~~manufacturing capabilities;

● the ~~progress~~effect of ~~the~~competing ~~development~~technological ofand ~~our~~market ~~product candidates~~developments;

● the ~~number~~terms and timing of ~~product~~any ~~candidates~~collaborative, licensing and other arrangements that we ~~pursue~~may establish;

19● general market conditions for offerings from biopharmaceutical companies;

● ~~the~~our ~~time~~ability to establish, enforce and ~~costs~~maintain ~~involved~~selected instrategic ~~obtaining~~alliances ~~regulatory~~and ~~approvals~~activities required for product commercialization; and

● ~~the~~our ~~costs~~revenues, ~~involved~~if inany, ~~filing~~from ~~and~~successful ~~prosecuting~~development ~~patent applications~~ and ~~enforcing~~commercialization orof ~~defending~~our ~~patent~~product ~~claims;~~candidates.

●In order to carry out our ~~plans~~business plan and implement our strategy, we anticipate that we will need to ~~establish~~obtain additional financing from time to time and may choose to raise additional funds through strategic collaborations, licensing arrangements, public or private equity or debt financing, bank lines of credit, asset sales, government grants, or other arrangements. We cannot be sure that any additional funding, if needed, will be available on terms favorable to us or at all. Furthermore, any additional equity or equity-related financing may be dilutive to our stockholders, and debt or equity financing, if available, may subject us to restrictive covenants and significant interest costs. If we obtain funding through a strategic collaboration or licensing arrangement, we may be required to relinquish our rights to certain of our product candidate or marketing territories. Our inability to raise capital when needed would harm our business, financial condition and/ results of operations, and could cause our stock price to decline or ~~manufacturing~~require ~~capabilities;~~that we wind down our operations altogether.

●Our ~~the~~independent ~~effect~~registered ofpublic ~~competing~~accounting firm ~~technological~~has ~~and~~expressed ~~market~~substantial ~~developments;~~doubt about our ability to continue as a going concern, which may hinder our ability to obtain future financing.

●Our consolidated financial statements as of September 30, 2022 were prepared under the ~~terms~~assumption that we will continue as a going concern for the next twelve months. Due to our recurring losses from operations, we concluded that there is substantial doubt in our ability to continue as a going concern within one year after the financial statements are issued without additional capital becoming available. Our independent registered public accounting firm has issued an audit opinion that included an explanatory paragraph referring to our projected future losses along with recurring losses from operations and ~~timing~~expressing ofsubstantial ~~any~~doubt ~~collaborative~~in our ability to continue as a going concern without additional capital becoming available. Our ability to continue as a going concern is dependent upon our ability to obtain additional equity or debt financing, ~~licensing~~attain further operating efficiencies, reduce expenditures, and, ~~other~~ultimately, ~~arrangements~~to generate revenue. The financial statements do not include any adjustments that wemight ~~may~~result ~~establish;~~from the outcome of this uncertainty.

●If ~~general~~we ~~market~~fail ~~conditions~~to ~~for~~select ~~offerings~~product ~~from~~candidates, fail ~~biopharmaceutical~~to ~~companies;~~successfully complete clinical trials and commercialize product candidates or fail to obtain regulatory approval, our business would be harmed and the value of our securities would decline.

●We must be evaluated in light of the uncertainties and complexities affecting a pre-commercial biopharmaceutical company. We have not completed preclinical or clinical research and have not completed the development of our ~~ability~~product candidates. Our failure to ~~establish,~~develop ~~enforce~~and commercialize such product candidates successfully may cause us to cease operations. We are performing preclinical research on LSD1. This research will require significant additional development efforts by us and ~~maintain~~significant ~~selected~~additional ~~strategic~~development ~~alliances~~efforts by us and ~~activities~~regulatory ~~required~~approvals ~~for~~prior ~~product~~to commercialization;. We cannot be certain that our efforts in this regard will lead to commercially viable therapeutics. We do not know what the final cost to select and commercialize product candidates will be.

●We ~~our~~do ~~revenues,~~not ifknow whether any, ~~from~~of ~~successful~~our molecular targets under development ~~and~~ultimately ~~commercialization~~will ofbe selected as product candidates or whether our product candidates will be shown to be effective. Moreover, governmental authorities may enact new legislation or regulations that could limit or restrict our development efforts. We may receive unfavorable results from pre-clinical studies or clinical studies on the molecular targets, which may cause us to abandon the product selection process and further development efforts.

In order to carry out our business plan and implement our strategy, we anticipate that we will need to obtain additional financing from time to time and may choose to raise additional funds through strategic collaborations, licensing arrangements, public or private equity or debt financing, bank lines of credit, asset sales, government grants, or other arrangements. We cannot be sure that any additional funding, if needed, will be available on terms favorable to us or at all. Furthermore, any additional equity or equity-related financing may be dilutive to our stockholders, and debt or equity financing, if available, may subject us to restrictive covenants and significant interest costs. If we obtain funding through a strategic collaboration or licensing arrangement, we may be required to relinquish our rights to certain of our product candidate or marketing territories. Our inability to raise capital when needed would harm our business, financial condition and results of operations, and could cause our stock price to decline or require that we wind down our operations altogether.20

Regulatory agencies must approve our product candidates, if any, before they can be marketed or sold. The approval process is lengthy, requires significant capital expenditures, and uncertain as to outcome. Our ability to obtain regulatory approval of any product candidate depends on, among other things, completion of additional ~~independent~~clinical ~~registered~~trials, ~~public~~whether ~~accounting~~our ~~firm~~clinical ~~has~~trials ~~expressed~~demonstrate ~~substantial~~statistically ~~doubt~~significant ~~about~~efficacy with safety issues that do not potentially outweigh the therapeutic benefit of the product candidates, and whether the regulatory agencies agree that the data from our ~~ability~~future clinical trials are sufficient to ~~continue~~support asapproval for any of our product candidates. The final results of our current and future preclinical or clinical trials may not meet FDA or other regulatory agencies’ requirements to approve a ~~going~~product ~~concern~~candidate for marketing, ~~which~~and the regulatory agencies may ~~hinder~~otherwise determine that our ~~ability~~manufacturing processes or facilities are insufficient to ~~obtain~~support ~~future~~approval. ~~financing~~We or our collaborators may need to conduct more preclinical or clinical trials than we currently anticipate. Even if we do receive FDA or other regulatory agency approval, we or our collaborators may not be successful in commercializing approved product candidates. If any of these events occur, our business could be materially harmed and the value of our securities would decline.

~~Our consolidated~~All ~~financial statements as~~ of ~~September~~our ~~30,~~current ~~2021~~data ~~were prepared under the assumption that we will continue as a going concern~~ for ~~the next twelve months. Due to~~ our ~~recurring~~lead ~~losses from operations, we concluded that there is substantial doubt in our ability~~product tocandidate ~~continue~~are ~~as a going concern within one year after~~ the ~~financial~~result ~~statements are~~of ~~issued~~Phase ~~without~~2 ~~additional~~clinical ~~capital~~trials ~~becoming~~conducted ~~available. Our~~by ~~independent~~third ~~registered~~parties ~~public~~and ~~accounting~~do ~~firm~~not ~~has~~necessarily ~~issued~~provide ansufficient ~~audit~~evidence ~~opinion~~ that ~~included an explanatory paragraph referring to our~~ ~~projected future losses along with recurring losses from operations and expressing substantial doubt in~~ our ~~ability~~product tocandidates ~~continue~~will asbe ~~a going~~viable ~~concern without additional capital becoming available. Our ability to continue~~ as apotential ~~going~~pharmaceutical ~~concern is dependent upon our ability to obtain additional equity or debt financing, attain further operating efficiencies, reduce expenditures, and, ultimately, to generate revenue~~products. ~~The financial statements do not include any adjustments that might result from the outcome of this uncertainty.~~

IfTo date, long-term safety and efficacy have not weyet ~~fail~~been todemonstrated ~~select~~in clinical trials for our product candidates,. ~~fail~~Favorable toresults ~~successfully~~in ~~complete~~early studies or trials may not be repeated in later studies or trials. Even if our clinical trials are initiated and ~~commercialize~~completed as planned, we cannot be certain that the results will support our product ~~candidates~~candidate claims. Success in preclinical testing and early clinical trials does not ensure that later clinical trials will be successful. We cannot be sure that the results of later clinical trials would replicate the results of prior clinical trials and preclinical testing, nor that they would satisfy the requirements of the FDA or ~~fail~~other regulatory agencies. Clinical trials may fail to ~~obtain~~demonstrate that our product candidate is safe for humans and effective for indicated uses. Preclinical and clinical results are frequently susceptible to varying interpretations that may delay, limit or prevent regulatory ~~approval~~approvals or commercialization. Any delay in, or termination of, our ~~business~~clinical trials would bedelay ~~harmed~~our ~~and~~obtaining FDA or EMA approval for the ~~value~~affected ofproduct candidate and, ultimately, our ~~securities~~ability to ~~would~~commercialize ~~decline~~that product candidate.

~~We must~~If bewe ~~evaluated~~cannot indemonstrate ~~light~~an ofacceptable ~~the uncertainties and complexities affecting a pre-commercial biopharmaceutical company. We have not completed~~toxicity ~~preclinical~~profile orfor ~~clinical research and have not completed the development of~~ our product candidates., ~~Our~~if ~~failure~~any, toin ~~develop~~non-clinical ~~and~~studies, ~~commercialize such~~we ~~product~~will ~~candidates~~not ~~successfully~~be ~~may~~able ~~cause us~~ to ~~cease~~initiate ~~operations.~~or Wecontinue ~~are~~clinical ~~performing~~trials ~~preclinical~~or ~~research on NPM1 and LSD1. This~~obtain ~~research~~approval ~~will~~for ~~require significant additional development efforts by us and significant additional development efforts by us and regulatory approvals prior to commercialization. We cannot be certain that~~ our ~~efforts in this regard will lead to commercially viable therapeutics. We do not know what the final cost to select and commercialize~~ product candidates ~~will be~~.

~~We do~~To ~~not~~move ~~know~~a ~~whether~~product ~~any~~candidate ofinto ~~our~~human ~~molecular~~clinical trials, ~~targets~~we ~~under~~must ~~development~~first ~~ultimately~~demonstrate ~~will~~an beacceptable ~~selected~~toxicity asprofile ~~product~~in ~~candidates~~preclinical ortesting. ~~whether~~Furthermore, ~~our~~to ~~product candidates~~obtain ~~will~~approval, bewe ~~shown~~must toalso demonstrate besafety ~~effective.~~in ~~Moreover,~~various ~~governmental~~non-clinical ~~authorities~~tests. We may ~~enact~~not ~~new~~have ~~legislation~~conducted or ~~regulations~~may ~~that~~not ~~could~~conduct ~~limit~~the types of non-clinical testing required by regulatory authorities, or ~~restrict~~future non-clinical tests may indicate that our ~~development~~product ~~efforts~~candidates are not safe for use. WePreclinical ~~may~~and non-clinical ~~receive~~testing ~~unfavorable~~is ~~results~~expensive, ~~from~~time-consuming ~~pre~~and has an uncertain outcome. In addition, success in initial non-clinical ~~studies~~testing ordoes not ensure that later non-clinical ~~studies~~testing onwill be successful. We may experience numerous unforeseen events during the ~~molecular~~non-clinical testing ~~targets~~process, which ~~may~~could ~~cause~~delay usor toprevent ~~abandon~~our ~~the~~ability ~~product~~to ~~selection~~develop ~~process~~or ~~and~~commercialize ~~further~~our ~~development~~product ~~efforts.~~candidates, including:

20● our preclinical and non-clinical testing may produce inconclusive or negative safety results, which may require us to conduct additional non-clinical testing or to abandon product candidates;

~~Regulatory agencies~~● ~~must approve~~ our product candidates, if any, before they can be marketed or sold. The approval process is lengthy, requires significant capital expenditures, and uncertain as to outcome. Our ability to obtain regulatory approval of any product candidate depends on, among other things, completion of additional clinical trials, whether our clinical trials demonstrate statistically significant efficacy with safety issues that do not potentially outweigh the therapeutic benefit of the product candidates, and whether the regulatory agencies agree that the data from our future clinical trials are sufficient to support approval for any of our product candidates. The final results of our current and future preclinical or clinical trials may ~~not~~have ~~meet~~unfavorable ~~FDA~~pharmacology or ~~other~~toxicity regulatory agencies’ requirements to approve a product candidate for marketing, and the regulatory agencies may otherwise determine that our manufacturing processes or facilities are insufficient to support approval. We or our collaborators may need to conduct more preclinical or clinical trials than we currently anticipate. Even if we do receive FDA or other regulatory agency approval, we or our collaborators may not be successful in commercializing approved product candidates. If any of these events occur, our business could be materially harmed and the value of our securities would decline. characteristics;

~~All of~~● our ~~current data for our lead~~ product ~~candidate~~candidates ~~are~~may ~~the~~cause ~~result~~undesirable ofside ~~Phase~~effects 2such ~~clinical~~as ~~trials~~negative ~~conducted~~immune byresponses ~~third parties and do not necessarily provide sufficient evidence~~ that ~~our~~lead ~~product~~to ~~candidates will be viable as potential pharmaceutical products.~~complications;

~~To date,~~● ~~long-term safety and efficacy have not yet been demonstrated in clinical trials for~~ our ~~product~~enrolled ~~candidates.~~patients ~~Favorable results in early studies or trials~~ may ~~not~~have beallergies ~~repeated in later studies or trials. Even if our clinical trials are initiated and completed as planned, we cannot be certain~~ that ~~the~~lead results will support our product candidate claims. Success in preclinical testing and early clinical trials does not ensure that later clinical trials will be successful. We cannot be sure that the results of later clinical trials would replicate the results of prior clinical trials and preclinical testing, nor that they would satisfy the requirements of the FDA or other regulatory agencies. Clinical trials may fail to ~~demonstrate~~complications ~~that~~after ~~our~~treatment; ~~product candidate is safe for humans~~ and effective for indicated uses. Preclinical and clinical results are frequently susceptible to varying interpretations that may delay, limit or prevent regulatory approvals or commercialization. Any delay in, or termination of, our clinical trials would delay our obtaining FDA or EMA approval for the affected product candidate and, ultimately, our ability to commercialize that product candidate.

~~If we~~● ~~cannot~~the ~~demonstrate~~FDA ~~an acceptable toxicity profile for our product candidates, if any, in non-clinical studies, we will not be able to initiate~~ or ~~continue~~other ~~clinical~~regulatory ~~trials~~authorities ormay ~~obtain~~determine ~~approval~~that ~~for~~additional ~~our~~safety ~~product~~testing ~~candidates~~is required.

~~To move~~Any asuch ~~product~~events ~~candidate~~would ~~into~~increase ~~human~~our ~~clinical~~costs ~~trials,~~and ~~we must first demonstrate an acceptable toxicity profile in preclinical testing.~~could ~~Furthermore,~~delay ~~to obtain approval, we must also demonstrate safety in various non-clinical tests. We may not have conducted~~ or ~~may~~prevent ~~not conduct~~our ~~the~~ability ~~types~~to ofcommercialize ~~non-clinical testing required by regulatory authorities, or future non-clinical tests may indicate that~~ our product ~~candidates~~ ~~are not safe for use. Preclinical and non-clinical testing is expensive~~candidates, time-consuming and has an uncertain outcome. In addition, success in initial non-clinical testing does not ensure that later non-clinical testing will be successful. We may experience numerous unforeseen events during the non-clinical testing process, which could ~~delay~~adversely orimpact ~~prevent~~ our ~~ability~~business, tofinancial ~~develop~~condition ~~or commercialize our product~~and ~~candidates,~~results ~~including:~~of operations.

~~● our preclinical and non-clinical testing may produce inconclusive or negative safety results, which may require us to conduct additional non-clinical testing or to abandon product candidates;~~21

●We, or our ~~product~~collaborators, ~~candidates~~ may ~~have~~face ~~unfavorable~~delays in ~~pharmacology~~completing our pre-clinical or ~~toxicity~~clinical ~~characteristics;~~trials, and may not be able to complete them at all.

●We have not completed the pre-clinical and clinical trials necessary to support an application for approval to market of our product candidates, if any. Our or our collaborators’ current and future clinical trials may ~~cause~~be ~~undesirable~~delayed, ~~side~~unsuccessful, ~~effects~~or ~~such~~terminated as ~~negative~~a ~~immune~~result ~~responses~~of ~~that~~many ~~lead~~factors, ~~to complications;~~including:

● ~~our~~delays ~~enrolled~~in ~~patients~~designing ~~may~~an ~~have~~appropriate ~~allergies~~clinical ~~that~~trial ~~lead~~protocol toand ~~complications~~reaching ~~after~~agreement ~~treatment;~~on trial design with investigators and regulatory authorities;

● ~~the~~governmental ~~FDA~~ or ~~other~~regulatory delays, failure to obtain regulatory ~~authorities~~approval ~~may~~or ~~determine~~changes ~~that~~in ~~additional~~regulatory ~~safety~~requirements, ~~testing~~policy isor ~~required.~~guidelines;

~~Any such~~● ~~events~~adding ~~would~~new ~~increase~~clinical ~~our~~trial ~~costs and could delay or prevent our ability to commercialize our product candidates, which could adversely impact our business, financial condition and results of operations.~~sites

21● reaching agreement on acceptable terms with prospective contract research organizations, or CROs, and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and trial sites;

~~We, or~~● ~~our~~the ~~collaborators,~~actual ~~may~~performance ~~face~~of ~~delays~~CROs inand ~~completing our pre-~~clinical ortrial ~~clinical~~sites ~~trials,~~in ~~and~~ensuring ~~may~~the ~~not~~proper beand ~~able~~timely toconduct ~~complete~~of ~~them~~our atclinical ~~all.~~trials;

~~We have~~● ~~not~~adverse ~~completed~~effects ~~the~~experienced ~~pre-clinical~~by ~~and~~subjects ~~clinical~~in ~~trials necessary to support an application for approval to market of our product candidates, if any. Our or our collaborators’ current and future~~ clinical trials ~~may be delayed, unsuccessful, or terminated as a result of many factors, including:~~;

● ~~delays~~manufacturing insufficient ~~designing~~quantities anof ~~appropriate~~product ~~clinical~~candidates ~~trial~~for ~~protocol~~use ~~and~~in ~~reaching~~clinical ~~agreement~~trials; ~~on trial design with investigators~~ and ~~regulatory authorities;~~

● ~~governmental or regulatory~~ delays, ~~failure~~in toachieving ~~obtain~~study ~~regulatory~~endpoints ~~approval~~and orcompleting ~~changes~~data inanalysis ~~regulatory~~for ~~requirements,~~a ~~policy or guidelines;~~trial.

●In ~~adding~~addition ~~new~~to ~~clinical~~these ~~trial~~factors, ~~sites~~our trials may be delayed, unsuccessful or terminated because:

● ~~reaching~~regulators ~~agreement~~or oninstitutional ~~acceptable~~review ~~terms with prospective contract research organizations~~boards, or ~~CROs~~IRBs, ~~and~~may ~~clinical~~not ~~trial~~authorize ~~sites,~~us ~~the terms of which can be subject~~ to ~~extensive~~commence ~~negotiation~~a ~~and~~clinical ~~may vary significantly among different CROs and~~ trial ~~sites~~;

● ~~the~~regulators ~~actual~~or ~~performance~~IRBs ofmay ~~CROs~~suspend ~~and~~or terminate clinical ~~trial~~research ~~sites~~for invarious ~~ensuring~~reasons, ~~the~~including ~~proper~~noncompliance ~~and~~with ~~timely~~regulatory ~~conduct~~requirements ofor ~~our~~concerns ~~clinical~~about ~~trials~~patient safety;

● ~~adverse~~we ~~effects~~may ~~experienced~~suspend byor ~~subjects~~terminate inour clinical trials if we believe that they expose the participating patients to unacceptable health risks;

● ~~manufacturing~~patients ~~sufficient~~may ~~quantities~~not complete clinical trials due to safety issues, side effects, such as injection site discomfort, a belief that they are receiving placebo instead of our product candidates, ~~for~~or ~~use~~other ~~in clinical trials~~reasons; ~~and~~

● ~~delays~~patients with serious diseases included in ~~achieving~~our ~~study~~clinical ~~endpoints~~trials ~~and~~may ~~completing~~die ~~data~~or ~~analysis~~suffer other adverse medical events for areasons ~~trial.~~that may not be related to our product candidates;

~~In addition~~● toin ~~these~~those ~~factors,~~trials where our ~~trials~~product candidate is being tested in combination with one or more other therapies, deaths may occur that may be ~~delayed,~~attributable ~~unsuccessful~~to orthe ~~terminated~~other ~~because:~~therapies;

● ~~regulators~~we ormay ~~institutional~~have ~~review~~difficulty ~~boards,~~in ormaintaining ~~IRBs,~~contact ~~may~~with ~~not~~patients ~~authorize~~after treatment, preventing us tofrom ~~commence~~collecting athe ~~clinical~~data ~~trial~~required by our study protocol;

● ~~regulators~~product orcandidates ~~IRBs~~ may ~~suspend~~demonstrate ora ~~terminate~~lack ~~clinical~~of ~~research~~efficacy ~~for~~during ~~various~~clinical ~~reasons, including noncompliance with regulatory requirements or concerns about patient safety~~trials;

● wepersonnel ~~may~~conducting ~~suspend or terminate our~~ clinical trials ifmay wefail ~~believe~~to ~~that~~properly ~~they~~administer ~~expose~~our ~~the~~product ~~participating patients to unacceptable health risks~~candidates; and

● ~~patients~~our collaborators may decide not ~~complete clinical trials due~~ to ~~safety~~pursue ~~issues,~~further ~~side~~clinical ~~effects, such as injection site discomfort, a belief that they are receiving placebo instead of our product candidates, or other reasons;~~trials.

~~● patients with serious diseases included in our clinical trials may die or suffer other adverse medical events for reasons that may not be related to our product candidates;~~22

●We incould ~~those~~encounter ~~trials~~delays ~~where~~if our ~~product~~clinical ~~candidate~~trials isare ~~being~~suspended ~~tested~~or terminated by us, by IRBs of the institutions in ~~combination~~which ~~with~~such trials ~~one~~are being conducted, by the Data Safety Monitoring Boards for such trials or ~~more~~by the FDA or other ~~therapies,~~regulatory ~~deaths~~authorities. Such authorities may ~~occur~~impose ~~that~~such ~~may~~a besuspension ~~attributable~~or termination due to a number of factors, including potential for unacceptable safety risks to patients, inspection of the ~~other~~clinical ~~therapies;~~trial operation or trial site, changes in government regulations or administrative actions.

●In addition, we ~~may~~rely on academic institutions, physician practices and CROs to conduct, supervise or monitor some or all aspects of clinical trials involving our product candidates. We have ~~difficulty~~less incontrol ~~maintaining~~over ~~contact~~the ~~with~~timing ~~patients~~and ~~after~~other ~~treatment,~~aspects ~~preventing~~of usthese ~~from~~clinical ~~collecting~~trials than if we conducted the ~~data~~monitoring ~~required~~and bysupervision entirely on our ~~study~~own. Third parties may not perform their responsibilities for our clinical trials on our anticipated schedule or consistent with a clinical trial protocol; or applicable regulations. We also may rely on CROs to perform our data management and analysis. They may not provide these services as required or in a timely or compliant manner, and we may be held legally responsible for any or all of their performance failures or inadequacies.

●Moreover, our development costs will increase because we will be required to complete additional or larger clinical trials for our product candidates prior to FDA or other regulatory approval. If we or our collaborators experience delays in the completion of, or termination of, any clinical trial of our product candidates, the commercial prospects of our product candidates will be harmed, and our ability to generate product revenues from any of these product candidates will be delayed or eliminated. In addition, any delays in completing our clinical trials will increase our costs, slow down our product candidate development and approval process, and jeopardize our ability to commence product sales and generate revenues. Any of these occurrences may ~~demonstrate~~harm aour ~~lack~~business, financial condition and prospects. In addition, many of ~~efficacy~~the ~~during~~factors that cause, or lead to, a delay in the commencement or completion of clinical trials; may also lead to the denial of regulatory approval of our product candidates.

●We ~~personnel~~have ~~conducting~~limited ~~clinical~~experience ~~trials~~in ~~may~~the ~~fail~~development of totherapeutic ~~properly~~product ~~administer~~candidates and therefore may encounter difficulties developing our product ~~candidates;~~candidate ~~and~~or managing our operations in the future.

●We ~~our~~have ~~collaborators~~limited ~~may~~experience ~~decide~~in ~~not~~the discovery, development and manufacturing of therapeutic compounds. In order to ~~pursue~~successfully ~~further~~develop our product candidate, we must continuously supplement our research, clinical ~~trials~~development, regulatory, medicinal chemistry, and manufacturing capabilities through the addition of key employees, consultants or third-party contractors to provide certain capabilities and skill sets that we do not possess.

22Furthermore, we have adopted an operating model that largely relies on the outsourcing of a number of responsibilities and key activities to third-party consultants, and contract research and manufacturing organizations in order to advance the development of our product candidates. Therefore, our success depends in part on our ability to retain highly qualified key management, personnel, and directors to develop, implement and execute our business strategy, operate the company and oversee the activities of our consultants and contractors, as well as academic and corporate advisors or consultants to assist us in this regard. We are currently highly dependent upon the efforts of our management team. In order to develop our product candidates, we need to retain or attract certain personnel, consultants or advisors with experience in drug development activities that include a number of disciplines, including research and development, clinical trials, medical matters, government regulation of pharmaceuticals, manufacturing, formulation and chemistry, business development, accounting, finance, regulatory affairs, human resources and information systems.

WeOur ~~could~~success ~~encounter~~depends ~~delays~~in ifpart on our ~~clinical~~continued ~~trials~~ability to ~~are~~attract, ~~suspended~~retain orand ~~terminated~~motivate byhighly usqualified management, ~~by IRBs of~~clinical ~~the~~and ~~institutions~~scientific inpersonnel ~~which~~and ~~such~~on our ability to develop and maintain ~~trials~~important ~~are~~relationships ~~being~~with ~~conducted,~~leading byacademic ~~the~~institutions, ~~Data~~clinicians ~~Safety~~and ~~Monitoring~~scientists. ~~Boards~~The competition for ~~such~~qualified ~~trials~~personnel orin by the biotechnology ~~FDA~~and orpharmaceuticals ~~other~~field ~~regulatory~~is ~~authorities~~intense. ~~Such~~We will need to hire additional personnel as we expand our clinical development and ~~authorities~~commercial ~~may~~activities. ~~impose~~While ~~such~~we ahave ~~suspension~~not orhad ~~termination~~difficulties ~~due~~recruiting qualified individuals, to adate, ~~number~~we ofmay ~~factors,~~not ~~including~~be ~~potential~~able to attract and retain quality personnel on acceptable terms given the competition for ~~unacceptable~~such ~~safety~~personnel ~~risks to~~among ~~patients~~biotechnology, ~~inspection~~pharmaceutical ofand ~~the~~other ~~clinical~~companies. Although ~~trial~~we ~~operation~~have ornot ~~trial~~experienced ~~site~~material difficulties in retaining key personnel in the past, ~~changes~~we may not be able to continue to do so in ~~government~~the ~~regulations~~future oron ~~administrative~~acceptable ~~actions~~terms, if at all.

In addition, we rely on academic institutions, physician practices and CROs to conduct, supervise or monitor some or all aspects of clinical trials involving our product candidates. We have less control over the timing and other aspects of these clinical trials than if we conducted the monitoring and supervision entirely on our own. Third parties may not perform their responsibilities for our clinical trials on our anticipated schedule or consistent with a clinical trial protocol or applicable regulations. We also may rely on CROs to perform our data management and analysis. They may not provide these services as required or in a timely or compliant manner, and we may be held legally responsible for any or all of their performance failures or inadequacies.23

~~Moreover, our~~We ~~development~~have ~~costs~~limited ~~will~~capacity ~~increase because we will be required to complete additional or larger clinical trials~~ for ~~our product candidates~~recruiting ~~prior~~and tomanaging ~~FDA or other regulatory approval. If we or our collaborators experience delays in the completion of, or termination of, any~~ clinical ~~trial of our product candidates~~trials, ~~the~~which ~~commercial~~could ~~prospects~~impair of our ~~product~~timing ~~candidates will be harmed, and our ability~~ to ~~generate product~~initiate ~~revenues from any of these product candidates will be delayed~~ or ~~eliminated.~~complete ~~In addition, any delays in completing our~~ clinical trials ~~will~~of ~~increase~~ our ~~costs, slow down our~~ product ~~candidate~~candidates ~~development~~ and ~~approval process, and jeopardize our ability to commence~~materially ~~product sales and generate revenues. Any of these occurrences may~~ harm our business~~, financial condition and prospects~~. ~~In addition, many of the factors that cause, or lead to, a delay in the commencement or completion of clinical trials may also lead to the denial of regulatory approval of our product candidates.~~

We have limited capacity to recruit and manage the clinical trials necessary to obtain FDA approval or approval by other regulatory authorities. By contrast, larger pharmaceutical and bio-pharmaceutical companies often have substantial staff with extensive experience in ~~the~~conducting ~~development~~clinical oftrials ~~therapeutic~~with multiple product candidates ~~and~~across ~~therefore~~multiple indications. In addition, they may ~~encounter~~have ~~difficulties~~greater ~~developing~~financial ~~our~~resources to compete for the same clinical investigators and patients that we ~~product~~are ~~candidate~~attempting orto ~~managing~~recruit for our ~~operations~~clinical trials. If potential competitors are successful in completing drug development for their product candidates and obtain approval from the ~~future~~FDA, they could limit the demand for our product candidates.

~~We have~~As ~~limited~~a ~~experience in the discovery~~result, ~~development~~we ~~and~~may ~~manufacturing~~be ofat ~~therapeutic~~a ~~compounds.~~competitive Indisadvantage that ~~order~~could todelay ~~successfully~~the ~~develop~~initiation, ~~our product~~recruitment, ~~candidate~~timing, wecompletion ~~must~~of ~~continuously supplement~~ our ~~research,~~ clinical ~~development,~~trials ~~regulatory, medicinal chemistry,~~ and ~~manufacturing capabilities~~obtaining ~~through~~regulatory ~~the addition of key employees~~approvals, ~~consultants~~if orat ~~third-party contractors to provide certain capabilities and skill~~all, ~~sets~~for ~~that~~our weproduct ~~do not possess~~candidate.

~~Furthermore,~~ If we ~~have~~encounter ~~adopted~~difficulties anenrolling ~~operating model that largely relies on the outsourcing of a number of responsibilities and key activities to third-party~~patients ~~consultants, and contract research and manufacturing organizations~~ in ~~order to advance the development of~~ our ~~product~~clinical ~~candidates. Therefore~~trials, ~~our~~ ~~success depends in part on~~ our ability to retain highly qualified key management, personnel, and directors to develop, implement and execute our business strategy, operate the company and oversee the activities of our consultants and contractors, as well as academic and corporate advisors or consultants to assist us in this regard. We are currently highly dependent upon the efforts of our management team. In order to develop our product candidates, we need to retain or attract certain personnel, consultants or advisors with experience in drug development activities that include a number of disciplines, including research and development, clinical trials, ~~medical~~could ~~matters, government~~be ~~regulation~~delayed ofor ~~pharmaceuticals,~~otherwise ~~manufacturing,~~adversely ~~formulation and chemistry, business development, accounting, finance, regulatory affairs, human resources and information systems~~affected..

~~Our~~Clinical ~~success~~trials ~~depends~~for ~~in part on~~ our ~~continued~~product ~~ability to attract~~candidates, ~~retain~~if ~~and motivate highly qualified management~~any, ~~clinical~~will ~~and~~require ~~scientific~~us ~~personnel and on our ability~~ to ~~develop~~identify and ~~maintain~~enroll ~~important~~a ~~relationships with~~large ~~leading~~number ~~academic~~of ~~institutions,~~patients ~~clinicians~~with ~~and scientists. The competition for qualified personnel in~~ the ~~biotechnology~~disease ~~and~~under ~~pharmaceuticals field is intense~~investigation. We ~~will need to hire additional personnel as we expand our clinical development and commercial activities. While we have not had difficulties recruiting qualified individuals, to date, we~~ may not be able to ~~attract and retain quality personnel on acceptable~~enroll ~~terms~~a ~~given~~sufficient ~~the~~number ~~competition~~of ~~for such personnel among biotechnology~~patients, ~~pharmaceutical~~or ~~and~~those ~~other~~with ~~companies.~~required ~~Although~~or wedesired ~~have~~characteristics, ~~not experienced material difficulties~~ in ~~retaining~~a ~~key~~timely ~~personnel~~manner. inPatient ~~the~~enrollment ~~past,~~is ~~we may not be able to continue to do so in the future on acceptable terms,~~affected ifby atfactors ~~all.~~ including:

23● severity of the disease under investigation;

~~We have~~● ~~limited~~design ~~capacity for recruiting and managing clinical trials, which could impair our timing to initiate or complete clinical trials~~ of ~~our~~the ~~product~~trial ~~candidates and materially harm our business.~~protocol;

~~We have~~● ~~limited capacity to recruit and manage~~ the ~~clinical~~size ~~trials necessary to obtain FDA approval or approval by other regulatory authorities. By contrast, larger pharmaceutical~~ and ~~bio-pharmaceutical companies~~ ~~often~~nature ~~have~~of substantial staff with extensive experience in conducting clinical trials with multiple product candidates across multiple indications. In addition, they may have greater financial resources to compete for the ~~same~~patient clinical investigators and patients that we are attempting to recruit for our clinical trials. If potential competitors are successful in completing drug development for their product candidates and obtain approval from the FDA, they could limit the demand for our product candidates.population;

~~As a~~● ~~result,~~eligibility wecriteria ~~may~~for ~~be at a competitive disadvantage that could delay~~ the ~~initiation,~~study ~~recruitment,~~in ~~timing, completion of our clinical trials and obtaining regulatory approvals, if at all, for our product candidate.~~question;

~~If we~~● ~~encounter~~lack ~~difficulties~~of ~~enrolling~~a ~~patients~~sufficient innumber ~~our~~of ~~clinical~~patients ~~trials,~~who ~~our~~meet ~~clinical~~the ~~trials~~enrollment ~~could~~criteria befor ~~delayed~~our orclinical ~~otherwise adversely affected.~~trials;

~~Clinical trials~~● ~~for~~delays ~~our~~required ~~product~~to ~~candidates,~~characterize ifthe ~~any,~~infection ~~will~~to ~~require~~allow us to ~~identify~~select ~~and enroll~~ a ~~large~~product ~~number~~candidate, ofwhich ~~patients with the disease under investigation. We~~ may ~~not~~lead bepatients ~~able~~to seek to enroll ain ~~sufficient~~other ~~number~~clinical oftrials ~~patients,~~ or ~~those~~seek ~~with~~alternative ~~required or desired characteristics, in a timely manner. Patient enrollment is affected by factors including:~~treatments;

● ~~severity~~perceived risks and benefits of the ~~disease~~product candidate under ~~investigation~~study;

● ~~design~~availability of ~~the~~competing ~~trial~~therapies ~~protocol~~and clinical trials;

● ~~the~~efforts ~~size~~to ~~and~~facilitate ~~nature~~timely ofenrollment ~~the~~in ~~patient~~clinical ~~population~~trials;

● ~~eligibility~~scheduling ~~criteria~~conflicts ~~for~~with ~~the~~participating ~~study in question~~clinicians;

● ~~lack~~patient ofreferral apractices ~~sufficient number~~ of ~~patients who meet the enrollment criteria for our clinical trials~~physicians;

● ~~delays required to characterize~~ the ~~infection~~ability to ~~allow~~monitor ~~us to select a product candidate, which may lead~~ patients toadequately ~~seek~~during toand ~~enroll~~after ~~in other clinical trials or seek alternative treatments~~treatment; and

● ~~perceived~~proximity ~~risks~~ and ~~benefits~~availability of ~~the~~clinical ~~product~~trial ~~candidate~~sites ~~under~~for ~~study;~~prospective patients.

●If ~~availability~~we have difficulty enrolling a sufficient number or diversity of ~~competing~~patients ~~therapies~~to ~~and~~conduct our clinical trials; as planned, we may need to delay or terminate ongoing or planned clinical trials, either of which would have an adverse effect on our business.

~~● efforts to facilitate timely enrollment in clinical trials;~~24

●Results ~~scheduling~~of ~~conflicts~~earlier ~~with~~studies ~~participating~~and ~~clinicians;~~clinical trials may not be predictive of future trial results.

●Clinical testing is expensive and can take many years to complete, and its outcome is inherently uncertain. Failure can occur at any time during the clinical trial process. The results of preclinical studies and early clinical trials of our product candidates, if any, may not be predictive of the design or results of later-stage clinical trials. Any positive results generated to date do not ensure that later trials will demonstrate similar results. While we have observed statistically significant improvements in the outcomes of some of our clinical trials, many of the improvements we have seen have not reached statistical significance. Statistical significance is a statistical term that means that an effect is unlikely to have occurred by chance. In order to be approved, product candidates must demonstrate that their effect on patients’ diseases in the trial is statistically significant. Product candidates in later stages of clinical trials may fail to show the desired safety and efficacy traits despite having progressed through preclinical studies and initial clinical trials. Early clinical trials frequently enroll patient ~~referral~~populations ~~practices~~that are different from the patient populations in later trials, resulting in different outcomes in later clinical trials from those in earlier stage clinical trials. In addition, adverse events may not occur in early clinical trials and only emerge in larger, late-stage clinical trials or after commercialization. A number of ~~physicians;~~companies in the biopharmaceutical industry have suffered significant setbacks in advanced clinical trials due to lack of efficacy or adverse safety profiles, notwithstanding promising results in earlier clinical trials. If later stage clinical trials do not demonstrate efficacy and safety of our product candidates we will not be able to market them and our business will be materially harmed.

●Regulatory ~~the~~authorities ~~ability~~may tonot ~~monitor~~approve ~~patients~~our product ~~adequately~~candidates, ~~during~~if ~~and~~any, ~~after~~even ~~treatment;~~if they meet safety and efficacy endpoints in clinical trials.

●Under ~~proximity~~certain ~~and~~circumstances, ~~availability~~regulatory authorities may revise or retract previous guidance during the course of our clinical activities or after the completion of our clinical trials. A regulatory authority may also disqualify a clinical trial ~~sites~~in whole or in part from consideration in support of approval of a potential product for ~~prospective~~commercial ~~patients~~sale or otherwise deny approval of that product. Prior to regulatory approval, a regulatory authority may elect to obtain advice from outside experts regarding scientific issues and/or marketing applications under a regulatory authority review. In the United States, these outside experts are convened through the FDA’s Advisory Committee process, which would report to the FDA and make recommendations that may differ from the views of the FDA. Should an Advisory Committee be convened, it would be expected to lengthen the time for obtaining regulatory approval, if such approval is obtained at all.

~~If we~~The ~~have~~FDA ~~difficulty~~and ~~enrolling~~foreign aregulatory ~~sufficient~~agencies ~~number or diversity of patients to conduct our clinical trials as planned, we~~ may ~~need to~~ delay, limit or ~~terminate~~deny ~~ongoing~~marketing orapproval ~~planned~~for ~~clinical~~many ~~trials~~reasons, ~~either of which would have an adverse effect on our business.~~including:

24● a product candidate may not be considered safe or effective;

~~Results of~~● ~~earlier~~our ~~studies~~manufacturing ~~and~~processes ~~clinical~~or ~~trials~~facilities may not bemeet ~~predictive~~the ofapplicable ~~future trial results.~~requirements;

~~Clinical testing~~● ischanges ~~expensive~~in ~~and can take many years to complete, and its outcome is inherently uncertain. Failure can occur at any time during~~ the ~~clinical~~agencies’ ~~trial~~approval ~~process.~~policies ~~The~~or ~~results~~adoption of ~~preclinical~~new ~~studies~~regulations ~~and early clinical trials of our product candidates, if any,~~ may ~~not~~require ~~be predictive~~additional ofwork ~~the~~on design or results of later-stage clinical trials. Any positive results generated to date do not ensure that later trials will demonstrate similar results. While we have observed statistically significant improvements in the outcomes of some of our ~~clinical trials~~part, ~~many~~for of the improvements we have seen have not reached statistical significance. Statistical significance is a statistical term that means that an effect is unlikely to have occurred by chance. In order to be approvedexample, ~~product candidates must demonstrate that their effect on patients’ diseases in~~ the ~~trial~~FDA ~~is statistically significant. Product candidates in later stages of clinical trials~~ may ~~fail~~require us to ~~show~~change the desired safety and efficacy traits despite having progressed through preclinical studies and initial clinical trials. Early clinical trials frequently enroll patient populations that are different from the patient populations in later trials, resulting in different outcomes in later clinical trials from those in earlier stage clinical trials. In addition, adverse events may not occur in early clinical trials and only emerge in larger, late-stage clinical trials or ~~after~~expand ~~commercialization. A number of companies in~~ the ~~biopharmaceutical~~ ~~industry~~endpoints ~~have suffered significant setbacks~~ in ~~advanced~~our clinical trials due to lack of efficacy or adverse safety profiles, notwithstanding promising results in earlier clinical trials. If later stage clinical trials do not demonstrate efficacy and safety of our product candidates we will not be able to market them and our business will be materially harmed.;

~~Regulatory authorities~~● ~~may~~different ~~not~~divisions ~~approve~~of ~~our~~the ~~product~~FDA ~~candidates,~~are ifreviewing ~~any,~~different ~~even~~product ifcandidates ~~they~~and ~~meet~~those ~~safety~~divisions ~~and~~may ~~efficacy~~have ~~endpoints~~different inrequirements ~~clinical~~for ~~trials.~~approval; and

~~Under certain~~● ~~circumstances,~~changes regulatory authorities may revise or retract previous guidance during the course of our clinical activities or after the completion of our clinical trials. A regulatory authority may also disqualify a clinical trial in ~~whole or in part from consideration in support of approval of a potential product for commercial sale or otherwise deny approval of that product. Prior to~~ regulatory ~~approval~~law, a ~~regulatory~~FDA ~~authority may elect to obtain advice from outside experts regarding scientific issues and/~~or ~~marketing~~foreign ~~applications under a~~ regulatory ~~authority~~agency ~~review. In the United States~~organization, ~~these~~or ~~outside~~personnel ~~experts are convened through the FDA’s Advisory Committee process, which would report to the FDA and make recommendations that~~ may ~~differ~~result ~~from~~in ~~the~~different ~~views~~requirements ~~of the FDA. Should an Advisory Committee be convened, it would be expected to lengthen the time~~ for ~~obtaining regulatory~~ approval, ifthan ~~such approval is obtained at all~~anticipated.

~~The~~Our product candidates may not be approved even if they achieve their endpoints in clinical trials. Regulatory agencies, including the FDA, or their advisors may disagree with our trial design and ~~foreign~~our ~~regulatory~~interpretations of data from preclinical studies and clinical trials. Regulatory agencies also may ~~delay,~~approve ~~limit~~a product candidate for fewer or ~~deny~~more ~~marketing~~limited indications than requested or may grant approval ~~for~~subject ~~many~~to ~~reasons~~the performance of post-marketing studies. In addition, regulatory ~~including:~~agencies may not approve the labeling claims that are necessary or desirable for the successful commercialization of our product candidates.

●Any adelay in or failure to receive or maintain approval for any of our product ~~candidate~~candidates ~~may~~could ~~not~~prevent beus ~~considered~~from ~~safe~~ever generating revenues or ~~effective;~~achieving profitability.

~~● our manufacturing processes or facilities may not meet the applicable requirements;~~25

●We ~~changes~~may inbe ~~the~~required ~~agencies’~~to ~~approval~~suspend, ~~policies~~repeat or terminate ~~adoption~~our ofclinical ~~new~~trials ~~regulations~~if ~~may~~they ~~require~~are ~~additional~~not ~~work~~conducted onin ~~our~~accordance ~~part,~~with ~~for~~regulatory ~~example~~requirements, the ~~FDA~~results ~~may~~are ~~require~~negative usor ~~to change~~ inconclusive, or ~~expand~~ the ~~endpoints~~trials inare ~~our~~not ~~clinical~~well ~~trials;~~designed.

●Clinical ~~different~~trials ~~divisions~~must ofbe ~~the~~conducted in accordance with FDA regulations governing clinical studies, or other applicable foreign government guidelines, and are ~~reviewing~~subject ~~different~~to oversight by the FDA, other foreign governmental agencies and IRBs at the medical institutions where the clinical trials are conducted. In addition, clinical trials must be conducted with product candidates produced under current Good Manufacturing Practices, or cGMP, and ~~those~~may ~~divisions~~require large numbers of test subjects. Clinical trials may ~~have~~be ~~different~~suspended ~~requirements~~by the FDA, other foreign governmental agencies or us for ~~approval;~~various ~~and~~reasons, including:

● ~~changes~~deficiencies in ~~regulatory~~the ~~law,~~conduct ~~FDA~~of orthe ~~foreign~~clinical ~~regulatory~~trials, ~~agency~~including ~~organization,~~failure orto ~~personnel~~conduct ~~may~~the ~~result~~clinical trial in ~~different~~accordance ~~requirements~~with ~~for~~regulatory ~~approval~~requirements ~~than~~or ~~anticipated.~~clinical protocols;

~~Our product~~● ~~candidates~~deficiencies ~~may not be approved even if they achieve their endpoints~~ in ~~clinical trials. Regulatory agencies, including~~ the ~~FDA, or~~clinical ~~their advisors may disagree with our~~ trial ~~design~~operations ~~and our interpretations of data from preclinical studies and clinical trials. Regulatory agencies also may approve a product candidate for fewer~~ or ~~more~~trial limited indications than requested or may grant approval subject to the performance of post-marketing studies. In addition, regulatory agencies may not approve the labeling claims that are necessary or desirable for the successful commercialization of our product candidates.sites;

~~Any delay~~● inthe ~~or failure to receive or maintain approval for any of our~~ product ~~candidates~~candidate ~~could~~may ~~prevent~~have usunforeseen ~~from~~adverse ~~ever~~side ~~generating revenues or achieving profitability.~~effects;

25● the time required to determine whether the product candidate is effective may be longer than expected;

~~We may~~● bedeaths ~~required~~or toother ~~suspend,~~adverse ~~repeat~~events orarising ~~terminate~~during ~~our~~a clinical ~~trials~~trial ifdue ~~they~~to ~~are~~medical ~~not~~problems ~~conducted~~that inmay ~~accordance~~not ~~with~~be ~~regulatory~~related ~~requirements, the~~to ~~results~~clinical ~~are~~trial ~~negative or inconclusive, or the trials are not well designed.~~treatments;

~~Clinical trials~~● ~~must be conducted in accordance with FDA regulations governing clinical studies, or other applicable foreign government guidelines, and are subject to oversight by~~ the ~~FDA, other foreign governmental agencies and IRBs at the medical institutions where the clinical trials are conducted. In addition, clinical trials must be conducted with~~ product ~~candidates~~candidate ~~produced under current Good Manufacturing Practices, or cGMP, and~~ may ~~require~~not ~~large~~appear ~~numbers~~to ~~of test subjects. Clinical trials may~~ be ~~suspended~~more byeffective ~~the~~than ~~FDA,~~current ~~other foreign governmental agencies or us for various reasons, including:~~therapies;

● ~~deficiencies~~the inquality ~~the~~or ~~conduct~~stability of the ~~clinical~~product ~~trials,~~candidate ~~including~~may ~~failure~~fall tobelow ~~conduct~~acceptable ~~the clinical trial in accordance with regulatory requirements or clinical protocols~~standards; and

● ~~deficiencies~~insufficient inquantities of the ~~clinical~~product ~~trial~~candidate ~~operations~~might orbe ~~trial~~available ~~sites;~~to complete the trials.

●In addition, changes in regulatory requirements and guidance may occur and we may need to amend clinical trial protocols to reflect these changes. Amendments may require us to resubmit our clinical trial protocols to IRBs for reexamination, which may impact the costs, timing or successful completion of a clinical trial. Due to these and other factors, our product ~~candidate~~candidates could take longer to gain regulatory approval than we expect or we may ~~have~~never ~~unforeseen~~gain approval ~~adverse~~for ~~side~~any ~~effects;~~product candidates, which could reduce or eliminate our revenue by delaying or terminating the commercialization of our product candidates.

●Any ~~the~~product ~~time~~candidate ~~required~~for which we, or our collaborators, obtain marketing approval could be subject to ~~determine~~restrictions ~~whether~~or ~~the~~withdrawal ~~product~~from ~~candidate~~the ismarket, ~~effective~~and we may be ~~longer~~subject ~~than~~to ~~expected;~~penalties if we fail to comply with regulatory requirements or if we experience unanticipated problems with our products, when and if any of them are approved.

●Any ~~deaths~~product candidate that we or our collaborators obtain marketing approval for, along with the manufacturing processes, post-approval clinical data, labeling, advertising and promotional activities for such product, will be subject to continual requirements of the FDA and other ~~adverse~~regulatory ~~events~~authorities. ~~arising~~These ~~during~~requirements include submissions of safety and other post-marketing information, reports, registration and listing requirements, cGMP requirements relating to quality control, quality assurance and corresponding maintenance of records and documents, requirements regarding the distribution of samples to physicians and recordkeeping. Even if marketing approval of a ~~clinical~~product ~~trial~~candidate ~~due~~is granted, the approval may be subject to ~~medical~~limitations ~~problems~~on ~~that~~the indicated uses for which the product may ~~not~~be marketed or to conditions of approval, or contain requirements for costly post-marketing testing and surveillance to monitor the safety or efficacy of the product. The FDA closely regulates the post-approval marketing and promotion of drugs to ensure drugs are marketed only for the approved indications and in accordance with the provisions of the approved labeling. The FDA imposes stringent restrictions on manufacturers’ communications regarding off-label use. If we market our products outside of their approved indications, we will be ~~related~~subject to ~~clinical~~enforcement ~~trial~~action ~~treatments;~~for off-label marketing.

●In ~~the~~addition, ~~product~~later ~~candidate~~discovery ~~may~~of ~~not~~previously ~~appear~~unknown problems with these products, manufacturers or manufacturing processes, or failure to becomply ~~more~~with ~~effective~~regulatory ~~than~~requirements, ~~current~~may ~~therapies;~~yield various results, including:

● ~~the~~restrictions ~~quality~~on orsuch ~~stability~~products, ofmanufacturers ~~the~~or ~~product~~manufacturing ~~candidate may fall below acceptable standards~~processes; ~~and~~

● ~~insufficient~~restrictions ~~quantities~~on of the ~~product~~labeling ~~candidate~~or ~~might~~marketing beof ~~available~~a ~~to complete the trials.~~product;

In addition, changes in regulatory requirements and guidance may occur and we may need to amend clinical trial protocols to reflect these changes. Amendments may require us to resubmit our clinical trial protocols to IRBs for reexamination, which may impact the costs, timing or successful completion of a clinical trial. Due to these and other factors, our product candidates could take longer to gain regulatory approval than we expect or we may never gain approval for any product candidates, which could reduce or eliminate our revenue by delaying or terminating the commercialization of our product candidates.26

~~Any product~~● ~~candidate for which we, or our collaborators, obtain marketing approval could be subject to~~ restrictions oron ~~withdrawal~~product ~~from~~distribution ~~the market, and we may be subject to penalties if we fail to comply with regulatory requirements~~ or ~~if we experience unanticipated problems with our products, when and if any of them are approved.~~use;

~~Any product~~● candidate that we or our collaborators obtain marketing approval for, along with the manufacturing processes, post-approval clinical data, labeling, advertising and promotional activities for such product, will be subject to continual requirements of the FDA and other regulatory authorities. These requirements include submissions of safety and other post-marketing information, reports, registration and listing requirements, cGMP requirements relating to ~~quality~~conduct control, quality assurance and corresponding maintenance of records and documents, requirements regarding the distribution of samples to physicians and recordkeeping. Even if marketing approval of a product candidate is granted, the approval may be subject to limitations on the indicated uses for which the product may be marketed or to conditions of approval, or contain requirements for costly post-marketing ~~testing~~clinical and surveillance to monitor the safety or efficacy of the product. The FDA closely regulates the post-approval marketing and promotion of drugs to ensure drugs are marketed only for the approved indications and in accordance with the provisions of the approved labeling. The FDA imposes stringent restrictions on manufacturers’ communications regarding off-label use. If we market our products outside of their approved indications, we will be subject to enforcement action for off-label marketing.trials;

~~In addition,~~● ~~later~~warning ~~discovery of previously unknown problems with these products, manufacturers~~ or ~~manufacturing~~untitled ~~processes, or failure to comply with regulatory requirements, may yield various results, including:~~letters;

● ~~restrictions~~withdrawal onof ~~such~~the products, ~~manufacturers~~from orthe ~~manufacturing processes~~market;

26● refusal to approve pending applications or supplements to approved applications that we submit;

● ~~restrictions~~recall onof ~~the~~products, ~~labeling~~fines, restitution or ~~marketing~~disgorgement of aprofits ~~product~~or revenue;

● ~~restrictions~~suspension onor ~~product~~withdrawal ~~distribution~~of ormarketing ~~use~~approvals;

● ~~requirements~~refusal to ~~conduct~~permit ~~post-marketing~~the ~~clinical~~import ~~trials~~or export of our products;

● ~~warning~~product ~~or untitled letters~~seizure; and

● ~~withdrawal~~injunctions ofor the ~~products~~imposition ~~from~~of ~~the~~civil ~~market;~~or criminal penalties.

●The ~~refusal~~FDA’s policies may change and additional government regulations may be enacted that could prevent, limit or delay regulatory approval of our product candidates. If we, or our collaborators, are slow or unable to ~~approve~~adapt ~~pending~~to ~~applications~~changes in existing requirements or ~~supplements~~the adoption of new requirements or policies, or if we, or our collaborators, are not able to ~~approved~~maintain ~~applications~~regulatory compliance, any marketing approval that wewas ~~submit;~~obtained could be lost, which would adversely affect our business, prospects and ability to achieve or sustain profitability.

●If ~~recall~~we, ofor ~~products,~~our ~~fines~~collaborators, ~~restitution~~are orunable to ~~disgorgement~~comply ofwith ~~profits~~foreign regulatory requirements or ~~revenue;~~obtain foreign regulatory approvals, our ability to develop foreign markets for our products could be impaired.

●Sales ~~suspension~~of orour ~~withdrawal~~product ofcandidates, if any, outside the United States will be subject to foreign regulatory requirements governing clinical trials, marketing approval, manufacturing, product licensing, pricing and reimbursement. These regulatory requirements vary greatly from country to country. As a result, the time required to obtain approvals; outside the United States may differ from that required to obtain FDA approval and we may not be able to obtain foreign regulatory approvals on a timely basis or at all. Approval by the FDA does not ensure approval by regulatory authorities in other countries, and approval by one foreign regulatory authority does not ensure approval by regulatory authorities in other countries or by the FDA and foreign regulatory authorities could require additional testing. Failure to comply with these regulatory requirements or obtain required approvals could impair our ability to develop foreign markets for our products.

●Competitive ~~refusal~~products tofor ~~permit~~treatment ~~the~~of ~~import~~AML may reduce or ~~export~~eliminate ofthe commercial opportunity for our ~~products;~~product candidates, if any.

●The ~~product~~clinical ~~seizure;~~and commercial landscape for AML is rapidly changing. New data from commercial and clinical-stage products continue to emerge. It is possible that these data may alter current standards of care, completely precluding us from further developing our product candidates, if any, or getting them approved by regulatory agencies. Further, it is possible that we may initiate a clinical trial or trials for these product candidates, only to find that data from competing products make it impossible for us to complete enrollment in these trials, resulting in our inability to file for marketing approval with regulatory agencies. Even if these products are approved for marketing in a particular indication or indications, they may have limited sales due to particularly intense competition in these markets.

~~● injunctions or the imposition of civil or criminal penalties.~~27

~~The FDA’s~~We ~~policies~~will ~~may~~need ~~change~~to ~~and~~develop ~~additional~~or ~~government~~acquire ~~regulations~~additional manufacturing ~~may~~and bedistribution ~~enacted~~capabilities ~~that~~in ~~could~~order ~~prevent,~~to ~~limit~~commercialize ~~or delay regulatory approval of~~ our product candidates~~. If we~~, ~~or our collaborators, are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or~~ if weany, orthat ~~our~~obtain ~~collaborators, are not able to maintain regulatory compliance, any~~ marketing approval, ~~that~~and ~~was~~we ~~obtained~~may ~~could~~encounter beunexpected ~~lost,~~costs ~~which~~or ~~would~~difficulties ~~adversely~~in ~~affect~~doing ~~our business, prospects and ability to achieve or sustain profitability~~so.

If we, independently develop and commercialize one or more of our ~~collaborators~~product candidates, ~~are~~if ~~unable~~any, towe ~~comply~~will ~~with~~need ~~foreign~~to ~~regulatory~~invest ~~requirements~~in acquiring or ~~obtain~~building ~~foreign~~additional ~~regulatory~~capabilities ~~approvals,~~and effectively manage our ~~ability~~operations and facilities to successfully pursue and complete future research, development and commercialization efforts. We will require additional investment and validation process development in order to ~~develop~~qualify ~~foreign~~our ~~markets~~commercial-scale ~~for~~manufacturing process to manufacture clinical trial materials and commercial material if any of our products ~~could~~are approved for marketing. This investment and validation process development may be ~~impaired~~expensive and time-consuming. We will require additional personnel with experience in commercial-scale manufacturing, managing of large-scale information technology systems and managing a large-scale distribution system. We will need to add personnel and expand our capabilities, which may strain our existing managerial, operational, regulatory compliance, financial and other resources. To do this effectively, we must:

~~Sales of~~● ~~our product candidates~~recruit, ~~if any~~hire, ~~outside the United States will be subject to foreign regulatory requirements governing clinical trials~~train, ~~marketing~~ ~~approval,~~manage ~~manufacturing, product licensing, pricing~~ and ~~reimbursement.~~motivate ~~These regulatory requirements vary greatly from country to country. As~~ a ~~result,~~growing ~~the~~employee time required to obtain approvals outside the United States may differ from that required to obtain FDA approval and we may not be able to obtain foreign regulatory approvals on a timely basis or at all. Approval by the FDA does not ensure approval by regulatory authorities in other countries, and approval by one foreign regulatory authority does not ensure approval by regulatory authorities in other countries or by the FDA and foreign regulatory authorities could require additional testing. Failure to comply with these regulatory requirements or obtain required approvals could impair our ability to develop foreign markets for our products.base;

~~Competitive products~~● ~~for~~accurately ~~treatment~~forecast ofdemand ~~AML may reduce or eliminate the commercial opportunity~~ for our ~~product candidates, if any.~~products;

~~The clinical~~● ~~and~~assemble ~~commercial landscape for AML is rapidly changing. New data from commercial~~ and ~~clinical-stage~~manage ~~products~~the ~~continue~~supply tochain emerge. It is possible that these data may alter current standards of care, completely precluding us from further developing our product candidates, if any, or getting them approved by regulatory agencies. Further, it is possible that we may initiate a clinical trial or trials for these product candidates, only to ~~find~~ensure ~~that data from competing products make it impossible for us to complete enrollment in these trials, resulting in~~ our ~~inability~~ability to ~~file~~meet ~~for~~demand; marketing approval with regulatory agencies. Even if these products are approved for marketing in a particular indication or indications, they may have limited sales due to particularly intense competition in these markets.and

27● expand existing operational, manufacturing, financial and management information systems.

We ~~will~~ ~~need~~may toseek ~~develop~~FDA orapproval ~~acquire~~for ~~additional~~our ~~manufacturing~~production process and ~~distribution~~facilities ~~capabilities~~simultaneously inwith ~~order~~seeking toapproval ~~commercialize~~for sale of our product candidates,. Should we not complete the development of adequate ifcapabilities, ~~any~~including manufacturing capacity, ~~that~~or ~~obtain~~fail ~~marketing~~to receive timely approval, of our manufacturing process and facilities, our ability to supply clinical trial materials for planned clinical trials or supply products following regulatory approval for sale could be delayed, which would further delay our clinical trials or the period of time when we ~~may~~would ~~encounter~~be ~~unexpected~~able ~~costs~~to generate revenues from the sale of such products, if we are even able to obtain approval or ~~difficulties~~generate inrevenues ~~doing~~at soall.

If Additionally, we ~~independently~~may ~~develop~~decide ~~and~~to ~~commercialize~~outsource ~~one~~ some or ~~more~~all of our ~~product~~manufacturing ~~candidates,~~activities ifto ~~any,~~a wethird ~~will~~party ~~need~~commercial tomanufacturing ~~invest~~organization, ~~in acquiring~~ or ~~building additional~~CMO. ~~capabilities~~Under ~~and~~any ~~effectively~~agreement ~~manage~~with ~~our~~a ~~operations and facilities to successfully pursue and complete future research~~CMO, ~~development~~ ~~and~~we ~~commercialization~~would ~~efforts.~~have Weless ~~will~~control ~~require~~over ~~additional~~the ~~investment~~timing and ~~validation~~quality ~~process~~of ~~development~~manufacturing inthan ~~order~~if towe ~~qualify~~were ~~our commercial-scale manufacturing process~~ to ~~manufacture~~perform ~~clinical~~such ~~trial~~manufacturing ~~materials~~ourselves. ~~and~~A ~~commercial~~CMO would ~~material~~be ifmanufacturing ~~any~~other ofpharmaceutical ~~our~~ products ~~are~~in ~~approved~~the ~~for~~same ~~marketing. This~~facilities ~~investment~~as ~~and~~our ~~validation~~product ~~process~~candidates, ~~development~~increasing ~~may~~the berisk ~~expensive~~of ~~and~~cross ~~time-consuming~~product contamination. ~~We will require additional personnel with experience in commercial-scale manufacturing~~Further, ~~managing~~there ofis ~~large-scale~~no ~~information~~guarantee ~~technology~~that ~~systems~~any ~~and~~CMO ~~managing a large-scale distribution system. We~~ will ~~need~~continue toongoing ~~add personnel and expand our capabilities~~operations, ~~which~~causing ~~may~~potential ~~strain~~delays ~~our~~in ~~existing~~product ~~managerial~~supply, ~~operational, regulatory compliance,~~ ~~financial~~reduced revenues and other ~~resources.~~liabilities Tofor ~~do this effectively, we must:~~us.

●Any ~~recruit,~~such ~~hire,~~events ~~train,~~would ~~manage~~increase our costs and ~~motivate~~could delay aor ~~growing~~prevent ~~employee~~our ~~base;~~ability to commercialize our product candidates, which could adversely impact our business, financial condition and results of operations.

●Our ~~accurately~~product ~~forecast~~candidates ~~demand~~may ~~for~~cause ~~our~~undesirable side ~~products;~~effects or have other properties that could delay or prevent their regulatory approval, limit the commercial profile of an approved label, or result in significant negative consequences following marketing approval, if any.

●Undesirable ~~assemble~~side effects caused by our product candidates, if any, could cause us, our collaborators, or regulatory authorities to interrupt, delay or halt clinical trials and ~~manage~~could result in a more restrictive label or the ~~supply~~delay ~~chain~~or denial of regulatory approval by the FDA or other comparable foreign regulatory authorities. As a result of any side effects, our clinical trials could be suspended or terminated and the FDA or comparable foreign regulatory authorities could order us to ~~ensure~~cease further development, or deny approval, of our product candidates for any or all targeted indications. The drug-related side effects could affect patient recruitment or the ability of enrolled patients to ~~meet~~complete ~~demand;~~the trial or result in potential product liability claims. Any of these occurrences may harm our business, financial condition and prospects significantly.

●Additionally, ~~expand~~if ~~existing~~one ~~operational~~or more of our product candidates receives marketing approval, ~~manufacturing~~and we, ~~financial~~our ~~and~~collaborators, ~~management~~or ~~information~~others ~~systems.~~later identify undesirable side effects caused by such products, a number of potentially significant negative consequences could result, including:

~~We may~~● seek FDA approval for our production process and facilities simultaneously with seeking approval for sale of our product candidates. Should we not complete the development of adequate capabilities, including manufacturing capacity, or fail to receive timely approval of our manufacturing process and facilities, our ability to supply clinical trial materials for planned clinical trials or supply products following regulatory ~~approval~~authorities ~~for~~may ~~sale~~withdraw ~~could~~approvals ~~be delayed, which would further delay our clinical trials or the period~~ of ~~time when we would be able to generate revenues from the sale of~~ such ~~products, if we are even able to obtain approval or generate revenues at all.~~product;

~~Additionally, we~~● ~~may~~regulatory ~~decide~~authorities tomay ~~outsource~~require ~~some~~additional orwarnings ~~all~~on ~~of our manufacturing activities to a third party commercial manufacturing organization, or CMO. Under any agreement with a CMO, we would have less control over~~ the timing and quality of manufacturing than if we were to perform such manufacturing ourselves. A CMO would be manufacturing other pharmaceutical products in the same facilities as our product candidates, increasing the risk of cross product contamination. Further, there is no guarantee that any CMO will continue ongoing operations, causing potential delays in product supply, reduced revenues and other liabilities for us.label;

Any such events would increase our costs and could delay or prevent our ability to commercialize our product candidates, which could adversely impact our business, financial condition and results of operations.28

~~Our product~~● ~~candidates~~we may ~~cause~~be ~~undesirable~~required ~~side~~to ~~effects~~create ora ~~have~~medication ~~other~~guide ~~properties~~outlining ~~that could delay or prevent their regulatory approval, limit~~ the ~~commercial~~risks ~~profile~~ of ansuch ~~approved~~side ~~label,~~effects orfor ~~result~~distribution into ~~significant negative consequences following marketing approval, if any.~~patients;

~~Undesirable side~~● ~~effects~~we ~~caused~~may by our product candidates, if any, could cause us, our collaborators, or regulatory authorities to interrupt, delay or halt clinical trials and could result in a more restrictive label or the delay or denial of regulatory approval by the FDA or other comparable foreign regulatory authorities. As a result of any side effects, our clinical trials could be ~~suspended~~sued ~~or terminated~~ and ~~the~~ ~~FDA~~held orliable ~~comparable~~for ~~foreign~~harm ~~regulatory~~caused ~~authorities could order us~~ to ~~cease further development, or deny approval, of our product candidates for any or all targeted indications. The drug-related side effects could affect patient recruitment or the ability of enrolled~~ patients to; ~~complete the trial or result in potential product liability claims. Any of these occurrences may harm our business, financial condition~~ and ~~prospects significantly.~~

~~Additionally if~~● ~~one or more of~~ our ~~product~~reputation ~~candidates~~may receives marketing approval, and we, our collaborators, or others later identify undesirable side effects caused by such products, a number of potentially significant negative consequences could result, including:suffer.

●Any ~~regulatory~~of ~~authorities~~these ~~may~~events ~~withdraw~~could ~~approvals~~prevent us from achieving or maintaining market acceptance of ~~such~~the particular product; candidate, if approved, and could significantly harm our business, results of operations and prospects.

●If ~~regulatory~~we ~~authorities~~are unable to establish sales and marketing capabilities or enter into agreements with third parties to sell and market our product candidates, we may ~~require~~not ~~additional~~be ~~warnings~~successful in oncommercializing ~~the~~our ~~label;~~product candidates if and when they are approved.

28We do not have a sales and marketing infrastructure or any experience in the sales, marketing or distribution of pharmaceutical products. We may seek additional third-party collaborators for the commercialization of our other product candidates. In the future, we may choose to build a focused sales and marketing infrastructure to market or co-promote some of our product candidates if and when they are approved, which would be expensive and time-consuming. Alternatively, we may elect to outsource these functions to third parties. Either approach carries significant risks. For example, recruiting and training a sales force is expensive and time-consuming and, if done improperly, could delay a product launch and result in limited sales. If the commercial launch of a product candidate for which we recruit a sales force and establish marketing capabilities is delayed or does not occur for any reason, we would have prematurely or unnecessarily incurred these commercialization expenses. This may be costly, and our investment would be lost if we cannot retain or reposition our sales and marketing personnel.

●Factors wethat may beinhibit ~~required~~our efforts to ~~create~~commercialize our aproducts ~~medication~~on ~~guide~~our ~~outlining~~own ~~the risks of such side effects for distribution to patients;~~include:

● weour ~~may~~inability beto ~~sued~~recruit, manage and ~~held~~retain ~~liable~~adequate ~~for~~numbers ~~harm~~of ~~caused~~effective tosales ~~patients;~~ and marketing personnel;

● ~~our~~the ~~reputation~~inability ~~may~~of ~~suffer.~~marketing personnel to develop effective marketing materials;

~~Any of~~● ~~these~~the ~~events~~inability ~~could prevent us from achieving or maintaining market acceptance~~ of ~~the~~sales ~~particular~~personnel ~~product~~to ~~candidate,~~obtain ifaccess ~~approved,~~to ~~and could~~or ~~significantly~~persuade ~~harm~~adequate ~~our~~numbers ~~business,~~of ~~results~~physicians ofto ~~operations~~prescribe ~~and~~any ~~prospects.~~future products;

~~If we~~● ~~are~~the ~~unable~~lack toof ~~establish~~complementary ~~sales~~products ~~and marketing capabilities or enter into agreements with third parties~~ to ~~sell~~be ~~and~~offered ~~market~~by ~~our~~sales ~~product candidates~~personnel, wewhich may ~~not~~put beus ~~successful~~at ina ~~commercializing~~competitive ~~our~~disadvantage ~~product~~relative ~~candidates~~to ifcompanies ~~and~~with ~~when~~more ~~they~~extensive ~~are~~product ~~approved.~~lines; and

~~We do~~● ~~not~~unforeseen ~~have~~costs ~~a sales~~ and ~~marketing~~expenses ~~infrastructure~~associated orwith ~~any~~creating ~~experience~~an inindependent ~~the~~ sales, marketing or distribution of pharmaceutical products. We may seek additional third-party collaborators for the commercialization of our other product candidates. In the future, we may choose to build a focused sales and marketing ~~infrastructure to market or co-promote some of our product candidates if and when they are approved, which would be expensive and time-consuming~~organization. Alternatively, we may elect to outsource these functions to third parties. Either approach carries significant risks. For example, recruiting and training a sales force is expensive and time-consuming and, if done improperly, could delay a product launch and result in limited sales. If the commercial launch of a product candidate for which we recruit a sales force and establish marketing capabilities is delayed or does not occur for any reason, we would have prematurely or unnecessarily incurred these commercialization expenses. This may be costly, and our investment would be lost if we cannot retain or reposition our sales and marketing personnel.

~~Factors~~The availability and amount of reimbursement, ~~that~~if ~~may~~approved, ~~inhibit~~for our ~~efforts~~product tocandidates, ~~commercialize~~if ~~our~~any, ~~products~~and onthe ~~our~~manner ~~own~~in ~~include:~~which government and private payors may reimburse for any potential products, are uncertain.

●In both U.S. and foreign markets, sales of any products will depend in part on the availability of reimbursement from third-party payors such as government health administration authorities, private health insurers and other organizations. The future magnitude of our ~~inability~~revenues and profitability may be affected by the continuing efforts of governmental and third-party payors to ~~recruit,~~contain ~~manage~~or reduce the costs of health care. We cannot predict the effect that private sector or governmental health care reforms may have on our business, and ~~retain~~there ~~adequate~~can ~~numbers~~be no assurance that any such reforms will not have a material adverse effect on our business, financial condition and results of ~~effective~~operations.In addition, in both the United States and elsewhere, sales of prescription drugs are dependent in part on the availability of reimbursement to the consumer from third-party payors, such as government and ~~marketing~~private ~~personnel;~~insurance plans. The ability to obtain reimbursement of our products from these parties is a critical factor in the commercial success for any of our products. Failure to obtain appropriate reimbursement could result in reduced or no sales of our products.

●Third-party payors are increasingly challenging the ~~inability~~price and cost-effectiveness of ~~marketing~~medical ~~personnel~~products and services. Significant uncertainty exists as to ~~develop~~the reimbursement status of newly-approved health care products. There can be no assurance that our products will be considered cost-effective or that adequate third-party reimbursement will be available to enable us to maintain price levels sufficient to realize an appropriate return on our investment in product development. Legislation and regulations affecting the pricing of pharmaceuticals may change before any of our products are approved for marketing. Adoption ~~materials;~~of such legislation could further limit reimbursement for medical products and services. We, or our collaborators, may elect not to market future products in certain markets.

~~● the inability of sales personnel to obtain access to or persuade adequate numbers of physicians to prescribe any future products;~~29

●We ~~the~~may ~~lack~~expend ofour ~~complementary~~limited ~~products~~resources to bepursue a ~~offered~~particular byresearch ~~sales personnel~~program, ~~which~~product ~~may~~candidate ~~put~~or usindication atand afail ~~competitive~~to ~~disadvantage~~capitalize ~~relative~~on toproduct ~~companies~~candidates ~~with~~or indications that may be more ~~extensive~~profitable ~~product~~or ~~lines;~~for ~~and~~which there is a greater likelihood of success.

●Because ~~unforeseen~~we ~~costs~~have limited financial and ~~expenses~~managerial resources, ~~associated~~we ~~with~~focus ~~creating~~on anresearch ~~independent~~programs ~~sales~~and eventually product candidates for the indications that we believe are the most scientifically and ~~marketing~~commercially ~~organization~~promising. Our resource allocation decisions may cause us to fail to capitalize on viable scientific or commercial products or profitable market opportunities. In addition, we may spend valuable time and managerial and financial resources on research programs and product candidates for specific indications that ultimately do not yield any scientifically or commercially viable products. If we do not accurately evaluate the scientific and commercial potential or target market for a particular product candidate, we may relinquish valuable rights to that product candidate through collaboration, licensing or other royalty arrangements in situations where it would have been more advantageous for us to retain sole rights to development and commercialization.

~~The availability~~Failure ~~and~~to ~~amount~~attract ofand ~~reimbursement,~~retain ifkey ~~approved,~~personnel could ~~for~~impede our ~~product~~ability ~~candidates,~~to ifdevelop ~~any,~~our ~~and~~products ~~the manner in which government~~ and ~~private payors~~to ~~may~~obtain ~~reimburse~~new ~~for~~collaborations ~~any~~or ~~potential~~other ~~products,~~sources ~~are~~of ~~uncertain~~funding.

~~In both~~Because ~~U.S.~~of ~~and~~the ~~foreign~~specialized ~~markets,~~scientific ~~sales~~ nature of ~~any~~our ~~products~~business, ~~will~~our ~~depend~~success inis ~~part~~highly ondependent ~~the~~upon ~~availability~~our ofability ~~reimbursement~~to ~~from~~attract ~~third-party~~and ~~payors such~~retain asqualified ~~government~~scientific ~~health~~and ~~administration~~technical ~~authorities~~personnel, consultants ~~private~~and ~~health~~advisors. We ~~insurers~~will ~~and~~also ~~other~~need ~~organizations.~~to ~~The~~recruit ~~future~~a ~~magnitude~~considerable number of additional personnel to achieve our ~~revenues~~operating goals and ~~profitability~~financial ~~may~~reporting beobligations. ~~affected~~To bypursue ~~the~~our ~~continuing~~product ~~efforts~~development ofand ~~governmental~~marketing and ~~third-party~~sales ~~payors~~plans, we will need to ~~contain~~hire oradditional qualified ~~reduce~~scientific ~~the~~personnel ~~costs~~to ~~of health~~perform ~~care.~~research Weand ~~cannot~~development, ~~predict~~as ~~the~~well ~~effect~~as ~~that~~personnel ~~private~~with ~~sector~~expertise orin ~~governmental~~clinical ~~health~~testing, ~~care~~government regulation, ~~reforms~~manufacturing, ~~may~~marketing ~~have~~and onsales, which may strain our ~~business~~existing managerial, ~~and~~operational, ~~there can~~regulatory becompliance, nofinancial and ~~assurance~~other ~~that~~resources. ~~any~~We ~~such~~also ~~reforms~~rely ~~will~~on ~~not~~consultants ~~have~~and aadvisors ~~material~~to ~~adverse~~assist ~~effect~~in onformulating our ~~business,~~research ~~financial~~and ~~condition~~development strategy and ~~results of~~adhering ~~operations.In~~to ~~addition,~~complex inregulatory ~~both~~requirements. ~~the~~We ~~United~~face ~~States~~competition ~~and~~for ~~elsewhere,~~qualified ~~sales~~individuals offrom ~~prescription~~numerous ~~drugs~~pharmaceutical ~~are~~and ~~dependent~~biotechnology incompanies, universities ~~part~~and onother ~~the~~research ~~availability of~~institutions. ~~reimbursement~~There tocan ~~the~~be ~~consumer~~no ~~from~~assurance ~~third-party payors,~~that ~~such~~we aswill ~~government~~be ~~and~~able ~~private~~to ~~insurance~~attract ~~plans.~~and ~~The~~retain ~~ability~~such toindividuals ~~obtain~~on ~~reimbursement~~acceptable ofterms, ~~our~~if ~~products~~at ~~from~~all. ~~these~~The ~~parties~~failure isto aattract ~~critical~~and ~~factor~~retain inqualified ~~the~~personnel, ~~commercial~~consultants ~~success~~and ~~for~~advisors ~~any~~could ofhave ~~our~~a ~~products.~~material ~~Failure to obtain~~adverse ~~appropriate~~effect ~~reimbursement~~on ~~could~~our ~~result~~business, infinancial ~~reduced~~condition orand noresults ~~sales~~ of ~~our products~~operations.

~~Third-party payors~~Increased ~~are~~Interest ~~increasingly~~Rates ~~challenging the price~~ and ~~cost-effectiveness of medical products~~ Inflation and ~~services. Significant uncertainty exists~~ asRecession to the reimbursement status of newly-approved health care products. There can be no assurance that our products will be considered cost-effective or that adequate third-party reimbursement will be available to enable us to maintain price levels sufficient to realize an appropriate return on our investment in product development. Legislation and regulations affecting the pricing of pharmaceuticals may change before any of our products are approved for marketing. Adoption of such legislation could further limit reimbursement for medical products and services. We, or our collaborators, may elect not to market future products in certain markets.Risk

29The Company’s financial performance is subject to global and US economic conditions. Recent increases in interest rates and inflation, globally, and in the US regions, have led to economic volatility, increased borrowing costs, price increases and risks of recessions. Economic recessions may have adverse consequences across industries, including the biotechnology industry, which may adversely affect the Company’s business and financial condition. As a result of the ongoing COVID-19 pandemic and actions taken by governments to attempt to slow down rising inflation, there is substantial uncertainty about the strength of the global economies, which may currently or in the near term be in a recession and have experienced rapid increases in uncertainty about the pace of potential recovery. In addition, changes in general market, economic and political conditions in domestic and foreign economies or financial markets, including fluctuation in stock markets resulting from, among other things, trends in the economy and inflation, as are being currently experienced, may impact our ability to raise funds.

We may expend our limited resources to pursue a particular research program, product candidate or indication and fail to capitalize on product candidates or indications that may be more profitable or for which there is a greater likelihood of success.30

~~Because we~~Risks ~~have~~Relating ~~limited~~to ~~financial and managerial resources, we focus on research programs and eventually product candidates for the indications that we believe are the most scientifically and commercially promising.~~ Our resource allocation decisions may cause us to fail to capitalize on viable scientific or commercial products or profitable market opportunities. In addition, we may spend valuable time and managerial and financial resources on research programs and product candidates for specific indications that ultimately do not yield any scientifically or commercially viable products. If we do not accurately evaluate the scientific and commercial potential or target market for a particular product candidate, we may relinquish valuable rights to that product candidate through collaboration, licensing or other royalty arrangements in situations where it would have been more advantageous for us to retain sole rights to development and commercialization.Industry

~~Failure~~The biopharmaceutical industry is subject to ~~attract~~significant regulation and ~~retain~~oversight ~~key~~in ~~personnel~~the ~~could~~United ~~impede~~States, ~~our~~in ~~ability~~addition to ~~develop~~approval ~~our~~of products for sale and tomarketing. ~~obtain~~We ~~new~~may ~~collaborations~~be subject, directly or ~~other~~indirectly, ~~sources~~to federal and state healthcare fraud and abuse laws, transparency, health information privacy and security laws ofand ~~funding~~other healthcare laws and regulations. If we are unable to comply, or have not fully complied, with such laws, we could face substantial penalties.

~~Because of~~Healthcare ~~the specialized scientific nature of our business~~providers, ~~our~~physicians ~~success is highly dependent upon our ability to attract~~ and ~~retain qualified~~third-party ~~scientific~~payors ~~and technical personnel, consultants and advisors. We~~ will ~~also~~play ~~need to recruit~~ a ~~considerable~~primary ~~number~~role ofin ~~additional~~the ~~personnel to~~recommendation ~~achieve our operating goals~~ and ~~financial~~prescription ~~reporting~~of ~~obligations.~~any Tofuture ~~pursue our~~ product ~~development~~candidates ~~and~~we ~~marketing~~may develop and ~~sales~~any ~~plans,~~product wecandidates ~~will~~for ~~need~~which towe ~~hire~~obtain ~~additional~~marketing ~~qualified~~approval. ~~scientific~~In ~~personnel~~addition to ~~perform~~FDA ~~research~~restrictions ~~and~~on ~~development,~~marketing asof ~~well~~biopharmaceutical asproducts, ~~personnel~~we ~~with expertise~~are ~~in clinical testing~~exposed, ~~government regulation~~directly, ~~manufacturing,~~or ~~marketing and sales~~indirectly, ~~which~~through ~~may strain~~ our ~~existing managerial~~customers, ~~operational, regulatory compliance, financial and other resources. We also rely on consultants and advisors~~ to ~~assist~~broadly inapplicable ~~formulating~~fraud ~~our research~~ and ~~development~~abuse ~~strategy~~ and ~~adhering~~other tohealthcare ~~complex~~laws ~~regulatory~~and ~~requirements.~~regulations that Wemay ~~face~~affect ~~competition~~the ~~for~~business ~~qualified~~or ~~individuals~~financial ~~from~~arrangements ~~numerous pharmaceutical~~ and ~~biotechnology~~relationships ~~companies,~~through ~~universities~~which ~~and other research institutions. There can be no assurance that~~ we ~~will~~would bemarket, ~~able to~~sell ~~attract~~ and ~~retain~~distribute ~~such~~our ~~individuals on acceptable terms, if at all~~products. The ~~failure~~laws tothat ~~attract~~may ~~and~~affect ~~retain~~our ~~qualified~~ability ~~personnel,~~to ~~consultants and~~operate ~~advisors could have a material adverse effect on our business~~include, ~~financial~~but ~~condition~~are ~~and~~not ~~results~~limited ~~of operations.~~to:

The ~~ongoing~~ ~~COVID~~federal Anti-19Kickback ~~pandemic~~Statute ~~may~~which prohibits any person or entity from, ~~directly~~among other things, knowingly and willfully offering, paying, soliciting or receiving any remuneration, directly or indirectly, ~~adversely~~overtly ~~affect~~or ~~our~~covertly, ~~business~~in cash or in-kind, ~~results~~to induce or reward either the referring of ~~operations~~an individual for, or the purchasing, leasing, ordering or arranging for the purchase, lease or order of any health care item or service reimbursable, in whole or in part, under Medicare, Medicaid or any other federally financed healthcare program. The term “remuneration” has been broadly interpreted to include anything of value. This statute has been interpreted to apply to arrangements between pharmaceutical manufacturers on one hand and ~~financial~~prescribers, ~~condition~~purchasers and formulary managers on the other hand. Although there are many statutory exemptions and regulatory safe harbors protecting certain common activities from prosecution, the exemptions and safe harbors are drawn narrowly, and practices that involve remuneration intended to induce prescribing, purchases or recommendations may be subject to scrutiny if they do not qualify for an exemption or safe harbor. Our practices may not in all cases meet all of the criteria for safe harbor protection from anti-kickback liability.

~~Our~~The federal false claims and civil monetary penalty ~~business~~laws, ~~could~~including the Federal False Claims Act, which imposes significant penalties and can be ~~materially~~enforced ~~adversely~~by ~~affected~~private citizens through civil qui tam actions, ~~directly~~prohibits any person or ~~indirectly~~entity from, byamong ~~the~~other ~~widespread~~things, ~~outbreak~~knowingly ofpresenting, ~~contagious~~or ~~disease~~causing to be presented, ~~including~~a false, fictitious or fraudulent claim for payment to the ~~ongoing~~federal ~~COVID-19~~government, ~~pandemic~~or knowingly making, ~~which~~using ~~has~~or ~~spread~~causing to ~~many~~be ofmade, a false statement or record material to a false or fraudulent claim to avoid, decrease or conceal an obligation to pay money to the ~~countries~~federal ingovernment. ~~which~~In weaddition, a ~~our~~claim ~~suppliers~~including ~~and~~items ~~our~~or ~~collaboration~~services ~~partners~~resulting dofrom a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent ~~business~~claim for purposes of the False Claims Act. ~~National,~~As ~~state~~a ~~and~~result ~~local~~of ~~governments~~a inmodification ~~affected~~made ~~regions~~by ~~have~~the ~~implemented~~Fraud Enforcement and ~~may~~Recovery ~~continue~~Act of 2009, a claim includes “any request or demand” for money or property presented to ~~implement~~the ~~safety~~U.S. ~~precautions~~government. Further, manufacturers can be held ~~including~~liable ~~quarantines,~~under ~~border~~the ~~closures,~~False ~~increased~~Claims ~~border~~Act ~~controls,~~even ~~travel~~when ~~restrictions,~~they ~~shelter~~do innot ~~place~~submit ~~orders~~claims ~~and~~directly ~~shutdowns,~~to ~~business~~government payors if they are deemed to “cause” ~~closures,~~the ~~cancellations~~submission of ~~public~~false ~~gatherings~~or ~~and~~fraudulent ~~other measures~~claims. ~~Organizations~~Criminal ~~and~~prosecution ~~individuals~~is ~~are~~also ~~taking~~possible ~~additional~~for ~~steps~~making toor ~~avoid~~presenting a false, fictitious or fraudulent ~~reduce~~claim ~~infection,~~to ~~including~~the ~~limiting~~federal ~~travel~~government. Several pharmaceutical and ~~staying~~other ~~home~~health ~~from~~care ~~work.~~companies ~~These~~have ~~measures~~been ~~are~~prosecuted ~~disrupting~~under ~~normal~~these ~~business~~laws ~~operations~~for ~~both~~allegedly inproviding ~~and~~free ~~outside~~product ofto ~~affected~~customers ~~areas~~with ~~and~~the expectation that the customers would bill federal programs for the product. Other companies have ~~had~~been ~~significant~~prosecuted ~~negative~~for ~~impacts~~causing onfalse ~~businesses~~claims ~~and~~to ~~financial~~be ~~markets~~submitted ~~worldwide~~because of marketing of the product for unapproved, and thus non-reimbursable, uses.

~~We continue~~The tofederal ~~monitor~~Health ~~our~~Insurance ~~operations~~Portability and ~~applicable~~Accountability Act ~~government~~of ~~recommendations~~1996, ~~and~~or weHIPAA, ~~have~~which, ~~made~~among ~~some~~other ~~modifications~~things, imposes criminal liability for executing or attempting to ~~our~~execute ~~normal~~a ~~operations~~scheme to defraud ~~because~~any ofhealthcare ~~the~~benefit ~~COVID~~program, including private third-19party ~~pandemic~~payors, ~~including~~knowingly ~~requiring~~and ~~most~~willfully ~~office-based~~embezzling ~~support~~or ~~staff~~stealing tofrom ~~work~~a ~~remotely.~~healthcare benefit ~~Notwithstanding~~program, ~~these~~willfully ~~measures~~obstructing a criminal investigation of a healthcare offense, ~~the~~ ~~COVID-19~~and ~~pandemic~~creates ~~could~~federal ~~affect~~criminal ~~the~~laws ~~health~~that prohibit knowingly and ~~availability~~willfully offalsifying, ~~our~~concealing ~~support~~or ~~staff~~covering asup ~~well~~a asmaterial ~~those~~fact ofor ~~the~~making ~~third~~any ~~parties~~materially wefalse, ~~rely~~fictitious onor fraudulent ~~taking~~statements ~~similar~~or ~~measures.~~representations, Weor ~~also~~making ~~recognize that~~or ~~the~~using ~~global~~any ~~economic~~false ~~climate~~writing ~~may~~or ~~impact~~document ~~our~~knowing ~~ability~~the same to ~~raise~~contain ~~funds~~any materially false, fictitious or fraudulent statement or entry in connection with the delivery of, or payment for, benefits, items or services.

30HIPAA, as amended by the Health Information Technology and Clinical Health Act of 2009, or HITECH, and its implementing regulations, which impose certain requirements relating to the privacy, security, transmission and breach reporting of individually identifiable health information upon entities subject to the law, such as health plans, healthcare clearinghouses and healthcare providers and their respective business associates that perform services for them that involve individually identifiable health information. HITECH also created new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates, and gave state attorneys general new authority to file civil actions for damages or injunctions in U.S. federal courts to enforce the federal HIPAA laws and seek attorneys’ fees and costs associated with pursuing federal civil actions.

~~Risks Relating to Our Industry~~31

The ~~biopharmaceutical~~ ~~industry~~federal isphysician ~~subject~~payment totransparency ~~significant~~requirements, sometimes ~~regulation~~referred ~~and~~to ~~oversight~~as in the ~~United~~“Physician ~~States~~Payments Sunshine Act,” inand ~~addition~~its toimplementing ~~approval~~regulations, ofwhich ~~products~~require certain manufacturers ~~for~~of ~~sale~~drugs, devices, biologics and ~~marketing.~~medical Wesupplies ~~may~~for bewhich ~~subject~~payment is available under Medicare, ~~directly~~Medicaid or ~~indirectly,~~the Children’s Health Insurance Program (with certain exceptions) to ~~federal~~report ~~and~~annually ~~state~~to ~~healthcare~~the ~~fraud~~United States Department of Health and ~~abuse~~Human ~~laws~~Services, ~~transparency~~or HHS, ~~health~~ information related ~~privacy~~to ~~and~~payments ~~security~~or ~~laws and~~ other ~~healthcare~~transfers ~~laws~~of ~~and~~value ~~regulations.~~made Ifto wephysicians ~~are~~(defined ~~unable~~ to ~~comply~~include doctors, ordentists, ~~have~~optometrists, ~~not~~podiatrists ~~fully~~and ~~complied,~~chiropractors) ~~with~~and ~~such~~teaching ~~laws~~hospitals, weas ~~could~~well ~~face~~as ~~substantial~~ownership ~~penalties~~and investment interests held by physicians and their immediate family members.

~~Healthcare providers,~~State ~~physicians~~ and ~~third-party~~foreign ~~payors~~law ~~will~~equivalents ~~play a primary role in the recommendation and prescription~~ of ~~any~~each ~~future product candidates we may develop and any product candidates for which we obtain marketing approval. In addition to FDA restrictions on marketing~~ of ~~biopharmaceutical~~the ~~products,~~above wefederal ~~are exposed~~laws, ~~directly,~~such oras ~~indirectly,~~anti-kickback ~~through our customers, to broadly applicable fraud~~ and ~~abuse~~false ~~and~~claims ~~other healthcare~~ laws, ~~and regulations~~ that may ~~affect~~impose ~~the~~similar ~~business~~ or ~~financial~~more ~~arrangements~~prohibitive ~~and relationships through which we would market~~restrictions, ~~sell~~ and ~~distribute~~ ~~our~~may ~~products.~~apply to ~~The~~items ~~laws~~or ~~that~~services ~~may~~reimbursed ~~affect~~by ~~our~~non-governmental ~~ability~~third-party ~~to operate include~~payors, ~~but~~including ~~are~~private ~~not limited to:~~insurers.

~~The federal~~State ~~Anti-Kickback~~and ~~Statute~~foreign ~~which~~laws ~~prohibits~~that ~~any~~require ~~person or entity from, among other things, knowingly and willfully offering, paying,~~pharmaceutical ~~soliciting~~companies orto ~~receiving~~implement ~~any~~compliance ~~remuneration~~programs, ~~directly~~comply orwith ~~indirectly,~~the ~~overtly~~pharmaceutical orindustry’s ~~covertly,~~voluntary incompliance ~~cash~~guidelines orand ~~in-kind,~~the ~~to induce or reward either~~relevant ~~the~~compliance ~~referring~~guidance ofpromulgated anby ~~individual for, or~~ the ~~purchasing,~~federal ~~leasing~~government, ~~ordering~~ or ~~arranging~~to ~~for~~track ~~the~~and ~~purchase~~report gifts, ~~lease~~compensation orand ~~order~~other ofremuneration ~~any health~~provided ~~care~~to ~~item~~physicians orand ~~service~~other ~~reimbursable,~~healthcare ~~in whole or in part~~providers, ~~under~~and ~~Medicare, Medicaid or any~~ other ~~federally~~federal, ~~financed~~state ~~healthcare~~and ~~program. The~~foreign ~~term~~laws ~~“remuneration”~~that ~~has~~govern ~~been~~the ~~broadly~~privacy ~~interpreted~~and tosecurity ~~include anything~~ of ~~value. This statute has been interpreted to apply~~health toinformation ~~arrangements~~or ~~between~~personally ~~pharmaceutical~~identifiable ~~manufacturers~~information onin ~~one~~certain ~~hand and prescribers~~circumstances, ~~purchasers~~including ~~and~~state ~~formulary~~health ~~managers~~information onprivacy ~~the~~and ~~other~~data ~~hand.~~breach ~~Although~~notification ~~there~~laws ~~are~~which ~~many~~govern ~~statutory~~the ~~exemptions~~collection, ~~and~~use, ~~regulatory safe harbors protecting certain common activities from prosecution~~disclosure, ~~the exemptions~~ and ~~safe~~protection ~~harbors~~of ~~are~~health-related ~~drawn narrowly,~~ and ~~practices~~other ~~that~~personal ~~involve remuneration intended to induce prescribing~~information, ~~purchases or recommendations~~many ~~may~~of bewhich ~~subject~~differ tofrom ~~scrutiny~~each ifother ~~they~~in dosignificant ~~not~~ways ~~qualify~~and ~~for~~often anare ~~exemption or safe harbor. Our practices may~~ not inpre-empted ~~all~~by ~~cases~~HIPAA, ~~meet~~thus ~~all~~requiring ofadditional ~~the criteria~~compliance ~~for safe harbor protection from anti-kickback liability~~efforts.

~~The federal~~Because ~~false~~of ~~claims~~the ~~and~~breadth ~~civil~~of ~~monetary~~these ~~penalty~~ laws, ~~including~~and the ~~Federal False Claims Act, which imposes significant penalties and~~narrowness ~~can~~of bethe ~~enforced~~safe ~~by private citizens through civil qui tam actions~~harbors, ~~prohibits~~it ~~any~~is ~~person~~possible orthat ~~entity~~some ~~from,~~of ~~among~~our ~~other~~business ~~things,~~activities ~~knowingly presenting,~~could ~~or causing to~~ be ~~presented,~~subject ~~a false, fictitious or fraudulent claim for payment~~ to ~~the~~challenge ~~federal~~under ~~government,~~one or ~~knowingly~~more making, using or causing to be made, a false statement or record material to a false or fraudulent claim to avoid, decrease or conceal an obligation to pay money to the federal government. In addition, a claim including items or services resulting from a violation of ~~the~~these ~~federal Anti-Kickback~~laws. ~~Statute~~The ~~constitutes~~scope aand ~~false~~enforcement ~~or fraudulent claim for purposes~~ of ~~the~~each ~~False Claims Act. As a result~~ of athese ~~modification~~laws ~~made~~is byuncertain ~~the Fraud Enforcement~~ and ~~Recovery~~subject ~~Act of 2009, a claim includes “any request or demand” for money or property presented~~ to ~~the~~rapid ~~U.S. government.~~change ~~Further,~~in ~~manufacturers can be held liable under~~ the ~~False~~current ~~Claims~~environment ~~Act~~of ~~even~~healthcare ~~when they do not submit claims directly to government~~reform, ~~payors~~especially ifconsidering ~~they are deemed to “cause”~~ the ~~submission~~lack of ~~false~~applicable orprecedent ~~fraudulent~~and ~~claims~~regulations. ~~Criminal~~Federal ~~prosecution is also possible for making or presenting a false, fictitious or fraudulent claim to the federal government. Several pharmaceutical~~ and ~~other~~state ~~health~~enforcement ~~care companies~~bodies have ~~been~~recently ~~prosecuted under these laws for allegedly providing free product to customers with the expectation that the customers~~increased ~~would~~their ~~bill~~scrutiny ~~federal~~of ~~programs~~interactions ~~for~~between ~~the~~healthcare ~~product. Other~~ companies ~~have~~and ~~been~~healthcare ~~prosecuted~~providers, ~~for~~which ~~causing~~has ~~false~~led ~~claims~~ to beseveral ~~submitted~~investigations, ~~because of~~prosecutions, ~~marketing~~convictions ofand ~~the~~settlements ~~product~~in ~~for~~the ~~unapproved,~~healthcare ~~and thus non-reimbursable, uses~~industry.

~~The~~Ensuring that our business arrangements with third ~~federal~~parties ~~Health~~comply ~~Insurance~~with ~~Portability~~applicable healthcare laws and ~~Accountability~~regulations ~~Act~~will oflikely ~~1996,~~be orcostly ~~HIPAA,~~and ~~which,~~time ~~among~~consuming. ~~other~~If ~~things,~~our ~~imposes~~operations ~~criminal~~are ~~liability~~found to ~~for~~be ~~executing~~in orviolation ~~attempting~~of toany ~~execute~~of athe ~~scheme~~laws todescribed ~~defraud~~above or any ~~healthcare~~other ~~benefit~~governmental ~~program,~~regulations ~~including~~that ~~private~~apply ~~third-party~~to ~~payors~~us, ~~knowingly and~~we ~~willfully~~may ~~embezzling~~be orsubject ~~stealing~~to ~~from~~penalties, including acivil, ~~healthcare~~criminal ~~benefit~~and ~~program~~administrative penalties, ~~willfully~~damages, ~~obstructing~~fines, adisgorgement, ~~criminal~~individual ~~investigation~~imprisonment, ofexclusion afrom ~~healthcare~~governmental ~~offense~~funded healthcare programs, such as Medicare and ~~creates~~Medicaid, ~~federal~~contractual ~~criminal~~damages, ~~laws~~reputational ~~that~~harm, ~~prohibit~~diminished ~~knowingly~~profits and ~~willfully~~future ~~falsifying~~earnings, additional ~~concealing~~reporting orobligations ~~covering~~and upoversight aif ~~material~~we ~~fact or~~become ~~making~~subject ~~any~~to ~~materially~~a ~~false,~~corporate ~~fictitious~~integrity oragreement ~~fraudulent statements~~ or ~~representations,~~other oragreement ~~making~~to orresolve ~~using~~allegations of ~~any~~non-compliance ~~false~~with ~~writing~~these orlaws, ~~document knowing~~and the ~~same~~curtailment toor ~~contain~~restructuring ~~any~~of ~~materially~~our ~~false~~operations, ~~fictitious~~any orof ~~fraudulent~~which ~~statement~~could oradversely ~~entry~~affect inour ~~connection~~ability to ~~with~~operate ~~the~~our ~~delivery~~business ~~of,~~and ~~or payment~~our ~~for,~~results ~~benefits,~~of ~~items or services~~operations.

~~HIPAA, as amended by the~~ Health ~~Information~~care ~~Technology~~reform ~~and~~measures ~~Clinical~~could ~~Health Act of 2009, or HITECH, and its implementing regulations, which impose~~adversely ~~certain~~affect ~~requirements~~our relating to the privacy, security, transmission and breach reporting of individually identifiable health information upon entities subject to the law, such as health plans, healthcare clearinghouses and healthcare providers and their respective business ~~associates that perform services for them that involve individually identifiable health information~~. HITECH also created new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates, and gave state attorneys general new authority to file civil actions for damages or injunctions in U.S. federal courts to enforce the federal HIPAA laws and seek attorneys’ fees and costs associated with pursuing federal civil actions.

31In the United States and foreign jurisdictions, there have been, and continue to be, many legislative and regulatory changes and proposed changes to the healthcare system that could affect our future results of operations. There have been and continue to be a number of initiatives at the U.S. federal and state levels that seek to reduce healthcare costs. In 2010, the PPACA was enacted, which includes measures to significantly change the way health care is financed by both governmental and private insurers. Among the provisions of the PPACA of greatest importance to the pharmaceutical and biotechnology industry are the following:

~~The federal~~● ~~physician~~an ~~payment transparency requirements~~annual, ~~sometimes~~nondeductible ~~referred~~fee toon asany ~~the~~entity ~~“Physician~~that ~~Payments~~manufactures ~~Sunshine~~or ~~Act,”~~imports ~~and its implementing regulations, which require~~ certain ~~manufacturers~~branded ofprescription drugs, ~~devices, biologics~~ and ~~medical~~biologic ~~supplies for which payment is available under Medicare~~agents, ~~Medicaid~~apportioned oramong ~~the~~these ~~Children’s~~entities ~~Health~~according ~~Insurance Program (with certain exceptions)~~ to ~~report~~their ~~annually~~market ~~to the~~share ~~United~~in ~~States~~certain ~~Department~~government ofhealthcare Health and Human Services, or HHS, information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors) and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members.programs;

~~State and~~● ~~foreign~~implementation ~~law equivalents~~ of ~~each of~~ the ~~above~~ federal ~~laws,~~physician ~~such~~payment astransparency ~~anti-kickback and false claims laws~~requirements, ~~that~~sometimes ~~may~~referred ~~impose similar or more prohibitive restrictions, and may apply~~ to ~~items~~as orthe ~~services~~“Physician ~~reimbursed~~Payments bySunshine ~~non-governmental third-party payors, including private insurers.~~Act”;

~~State and~~● ~~foreign~~a ~~laws~~licensure ~~that~~framework ~~require~~for pharmaceutical companies to implement compliance programs, comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government, or to track and report gifts, compensation and other remuneration provided to physicians and other healthcare providers, and other federal, state and foreign laws that govern the privacy and security of health information or personally identifiable information in certain circumstances, including state health information privacy and data breach notification laws which govern the collection, use, disclosure, and protection of healthfollow-~~related and~~on ~~other~~biologic ~~personal information, many of which differ from each other in significant ways and often are not pre-empted by HIPAA, thus requiring additional compliance efforts.~~products;

~~Because of~~● ~~the~~a ~~breadth~~new ofPatient-Centered ~~these~~Outcomes ~~laws~~Research ~~and~~Institute ~~the~~to ~~narrowness of the safe harbors~~oversee, itidentify ispriorities ~~possible that some of our business activities could be subject to challenge under one or more of these laws. The scope and enforcement of each of these laws is uncertain and subject to rapid change~~ in ~~the current environment of healthcare reform~~, ~~especially considering the lack of applicable precedent~~ and ~~regulations.~~conduct ~~Federal~~comparative ~~and state~~clinical ~~enforcement~~effectiveness ~~bodies have recently increased their scrutiny of interactions between healthcare companies and healthcare providers~~research, ~~which~~ ~~has~~along ~~led~~with tofunding ~~several~~for ~~investigations,~~such ~~prosecutions, convictions and settlements in the healthcare industry.~~research;

Ensuring that our business arrangements with third parties comply with applicable healthcare laws and regulations will likely be costly and time consuming. If our operations are found to be in violation of any of the laws described above or any other governmental regulations that apply to us, we may be subject to penalties, including civil, criminal and administrative penalties, damages, fines, disgorgement, individual imprisonment, exclusion from governmental funded healthcare programs, such as Medicare and Medicaid, contractual damages, reputational harm, diminished profits and future earnings, additional reporting obligations and oversight if we become subject to a corporate integrity agreement or other agreement to resolve allegations of non-compliance with these laws, and the curtailment or restructuring of our operations, any of which could adversely affect our ability to operate our business and our results of operations. 32

~~Health care~~● ~~reform~~establishment ~~measures~~of ~~could~~a ~~adversely~~Center ~~affect~~for ~~our~~Medicare ~~business.~~Innovation at the Centers for Medicare & Medicaid Services to test innovative payment and service delivery models to lower Medicare and Medicaid spending, potentially including prescription drug spending;

~~In the~~● ~~United~~an ~~States~~increase ~~and~~in ~~foreign~~the ~~jurisdictions,~~statutory ~~there~~minimum ~~have~~rebates ~~been,~~a ~~and~~manufacturer ~~continue~~must topay ~~be,~~under ~~many~~the ~~legislative~~Medicaid ~~and~~Drug ~~regulatory~~Rebate ~~changes~~Program, ~~and proposed changes~~ to ~~the healthcare system that could affect our future results of operations~~23.1% ~~There have been~~ and ~~continue~~13% ~~to be a number~~ of ~~initiatives at~~ the ~~U.S.~~average ~~federal~~manufacturer ~~and~~price ~~state~~for ~~levels~~most ~~that~~branded ~~seek~~and togeneric ~~reduce healthcare costs. In 2010~~drugs, ~~the~~respectively ~~PPACA~~and ~~was~~capped ~~enacted, which includes measures to significantly change~~ the ~~way~~total ~~health~~rebate ~~care~~amount isfor ~~financed~~innovator bydrugs ~~both~~at ~~governmental~~100% ~~and private insurers. Among the provisions~~ of the ~~PPACA~~Average ~~of greatest~~Manufacturer ~~importance~~Price, toor ~~the pharmaceutical and biotechnology industry are the following:~~AMP;

● ~~implementation~~extension of ~~the~~manufacturers’ ~~federal~~Medicaid ~~physician~~rebate ~~payment~~liability ~~transparency~~to ~~requirements,~~covered ~~sometimes~~drugs ~~referred~~dispensed to asindividuals ~~the~~who ~~“Physician~~are ~~Payments~~enrolled ~~Sunshine~~in ~~Act”~~Medicaid managed care organizations;

● aexpansion ~~licensure~~of ~~framework~~eligibility criteria for ~~follow-on~~Medicaid ~~biologic~~programs ~~products~~by, among other things, allowing states to offer Medicaid coverage to additional individuals and by adding new mandatory eligibility categories for individuals with income at or below 133% of the federal poverty level, thereby potentially increasing manufacturers’ Medicaid rebate liability;

● a new ~~Patient-Centered~~Medicare ~~Outcomes~~Part ~~Research~~D ~~Institute~~coverage togap ~~oversee~~discount program, ~~identify~~in ~~priorities~~which ~~in,~~manufacturers ~~and~~must ~~conduct~~agree ~~comparative~~to ~~clinical~~offer ~~effectiveness~~50% ~~research~~point-of-sale discounts off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, ~~along~~as ~~with~~a ~~funding~~condition for ~~such~~the ~~research~~manufacturer’s outpatient drugs to be covered under Medicare Part D; and

32● expansion of the entities eligible for discounts under the Public Health program.

●Some ~~establishment~~of the provisions of athe ~~Center~~PPACA ~~for~~have ~~Medicare~~yet ~~Innovation~~to be atimplemented, ~~the~~and ~~Centers~~there ~~for~~have ~~Medicare~~been &legal ~~Medicaid~~and ~~Services~~political challenges to ~~test~~certain ~~innovative~~aspects ~~payment~~of the PPACA. Since January 2017, former President Trump has signed two executive orders and ~~service~~other ~~delivery~~directives ~~models~~designed to ~~lower~~delay, ~~Medicare~~circumvent, or loosen certain requirements mandated by the PPACA. Concurrently, Congress has considered legislation that would repeal or repeal and ~~Medicaid~~replace ~~spending~~all or part of the PPACA. While Congress has not passed repeal legislation, ~~potentially~~the ~~including~~Tax ~~prescription~~Cuts ~~drug~~and ~~spending;~~Jobs Act of 2017 includes a provision repealing, effective January 1, 2019, the tax-based shared responsibility payment imposed by the PPACA on certain individuals who fail to maintain qualifying health coverage for all or part of a year that is commonly referred to as the “individual mandate”. Congress may consider other legislation to repeal or replace elements of the PPACA.

●Many anof ~~increase~~the indetails regarding the ~~statutory~~implementation of ~~minimum~~the ~~rebates~~PPACA aare ~~manufacturer~~yet ~~must~~to ~~pay~~be determined, and at this time, the full effect that the PPACA would have on our business remains unclear. There is uncertainty surrounding the applicability of the biosimilars provisions under the ~~Medicaid~~PPACA ~~Drug~~to ~~Rebate~~our ~~Program~~product candidates. The FDA has issued several guidance documents, tobut 23no implementing regulations, on biosimilars.1% ~~and~~Many ~~13%~~biosimilar ofapplications have been approved over the past ~~average~~few ~~manufacturer~~years. ~~price~~It is not certain that we will receive 12 years of biologics marketing exclusivity for ~~most~~any ~~branded~~of ~~and~~our ~~generic~~products. ~~drugs,~~The ~~respectively~~regulations that are ultimately promulgated and ~~capped~~their implementation are likely to have considerable impact on the ~~total~~way ~~rebate~~we ~~amount~~conduct our business and may require us to change current strategies. A biosimilar is a biological product that is highly similar to an approved drug notwithstanding minor differences in clinically inactive components, and for ~~innovator~~which ~~drugs~~there atare ~~100%~~no ofclinically meaningful differences between the ~~Average~~biological product ~~Manufacturer~~and ~~Price~~the approved drug in terms of the safety, orpurity, ~~AMP;~~and potency of the product.

●Individual astates ~~new~~have ~~methodology~~become byincreasingly ~~which~~aggressive in ~~rebates~~passing ~~owed~~legislation byand ~~manufacturers~~implementing ~~under~~regulations ~~the~~designed ~~Medicaid~~to ~~Drug~~control ~~Rebate~~pharmaceutical ~~Program~~and ~~are~~biological ~~calculated~~product ~~for~~pricing, including price or patient reimbursement constraints, discounts, restrictions on certain ~~drugs~~product access, and ~~biologics~~marketing cost disclosure and transparency measures, ~~including~~and to encourage importation from other countries and bulk purchasing. Legally mandated price controls on payment amounts by third-party payors or other restrictions could harm our ~~product~~business, ~~candidates~~results of operations, ~~that~~financial condition and prospects. In addition, regional healthcare authorities and individual hospitals are ~~inhaled~~increasingly using bidding procedures to determine what pharmaceutical products and which suppliers will be included in their prescription drug and other healthcare programs. This could reduce ultimate demand for our products or put pressure on our product pricing, ~~infused~~which could negatively affect our business, ~~instilled~~results of operations, ~~implanted~~financial orcondition and ~~injected;~~prospects.

~~● extension of manufacturers’ Medicaid rebate liability to covered drugs dispensed to individuals who are enrolled in Medicaid managed care organizations;~~33

●In ~~expansion~~addition, given recent federal and state government initiatives directed at lowering the total cost of ~~eligibility~~healthcare, ~~criteria~~Congress ~~for~~and state legislatures will likely continue to focus on healthcare reform, the cost of prescription drugs and biologics and the reform of the Medicare and Medicaid programs. byWhile we cannot predict the full outcome of any such legislation, ~~among~~it ~~other~~may ~~things~~result in decreased reimbursement for drugs and biologics, ~~allowing~~which ~~states~~may further exacerbate industry-wide pressure to ~~offer~~reduce ~~Medicaid~~prescription ~~coverage~~drug prices. This could harm our ability to ~~additional~~generate ~~individuals~~revenues. Increases in importation or re-importation of pharmaceutical products from foreign countries into the United States could put competitive pressure on our ability to profitably price our products, which, in turn, could adversely affect our business, results of operations, financial condition and byprospects. ~~adding~~We ~~new~~might elect ~~mandatory~~not ~~eligibility~~to ~~categories~~seek approval for ~~individuals~~or ~~with~~market ~~income~~our atproducts orin ~~below~~foreign ~~133%~~jurisdictions ofto minimize the ~~federal~~risk ~~poverty~~of ~~level~~re-importation, ~~thereby~~which ~~potentially~~could ~~increasing~~also reduce ~~manufacturers’~~the ~~Medicaid~~revenue ~~rebate~~we ~~liability;~~generate from our product sales. It is also possible that other legislative proposals having similar effects will be adopted.

●Furthermore, aregulatory ~~new~~authorities’ ~~Medicare~~assessment of ~~Part~~the Ddata ~~coverage~~and ~~gap~~results ~~discount~~required ~~program,~~to indemonstrate ~~which~~safety ~~manufacturers~~and ~~must~~efficacy ~~agree~~can tochange ~~offer~~over ~~50%~~time ~~point-of-sale~~and ~~discounts~~can ~~off~~be ~~negotiated~~affected ~~prices~~by many factors, such as the emergence of ~~applicable~~additional ~~brand~~information, ~~drugs~~including toon ~~eligible~~other ~~beneficiaries~~products, ~~during~~changing ~~their~~policies ~~coverage~~and ~~gap~~agency ~~period~~funding, asstaffing aand ~~condition~~leadership. ~~for~~We cannot be sure whether future changes to the ~~manufacturer’s~~regulatory ~~outpatient~~environment ~~drugs~~will be favorable or unfavorable to our business prospects. For example, average review times at the FDA for marketing approval applications can be ~~covered~~affected ~~under~~by ~~Medicare~~a ~~Part~~variety D;of factors, including budget and funding levels and statutory, regulatory and policy changes.

●We ~~expansion~~are ofsubject ~~the~~to ~~entities~~U.S. ~~eligible~~and certain foreign export and import controls, sanctions, embargoes, anti-corruption laws, and anti-money laundering laws and regulations. Compliance with these legal standards could impair our ability to compete in domestic and international markets. We can face criminal liability and other serious consequences for ~~discounts~~violations, ~~under~~which ~~the~~can ~~Public~~harm ~~Health~~our ~~program~~business.

~~Some~~We ofare ~~the~~subject ~~provisions~~to ofexport ~~the~~control ~~PPACA~~and ~~have~~import ~~yet to~~laws beand ~~implemented~~regulations, ~~and~~including ~~there~~the ~~have~~U.S. ~~been~~Export ~~legal~~Administration Regulations, U.S. Customs regulations, various economic and ~~political~~trade ~~challenges~~sanctions regulations toadministered ~~certain~~by ~~aspects~~the U.S. Treasury Department’s Office of Foreign Assets Controls, the ~~PPACA~~U.S. ~~Since~~Foreign ~~January~~Corrupt ~~2017~~Practices Act of 1977, ~~former~~as ~~President Trump~~amended, ~~has~~or ~~signed~~FCPA, ~~two~~the ~~executive~~U.S. ~~orders~~domestic ~~and~~bribery ~~other~~statute ~~directives~~contained ~~designed~~in to18 ~~delay~~U.S.C. § 201, ~~circumvent~~the U.S. Travel Act, orthe ~~loosen~~USA ~~certain~~PATRIOT Act, ~~requirements~~and ~~mandated~~other bystate and national anti-bribery and anti-money laundering laws in the ~~PPACA~~ countries in which we conduct activities. ~~Concurrently~~Anti-corruption laws are interpreted broadly and prohibit companies and their employees, ~~Congress~~agents, ~~has~~contractors, ~~considered~~and ~~legislation~~other ~~that~~collaborators ~~would~~from ~~repeal~~authorizing, promising, offering, or ~~repeal~~providing, ~~and~~directly ~~replace~~or ~~all~~indirectly, improper payments or ~~part~~anything else of value to recipients in the ~~PPACA~~public or private sector. ~~While~~We ~~Congress has~~may ~~not~~engage ~~passed~~third ~~repeal~~parties ~~legislation,~~for clinical trials outside of the ~~Tax~~United ~~Cuts~~States, ~~and~~to ~~Jobs~~sell ~~Act~~our ofproducts ~~2017~~abroad ~~includes~~once we enter a ~~provision~~commercialization ~~repealing~~phase, ~~effective~~and/or ~~January~~to 1obtain necessary permits, ~~2019~~licenses, ~~the~~patent ~~tax-based~~registrations, and other regulatory approvals. We have ~~shared~~direct ~~responsibility~~or ~~payment~~indirect ~~imposed~~interactions bywith ~~the~~officials ~~PPACA~~and onemployees ~~certain~~of ~~individuals~~government ~~who~~agencies ~~fail~~or togovernment-affiliated ~~maintain~~hospitals, ~~qualifying~~universities, and ~~health~~other ~~coverage~~organizations. We can be held liable for ~~all~~the corrupt or ~~part~~ other illegal activities of aour ~~year~~employees, ~~that~~agents, iscontractors, ~~commonly~~and other ~~referred~~collaborators, toeven asif ~~the~~we ~~“individual~~do ~~mandate”~~not explicitly authorize or have actual knowledge of such activities. ~~Congress~~Any violations of the laws and regulations described above may ~~consider~~result ~~other~~in ~~legislation~~substantial tocivil ~~repeal~~and criminal fines and penalties, imprisonment, the loss of export or ~~replace~~import ~~elements~~privileges, debarment, tax reassessments, breach of ~~the~~contract ~~PPACA~~and fraud litigation, reputational harm, and other consequences.

~~Many of~~An ~~the~~NDA ~~details~~submitted ~~regarding~~under ~~the~~Section ~~implementation of the PPACA are yet to be determined, and at this time, the full effect that the PPACA would~~505(b)(2) ~~have~~subjects onus ~~our business remains unclear. There is uncertainty surrounding the applicability of the biosimilars provisions under the PPACA~~ to ~~our product candidates. The FDA has issued several guidance documents, but no implementing regulations, on biosimilars. Many biosimilar applications have been approved over~~ the ~~past~~risk ~~few years. It is not certain~~ that we will receive 12 years of biologics marketing exclusivity for any of our products. The regulations that are ultimately promulgated and their implementation are likely to have considerable impact on the way we conduct our business and may ~~require~~be ussubject to ~~change current strategies. A biosimilar is~~ a ~~biological~~patent ~~product~~infringement lawsuit that iswould ~~highly similar~~delay toor anprevent ~~approved drug notwithstanding minor differences in clinically inactive components, and for which there are no clinically meaningful differences between~~ the ~~biological~~review ~~product~~or ~~and~~approval ~~the approved drug in terms~~ of our ~~the safety, purity, and potency of the~~ product candidate.

~~Individual states~~Section ~~have~~505(b)(2) ~~become~~permits ~~increasingly~~the ~~aggressive~~submission inof ~~passing~~an NDA ~~legislation~~where ~~and~~at ~~implementing~~least ~~regulations~~some ~~designed~~of tothe ~~control~~information ~~pharmaceutical~~required ~~and biological~~for ~~product~~approval ~~pricing,~~comes ~~including~~from ~~price~~studies orthat ~~patient~~were ~~reimbursement~~not ~~constraints~~conducted by, ~~discounts~~or for, ~~restrictions~~the applicant and on ~~certain~~which ~~product~~the ~~access, and~~applicant ~~marketing~~has ~~cost~~not ~~disclosure~~obtained ~~and~~a ~~transparency~~right ~~measures,~~of ~~and~~reference. toThe ~~encourage~~505(b)(2) ~~importation~~application ~~from~~would ~~other~~enable ~~countries~~us ~~and~~to ~~bulk~~reference ~~purchasing.~~published ~~Legally~~literature ~~mandated~~and/or ~~price~~the ~~controls~~FDA’s onprevious ~~payment~~findings ~~amounts~~of bysafety ~~third-party~~and ~~payors~~effectiveness orfor ~~other~~the ~~restrictions~~branded ~~could~~reference ~~harm~~drug. ~~our~~For ~~business,~~NDAs ~~results~~submitted under Section 505(b)(2) of ~~operations~~the FDCA, ~~financial~~ ~~condition~~the patent certification and ~~prospects~~related provisions of the Hatch-Waxman Act apply. In ~~addition~~accordance with the Hatch- Waxman Act, ~~regional~~such ~~healthcare~~NDAs ~~authorities~~may ~~and~~be ~~individual~~required ~~hospitals~~to ~~are~~include ~~increasingly~~certifications, ~~using~~known ~~bidding procedures~~as toparagraph ~~determine~~IV ~~what~~certifications, ~~pharmaceutical~~that ~~products~~certify that any patents listed in the Patent and ~~which~~Exclusivity ~~suppliers~~Information ~~will~~Addendum beof ~~included~~the inFDA’s ~~their~~publication, ~~prescription~~Approved ~~drug~~Drug ~~and~~Products ~~other~~with ~~healthcare~~Therapeutic Equivalence Evaluations, ~~programs.~~commonly ~~This~~known ~~could~~as ~~reduce~~the ~~ultimate~~Orange ~~demand~~Book, ~~for~~with ~~our~~respect ~~products~~to orany ~~put~~product ~~pressure~~referenced onin ~~our~~the ~~product~~505(b)(2) ~~pricing~~application, ~~which~~are ~~could~~invalid, ~~negatively~~unenforceable ~~affect our~~or ~~business~~will not be infringed by the manufacture, ~~results~~use or sale of ~~operations,~~the ~~financial~~product ~~condition~~that ~~and~~is ~~prospects~~the subject of the 505(b)(2) NDA.

33Under the Hatch-Waxman Act, the holder of patents that the 505(b)(2) application references may file a patent infringement lawsuit after receiving notice of the paragraph IV certification. Filing of a patent infringement lawsuit against the filer of the 505(b)(2) applicant within 45 days of the patent owner’s receipt of notice triggers a one-time, automatic, 30-month stay of the FDA’s ability to approve the 505(b)(2) NDA, unless patent litigation is resolved in the favor of the paragraph IV filer or the patent expires before that time. Accordingly, we may invest a significant amount of time and expense in the development of one or more product candidates only to be subject to significant delay and patent litigation before such product candidates may be commercialized, if at all. In addition, a 505(b)(2) application will not be approved until any non-patent exclusivity, such as exclusivity for obtaining approval of a new chemical entity, or NCE, listed in the Orange Book for the referenced product has expired. The FDA may also require us to perform one or more additional clinical studies or measurements to support the change from the branded reference drug, which could be time consuming and could substantially delay our achievement of regulatory approvals for such product candidates. The FDA may also reject our future 505(b)(2) submissions and require us to file such submissions under Section 505(b)(1) of the FDCA, which would require us to provide extensive data to establish safety and effectiveness of the drug for the proposed use and could cause delay and be considerably more expensive and time consuming. These factors, among others, may limit our ability to successfully commercialize our product candidates.

In addition, given recent federal and state government initiatives directed at lowering the total cost of healthcare, Congress and state legislatures will likely continue to focus on healthcare reform, the cost of prescription drugs and biologics and the reform of the Medicare and Medicaid programs. While we cannot predict the full outcome of any such legislation, it may result in decreased reimbursement for drugs and biologics, which may further exacerbate industry-wide pressure to reduce prescription drug prices. This could harm our ability to generate revenues. Increases in importation or re-importation of pharmaceutical products from foreign countries into the United States could put competitive pressure on our ability to profitably price our products, which, in turn, could adversely affect our business, results of operations, financial condition and prospects. We might elect not to seek approval for or market our products in foreign jurisdictions to minimize the risk of re-importation, which could also reduce the revenue we generate from our product sales. It is also possible that other legislative proposals having similar effects will be adopted.34

~~Furthermore, regulatory~~We ~~authorities’~~may ~~assessment~~seek ofFast ~~the~~Track ~~data~~designation ~~and~~for ~~results required to demonstrate safety and efficacy can change over time and~~one ~~can~~or bemore ~~affected~~of byour ~~many~~product ~~factors~~candidates, ~~such~~but aswe ~~the~~might ~~emergence~~not ofreceive ~~additional~~such ~~information~~designation, ~~including~~and oneven ~~other~~if ~~products,~~we ~~changing policies and agency funding~~do, ~~staffing~~such ~~and~~designation ~~leadership.~~may Wenot ~~cannot~~actually ~~be sure whether future changes~~ lead to ~~the~~a ~~regulatory~~faster ~~environment~~development ~~will be favorable~~ or ~~unfavorable~~ toregulatory ~~our business prospects. For example, average~~ review ~~times~~or ~~at the FDA for marketing~~ approval ~~applications can be affected by a variety of factors, including budget and funding levels and statutory, regulatory and policy changes~~process.

WeIf a product is intended for the treatment of ~~are~~a ~~subject~~serious condition and nonclinical or clinical data demonstrate the potential to Uaddress unmet medical need for this condition, a product sponsor may apply for FDA Fast Track designation.S. ~~and~~If ~~certain~~we ~~foreign~~seek ~~export~~Fast ~~and~~Track ~~import~~designation ~~controls,~~for ~~sanctions~~a product candidate, ~~embargoes~~we may not receive it from the FDA. However, ~~anti-corruption~~even ~~laws~~if we receive Fast Track designation, ~~and~~Fast ~~anti-money~~Track ~~laundering laws~~designation ~~and~~does ~~regulations.~~not ~~Compliance~~ensure ~~with~~that ~~these~~we ~~legal~~will ~~standards~~receive ~~could~~marketing ~~impair~~approval or ~~our~~that ~~ability~~approval towill ~~compete~~be ingranted ~~domestic~~within ~~and~~any ~~international~~particular ~~markets~~timeframe. We ~~can~~may ~~face~~not ~~criminal~~experience ~~liability~~a ~~and~~faster ~~other~~development ~~serious~~or ~~consequences~~regulatory ~~for~~review ~~violations~~or approval process with Fast Track designation compared to conventional FDA procedures. In addition, ~~which~~the ~~can~~FDA ~~harm~~may withdraw Fast Track designation if it believes that the designation is no longer supported by data from our ~~business~~clinical development program. Fast Track designation alone does not guarantee qualification for the FDA’s priority review procedures.

~~We are~~If ~~subject to export control and import laws and regulations, including~~ the ~~U.S.~~FDA ~~Export~~does ~~Administration~~not ~~Regulations,~~conclude ~~U.S.~~that ~~Customs~~our ~~regulations,~~product ~~various~~candidates ~~economic~~satisfy ~~and trade sanctions regulations administered by~~ the ~~U.S.~~requirements ~~Treasury~~for ~~Department’s Office of Foreign Assets Controls,~~ the ~~U.S.~~505(b)(2) ~~Foreign~~regulatory ~~Corrupt~~approval ~~Practices Act of 1977~~pathway, ~~as amended,~~ or ~~FCPA,~~if the ~~U.S.~~requirements ~~domestic~~for ~~bribery~~approval ~~statute~~of ~~contained~~any inof 18our ~~U.S.C. §~~product ~~201,~~candidates ~~the~~under ~~U.S.~~Section ~~Travel~~505(b)(2) ~~Act,~~are ~~the~~not ~~USA~~as ~~PATRIOT Act, and other state and national anti-bribery and anti-money laundering laws in the countries in which~~ we ~~conduct activities. Anti-corruption laws are interpreted broadly and prohibit companies and their employees~~expect, ~~agents, contractors, and other collaborators from authorizing, promising, offering, or providing, directly or indirectly, improper payments or anything else of value to recipients in~~ the ~~public~~approval orpathway ~~private sector. We may engage third parties~~ for ~~clinical trials outside of the United States, to sell~~ our ~~products~~product ~~abroad~~candidates ~~once~~will welikely ~~enter~~take ~~a commercialization phase~~significantly longer, ~~and/or~~cost tosignificantly ~~obtain~~more ~~necessary permits, licenses, patent registrations,~~ and ~~other~~encounter ~~regulatory~~significantly ~~approvals.~~greater Wecomplications ~~have direct or indirect interactions with officials~~ and ~~employees~~risks ofthan ~~government agencies or government-affiliated hospitals~~anticipated, ~~universities,~~ and ~~other~~in ~~organizations.~~any Wecase ~~can~~may ~~be held liable for the corrupt or other illegal activities of our employees, agents, contractors, and other collaborators, even if we do~~ not ~~explicitly authorize or have actual knowledge of such activities. Any~~ ~~violations~~be of the laws and regulations described above may result in substantial civil and criminal fines and penalties, imprisonment, the loss of export or import privileges, debarment, tax reassessments, breach of contract and fraud litigation, reputational harm, and other consequencessuccessful.

AnWe intend to seek FDA approval through the 505(b)(2) ~~NDA~~regulatory ~~submitted~~pathway ~~under~~for certain of our product candidates. The Hatch-Waxman Act, added Section 505(b)(2) ~~subjects~~to the FDCA. Section 505(b)(2) permits the filing of an NDA where at least some of the information required for approval comes from studies that were not conducted by or for the applicant. If the FDA does not allow us to pursue the ~~risk~~505(b)(2) ~~that~~regulatory pathway for our product candidates as anticipated, we may beneed ~~subject~~to conduct additional clinical trials, provide additional data and information and meet additional standards for regulatory approval. If this were to occur, the time and financial resources required to obtain FDA approval for our product candidates would likely substantially increase. Moreover, the inability to pursue the 505(b)(2) regulatory pathway could result in new competitive products reaching the market faster than our product candidates, which could materially adversely impact our competitive position and prospects. Even if we are allowed to pursue the 505(b)(2) regulatory pathway for a ~~patent~~product ~~infringement~~candidate, ~~lawsuit~~we cannot assure you that ~~would~~we ~~delay~~will receive the requisite or ~~prevent~~timely approvals for commercialization of such product candidate. In addition, we expect that our competitors will file citizens’ petitions with the ~~review~~FDA in an attempt to persuade the FDA that our product candidates, or the clinical studies that support their approval, contain ofdeficiencies. Such actions by our ~~product~~competitors ~~candidate~~could delay or even prevent the FDA from approving any NDA that we submit under Section 505(b)(2).

~~Section 505(b)(2)~~We ~~permits~~expect ~~the~~to ~~submission~~rely ofheavily anon ~~NDA~~orphan ~~where~~drug status atto ~~least~~commercialize some of ~~the~~our ~~information~~product ~~required for approval comes from studies that were not conducted by~~candidates, orif ~~for~~approved, ~~the~~but ~~applicant~~we ~~and~~might ~~on which the applicant has~~ not ~~obtained~~receive asuch ~~right~~designation ~~of reference. The 505(b)(2) application would enable us to reference published literature~~ and~~/or~~ ~~the~~any ~~FDA’s~~orphan ~~previous findings of safety and effectiveness for the branded reference~~ drug. ~~For NDAs submitted under Section 505(b)(2) of the FDCA, the patent certification and related provisions of the Hatch-Waxman Act~~designations ~~apply.~~we Inreceive ~~accordance with the Hatch- Waxman Act, such NDAs~~ may be required to include certifications, known as paragraph IV certifications, that certify that any patents listed in the Patent and Exclusivity Information Addendum of the FDA’s publication, Approved Drug Products with Therapeutic Equivalence Evaluations, commonly known as the Orange Book, with respect to any product referenced in the 505(b)(2) application, are invalid, unenforceable or will not beconfer ~~infringed~~marketing byexclusivity ~~the manufacture, use~~ or ~~sale~~other ofexpected ~~the~~commercial ~~product that is the subject of the 505(b)(2) NDA~~benefits.

~~Under~~We expect to rely heavily on orphan drug exclusivity ~~the~~for ~~Hatch-Waxman~~our ~~Act,~~product candidates. Designation of orphan drug status is within the ~~holder~~discretion of ~~patents~~the FDA and the FDA may determine that we do not meet the ~~505(b)(2)~~criteria ~~application~~for ~~references~~orphan ~~may~~drug ~~file~~status. In the United States, orphan drug designation entitles a ~~patent~~party ~~infringement~~to ~~lawsuit~~financial ~~after~~incentives ~~receiving~~such ~~notice~~as ofopportunities ~~the~~for ~~paragraph~~grant IVfunding ~~certification~~towards clinical trial costs, tax advantages and user-fee waivers. ~~Filing~~In ofaddition, if a ~~patent~~product ~~infringement~~that ~~lawsuit~~has orphan ~~against~~drug designation subsequently receives the ~~filer~~first ofFDA approval for the ~~505(b)(2)~~disease ~~applicant~~for ~~within 45~~which ~~days~~it ofhas such designation, the ~~patent~~product ~~owner’s~~is entitled ~~receipt~~to oforphan ~~notice~~drug ~~triggers~~exclusivity. aOrphan ~~one-time,~~drug ~~automatic,~~exclusivity ~~30-month~~in ~~stay~~the ofUnited States provides that the FDA’s ~~ability~~may tonot approve any other applications, ~~the~~including ~~505(b)(2)~~a full NDA, ~~unless~~to ~~patent~~market ~~litigation~~the issame ~~resolved~~drug for the same indication for seven years, except in limited circumstances the ~~favor~~applicable exclusivity ofperiod is ten years in Europe. The European exclusivity period can be reduced to six years if a drug no longer meets the ~~paragraph~~criteria for IVorphan ~~filer~~drug designation or if the ~~patent~~drug ~~expires~~is ~~before~~sufficiently profitable so that ~~time~~market exclusivity is no longer justified. Even if we, or ~~Accordingly~~any future collaborators, weobtain ~~may~~orphan ~~invest~~drug designation for a ~~significant~~product ~~amount~~candidate, ofwe, ~~time~~or ~~and~~they, ~~expense~~may innot ~~the~~be ~~development~~able ofto ~~one~~obtain or ~~more~~maintain orphan drug exclusivity for that product ~~candidates~~candidate. ~~only~~We tomay not be ~~subject~~the first to obtain marketing approval of any product candidate for which we have obtained orphan drug designation for the orphan-designated indication due to ~~significant~~the ~~delay~~uncertainties associated with developing pharmaceutical products, and ~~patent~~it ~~litigation~~is ~~before~~possible ~~such~~that another company also holding orphan drug designation for the same product ~~candidates~~candidate ~~may~~will bereceive ~~commercialized,~~marketing approval iffor atthe ~~all~~same indication before we do. InIf ~~addition~~that were to happen, aour ~~505(b)(2) application~~applications ~~will~~for that indication may not be approved until the ~~any~~competing ~~non-patent~~company’s period of exclusivity expires. In addition, ~~such~~exclusive asmarketing ~~exclusivity~~rights ~~for~~in ~~obtaining~~the United States may be limited if we seek approval offor aan ~~new~~indication ~~chemical~~broader ~~entity,~~ than the orphan-designated indication or ~~NCE,~~may ~~listed~~be inlost if the ~~Orange~~FDA ~~Book~~later ~~for~~determines that the request ~~referenced~~for ~~product~~designation ~~has~~was ~~expired.~~materially ~~The~~defective ~~FDA~~or ~~may~~if ~~also~~we ~~require~~are usunable to ~~perform~~assure ~~one~~sufficient orquantities ~~more~~of ~~additional~~the product to meet the needs ~~clinical~~of ~~studies~~patients with the rare disease or ~~measurements~~condition. toFurther, ~~support~~even ~~the~~if ~~change~~we, ~~from~~or ~~the~~any ~~branded~~future ~~reference~~collaborators, obtain orphan drug exclusivity for a product, ~~which~~that ~~could~~exclusivity bemay ~~time~~not ~~consuming~~effectively ~~and~~protect ~~could~~the ~~substantially delay~~product ~~our~~from ~~achievement~~competition ofbecause ~~regulatory~~different ~~approvals~~drugs with different active moieties may be approved for ~~such~~the ~~product~~same ~~candidates~~condition. ~~The~~Even after an orphan drug is approved, the FDA ~~may~~can ~~also~~subsequently ~~reject~~approve ~~our~~the ~~future~~same ~~505(b)(2)~~drug ~~submissions~~with ~~and~~the ~~require~~same usactive tomoiety ~~file~~for ~~such~~the ~~submissions~~same ~~under~~condition ~~Section~~if ~~505(b)(1)~~the ofFDA concludes that the ~~FDCA~~later drug is clinically superior in that it is shown to be safer, more ~~which~~effective ~~would~~or ~~require~~makes usa major contribution to ~~provide~~patient ~~extensive~~care ~~data~~or the manufacturer of the product with orphan exclusivity is unable to ~~establish~~maintain ~~safety~~sufficient ~~and~~product ~~effectiveness~~quantity. Orphan drug designation neither shortens the development time or regulatory review time of a drug nor gives the drug ~~for~~any advantage in the ~~proposed~~regulatory ~~use~~review ~~and~~or ~~could~~approval ~~cause~~process, ~~delay~~nor ~~and~~does beit ~~considerably~~prevent ~~more~~competitors ~~expensive~~from ~~and~~obtaining ~~time~~approval ~~consuming.~~of the same ~~These~~product ~~factors,~~candidate ~~among~~as ~~others,~~ours ~~may~~for ~~limit~~indications ~~our~~other ~~ability~~than tothose ~~successfully~~in ~~commercialize~~which ~~our~~we ~~product~~have ~~candidates~~been granted orphan drug designation.

3435

We may seek ~~Fast~~a ~~Track~~breakthrough ~~designation~~therapy designation for one or more of our other product candidates, ~~but~~ we might not receive such designation, and even if we do, such designation may not ~~actually~~ lead to a faster development or regulatory review or approval process.

If We may seek a breakthrough therapy designation for one or more of our other product candidates. A breakthrough therapy is defined as a drug that is intended, ~~for~~alone ~~the~~or ~~treatment~~in ofcombination with one or more other drugs, to treat a serious condition, and ~~nonclinical~~preliminary or clinical ~~data~~evidence ~~demonstrate~~indicates that the ~~potential~~drug tomay ~~address~~demonstrate ~~unmet~~substantial ~~medical~~improvement ~~need~~over ~~for~~existing ~~this~~therapies ~~condition~~on one or more clinically significant endpoints, asuch ~~product~~as substantial treatment effects observed early in clinical development. For drugs and biologics that have been designated as breakthrough therapies, interaction and communication between the FDA and the sponsor ~~may~~of ~~apply~~the trial can help to identify the most efficient path for ~~FDA~~clinical ~~Fast~~development ~~Track~~while ~~designation~~minimizing the number of patients placed in ineffective control regimens. IfDrugs wedesignated ~~seek~~as ~~Fast~~breakthrough ~~Track~~therapies ~~designation~~by the FDA may also be eligible for apriority ~~product~~review ~~candidate,~~if wesupported ~~may~~by ~~not~~clinical ~~receive~~data itat ~~from~~the time the NDA is submitted to the FDA. ~~However~~Designation as a breakthrough therapy is within the discretion of the FDA. Accordingly, even if we ~~receive~~believe ~~Fast~~that ~~Track~~one ~~designation,~~of ~~Fast~~our ~~Track~~product candidates meets the criteria for designation ~~does~~as a breakthrough therapy, the FDA may disagree and instead determine not ~~ensure~~to ~~that~~make wesuch ~~will~~designation. ~~receive~~Even ~~marketing~~if ~~approval~~we orreceive ~~that~~breakthrough ~~approval~~therapy designation, ~~will~~the bereceipt ~~granted~~of ~~within~~such ~~any~~designation ~~particular~~for ~~timeframe.~~a Weproduct candidate may not ~~experience~~ result in a faster development or regulatory review or approval process ~~with~~compared ~~Fast~~to ~~Track~~drugs ~~designation~~considered ~~compared~~for toapproval under conventional FDA procedures and does not assure ultimate approval by the FDA. In addition, ~~the~~even ~~FDA~~if ~~may~~one ~~withdraw~~or ~~Fast~~more ~~Track~~of ~~designation~~our ifproduct itcandidates ~~believes~~qualify ~~that~~as ~~the~~breakthrough ~~designation~~therapies, isthe noFDA ~~longer~~may ~~supported~~later bydecide ~~data~~that ~~from~~the ~~our~~product ~~clinical~~candidates ~~development~~no ~~program.~~longer ~~Fast~~meet ~~Track~~the ~~designation~~conditions ~~alone~~for ~~does~~qualification ~~not~~or ~~guarantee~~decide ~~qualification~~that ~~for~~ the ~~FDA’s~~time ~~priority~~period for FDA review ~~procedures~~or approval will not be shortened.

~~If the~~We ~~FDA~~may ~~does~~seek ~~not~~priority ~~conclude~~review ~~that our product candidates satisfy the requirements~~ designation for ~~the~~one ~~505(b)(2) regulatory approval pathway,~~ or ifmore ~~the requirements for approval~~ of ~~any of~~ our other product candidates, ~~under~~but ~~Section~~we ~~505(b)(2)~~might ~~are~~ not asreceive wesuch ~~expect~~designation, ~~the~~and ~~approval~~even ~~pathway~~if ~~for~~we ~~our product candidates will likely take significantly longer~~do, ~~cost~~such ~~significantly~~designation ~~more~~may ~~and encounter significantly greater complications and~~not ~~risks~~lead ~~than~~to ~~anticipated,~~a ~~and~~faster indevelopment ~~any~~or ~~case~~regulatory ~~may~~review ~~not~~or beapproval ~~successful~~process.

~~We intend~~If tothe ~~seek~~ FDA ~~approval~~determines ~~through~~that ~~the~~a ~~505(b)(2)~~product ~~regulatory~~candidate offers ~~pathway~~a treatment for ~~certain~~a ofserious ~~our~~condition ~~product~~and, ~~candidates.~~if ~~The Hatch-Waxman Act~~approved, ~~added Section 505(b)(2) to~~ the ~~FDCA.~~product ~~Section~~would ~~505(b)(2)~~provide ~~permits~~a ~~the~~significant ~~filing~~improvement ofin ansafety ~~NDA~~or ~~where~~effectiveness, the atFDA ~~least~~may ~~some~~designate of the ~~information~~product ~~required~~candidate for ~~approval comes~~priority ~~from~~review. ~~studies~~A ~~that~~priority ~~were~~review ~~not~~designation ~~conducted~~means bythat ~~or for~~ the ~~applicant.~~goal Iffor the FDA ~~does not allow us~~ to ~~pursue the 505(b)(2) regulatory pathway~~review ~~for~~an ~~our~~application ~~product~~is ~~candidates~~six ~~as anticipated~~months, werather ~~may~~than ~~need~~the tostandard ~~conduct~~review ~~additional~~period ~~clinical~~of ~~trials,~~ten ~~provide additional data and information and meet additional standards for regulatory approval~~months. IfWe ~~this~~may ~~were~~request topriority ~~occur,~~review ~~the time and financial resources required to obtain FDA approval~~ for our product candidates. The ~~would~~FDA ~~likely~~has ~~substantially~~broad ~~increase.~~discretion ~~Moreover,~~with ~~the~~respect ~~inability~~ to ~~pursue~~whether ~~the~~or ~~505(b)(2)~~not ~~regulatory~~to ~~pathway could~~grant ~~result~~priority inreview ~~new~~status ~~competitive~~to ~~products~~a ~~reaching the market faster than our~~ product ~~candidates~~candidate, ~~which~~so ~~could~~even ~~materially adversely impact our competitive position and prospects. Even~~ if we ~~are allowed to pursue the 505(b)(2) regulatory pathway for~~ believe a particular product candidate, ~~we cannot~~is ~~assure~~eligible ~~you~~for ~~that~~such wedesignation ~~will~~or ~~receive~~status, the ~~requisite~~FDA ormay ~~timely~~decide ~~approvals~~not ~~for~~to ~~commercialization~~grant ~~of such product candidate~~it. ~~In addition~~Moreover, we ~~expect~~a ~~that~~priority ~~our~~review designation ~~competitors~~does ~~will~~not ~~file~~necessarily ~~citizens’~~mean ~~petitions~~a ~~with~~faster ~~the~~development ~~FDA~~or inregulatory anreview ~~attempt~~or toapproval ~~persuade~~process ~~the~~or ~~FDA~~necessarily ~~that~~confer ~~our~~any ~~product candidates,~~advantage orwith ~~the~~respect ~~clinical~~to ~~studies~~approval ~~that~~compared ~~support~~to ~~their~~conventional ~~approval,~~FDA ~~contain deficiencies~~procedures. ~~Such~~Receiving ~~actions~~priority byreview ~~our~~from ~~competitors could delay or even prevent~~ the FDA ~~from~~does ~~approving~~not ~~any~~guarantee ~~NDA~~approval ~~that~~within the wesix-month ~~submit~~review ~~under~~cycle ~~Section~~or ~~505(b)(2)~~at all.

~~We expect~~Risks toRelated ~~rely heavily on orphan drug status~~ to ~~commercialize~~Third some of our product candidates, if approved, but we might not receive such designation and any orphan drug designations we receive may not confer marketing exclusivity or other expected commercial benefits.Parties

We ~~expect~~ tomay rely ~~heavily~~ on ~~orphan~~third ~~drug~~parties ~~exclusivity~~to ~~for~~ conduct our ~~product~~non-clinical ~~candidates.~~studies ~~Designation of orphan drug status is within the discretion of the FDA~~ and ~~the~~our FDA may determine that we do not meet the criteria for orphan drug status. In the United States, orphan drug designation entitles a party to financial incentives such as opportunities for grant funding towards clinical ~~trial costs, tax advantages and user-fee waivers~~studies. InIf ~~addition,~~these ifthird aparties ~~product~~do that has orphan drug designation subsequently receives the first FDA approval for the disease for which it has such designation, the product is entitled to orphan drug exclusivity. Orphan drug exclusivity in the United States provides that the FDA may not ~~approve~~perform ~~any~~as ~~other~~contractually ~~applications,~~required including a full NDA, to market the same drug for the same indication for seven years, except in limited circumstances the applicable exclusivity period is ten years in Europe. The European exclusivity period can be reduced to six years if a drug no longer meets the criteria for orphan drug designation or ~~if the drug is sufficiently profitable so that market exclusivity is no longer justified. Even if we~~expected, ~~or any future collaborators, obtain orphan drug designation for a product candidate,~~ we, ~~or they,~~ may not be able to ~~obtain~~select ~~or maintain orphan drug exclusivity for that~~ product ~~candidate.~~candidates Weor ~~may not be the first to~~ obtain ~~marketing~~market ~~approval~~acceptance ~~of any product candidate~~ for which we have obtained orphan drug designation for the orphan-designated indication due to the uncertainties associated with developing pharmaceutical products, and it is possible that another company also holding orphan drug designation for the same product candidate will receive marketing approval for the same indication before we do. If that were to happen, our applications for that indication may not be approved until the competing company’s period of exclusivity expires. In addition, exclusive marketing rights in the United States may be limited if we seek approval for an indication broader than the orphan-designated indication or may be lost if the FDA later determines that the request for designation was materially defective or if we are unable to assure sufficient quantities of the product ~~to meet the needs of patients with the rare disease or condition. Further~~candidates, ~~even~~ if weany, or ~~any~~ ~~future~~we ~~collaborators, obtain orphan drug exclusivity for a product, that exclusivity~~ may ~~not effectively protect the product from competition because different drugs with different active moieties may~~ be ~~approved~~delayed for the same condition. Even after an orphan drug is approved, the FDA can subsequently approve the same drug with the same active moiety for the same condition if the FDA concludes that the later drug is clinically superior in ~~that it is shown to be safer, more effective or makes a major contribution to patient care or~~doing ~~the manufacturer of the product with orphan exclusivity is unable to maintain sufficient product quantity~~so. Orphan drug designation neither shortens the development time or regulatory review time of a drug nor gives the drug any advantage in the regulatory review or approval process, nor does it prevent competitors from obtaining approval of the same product candidate as ours for indications other than those in which we have been granted orphan drug designation.

35We often rely on third parties, such as CROs, medical institutions, academic institutions, clinical investigators and contract laboratories, to conduct our clinical studies. We are responsible for confirming that our clinical studies are conducted in accordance with applicable regulations and in accordance with its general investigational plan and protocol. Our reliance on third parties does not relieve us of these responsibilities. If the third parties conducting our clinical studies do not perform their contractual duties or obligations, do not meet expected deadlines, fail to comply with Good clinical practice (GCP), do not adhere to our clinical study protocols or otherwise fail to generate reliable clinical data, we may need to enter into new arrangements with alternative third parties and our clinical study may be more costly than expected or budgeted, extended, delayed or terminated or may need to be repeated, and we may not be able to obtain regulatory approval for or commercialize the target molecules or product candidates, if any, tested in such studies.

We may ~~seek~~explore astrategic ~~breakthrough therapy designation for one or more of our other product candidates, we might not receive such designation, and~~collaborations ~~even~~that ~~if we do, such designation~~ may ~~not~~never ~~lead~~materialize ~~to a faster development~~ or ~~regulatory~~may ~~review or approval process~~fail.

We ~~may~~ ~~seek a breakthrough therapy designation for one or more of our other product candidates. A breakthrough therapy is defined as a drug that is intended~~may, ~~alone or~~ in ~~combination~~the ~~with one or more other drugs~~future, toperiodically ~~treat~~explore a ~~serious condition, and preliminary clinical evidence~~ ~~indicates~~variety ~~that~~of ~~the~~possible ~~drug~~strategic ~~may~~collaborations ~~demonstrate~~including ~~substantial~~international ~~improvement~~distributors ~~over~~and ~~existing therapies on one or more clinically significant endpoints~~partners, ~~such~~ ~~as substantial treatment effects observed early~~ in ~~clinical~~an ~~development.~~effort ~~For~~to ~~drugs~~gain ~~and~~access ~~biologics that have been designated as breakthrough therapies, interaction and communication between the FDA and the sponsor of the trial can help~~ to ~~identify~~new ~~the most efficient path for~~product ~~clinical~~candidates ~~development~~or ~~while minimizing the number of patients placed in ineffective control regimens~~resources. ~~Drugs~~At ~~designated as breakthrough therapies by~~ the ~~FDA~~current ~~may also be eligible for priority review if supported by clinical data at the~~ time, ~~the~~we ~~NDA~~cannot ispredict ~~submitted~~what toform ~~the~~such ~~FDA. Designation as~~ a ~~breakthrough~~strategic ~~therapy~~collaboration ismight ~~within the discretion of the FDA~~take. ~~Accordingly,~~We ~~even~~are iflikely ~~we believe that one of our product candidates~~to ~~meets~~face ~~the~~significant ~~criteria~~competition ~~for~~in ~~designation~~seeking asappropriate astrategic ~~breakthrough therapy~~collaborators, ~~the~~and ~~FDA~~these ~~may~~strategic ~~disagree~~collaborations ~~and~~can ~~instead~~be ~~determine~~complicated ~~not~~and time-consuming to ~~make~~negotiate ~~such~~and ~~designation~~document. ~~Even~~ ifWe ~~we receive breakthrough therapy designation, the receipt of such designation for a product candidate~~ may not ~~result~~be inable ~~a faster development or regulatory review or approval process compared~~ to ~~drugs~~negotiate ~~considered~~strategic ~~for~~collaborations ~~approval~~on ~~under~~acceptable ~~conventional~~terms, ~~FDA~~or ~~procedures~~at ~~and~~all. We ~~does~~are ~~not~~unable ~~assure~~to ~~ultimate~~predict ~~approval by the FDA. In addition~~when, ~~even~~ if ~~one or more of our product candidates qualify as breakthrough therapies~~ever, ~~the~~ ~~FDA~~we ~~may~~will ~~later~~enter ~~decide~~into ~~that~~any ~~the~~additional ~~product~~strategic ~~candidates~~collaborations nobecause ~~longer~~of ~~meet~~ the ~~conditions~~numerous ~~for~~risks ~~qualification~~and ~~or decide that the time period for~~uncertainties ~~FDA~~associated ~~review~~with orestablishing ~~approval~~strategic ~~will not be shortened~~collaborations.

We may seek priority review designation for one or more of our other product candidates, but we might not receive such designation, and even if we do, such designation may not lead to a faster development or regulatory review or approval process.36

~~If the~~Risks ~~FDA~~Related determines that a product candidate offers a treatment for a serious condition and, if approved, the product would provide a significant improvement in safety or effectiveness, the FDA may designate the product candidate for priority review. A priority review designation means that the goal for the FDA to ~~review~~Our anIntellectual application is six months, rather than the standard review period of ten months. We may request priority review for our product candidates. The FDA has broad discretion with respect to whether or not to grant priority review status to a product candidate, so even if we believe a particular product candidate is eligible for such designation or status, the FDA may decide not to grant it. Moreover, a priority review designation does not necessarily mean a faster development or regulatory review or approval process or necessarily confer any advantage with respect to approval compared to conventional FDA procedures. Receiving priority review from the FDA does not guarantee approval within the six-month review cycle or at all. Property

~~Risks~~If we are unable to protect our proprietary ~~Related~~rights or to ~~Third~~defend ~~Parties~~against infringement claims, we may not be able to compete effectively or operate profitably.

~~We may~~Our ~~rely~~success onwill ~~third~~depend, ~~parties~~in topart, ~~conduct~~on our ~~non-clinical~~ability to ~~studies~~obtain ~~and~~patents, ~~our~~operate ~~clinical~~without ~~studies.~~infringing Ifthe ~~these~~proprietary ~~third~~rights ~~parties~~of doothers ~~not~~and ~~perform~~maintain astrade ~~contractually~~secrets, both in the United States and ~~required~~other orcountries. ~~expected,~~Patent wematters ~~may~~in ~~not~~the bebiotechnology ~~able~~and topharmaceutical ~~select~~industries ~~product~~can ~~candidates~~be orhighly ~~obtain~~uncertain ~~market~~and ~~acceptance~~involve ~~for~~complex ~~our~~legal ~~product~~and factual ~~candidates~~questions. Accordingly, ifthe ~~any~~validity, breadth and enforceability of our patents and the existence of potentially blocking patent orrights weof ~~may~~others cannot be ~~delayed~~predicted, either in ~~doing~~the soUnited States or in other countries.

~~We often~~There ~~rely~~can onbe ~~third~~no ~~parties,~~assurance ~~such~~that aswe ~~CROs,~~will ~~medical~~discover or ~~institutions,~~develop ~~academic~~patentable ~~institutions,~~products ~~clinical~~or ~~investigators~~processes ~~and~~or ~~contract~~that ~~laboratories, to~~patents ~~conduct~~will ~~our~~issue ~~clinical~~from ~~studies.~~any Weof ~~are~~the ~~responsible~~currently ~~for~~pending ~~confirming~~patent ~~that~~applications ~~our~~or ~~clinical~~that ~~studies~~claims granted ~~are~~on ~~conducted~~issued inpatents ~~accordance~~will ~~with~~be ~~applicable regulations~~sufficient ~~and~~to inprotect ~~accordance~~our ~~with~~technology ~~its~~or ~~general~~adequately ~~investigational~~cover ~~plan~~the ~~and~~actual ~~protocol.~~products ~~Our~~we ~~reliance~~may onactually ~~third~~sell. ~~parties~~Potential competitors ~~does~~or ~~not~~other ~~relieve~~researchers usin ~~of these~~the ~~responsibilities.~~field Ifmay ~~the~~have ~~third~~filed ~~parties~~patent ~~conducting~~applications, ~~our~~been ~~clinical~~issued ~~studies~~patents, dopublished ~~not~~articles ~~perform~~or ~~their~~otherwise created ~~contractual~~prior ~~duties~~art orthat ~~obligations, do~~could ~~not~~restrict ~~meet~~or ~~expected~~block ~~deadlines,~~our ~~fail~~efforts to ~~comply~~obtain ~~with~~additional ~~Good~~patents. ~~clinical~~There ~~practice~~also ~~(GCP),~~can dobe ~~not~~no ~~adhere~~assurance tothat our ~~clinical study protocols~~issued patents or ~~otherwise~~pending ~~fail~~patent toapplications, ~~generate~~if ~~reliable clinical data~~issued, wewill ~~may~~not ~~need~~be tochallenged, ~~enter~~invalidated, ~~into~~rendered ~~new~~unenforceable ~~arrangements~~or ~~with~~circumvented ~~alternative~~or ~~third~~that the ~~parties~~rights ~~and~~granted ~~our clinical~~hereunder ~~study~~will ~~may~~provide beus ~~more~~with ~~costly~~proprietary ~~than~~protection ~~expected~~ or ~~budgeted,~~competitive ~~extended,~~advantages. ~~delayed~~Our orpatent ~~terminated~~rights oralso ~~may~~depend ~~need~~on toour compliance bewith ~~repeated,~~technology and wepatent ~~may~~licenses ~~not be~~upon ~~able~~which toour ~~obtain~~patent ~~regulatory~~rights ~~approval~~are ~~for~~based orand ~~commercialize~~upon the ~~target~~validity ~~molecules~~of orassignments ~~product~~of ~~candidates~~patent rights from consultants and other inventors that were, ifor ~~any~~are, ~~tested~~not inemployed ~~such~~by ~~studies~~us.

We In addition, competitors may ~~explore~~manufacture ~~strategic~~and ~~collaborations~~sell our ~~that~~potential products in those foreign countries where we have not filed for patent protection or where patent protection may ~~never~~be ~~materialize~~unavailable, not obtainable or ultimately not enforceable. In addition, even where patent protection is obtained, third-party competitors may ~~fail~~challenge our patent claims in the various patent offices, for example via opposition in the European Patent Office or reexamination or interference proceedings in the United States Patent and Trademark Office, or USPTO. The ability of such competitors to sell such products in the United States or in foreign countries where we have obtained patents is usually governed by the patent laws of the countries in which the product is sold.

We ~~may,~~ inwill ~~the~~incur ~~future,~~significant ~~periodically~~ongoing ~~explore~~expenses ain maintaining ~~variety~~our ofpatent ~~possible~~portfolio. ~~strategic~~Should ~~collaborations~~we ~~including~~lack ~~international~~the ~~distributors~~funds ~~and partners, in an effort~~ to ~~gain~~maintain ~~access~~our topatent ~~new~~portfolio ~~product candidates~~ or ~~resources.~~to Atenforce ~~the~~our ~~current~~rights ~~time,~~against infringers, we ~~cannot~~could ~~predict~~be ~~what~~adversely ~~form~~impacted. ~~such~~Even aif ~~strategic collaboration~~claims ~~might~~of ~~take.~~infringement We are ~~likely~~without ~~to face significant competition in seeking appropriate strategic collaborators~~merit, ~~and~~any ~~these~~such ~~strategic collaborations~~action ~~can~~could bedivert ~~complicated~~the ~~and~~ time~~-consuming~~ ~~to negotiate~~ and ~~document. We may not be able to negotiate strategic collaborations~~attention onof ~~acceptable~~management ~~terms,~~and orimpair atour ~~all.~~ability ~~We are unable~~ to ~~predict~~access ~~when, if ever, we will enter into any~~ additional ~~strategic~~capital ~~collaborations because of the numerous risks~~ and/or ~~uncertainties~~cost ~~associated~~us ~~with~~significant ~~establishing~~funds ~~strategic~~to ~~collaborations~~defend.

36Intellectual property rights do not necessarily address all potential threats to our competitive advantage.

~~Risks~~The degree of future protection afforded by our ~~Related~~intellectual property rights is uncertain because intellectual property rights have limitations, and may not adequately protect our business, or permit us to ~~Our~~maintain ~~Intellectual~~our ~~Property~~competitive advantage. The following examples are illustrative:

~~If we~~● ~~are~~Others ~~unable~~may be able to ~~protect~~make ~~our~~compounds ~~proprietary~~that ~~rights~~are orsimilar to ~~defend~~our ~~against~~product ~~infringement~~candidates ~~claims,~~but wethat ~~may~~are not becovered ~~able~~by tothe ~~compete~~claims ~~effectively~~of the patents that we own or ~~operate~~ ~~profitably~~have exclusively licensed.

~~Our success~~● ~~will~~We ~~depend,~~or ~~in part, on~~ our ~~ability~~licensors toor ~~obtain~~strategic ~~patents,~~collaborators ~~operate~~might ~~without~~not ~~infringing~~have ~~the~~been ~~proprietary rights of others and maintain trade secrets, both in~~ the ~~United~~first ~~States~~to ~~and~~make ~~other countries. Patent matters in~~ the ~~biotechnology~~inventions ~~and~~covered ~~pharmaceutical~~by ~~industries can be highly uncertain and involve complex legal and factual questions. Accordingly,~~ the ~~validity,~~issued ~~breadth~~patent ~~and~~or ~~enforceability~~pending ~~of our patents and the existence of potentially blocking~~ patent ~~rights~~application ofthat ~~others~~we ~~cannot~~own ~~be predicted, either in the United States~~ or inhave ~~other~~exclusively ~~countries~~licensed.

~~There can~~● beWe ~~no assurance that we will discover~~ or ~~develop patentable products or processes or that patents will issue from any of the currently pending patent applications or that claims granted on issued patents will be sufficient to protect~~ our ~~technology~~licensors or ~~adequately~~strategic ~~cover the~~collaborators ~~actual~~might ~~products~~not ~~we may actually sell. Potential competitors or other researchers in the field may~~ have ~~filed patent applications,~~ been ~~issued~~the ~~patents,~~first ~~published articles or otherwise created prior art that could restrict or block our efforts~~ to ~~obtain~~file ~~additional patents. There also can be no assurance that our issued patents or pending~~ patent applications, ifcovering ~~issued,~~certain ~~will~~of not be challenged, invalidated, rendered unenforceable or circumvented or that the rights granted hereunder will provide us with proprietary protection or competitive advantages. Our patent rights also depend on our compliance with technology and patent licenses upon which our patent rights are based and upon the validity of assignments of patent rights from consultants and other inventors that were, or are, not employed by usinventions.

~~In addition,~~● ~~competitors~~Others may ~~manufacture~~independently ~~and~~develop ~~sell~~similar ~~our potential products in those foreign countries where we have not filed for patent protection~~ or ~~where~~alternative ~~patent~~technologies ~~protection may be unavailable, not obtainable~~ or ~~ultimately~~duplicate ~~not~~any ~~enforceable.~~of Inour ~~addition,~~technologies ~~even~~without ~~where~~infringing ~~patent protection is obtained, third-party competitors may challenge~~ our ~~patent~~intellectual ~~claims~~property ~~in the various patent offices, for example via opposition in the European Patent Office or reexamination or interference proceedings in the United States Patent and Trademark Office, or USPTO~~rights. The ability of such competitors to sell such products in the United States or in foreign countries where we have obtained patents is usually governed by the patent laws of the countries in which the product is sold.

~~We will~~● ~~incur~~It ~~significant~~is ~~ongoing~~possible ~~expenses~~that ~~in maintaining~~ our ~~patent~~pending ~~portfolio. Should we lack the funds to maintain our~~ patent ~~portfolio or~~applications towill ~~enforce~~not ~~our~~lead ~~rights against infringers, we could be adversely impacted. Even if claims of infringement are without merit, any such action could divert the time and attention of management and impair our ability~~ to ~~access~~issued ~~additional capital and/or cost us significant funds to defend~~patents.

~~Intellectual property~~● ~~rights~~Issued dopatents ~~not~~that ~~necessarily~~we ~~address~~own ~~all~~or ~~potential~~have ~~threats~~exclusively tolicensed ~~our~~may not provide us with any competitive ~~advantage~~advantages, or may be held invalid or unenforceable, as a result of legal challenges by our competitors.

The degree of future protection afforded by our intellectual property rights is uncertain because intellectual property rights have limitations, and may not adequately protect our business, or permit us to maintain our competitive advantage. The following examples are illustrative:37

● ~~Others~~Our ~~may~~competitors bemight ~~able~~conduct toresearch ~~make~~and ~~compounds~~development ~~that~~activities ~~are~~in ~~similar~~countries towhere ~~our~~we ~~product~~do ~~candidates~~not ~~but~~have ~~that~~patent ~~are~~rights ~~not~~and ~~covered~~then byuse the ~~claims~~information oflearned ~~the~~from ~~patents~~such ~~that~~activities weto ~~own~~develop orcompetitive ~~have~~products ~~exclusively~~for ~~licensed~~sale in our major commercial markets.

● We ormay ~~our licensors or strategic collaborators might~~ not ~~have~~develop ~~been~~additional ~~the~~proprietary ~~first~~technologies ~~to make the inventions covered by the issued patent or pending patent application~~ that weare ~~own or have exclusively licensed~~patentable.

● WeThe orpatents ~~our~~of ~~licensors~~others ormay ~~strategic collaborators might not~~ have ~~been~~an ~~the~~adverse ~~first~~effect toon ~~file patent applications covering certain of~~ our ~~inventions~~business.

●Should ~~Others~~any ~~may~~of ~~independently~~these ~~develop~~events ~~similar~~occur, orthey ~~alternative~~could ~~technologies~~significantly harm orour ~~duplicate~~business, ~~any~~results of ~~our~~operations ~~technologies~~and ~~without infringing our intellectual property rights~~prospects.

●Patent Itreform islegislation ~~possible~~could ~~that~~increase the ~~our~~uncertainties ~~pending~~and costs surrounding the prosecution of our patent applications ~~will~~and ~~not~~the ~~lead~~enforcement toor defense of our issued patents.

●On ~~Issued~~September ~~patents~~16, ~~that~~2011, wethe ~~own~~Leahy-Smith America Invents Act, or ~~have~~the ~~exclusively~~Leahy-Smith ~~licensed~~Act, was signed into law. The Leahy-Smith Act includes a number of significant changes to U.S. patent law. These include provisions that affect the way patent applications will be prosecuted and may ~~not~~also ~~provide~~affect uspatent litigation. The USPTO is currently developing regulations and procedures to govern administration of the Leahy-Smith Act, and many of the substantive changes to patent law associated with the Leahy-Smith Act will not become effective until one year or 18 months after its enactment. Accordingly, it is not clear what, if any, ~~competitive~~impact ~~advantages~~the Leahy-Smith Act will have on the operation of our business, orour ~~may~~current beand ~~held~~pending ~~invalid~~patent orportfolio and ~~unenforceable~~future intellectual property strategy. However, asthe aLeahy-Smith ~~result~~Act and its implementation could increase the uncertainties and costs surrounding the prosecution of ~~legal~~our ~~challenges~~patent byapplications and the enforcement or defense of our ~~competitors~~issued patents, all of which could have a material adverse effect on our business and financial condition.

37We may be subject to litigation with respect to the ownership and use of intellectual property that will be costly to defend or pursue and uncertain in its outcome.

● Our ~~competitors~~success ~~might~~also ~~conduct~~will depend, in part, on our refraining from infringing patents or otherwise violating intellectual property owned or controlled by others. Pharmaceutical companies, biotechnology companies, universities, research institutions and ~~development~~others ~~activities~~may have filed patent applications or have received, or may obtain, issued patents in ~~countries~~the ~~where~~United weStates door ~~not~~elsewhere ~~have~~relating ~~patent~~to ~~rights~~aspects ~~and~~of ~~then~~our ~~use~~technology. It is uncertain whether the ~~information~~issuance ~~learned~~of ~~from~~any ~~such~~third-party patents ~~activities~~will require us to ~~develop~~alter ~~competitive~~our products ~~for~~or ~~sale~~processes, obtain licenses, or cease certain activities. Some third-party applications or patents may conflict with our issued patents or pending applications. Any such conflict could result in a significant reduction of the scope or value of our ~~major~~issued ~~commercial~~or ~~markets~~licensed patents.

●In Weaddition, if patents issued to other companies contain blocking, dominating or conflicting claims and such claims are ultimately determined to be valid, we may ~~not~~be required to obtain licenses to these patents or to develop ~~additional~~or ~~proprietary~~obtain ~~technologies~~alternative non-infringing technology and cease practicing those activities, including potentially manufacturing or selling any products deemed to infringe those patents. If any licenses are required, there can be no assurance that we will be able to obtain any such licenses on commercially favorable terms, if at all, and if these licenses are ~~patentable~~not obtained, we might be prevented from pursuing the development and commercialization of certain of our potential products. Our failure to obtain a license to any technology that we may require to commercialize our products on favorable terms may have a material adverse impact on our business, financial condition and results of operations.

●Litigation, ~~The~~which could result in substantial costs to us (even if determined in our favor), may also be necessary to enforce any patents issued or licensed to us or to determine the scope and validity of the proprietary rights of others. The FDA has only recently published draft guidance documents for implementation of the Biologics Price Competition and Innovation Act (BPCIA) under the PPACA, related to the development of follow-on biologics (biosimilars), and detailed guidance for patent litigation procedures under this act has not yet been provided. If another company files for approval to market a competing follow-on biologic, and/or if such approval is given to such a company, we may ~~have~~be anrequired ~~adverse~~to ~~effect~~promptly initiate patent litigation to prevent the marketing of such biosimilar version of our product prior to the normal expiration of the patent. There can be no assurance that our issued or licensed patents would be held valid by a court of competent jurisdiction or that any follow-on biologic would be found to infringe our ~~business~~patents.

~~Should~~In addition, if our competitors file or have filed ~~any~~patent applications in the United States that claim technology also claimed by us, we may have to participate in interference proceedings to determine priority of ~~these~~invention. ~~events~~These ~~occur~~proceedings, ~~they~~if initiated by the USPTO, could ~~significantly~~result ~~harm~~in substantial costs to us, even if the eventual outcome is favorable to us. Such proceedings can be lengthy, are costly to defend and involve complex questions of law and fact, the outcomes of which are difficult to predict. Moreover, we may have to participate in post-grant proceedings or third-party ex parte or inter partes reexamination proceedings under the USPTO. An adverse outcome with respect to a third-party claim or in an interference proceeding could subject us to significant liabilities, require us to license disputed rights from third parties, or require us to cease using such technology, any of which could have a material adverse effect on our business, financial condition and results of operations ~~and prospects~~.

~~Patent reform legislation could increase the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement or defense of our issued patents.~~38

~~On September 16, 2011, the Leahy-Smith America Invents Act, or the Leahy-Smith Act, was signed into law.~~ The ~~Leahy-Smith Act includes a number of significant changes to U.S.~~ patent ~~law.~~protection ~~These include provisions that affect the way patent applications will be prosecuted~~ and ~~may also affect~~ patent ~~litigation. The USPTO is currently developing regulations and procedures to govern administration of the Leahy-Smith~~prosecution ~~Act,~~for ~~and~~some ~~many~~ of ~~the~~our ~~substantive~~target ~~changes~~molecules toand ~~patent~~product ~~law associated with the Leahy-Smith Act will not become effective until one year or 18 months after its enactment. Accordingly~~candidates, ~~it is not clear what,~~ if any, ~~impact~~is ~~the~~dependent ~~Leahy-Smith~~or ~~Act~~may ~~will~~be ~~have~~dependent onin the ~~operation of our business, our current and pending patent portfolio and~~ future intellectual property strategy. However, the Leahy-Smith Act and its implementation could increase the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement or defense of our issued patents, all of which could have a material adverse effect on ~~our~~third ~~business and financial condition~~parties.

WeWhile we normally seek and gain the right to fully prosecute the patents relating to our target molecules and product candidates, if any, there may be ~~subject~~times when platform technology patents or product-specific patents that relate to ~~litigation~~the ~~with~~target ~~respect~~molecules or product candidates are controlled by our licensors. In addition, our licensors and/or licensees may have back-up rights to prosecute patent applications in the ~~ownership~~event that we do not do so or choose not to do so, and ~~use~~our licensees may have the right to assume patent prosecution rights after certain milestones are reached. If any of ~~intellectual~~our ~~property~~licensing collaborators ~~that~~fails ~~will~~to beappropriately ~~costly~~prosecute and maintain patent protection for patents covering any of our product candidates, our ability to ~~defend~~develop orand ~~pursue~~commercialize those product candidates may be adversely affected and we may not be able to prevent competitors ~~uncertain~~from inmaking, ~~its~~using ~~outcome~~and selling competing products.

~~Our success~~We ~~also~~have ~~will depend~~licensed, inor ~~part~~will license, ~~on our refraining~~ from third ~~infringing~~parties ~~patents~~certain ortechnology ~~otherwise~~necessary ~~violating~~to ~~intellectual~~develop ~~property~~and ~~owned~~commercialize orits ~~controlled by others~~therapeutics. ~~Pharmaceutical~~If ~~companies,~~these ~~biotechnology~~licenses ~~companies~~terminate, ~~universities,~~or ~~research~~if ~~institutions~~these ~~and others may have filed patent applications~~third orparties ~~have~~do ~~received,~~not orcomply ~~may~~with ~~obtain,~~the ~~issued~~terms ~~patents~~of in the ~~United~~license, ~~States~~ or ~~elsewhere~~if ~~relating to aspects of our technology. It is uncertain whether~~ the ~~issuance~~underlying oflicensed ~~any third-party~~ patents ~~will~~are ~~require~~found us to ~~alter~~be ~~our products or processes~~invalid, ~~obtain licenses, or cease certain activities. Some third-party applications or patents may conflict with~~ our ~~issued~~business ~~patents or pending applications. Any such conflict~~ could be ~~result~~negatively ~~in a significant reduction of the scope or value of our issued or licensed patents~~impacted.

~~In addition,~~We ifhave ~~patents~~licensed, ~~issued~~or towill ~~other~~license, ~~companies~~from ~~contain~~third ~~blocking~~parties, ~~dominating~~technology ornecessary to ~~conflicting~~research, ~~claims~~develop and ~~such~~commercialize ~~claims~~our ~~are~~product candidates. ~~ultimately~~In ~~determined to~~return befor ~~valid,~~the weuse ~~may~~of betheir ~~required~~technology, towe ~~obtain~~have ~~licenses~~paid ~~to these patents~~ or ~~to develop~~ agreed, or ~~obtain~~will ~~alternative~~agree, ~~non-infringing~~to ~~technology~~pay ~~and cease~~the ~~practicing~~licensor ~~those~~certain ~~activities,~~fees. ~~including~~We ~~potentially~~may ~~manufacturing~~need orto ~~selling~~license ~~any~~additional ~~products~~technology ~~deemed~~ to ~~infringe~~in ~~those~~the ~~patents~~future. If ~~any~~ these licenses ~~are required~~terminate, if ~~there~~the ~~can~~licensors befail noto ~~assurance~~abide ~~that~~by wethe ~~will~~terms beof ~~able~~the tolicense ~~obtain~~or ~~any~~fail ~~such~~to ~~licenses~~prevent oninfringement ~~commercially~~by ~~favorable~~third ~~terms~~parties, if at ~~all, and if these licenses are not obtained, we might be prevented from pursuing~~ the ~~development~~licensed ~~and~~patents ~~commercialization of certain~~or ofother ~~our~~rights ~~potential~~are ~~products.~~found ~~Our failure~~ to ~~obtain~~be ainvalid ~~license~~or toif ~~any technology that~~ we ~~may~~are ~~require~~unable to ~~commercialize~~enter ~~our~~into ~~products~~necessary licenses on ~~favorable~~ acceptable terms, ~~may have a material adverse impact on~~ our business, ~~financial~~could ~~condition~~be ~~and results of operations~~negatively impacted.

~~Litigation, which~~We ~~could~~may ~~result~~become ininvolved ~~substantial costs to us (even if determined~~ in ~~our~~lawsuits ~~favor), may also be necessary~~ to ~~enforce any patents issued~~protect or ~~licensed~~enforce toour uspatents or toother ~~determine~~intellectual the scope and validity of the proprietary rights of others. The FDA has only recently published draft guidance documents for implementation of the Biologics Price Competition and Innovation Act (BPCIA) under the PPACAproperty, ~~related~~which tocould ~~the~~be ~~development of follow-on biologics (biosimilars)~~expensive, ~~and~~time ~~detailed~~consuming ~~guidance for patent litigation procedures under this act has not yet been provided. If another company files for approval to market a competing follow-on biologic,~~ and~~/or~~ if such approval is given to such a company, we may be required to promptly initiate patent litigation to prevent the marketing of such biosimilar version of our product prior to the normal expiration of the patentunsuccessful. ~~There can be no assurance that our issued or licensed patents would be held valid by a court of competent jurisdiction or that any follow-on biologic would be found to infringe our patents.~~

InCompetitors may infringe our patents, trademarks, ~~addition~~copyrights or other intellectual property. To counter infringement or unauthorized use, ifwe ~~our~~may ~~competitors~~be required to file orinfringement ~~have~~claims, which ~~filed~~can ~~patent~~be ~~applications~~expensive inand time consuming and divert the ~~United~~time ~~States~~and ~~that~~attention ~~claim~~of ~~technology~~our ~~also~~management ~~claimed~~and byscientific ~~us,~~personnel. Any claims we ~~may~~assert ~~have~~against perceived infringers could provoke these parties to ~~participate~~assert incounterclaims ~~interference~~against ~~proceedings~~us alleging that we infringe their patents, in addition to ~~determine~~counterclaims ~~priority~~asserting ofthat ~~invention.~~our ~~These~~patents ~~proceedings~~are invalid or unenforceable, ifor ~~initiated~~both. byIn ~~the~~any ~~USPTO~~patent infringement proceeding, ~~could~~there ~~result~~is ina ~~substantial~~risk ~~costs~~that toa ~~us,~~court ~~even~~will ifdecide ~~the~~that ~~eventual~~a ~~outcome~~patent of ours is ~~favorable~~invalid toor ~~us.~~unenforceable, ~~Such~~in ~~proceedings~~whole ~~can~~or bein ~~lengthy~~part, ~~are~~and ~~costly~~that we do not have the right to ~~defend~~stop ~~and~~the ~~involve~~other ~~complex~~party ~~questions~~from ofusing ~~law~~the ~~and~~invention ~~fact~~at issue. There is also a risk that, even if the ~~outcomes~~validity of ~~which~~such ~~are~~patents ~~difficult~~is upheld, tothe ~~predict.~~court ~~Moreover,~~will construe the patent’s claims narrowly or decide that we ~~may~~do not have the right to ~~participate~~stop the other party from inusing ~~post-grant~~the ~~proceedings~~invention orat ~~third-party~~issue exon ~~parte~~the orgrounds ~~inter~~that ~~partes~~our ~~reexamination~~patent ~~proceedings~~claims ~~under~~do not cover the ~~USPTO~~invention. An adverse outcome ~~with respect~~in to a ~~third-party~~litigation ~~claim~~ or inproceeding involving anour ~~interference~~patents ~~proceeding~~ could ~~subject~~limit usour ability to ~~significant~~assert ~~liabilities~~our patents against those parties or other competitors, ~~require~~and usmay tocurtail ~~license~~or ~~disputed~~preclude ~~rights~~our ~~from~~ability to exclude third parties, orfrom ~~require~~making usand toselling ~~cease~~similar ~~using~~or ~~such~~competitive ~~technology,~~products. ~~any~~Any of ~~which~~these occurrences could ~~have~~adversely affect our competitive business position, business prospects and financial condition. Similarly, if we assert trademark infringement claims, a ~~material~~court ~~adverse~~may ~~effect~~determine onthat ~~our~~the ~~business~~marks we have asserted are invalid or unenforceable, or that the party against whom we have asserted trademark ~~financial~~infringement ~~condition~~has ~~and~~superior ~~results~~rights to the marks in question. In this case, we could ultimately be forced to cease use of ~~operations~~such trademarks.

38Even if we establish infringement, the court may decide not to grant an injunction against further infringing activity and instead award only monetary damages, which may or may not be an adequate remedy. Furthermore, because of the substantial amount of discovery required in connection with intellectual property litigation, there is a risk that some of our confidential information could be compromised by disclosure during litigation. There could also be public announcements of the results of hearings, motions or other interim proceedings or developments. If securities analysts or investors perceive these results to be negative, it could have a material adverse effect on the price of shares of our common stock. Moreover, there can be no assurance that we will have sufficient financial or other resources to file and pursue such infringement claims, which typically last for years before they are concluded. Even if we ultimately prevail in such claims, the monetary cost of such litigation and the diversion of the attention of our management and scientific personnel could outweigh any benefit we receive as a result of the proceedings.

~~The patent protection and patent prosecution for some of our target molecules and product candidates, if any, is dependent or may be dependent in the future on third parties.~~39

~~While we~~We ~~normally~~may ~~seek~~rely ~~and~~on ~~gain~~trade ~~the~~secret ~~right~~and toproprietary know-how ~~fully~~which ~~prosecute~~can ~~the~~be ~~patents~~difficult ~~relating~~ to ~~our~~trace ~~target molecules~~ and ~~product~~enforce ~~candidates~~and, if ~~any,~~we ~~there may be times when platform technology patents or product-specific patents that relate to the target molecules or product candidates~~ are ~~controlled~~ byunable ~~our licensors. In addition, our licensors and/or licensees may have back-up rights~~ to ~~prosecute~~protect ~~patent applications in~~ the ~~event~~confidentiality ~~that we do not do so or choose not to do so, and our licensees may have the right to assume patent prosecution rights after certain milestones are reached. If any~~ of our ~~licensing~~trade ~~collaborators fails to appropriately prosecute and maintain patent protection for patents covering any of our product candidates~~secrets, our ~~ability to develop and commercialize those product candidates may be adversely~~business ~~affected~~ and wecompetitive ~~may~~position ~~not~~would be ~~able to prevent competitors from making, using and selling competing products~~harmed.

We also rely on trade secrets to protect technology, especially where patent protection is not believed to be appropriate or obtainable or where patents have ~~licensed~~not issued. For example, orour manufacturing ~~will~~process ~~license~~involves many trade secret steps, ~~from~~processes, ~~third~~and ~~parties~~conditions. ~~certain~~Trade ~~technology~~secrets ~~necessary~~and know-how can be difficult to ~~develop~~protect. We attempt to protect our proprietary technology and ~~commercialize~~processes, ~~its~~in ~~therapeutics~~part, with confidentiality agreements and assignment of invention agreements with our employees and confidentiality agreements with our consultants and certain contractors. IfDespite these ~~licenses~~ ~~terminate~~efforts, orany ifof these ~~third~~ parties may dobreach the agreements and disclose our proprietary information, including our trade secrets, and we may not ~~comply~~be ~~with~~able ~~the~~to ~~terms~~obtain ofadequate remedies ~~the~~for ~~license~~such breaches. Any disclosure, either intentional or ifunintentional, by our employees, the ~~underlying~~employees ~~licensed~~of ~~patents~~third ~~are~~parties with ~~found~~whom we share our facilities or third party consultants and vendors that we engage to beperform ~~invalid~~research, clinical studies or manufacturing activities, or misappropriation by third parties (such as through a cybersecurity breach) of our ~~business~~trade secrets or proprietary information could beenable ~~negatively~~competitors ~~impacted~~to duplicate or surpass our technological achievements, thus eroding our competitive position in our market.

~~We have~~Enforcing ~~licensed,~~a orclaim ~~will~~that ~~license,~~a ~~from~~party ~~third~~illegally ~~parties,~~disclosed or ~~technology~~misappropriated ~~necessary~~a totrade ~~research~~secret is difficult, ~~develop~~expensive and ~~commercialize~~time-consuming, ~~our~~and ~~product candidiates~~the outcome is unpredictable. In ~~return~~addition, ~~for~~some ~~the~~courts inside ~~use~~and ofoutside ~~their~~the ~~technology,~~United weStates ~~have~~are ~~paid~~less orwilling ~~agreed,~~ or ~~will~~unwilling ~~agree,~~ to ~~pay~~protect ~~the~~trade ~~licensor certain fees~~secrets. WeIf ~~may~~any ~~need~~of toour ~~license additional~~trade ~~technology~~secrets were to inbe ~~the~~lawfully obtained ~~future.~~or Ifindependently ~~these~~developed ~~licenses~~by ~~terminate,~~a ifcompetitor ~~the~~or ~~licensors~~other ~~fail~~third toparty, ~~abide~~we bywould ~~the~~have ~~terms~~no ofright ~~the~~to ~~license~~prevent orthem ~~fail to~~from ~~prevent~~using ~~infringement~~that bytechnology or ~~third~~information ~~parties,~~to ifcompete ~~the~~with ~~licensed~~us. ~~patents~~If orany ~~other~~of ~~rights~~our ~~are~~trade ~~found~~secrets were to be ~~invalid~~disclosed to or ifindependently wedeveloped ~~are~~by ~~unable~~a tocompetitor ~~enter~~or other ~~into~~third ~~necessary licenses on acceptable terms~~party, our ~~business~~competitive ~~could~~position would be ~~negatively impacted~~harmed.

WeThere can be no assurance that these agreements ~~may~~are valid and enforceable, will not be breached, that we would have adequate remedies for any breach, or that our trade secrets will not otherwise become ~~involved~~known or be independently discovered by competitors. We may fail in ~~lawsuits~~certain circumstances to ~~protect~~obtain the necessary confidentiality agreements or ~~enforce~~assignment ~~our~~of ~~patents~~invention agreements, or ~~other~~their ~~intellectual~~scope ~~property,~~or ~~which~~term ~~could~~may not be ~~expensive,~~sufficiently ~~time~~broad ~~consuming~~to protect our interests or transfer ~~and~~adequate ~~unsuccessful~~rights to us.

~~Competitors may~~If ~~infringe~~ our ~~patents,~~trade ~~trademarks,~~secrets ~~copyrights~~ or other intellectual property~~. To counter infringement or unauthorized use, we may~~ bebecome ~~required~~known to ~~file~~our ~~infringement claims~~competitors, ~~which~~it ~~can be expensive and time consuming and divert the time and attention of our management and scientific personnel. Any claims we assert against perceived infringers~~ could ~~provoke~~result ~~these parties to assert counterclaims against us alleging that we infringe their patents,~~ in ~~addition~~a tomaterial ~~counterclaims~~adverse ~~asserting~~effect ~~that~~on our ~~patents are invalid or unenforceable~~business, ~~or both.~~financial Incondition ~~any~~and ~~patent~~results ~~infringement proceeding, there is a risk that a court will decide that a patent~~ of ~~ours is invalid or unenforceable, in whole or in part, and that we do not have the right to stop the other party from using the invention at issue~~operations. ~~There is also a risk~~ ~~that,~~To ~~even if~~ the ~~validity~~extent ~~of such patents is upheld, the court will construe the patent’s claims narrowly or decide~~ that we ~~do not have the right to stop the other party from using the invention at issue on the grounds that our patent claims do not cover the invention. An adverse outcome in a litigation~~ or ~~proceeding involving~~ our ~~patents~~consultants ~~could limit our ability to assert our patents against those parties~~ or ~~other~~research ~~competitors,~~collaborators ~~and~~use ~~may~~intellectual ~~curtail~~property orowned ~~preclude~~by ~~our~~others ~~ability~~in towork ~~exclude~~for ~~third parties from making and selling similar or competitive products. Any of these occurrences could adversely affect our competitive business position~~us, ~~business prospects and financial condition.~~disputes ~~Similarly, if we assert trademark infringement claims, a court~~ may ~~determine~~also ~~that~~arise ~~the~~as ~~marks~~to ~~we have asserted are invalid or unenforceable, or that~~ the ~~party against whom we have asserted trademark infringement has superior~~ rights to ~~the~~related ~~marks~~or inresulting ~~question.~~know-how Inand ~~this case, we could ultimately be forced to cease use of such trademarks~~inventions.

~~Even if~~We ~~we establish infringement, the court~~ may ~~decide~~ not ~~to grant an injunction against further infringing activity and instead award only monetary damages, which may or may not~~ be anable adequate remedy. Furthermore, because of the substantial amount of discovery required in connection with intellectual property litigation, there is a risk that some of our confidential information could be compromised by disclosure during litigation. There could also be public announcements of the results of hearings, motions or other interim proceedings or developments. If securities analysts or investors perceive these results to beprotect ~~negative, it could have a material adverse effect on the price of shares of~~ our ~~common stock. Moreover, there can be no assurance that we will have sufficient financial or other resources to file and pursue~~intellectual ~~such~~property ~~infringement~~rights ~~claims,~~throughout ~~which typically last for years before they are concluded. Even if we ultimately prevail in such claims,~~ the ~~monetary~~ ~~cost of such litigation and the diversion of the attention of our management and scientific personnel could outweigh any benefit we receive as a result of the proceedings~~world.

39Patents are of national or regional effect, and filing, prosecuting and defending patents on all of our product candidates throughout the world would be prohibitively expensive. As such, we may not be able to prevent third parties from practicing our inventions in all countries outside the United States, or from selling or importing products made using our inventions in and into the United States or other jurisdictions. Further, the legal systems of certain countries, particularly certain developing countries, do not favor the enforcement of patents and other intellectual property protection, particularly those relating to pharmaceuticals or biologics, which could make it difficult for us to stop the infringement of our patents or marketing of competing products in violation of our proprietary rights generally. In addition, certain developing countries, including China and India, have compulsory licensing laws under which a patent owner may be compelled to grant licenses to third parties. In those countries, we and our licensors may have limited remedies if patents are infringed or if we or our licensors are compelled to grant a license to a third party, which could materially diminish the value of those patents. This could limit our potential revenue opportunities. Accordingly, our efforts to enforce our intellectual property rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property that we develop or license.

We may rely on trade secret and proprietary know-how which can be difficult to trace and enforce and, if we are unable to protect the confidentiality of our trade secrets, our business and competitive position would be harmed.40

~~We also~~Patent ~~rely~~terms onmay ~~trade secrets to protect technology, especially where patent protection is not believed to~~ be ~~appropriate~~inadequate ~~or obtainable or where patents have not issued. For example, our manufacturing process involves many trade secret steps, processes, and conditions. Trade secrets and know-how can be difficult~~ to protect~~. We attempt to protect our proprietary technology and processes, in part, with~~ ~~confidentiality agreements and assignment of invention agreements with~~ our ~~employees~~competitive ~~and~~position ~~confidentiality~~on ~~agreements with~~ our ~~consultants and~~product ~~certain~~candidates ~~contractors.~~for ~~Despite~~an ~~these efforts, any of these parties may breach the agreements and disclose our proprietary information, including our trade secrets, and we may not be able to obtain~~ adequate ~~remedies~~amount ~~for such breaches. Any disclosure, either intentional or unintentional, by our employees, the employees~~ of third parties with whom we share our facilities or third party consultants and vendors that we engage to perform research, clinical studies or manufacturing activities, or misappropriation by third parties (such as through a cybersecurity breach) of our trade secrets or proprietary information could enable competitors to duplicate or surpass our technological achievements, thus eroding our competitive position in our markettime.

~~Enforcing a~~Patent ~~claim~~rights ~~that~~are aof ~~party~~limited ~~illegally~~duration. ~~disclosed~~Given orthe amount ~~misappropriated~~of atime ~~trade~~required ~~secret~~for isthe ~~difficult~~development, ~~expensive~~testing and ~~time-consuming~~regulatory review of new product candidates, ~~and~~patents ~~the~~protecting ~~outcome~~such candidates ismight ~~unpredictable~~expire before or shortly after such product candidates are commercialized. InEven ~~addition~~if patents covering our product candidates are obtained, once ~~some~~the ~~courts~~patent ~~inside~~life ~~and~~has ~~outside~~expired for a product, we may be open to competition from biosimilar or generic products. A patent term extension based on regulatory delay may be available in the United States. ~~are~~However, ~~less~~only ~~willing~~a orsingle ~~unwilling~~patent tocan ~~protect~~be ~~trade~~extended ~~secrets.~~for each marketing approval, Ifand any patent can be extended only once, for a single product. Moreover, the scope of ~~our~~protection ~~trade~~during ~~secrets~~the ~~were~~period toof bethe ~~lawfully~~patent ~~obtained~~term extension ordoes ~~independently~~not ~~developed~~extend byto athe ~~competitor~~full orscope ~~other~~of ~~third~~the ~~party~~claim, webut ~~would~~instead ~~have~~only to the scope of the product as approved. Laws governing analogous nopatent ~~right~~term extensions in foreign jurisdictions vary widely, as do laws governing the ability to ~~prevent~~obtain ~~them~~multiple patents from ~~using~~a ~~that~~single patent ~~technology~~family. Additionally, we may not receive an extension if we fail to apply within applicable deadlines, fail to apply prior to expiration of relevant patents or ~~information~~otherwise fail to ~~compete~~satisfy ~~with~~applicable usrequirements. If ~~any~~we are unable to obtain patent term extension or restoration, or the term of ~~our~~any ~~trade~~such ~~secrets~~extension ~~were~~is less than we request, the period during which we will have the right to beexclusively ~~disclosed~~market our product towill orbe ~~independently~~shortened ~~developed~~and byour acompetitors ~~competitor~~may orobtain ~~other~~approval ~~third~~of ~~party,~~competing products following our ~~competitive~~patent ~~position~~expiration, ~~would~~and our revenue could be ~~harmed~~reduced, possibly materially.

~~There can~~We bemay ~~no assurance that these agreements are valid and enforceable, will not~~ be ~~breached,~~subject ~~that~~to weclaims ~~would~~by ~~have~~third ~~adequate remedies for any~~parties ~~breach,~~asserting or that our ~~trade~~employees ~~secrets will not otherwise become known~~ or bewe ~~independently~~have ~~discovered~~misappropriated bytheir ~~competitors.~~intellectual Weproperty ~~may fail in certain circumstances to obtain the necessary confidentiality agreements~~ or ~~assignment~~claiming ownership of ~~invention~~what ~~agreements,~~we orregard ~~their~~as ~~scope~~our ~~or term may not~~own beintellectual ~~sufficiently broad to protect our interests or transfer adequate rights to us~~property.

IfSome of our employees and our licensors’ employees, including our ~~trade~~senior ~~secrets~~management, were previously employed at universities or at other ~~intellectual~~biotechnology ~~property~~or ~~become~~pharmaceutical ~~known~~companies, including to our competitors or potential competitors. Some of these employees may have executed proprietary rights, itnon-disclosure ~~could~~and ~~result~~non-competition agreements, or similar agreements, in aconnection ~~material~~with ~~adverse~~such ~~effect~~previous onemployment. Although we try to ensure that our employees do not use ~~business,~~the ~~financial~~proprietary ~~condition~~information ~~and~~or ~~results~~know-how of ~~operations.~~others Toin ~~the~~their ~~extent~~work for us, we may be subject to claims that we or ~~our~~these ~~consultants~~employees have used or ~~research~~disclosed ~~collaborators~~intellectual ~~use~~property, ~~intellectual~~including trade secrets or other proprietary information, of any such third party. Litigation may ~~property~~be ~~owned~~necessary byto ~~others~~defend against such claims. If we fail in ~~work~~defending ~~for~~any ussuch claims, ~~disputes~~in addition to paying monetary damages, we may ~~also~~lose valuable ~~arise~~intellectual asproperty torights ~~the~~or personnel or sustain damages. Such intellectual property rights could be awarded to ~~related~~a third party, and we could be required to obtain a license from such third party to commercialize our technology or ~~resulting~~products. ~~know-how~~Such a license may not be available on commercially reasonable terms or at all. Even if we are successful in defending against such claims, litigation could result in substantial costs and ~~inventions~~be a distraction to management.

WeIn addition, while we typically require our employees, ~~may~~consultants ~~not~~and contractors who may be ~~able~~involved in the development of intellectual property to ~~protect~~execute agreements assigning such intellectual property to us, we may be unsuccessful in executing such an agreement with each party who in fact develops intellectual property that we regard as our own, which may result in claims by or against us related to the ownership of such intellectual property. If we fail in prosecuting or defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights. ~~throughout~~Even if ~~the~~we ~~world~~are successful in prosecuting or defending against such claims, litigation could result in substantial costs and be a distraction to our senior management and scientific personnel.

~~Patents are~~Obtaining ~~of national or regional effect,~~ and ~~filing,~~maintaining ~~prosecuting and defending patents on all of~~ our ~~product~~patent ~~candidates throughout the world~~protection ~~would~~depends beon ~~prohibitively~~compliance ~~expensive.~~with Asvarious ~~such~~procedural, wedocument ~~may not be able to prevent third parties from practicing our inventions in all countries outside the United States~~submissions, orfee ~~from~~payment ~~selling or importing products made using our inventions in~~ and ~~into the United States or~~ other ~~jurisdictions. Further,~~requirements ~~the~~imposed ~~legal~~by ~~systems~~governmental of certain countries, particularly certain developing countries, do not favor the enforcement of patents and other intellectual property protection, particularly those relating to pharmaceuticals or biologics, which could make it difficult for us to stop the infringement of our patents or marketing of competing products in violation of our proprietary rights generally. In addition, certain developing countries, including China and India, have compulsory licensing laws under which a patent ~~owner may be compelled to~~ ~~grant licenses to third parties. In those countries~~agencies, we and our ~~licensors~~patent ~~may~~protection ~~have limited remedies if patents are infringed or if we or our licensors are compelled to grant a license to a third party, which~~ could ~~materially diminish the value of those patents. This could limit our potential revenue opportunities. Accordingly, our efforts to enforce our intellectual property rights around the world may~~ be ~~inadequate~~reduced toor ~~obtain~~eliminated afor ~~significant~~non-compliance ~~commercial~~with ~~advantage~~these ~~from the intellectual property that we develop or license~~requirements.

40Periodic maintenance fees on any issued patent are due to be paid to the USPTO and foreign patent agencies in several stages over the lifetime of the patent. The USPTO and various foreign governmental patent agencies require compliance with a number of procedural, documentary, fee payment and other similar provisions during the patent application process. While an inadvertent lapse can in many cases be cured by payment of a late fee or by other means in accordance with the applicable rules, there are situations in which noncompliance can result in abandonment or lapse of the patent or patent application, resulting in partial or complete loss of patent rights in the relevant jurisdiction. Non-compliance events that could result in abandonment or lapse of a patent or patent application include, but are not limited to, failure to respond to official actions within prescribed time limits, non-payment of fees and failure to properly legalize and submit formal documents. If we fail to maintain the patents and patent applications covering our product candidates, our competitive position would be adversely affected.

~~Patent terms may be inadequate to protect our competitive position on our product candidates for an adequate amount of time.~~41

~~Patent rights~~Risks ~~are~~Relating of limited duration. Given the amount of time required for the development, testing and regulatory review of new product candidates, patents protecting such candidates might expire before or shortly after such product candidates are commercialized. Even if patents covering our product candidates are obtained, once the patent life has expired for a product, we may be open to competition from biosimilar or generic products. A patent term extension based on regulatory delay may be available in the United States. However, only a single patent can be extended for each marketing approval, and any patent can be extended only once, for a single product. Moreover, the scope of protection during the period of the patent term extension does not extend to the full scope of the claim, but instead only to the scope of the product as approved. Laws governing analogous patent term extensions in foreign jurisdictions vary widely, as do laws governing the ability to obtain multiple patents from a single patent family. Additionally, we may not receive an extension if we fail to apply within applicable deadlines, fail to apply prior to expiration of relevant patents or otherwise fail to satisfy applicable requirements. If we are unable to obtain patent term extension or restoration, or the term of any such extension is less than we request, the period during which we will have the right to exclusively market our product will be shortened and our competitors may obtain approval of competing products following our patent expiration, and our revenue could be reduced, possibly materially.Litigation

We ~~may~~ beare ~~subject~~exposed to ~~claims~~potential byproduct ~~third~~liability or ~~parties~~similar ~~asserting~~claims, ~~that~~and ~~our~~insurance ~~employees~~against orthese weclaims ~~have~~may ~~misappropriated~~not ~~their~~be ~~intellectual~~available ~~property~~to orus ~~claiming ownership~~at ofa ~~what~~reasonable werate ~~regard~~in asthe ~~our own intellectual property~~future.

~~Some of~~Our ~~our~~business ~~employees~~exposes ~~and~~us ~~our~~to ~~licensors’~~potential ~~employees, including our senior management, were previously employed at universities or at~~liability ~~other~~risks ~~biotechnology~~that orare ~~pharmaceutical~~inherent ~~companies,~~in ~~including~~the ~~our competitors or potential competitors. Some of these employees may have executed proprietary rights~~testing, ~~non-disclosure~~manufacturing and ~~non-competition~~marketing ~~agreements,~~of orhuman ~~similar~~therapeutic ~~agreements, in connection with such previous employment~~products. ~~Although~~ weClinical ~~try~~trials toinvolve ~~ensure that our employees do not use~~ the ~~proprietary information or know-how~~ testing of ~~others~~product incandidates ~~their~~on ~~work~~human ~~for~~subjects ~~us, we may be subject to claims that we~~ or ~~these~~volunteers ~~employees~~under ~~have~~a ~~used~~research ~~or disclosed intellectual property~~plan, ~~including~~and ~~trade~~carry ~~secrets~~a orrisk ~~other proprietary information,~~ of ~~any~~liability ~~such~~for ~~third~~personal ~~party.~~injury ~~Litigation~~or ~~may~~death to bepatients ~~necessary~~due to ~~defend~~unforeseen ~~against~~adverse ~~such~~side ~~claims.~~effects, Ifimproper weadministration ~~fail~~of inthe ~~defending~~product ~~any such claims~~candidate, in ~~addition to paying monetary damages, we may lose valuable intellectual property rights~~ or ~~personnel~~other ~~or sustain damages~~factors. ~~Such~~Many ~~intellectual~~of these ~~property~~patients ~~rights~~are ~~could~~already beseriously ~~awarded~~ill ~~to a third party,~~ and weare ~~could~~therefore beparticularly ~~required~~vulnerable to ~~obtain~~further aillness ~~license from such third party to commercialize our technology~~ or ~~products~~death. Such a license may not be available on commercially reasonable terms or at all. Even if we are successful in defending against such claims, litigation could result in substantial costs and be a distraction to management.

InWe currently do not carry clinical trial liability ~~addition,~~insurance ~~while~~but we ~~typically~~will ~~require~~need ~~our~~to ~~employees,~~once ~~consultants~~we ~~and~~begin ~~contractors~~clinical ~~who~~trials. ~~may~~There can be ~~involved~~no inassurance ~~the~~that ~~development~~we ofwill ~~intellectual property~~be able to ~~execute~~obtain ~~agreements~~such ~~assigning~~insurance or that the amount of such ~~intellectual~~insurance ~~property~~will be adequate to ~~us,~~cover weclaims. ~~may~~We could be ~~unsuccessful~~materially inand ~~executing~~adversely ~~such~~affected anif ~~agreement~~we ~~with~~were required ~~each~~to ~~party~~pay ~~who~~damages or incur defense costs in ~~fact~~connection ~~develops~~with ~~intellectual~~a ~~property~~claim ~~that~~outside wethe ~~regard~~scope asof ~~our~~indemnity ~~own~~or insurance coverage, ~~which~~if ~~may~~the ~~result~~indemnity is not performed or enforced in ~~claims~~accordance bywith its terms, or ~~against~~if usour ~~related to~~liability exceeds the ~~ownership~~amount of ~~such~~applicable ~~intellectual property~~insurance. IfIn weaddition, there ~~fail~~can inbe ~~prosecuting~~no orassurance ~~defending~~that ~~any~~insurance ~~such~~will ~~claims,~~continue into ~~addition~~be toavailable ~~paying~~on ~~monetary damages,~~terms weacceptable ~~may~~to ~~lose~~us, ~~valuable~~if ~~intellectual~~at ~~property~~all, ~~rights.~~or ~~Even~~that if weobtained, ~~are~~the insurance ~~successful~~coverage inwill ~~prosecuting~~be orsufficient ~~defending~~to ~~against~~cover ~~such~~any potential claims~~, litigation~~ ~~could~~or ~~result~~liabilities. inSimilar ~~substantial~~risks ~~costs~~would ~~and~~exist beupon athe ~~distraction~~commercialization or tomarketing ~~our~~of ~~senior~~any ~~management~~products ~~and~~by ~~scientific~~us ~~personnel~~or our collaborators.

~~Obtaining and~~Regardless ~~maintaining~~of ~~our~~their ~~patent~~merit ~~protection~~or ~~depends~~eventual ~~on compliance with various procedural~~outcome, ~~document submissions, fee payment and other requirements~~ ~~imposed~~product byliability ~~governmental~~claims ~~patent~~may ~~agencies,~~result ~~and our patent protection could be reduced or eliminated for non-compliance with these requirements.~~in:

~~Periodic maintenance~~● ~~fees~~decreased ondemand ~~any~~for issued patent are due to be paid to the USPTO and foreign patent agencies in several stages over the lifetime of the patent. The USPTO and various foreign governmental patent agencies require compliance with a number of procedural, documentary, fee payment and other similar provisions during the patent application process. While an inadvertent lapse can in many cases be cured by payment of a late fee or by other means in accordance with the applicable rules, there are situations in which noncompliance can result in abandonment or lapse of the patent or patent application, resulting in partial or complete loss of patent rights in the relevant jurisdiction. Non-compliance events that could result in abandonment or lapse of a patent or patent application include, but are not limited to, failure to respond to official actions within prescribed time limits, non-payment of fees and failure to properly legalize and submit formal documents. If we fail to maintain the patents and patent applications covering our product ~~candidates, our competitive position would be adversely affected.~~;

41● injury to our reputation and significant negative media attention;

~~Risks Relating~~● towithdrawal ~~Litigation~~of clinical trial volunteers;

~~We are~~● ~~exposed~~costs toof ~~potential product liability or similar claims, and insurance against these claims may not be available to us at a reasonable rate in the future.~~litigation;

~~Our business~~● ~~exposes~~distraction ~~us to potential liability risks that are inherent in the testing, manufacturing and marketing~~ of ~~human~~management; ~~therapeutic products. Clinical trials involve the testing of product candidates on human subjects or volunteers under a research plan,~~ and carry a risk of liability for personal injury or death to patients due to unforeseen adverse side effects, improper administration of the product candidate, or other factors. Many of these patients are already seriously ill and are therefore particularly vulnerable to further illness or death.

~~We currently~~● dosubstantial ~~not~~monetary ~~carry~~awards ~~clinical trial liability insurance but we will need~~ to ~~once we begin clinical trials~~plaintiffs. There can be no assurance that we will be able to obtain such insurance or that the amount of such insurance will be adequate to cover claims. We could be materially and adversely affected if we were required to pay damages or incur defense costs in connection with a claim outside the scope of indemnity or insurance coverage, if the indemnity is not performed or enforced in accordance with its terms, or if our liability exceeds the amount of applicable insurance. In addition, there can be no assurance that insurance will continue to be available on terms acceptable to us, if at all, or that if obtained, the insurance coverage will be sufficient to cover any potential claims or liabilities. Similar risks would exist upon the commercialization or marketing of any products by us or our collaborators.

~~Regardless of~~Should ~~their~~any ~~merit~~of orthese ~~eventual~~events ~~outcome~~occur, ~~product~~it ~~liability~~could ~~claims~~have a ~~may~~material ~~result~~adverse ~~in:~~effect on our business and financial condition.

●Information ~~decreased~~technology ~~demand~~security ~~for~~breaches and ~~our~~other ~~product;~~disruptions ●could ~~injury~~compromise to our ~~reputation~~information and ~~significant~~expose ~~negative~~us ~~media~~to ~~attention;~~legal ●responsibility ~~withdrawal~~which ofwould ~~clinical~~cause ~~trial~~our ~~volunteers;~~business ~~● costs of litigation; ● distraction of management;~~ and ~~● substantial monetary awards~~ reputation to ~~plaintiffs~~suffer.

~~Should~~We are increasingly dependent on information ~~any~~technology systems and infrastructure, much of ~~these~~which ~~events~~is ~~occur~~outsourced to third parties including on “cloud” based platforms. We collect, itstore, and use sensitive or confidential data, including intellectual property, our proprietary business information and that of our suppliers, and business partners. The secure maintenance of this information is critical to our operations and business strategy. We are subject to laws and regulations in the United States and abroad, such as the Health Insurance Portability and Accountability Act of 1996 and European Union regulations related to data privacy, which require us to protect the privacy and security of certain types of information. Our information technology and infrastructure may be vulnerable to attacks by hackers, breached due to employee error, malfeasance, or other disruptions, or subject to system failures. Because the techniques used to obtain unauthorized access, disable, or degrade service, or sabotage systems change frequently and may be difficult to detect for long periods of time, we may be unable to anticipate these techniques or implement adequate preventive measures. Any breaches or failures could ~~have~~compromise asensitive ~~material~~and ~~adverse~~confidential information ~~effect~~stored on our ~~business~~networks or those of third parties and expose such information to public disclosure, loss, or theft. Any actual or alleged unauthorized access, disclosure or other loss of information could result in legal claims or proceedings, liability under laws that protect the privacy of personal information, disruption of our operations, and damage to our reputation, any of which could adversely affect our business, financial condition, or results of operations. Costs we may incur as a result of any of the foregoing, could adversely affect our business, financial condition, or results of operations. Given the increasing use of conferencing technologies to conduct business virtually in light of the COVID-19 pandemic, these cybersecurity risks are becoming more prevalent.

~~Information~~Risks ~~technology security~~Relating ~~breaches and other disruptions could compromise our information and expose us~~ to ~~legal~~Our ~~responsibility which would cause our business and reputation to suffer.~~Stock

WeOur ~~are~~common ~~increasingly~~stock ~~dependent on information technology systems and infrastructure, much of which~~ is ~~outsourced~~deemed toa ~~third parties including on~~ “~~cloud” based~~penny ~~platforms. We collect~~stock,” store, and use sensitive or confidential data, including intellectual property, our proprietary business information and that of our suppliers, and business partners. The secure maintenance of this information is critical to our operations and business strategy. We are subject to laws and regulations in the United States and abroad, such as the Health Insurance Portability and Accountability Act of 1996 and European Union regulations related to data privacy, which ~~require~~would usmake toit ~~protect~~more the privacy and security of certain types of information. Our information technology and infrastructure may be vulnerable to attacks by hackers, breached due to employee error, malfeasance, or other disruptions, or subject to system failures. Because the techniques used to obtain unauthorized access, disable, or degrade service, or sabotage systems change frequently and may be difficult ~~to detect~~ for long periods of time, we may be unable to anticipate these techniques or implement adequate preventive measures. Any breaches or failures could compromise sensitive and confidential information stored on our ~~networks~~investors ~~or those of third parties and expose such information~~ to ~~public~~sell ~~disclosure,~~their ~~loss, or theft~~shares. Any actual or alleged unauthorized access, disclosure or other loss of information could result in legal claims or proceedings, liability under laws that protect the privacy of personal information, disruption of our operations, and damage to our reputation, any of which could adversely affect our business, financial condition, or results of operations. Costs we may incur as a result of any of the foregoing, could adversely affect our business, financial condition, or results of operations. Given the increasing use of conferencing technologies to conduct business virtually in light of the COVID-19 pandemic, these cybersecurity risks are becoming more prevalent.

~~Risks~~Our common stock is subject to the “penny ~~Relating~~stock” rules adopted under Section 15(g) of the Exchange Act. The penny stock rules generally apply to ~~Our~~companies whose common stock is not listed on the NASDAQ Stock Market or other national securities exchange and trades at less than $4.00 per share, other than companies that have had average revenue of at least $6,000,000 for the last three years or that have tangible net worth of at least $5,000,000 ($2,000,000 if the company has been operating for three or more years). These rules require, among other things, that brokers who trade penny stock to persons other than “established customers” complete certain documentation, make suitability inquiries of investors and provide investors with certain information concerning trading in the security, including a risk disclosure document and quote information under certain circumstances. Many brokers have decided not to trade penny stocks because of the requirements of the penny stock rules and, as a result, the number of broker-dealers willing to act as market makers in such securities is limited. If we remain subject to the penny stock rules for any significant period, it could have an adverse effect on the market, if any, for our securities. If our securities are subject to the penny stock rules, investors will find it more difficult to dispose of our securities.

~~Our common stock is deemed a “penny stock,” which would make it more difficult for our investors to sell their shares.~~42

~~Our common~~We ~~stock~~have ~~is subject to the “penny stock” rules adopted under Section 15(g) of the Exchange Act. The penny stock rules generally apply to companies whose common stock is~~ not ~~listed~~paid oncash ~~the~~dividends NASDAQ Stock Market or other national securities exchange and trades at less than $4.00 per share, other than companies that have had average revenue of at least $6,000,000 for the last three years or that have tangible net worth of at least $5,000,000 ($2,000,000 if the company has been operating for three or more years). These rules require, among other things, that brokers who trade penny stock to persons other than “established customers” complete certain documentation, make suitability inquiries of investors and provide investors with certain information concerning trading in the ~~security, including~~ apast ~~risk disclosure document~~ and ~~quote~~do ~~information under certain circumstances. Many brokers have decided~~ not toexpect ~~trade penny stocks because of the requirements of the penny stock rules and, as a result, the number of broker-dealers willing~~ to ~~act~~pay asdividends ~~market makers~~ in ~~such~~the ~~securities is limited~~future. IfAny wereturn ~~remain subject to the penny stock rules for any significant period, it could have an adverse effect~~ on ~~the~~investment ~~market, if~~may ~~any,~~be ~~for~~limited ~~our securities. If our securities are subject~~ to the ~~penny~~value ~~stock rules, investors will find it more difficult to dispose~~ of our ~~securities~~common stock.

42We have never paid cash dividends on our common stock and do not anticipate doing so in the foreseeable future. The payment of dividends on our common stock will depend on earnings, financial condition and other business and economic factors affecting us at such time as our board of directors may consider relevant. If we do not pay dividends, our common stock may be less valuable because a return on your investment will only occur if our stock price appreciates.

~~We have~~The ~~not~~price ~~paid cash dividends in the past and do not expect to pay dividends in the future. Any return on investment may be limited to the value~~ of our common stock may fluctuate substantially.

~~We have~~You ~~never~~should ~~paid~~consider ~~cash~~an ~~dividends~~investment onin our common stock ~~and~~to dobe ~~not~~risky, ~~anticipate~~and ~~doing~~you soshould invest in ~~the foreseeable future. The payment of dividends on~~ our common stock ~~will~~only ~~depend~~if onyou ~~earnings,~~can ~~financial~~withstand ~~condition~~a ~~and~~significant ~~other~~loss ~~business~~ and ~~economic~~wide ~~factors~~fluctuations ~~affecting~~in ~~us at such time as~~the ~~our~~market ~~board~~value of ~~directors~~your ~~may~~investment. ~~consider~~Some ~~relevant.~~factors Ifthat wemay docause ~~not~~the ~~pay~~market ~~dividends,~~price of our common stock ~~may~~to befluctuate, ~~less~~in ~~valuable~~addition ~~because~~to athe ~~return~~other risks onmentioned ~~your investment~~in ~~will~~this ~~only~~“Risk ~~occur~~Factors” ifsection ~~our~~and ~~stock~~elsewhere ~~price~~in ~~appreciates.~~this prospectus, are:

~~The price~~● sale of our common stock ~~may~~by ~~fluctuate~~our ~~substantially.~~stockholders, executives, and directors;

~~You should~~● ~~consider~~volatility ~~an investment in our common stock to be risky,~~ and ~~you~~limitations ~~should invest~~ in ~~our~~trading ~~common~~volumes ~~stock only if you can withstand a significant loss and wide fluctuations in the market value~~ of ~~your~~our ~~investment.~~shares ~~Some factors that may cause the market price~~ of ~~our~~ common ~~stock~~ ~~to fluctuate, in addition to the other risks mentioned in this “Risk Factors” section and elsewhere in this prospectus, are:~~stock;

● ~~sale~~our ofability ~~our~~to ~~common~~obtain ~~stock~~financings byto ~~our~~conduct ~~stockholders~~and complete research and development activities including, ~~executives~~but not limited to, our human clinical trials, and ~~directors~~other business activities;

● ~~volatility~~our ~~and~~announcements ~~limitations~~or inour ~~trading~~competitors’ ~~volumes~~announcements ofregarding ~~our~~new ~~shares~~products ofor ~~common~~services, ~~stock~~enhancements, significant contracts, acquisitions or strategic investments;

● ~~our~~failures ~~ability~~ to ~~obtain~~meet ~~financings~~external toexpectations ~~conduct~~or ~~and~~management ~~complete research and development activities including, but not limited to, our human clinical trials, and other business activities~~guidance;

● ~~our~~changes ~~announcements~~in or our ~~competitors’~~capital ~~announcements~~structure ~~regarding new products~~ or ~~services,~~dividend ~~enhancements, significant contracts, acquisitions or strategic investments~~policy;

● ~~failures~~our tocash ~~meet external expectations or management guidance~~position;

● ~~changes~~announcements inand ~~our~~events ~~capital~~surrounding ~~structure~~financing orefforts, ~~dividend~~including ~~policy~~debt and equity securities;

● our ~~cash~~inability ~~position~~to enter into new markets or develop new products;

● ~~announcements~~reputational ~~and events surrounding financing efforts, including debt and equity securities~~issues;

● ~~our~~announcements ~~inability~~of toacquisitions, ~~enter~~partnerships, ~~into~~collaborations, joint ventures, new ~~markets~~products, capital commitments, or ~~develop~~other ~~new~~events ~~products~~by us or our competitors;

● ~~reputational~~changes ~~issues~~in general economic, political and market conditions in any of the regions in which we conduct our business;

● ~~announcements~~changes ofin ~~acquisitions,~~industry ~~partnerships,~~conditions ~~collaborations, joint ventures, new products, capital commitments,~~ or ~~other events by us or our competitors~~perceptions;

● changes in ~~general~~valuations ~~economic,~~of ~~political~~similar ~~and~~companies ~~market~~or ~~conditions~~groups ~~in any~~ of ~~the regions in which we conduct our business~~companies;

● analyst research reports, recommendation and changes in ~~industry~~recommendations, ~~conditions~~price ortargets, ~~perceptions~~and withdrawals of coverage;

● ~~changes~~departures inand ~~valuations~~additions of ~~similar~~key ~~companies or groups of companies~~personnel;

● ~~analyst~~disputes ~~research reports, recommendation~~ and ~~changes~~litigations inrelated ~~recommendations,~~to ~~price~~contractual ~~targets, and withdrawals of coverage~~obligations;

~~● departures and additions of key personnel;~~43

● ~~disputes~~changes ~~and~~in ~~litigations~~applicable ~~related~~laws, torules, ~~contractual~~regulations, ~~obligations~~or accounting practices and other dynamics; or

43● other events or factors, many of which may be out of our control.

●In ~~changes~~addition, if the market for stocks in ~~applicable~~our industry ~~laws~~or industries related to our industry, ~~rules~~or the stock market in general, ~~regulations~~experiences a loss of investor confidence, orthe ~~accounting~~trading price ~~practices~~of our common stock could decline for reasons unrelated to our business, financial condition and ~~other~~results ~~dynamics;~~of oroperations. If any of the foregoing occurs, it could cause our stock price to fall and may expose us to lawsuits that, even if unsuccessful, could be costly to defend and a distraction to management.

●Our ability to use our net operating loss carry-forwards and certain other ~~events~~tax orattributes ~~factors,~~is ~~many~~limited ofby ~~which~~Sections ~~may~~382 beand ~~out~~383 of ~~our~~the ~~control~~Internal Revenue Code.

~~In addition,~~Net ifoperating ~~the~~loss ~~market~~carryforwards ~~for~~allow ~~stocks~~companies to inuse ~~our~~past ~~industry~~year ornet ~~industries~~operating ~~related~~losses to ~~our~~offset ~~industry,~~against orfuture ~~the~~years’ ~~stock~~profits, ~~market~~if ~~in general~~any, ~~experiences a~~to ~~loss~~reduce offuture ~~investor~~tax ~~confidence,~~liabilities. ~~the~~Sections 382 ~~trading~~and ~~price~~383 of ~~our~~the ~~common~~Internal ~~stock~~Revenue ~~could~~Code ~~decline~~of ~~for~~1986 ~~reasons~~limit ~~unrelated~~a corporation’s ability to ~~our~~utilize ~~business,~~its ~~financial~~net ~~condition~~operating loss carryforwards and ~~results~~certain ofother ~~operations.~~tax Ifattributes (including research credits) to offset any offuture taxable income or tax if the ~~foregoing~~corporation ~~occurs,~~experiences a itcumulative ~~could~~ownership ~~cause~~change ~~our~~of ~~stock~~more ~~price~~than to50% ~~fall~~over any rolling three-year period. State net operating loss carryforwards (and certain other tax attributes) may ~~expose~~be ussimilarly tolimited. ~~lawsuits~~An ~~that,~~ownership change can therefore result in significantly greater tax liabilities than ~~even~~a ifcorporation ~~unsuccessful,~~would ~~could~~incur bein ~~costly~~the toabsence ~~defend~~of ~~and~~such a ~~distraction~~change toand ~~management~~any increased liabilities could adversely affect the corporation’s business, results of operations, financial condition and cash flow.

~~Our~~Even if another ownership change has not occurred ~~ability~~and todoes ~~use~~not ~~our~~occur ~~net~~as ~~operating~~a ~~loss~~result ~~carry-forwards~~of ~~and~~this ~~certain~~offering, ~~other~~additional ~~tax~~ownership ~~attributes~~changes ismay ~~limited~~occur byin ~~Sections~~the ~~382~~future as a result of additional equity offerings or events over which we will have little or no control, including purchases and ~~383~~sales of our equity by our five percent security holders, the ~~Internal~~emergence of new five percent security holders, redemptions of our securities or certain changes in the ownership of any ~~Revenue~~of ~~Code~~our five percent security holders.

~~Net operating~~Our ~~loss~~principal ~~carryforwards~~stockholders ~~allow companies to use past year net operating losses to offset against future years’ profits, if any, to reduce future tax liabilities. Sections 382~~ and ~~383 of the Internal Revenue Code of 1986 limit a corporation’s ability~~management toown ~~utilize its net operating loss carryforwards and certain other tax attributes (including research credits) to offset any future taxable income or tax if the corporation experiences~~ a ~~cumulative~~significant ~~ownership~~percentage ~~change~~ of ~~more~~our ~~than~~stock ~~50% over any rolling three-year period. State net operating loss carryforwards (~~and ~~certain~~will ~~other tax attributes) may~~ be ~~similarly~~able ~~limited.~~to Anexercise ~~ownership~~significant ~~change~~influence ~~can~~over ~~therefore~~matters ~~result in~~subject ~~significantly~~to ~~greater~~stockholder tax liabilities than a corporation would incur in the absence of such a change and any increased liabilities could adversely affect the corporation’s business, results of operations, financial condition and cash flowapproval.

~~Even if~~As ~~another~~of ~~ownership~~September ~~change~~30, ~~has~~2022, ~~not~~our ~~occurred~~executive officers, directors and ~~does~~principal ~~not~~security ~~occur~~holders, astogether awith ~~result~~their respective affiliates, owned approximately 36.50% of ~~this~~our ~~offering~~outstanding securities. Accordingly, ~~additional~~this ~~ownership~~group ~~changes~~of ~~may~~security ~~occur in~~holders ~~the~~will ~~future~~be asable to exert a ~~result~~significant degree of ~~additional~~influence ~~equity~~over ~~offerings~~our ormanagement ~~events~~and affairs and over ~~which~~matters werequiring ~~will~~security ~~have~~holder ~~little~~approval, orincluding nothe ~~control~~election of our Board of Directors, ~~including~~future ~~purchases~~issuances of our securities, declaration of dividends and ~~sales~~approval of ~~our~~other ~~equity~~significant bycorporate ~~our~~transactions. ~~five~~This ~~percent~~concentration ~~security~~of ~~holders,~~ownership ~~the~~could ~~emergence~~have the effect of ~~new~~delaying ~~five~~or ~~percent~~preventing ~~security~~a ~~holders,~~change-of-control ~~redemptions~~ of our ~~securities~~ company or ~~certain~~otherwise ~~changes~~discouraging a potential acquirer from attempting to obtain control of us, which in turn could have a material and adverse effect on the ~~ownership~~fair market value of ~~any~~our securities. In addition, this significant concentration of share ownership may adversely affect the trading price for our ~~five~~common ~~percent~~stock ~~security~~if ~~holders~~investors perceive disadvantages in owning stock in a company with such concentrated ownership.

~~Our principal~~U.S. ~~stockholders~~federal ~~and~~income ~~management~~tax ~~own~~reform acould ~~significant percentage of our stock and will be able to exercise significant influence over~~adversely ~~matters~~affect ~~subject to stockholder approval~~us.

~~As of~~On ~~September~~December 3022, ~~2021~~2017, ~~our~~former ~~executive~~President ~~officers,~~Trump signed ~~directors~~into law the “Tax Cuts and ~~principal~~Jobs ~~security~~Act” ~~holders,~~(TCJA) ~~together~~that ~~with~~significantly ~~their~~reforms ~~respective~~the ~~affiliates,~~Internal ~~owned approximately~~Revenue ~~51.1%~~Code of ~~our~~1986, ~~outstanding~~as ~~securities~~amended. The ~~Accordingly~~TCJA, ~~this~~among ~~group~~other ofthings, ~~security~~includes ~~holders~~changes ~~will~~to beU.S. ~~able~~federal totax ~~exert~~rates, aimposes significant ~~degree~~additional limitations on the deductibility of ~~influence~~interest, ~~over~~allows ~~our~~for ~~management~~the ~~and~~expensing ~~affairs~~of ~~and~~capital ~~over~~expenditures, ~~matters~~and ~~requiring~~puts ~~security~~into ~~holder~~effect ~~approval,~~the ~~including~~migration ~~the~~from ~~election~~a “worldwide” system of taxation to a territorial system. The tax reform did not have a material impact to our ~~Board~~ projection of ~~Directors,~~minimal ~~future~~cash ~~issuances~~taxes ofor to our net ~~securities,~~operating ~~declaration~~losses. ofOur ~~dividends~~net deferred tax assets and ~~approval~~liabilities are ofrevalued ~~other~~at ~~significant~~the ~~corporate~~newly ~~transactions~~enacted U.S. corporate rate, and the ~~This~~impact has ~~concentration~~been ofrecognized ~~ownership~~in ~~could~~our ~~have~~tax expense in the ~~effect~~year of ~~delaying~~enactment. orFurther, ~~preventing~~any aeligibility ~~change-of-control~~we ofmay ~~our~~have ~~company~~ or ~~otherwise~~may ~~discouraging~~someday have afor ~~potential~~tax ~~acquirer~~credits ~~from~~associated ~~attempting~~with tothe ~~obtain~~qualified ~~control~~clinical testing expenses arising out of ~~us,~~the ~~which~~development inof ~~turn~~orphan ~~could~~drugs was ~~have~~reduced to 25% as a ~~material~~result ~~and~~of ~~adverse~~the ~~effect~~TCJA; onthus, our net taxable income is affected. We continue to examine the ~~fair~~impact ~~market~~this tax reform legislation ~~value~~may ofhave on our ~~securities~~business. InThe ~~addition,~~impact of this ~~significant~~tax ~~concentration~~reform on holders of ~~share~~our ~~ownership~~common ~~may~~stock ~~adversely~~is ~~affect~~uncertain and could be adverse. This prospectus does not discuss any such tax legislation or the ~~trading~~way ~~price~~it ~~for~~might affect purchasers of our common stock. ifWe ~~investors~~urge ~~perceive~~our ~~disadvantages~~stockholders, inincluding purchasers ~~owning~~of common stock in athis ~~company~~offering, to consult with their legal and tax advisors with respect to such ~~concentrated~~legislation ~~ownership~~and the potential tax consequences of investing in our common stock.

~~U.S. federal income tax reform could adversely affect us.~~44

OnIn ~~December~~preparing ~~22,~~our ~~2017,~~consolidated ~~former President Trump signed~~financial ~~into law the “Tax Cuts and Jobs Act” (TCJA) that significantly reforms the Internal Revenue Code of 1986~~statements, as amended. The TCJA, among other things, includes changes to U.S. federal tax rates, imposes significant additional limitations on the deductibility of interest, allows for the expensing of capital expenditures, and puts into effect the migration from a “worldwide” system of taxation to a territorial system. The tax reform did not have a material impact to our ~~projection~~management ofdetermined ~~minimal~~that ~~cash taxes or to~~ our ~~net operating~~disclosure ~~losses.~~controls ~~Our net deferred tax assets~~ and ~~liabilities are~~procedures ~~revalued at the newly enacted U.S. corporate rate,~~ and ~~the~~internal ~~impact has been~~controls ~~recognized~~were inineffective our tax expense in the year of enactment. Further, any eligibility we may have or may someday have for tax credits associated with the qualified clinical testing expenses arising out of the development of orphan drugs was reduced to 25% as ~~a result~~ of ~~the TCJA; thus~~September 30, ~~our~~2022 ~~net~~and ~~taxable~~if ~~income~~they ~~is affected. We~~ continue to ~~examine~~be ~~the~~ineffective ~~impact this tax reform legislation may have on our business. The impact of this tax reform on holders of our common stock is uncertain and~~ could becontinue ~~adverse.~~to ~~This~~result ~~prospectus does not discuss any such tax legislation or the way it might affect purchasers of our common stock. We urge our stockholders, including purchasers of common stock~~ in ~~this~~material ~~offering,~~misstatements ~~to consult with their legal and tax advisors with respect to such legislation and the potential tax consequences of investing~~ in our ~~common~~financial ~~stock~~statements.

44Our management is responsible for establishing and maintaining adequate internal control over our financial reporting, as defined in Rule 13a-15(f) under the Securities Exchange Act of 1934, as amended, or the Exchange Act. As of September 30, 2022, our management has determined that our disclosure controls and procedures and internal controls were ineffective due to weaknesses in our financial closing process, inadequate segregation of duties over authorization, review and recording of transactions, lack of accounting resources, as well as the financial reporting of such transactions.

InWe ~~preparing~~intend ~~our~~to ~~consolidated~~implement ~~financial~~remedial measures designed ~~statements,~~to address the ineffectiveness of our ~~management~~disclosure ~~determined~~controls ~~that~~and procedures and internal controls. If these remedial measures are insufficient to address the ineffectiveness of our disclosure controls and procedures and internal controls, ~~were~~or ~~ineffective~~if asmaterial weaknesses or significant deficiencies in our internal control are discovered or occur in the future and the ineffectiveness of ~~September~~our disclosure controls and procedures 30and internal controls continues, ~~2021~~we may fail to meet our future reporting obligations on a timely basis, our consolidated financial statements may contain material misstatements, we could be required to restate our prior period financial results, our operating results may be harmed, we may be subject to class action litigation, and ifour ~~they~~common ~~continue~~stock could be delisted. Any failure to address the ineffectiveness of our disclosure controls and procedures could also adversely affect the results of the periodic management evaluations regarding the effectiveness of our internal control over financial reporting and our disclosure controls and procedures that are required to be included in our annual report on Form 10-K. Internal control deficiencies and ineffective disclosure controls and procedures could ~~continue~~also cause investors to ~~result~~lose confidence in our reported financial information. We can give no assurance that the measures we plan to take in the future will remediate the ineffectiveness of our disclosure controls and procedures or that any material ~~misstatements~~weaknesses or restatements of financial results will not arise in the future due to a failure to implement and maintain adequate internal control over financial reporting or adequate disclosure controls and procedures or circumvention of these controls. In addition, even if we are successful in strengthening our controls and procedures, in the future those controls, and procedures may not be adequate to prevent or identify irregularities or errors or to facilitate the fair presentation of our consolidated financial statements.

~~Our~~Future ~~management~~sales ~~is responsible for establishing~~ and ~~maintaining~~issuances ~~adequate~~of ~~internal control over~~ our ~~financial reporting, as defined in Rule 13a-15(f) under the Securities Exchange~~common ~~Act~~stock ~~of 1934, as amended,~~ or ~~the~~rights ~~Exchange~~to ~~Act.~~purchase Ascommon ofstock ~~September~~pursuant ~~30,~~to ~~2021,~~ our ~~management~~equity ~~has~~incentive ~~determined~~plan ~~that~~could ~~our~~result ~~disclosure controls and procedures and internal controls were ineffective due to weaknesses~~ in ~~our~~additional ~~financial~~dilution ~~closing~~of ~~process,~~the ~~inadequate~~percentage ~~segregation~~ownership of ~~duties~~our ~~over~~stockholders ~~authorization, review~~ and ~~recording~~could ofcause ~~transactions,~~our ~~lack~~share ofprice ~~accounting~~to ~~resources, as well as the financial reporting of such transactions~~fall.

We ~~intend~~ toexpect ~~implement~~that

Filing Compare · ACTAVIA LIFE SCIENCES, INC.