7Table of Contents

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 10-K

(Mark One)e

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

For the fiscal year ended December 31, ~~2024~~2025

☐	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 001-39927

SEASTAR MEDICAL HOLDING CORPORATION

(Exact name of Registrant as specified in its Charter)

Delaware	85-3681132
(State or other jurisdiction ofincorporation or organization)	(I.R.S. EmployerIdentification No.)
(State or other jurisdiction of incorporation or organization)	(I.R.S. Employer Identification No.)
3513 Brighton Blvd., Suite 410Denver, CO	80216
(Address of principal executive offices)	(Zip Code)

3513 Brighton Blvd., Suite 410

Denver, CO

80216

(Address of principal executive offices)

(Zip Code)

Registrant’s telephone number, including area code: (844) 427-8100

Securities registered pursuant to Section 12(b) of the Act:

Title of each class	~~TradingSymbol~~Trading Symbol(s)	Name of each exchange on which registered
Common Stock, $0.0001 par value	ICU	The Nasdaq Stock Market LLC
Warrants, each whole warrant exercisable for one share of Common Stock for $287.50 per share	ICUCW	The Nasdaq Stock Market LLC
Warrants, each whole warrant exercisable for one share of Common Stock for $2,875 per share	ICUCW	The Nasdaq Stock Market LLC

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 mark if the Registrant is not required to file reports pursuant to Section 13 or 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 (or for such shorter period that the Registrant was required to file such reports), 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 every Interactive Data File required to be submitted 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 such files). Yes ☒ No ☐

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, smaller reporting company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act.

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. ☐

If securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the registrant included in the filing reflect the correction of an error to previously issued financial statements. ☐

Indicate by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based compensation received by any of the registrant’s executive officers during the relevant recovery period pursuant to §240.10D-1(b). ☐

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

Based on the closing sales price of the Registrant’s common stock on Nasdaq on June 2830, ~~2024~~2025, the last business day of the Registrant’s second fiscal quarter, the aggregate market value of the voting stock held by non-affiliates of the Registrant was approximately $237.93 million. All executive officers and directors of the Registrant, and all shareholders holding more than 10% of the Registrant’s outstanding voting stock (other than institutional investors, such as registered investment companies, eligible to file beneficial ownership reports on Schedule 13G), have been deemed, solely for the purpose of the foregoing calculation, to be “affiliates” of the Registrant.

The number of shares of Registrant’s Common Stock outstanding as of ~~February~~March 2824, ~~2025~~2026, was 83,~~721~~993,~~036.~~719

DOCUMENTS INCORPORATED BY REFERENCE

Portions of the Registrant’s definitive proxy statement relating to its ~~2024~~ 2026 annual meeting of stockholders are incorporated herein by reference in Part III of this Annual Report on Form 10-K. We anticipate that we will file the ~~2024~~ 2026 proxy statement on or before April 29, ~~2025~~2026.

Table of Contents

		Page
	Cautionary Note Regarding Forward-Looking Statements	1
PART I
Item 1.	Business	3
Item 1A.	Risk Factors	29
Item 1B.	Unresolved Staff Comments	60
Item 1C.	Cybersecurity	60
Item 2.	Properties	60
Item 3.	Legal Proceedings	60
Item 4.	Mine Safety Disclosures	61
PART II
Item 5.	Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities	62
Item 6.	[Reserved]	62
Item 7.	Management’s Discussion and Analysis of Financial Condition and Results of Operations	63
Item 7A.	Quantitative and Qualitative Disclosures About Market Risk	72
Item 8.	Financial Statements and Supplementary Data	76
Item 9.	Changes in and Disagreements With Accountants on Accounting and Financial Disclosure.	112
Item 9A.	Controls and Procedures	112
Item 9B.	Other Information	113
Item 9C.	Disclosure Regarding Foreign Jurisdictions that Prevent Inspections	113
PART III
Item 10.	Directors, Executive Officers and Corporate Governance	114
Item 11.	Executive Compensation	114
Item 12.	Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters	114
Item 13.	Certain Relationships and Related Transactions, and Director Independence	114
Item 14.	Principal Accounting Fees and Services	114
PART IV
Item 15.	Exhibits, Financial Statement Schedules	115
Item 16.	Form 10-K Summary	117

Table of Contents


		Page
	Cautionary Note Regarding Forward-Looking Statements	1
PART I
Item 1.	Business	3
Item 1A.	Risk Factors	29
Item 1B.	Unresolved Staff Comments	60
Item 1C.	Cybersecurity	60
Item 2.	Properties	60
Item 3.	Legal Proceedings	60
Item 4.	Mine Safety Disclosures	60

PART II
Item 5.	Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities	61
Item 6.	[Reserved]	61
Item 7.	Management’s Discussion and Analysis of Financial Condition and Results of Operations	62
Item 7A.	Quantitative and Qualitative Disclosures About Market Risk	72
Item 8.	Financial Statements and Supplementary Data	73
Item 9.	Changes in and Disagreements With Accountants on Accounting and Financial Disclosure.	103
Item 9A.	Controls and Procedures	103
Item 9B.	Other Information	104
Item 9C.	Disclosure Regarding Foreign Jurisdictions that Prevent Inspections	104

PART III
Item 10.	Directors, Executive Officers and Corporate Governance	105
Item 11.	Executive Compensation	105
Item 12.	Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters	105
Item 13.	Certain Relationships and Related Transactions, and Director Independence	105
Item 14.	Principal Accounting Fees and Services	105

PART IV
Item 15.	Exhibits, Financial Statement Schedules	106
Item 16.	Form 10-K Summary	108

Table of Contents

CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS

This Annual Report on Form 10-K (this “Annual Report”) contains statements that are forward-looking and as such are not historical facts. These statements are based on the beliefs and assumptions of management. Although we believe that our plans, intentions, and expectations reflected in or suggested by these forward-looking statements are reasonable, we cannot assure you that we will achieve or realize these plans, intentions, or expectations. Forward-looking statements are inherently subject to risks, uncertainties, and assumptions. Generally, statements that are not historical facts, including statements concerning the ~~our~~ possible or assumed future actions, business strategies, events, or results of operations, are forward-looking statements. In some instances, these statements may be preceded by, followed by or include the words “believes,” “estimates,” “expects,” “projects,” “forecasts,” “may,” “will,” “should,” “seeks,” “plans,” “scheduled,” “anticipates” or “intends” or the negatives of these terms or variations of them or similar terminology.

Forward-looking statements are not guarantees of performance. You should not put undue reliance on these statements which speak only as of the date hereof. You should understand that the following important factors, among others, could affect our future results and could cause those results or other outcomes to differ materially from those expressed or implied in our forward-looking statements:

• our expectations regarding ongoing clinical trials and our plans to conduct further clinical trials, ~~and~~including anticipated enrollment, clinical ~~sites~~site activation, completion, results, and timing thereof;

• our plans and expected timeline related to our products, including timing of commercial launch, or developing new products, to address additional indications or to obtain regulatory approvals or clearances or otherwise;

• the expected use of our products by clinicians, including market awareness, acceptance and adoption of our products, and anticipated utilization of our products;

• our expectations regarding the number of procedures that will be performed with our products, the number of clinicians we expect to train, and the number of our sales territories;

• our ability to obtain, maintain, and expand regulatory clearances for our current products and any new products we create;

• the expected growth of our business and our organization;

• our expectations regarding pricing of our products, cost of sales, government and third-party payer coverage and reimbursement;

• our ability to retain and recruit key personnel;

• our ability to obtain an adequate supply of materials and components for our products from our third-party suppliers, most of whom are single-source suppliers;

• our ability to manufacture sufficient quantities of our products with sufficient quality and the sufficiency of our current manufacturing capabilities;

• our ability to obtain and maintain intellectual property protection for our products and our business;

• our ability to expand our business into new geographic markets and the anticipated timing thereof;

• our compliance with extensive Nasdaq and SEC requirements and government laws, rules and regulations both in the United States and internationally;

• our expectations regarding operating trends, future financial performance and expense management and our estimates of our future expenses, ongoing losses, future revenue, capital requirements and our need for, or ability to obtain, additional financing;

• our ability to identify and develop new and planned products and/or acquire new products;

• our experience with inflationary and price pressures and increased labor costs and labor and staffing shortages as a result of general macroeconomic factors;

~~developments~~ Table ~~and~~of ~~projections relating to our market opportunity and penetration, competitors, or our industry;~~Contents

• developments and projections relating to our ~~intended~~market ~~use~~opportunity ofand ~~net~~penetration, ~~proceeds~~competitors, ~~from~~or our ~~public offerings.~~industry;

• our ~~future~~intended ~~capital~~use ~~requirements~~of ~~and~~net ~~sources~~proceeds ~~and~~from ~~uses~~our ofpublic ~~cash;~~offerings.

• our ~~ability~~future ~~to obtain funding or raise~~ capital ~~for~~requirements ~~its~~and ~~operations~~sources and ~~future~~uses ~~growth~~of cash;

~~any~~• ~~delays~~our orability ~~challenges~~to inobtain ~~obtaining~~funding ~~FDA~~or ~~approval~~raise ofcapital ~~our~~for ~~SCD~~its ~~product~~operations ~~candidates~~and future growth;

~~economic~~• ~~downturns~~any ~~and~~delays ~~the~~or ~~possibility~~challenges ~~of rapid change~~ in ~~the~~obtaining ~~highly~~FDA ~~competitive~~approval ~~industry~~of inour ~~which~~SCD ~~our~~product ~~operates~~candidates;

~~the~~• ~~ability~~economic todownturns ~~develop~~ and ~~commercialize~~the ~~its~~possibility ~~products~~of orrapid ~~services~~change ~~following~~in ~~regulatory~~the ~~approval~~highly ofcompetitive ~~our~~industry ~~product~~in ~~candidates~~which we operate;

• the ~~failure~~ability ofto ~~third-party~~develop ~~suppliers~~ and ~~manufacturers~~commercialize toour ~~fully~~products ~~and~~or ~~timely~~services ~~meet~~following ~~their~~regulatory ~~obligations~~approval of our product candidates;

~~product~~• ~~liability~~the orfailure ~~regulatory~~of ~~lawsuits~~third-party orsuppliers ~~proceedings~~and ~~relating~~manufacturers to ~~our~~fully ~~products~~ and ~~services~~timely meet their obligations;

~~inability~~• product liability lawsuits, regulatory lawsuits proceedings relating to ~~secure~~our products and services, or ~~protect~~any ~~its~~other ~~intellectual~~litigation ~~property~~matters;

~~dispute~~• orinability ~~deterioration~~to ofsecure ~~relationship~~or ~~with~~protect our ~~major~~intellectual ~~partners and collaborators~~property;

~~the~~• ~~ability~~dispute toor ~~maintain~~deterioration ~~the~~of ~~listing~~relationship ofwith ~~its~~our ~~Common~~major ~~Stock~~partners onand ~~Nasdaq~~collaborators;

~~delays~~• ~~associated~~the ~~with~~ability ~~government~~to ~~and~~maintain ~~other~~the ~~grant~~listing ~~funding;~~of our Common Stock on Nasdaq;

~~the~~• ~~ability~~delays toassociated ~~recognize~~with ~~the~~government ~~anticipated~~and ~~benefits of the Business Combination, which may be affected by, among~~ other ~~things,~~grant ~~competition, and the ability of our to grow and manage growth profitably~~funding; ~~and~~

• other risks and uncertainties indicated in this Annual Report, including those under “Risk Factors” herein, and other filings that have been made or will be made with the SEC.

These and other factors that could cause actual results to differ from those implied by the forward-looking statements in this Annual Report are more fully described in the “Risk Factors” section. The risks described in “Risk Factors” are not exhaustive. New risk factors emerge from time to time, and it is not possible for us to predict all such risk factors, nor can we assess the impact of all such risk factors on our business or the extent to which any factor or combination of factors may cause actual results to differ materially from those contained in any forward-looking statements. All forward-looking statements attributable to us or persons acting on ~~its~~our behalf are expressly qualified in their entirety by the foregoing cautionary statements. We undertake no obligations to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

Table of Contents

PART I

Item 1. Business.

Unless the context otherwise requires, all references in this section to “SeaStar Medical”, the “Company”, “we” “us” or “our” refer to SeaStar Medical Holding Corporation and our consolidated subsidiaries following the Business Combination (as defined herein), other than certain historical information that refers to the business of SeaStar Medical, Inc. (the “Predecessor”) prior to the consummation of the Business Combination.

Overview

We are a commercial-stage healthcare company focused on ~~transforming~~ transformational treatments for critically ill patients facing organ failure and potential loss of life. Our Selective Cytopheretic Device (“SCD”) is designed as a disease-modifying device that neutralizes over-active immune cells and stops the cytokine storm that yields destructive hyperinflammation and creates a cascade of events that wreak havoc in the patient’s body. It has broad potential applications for patients suffering from both acute and chronic kidney disease as well as cardiovascular and other serious inflammatory diseases.

We received Food and Drug Administration (“FDA”) approval on February 21, 2024, under a Humanitarian Device Exemption (“HDE”) for our pediatric SCD therapy. It is the only FDA approved product for use in pediatric patients with acute kidney injury (“AKI”) due to sepsis or a septic condition requiring kidney replacement therapy. We shipped our first commercial pediatric SCD (“QUELIMMUNE”) in July 2024. In addition, we are currently conducting a pivotal clinical trial, also referred to as "NEUTRALIZE-AKI" to assess the safety and efficacy of the SCD therapy in critically ill adult patients with AKI requiring continuous renal replacement therapy (“CRRT”). We are also conducting a feasibility study of the SCD therapy in adult patients with Cardiorenal Syndrome ("CRS") awaiting left ventricular assist device ("LVAD") implantation.

Our SCD therapy has been awarded six Breakthrough Device ~~Designation~~Designations (“BDD”) ~~for~~by ~~four~~the ~~therapeutic~~FDA. ~~indications~~These byBDDs ~~the~~cover ~~FDA,~~multiple ~~including~~therapeutic indications for the use of ~~the~~our SCD therapy ~~for~~in adult patients with AKI, ~~patients~~CRS ~~with cardiorenal syndrome~~ awaiting ~~left ventricular assist device (“~~LVAD”) implantation, ~~patients with~~ hepatorenal syndrome, ~~and patients with~~ end stage renal disease (“ESRD”), and systemic inflammatory response while undergoing cardiac surgery. The BDD enables the potential for a speedier pathway to approval and the ability to have more frequent and flexible meetings with FDA.

The inflammatory response is essential to the healing process of critical organs; however, the overactivation of inflammatory cells, which can be triggered by many different bodily insults such as trauma, surgery or infection, can send the body into shock and cause severe damage to a variety of critical organs such as the heart, lungs and ~~kidney~~kidneys. Central to inflammation are the cells within blood and lymph circulatory systems, called white blood cells (primarily neutrophils and monocytes). In a normal inflammatory response, neutrophils are the first immune cells to arrive at the site and are key to the entire immune response that kills pathogens and promotes tissue repair. These inflammatory cells release chemicals (cytokines) that trigger the immune system to eliminate foreign pathogens or damaged tissue, enhancing the immune response.

If the inflammatory response becomes excessive and dysregulated (referred to as proinflammatory), the inflammatory cells will continue to produce cytokines and other damaging molecules, further enhancing the dysregulated immune response, and altering feedback mechanisms that regulate the immune system. This results in damaging hyperinflammation spreading uncontrollably to other parts of the body, often leading to acute and potentially chronic solid organ dysfunction or failure, including the heart, lung, kidney, liver, and even death. This hyperinflammatory response is also known as the “cytokine storm,” referring to the body’s reaction to the category of small-secreted proteins released by hyperinflammatory cells that affect communication between cells.

Currently, there are no therapeutic options that specifically neutralize the white blood cells that are primarily responsible for the destructive hyperinflammatory response. Clinicians typically address hyperinflammation with therapies that are either immunosuppressive or that target ~~one~~a specific cytokine, both of which are generally suboptimal in the treatment of hyperinflammation. We believe our technology has the potential to overcome limitations in existing anti-inflammatory treatments and address the challenge of selectively targeting activated neutrophils and monocytes.

Clinical and preclinical studies conducted over the last 15 years have demonstrated that our SCD therapy can modulate the degree of activity of proinflammatory cells to help reduce tissue damage and speed the repair and recovery of organ function. Data from our trials demonstrated that the use of our SCD therapy to reverse the cytokine storm in more than 150 pediatric and adult patients with acute kidney injury on CRRT reduced mortality rates by 50%, and of those patients who survived 60 days, none have required dialysis. We believe our SCD therapy has the potential to transform the treatment of acute organ failure in the intensive care unit (“ICU”) and to improve organ function in patients with chronic kidney disease, certain cardiovascular diseases, and other serious inflammatory diseases.

~~pediatric~~ Table ~~and adult patients with acute kidney injury on CRRT reduced mortality rates by 50%, and~~ of those patients who survived 60 days, none have required dialysis. We believe our SCD therapy has the potential to transform the treatment of acute organ failure in the intensive care unit (“ICU”) and to improve organ function in patients with chronic kidney disease, certain cardiovascular diseases, and other serious inflammatory diseases.Contents

Preclinically, we evaluated our SCD therapy in various animal models representing multiple hyperinflammatory indications, including acute myocardial infarction, intracranial hemorrhage, chronic heart failure, sepsis, and acute respiratory distress syndrome. The animal models demonstrated the inflammatory response and how it was modified by our SCD therapy. We will continue to explore the application of our SCD therapy across a broad range of indications where proinflammatory activated neutrophils and monocytes contribute to disease progression or severity in both acute and chronic indications.

We are leveraging our patent protected and scalable SCD therapy platform to develop proprietary treatments that are organ agnostic and target both acute and chronic indications. The SCD therapy is delivered via an extracorporeal synthetic membrane device that easily integrates into existing CRRT systems that are commonly employed for patients with acute organ injury in hospitals, including in ICUs throughout the United States. It also has the potential to be integrated into kidney dialysis systems for chronic kidney disease patients receiving renal replacement therapy at centers throughout the United States. We believe that the ease of use and broad applicability of the therapy across multiple disease states should enable us to capture a sizable market for our SCD therapy with increasingly favorable economics.

Our senior management team and Board have anextensive ~~average of over 19 years of~~ experience in the healthcare industry, including expertise in regulatory and medical affairs, commercialization and distribution in our initial therapeutic priority areas. We also have assembled a team of well-respected scientific advisors who are experts in the development of our technology and products.

There is a substantial clinical need for safe and effective control of hyperinflammation and we believe that our first-in-class SCD therapy can address the large potential market of over one million patients each year that face life-threatening hyperinflammatory conditions, including organ failure and potential loss of life.

SCD Therapy for Pediatric Patients

We are currently commercializing our first product, QUELIMMUNE, under an HDE that was approved by the FDA on February 21, 2024. QUELIMMUNE is currently the only FDA -approved product for critically ill pediatric patients with life-threatening acute kidney injury (AKI) due to sepsis or a septic condition.

We commenced our first product shipment of QUELIMMUNE in July 2024 and ~~are~~continue ~~now targeting~~ to target top-tier pediatric medical facilities for adoption of the QUELIMMUNE therapy. As a condition of the approval, the FDA stipulated that we would need to institute a post approval patient surveillance registry to track certain safety and performance metrics (the "SAVE Surveillance Registry"). This typically requires an ~~Internal~~Institutional Review Board (“IRB”) review and approval to use QUELIMMUNE therapy at the medical facility, which can lengthen the QUELIMMUNE adoption process. ToAs ~~date,~~of weDecember ~~have~~31, 52025, we had 10 active commercial ~~sites~~hospital customers that have completed the ~~registry~~ process ~~and~~for ~~have~~the ~~purchased~~SAVE Surveillance Registry and ~~used~~have purchased QUELIMMUNE therapy. Additional ~~site~~ customer activations are planned for ~~2025~~2026.

~~SCD~~A ~~Therapy~~benefit ~~for~~of ~~Adult~~the ~~Patients~~SAVE Surveillance Registry is the opportunity to collect real-world data from the commercial use of QUELIMMUNE therapy. Early results from the first 21 critically ill pediatric patients with life-threatening AKI and sepsis or a septic condition in the commercial setting in the SAVE Surveillance Registry showed no device related safety events with the QUELIMMUNE therapy with 76% of patients surviving through 60 days and 71% surviving through 90 days. We believe these data are on track to validate a 50% reduction in loss of life compared to historical data. Additionally, in December of 2025, based on the safety data from this set of patients, the FDA approved a reduction in the mandatory enrollment size of the SAVE Surveillance Registry from the originally-required 300 patients to only 50 patients. We enrolled the 50th patient of the SAVE Surveillance Registry on March 4, 2026.

We are ~~currently~~also ~~conducting~~evaluating aadditional ~~pivotal~~clinical ~~trial,~~development ~~NEUTRALIZE-AKI,~~opportunities ~~to evaluate the safety and efficacy of our SCD therapy~~ in ~~200~~children ~~adults~~based ~~with~~on ~~AKI~~unmet inmedical ~~the ICU receiving CRRT~~needs. ~~The~~One ~~trial’s~~such ~~primary~~indication ~~endpoint~~ is afor ~~composite~~the ofuse ~~90-day mortality or dialysis dependency~~ of ~~patients~~our ~~treated with~~ SCD therapy infor ~~addition to CRRT as~~ the ~~standard~~treatment of ~~care,~~systemic ~~compared~~inflammatory ~~with~~response ~~the~~in ~~control~~pediatric ~~group~~patients ~~receiving~~undergoing ~~only~~cardiac ~~CRRT~~surgery, ~~standard~~aimed ~~of care. The trial protocol includes an interim analysis by an independent Data Safety Monitoring Board (“DSMB”)~~ at ~~the~~preventing ~~trial’s 90~~post-~~day~~operative ~~primary~~complications ~~endpoint~~and ~~with~~adverse ~~the first 100 subjects. As of March 25~~outcomes, ~~2025,~~for wewhich ~~had~~FDA ~~enrolled~~awarded 94BDD ~~patients~~on inMarch ~~the~~27, ~~pivotal trial~~2025. ~~We anticipate reporting topline clinical trial results and the submission of a Pre-market Approval ("PMA") application in 2026.~~

~~We are also evaluating additional clinical development of the~~ SCD ~~therapy~~Therapy infor ~~adults~~Adult ~~based on unmet clinical needs and market opportunity. Our BDD awards by the FDA in four therapeutic areas are expected to expedite the clinical development~~ Patients

4We are currently conducting a pivotal trial, NEUTRALIZE-AKI, to evaluate the safety and efficacy of our SCD therapy in adults with AKI in the ICU receiving CRRT. The trial’s primary endpoint is a composite of 90-day mortality or dialysis dependency of patients treated with SCD therapy in addition to CRRT as the standard of care, compared with the control group receiving only CRRT standard of care. The trial protocol includes an interim analysis by an independent Data Safety Monitoring Board (“DSMB”) at the trial’s 90-day primary endpoint with the first 100 subjects. This pivotal trial is expected to enroll a total of 339 patients and as of March 13, 2026, we had enrolled 178 patients. We anticipate reporting topline clinical trial results and, assuming a successful trial outcome, submission of a Pre-market Approval ("PMA") application in 2027.

and regulatory review of the SCD therapy for use in the designated patient populations and are the primary focus of our future clinical development decisions. We received our first BDD in 2022, two additional BDDs in 2023, and a fourth BDD in 2024. 4

On Table ~~April 29, 2022, we received a BDD for the use~~ of ~~our SCD in the treatment of immunomodulatory dysregulation in adult patients (18 and older) with AKI, which is expected to accelerate the regulatory approval process for our ongoing pivotal trial.~~ Contents

OnWe ~~September~~are ~~28,~~also ~~2023,~~evaluating weadditional ~~received~~clinical ~~BDD~~development ~~for~~of ~~our~~the SCD ~~for~~therapy ~~use~~ in ~~patients~~adults inbased on unmet clinical needs and market opportunity. Our BDD awards by the ~~hospital~~FDA ~~ICU~~in ~~with~~multiple therapeutic ~~acute~~areas orare ~~chronic~~expected ~~systolic~~to ~~heart~~expedite ~~failure~~the clinical development and ~~worsening~~regulatory ~~renal~~review ~~function~~of ~~due~~the toSCD ~~cardiorenal~~therapy ~~syndrome~~for oruse ~~right~~in ~~ventricular~~the ~~dysfunction~~designated ~~awaiting~~patient ~~implantation~~populations and are the primary focus of aour ~~left~~future ~~ventricular~~clinical ~~assist~~development ~~device~~decisions. We received our first BDD awards in 2022 with the following additional BDDs in adult patient indications thereafter:

• On ~~October~~April 1829, ~~2023~~2022, we received a BDD ~~designation~~ for the use of our SCD ~~for~~in ~~use~~the ~~with~~treatment ~~patients~~of immunomodulatory dysregulation in ~~the~~adult ~~hospital~~patients ~~ICU~~(18 and older) with AKI, ~~and~~which ~~acute~~is onexpected ~~chronic~~to ~~liver~~accelerate ~~failure~~the regulatory approval process for our ongoing pivotal trial.

• On ~~November~~September 628, ~~2024~~2023, we received BDD for our SCD tofor ~~treat~~use ~~chronic~~in ~~systemic~~patients ~~inflammation~~ in ~~end-stage~~the ~~renal~~hospital ~~disease~~ICU ~~(ESRD)~~with ~~patients~~acute ~~who~~or ~~require~~ chronic ~~hemodialysis,~~systolic ~~also~~heart ~~known~~failure asand ~~chronic~~worsening ~~dialysis.~~renal ~~This~~function isdue ~~our~~to ~~first~~cardiorenal ~~BDD~~syndrome inor right ventricular dysfunction awaiting implantation of a ~~chronic~~left ~~disease~~ventricular ~~setting~~assist device.

We• ~~believe~~On ~~that~~October ~~our~~18, ~~SCD~~2023, ~~therapy~~we isreceived ~~readily~~BDD ~~applicable~~designation for ~~use~~our inSCD ~~other~~for ~~indications,~~use ~~which~~with ~~will~~patients ~~increase~~in the ~~addressable~~hospital ~~market~~ICU ~~for~~with ~~our~~AKI ~~SCD~~and ~~therapy,~~acute ~~but~~on ~~will~~chronic ~~also~~liver ~~require additional clinical studies and FDA approval~~failure.

We have pursued patent protection for our SCD therapy as well as other technologies. Our patent portfolio consists of 34 patents and 7 pending patent applications in the U.S. and certain foreign jurisdictions. Of these patents and patent applications 20 patents and 4 patent applications are owned exclusively by us, and 14 patents and 3 patent applications are co-owned with the University of Michigan (“UOM”). The UOM has granted to us an exclusive worldwide, royalty bearing license to the UOM’s interest in all of the co-owned patents and applications. This license permits us to commercialize our SCD therapy in all human therapeutic indications. For more information, see “Intellectual Property” below.

	•	On November 6, 2024, we received BDD for our SCD to treat chronic systemic inflammation in end-stage renal disease (ESRD) patients who require chronic hemodialysis, also known as chronic dialysis. This is our first BDD in a chronic disease setting.
	•	On March 27, 2025, the FDA awarded a BDD for our SCD therapy for the treatment of systemic inflammatory response in adult patients undergoing cardiac surgery, aimed at preventing post-operative complications and adverse outcomes.

~~Our~~We ~~Approach~~believe -that ~~The~~our SCD ~~Therapeutic~~therapy ~~Device~~is readily applicable for use in other indications as well, which will increase the addressable market for our SCD therapy, but will also require additional clinical studies and FDA approval.

~~Our~~We have pursued patent protection for our SCD therapy isas ~~designed~~well as aother ~~disease-modifying~~technologies. ~~device~~Our ~~that~~patent ~~neutralizes~~portfolio ~~over-active~~consists ~~immune~~of ~~cells~~46 patents and ~~stops~~1 pending patent applications in the ~~cytokine~~U.S. ~~storm~~and ~~that~~certain ~~yields~~foreign ~~destructive~~jurisdictions. ~~hyperinflammation~~Of these patents and ~~creates~~patent aapplications, ~~cascade~~21 patents ofand ~~events~~1 patent ~~that~~applications ~~wreak~~are ~~havoc~~owned inexclusively ~~the~~by ~~patient’s~~us, ~~body.~~and In25 patents are ~~many~~co-owned ~~serious~~with ~~acute~~the ~~illnesses,~~University aof ~~hyperinflammatory~~Michigan ~~response~~(“UOM”). ~~occurs~~The asUOM ahas ~~well-defined~~granted ~~coordinated~~us ~~sequential~~an ~~response.~~exclusive ~~Neutrophils~~worldwide, ~~are~~royalty-bearing ~~the~~license ~~first~~to ~~responders~~the ~~followed~~UOM’s byinterest ~~monocytes.~~in ~~The~~all ~~monocytes,~~of asthe ~~they~~co-owned ~~egress~~patents ~~into~~and ~~tissue~~applications. ~~also~~This ~~follow~~license ~~another~~permits ~~sequence~~us ofto ~~differentiation~~commercialize ~~into~~our ~~tissue~~SCD ~~macrophages.~~therapy ~~The~~in ~~first~~all ~~are~~human ~~proinflammatory~~therapeutic ~~macrophages,~~indications. ~~followed~~For bymore ~~patrolling~~information, ~~reparative~~see ~~macrophages~~“Intellectual Property” below.

~~This~~Our ~~complex~~Approach highly coordinated process is critical for host defense and tissue repair but needs to be tightly regulated by the body’s inflammatory signaling and cellular apoptosis. If it is not tightly regulated and begins to spiral out of control, further tissue destruction may occur when uncontrolled hyperinflammation leads to degradative reparative processes with worsening tissue or organ function. If this excessive systemic inflammation is severe and prolonged, multi-~~organ~~ ~~failure,~~The including cardiovascular, respiratory, kidney, liver and neurologic dysfunction may occur, resulting in poor clinical outcomes. Prior therapeutic approaches to block soluble mediator targets, such as cytokines or free radicals have not proven successful. We believe that our SCD ~~approach,~~Therapeutic ~~which~~Device ~~targets activated cells, is a potentially transformative, if not disruptive, therapeutic approach to a range of acute and chronic inflammatory disorders.~~

Our SCD therapy is andesigned ~~extracorporeal~~as ~~synthetic~~a ~~membrane~~disease-modifying device ~~designed~~that toneutralizes ~~bind~~overactive ~~activated~~immune ~~leukocytes~~cells ~~(neutrophils~~ and ~~monocytes)~~stops ~~when~~the ~~integrated~~cytokine ~~into~~storm anthat ~~existing~~yields ~~CRRT~~destructive ~~circuit~~hyperinflammation inand ~~conjunction~~creates ~~with~~a ~~the~~cascade ~~use~~ of ~~regional~~events ~~citrate~~that ~~anticoagulation~~wreak ~~(“RCA”).~~havoc ~~The~~in ~~SCD~~the ispatient’s ~~simply~~body. ~~added~~In tomany ~~the~~serious ~~standard~~acute ~~CRRT~~illnesses, ~~circuit~~a ~~that~~hyperinflammatory ~~uses~~response ~~regional~~occurs ~~citrate~~as ~~anticoagulation~~a ~~and~~well-defined iscoordinated ~~placed~~sequential ~~immediately~~response. ~~following~~Neutrophils are the ~~standard~~first ~~hemofilter~~responders ~~cartridge.~~followed ~~Highly~~by ~~inflamed~~monocytes. ~~blood~~The ~~from~~monocytes, ~~the~~as ~~patient~~they ~~passes~~egress ~~through~~into ~~the~~tissue ~~CRRT~~also ~~system~~follow ~~and~~another ~~hemofilter~~sequence ~~and~~of differentiation into ~~the~~tissue ~~SCD~~macrophages. InThe ~~the~~first ~~low~~are ~~calcium~~proinflammatory ~~environment~~macrophages, ~~mediated~~followed by ~~RCA~~patrolling, ~~the~~reparative ~~inflamed cells in the blood are~~ macrophages.

5This complex highly coordinated process is critical for host defense and tissue repair but needs to be tightly regulated by the body’s inflammatory signaling and cellular apoptosis. If it is not tightly regulated and begins to spiral out of control, further tissue destruction may occur when uncontrolled hyperinflammation leads to degradative processes with worsening tissue or organ function. If this excessive systemic inflammation is severe and prolonged, multi-organ failure, including cardiovascular, respiratory, renal, hepatic and neurologic dysfunction may occur, resulting in poor clinical outcomes. Prior therapeutic approaches to block soluble mediator targets, such as cytokines or free radicals have not proven successful. We believe that our SCD approach, which targets only highly activated cells, is a potentially transformative, if not disruptive, therapeutic approach to a range of acute and chronic inflammatory disorders.

Our SCD therapy is an extracorporeal synthetic membrane device designed to bind activated leukocytes (neutrophils and monocytes) when integrated into an existing CRRT circuit in conjunction with the use of regional citrate anticoagulation (“RCA”). The SCD is simply added to the standard CRRT circuit that uses RCA and is placed immediately following the standard hemofilter cartridge. Highly inflamed blood from the patient passes through the CRRT system and hemofilter, and into the SCD. In the low calcium environment mediated by RCA, the inflamed cells in the blood are modulated towards a less inflammatory state. Upon exiting our SCD, ~~under a low~~ calcium ~~environment,~~is replaced and the blood is returned to the patient’s body.

Our SCD therapy delivers its therapeutic benefit by attenuating the excessive inflammatory response of activated neutrophils and monocytes. Uninterrupted, the excessive inflammatory response progresses to multi-organ failure, with documented increases in both morbidity and mortality in critically ill patients. Our initial approved product, QUELIMMUNE, is focused on critically ill AKI pediatric patients on CRRT. Our SCD therapy leverages the existing footprint of CRRT pump systems in ICUs today, as well as the growing use and adoption of regional citrate as an anticoagulant. Citrate is used to bind the free ionized calcium within the extracorporeal circuit which is needed to impact the neutrophils and monocytes. A recent study in the Journal of the American Medical Association in 2020 demonstrated that while the use of regional citrate anticoagulation has the same mortality profile as heparin, regional citrate anticoagulation has been shown to be more effective in preserving filter life and is used to create the low calcium environment for our SCD therapy, which impacts the white cells interaction with the SCD membrane leading to the reduction in inflammation. 5

~~Mechanism~~ Table of ~~Action~~Contents

~~The~~Our ~~mechanism~~SCD oftherapy ~~action~~delivers ofits ~~our~~therapeutic ~~SCD~~benefit ~~therapy~~by ~~consists~~attenuating ofthe ~~three~~excessive ~~elements:~~inflammatory ~~(i)~~response ~~selectively~~of ~~binding~~ activated neutrophils and monocytes. onUninterrupted, ~~our~~the ~~SCD~~excessive ~~biomimetic~~inflammatory ~~membrane~~response ~~(ii)~~progresses ~~deactivating~~to ~~the~~multi-organ ~~activated~~failure, ~~neutrophils~~with bydocumented ~~maintaining~~increases ain ~~specified~~both ~~ionized~~morbidity ~~calcium~~and ~~level~~mortality ~~within~~in ~~our~~critically ~~SCD~~ill patients. Our initial approved product, ~~and~~QUELIMMUNE, ~~(iii)~~is ~~shifting~~focused ~~proinflammatory~~on ~~monocytes~~critically toill pediatric aAKI ~~lower~~patients ~~inflammatory~~on ~~profile~~CRRT. Our SCD ~~utilizes~~therapy ~~clinically~~leverages ~~validated~~the ~~regional~~existing ~~citrate~~footprint ~~anticoagulation~~of ~~protocols~~CRRT pump systems in ICUs today, as well as the growing use and adoption of RCA. Citrate is used to ~~lower~~bind the free ionized calcium ~~level,~~within the extracorporeal circuit which ~~not~~is ~~only~~needed ~~prevents~~to ~~clotting~~impact ~~within~~the neutrophils and monocytes. A study in the ~~circuit~~Journal ~~but~~of ~~also~~the ~~immuno-modulates~~American Medical Association in 2020 demonstrated that while the ~~activated~~use ~~neutrophils~~of RCA has the same mortality profile as heparin, RCA has been shown to be more effective in preserving filter life and ~~monocytes~~is used to create the low calcium environment for our SCD therapy, which ~~are~~impacts ~~then~~the ~~returned~~white blood cells interaction with the SCD membrane leading to the ~~patient.~~reduction in inflammation.

6Mechanism of Action

The mechanism of action of our SCD therapy consists of three elements: (i) selectively binding activated neutrophils and monocytes on our SCD biomimetic membrane (ii) deactivating the activated neutrophils by maintaining a specified ionized calcium level within our SCD, and (iii) shifting proinflammatory monocytes to a lower inflammatory profile. Our SCD utilizes clinically validated RCA protocols to lower the ionized calcium level, which not only prevents clotting within the circuit but also immuno-modulates the activated neutrophils and monocytes, which are then returned to the patient. Calcium is then infused into the blood line returning to the patient from the SCD, thereby maintaining normal calcium levels in the patient throughout the process.

~~Our SCD and Neutrophils~~ 6

~~Calcium~~ Table ~~plays a critical role in many biological processes. In the case~~ of neutrophils, calcium can have a profound effect on their activity. It has been shown that lowering calcium to critical levels in the regional circuit can lead to higher levels of neutrophil apoptosis (deactivation). Our SCD is designed to selectively bind the most highly activated neutrophils, associated with hyperinflammation, and in a low ionized calcium (“iCa”) environment, the activated neutrophils are deactivated, which has the downstream effect of reducing hyperinflammation. These deactivated cells are then released back into circulation, resulting in no downstream immunodepletion or immunosuppression. When neutrophils are in homeostasis, the normal half-life is six to eight hours, but in a hyperinflammatory state, neutrophil apoptosis is delayed, leading to increased numbers of activated neutrophils in circulation. Through clinical and preclinical studies, our SCD has been shown to selectively sequester and deactivate the most highly activated neutrophils, allowing the body to restore neutrophil homeostasis.Contents

Our SCD and ~~Monocytes~~Neutrophils

WeCalcium ~~believe~~plays ~~the~~a critical role ~~of circulating monocytes~~ in ~~systemic~~many ~~inflammation~~biological ~~and organ-specific injury is becoming more appreciated by healthcare professionals~~processes. ~~Similar~~In tothe ~~calcium’s~~case ~~effect~~of on neutrophils, calcium ~~also~~can ~~has~~have ana ~~important~~profound ~~influence~~effect on ~~monocyte~~their activity. AIt ~~high~~has ~~percentage~~been ofshown ~~the~~that ~~circulating~~lowering ~~monocyte-derived~~calcium ~~macrophage~~to ~~subtypes~~critical ~~(M1~~levels ~~proinflammatory~~in ~~versus~~the M2regional ~~patrolling,~~circuit ~~reparative)~~can ~~have~~lead ~~been~~to ~~shown~~higher tolevels ~~influence~~of ~~the~~neutrophil ~~degree~~apoptosis of(deactivation). ~~acute~~Our ~~organ~~SCD ~~injury~~is ~~and~~designed ~~chronic~~to ~~organ~~selectively ~~dysfunction.~~bind Inthe inmost ~~vitro~~highly ~~testing~~activated neutrophils, weassociated ~~have~~with ~~shown that~~hyperinflammation, and in a low ionized calcium (“iCa”) environment, ~~our~~the ~~SCD~~activated ~~membrane~~neutrophils ~~binds~~are ~~the~~deactivated, ~~proinflammatory~~which ~~monocytes~~has ~~within~~ the ~~blood~~downstream ~~more~~effect ~~selectively~~of ~~and~~reducing ~~lowers~~hyperinflammation. ~~their~~These ~~inflammatory~~deactivated ~~activity.~~cells ~~This~~are ~~selective~~then ~~binding~~released ~~and~~back ~~immunomodulation~~into ~~has~~circulation, ~~also~~resulting ~~been~~in ~~shown~~no indownstream immunosuppression, ~~human~~immunodepletion, ~~clinical~~leukopenia ~~trials~~or ~~and~~neutropenia. ~~results~~When inneutrophils ~~fewer~~are ~~proinflammatory~~in ~~circulating~~homeostasis, ~~monocytes.~~the Itnormal half-life is ~~important~~six to ~~note~~eight ~~that~~hours, ~~our~~but ~~SCD~~in ~~does~~a ~~not~~hyperinflammatory ~~sequester~~state, ~~100%~~neutrophil ofapoptosis ~~these~~is ~~monocytes~~delayed, asleading ~~they are important~~ to ~~maintaining~~increased ~~immune~~numbers ~~homeostasis.~~of ~~Similar~~activated to neutrophils ~~above,~~in ~~immunomodulated~~circulation. ~~monocytes~~Through ~~are~~clinical ~~also~~and ~~released~~preclinical ~~back~~studies, ~~into~~our ~~circulation~~SCD ~~following~~has ~~treatment,~~been ~~resulting~~shown into noselectively ~~downstream~~sequester ~~immunodepletion~~and ordeactivate ~~immunosuppression. We call~~ the ~~SCD~~most ~~mechanistic~~highly ~~process~~activated ~~of binding these cells~~neutrophils, ~~deactivating~~allowing ~~them,~~the ~~and~~body ~~releasing~~to ~~them~~restore ~~back~~neutrophil ~~into circulation as “catch-and-release” system~~homeostasis.

7Our SCD and Monocytes

~~Histological~~We ~~evaluation~~believe the role of circulating monocytes in systemic inflammation and organ-specific injury is becoming more appreciated by healthcare professionals. Similar to calcium’s effect on neutrophils, calcium also has an important influence on monocyte activity. A high percentage of the circulating monocyte-derived macrophage subtypes (M1 proinflammatory versus M2 patrolling, reparative) have been shown to influence the degree of acute organ injury and chronic organ dysfunction. In in-vitro testing, we have shown that, in a low iCa environment, our SCD membrane binds the proinflammatory monocytes within the blood more selectively and lowers their inflammatory activity. This selective binding and immunomodulation has also been shown in human clinical trials and results in fewer proinflammatory circulating monocytes. It is important to note that our SCD does not sequester 100% of these monocytes as they are important to maintaining immune homeostasis. Similar to neutrophils above, immunomodulated monocytes are also released back into circulation following treatment, resulting in no downstream immunosuppression, immunodepletion, leukopenia or neutropenia. We call the SCD mechanistic process of binding these cells, deactivating them, and releasing them back into circulation, a “catch-and-release” system.

Microscopy of our SCD after being used for patient treatment demonstrated the binding of leukocytes on the outer surface of the hollow fiber membranes of the cartridge along the blood flow path within the extracorporeal circuit. Flow cytometry confirmed that they were the most activated neutrophils and monocytes (see Figure 1 below). 7

~~Above~~ Table image: Activated leukoctyes adherence to the membranes. Light micrograph stained with Hematoxylin and Eosin (H&E). Panel A: Low-power micrograph showing adherent cells around each fiber (160x). Panel B and C: Higher-power micrographs showing the clustering of ~~bound leukocytes (400x). Panel D: High-power micrograph displaying predominance of neutrophils and monocytes in the adherent cell clusters (1600x)~~Contents

~~The~~Histological ~~unique~~evaluation ~~blood path within the SCD mimics capillary flow, providing a more stable microenvironment for the neutrophils and monocytes, enabling the cells to bind to the outer surface~~ of ~~the~~our ~~hollow fibers long enough for the critically low iCa to have its impact. This is then followed by cells being released back into the circulation. (i.e. – “catch and release”).~~SCD

8Microscopy of our SCD after being used for patient treatment demonstrated the binding of leukocytes on the outer surface of the hollow fiber membranes of the cartridge along the blood flow path within the extracorporeal circuit. Flow cytometry confirmed that they were the most activated neutrophils and monocytes (see below)

~~Our~~Above ~~Market~~image: ~~Opportunity~~Activated leukocytes adherence to the membranes. Light micrograph stained with Hematoxylin and Eosin (H&E). Panel A: Low-power micrograph showing adherent cells around each fiber (160x). Panel B and Panel C: Higher-power micrographs showing the clustering of bound leukocytes (400x). Panel D: High-power micrograph displaying predominance of neutrophils and monocytes in the adherent cell clusters (1600x)

WeThe ~~are~~unique ablood ~~therapeutic~~path ~~medical~~within ~~device~~the ~~company pursuing multiple large market indications with our~~ SCD .mimics ~~Our~~capillary ~~clinical~~flow, ~~data~~providing ~~was~~a ~~initially~~more ~~used~~stable tomicroenvironment ~~support~~for ~~an HDE submission to~~ the ~~FDA~~neutrophils toand ~~request~~monocytes, ~~approval~~enabling tothe ~~market~~cells ~~our SCD~~ to ~~hospitals~~bind ~~and clinicians with pediatric patients suffering from AKI. Our clinical data has also been used~~ to ~~support~~ the ~~initiation~~outer surface of ~~a pivotal PMA study in adult AKI which has an estimated 210,000 patients annually in~~ the ~~United~~hollow ~~States.~~fibers ~~In the~~ long ~~term,~~enough ~~based~~for ~~on preliminary clinical evidence, we intend to expand~~ the ~~application~~critically oflow ~~our~~iCa ~~SCD technology~~ to ~~additional~~have ~~indications~~its ~~with~~impact. ~~large~~This ~~patient~~is ~~populations,~~then ~~including~~followed ~~acute~~by ~~respiratory~~cells ~~distress~~being ~~syndrome,~~released ~~chronic~~back ~~dialysis,~~into ~~cardiorenal~~circulation. ~~syndrome~~(i.e. ~~and~~– ~~hepatorenal~~“catch ~~syndrome~~ and ~~others~~release”).

~~Our Initial Market Opportunity in Acute Kidney Injury~~ 8

We Table ~~believe AKI has increasingly received the attention~~ of healthcare professionals and academic publications that reveal the devastating clinical and financial impact of what is most-often a multi-organ syndrome. A 2017 study by Samuel A. Silver and Glenn M Chertow titled “The Economic Consequences of Acute Kidney Injury” stated hospital costs associated with AKI in the U.S. are between $5.4 billion and $20 billion per year.Contents

~~The~~Our ~~kidneys~~Market are a silent killer within medical triage. They do not present clear symptoms or tell the body they are suffering like other major organs such as the heart or lungs. For example, one does not feel pain with a “kidney attack” and symptoms are delayed until irreversible damage may have already occurred. Kidneys also refrain from revealing the impact to the rest of body and organs (and vice-versa) and often are not considered systemically for co-treatment.Opportunity

~~Globally~~We ~~consistent~~are ~~criteria~~a ~~for~~commercial-stage ~~diagnosing~~healthcare ~~AKI~~company ~~have~~pursuing ~~recently~~multiple indications, ~~emerged~~both ~~with~~small ~~Risk,~~and ~~Injury,~~large ~~Failure~~market opportunities, ~~Loss~~with ofour ~~kidney~~SCD ~~function,~~therapy. ~~and~~Our ~~End-stage~~clinical ~~kidney~~data ~~disease,~~was initially used to support an ~~international~~HDE ~~consensus~~submission ~~classification~~to ~~for~~the ~~AKI~~FDA ~~staging~~to request approval to market our SCD to hospitals and ~~diagnosing~~clinicians ~~guidelines~~with ~~introduced~~pediatric inpatients ~~2004,~~suffering from AKI. Our clinical data has also been used to support the ~~Acute~~initiation ~~Kidney~~of ~~Injury~~a ~~Network~~pivotal ~~staging~~study ~~system~~that would support a PMA submission in ~~2007~~adult AKI which has an estimated incidence of approximately 200,000 ~~and~~patients ~~finally~~annually in the ~~Kidney~~United ~~Disease:~~States. ~~Improving~~In ~~Global~~the ~~Outcomes~~long term, ~~AKI~~based ~~Staging~~on ~~and~~preliminary ~~Diagnosing~~clinical ~~Guidelines~~evidence, ~~published~~we inintend ~~2012.~~to ~~These~~expand ~~sources~~the ~~have~~application ~~helped~~of ~~clinicians~~our SCD technology to ~~improve~~additional ~~recognition~~indications with large patient populations, ~~staging~~including acute respiratory distress syndrome, chronic dialysis, cardiorenal syndrome and hepatorenal syndrome and others.

9Our Initial Market Opportunity in Acute Kidney Injury

~~diagnosing~~With over 5 million ICU admissions in the U.S. each year, and ~~subsequent~~approximately ~~documentation~~50-60% of ~~less~~these ~~obvious~~patients ~~cases~~experiencing AKI, AKI has increasingly received the attention of ~~AKI~~healthcare ~~secondary~~professionals ~~diagnoses.~~and ~~While~~academic ~~our~~publications ~~initial~~that ~~market~~elucidate the devastating clinical and financial impact of what is ~~focused~~most-often ona ~~AKI~~multi-organ ~~patients~~syndrome. onIn ~~CRRT~~fact, ~~future~~a ~~indications~~2017 ~~will~~study ~~likely~~by ~~benefit~~Samuel ~~from~~A. ~~improved~~Silver ~~characterization~~ and ~~diagnosis~~Glenn M. Chertow titled “The Economic Consequences of ~~patients~~Acute Kidney Injury” stated hospital costs associated with AKI in the U.S. are between $5.4 billion and $20 billion per year.

AsThe akidneys ~~result,~~are ~~demand~~a ~~for~~silent ~~ICU~~killer ~~renal~~within ~~replacement~~medical ~~therapy is growing~~triage. ~~CRRT~~They isdo ~~the~~not ~~newest~~present ofclear ~~AKI~~symptoms ~~dialysis~~or ~~modality~~tell in the ~~market,~~body ~~first~~they ~~becoming~~are ~~available~~suffering inlike ~~1997,~~other ~~and~~major ~~according~~organs tosuch ~~Fortune~~as ~~Business~~the ~~Insights,~~heart itor islungs. ~~estimated~~For ~~that~~example, itone ~~has~~does ~~grown~~not tofeel pain with a ~~$986~~“kidney ~~million~~attack” ~~global~~and ~~market~~symptoms ~~($354~~are ~~million~~delayed ~~market~~until inirreversible ~~the~~damage ~~U.S.)~~may ashave ofalready ~~2019~~occurred. ~~The~~Kidneys ~~two~~also ~~largest~~refrain ~~operators~~from inrevealing the ~~CRRT~~impact ~~market~~to bythe ~~revenue~~rest ~~are~~of ~~Fresenius~~body ~~Medical~~and ~~Care~~organs ~~Holdings,~~(and ~~Inc.~~vice-versa) and ~~Baxter~~often ~~International,~~are ~~which~~not ~~represent~~considered ~~over~~systemically ~~80%~~for ~~of the market today in the U~~co-treatment.S.

~~Since~~Globally ~~2010,~~consistent acriteria ~~significant~~for ~~amount~~diagnosing ofAKI ~~data~~have ~~has~~recently ~~been~~emerged ~~published~~with ~~to quantify~~ the ~~clinical~~RIFLE ~~and~~classification ~~financial~~(Risk, ~~impact~~Injury, ~~of AKI~~Failure, ~~resulting~~Loss ~~in a broadening AKI treatment “boom” beyond dialysis to areas~~ of ~~diagnostics,~~kidney ~~complementary therapies~~function, and ~~pharmacoeconomics.~~End-stage Askidney ~~hospital~~disease), ~~administrators~~an ~~and~~international ~~government~~consensus ~~officials~~classification ~~gain~~for ~~understanding~~AKI ofstaging ~~the impact~~ and ~~burden~~diagnosing ofguidelines ~~AKI~~introduced ~~increases~~in 2004, wethe ~~believe~~Acute ~~that~~Kidney ~~attention~~Injury ~~will~~Network ~~continue~~staging tosystem ~~grow. According to Hobson~~ in ~~his~~2007, ~~article titled “Cost~~ and ~~Mortality~~finally ~~Associated~~the ~~with Postoperative Acute~~ Kidney ~~Injury,”~~Disease: aImproving ~~2015~~Global ~~study of 50~~Outcomes,~~314~~ ~~patients~~AKI ~~(over~~Staging 11and ~~years)~~Diagnosing ~~found~~Guidelines ~~that~~published ~~upon~~in ~~greater~~2012. ~~scrutiny,~~These ~~AKI~~sources ~~was~~have ~~found~~helped inclinicians ~~39%~~to ofimprove ~~post-surgical~~recognition, ~~patients~~staging, diagnosing and ~~19%~~subsequent documentation of ~~patients~~less ~~had~~obvious ~~stage~~cases 2of ~~or 3~~ AKI ~~with~~secondary andiagnoses. ~~average~~While ~~incremental~~our ~~cost~~initial ofmarket ~~$29,800~~is ~~per~~focused ~~patient.~~on ~~Additionally,~~AKI ~~with~~patients ~~historical~~on ~~mortality rates approximately 50%~~CRRT, ~~treating~~future ~~AKI~~indications iswill ~~increasingly~~likely ofbenefit ~~interest~~from toimproved ~~clinicians,~~characterization ~~hospitals,~~ and ~~product~~diagnosis ~~manufacturers~~of ~~alike~~patients.

~~The AKI patient population is growing on average 6.~~ 9% per year according to the Healthcare Cost and Utilization Project commissioned by the Agency for Healthcare Research and Quality, a U.S. federal agency. According to Massicotte and Azarniouch in their 2015 work titled “Acute Kidney Injury in the Intensive Care Unit: Risk Factors and Outcomes of Physician Recognition Compared with KDIGO Classification,” around 80% of moderate or severe cases of AKI are not diagnosed and documented, suggesting the U.S. AKI patient population is higher than the estimated 6 million patients annually. The pediatric population for AKI patients in the U.S. on CRRT is estimated to be less than 8,000 patients per year, which is a substantially small sub-set of the 6 million AKI patient population.

~~The~~ Table ~~AKI~~of market needs new and effective solutions, and hospitals continue to search for and evaluate new products. For a product to succeed in the AKI space, it must demonstrate and achieve clear and significant clinical benefit to patients, while providing positive financial incentives for hospitals to generate revenue and profitability.Contents

~~Our~~As ~~Growth~~a ~~Strategies~~result, demand for ICU renal replacement therapy is growing. CRRT is the newest AKI dialysis modality in the market, first becoming available in 1997, and according to Fortune Business Insights, it is estimated that it has grown to a $986 million global market ($354 million market in the U.S.) as of 2019. The two largest operators in the CRRT market by revenue are Fresenius Medical Care Holdings, Inc. and Vantive, Inc. (formerly a business of Baxter International), which represent over 80% of the market today in the U.S.

~~Key~~Since ~~elements~~2010, a significant amount of ~~our~~data ~~growth~~has ~~strategy~~been ~~include~~published ~~innovating~~to quantify the clinical and ~~expand~~financial ~~our~~impact ~~applications~~of ~~through~~AKI, ~~clinical~~resulting ~~trials;~~in ~~differentiation~~a ~~through~~broadening ~~medical~~AKI ~~education;~~treatment ~~business~~“boom” ~~development~~beyond dialysis to areas of diagnostics, complementary therapies, and ~~out~~pharmacoeconomics. As hospital administrators and government officials gain an increasing understanding of the impact and burden of AKI, we believe that attention will continue to grow. According to Hobson in his article titled “Cost and Mortality Associated with Postoperative Acute Kidney Injury,” a 2015 study of 50,314 patients (over 11 years) found that upon greater scrutiny, AKI was found in 39% of post-~~licensing~~surgical ~~activities~~patients, and ~~scaling~~19% ~~production~~of patients had stage 2 or 3 AKI with ~~manufacturing~~an ~~partners~~average incremental cost of $29,800 per patient. WeAdditionally, ~~expect~~with historical mortality rates of approximately 50%, treating AKI is of increasing interest to ~~employ~~clinicians, ~~several~~hospitals, ~~core~~and ~~growth~~product ~~strategies:~~manufacturers alike.

~~Execute~~The onAKI ~~clinical~~patient ~~plan~~population ~~through~~is ~~key~~growing ~~relationships:~~on ~~Our~~average ~~initial~~6.9% ~~focus~~per onyear ~~the~~according ~~treatment~~to ofthe ~~AKI~~Healthcare inCost ~~adults~~ and ~~pediatrics~~Utilization isProject ~~supported~~commissioned by ~~our long and established relationship with~~ the ~~UOM,~~Agency ~~which~~for ~~licenses~~Healthcare toResearch usand ~~certain key technology underpinning our novel immunomodulatory therapy~~Quality, asa ~~well as other leading academic hospitals and institutions throughout the~~ U.S. ~~Such~~federal ~~relationships~~agency. ~~enable~~According us to ~~expand~~Massicotte and ~~refine~~Azarniouch ~~the~~in ~~design~~their ~~and~~2015 ~~execution~~work oftitled ~~our~~“Acute ~~clinical~~Kidney ~~plans~~Injury ~~with~~in athe ~~more~~Intensive ~~targeted~~Care ~~outcome~~Unit: ~~and~~Risk ~~objectives.~~Factors Onand ~~February~~Outcomes ~~21,~~of ~~2024,~~Physician weRecognition ~~received~~Compared ~~the~~with ~~FDA~~KDIGO ~~HDE Approval Order~~Classification,” ~~which~~around ~~allows~~80% ~~sales~~of tomoderate ~~qualified~~or ~~healthcare~~severe ~~facilities.~~cases Inof ~~February~~AKI ~~2023,~~are wenot ~~received~~diagnosed ~~FDA~~and ~~IDE~~documented, ~~approval~~suggesting ~~for~~ the ~~adult AKI indication~~U.S. ~~This indication has received the FDA BDD for our SCD therapy targeting~~ AKI ~~adult~~patient ~~patients,~~population is ~~expected~~higher tothan ~~accelerate and streamline~~ the ~~regulatory~~estimated ~~approval~~6 ~~process~~million ~~prior~~patients ~~to the commercial launch of our product candidates~~annually. OnThe ~~September~~pediatric ~~28,~~population ~~2023, we received Breakthrough Device Designation~~ for ~~our~~AKI ~~patented and cell-directed SCD for use with~~ patients in the hospital ICU with acute or chronic systolic heart failure and worsening renal function due to cardiorenal syndrome or right ventricular dysfunction awaiting implantation of a left ventricular assist deviceU.S. ~~On October 18, 2023, we received a BDD for our patented and cell-directed SCD for use with patients in the hospital ICU with AKI and acute~~ on ~~chronic~~CRRT ~~liver~~is ~~failure.~~estimated ~~On November 6, 2024, we received Breakthrough Device Designation for our patented and cell-directed SCD~~ to ~~treat~~be ~~chronic~~less ~~systemic~~than ~~inflammation~~8,000 ~~in end-stage renal disease (ESRD)~~ patients ~~who~~per ~~require chronic hemodialysis~~year, ~~also known as chronic dialysis. We have been granted four Breakthrough Device Designations from the FDA for the SCD device, each of~~ which is ~~expected~~a tosubstantially ~~expedite~~small ~~the~~subset ~~clinical development and regulatory review~~ of the ~~SCD~~combined 6 ~~for~~million ~~use~~AKI inadult ~~the~~and ~~designated~~pediatric patient population.

~~Differentiation~~AKI ~~through~~patients ~~medical~~need new ~~education:~~and Weeffective ~~intend~~solutions, toand ~~dedicate~~hospitals ~~resources~~continue to ~~educate~~search ~~physicians,~~for ~~hospital~~and ~~clinicians~~evaluate ~~and~~new ~~other~~products. ~~decision~~For ~~makers~~a product to succeed in the ~~medical~~AKI ~~communities~~space, onit ~~the~~must ~~role~~demonstrate ofand ~~neutrophils~~achieve clear and ~~monocytes~~significant inclinical ~~both~~benefit to patients, while providing positive financial incentives for hospitals to generate revenue and profitability.

10Our Growth Strategies

~~acute~~Key ~~and~~elements ~~chronic indications, and therapeutic benefit~~ of ~~controlling and modulating excessive inflammatory response. We intend to focus~~ our ~~marketing~~growth ~~strategies~~strategy ~~not~~include ~~only~~innovating onand ~~the~~expanding ~~therapeutic capabilities of~~ our ~~technology,~~applications ~~but~~through ~~also~~clinical ~~the~~trials; ~~economic~~differentiation ~~consequences~~through ofmedical ~~hyper-inflammation~~education; inbusiness ~~the~~development ~~current standard of care~~ and ~~treatment~~out-licensing ~~infrastructure~~activities, and ~~highlight~~scaling ~~the~~production ~~differentiating~~with ~~factors~~manufacturing ofpartners. ~~our~~We ~~SCD~~expect ~~product~~to ~~candidates~~employ ~~that~~several ~~can~~core ~~provide~~growth ~~a cost-effective solution.~~ strategies:

~~Business~~• ~~development~~Execute ~~and~~on ~~out-licensing~~clinical ~~activities~~plan through key relationships: WeOur ~~intend~~initial tofocus ~~explore~~on ~~and~~the ~~pursue~~treatment ~~business~~of ~~development~~AKI ~~opportunities~~in ~~with~~adults ~~major~~and ~~medical~~pediatrics is supported by our long and ~~pharmaceutical~~established ~~companies~~relationship with the UOM, which licenses to ~~establish~~us ~~partnerships~~certain key technology underpinning our novel immunomodulatory therapy, ~~including~~as ~~outbound~~well ~~licensing~~as ~~arrangements~~other leading academic hospitals and institutions throughout the U.S. WeSuch ~~believe~~relationships ~~that~~enable us to expand and refine the design and execution of our clinical ~~experience~~plans with a more targeted outcome and ~~depth~~objectives. On February 21, ~~combined~~2024, ~~with~~we ~~our~~received ~~understanding~~the FDA HDE Approval Order, which allows sales of QUELIMMUNE to qualified healthcare facilities. In February 2023, we received FDA IDE approval for the ~~scientific~~adult ~~mechanism~~AKI ofindication. ~~our~~Our patented and cell-directed SCD therapy has received the FDA BDD for use in adult AKI patients, which is expected to accelerate and ~~our~~streamline the regulatory ~~submissions~~approval ~~around~~process prior to the ~~world~~commercial launch of our product candidates. On September 28, ~~can~~2023, ~~drive~~we ~~value~~received BDD for our ~~partners~~SCD therapy for use with patients in the hospital ICU with acute or chronic systolic heart failure and ~~reduce~~worsening ~~their~~renal ~~market~~function ~~risk~~due to cardiorenal syndrome or right ventricular dysfunction awaiting implantation of a left ventricular assist device. WeOn ~~believe~~October ~~our~~18, ~~partners~~2023, ~~will~~we ~~benefit~~received ~~from~~a ~~insight~~BDD infor ~~other~~our SCD ~~trials~~therapy ~~around~~for use with patients in the ~~world~~hospital asICU ~~well~~with asAKI ~~data~~and ~~generation~~acute ~~that~~on ischronic ~~being~~liver ~~conducted~~failure. byOn November 6, 2024, we received BDD for our ~~trials~~SCD therapy to treat chronic systemic inflammation in end-stage renal disease (ESRD) patients who require chronic hemodialysis, also known as chronic dialysis. WeOn ~~believe~~March ~~that~~27, 2025, the FDA awarded two BDDs for our SCD therapy ~~has~~for the ~~potential~~treatment toof ~~apply~~systemic toinflammatory ~~multiple~~response, ~~indications.~~one Byin ~~pursuing~~adults and ~~establishing~~one ~~business~~in ~~relationships~~pediatric ~~with~~patients, ~~partners~~undergoing ~~who~~cardiac ~~may~~surgery, ~~have~~aimed ~~strong~~at ~~capabilities~~preventing ~~beyond~~post-operative ~~AKI,~~complications ~~such~~and asadverse outcomes. We have been granted six BDDs by the ~~markets~~FDA for ~~respiratory~~the ~~distress~~SCD ~~syndrome~~device, weeach ~~may~~of bewhich ~~able~~is expected to ~~expand~~expedite ~~our~~the ~~solutions~~clinical todevelopment and regulatory review of the ~~chronic~~SCD ~~disease~~therapy ~~setting~~for use in the designated patient population.

~~Scaling~~• ~~production~~Differentiation ~~with~~through ~~manufacturing~~medical ~~partners~~education: AsWe weintend ~~progress~~to ~~through~~dedicate ~~our~~resources ~~planned~~to ~~clinical~~educate ~~trials~~physicians, ~~and~~hospital ~~the~~clinicians ~~commercial~~and ~~launch~~other ofdecision ~~our~~makers ~~SCD~~ in ~~pediatrics~~the ~~(QUELIMMUNE)~~medical ascommunities ~~well~~on asthe ~~additional~~role ~~adult~~of ~~product~~neutrophils ~~candidates~~and ifmonocytes ~~FDA~~in ~~approval~~both isacute ~~received, we are focused on identifying~~ and ~~securing~~chronic ~~various~~indications, ~~suppliers~~ and ~~manufacturing~~the ~~partners~~therapeutic tobenefit ~~scale~~of ~~production~~controlling inand ~~response~~modulating toexcessive ~~the~~inflammatory ~~expected demand for our solutions~~response. We ~~continue~~intend to ~~negotiate~~focus ~~with~~our ~~suppliers~~marketing ofstrategies ~~raw~~not ~~materials,~~only ~~including~~on ~~cartridges,~~the ~~tubing~~therapeutic ~~and~~capabilities ~~other~~of ~~components~~our technology, tobut ~~establish~~also ~~redundancies~~the ~~and~~economic ~~alternative~~consequences ~~sources~~of tohyper-inflammation ~~mitigate interruptions~~ in the ~~supply~~current ~~chain~~standard inof ~~the~~care ~~future.~~and Intreatment ~~addition,~~infrastructure weand ~~may~~highlight ~~also~~the ~~explore~~differentiating ~~strategic~~factors ~~relationships~~of ~~with~~our ~~partners~~SCD ~~who~~therapy that can provide ~~sources~~a ofcost-effective ~~raw materials while collaborating with us on the marketing and distribution of our product candidates~~solution.

~~Our Commercial Stage Product~~ 10

~~The~~ Table ~~following~~of disclosure summarizes the key clinical studies in which our SCD product candidates (QUELIMMUNE for pediatrics) have been evaluated. All trials and studies below are conducted under IDEs approved by the FDA. Contents

• Business development and out-licensing activities: We ~~submitted~~intend anto ~~HDE~~explore ~~application~~and ~~for~~pursue business development opportunities with major medical and pharmaceutical companies to establish partnerships, including outbound licensing arrangements. We believe that our ~~SCD~~clinical ~~for~~experience and depth, combined with our understanding of the ~~treatment~~scientific mechanism of ~~pediatric~~our ~~patients~~SCD ~~with~~and ~~acute~~our ~~kidney~~regulatory ~~injury~~submissions ~~undergoing~~around ~~Continuous~~the ~~Renal~~world, ~~Replacement~~can ~~Therapy~~drive ~~(CRRT)~~value tofor ~~the~~our ~~FDA~~partners inand ~~June~~reduce ~~2022~~their market risk. We ~~obtained~~believe anour ~~Approvable~~partners ~~Letter~~will ~~for~~benefit from insight into other SCD trials around the ~~HDE~~world inas ~~October~~well ~~2023.~~as Ondata ~~February~~generation ~~23,~~that ~~2024,~~is webeing ~~announced~~conducted aby ~~final~~our ~~Approval~~trials. ~~Order~~We ~~for~~believe ~~the~~that ~~HDE,~~our ~~which~~SCD ~~allows~~therapy ushas the potential to ~~commercialize~~apply ~~QUELIMMUNE~~to multiple indications. AsBy ofpursuing and establishing business relationships with partners who may have strong capabilities beyond AKI, such as the ~~date~~markets offor ~~this~~ESRD ~~report~~and respiratory distress syndrome, we ~~have~~may ~~five~~be ~~commercial~~able ~~customers~~to ~~and~~expand ~~several~~our ~~potential~~solutions ~~customers~~to ~~evaluating~~the ~~QUELIMMUNE~~chronic disease setting.

~~Clinical~~• ~~Progression~~Scaling production with manufacturing partners: As we progress through our planned clinical trials and the commercial launch of our QUELIMMUNE in pediatrics as well as potential additional adult indications for our SCD therapy if FDA approval is received, we are focused on identifying and securing various suppliers and manufacturing partners to scale production in response to the expected demand for our solutions. We continue to negotiate with suppliers of raw materials, including cartridges, tubing and other components, to establish redundancies and alternative sources to mitigate interruptions in the supply chain in the future. In addition, we may also explore strategic relationships with partners who can provide sources of raw materials while collaborating with us on the marketing and distribution of our product candidates.

~~SCD~~Our ~~006~~Clinical ~~Pivotal~~Development ~~Study~~of (“the SCD ~~006”)~~Product ~~Design~~Candidates

WeThe ~~are~~following ~~actively~~disclosure ~~enrolling~~summarizes ~~and~~the ~~treating~~key ~~patients in a pivotal~~ clinical ~~trial~~studies ~~of the SCD for the treatment of AKI~~ in ~~adults~~which ~~under~~our ~~a granted BDD (April 2022) by the FDA. This trial (NCT05758077) is a 200 subject, prospective, multi-center, open-label, randomized, two-arm comparative pivotal study conducted in the United States.~~ SCD~~-006~~ isproduct ~~designed~~candidates ~~to assess a composite endpoint of both mortality or dialysis dependency at Day 90~~ (~~see~~QUELIMMUNE ~~schematic~~for ~~figure below~~pediatrics). ~~The control arm will consist of adults with AKI who undergo CRRT in hospital ICUs who typically~~ have ~~estimated~~been ~~mortality of nearly 50%~~evaluated. ~~Among~~All ~~those~~trials ~~with AKI who undergo CRRT~~ and ~~survive~~studies ~~hospitalization,~~below ~~nearly~~are ~~one~~conducted inunder ~~four~~IDEs ~~(25%)~~approved ~~usually~~by ~~require long-term dialysis. The study design was recently published in~~ the ~~journal Nephron (Yessayan et al~~FDA., Nephron. 2023 Jul 13. doi: 10.1159/000531880). The study title is also being referred to as NEUTRALIZE-AKI (NEUTRophil and monocyte deactivation via seLective cytopheretIc device – a randomiZEd clinical trial in Acute Kidney Injury).

11We submitted an HDE application for our SCD for the treatment of pediatric patients with acute kidney injury undergoing Continuous Renal Replacement Therapy (CRRT) to the FDA in June 2022. We obtained an Approvable Letter for the HDE in October 2023. On February 21, 2024, we announced a final Approval Order for the HDE, which allows us to commercialize QUELIMMUNE.

~~Current~~Clinical ~~Trial Status~~Progression

~~As of March 25, 2025, we have enrolled 94 patients into our SCD~~NEUTRALIZE-006 pivotal trial. We submitted the SCD-006 IDE Protocol to the FDA on January 6, 2023, and attained approval in March 2023. We began enrollment in the second quarter of 2023, and we anticipate the enrollment period to last 24 to 28 months. On April 29, 2022, we received a BDD for the use of our SCD in the treatment of immunomodulatory dysregulation in adult patients (18 and older) with AKI~~, which is expected to aid our discussions related to the regulatory review and approval process for SCD-006.~~ Design

We ~~currently~~are ~~anticipate~~actively ~~generating~~enrolling ~~interim~~and ~~results~~treating ~~from~~patients ~~this~~in a pivotal clinical trial inof the ~~middle~~SCD offor the ~~2025~~ ~~calendar~~treatment ~~year~~of ~~and~~AKI ~~topline~~in ~~study~~adults, ~~results~~an ~~and~~indication ~~submission~~awarded ofBDD by the FDA in April 2022. This trial (NCT05758077) is a ~~PMA~~339 ~~application~~subject, prospective, multi-center, open-label, randomized, two-arm comparative pivotal study conducted in the ~~middle~~United ofStates. ~~the~~NEUTRALIZE-AKI ~~2026~~is ~~calendar~~designed ~~year.~~to ~~Additional~~assess ~~clinical~~a ~~studies~~composite ~~under~~endpoint ~~IDEs~~of ~~include~~both ~~cardiorenal~~mortality ~~syndrome~~or ~~and~~dialysis ~~hepatorenal~~dependency ~~syndrome~~at Day 90 (see schematic figure below). WeThe ~~are~~control ~~also~~arm ~~conducting~~will ~~exploratory~~consist ~~clinical~~of ~~research~~adults with ~~the~~AKI ~~University~~who ofundergo ~~Michigan~~CRRT toin ~~define~~hospital ~~the~~ICUs ~~patient~~who ~~population~~typically ~~for~~have ~~potential~~estimated ~~treatment~~mortality of nearly 50%. Among those with ~~SCD~~AKI ~~product~~who ~~candidates~~undergo CRRT and survive hospitalization, nearly one in four (25%) usually require long-term dialysis. The study design was published in the journal Nephron (Yessayan et al., Nephron. 2023 Jul 13. doi: 10.1159/000531880). The study title is also being referred to as NEUTRALIZE-AKI (NEUTRophil and ~~any~~monocyte ~~future~~deactivation ~~studies~~via ~~will~~seLective becytopheretIc ~~based~~device ~~upon~~– ~~initial~~a randomiZEd clinical ~~data~~trial ~~collected~~ in ~~these~~Acute ~~studies~~Kidney Injury).

~~Other Clinical Studies~~ 11

~~The~~ Table ~~table~~of ~~below lists the major studies conducted in AKI to date with our SCD. Except for SCD-003 and SCD-006, our clinical studies have not included a randomized control arm.~~ Contents

12Current Trial Status

Study Name	Objective	Primary Endpoint	Study Population	Total Enrolled	Device-Related SAEs	Key Outcomes
China Study	AKI Safety, Mortality and Device Integrity Study	Safety and in-hospital mortality	AKI	N=9	None	The mortality for the case-matched controls was 77% (7/9), vs 22% (2/9) in the SCD treatment group (P=0.027) (Ding F, et al. ASAIO J. 2011;57(5):426-432).
ARF-002	AKI Safety, Mortality and Device Integrity Study	Safety and 60-day survival	AKI	N=35	None	Death from any cause at day 60 was 31.4% (11/35). Renal recovery, defined as dialysis independence, was observed in all of the surviving subjects at day 60. (Standard of care therapy is associated with a >50% 60-day mortality (Tumlin JA, et al. Semin Dial. 2013;26(5):616-623).
SCD-003	To determine the difference between SCD therapy and CKRT alone in survival	Day 60 survival	AKI	N=134	None	This was a Phase 3A randomized controlled trial. Due to a nationwide calcium shortage during the study, most patients received ineffective therapy as regional ionized calcium (iCa) levels couldn’t be maintained at the target range. This resulted in no differences in outcomes in the intent-to-treat patient population. However, the subset of patients who achieved the target iCa ranges showed a significant clinical benefit in a per-protocol (PP) analysis. In this group, the 60-day mortality rate was 16% in the SCD-treated group compared to 41% in the control group. Furthermore, the composite endpoint of mortality and/or dialysis dependency at day 60 was lower in the PP SCD-treated group compared to the control group (16% vs. 58%, respectively, p = 0.01) (Tumlin JA, et al. PLoS One. 2015;10(8):e0132482). See additional details below on the SCD-003 study
SCD-PED-01	To determine safety and efficacy of SCD therapy + CKRT in pediatric patients	Day 60 survival and 60-day dialysis dependency	AKI	N=16	None	75% of patients (12/16) survived to hospital discharge. 100% of surviving patients (12/12) were dialysis independent by day 60 (Goldstein SL, et al. Kidney Int Rep. 2020;6(3):775-784; Goldstein SL, et al. Kidney Medicine.2024, doi: https://doi.org/10.1016/j.xkme.2024.100). See additional details below on the SCD-PED studies.
SCD-PED-02	To assess the safety of SCD in children with AKI weighing ≥10 kg and ≤20 kg	Safety	AKI	N=6	None	5/6 (83%) patients survived to ICU discharge and all surviving patients were dialysis-independent by day 60 (Goldstein SL, et al. Kidney Medicine. 2024, doi: https://doi.org/10.1016/j.xkme.2024.100). See additional details below on the SCD-PED studies.
SCD-005	To assess the safety and efficacy of SCD in AKI or ARDS patients associated with COVID-19 infections	Mortality at day 60; dialysis dependency at day 60; ventilation at day 28	AKI or ARDS after COVID-19	N=22	None	SCD-treated patients had a reduction in 60-day mortality of 50% (11/22), vs 81% (13/16) in a contemporary control group from a concurrent prospective CKRT registry (P=0.102). The subjects who received >96 hours of SCD treatment, per protocol, had a further reduction in mortality to 31% (5/16) (P<0.012) (Yessayan LT, et al. Crit Care Explor. 2022;4(5):e0694).

We submitted the NEUTRALIZE-AKI protocol to the FDA on January 6, 2023, and attained approval to proceed in March 2023. We began enrollment in the second quarter of 2023, and we anticipate the enrollment period to last up to 48 months. As of March 21, 2026, we have enrolled 181 patients into the NEUTRALIZE-AKI study. On April 29, 2022, we received a BDD for the use of our SCD in the treatment of immunomodulatory dysregulation in adult patients (18 and older) with AKI, which is expected to aid our discussions related to the regulatory review and PMA process for NEUTRALIZE-AKI.

Additional clinical studies under IDEs include cardiorenal syndrome and hepatorenal syndrome. We have also conducted exploratory clinical research with the University of Michigan to define the patient population for potential treatment with SCD~~-003:~~ ~~Additional~~product ~~Details~~candidates, and any future studies will be based upon initial clinical data collected in these studies.

SCD-003 was a controlled, randomized, and multicenter clinical trial that was initiated in September 2011 and terminated in September 2013 under an FDA approved IDE. For this trial, the control group received standard CRRT with regional citrate 12

13 Table of Contents

~~anticoagulation~~Other ~~(“RCA”)~~Clinical ~~and~~Studies ~~the~~in ~~SCD-treated group received up to seven days of SCD therapy. The study was sponsored by the Predecessor with the support of a third-party contract research organization.~~ AKI

The ~~primary~~table ~~objective~~below oflists the ~~study~~major ~~was~~studies toconducted ~~determine~~in ifAKI ~~the~~to ~~SCD,~~date ~~when used in conjunction~~ with ~~CRRT,~~our ~~results in clinical and statistical improvement in mortality rate based on all causes through Day 60~~SCD. ~~Secondary~~Except ~~objectives~~for ~~included~~SCD-003 anand ~~assessment of renal replacement therapy dependency at Day 60~~SCD-006, ~~mortality~~our atclinical ~~Day~~studies ~~28,~~have ~~the~~not ~~number~~included ofa ~~ventilator~~randomized ~~free~~control ~~days at Day 28, and the mortality of the subset of patients with severe sepsis at Day 60~~arm.

A total of 134 patients were enrolled in 21 United States medical centers. Patients receiving care in the ICU of each participating hospital were randomized to intensive care treatment for patients undergoing CRRT or CRRT + SCD. Each participating clinical site used their established RCA protocol for the CRRT + SCD circuits (treatment group) and for the CRRT only (control group). The recommended calcium (iCal) level (measured post SCD) in the CRRT and SCD blood circuit was specified to be between 0.25 and 0.40 mmol/L. Inclusion and exclusion criteria were similar to the previous IDE multicenter pilot clinical study except for an age range of 8-80 years and body weight of over 135 kilograms. Once the patient met all eligibility criteria, including being on CRRT for a minimum of four hours, but no longer than 24 hours, and had signed an informed consent, the subject was randomized in a 1:1 allocation utilizing a random permuted block design into either the control or treatment group, stratified by study center and the presence of severe sepsis. An overall two-sided 0.05 level of significance at 80% power was used to calculate a sample size of 344 patients, assuming a mortality rate of 50% for the control group and 35% for the treatment group. Adaptive design and interim analysis were planned at the mid-point of enrollment (i.e., 172 patients). Several exploratory biomarkers were also compared between the control and treatment groups, including urine output, serum levels of elastase, cytokines, and total absolute white blood cell, neutrophil and platelet counts throughout treatment.


Study Name	Objective	Primary Endpoint	Study Population	Total Enrolled	Device-Related SAEs	Key Outcomes
China Study	AKI Safety, Mortality and Device Integrity Study	Safety and in-hospital mortality	AKI	N=9	None	The mortality for the case-matched controls was 77% (7/9), vs 22% (2/9) in the SCD treatment group (P=0.027) (Ding F, et al. ASAIO J. 2011;57(5):426-432).
ARF-002	AKI Safety, Mortality and Device Integrity Study	Safety and 60-day survival	AKI	N=35	None	Death from any cause at day 60 was 31.4% (11/35). Renal recovery, defined as dialysis independence, was observed in all of the surviving subjects at day 60. (Standard of care therapy is associated with a >50% 60-day mortality (Tumlin JA, et al. Semin Dial. 2013;26(5):616-623).
SCD-003	To determine the difference between SCD therapy and CKRT alone in survival	Day 60 survival	AKI	N=134	None	This was a Phase 3A randomized controlled trial. Due to a nationwide calcium shortage during the study, most patients received ineffective therapy as regional ionized calcium (iCa) levels couldn’t be maintained at the target range. This resulted in no differences in outcomes in the intent-to-treat patient population. However, the subset of patients who achieved the target iCa ranges showed a significant clinical benefit in a per-protocol (PP) analysis. In this group, the 60-day mortality rate was 16% in the SCD-treated group compared to 41% in the control group. Furthermore, the composite endpoint of mortality and/or dialysis dependency at day 60 was lower in the PP SCD-treated group compared to the control group (16% vs. 58%, respectively, p = 0.01) (Tumlin JA, et al. PLOS One. 2015;10(8):e0132482). See additional details below on the SCD-003 study
SCD-PED-01	To determine safety and efficacy of SCD therapy + CKRT in pediatric patients	Day 60 survival and 60-day dialysis dependency	AKI	N=16	None	75% of patients (12/16) survived to hospital discharge. 100% of surviving patients (12/12) were dialysis independent by day 60 (Goldstein SL, et al. Kidney Int Rep. 2020;6(3):775-784; Goldstein SL, et al. Kidney Medicine.2024). See additional details below on the SCD-PED studies.
SCD-PED-02	To assess the safety of SCD in children with AKI weighing ≥10 kg and ≤20 kg	Safety	AKI	N=6	None	5/6 (83%) patients survived to ICU discharge and all surviving patients were dialysis-independent by day 60 (Goldstein SL, et al. Kidney Medicine. 2024). See additional details below on the SCD-PED studies.
SCD-005	To assess the safety and efficacy of SCD in AKI or ARDS patients associated with COVID-19 infections	Mortality at day 60; dialysis dependency at day 60; ventilation at day 28	AKI or ARDS after COVID-19	N=22	None	SCD-treated patients had a reduction in 60-day mortality of 50% (11/22), vs 81% (13/16) in a contemporary control group from a concurrent prospective CKRT registry (P=0.102). The subjects who received >96 hours of SCD treatment, per protocol, had a further reduction in mortality to 31% (5/16) (P<0.012) (Yessayan LT, et al. Crit Care Explor. 2022;4(5):e0694).

During the second quarter of the enrollment period, a national calcium shortage occurred in the United States due to certain FDA-related quality manufacturing issues at major U.S. suppliers. Due to the reliance of the SCD on a narrow intra-circuit iCal range for functional efficacy and the concern that patients randomized to the SCD were not receiving effective therapy due to insufficient iCal levels, the interim analysis was performed early, after enrollment of 134 patients. Enrollment was paused on May 24, 2013, to assess the clinical impact of the calcium shortage on study endpoints. The shortage of calcium infusion solutions resulted in a tendency to minimize citrate infusion rates. Accordingly, the iCal levels within the blood circuit tended to be above the recommended range of 0.25 to 0.40 mmol/L. No significant differences were noted between the control and treatment groups in terms of baseline characteristics. Of the 134 patients in the analysis, 69 received CRRT alone and 65 received CRRT + SCD therapy. No statistically significant difference was found between the treated and control patients with a 60-day mortality of 39% (27/69) and 36% (21/59), respectively. No statistically significant difference was found between the SAEs of the control and treatment groups. Furthermore, none of the SAEs were considered ‘definitely’ device related per the principal investigator. The amount of time patients in both the control and treatment groups were maintained in the recommended iCal range (0.23 - 0.40 mmol/L), as specified in the study protocol, was substantially lower than expected. Of the 134 patients enrolled in the SCD-003 protocol at the time of the interim analysis, 19 SCD patients (CRRT + SCD) and 31 control patients (CRRT alone) were maintained in the protocol’s recommended range for greater or equal to 90% of the therapy time. The study was subsequently terminated. 13

No Table ~~statistically significant difference was found between the SAEs~~ of the control and treatment groups. The study reported 71 SAEs in the control group (40 of the 63 patients) and 80 SAEs in the SCD treatment group (45 of the 69 patients). The most frequent categories of SAEs were infections and infestations as well as cardiac, respiratory, thoracic and mediastinal disorders. Furthermore, none of the SAEs were considered “definitely” related to the SCD device per the principal investigator. Overall adverse events did not differ between the treatment and control groups in the intent to treat analysis. Contents

~~Among the per-protocol (PP) cohort of patients who achieved the recommended iCal range, the composite of death or dialysis dependency at 60 days was observed in 16% of~~ SCD-~~treated~~003: ~~subjects~~Additional ~~versus~~Details ~~58% of control subjects. The incidence of serious adverse events did not differ between the treated and control groups.~~

SCD-~~PED~~003 was a controlled, randomized, and multicenter clinical trial that was initiated in September 2011 and terminated in September 2013 under an FDA-01approved IDE. For this trial, the control group received standard CRRT with regional citrate anticoagulation (“RCA”) and 02the ~~Studies~~SCD-treated –group ~~Additional~~received ~~Details~~ up to seven days of SCD therapy. The study was sponsored by the Predecessor with the support of a third-party contract research organization.

AThe ~~multi-center,~~primary ~~prospective~~objective ~~pilot~~of the study ~~SCD-PED-01~~ was ~~undertaken~~ to ~~assess~~determine if the ~~safety~~SCD, ~~and~~when ~~efficacy~~used ofin ~~our~~conjunction ~~SCD~~with CRRT, results in ~~pediatric~~clinical ~~patients~~and ~~with~~statistical ~~AKI~~improvement ~~(weighing~~in atmortality ~~least~~rate 20based ~~kg)~~on ~~being~~all ~~treated~~causes ~~with~~through ~~continuous~~Day ~~kidney~~60. Secondary objectives included an assessment of renal replacement therapy dependency at Day 60, mortality at Day 28, the number of ventilator free days at Day 28, and the mortality of the subset of patients with ~~RCA~~severe sepsis at Day 60. ~~The~~An ~~primary~~overall ~~objective~~two-sided 0.05 level of ~~the~~significance ~~study~~at 80% power was used to ~~evaluate~~calculate ~~the~~a ~~safety~~sample size of up344 topatients, ~~seven~~assuming ~~consecutive~~a 24mortality rate of 50% for the control group and 35% for the treatment group. Adaptive design and interim analysis were planned at the mid-~~hour~~point ~~treatments~~of enrollment (i.e., 172 patients). Several exploratory biomarkers were also compared between the control and treatment groups, including urine output, serum levels of ~~our~~elastase, cytokines, and total absolute white blood cell, neutrophil and platelet counts throughout treatment. Patients receiving care in the ICU of each participating hospital were randomized to intensive care treatment for patients undergoing CRRT or CRRT + SCD. Each participating clinical site used their established RCA protocol for the CRRT + SCD circuits (treatment group) and for the CRRT only (control group). The ~~secondary~~recommended ~~objective~~calcium (iCal) level (measured post SCD) in the CRRT and SCD blood circuit was specified to ~~evaluate~~be ~~the~~between ~~efficacy~~0.25 ofand up0.40 mmol/L. Inclusion and exclusion criteria were similar to ~~seven~~the ~~consecutive~~previous 24IDE multicenter pilot clinical study except for an age range of 8-~~hour~~80 ~~SCD~~years ~~treatments~~and onbody weight of over 135 kilograms. Once the patient met all~~-cause~~ ~~mortality~~eligibility criteria, including being on CRRT for a minimum of four hours, but no longer than 24 hours, and ~~dialysis~~had signed an informed consent, the subject was randomized in a 1:1 allocation utilizing a random permuted block design into either the control or treatment group, stratified by study center and the presence of severe sepsis.

14During the second quarter of the enrollment period, a national calcium shortage occurred in the United States due to certain FDA-related quality manufacturing issues at major U.S. suppliers. At the time of the shortage a total of 134 patients had been enrolled in 21 United Stated Medical centers. Due to the reliance of the SCD on a narrow intra-circuit iCal range for functional efficacy, there was a concern that patients randomized to the SCD were not receiving effective therapy due to insufficient iCal levels. Enrollment was paused on May 24, 2013, to assess the clinical impact of the calcium shortage on study endpoints and the interim analysis was performed early using data from the 134 patients enrolled. The shortage of calcium infusion solutions resulted in a tendency to minimize citrate infusion rates. Accordingly, the iCal levels within the blood circuit tended to be above the recommended range of 0.25 to 0.40 mmol/L. No significant differences were noted between the control and treatment groups in terms of baseline characteristics. Of the 134 patients in the analysis, 69 received CRRT alone and 65 received CRRT + SCD therapy. No statistically significant difference was found between the treated and control patients with a 60-day mortality of 39% (27/69) and 36% (21/59), respectively. No statistically significant difference was found between the SAEs of the control and treatment groups. None of the SAEs were considered “definitely” device related per the principal investigator. The amount of time patients in both the control and treatment groups were maintained in the recommended iCal range (0.23 - 0.40 mmol/L), as specified in the study protocol, was substantially lower than expected. Of the 134 patients enrolled in the SCD-003 protocol at the time of the interim analysis, 19 SCD patients (CRRT + SCD) and 31 control patients (CRRT alone) were maintained in the protocol’s recommended range for greater or equal to 90% of the therapy time. The study was subsequently terminated.

~~dependency~~No atstatistically ~~Day~~significant 28difference was found between the SAEs of the control and ~~Day~~treatment 60groups. ~~This~~The study ~~was~~reported ~~sponsored~~71 bySAEs in the ~~Predecessor~~control ~~with~~group (40 of the ~~support~~63 patients) and 80 SAEs in the SCD treatment group (45 of athe ~~third-party~~69 ~~contract~~patients). ~~research~~The ~~organization~~most frequent categories of SAEs were infections and infestations as well as cardiac, respiratory, thoracic and mediastinal disorders. None of the SAEs were considered “definitely” related to the SCD device per the principal investigator. Overall adverse events did not differ between the treatment and control groups in the intent to treat analysis.

~~Sixteen~~Among ~~patients~~the per-protocol (~~eight~~PP) ~~male~~cohort ~~and~~of ~~eight~~patients ~~female)~~who ~~were~~achieved ~~enrolled in~~ the ~~study~~recommended atiCal ~~four United States pediatric medical centers~~range, ~~which~~the ~~ran~~composite ~~from~~of ~~December~~death ~~2016~~or ~~through~~dialysis ~~February~~dependency ~~2020.~~at ~~The~~60 ~~most~~days ~~common~~was ~~diagnosis~~observed ~~leading~~in to16% ~~ICU~~(03/19) ~~admission~~of ~~was~~SCD-treated ~~septic~~subjects ~~shock~~versus ~~followed~~58% ~~by,~~(18/31) inof ~~diminishing~~control ~~order,~~subjects. ~~pneumonia,~~The ~~rhabdomyolysis,~~incidence ~~pulmonary~~of ~~hypertension,~~serious ~~hemolytic~~adverse ~~uremic~~events ~~syndrome,~~did ~~encephalomyelitis,~~not ~~disseminated~~differ ~~adenoviral~~between ~~infection,~~the ~~cardiac~~treated ~~arrest, acute respiratory failure~~ and ~~acute~~control ~~liver failure~~groups.

~~Twelve~~SCD-PED-01 ~~of the 16 patients survived (75%) to hospital discharge (versus historical control of 50%)~~ and ~~none~~02 ofStudies ~~the~~– 12Additional ~~patients~~Details ~~required dialysis at 60 days (versus historical control of 15% to 20%). There were 14 SAEs that occurred in fourteen patients in the study. None of the SAEs were device related.~~

A ~~similar~~multi-center, ~~study~~prospective ~~known~~pilot asstudy SCD-PED-0201 was undertaken to assess the safety and efficacy of our SCD in pediatric patients ~~weighing~~with ~~between~~AKI 10(weighing ~~and~~at least 20 kg) being treated with continuous kidney replacement therapy with RCA. The primary objective of the study ~~enrolled~~was 6to ~~patients~~evaluate ~~(proposed~~the ~~maximum~~safety of up to 10seven ~~patients)~~consecutive 24-hour treatments of our SCD. ~~5/6~~ ~~(83%)~~The ~~patients~~secondary ~~survived~~objective was to ~~ICU~~evaluate ~~discharge~~the ~~and~~efficacy ~~all~~of ~~surviving~~up ~~patients~~to ~~were~~seven ~~dialysis~~consecutive 24-~~independent~~hour bySCD treatments on all-cause mortality and dialysis dependency at Day 28 and Day 60. This study was sponsored by the Predecessor with the support of a third-party contract research organization.

A combined pooled analysis of both the PED-01 and PED-02 studies (N=22 total) demonstrated a survival rate of ~77% at Day 60 in pediatric patients weighing at least 10 kg. This data was published in the journal Kidney Medicine in February 2024. 14

~~Chronic~~ Table ~~Applications~~of ~~in Inflammatory Disorders and Corresponding Studies at the UOM~~Contents

WeSixteen ~~are~~patients ~~evaluating~~(eight ~~the~~male ~~safety~~ and ~~efficacy~~eight offemale) ~~our~~were ~~SCD~~enrolled in ~~preliminary~~the ~~clinical~~study ~~trials~~at ~~that~~four ~~may~~United ~~lead~~States topediatric ~~applications~~medical ~~for~~centers, ~~our~~which ~~SCD~~ran infrom ~~additional~~December ~~patient~~2016 ~~populations~~through February 2020. The ~~following~~most ~~are~~common ~~examples~~diagnosis ofleading ~~our~~to ~~ongoing~~ICU ~~efforts~~admission towas ~~identify~~septic ~~additional~~shock ~~patient~~followed ~~populations~~by, ~~that~~in ~~may~~diminishing ~~benefit~~order, ~~from~~pneumonia, ~~treatment~~rhabdomyolysis, ~~with~~pulmonary ~~our~~hypertension, ~~SCD~~hemolytic uremic syndrome, encephalomyelitis, disseminated adenoviral infection, cardiac arrest, acute respiratory failure and acute liver failure.

~~Pilot~~Twelve ~~Feasibility~~of ~~Trial~~the 16 patients survived (75%) to hospital discharge (versus historical control of ~~SCD~~50%) ~~Therapy~~and none of the 12 patients required dialysis at 60 days (versus historical control of 15% to 20%). There were 14 SAEs that occurred in ~~ESRD~~fourteen ~~Patients~~patients in the study. None of the SAEs were device related.

~~The~~A ~~SCD~~similar ~~therapy~~study ~~was~~known ~~evaluated~~as inSCD-PED-02 awas ~~cohort~~undertaken ofin 15pediatric ~~end-stage~~patients ~~renal~~weighing ~~disease~~between ~~(ESRD)~~10 ~~patients~~and on20 ~~chronic hemodialysis~~kg. The ~~therapy~~study ~~promoted~~enrolled a6 ~~shift~~patients in(proposed ~~monocytes~~maximum ~~from~~of ~~a predominantly proinflammatory to a reparative anti-inflammatory phenotype for~~ up to ~~two~~10 ~~weeks~~patients). ~~Adverse~~5 of ~~events~~the ~~or serious adverse events~~ 6 (~~SAEs~~83%) ~~were~~patients ~~minimal~~survived ~~during~~to ~~SCD~~ICU ~~treatment~~discharge and ~~RCA,~~all ~~with~~surviving ~~four of the 13~~ patients ~~experiencing adverse events. None of these adverse events~~ were ~~definitively~~dialysis-independent ~~linked~~by toDay ~~SCD therapy~~60.

~~Cardiorenal~~A ~~Syndrome~~combined pooled analysis of both the PED-01 and PED-02 studies (N=22 total) demonstrated a survival rate of ~77% at Day 60 in pediatric patients weighing at least 10 kg. This data was published in the journal Kidney Medicine in February 2024.

~~Cardiorenal~~Study ~~syndrome (“CRS”) is a clinical disorder~~ in ~~which~~Cardiorenal ~~therapy~~Syndrome to relieve the congestive symptoms of chronic heart failure is limited by a decline in renal function. Up to one-third of patients with acute decompensated chronic heart failure present with this disorder; this condition is increasing in incidence with an estimated one million hospital admissions annually in the United States. Once hospitalized, these patients are treated with a high dose of intravenous diuretics to relieve persistent congestion. The use of diuretics, however, frequently results in worsening renal function, progression of heart failure and death. Immune dysregulation plays a key role in cardiorenal syndrome. Patients

~~The~~Cardiorenal syndrome (“CRS”) ~~clinical trial at the UOM~~ is a ~~safety~~clinical ~~and~~disorder ~~efficacy dose escalation study~~ in 10which ~~patients~~therapy ~~that was designed~~ to ~~evaluate~~relieve ~~whether ultrafiltration therapy in CRS, a disease with a dismal prognosis and currently ineffective therapy, with SCD therapy will improve cardiac and renal (production of urine) functions. In~~ the ~~study,~~congestive ansymptoms ~~improvement~~ of ~~cardiac~~chronic ~~function is measured by the rate of ejection fraction, which is the percentage of blood leaving the~~ heart ~~each~~failure ~~time it contracts. An improvement of renal function~~ is ~~measured~~limited by ~~serum~~a ~~creatinine~~decline ~~and~~in ~~blood urine nitrogen (two common biomarkers to assess~~ renal function~~) levels~~. InUp ~~addition,~~to aone-third ~~variety~~ of ~~other~~patients ~~biomarkers~~with ~~will~~acute ~~also~~decompensated bechronic ~~measured.~~heart ~~One~~failure ~~patient~~admitted ~~has~~into ~~been~~a ~~successfully~~hospital ~~treated with the SCD thus far~~ in ~~this study. The effect of~~ the ~~SCD~~United onStates ~~cardiac~~present ~~function was recently demonstrated in a first-in-human case report of a 71-year-old male patient~~ with ~~cardiorenal~~this ~~syndrome~~disorder ~~including severe heart failure with reduced ejection fraction~~ and ~~was~~this ~~deemed~~condition ~~ineligible~~is ~~for~~increasing ~~cardiac~~in ~~transplantation~~incidence. orOnce ~~LVAD~~hospitalized, ~~due~~these topatients ~~worsening~~are ~~renal function (WRF) and right ventricular dysfunction. The patient was~~ treated with ~~the~~a ~~SCD~~high ~~and~~dose ~~effectively bridged to LVAD and demonstrated proof-~~of~~-concept~~ ~~for~~intravenous andiuretics ~~innovative approach~~ to ~~the~~relieve ~~treatment~~persistent ofcongestion. ~~CRS~~The ~~using~~use ~~our~~of ~~device.~~diuretics, ~~These~~however, ~~initial~~frequently results ~~now~~in ~~provide~~worsening ~~important~~renal ~~feasibility~~function, ~~data~~progression ~~for a follow-on study to undertake a controlled randomized clinical trial to evaluate the clinical efficacy~~ of ~~our~~heart ~~SCD~~failure inand ~~CRS patients that have failed ultrafiltration therapy~~death. ~~Based~~Immune ondysregulation ~~this~~plays ~~data,~~a ~~our~~key ~~SCD~~role ~~recently received BDD for CRS~~ in ~~October~~cardiorenal ~~2023~~syndrome. ~~These results were recently published in~~

15We are actively enrolling patients in a clinical trial of our SCD therapy for the treatment of adult patients with acute or chronic systolic heart failure with worsening renal function due to CRS or severe right ventricular failure awaiting LVAD Implantation, an indication awarded BDD by the FDA in September 2023. This trial (NCT03836482) is a 20 subject, multi-center, open-label, feasibility study conducted in the United States. The study is designed to assess safety and a number of endpoints including mortality, the occurrence of acute myocardial infarction, or the need for continuous IV vasopressor support amongst others. Of note, SCD therapy in this study will be delivered for 4 hours a day for up to 6 consecutive days. This regimen is distinct from previous trials of our SCD therapy, all of which used continuous delivery for 24 hours a day.

~~the~~Chronic ~~journal~~Applications ~~PLoS One~~ in ~~April~~Inflammatory ~~2023~~Disorders and anCorresponding ~~additional~~Studies ~~perspective~~at ~~article was published in~~ the ~~journal European Journal of Heart Failure in February 2024.~~ UOM

~~Hepatorenal~~We ~~Syndrome~~are ~~(HRS)~~ evaluating the safety and efficacy of our SCD in preliminary clinical trials that may lead to applications for our SCD in additional patient populations. The following are examples of our ongoing efforts to identify additional patient populations that may benefit from treatment with our SCD.

~~Hepatorenal~~Pilot ~~syndrome~~Feasibility isTrial ~~characterized by an abrupt deterioration~~ of ~~kidney~~SCD ~~function,~~Therapy ~~driven by a hyperinflammatory process~~ in ~~patients~~ESRD ~~with~~Patients advanced liver cirrhosis, and is associated with an unacceptably high mortality. Without treatment, the prognosis for patients with hepatorenal syndrome is poor with most dying within weeks of the onset of renal failure. In fact, the mortality rate for patients with severe acute or chronic liver failure with four or more organ failures at 28 days is 100%. Approximately 700,000 cases of hepatorenal syndrome are reported in the U.S. annually. In 2019 the economic burden for hepatorenal syndrome hospitalization was estimated at $4.2 billion.

The ~~NCT04898010~~SCD ~~study~~therapy iswas anevaluated ~~investigator-initiated~~in ~~pilot~~a ~~study~~cohort ~~to assess the safety and efficacy~~ of ~~the~~15 ~~SCD~~end-stage inrenal ~~treating~~disease up(ESRD) ~~to 10 ICU~~ patients ~~with~~on ~~AKI~~chronic ~~and HRS Type I~~hemodialysis. The ~~study~~therapy ~~aims~~promoted toa ~~understand~~shift ~~the effect of 7 days of treatment with the SCD on white blood cells~~ in ~~the~~monocytes ~~bloodstream~~from ofa ~~patients~~predominantly ~~with~~proinflammatory ~~hepatorenal syndrome and its impact on blood circulation and kidney function. Two patients with type 1 hepatorenal syndrome have been treated~~ to ~~date~~a inreparative ~~this study. Positive clinical outcomes were seen in both cases~~ anti-inflammatory ~~one~~phenotype ~~patient~~for ~~with~~up ~~hepatorenal syndrome due~~ to ~~acute~~two ~~alcoholic~~weeks. ~~hepatitis~~Adverse ~~was~~events ~~alive~~or atserious ~~day~~adverse 90events ~~after~~(SAEs) ~~seven~~were ~~days~~minimal ofduring SCD treatment and ~~undergoing liver transplantation evaluation~~RCA, ~~and the other patient~~ with ~~hepatorenal~~four ~~syndrome due to non-alcoholic steatohepatitis or NASH had a successful liver transplantation 6 days after SCD therapy ended. This suggested a role~~ of ~~SCD immunomodulation to treat acute or chronic liver failure, regardless of~~ the ~~etiology,~~13 aspatients aexperiencing ~~bridge~~adverse ~~to evaluation or successful intervention for liver transplantation~~events. ~~Both~~None of these ~~cases~~adverse events were ~~recently~~definitively ~~published~~linked ~~in the American Society for Artificial Internal Organs Journal in August of this year (Yessayan et al., ASAIO J. 2023., doi: 10.1097/MAT.0000000000002033). This led~~ to ~~the FDA granting the~~ SCD ~~a BDD for HRS in October 2023~~therapy.

~~Myocardial~~Pilot ~~Ischemia~~Safety inTrial ~~End-Stage~~of ~~Renal~~SCD ~~Disease~~Therapy ~~Patients~~in onCardiorenal ~~Chronic~~Syndrome ~~Hemodialysis~~ Patients

AThe ~~major~~CRS ~~cause~~clinical oftrial ~~death~~(NEUTRALIZE-CRS) inis ~~patients~~a onsafety ~~chronic~~and ~~dialysis~~efficacy isdose ~~due~~escalation tostudy ~~cardiovascular~~in ~~disease.~~20 ~~Novel~~patients ~~interventions~~that ~~need~~was designed to beevaluate ~~identified~~whether CRS, a disease with a dismal prognosis and ~~tested~~currently toineffective ~~ameliorate~~therapy, ~~the~~will ~~high~~improve ~~morbidity~~cardiac and ~~mortality~~renal (production of ~~myocardial~~urine) ~~disease~~functions inafter ~~these~~SCD ~~patients~~therapy. ~~Multiple~~In ~~hemodynamic~~the ~~and~~study, ~~inflammatory~~an ~~factors~~improvement ~~contribute~~of tocardiac function is measured by the ~~elevated~~rate ~~risk~~of ejection fraction, which is the percentage of ~~cardiac~~blood ~~disease~~leaving inthe ~~chronic~~heart ~~hemodialysis~~each ~~patient~~time ~~populations~~it contracts. ~~Hemodialysis~~An ~~treatment~~improvement of renal function is ~~associated~~measured ~~with~~by ~~repetitive~~serum ~~ischemic~~creatinine ~~events,~~and orblood ~~myocardial~~urine ~~stunning,~~nitrogen ~~and~~(two iscommon ~~identified~~biomarkers ~~with~~to ~~regional~~assess ~~wall~~renal ~~motion~~function) ~~abnormalities~~levels. onIn ~~echocardiograms~~addition, a variety of other biomarkers will also be measured. ~~This~~The ~~repetitive~~effect ~~ischemic~~of ~~stress~~the ~~results~~SCD inon ~~progressive~~cardiac ~~damage~~function ~~resulting~~was recently demonstrated in ~~declines~~a first-in-human ~~left~~case ~~ventricular~~report of a 71-year-old male patient with cardiorenal syndrome including severe heart failure with reduced ejection fraction and ~~risk~~was ~~for~~deemed ~~sudden~~ineligible for cardiac ~~death~~transplantation or LVAD due to worsening renal function (WRF) and right ventricular dysfunction. ~~Both~~The ~~acute~~patient was treated with the SCD and ~~chronic~~effectively ~~inflammation~~bridged to LVAD and ~~its~~demonstrated ~~cellular~~proof-of-concept ~~immunologic~~for ~~effector,~~an innovative approach to the ~~activated~~treatment ~~monocyte,~~of ~~are~~CRS ~~central~~using our device. These initial results now provide important feasibility data for a follow-on study to undertake a controlled randomized clinical trial to evaluate the ~~accelerated~~clinical ~~cardiovascular~~efficacy ~~disease~~of our SCD in CRS patients ~~with~~that ~~chronic~~have ~~end-stage~~failed ~~renal~~ultrafiltration ~~disease~~therapy. Based on this data, our SCD recently received BDD for CRS in October 2023. These results were recently published in the journal PLOS One in April 2023 and an additional perspective article was published in the journal European Journal of Heart Failure in February 2024.

A pilot safety and efficacy study in 10 patients to evaluate the reduction in myocardial stunning events in hemodialysis patients is planned at the UOM. The primary outcome is expected to measure the change in regional wall abnormalities identified on an echocardiogram. Initial results are expected to provide important feasibility data for a follow-on study to undertake a controlled randomized clinical trial to evaluate the clinical efficacy of our SCD in myocardial stunning hemodialysis patients. 15

~~Suppliers~~ Table of Contents

WePilot ~~procure~~Safety ~~conventional~~Trial ~~components such as tubing sets, clamps, fittings, and labels from various suppliers. These components are then used in our assembly~~ of SCD ~~clinical~~Therapy ~~kits.~~Hepatorenal ~~Critical~~Syndrome ~~components are procured from suppliers that have been approved and qualified through our supplier management program. Fresenius Medical Care North America~~ (~~“FMCNA”~~HRS) ~~is the current supplier of the cartridges used in our SCD.~~ Patients

InHepatorenal ~~March~~syndrome ~~2022,~~is wecharacterized ~~entered~~by ~~into a supply agreement (the “Supply Agreement”) with~~ an ~~FMCNA~~abrupt ~~affiliate,~~deterioration ~~Fresenius~~of ~~USA~~kidney ~~Marketing~~function, ~~Inc.~~driven ~~(“FUSA”),~~by toa ~~supply~~hyperinflammatory ~~certain~~process ~~cartridges~~in atpatients anwith ~~agreed~~advanced ~~amount~~liver ~~per case for use in our SCD product~~cirrhosis, ~~including~~and inis ~~our~~associated ~~upcoming~~with ~~clinical~~an ~~trial~~unacceptably ~~and~~high ~~any additional clinical trials~~mortality. WeWithout ~~may~~treatment, ~~resell~~ the ~~cartridges~~prognosis asfor ~~part~~patients ofwith ~~the~~hepatorenal ~~SCD~~syndrome ~~system~~is ~~under~~poor ~~our~~with ~~HDE~~most ~~approval,~~dying ~~pursuant~~within toweeks anof ~~Emergency Use Authorization application as well as a future PMA-approved product. Either party may terminate~~ the ~~Supply~~onset ~~Agreement for uncured material breach or for the insolvency~~ of ~~the~~renal ~~other party~~failure. In ~~addition~~fact, ~~either party may terminate~~ the ~~Supply~~mortality ~~Agreement~~rate ~~if in the reasonable opinion of legal counsel~~ for ~~either~~patients ~~party,~~with ~~any~~severe ~~future~~acute ~~changes~~or inchronic ~~federal~~liver orfailure ~~state~~with ~~law~~four or ~~regulations~~more ~~make~~organ ~~any~~failures ~~portion~~at of28 ~~the~~days ~~Supply~~is ~~Agreement~~100%. ~~invalid~~Approximately or700,000 ~~illegal~~cases ~~and~~of ~~the~~hepatorenal ~~parties~~syndrome are ~~not~~reported ~~able~~in tothe ~~agree~~U.S. onannually. ~~mutually~~In ~~acceptable~~2019 ~~addendum to~~ the ~~Supply~~economic ~~Agreement.~~burden Wefor ~~have~~hepatorenal ~~agreed~~syndrome tohospitalization ~~indemnify~~was ~~FUSA~~estimated ~~against~~at ~~certain third-party claims~~$4.2 billion.

16The NCT04898010 study is an investigator-initiated pilot study to assess the safety and efficacy of the SCD in treating up to 10 ICU patients with AKI and HRS Type I. The study aims to understand the effect of 7 days of treatment with the SCD on white blood cells in the bloodstream of patients with hepatorenal syndrome and its impact on blood circulation and kidney function. Two patients with type 1 hepatorenal syndrome have been treated to date in this study. Positive clinical outcomes were seen in both cases - one patient with hepatorenal syndrome due to acute alcoholic hepatitis was alive at day 90 after seven days of SCD treatment and undergoing liver transplantation evaluation, and the other patient with hepatorenal syndrome due to non-alcoholic steatohepatitis or NASH had a successful liver transplantation 6 days after SCD therapy ended. This suggested a role of SCD immunomodulation to treat acute or chronic liver failure, regardless of the etiology, as a bridge to evaluation or successful intervention for liver transplantation. Both of these cases were recently published in the American Society for Artificial Internal Organs Journal in August of this year (Yessayan et al., ASAIO J. 2023., doi: 10.1097/MAT.0000000000002033). This led to the FDA granting the SCD a BDD for HRS in October 2023.

InPilot ~~December~~Safety ~~2024,~~Trial weof ~~entered~~SCD ~~into~~Therapy the Second Amendment to the initial Supply Agreement, which extended the Supply Agreement through December 31, 2027, updated a part number as well as clarified that FMCNA has 90 days to provide notice to us in ~~the~~Myocardial ~~event~~Ischemia ~~that FUSA intends to switch the fibers within the SCD as well as the first right of refusal to be the exclusive distributor of the SCD~~ in ~~the~~End-Stage ~~United~~Renal ~~States.~~Disease InPatients ~~addition~~on toChronic ~~the~~Hemodialysis ~~Supply Agreement with FUSA, we are developing a second source for both adult and pediatric cartridges, which will enable us to better manage potential supply disruptions.~~

~~Additionally,~~A ~~use~~major cause of ~~the~~death ~~SCD~~ in ~~hospital~~patients ~~settings~~on ~~requires~~chronic dialysis is due to cardiovascular disease. Novel interventions need to be identified and tested to ameliorate the ~~administration~~high morbidity and mortality of ~~RCA~~myocardial disease in these patients. Multiple hemodynamic and ~~calcium~~inflammatory ~~replacement~~factors ~~into~~contribute ~~CRRT~~to ~~circuitry~~the ~~for~~elevated ~~safe~~risk ~~and~~of ~~effective~~cardiac ~~use~~disease in chronic hemodialysis patient populations. ~~Both~~ ~~components~~Hemodialysis ~~are~~treatment ~~intravenous~~is ~~(“IV”)~~associated ~~solutions~~with repetitive ischemic events, ~~which~~or ~~are~~myocardial ~~commonly~~stunning, ~~stocked~~and byis ~~hospital~~identified ~~systems~~with regional wall motion abnormalities on echocardiograms. ~~However,~~ ~~there~~This ~~are~~repetitive ~~limited~~ischemic ~~manufacturers/suppliers~~stress ofresults ~~these~~in IVprogressive ~~solutions~~damage ~~nationwide,~~resulting ~~and~~in ~~any~~declines ~~supply~~in ~~chain~~left ~~disruptions~~ventricular ~~may~~ejection ~~have~~fraction ~~detrimental~~and ~~effects~~risk tofor ~~the~~sudden ~~utilization~~cardiac ofdeath. ~~CRRT,~~Both acute and ~~subsequently~~chronic inflammation and its cellular immunologic effector, ~~use~~the ofactivated ~~commercial~~monocyte, ~~QUELIMMUNE~~are orcentral to the ~~adult~~accelerated ~~SCD~~cardiovascular disease in ~~clinical~~patients ~~studies.~~with chronic end-stage renal disease.

~~Distribution~~A pilot safety and efficacy study in 10 patients to evaluate the reduction in myocardial stunning events in hemodialysis patients is planned at the UOM. The primary outcome is expected to measure the change in regional wall abnormalities identified on an echocardiogram. Initial results are expected to provide important feasibility data for a follow-on study to undertake a controlled randomized clinical trial to evaluate the clinical efficacy of our SCD in myocardial stunning hemodialysis patients.

The Supply Agreement contains a provision granting FUSA a right of first refusal for the first three years after regulatory approval of our SCD product candidate to distribute QUELIMMUNE and adult SCD products in the United States. If during such period, we elect to promote and sell the SCD through distributors, we will be required to provide FUSA with a right of first refusal to be our exclusive distributor of the SCD in the United States and its territories, provided that the SCD is not promoted or sold in a manner that is incompatible with any devices manufactured and/or sold by FUSA or its affiliates. Suppliers

OnWe ~~December~~procure ~~27,~~conventional ~~2022,~~components wesuch ~~entered~~as ~~into~~tubing asets, ~~license~~clamps, fittings, and ~~distribution~~labels ~~agreement~~from ~~with~~various ~~Nuwellis~~suppliers. WeThese ~~appointed~~components ~~Nuwellis~~are asthen ~~our~~used ~~exclusive~~in ~~distributor~~our ~~for~~assembly ~~the sale and distribution~~ of SCD ~~product~~clinical ~~throughout~~kits. ~~the~~Critical ~~United~~components ~~States~~are ~~once~~procured ~~we receive written authorization~~ from ~~the~~suppliers ~~FDA to market our SCD for pediatric use pursuant to our HDE application. In May 2024, we provided notice to Nuwellis~~ that ~~Nuwellis~~have ~~had~~been ~~breached~~approved ~~the Distribution Agreement~~ and ~~that~~qualified ~~the~~through ~~Distribution~~our ~~Agreement~~supplier ~~would~~management ~~terminate effective August 18, 2024~~program. ~~Nuwellis~~ ~~disputed~~Fresenius ~~the~~Medical ~~validity~~Care ofNorth ~~the~~America ~~termination~~(“FMCNA”) ~~and~~is ~~on October 20, 2024, we entered into~~ the ~~Settlement~~current ~~Agreement~~supplier ~~with Nuwellis, pursuant to which we agreed to pay Nuwellis an aggregate~~ of ~~$900,000~~the ~~payable~~cartridges used in ~~three installments through December 31, 2024. As of December 31, 2024, we fulfilled all of~~ our ~~obligations to Nuwellis and have hired sales and marketing employees focused on the commercialization of QUELIMMUNE into the U~~SCD.~~S. market.~~

~~Third~~In March 2022, we entered into a supply agreement (the “Supply Agreement”) with an FMCNA affiliate, Fresenius USA Marketing, Inc. (“FUSA”), to supply certain cartridges at an agreed amount per case for use in our SCD product, including in our upcoming clinical trial and any additional clinical trials. We may resell the cartridges as part of the SCD system under our HDE approval, pursuant to an Emergency Use Authorization application as well as a future PMA-~~Party~~approved ~~Reimbursement~~product. Either party may terminate the Supply Agreement for uncured material breach or for the insolvency of the other party. In addition, either party may terminate the Supply Agreement if in the reasonable opinion of legal counsel for either party, any future changes in federal or state law or regulations make any portion of the Supply Agreement invalid or illegal and the parties are not able to agree on mutually acceptable addendum to the Supply Agreement. We have agreed to indemnify FUSA against certain third-party claims.

We anticipate that coverage and reimbursement by Centers for Medicare and Medicaid Services CMS and private payors will be necessary for most adult patients and health care providers to pay for our treatments, particularly in the applications of continuous renal replacement therapy for dialysis access and the treatment of hyperinflammatory conditions, including AKI. Accordingly, future sales of our products will depend substantially, both domestically and abroad, on reimbursement by government authorities, private health coverage insurers and other third-party payors. Our strategy around reimbursement focuses on achieving alignment and agreement from CMS on coding and payment pathways; both are critical to influencing and achieving optimal reimbursement payment from private payor sources. Therefore, we continue to develop a comprehensive reimbursement strategy including CMS, private payors and other key stakeholders to ensure a clear and sustainable reimbursement path for all SCD product opportunities. 16

We Table are pursuing a regulatory reimbursement strategy to ensure separate Medicare payment for our SCD at an appropriate price. The regulatory strategy includes engaging CMS political and career staff directly on coverage, payment and coding followed by submission of formal applications in these areas once FDA approval is obtained. It is difficult to predict what CMS will decide with respect to coverage and reimbursement for fundamentally novel products. See “Risk Factors — Risks Related to Our Business Operations — Should our products be approved for commercialization, lack of third-party coverage and reimbursement for our devices could delay or limit their adoption.”Contents

~~Intellectual~~In ~~Property~~December 2024, we entered into the Second Amendment to the initial Supply Agreement, which extended the Supply Agreement through December 31, 2027, updated a part number as well as clarified that FMCNA has 90 days to provide notice to us in the event that FUSA intends to switch the fibers within the SCD as well as the first right of refusal to be the exclusive distributor of the SCD in the United States. In addition to the Supply Agreement with FUSA, we are developing a second source for both adult and pediatric cartridges, which will enable us to better manage potential supply disruptions.

WeAdditionally, ~~currently~~use ~~have~~of ~~multiple~~the ~~U.S.~~SCD ~~and~~in ~~foreign~~hospital ~~patents~~settings ~~and~~requires ~~patent~~the ~~applications~~administration ~~that~~of ~~protect~~RCA ~~our~~and ~~proprietary~~calcium ~~technologies.~~replacement Weinto ~~strive~~CRRT tocircuitry ~~protect~~for ~~the~~safe ~~proprietary~~and ~~technologies~~effective ~~that~~use. weBoth ~~believe~~components are ~~important~~intravenous to(“IV”) ~~our~~solutions, ~~business.~~which Weare ~~have~~commonly ~~and~~stocked ~~will~~by ~~continue~~hospital tosystems. ~~seek~~However, ~~patent~~there ~~protection~~are ~~for~~limited ~~our~~manufacturers/suppliers ~~SCD~~of ~~product~~these ~~and~~IV ~~related~~solutions ~~technologies~~nationwide, asand ~~well for~~ any ~~future~~supply ~~products.~~chain Indisruptions ~~addition~~may tohave ~~seeking~~detrimental ~~patent~~effects ~~protection, we also rely on trade secrets~~ to ~~protect~~the ~~aspects~~utilization of ~~our~~CRRT, ~~business~~and ~~that~~subsequently, ~~are~~use ~~not~~of ~~amenable~~commercial ~~to,~~QUELIMMUNE or ~~that~~the weadult doSCD ~~not~~in ~~consider~~clinical studies.

17Distribution

~~appropriate~~The ~~for,~~Supply ~~patent~~Agreement ~~protection.~~contains Wea ~~also~~provision ~~rely~~granting onFUSA ~~know-how,~~a ~~confidentiality~~right ~~agreements,~~of ~~license~~first ~~agreements~~refusal ~~and~~for ~~other~~the ~~agreements~~first tothree ~~establish~~years ~~and~~after ~~protect~~regulatory approval of our ~~proprietary~~SCD ~~rights.~~product ~~Our~~candidate ~~success~~to ~~depends~~distribute the adult SCD products in ~~large~~the ~~part~~United onStates. ~~our~~If ~~ability~~during such period, we elect to ~~protect~~promote ~~our~~and ~~proprietary~~sell ~~technology~~the SCD through distributors, ~~including~~we will be required to provide FUSA with a right of first refusal to be our exclusive distributor of the SCD ~~technologies,~~in the United States and toits ~~operate~~territories, ~~without~~provided ~~infringing~~that the ~~proprietary~~SCD ~~rights~~is ofnot ~~third~~promoted ~~parties.~~or sold in a manner that is incompatible with any devices manufactured and/or sold by FUSA or its affiliates.

~~The~~On ~~term~~December of27, ~~individual~~2022, ~~patents~~we ~~depends~~entered oninto a license and distribution agreement with Nuwellis. We appointed Nuwellis as our exclusive distributor for the ~~legal~~sale ~~term~~and distribution of SCD product throughout the ~~patents~~United inStates once we received written authorization from the ~~countries~~FDA into ~~which~~market ~~they~~our ~~are~~SCD ~~obtained~~for pediatric use pursuant to our HDE application. In ~~most~~May ~~countries~~2024, inwe ~~which~~provided wenotice ~~file,~~to ~~the~~Nuwellis ~~patent~~that ~~term~~Nuwellis ishad 20breached ~~years~~the ~~from~~Distribution Agreement and that the ~~earliest~~Distribution ~~date~~Agreement ofwould ~~filing~~terminate aeffective ~~non-provisional~~August ~~patent~~18, ~~application~~2024. InNuwellis disputed the ~~United~~validity ~~States~~of the termination and, aon ~~patent’s~~October ~~term~~20, ~~may~~2024, bewe ~~lengthened~~entered byinto ~~patent~~the ~~term~~Settlement ~~adjustment~~Agreement with Nuwellis, pursuant to which ~~compensates~~we aagreed ~~patentee~~to ~~for~~pay ~~administrative~~Nuwellis ~~delays~~an byaggregate ~~the~~of ~~U.S.~~$900,000 ~~Patent~~payable ~~and~~in ~~Trademark~~three ~~Office~~installments inthrough ~~granting~~December a31, ~~patent~~2025. ~~The~~As ~~term~~of December 31, 2025, we fulfilled all of aour ~~U.S.~~obligations ~~patent~~to ~~may~~Nuwellis beand ~~shortened,~~have ifhired asales ~~patent~~and ismarketing ~~terminally~~employees ~~disclaimed~~focused byon ~~its~~the ~~owner,~~commercialization ~~over~~of ~~another~~QUELIMMUNE ~~patent~~into the U.S. market.

WeThird-Party currently have 16 issued U.S. patents and 4 pending U.S. patent applications. We also have 18 issued foreign patents and 3 pending foreign patent applications. We have issued patents that have terms expiring from 2025 through 2034, although terminal disclaimers, patent term extension or patent term adjustment can shorten or lengthen the patent term.Reimbursement

~~The~~We ~~following~~anticipate ~~table~~that ~~summarizes~~coverage and reimbursement by Centers for Medicare and Medicaid Services ("CMS") and private payors will be necessary for most adult patients and health care providers to pay for our treatments, particularly in the ~~number~~applications of ~~our~~continuous ~~patents~~renal replacement therapy for dialysis access and ~~patent~~the ~~applications~~treatment asof hyperinflammatory conditions, including AKI. Accordingly, future sales of ~~December~~our 31products will depend substantially, ~~2024:~~both domestically and abroad, on reimbursement by government authorities, private health coverage insurers and other third-party payors. Our strategy around reimbursement focuses on achieving alignment and agreement from CMS on coding and payment pathways; both are critical to influencing and achieving optimal reimbursement payment from private payor sources. Therefore, we continue to develop a comprehensive reimbursement strategy including CMS, private payors and other key stakeholders to ensure a clear and sustainable reimbursement path for all SCD product opportunities.

	U.S. Patents	Foreign Patents	U.S. Applications	Foreign Applications
SCD Technology (Patent Families 1-5)	14	18	2	3
Other Technology (Patent Families 6-9)	2	—	2	—
Total	16	18	4	3

We are pursuing a regulatory reimbursement strategy to ensure separate Medicare payment for our SCD at an appropriate price. The regulatory strategy includes engaging CMS political and career staff directly on coverage, payment and coding followed by submission of formal applications in these areas once FDA approval is obtained. It is difficult to predict what CMS will decide with respect to coverage and reimbursement for fundamentally novel products. See “Risk Factors — Risks Related to Our Business Operations — Should our products be approved for commercialization, lack of third-party coverage and reimbursement for our devices could delay or limit their adoption.”

~~With~~Intellectual respect to our SCD technologies, we own patents and patent applications in four patent families. The patents and applications in Patent Family 1 are co-owned by us and the UOM. The patents and applications in Patent Families 2-4 are solely owned by us. The inventions disclosed in Patent Families 1-4 were developed with U.S. government funding and are subject to the obligations under the Bayh-Dole Act. Property

~~Patent~~We ~~Family~~currently 1have ~~contains~~multiple ~~nine~~ U.S. and foreign patents and ~~one~~patent ~~pending~~applications ~~U.S.~~that ~~patent~~protect ~~application~~our ~~directed~~proprietary technologies. We strive to ~~systems~~protect ~~and~~the ~~methods~~proprietary ~~for~~technologies ~~processing~~that ~~leukocytes~~we ~~and~~believe ~~for~~are ~~treating~~important ~~subjects~~to ~~with~~our ~~various~~business. ~~inflammatory~~We ~~conditions~~have ~~using~~and awill continue to seek patent protection for our SCD ~~cartridge,~~product and torelated atechnologies, ~~SCD~~as ~~cartridge~~well as for any future products. ~~These~~In ~~patents~~addition ~~will~~to ~~expire~~seeking ~~from~~patent ~~2028-2031~~protection, ~~and~~we ~~the~~also ~~pending~~rely ~~application,~~on iftrade ~~granted,~~secrets ~~will~~to ~~expire~~protect inaspects ~~2028,~~of ~~assuming~~our business that ~~the~~are ~~required~~not ~~maintenance~~amenable ~~fees~~to, ~~are~~or ~~paid.~~that Wewe ~~also~~do ~~co-own~~not ~~with~~consider ~~the~~appropriate ~~UOM~~for, ~~counterpart~~patent ~~patents~~protection. ~~granted~~We inalso ~~Canada,~~rely ~~Japan~~on ~~and~~know-how, ~~New~~confidentiality ~~Zealand~~agreements, license agreements and ~~pending~~other ~~applications~~agreements into ~~Europe~~establish and ~~Hong~~protect ~~Kong.~~our ~~These~~proprietary ~~counterpart~~rights. ~~patents,~~Our ~~and~~success ~~pending~~depends ~~applications,~~in iflarge ~~granted,~~part ~~will~~on ~~expire~~our inability ~~2028,~~to ~~assuming~~protect ~~that~~our ~~the~~proprietary ~~required~~technology, ~~maintenance~~including ~~fees~~our ~~are~~SCD ~~paid.~~technologies, ~~The~~and ~~patents~~to ~~and~~operate ~~applications~~without ininfringing ~~Patent~~the ~~Family~~proprietary 1rights ~~are~~of asthird ~~follows:~~parties.

18 17

~~Patent~~ Table ~~Family~~of 1†Contents

Jurisdiction	Status	Expiration	Subject Matter
		Date
United States	Granted	2031	Methods for processing leukocytes and methods for treating subjects having inflammatory conditions using such methods
United States	Granted	2029	Methods for treating subjects undergoing a cardiopulmonary bypass
United States	Granted	2029	Methods for treating subjects with end-stage renal disease
United States	Granted	2029	Methods for treating subjects with acute renal failure
United States	Granted	2029	Methods for treating subjects with sepsis
United States	Granted	2031	A device that processes activated leukocytes and platelets
United States	Granted	2029	Methods for treating acute lung injury and acute respiratory distress syndrome
United States	Granted	2029	Systems for treating activated platelets
United States	Granted	2028	Systems for treating activated leukocytes
United States	Pending	2028*	Systems for treating leukocytes and platelets and methods for treating subject having inflammatory conditions by processing leukocytes or platelets
Canada	Granted	2028	Systems and methods for processing leukocytes and platelets and systems for treating inflammatory conditions
Canada	Granted	2028	A device for processing activated leukocytes and platelets
Japan	Granted	2028	A device and methods for treating leukocytes
Japan	Granted	2028	A device for processing activated leukocytes
New Zealand	Granted	2028	Systems and methods for processing leukocytes and platelets and for treating inflammatory conditions
Europe	Pending	2028*	A device that processes platelets or leukocytes
Hong Kong	Pending	2028*	A device for treating an inflamatory condition

The term of individual patents depends on 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’s 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. The term of a U.S. patent may be shortened, if a patent is terminally disclaimed by its owner, over another patent.

*We ~~Expiration~~currently ~~date~~have if17 issued U.S. patents. We also have 29 issued foreign patents and 1 pending foreign patent application. isWe ~~granted~~have issued patents that have terms expiring from 2025 through 2032, although terminal disclaimers, patent term extension or patent term adjustment can shorten or lengthen the patent term.

†The ~~This~~following ~~patent~~table ~~family~~summarizes ~~was~~the ~~developed~~number ~~with~~of ~~U.S.~~our ~~federal~~patents ~~government funding~~ and ispatent ~~subject~~applications toas ~~obligations~~of ~~under~~December ~~the~~31, ~~Bayh-Dole Act.~~2025:

Pursuant to a license agreement with the UOM (as amended and restated, the “UOM License Agreement”), UOM has granted us a worldwide, royalty bearing, exclusive license to their interest in the co-owned patents and applications in Patent Family 1 in the field of medical devices for use in human therapeutics for certain technologies used in the SCD technology platform, including composition of matter and methods of use patents. In consideration for such exclusive license, during the term of the UOM License Agreement, we agreed to pay the UOM a royalty fee equal to 1% of net sales as well as a one-time milestone payment of $0.1 million upon FDA approval of the first licensed product under the license, and to reimburse patent costs. As of December 31, 2024, we have incurred less than $5 thousand in royalties owed from sales of the Pediatric SCD. Since January 2020, we have paid approximately $0.1 million to the UOM to reimburse patent costs under the license. The UOM License Agreement also imposes certain diligence obligations on us and requires us to achieve specified milestone events by a certain date. Under the UOM License Agreement, the UOM’s liability is limited and we agreed to indemnify and hold the UOM harmless in connection with the use of the licensed technology and activities related to the products created using such licensed patents and/or technology. In October 2024, the parties amended the agreement to eliminate the 10% of any milestone payments, fees, etc. in exchange for extending the 1% royalty on net sales until the later of (a) expiration of the last to expire of the patent rights or (b) the ten (10) year anniversary of the first commercial sale, unless sooner terminated as provided in another specific article of this agreement.

	U.S. Patents		Foreign Patents		U.S. Applications		Foreign Applications
SCD Technology (Patent Families 1-5)		15		29		—		1
Other Technology (Patent Families 6-9)		2		—		—		—
Total		17		29		—		1

~~The~~With ~~UOM~~respect ~~License~~to ~~Agreement~~our ~~will~~SCD ~~remain~~technologies, inwe ~~effect~~own ~~until the later of the expiration of all licensed~~ patents orand ~~the~~patent ~~ten-year~~applications ~~anniversary~~in offour ~~the~~patent ~~first commercial sale under the agreement, unless terminated early~~families. IfThe wepatents ~~materially~~and ~~breach~~applications ~~the~~in ~~terms~~Patent ofFamily ~~the~~1 ~~UOM~~are ~~License~~co-owned ~~Agreement,~~by ~~the~~us ~~UOM~~and ~~has a right to terminate~~ the ~~agreement~~UOM. InThe ~~some~~patents ~~cases,~~and weapplications ~~may~~in ~~have~~Patent anFamilies ~~opportunity~~2-4 toare ~~cure~~solely aowned ~~material~~by ~~breach~~us. ~~within~~The 30inventions ~~days~~disclosed ~~or 90 days, but~~ in ~~some~~Patent ~~cases~~Families ~~the~~1-4 ~~UOM~~were ~~may~~developed ~~terminate~~with ~~the~~U.S. ~~agreement~~government ~~immediately~~funding ~~upon~~and ~~our~~are ~~breach.~~subject Weto ~~may also terminate~~ the ~~agreement~~obligations byunder ~~giving~~ the ~~UOM 90~~Bayh-~~day~~Dole ~~advance notice provided certain conditions are met~~Act.

19Patent Family 1 contains nine U.S. patents directed to systems and methods for processing leukocytes and for treating subjects with various inflammatory conditions using a SCD cartridge, and to a SCD cartridge. These patents will expire from 2028-2031, assuming that the required maintenance fees are paid. We also co-own with the UOM counterpart patents granted in Canada, Europe, Japan and New Zealand, with the European patent having been validated in Austria, Belgium, Denmark, Finland, France, Germany, Italy, The Netherlands, Spain, Sweden, and The United Kingdom. These counterpart patents will expire in 2028, assuming that the required maintenance fees are paid. The patents and applications in Patent Family 1 are as follows:

In addition to the co-owned patents and patent applications in Family 1, we also solely own three additional patent families (Families 2-4) directed to the SCD Technology. Patent Family 2 includes two U.S. patents, and one pending U.S. patent application directed to a second generation of the SCD cartridge and methods for using our SCD cartridge to process leukocytes. The patents will expire in 2032, and the application, if granted, will expire in 2031, assuming that the required maintenance fees are paid. Counterpart patents have been granted in Australia, Canada, Europe, and Japan with the European patent having been validated in France, Germany, Italy, Spain, and the United Kingdom. These patents will expire in 2031, assuming that the required maintenance fees are paid. The patents and the application in Patent Family 2 are as follows: 18

~~Patent~~ Table ~~Family~~of 2†Contents

Jurisdiction	Status	Expiration	Subject Matter
		Date
United States	Granted	2032	Cartridge for treating leukocytes or platelets
United States	Granted	2032	Methods for processing leukocytes or platelets and for treating a subject with an inflammatory condition
United States	Pending	2031*	Methods for processing leukocytes or platelets and for treating a subject with an inflammatory condition
Australia	Granted	2031	Cartridge for treating leukocytes or platelets and methods for treating a subject with an inflammatory condition
France, Germany, Italy, Spain and the United Kingdom	Granted	2031	Cartridge for sequestering leukocytes or platelets
Canada	Granted	2031*	Cartridge for processing leukocytes or platelets
Japan	Granted	2031	Cartridge for treating leukocytes or platelets
Japan	Granted	2031	Cartridge for treating leukocytes or platelets

Patent Family 1†

* Expiration date if application is granted.


Jurisdiction	Status	Expiration	Subject Matter
		Date
United States	Granted	2031	Methods for processing leukocytes and methods for treating subjects having inflammatory conditions using such methods
United States	Granted	2029	Methods for treating subjects undergoing a cardiopulmonary bypass
United States	Granted	2029	Methods for treating subjects with end-stage renal disease
United States	Granted	2029	Methods for treating subjects with acute renal failure
United States	Granted	2029	Methods for treating subjects with sepsis
United States	Granted	2031	A device that processes activated leukocytes and platelets
United States	Granted	2029	Methods for treating acute lung injury and acute respiratory distress syndrome
United States	Granted	2029	Systems for treating activated platelets
United States	Granted	2028	Systems for treating activated leukocytes
Canada	Granted	2028	Systems and methods for processing leukocytes and platelets and systems for treating inflammatory conditions
Canada	Granted	2028	A device for processing activated leukocytes and platelets
Japan	Granted	2028	A device and methods for treating leukocytes
Japan	Granted	2028	A device for processing activated leukocytes
New Zealand	Granted	2028	Systems and methods for processing leukocytes and platelets and for treating inflammatory conditions
Austria, Belgium, Denmark, Finland, France, Germany, Italy, Netherlands, Spain, Sweden, and United Kingdom	Granted	2028	A device that processes platelets or leukocytes

† This patent family was developed with U.S. federal government funding and is subject to obligations under the Bayh-Dole Act.

Pursuant to a license agreement with the UOM (as amended and restated, the “UOM License Agreement”), UOM has granted us a worldwide, royalty bearing, exclusive license to their interest in the co-owned patents and applications in Patent Family 31 ~~includes~~in ~~one~~the Ufield of medical devices for use in human therapeutics for certain technologies used in the SCD technology platform, including composition of matter and methods of use patents.S. ~~patent~~In ~~directed~~consideration for such exclusive license, during the term of the UOM License Agreement, we agreed to ~~methods~~pay the UOM a royalty fee equal to 1% of ~~treating~~net ~~chronic~~sales ~~heart~~as ~~failure~~well ~~using~~as a ~~SCD~~one-time ~~cartridge,~~milestone ~~which~~payment ~~will~~of ~~expire~~$0.1 million upon FDA approval of the first licensed product under the license (paid in ~~2032~~2024), ~~assuming~~and ~~that~~to reimburse patent costs. As of December 31, 2025, we have incurred less than $20 thousand in royalties owed from sales of the ~~required~~QUELIMMUNE. ~~maintenance~~Since ~~fees~~January ~~are~~2020, we have paid approximately $0.1 Amillion ~~counterpart~~to the UOM to reimburse patent ~~has~~costs ~~been~~under ~~granted~~the inlicense. ~~Japan~~Under the UOM License Agreement, ~~that~~the ~~will~~UOM’s ~~expire~~liability is limited and we agreed to indemnify and hold the UOM harmless in ~~2032,~~connection ~~assuming~~with ~~that~~the use of the ~~required~~licensed ~~maintenance~~technology ~~fees~~and ~~are~~activities ~~paid.~~related ~~The~~to the products created using such licensed patents and/or ~~applications~~technology. In October 2024, the parties amended the agreement to eliminate the 10% of any milestone payments, fees, etc. in ~~Patent~~exchange ~~Family~~for 3extending ~~are~~the 1% royalty on net sales until the later of (a) expiration of the last to expire of the patent rights or (b) the ten (10) year anniversary of the first commercial sale, unless sooner terminated as ~~follows:~~provided in another specific article of this agreement.

~~Patent~~The ~~Family~~UOM 3†License Agreement will remain in effect until the later of the expiration of all licensed patents or the ten-year anniversary of the first commercial sale under the agreement, unless terminated early. If we materially breach the terms of the UOM License Agreement, the UOM has a right to terminate the agreement. In some cases, we may have an opportunity to cure a material breach within 30 days or 90 days, but in some cases the UOM may terminate the agreement immediately upon our breach. We may also terminate the agreement by giving the UOM 90-day advance notice provided certain conditions are met.

Jurisdiction	Status	ExpirationDate	Subject Matter
United States	Granted	2032	Methods for treating chronic heart failure
Japan	Granted	2032	Device for use in treating chronic heart failure

† Table ~~This~~of ~~patent family was developed with U.S. federal government funding and is subject to obligations under the Bayh-Dole Act.~~Contents

~~Patent~~In addition to the co-owned patents and patent applications in Family 1, we also solely own three additional patent families (Families 2-4) ~~includes~~directed ~~two~~to the SCD technology. Patent Family 2 includes 3 U.S. patents directed to ~~methods~~a ofsecond ~~treating~~generation ~~chronic~~of ~~heart~~the ~~failure~~SCD cartridge and ~~acute~~methods ~~decompensated~~for ~~heart failure~~ using aour SCD cartridge to process leukocytes. ~~These~~The patents will expire infrom 2031 to 2032, assuming that the required maintenance fees are paid. Counterpart patents have been granted in Australia, ~~and~~ Canada, Europe, and aJapan with the European patent ~~application~~having isbeen ~~pending~~validated in ~~Europe.~~France, ~~These~~Germany, ~~patents~~Italy, Spain, and ~~patent~~the ~~application,~~United ifKingdom. ~~granted,~~These patents will expire in ~~2032~~2031, assuming that the required maintenance fees are paid. The patents and ~~applications~~the application in Patent Family 42 are as follows:

20Patent Family 2†

Patent Family 4†


Jurisdiction	Status	Expiration	Subject Matter
		Date
United States	Granted	2032	Cartridge for treating leukocytes or platelets
United States	Granted	2032	Methods for processing leukocytes or platelets and for treating a subject with an inflammatory condition
United States	Granted	2031	Methods for processing leukocytes or platelets and for treating a subject with an inflammatory condition
Australia	Granted	2031	Cartridge for treating leukocytes or platelets and methods for treating a subject with an inflammatory condition
France, Germany, Italy, Spain and the United Kingdom	Granted	2031	Cartridge for sequestering leukocytes or platelets
Canada	Granted	2031	Cartridge for processing leukocytes or platelets
Japan	Granted	2031	Cartridge for treating leukocytes or platelets
Japan	Granted	2031	Cartridge for treating leukocytes or platelets

Jurisdiction	Status	Expiration	Subject Matter
		Date
United States	Granted	2032	Methods for increasing myocardial function in subject with acute decompensated heart failure
United States	Granted	2032	Methods for increasing myocardial function in subject with chronic heart failure
Australia	Granted	2032	Methods for increasing myocardial function in a subject with acute chronic heart failure or chronic heart failure
Australia	Granted	2032	Methods, cartridges, and systems for improving myocardial function and treating inflammation associated with acute decompensated heart failure and chronic heart failure
Canada	Granted	2032*	Devices for use in treating subjects with chronic heart failure and acute decompensated heart failure
Europe	Pending	2032*	Devices for use in treating subjects with chronic heart failure or acute decompensated heart failure

† This patent family was developed with U.S. federal government funding and is subject to obligations under the Bayh-Dole Act.

*Patent ~~Expiration~~Family ~~date~~3 ifincludes ~~application~~one isU.S. patent directed to methods of treating chronic heart failure using a SCD cartridge, which will expire in 2032, assuming that the required maintenance fees are paid. A counterpart patent has been granted in Japan, that will expire in 2032, assuming that the required maintenance fees are paid. The patents and applications in Patent Family 3 are as follows:

†Patent ~~This~~Family ~~patent family was developed with U.S. federal government funding and is subject to obligations under the Bayh-Dole Act.~~3†

With respect to our other technologies, we solely own patents and patent applications in four additional patent families (Patent Families 5-8) which are summarized as follows:


Jurisdiction	Status	Expiration Date	Subject Matter
United States	Granted	2032	Methods for treating chronic heart failure
Japan	Granted	2032	Device for use in treating chronic heart failure

~~Patent~~† ~~Family~~This 5patent family was developed with U.S. federal government funding and is subject to obligations under the Bayh-Dole Act.

Jurisdiction	Status	Expiration	Subject Matter
		Date
United States	Pending	2040*	Device and methods for reducing rejection of a transplanted organ in a recipient

*Expiration Table ~~date~~of ~~if application is granted.~~ Contents

Patent Family 64 includes two U.S. patents directed to methods of treating chronic heart failure and acute decompensated heart failure using a SCD cartridge. These patents will expire in 2032, assuming that the required maintenance fees are paid. Counterpart patents have been granted in Australia and Canada, and a patent application is pending in Europe. These patents, and patent application, if granted, will expire in 2032, assuming that the required maintenance fees are paid. The patents and applications in Patent Family 4 are as follows:

Jurisdiction	Status	Expiration	Subject Matter
		Date
PCT	Pending	2041*	Devices and methods for treating cytokine release syndrome and tumor lysis syndrome

Patent Family 4†

*Expiration date if application is granted.


Jurisdiction	Status	Expiration	Subject Matter
		Date
United States	Granted	2032	Methods for increasing myocardial function in subject with acute decompensated heart failure
United States	Granted	2032	Methods for increasing myocardial function in subject with chronic heart failure
Australia	Granted	2032	Methods for increasing myocardial function in a subject with acute chronic heart failure or chronic heart failure
Australia	Granted	2032	Methods, cartridges, and systems for improving myocardial function and treating inflammation associated with acute decompensated heart failure and chronic heart failure
Canada	Granted	2032	Devices for use in treating subjects with chronic heart failure and acute decompensated heart failure
Europe	Pending	2032*	Devices for use in treating subjects with chronic heart failure or acute decompensated heart failure

~~Patent~~* ~~Family~~Expiration 7date if application is granted.

Jurisdiction	Status	Expiration	Subject Matter
		Date
United States	Granted	2027	Extracorporeal cell-based therapeutic device and delivery system for renal cells

† This patent family was developed with U.S. federal government funding and is subject to obligations under the Bayh-Dole Act.

With respect to our other technologies, we solely own patents and patent applications in two additional patent families (Patent ~~Family~~Families 85-6) which are summarized as follows:

21Patent Family 5

Jurisdiction	Status	Expiration	Subject Matter
		Date
United States	Granted	~~2031~~2027	~~Methods~~Extracorporeal ~~for~~cell-based ~~enhanced~~therapeutic ~~propagation~~device ofand delivery system for renal cells

In addition to seeking patent protection, we also rely on trade secrets and other confidential information to protect aspects of our business that are not amenable to, or that we do not consider appropriate for, patent protection. 21

~~Competition~~ Table of Contents

~~The~~Patent ~~industry~~Family for treating inflammation is extremely competitive, and companies developing new treatment procedures face significant capital and regulatory challenges. As our SCD product is a clinical-stage device in adults and commercial stage device in pediatrics, we have the additional challenge of establishing medical industry support, which will be driven by treatment outcomes data resulting from human clinical studies and commercial usage. With QUELIMMUNE cleared by the FDA in pediatrics or any future regulatory body of another country, we may face significant competition from well-funded pharmaceutical and medical device companies. Additionally, we would likely need to establish large-scale production of our device in order to be competitive. We believe that our SCD is able to compete effectively in the market and we are not aware of any similar device that has completed regulatory approval in any country for the treatment of adults or children with acute kidney injury requiring continuous renal replacement therapy.6

In both the United States and international markets, the use of medical devices is related in part to the availability of reimbursement from third-party payors, such as government and private insurance plans. Healthcare providers that use medical devices generally rely on third-party payors to pay for all or part of the costs and fees associated with the medical procedures being performed or to compensate them for their patient care services. Therapies that present a cost-neutral to cost-beneficial impact to the health economic system are generally viewed as more favorable from a reimbursement perspective. To this end, we conducted health economic outcomes research (HEOR) to estimate the economic impact of the SCD-PED (QUELIMMUNE) within the pediatric AKI-CKRT patient population. Our analysis revealed that pediatric AKI hospitalizations involving CKRT were estimated to cost over $450,000 per event, reflecting an enormous burden to healthcare institutions. The median length of stay (“LOS”) was 31 days per hospitalization. QUELIMMUNE therapy was projected to be cost-beneficial by lowering mortality as well as reducing hospital LOS by 3 days in pediatric AKI patients requiring CKRT, with estimated savings of ~$70,000 per hospitalization. These data were presented at the American Society of Nephrology Kidney Week 2024 and at the AKI-CRRT Annual meeting in March 2025, and have been submitted to a leading kidney disease journal for publication. The manuscript is currently in peer review. However, lack of third-party coverage and reimbursement for our devices could delay or limit their adoption, and as such harm our competitive advantage in the market.


Jurisdiction	Status	Expiration	Subject Matter
		Date
United States	Granted	2031	Methods for enhanced propagation of renal cells

~~Sales~~In addition to seeking patent protection, we also rely on trade secrets and ~~Marketing~~other confidential information to protect aspects of our business that are not amenable to, or that we do not consider appropriate for, patent protection.

We use a direct model for marketing and selling QUELIMMUNE. Since obtaining FDA HDE approval for pediatrics with AKI in February 2024, we terminated a distribution agreement with a third party, built a customer-facing infrastructure to support our direct sales model and will efficiently expand our footprint as new sites are added and QUELIMMUNE utilization increases. Competition

OnThe ~~December~~industry ~~27,~~for ~~2022~~treating inflammation is extremely competitive, weand ~~entered~~companies ~~into~~developing anew ~~U.S.~~treatment ~~License~~procedures face significant capital and ~~Distribution~~regulatory ~~Agreement~~challenges. ~~with~~As ~~Nuwellis~~our ~~(the~~SCD ~~“Distribution~~product ~~Agreement”),~~is ~~for~~a ~~the~~clinical-stage ~~pediatric~~device ~~SCD. On~~in ~~December~~adults ~~29,~~and ~~2023~~commercial stage device in pediatrics, we ~~amended~~have the ~~Distribution~~additional ~~Agreement~~challenge ~~with~~of ~~Nuwellis.~~establishing Inmedical ~~May~~industry ~~2024~~support, wewhich ~~provided~~will ~~notice~~be todriven ~~Nuwellis~~by ~~that~~treatment ~~Nuwellis~~outcomes ~~had~~data ~~breached~~resulting ~~the~~from ~~Distribution~~human ~~Agreement~~clinical studies and ~~that~~commercial ~~the~~usage. ~~Distribution~~With ~~Agreement~~QUELIMMUNE ~~would~~cleared ~~terminate~~by ~~effective~~the ~~August~~FDA ~~18,~~in ~~2024.~~pediatrics ~~Nuwellis~~or ~~disputed~~any ~~the~~future ~~validity~~regulatory body of ~~the~~another ~~termination~~country, we may face significant competition from well-funded pharmaceutical and onmedical ~~October~~device ~~20,~~companies. ~~2024~~Additionally, we ~~entered~~would ~~into~~likely ~~the~~need ~~Settlement~~to ~~Agreement~~establish ~~with~~large-scale ~~Nuwellis,~~production ~~pursuant~~of toour ~~which~~device wein ~~agreed~~order to ~~pay~~be ~~Nuwellis~~competitive. anWe ~~aggregate~~believe ofthat ~~$900,000~~our ~~payable~~SCD is able to compete effectively in ~~three~~the ~~installments~~market ~~through~~and ~~December~~we ~~31,~~are ~~2024.~~not Asaware of ~~December~~any ~~31,~~similar ~~2024,~~device wethat ~~have~~has ~~fulfilled~~completed ~~all~~regulatory ~~obligations~~approval ~~under~~in any country for the ~~settlement~~treatment ~~agreement.~~of adults or children with acute kidney injury requiring continuous renal replacement therapy.

In ~~conjunction~~both ~~with~~the ~~terminating~~United ~~the~~States ~~Distribution~~and ~~Agreement~~international markets, wethe ~~have~~use ~~hired~~of ~~internal~~medical ~~sales~~devices ~~and~~is ~~marketing~~related ~~employees~~in ~~focused~~part onto the ~~initial~~availability ~~launch~~of ~~into~~reimbursement ~~the~~from ~~U.S.~~third-party ~~Pediatric~~payors, ~~Market~~such as government and private insurance plans. ~~Our~~Healthcare ~~traction~~providers ~~with~~that ~~QUELIMMUNE~~use inmedical ~~pediatric~~devices ~~hospitals~~generally ~~continues~~rely on third-party payors to ~~increase~~pay asfor weall ~~add~~or ~~new~~part ~~commercial~~of ~~accounts~~the costs and ~~work~~fees ~~through~~associated with the ~~IRB~~medical ~~process~~procedures inbeing ~~target~~performed ~~accounts~~or to compensate them for their patient care services. WeTherapies that present a cost-neutral to cost-beneficial impact to the health economic system are ~~also~~generally ~~preparing~~viewed ~~for~~as more favorable from a reimbursement perspective. To this end, we conducted health economic outcomes research (HEOR) to estimate the ~~launch~~economic impact of the ~~SCD~~QUELIMMUNE inwithin the Upediatric AKI-CKRT patient population.S. ~~adult~~Our analysis revealed that pediatric AKI ~~population~~hospitalizations involving CKRT were estimated to cost over $450,000 per event, reflecting an enormous burden to healthcare institutions. WeThe ~~are~~median ~~conducting~~length ~~comprehensive~~of ~~analyses~~stay (“LOS”) was 31 days per hospitalization. QUELIMMUNE therapy was projected to be cost-beneficial by lowering mortality as well as reducing hospital LOS by 3 days in ~~the~~pediatric ~~development~~AKI patients requiring CKRT, with estimated savings of a~$40,000 ~~U.S.~~per ~~launch~~hospitalization ~~strategy~~after six days of ~~our~~QUELIMMUNE ~~SCD~~use. ~~technology~~These ~~into~~data were presented at the ~~adult~~American Society of Nephrology Kidney Week 2024 and at the AKI-CRRT ~~population. Our~~Annual ~~plans~~meeting ~~are~~in ~~focused~~March on2025, ~~developing~~and were anpublished ~~optimal~~in ~~infrastructure~~the ~~for~~Journal anof ~~effective~~Medical ~~U.S.~~Economics, ~~commercial~~titled ~~launch~~"Projected ~~inclusive~~hospitalization cost impact of ~~commercial~~selective ~~staff~~cytpheretic ~~requirements~~device in pediatric acute kidney injury" on December 28, ~~marketing~~2025 (1): 1467-1475 (doi: 10.1080/1369998.2025.2550860). However, ~~sales~~lack of third-party coverage and reimbursement ~~strategies~~for our devices could delay or limit their adoption, and ~~refinement~~as ofsuch ~~the~~harm ~~target~~our ~~account~~competitive ~~universe~~advantage in the market.

22Sales and Marketing

~~Government~~We ~~Regulation~~use a direct model for marketing and sales of QUELIMMUNE. Since obtaining FDA HDE approval for pediatric patients with AKI in February 2024, we terminated a distribution agreement with a third party, built a customer-facing infrastructure to support our direct sales model and will efficiently expand our footprint as new customers are added and QUELIMMUNE utilization increases.

~~Our~~We ~~SCD~~have ~~product~~hired isinternal ~~subject~~sales toand ~~regulation~~marketing byemployees ~~various~~focused ~~regulatory~~on ~~bodies, primarily~~ the ~~FDA~~initial ~~and~~launch ~~comparable~~of ~~international~~QUELIMMUNE ~~regulatory~~into ~~agencies,~~the ~~as applicable~~U.S. ~~These~~Pediatric ~~agencies~~Market. ~~require~~Our ~~manufacturers~~traction ~~of medical devices to comply~~ with ~~applicable~~QUELIMMUNE ~~laws~~in ~~and~~pediatric ~~regulations~~hospitals ~~governing~~continues ~~the~~to ~~development,~~increase ~~testing,~~as ~~manufacturing,~~we ~~labeling,~~add ~~marketing,~~new ~~storage,~~commercial ~~distribution,~~accounts ~~advertising~~ and ~~promotion,~~work ~~and~~through ~~post-marketing~~the ~~surveillance~~IRB ~~reporting~~process ofin ~~medical~~target ~~devices~~accounts. ~~The~~We ~~SCD~~are ~~cartridge~~also ~~interacts~~conducting ~~with~~analyses and preparing ~~deactivates~~for the ~~patient’s~~launch ~~hyperinflammatory~~of ~~cells~~the ~~prior~~SCD totherapy ~~their~~in ~~return to~~ the ~~patient~~U.S. Asin the ~~primary~~adult ~~therapeutic~~AKI ~~mode~~population. ofOur ~~action~~plans ofare ~~our~~focused ~~SCD is attributable to the device’s impact~~ on ~~these~~developing ~~autologous~~an ~~cells~~optimal ~~and~~infrastructure ~~their timely return to patients, FDA’s Center~~ for ~~Biological~~an ~~Evaluation~~effective ~~and~~U.S. ~~Research~~commercial ~~has~~launch ~~primary~~inclusive ~~jurisdiction over the premarket development, review and approval~~ of ~~the~~commercial ~~SCD~~staff ~~as a medical device. Failure to comply with applicable~~ requirements ~~may subject a device and/or its manufacturer to a variety of administrative sanctions~~, ~~such as issuance of warning letters~~marketing, ~~import~~sales ~~detentions, mandatory safety notifications, repair/replace/refund actions, recalls;~~ and~~/or,~~ ~~civil~~reimbursement ~~monetary~~strategies ~~penalties~~ and~~/or~~ ~~judicial~~refinement ~~sanctions,~~of ~~such~~the astarget ~~product~~account ~~seizures, injunctions and criminal prosecution~~universe.

~~FDA’s Pre-market Clearance and Approval Requirements~~ 22

~~Each~~ Table medical device we seek to commercially distribute in the United States will require either a prior 510(k) clearance, unless it is exempt, a de novo request or a PMA or HDE approval from the FDA. Generally, if a new device has a predicate that is already on the market under a 510(k) clearance, the FDA will allow that new device to be marketed under a 510(k) clearance; otherwise, a de novo PMA, or HDE application (if applicable) is required. Medical devices are classified into one of three classes—Class I, Class II or Class III—depending on the degree of risk associated with each medical device and the extent of control needed to provide reasonable assurance of safety and effectiveness. Class I devices are deemed to be low risk and are subject to the general controls of the Federal Food, Drug, and Cosmetic Act (“FD&C Act”), such as provisions that relate to: adulteration; misbranding; registration and listing; notification, including repair, replacement, or refund; records and reports; and good manufacturing practices. Most Class I devices are classified as exempt from premarket notification under section 510(k) of the FD&C Act, and therefore may be commercially distributed without obtaining 510(k) clearance from the FDA. Class II devices are subject to both general controls and special controls to provide reasonable assurance of safety and effectiveness. Special controls are usually device-specific and may include performance standards, post market surveillance requirements, patient registries, special labeling requirements, premarket data requirements and guidelines. Most Class II devices require the manufacturer to submit to the FDA a premarket notification requesting permission to commercially distribute the devices. Devices deemed by the FDA to pose the greatest risk, such as life-sustaining, life-supporting or implantable devices, are classified as Class III. In addition, novel devices that have not been previously classified by the FDA or which have been deemed not substantially equivalent to a previously cleared 510(k) device are considered Class III by default, unless and until they are down-classified by the FDA (e.g., via the de novo request process). High risk devices formally classified as Class III by regulation or administrative order cannot be marketed in the U.S. unless the FDA approves the device after submission of a PMA or, if applicable, an HDE. Novel devices that are Class III by default may be eligible for down-classification through the de novo request process, if the device manufacturer can demonstrate that the device is lower risk and should therefore be classified as Class I or Class II. The FDA can also impose post-market sales, marketing, or other restrictions on devices in order to ensure that they are used in a safe and effective manner. The SCD is classified as a Class III medical device and as such is subject to PMA or HDE submission and approval.Contents

~~Premarket~~Government ~~Approval Pathway~~Regulation

AOur ~~premarket~~SCD ~~approval~~product ~~application~~is ~~must~~subject beto ~~submitted~~regulation toby various regulatory bodies, primarily the FDA ~~for~~and ~~Class~~comparable ~~III~~international regulatory agencies, as applicable. These agencies require manufacturers of medical devices ~~for~~to ~~which~~comply with applicable laws and regulations governing the ~~FDA~~development, ~~has~~testing, ~~required~~manufacturing, alabeling, ~~PMA~~marketing, storage, distribution, advertising and promotion, and post-marketing surveillance reporting of medical devices. The ~~premarket~~SCD ~~approval~~therapy ~~application~~interacts ~~process~~with isand ~~more~~deactivates ~~extensive~~the ~~than~~patient’s ~~the~~hyperinflammatory ~~510(k)~~cells ~~premarket~~prior ~~notification~~to ~~and~~their dereturn ~~novo~~to ~~request~~the ~~processes~~patient. AAs ~~PMA~~the ~~application~~primary ~~must~~therapeutic bemode ~~supported~~of byaction ~~extensive~~of ~~data,~~our ~~including~~SCD ~~but~~is ~~not~~attributable ~~limited~~ to ~~technical,~~the ~~preclinical,~~device’s ~~clinical~~impact ~~trials,~~on ~~manufacturing~~these autologous cells and ~~labeling~~their totimely ~~demonstrate~~return to ~~the~~patients, FDA’s ~~satisfaction~~Center ~~reasonable~~for ~~evidence~~Biological ofEvaluation ~~safety~~and Research has primary jurisdiction over the premarket development, review and ~~effectiveness~~approval of the SCD as a medical device. Failure to comply with applicable requirements may subject a device and/or its manufacturer to a variety of administrative sanctions, such as issuance of warning letters, import detentions, mandatory safety notifications, repair/replace/refund actions, recalls; and/or, civil monetary penalties and/or judicial sanctions, such as product seizures, injunctions and criminal prosecution.

~~After a premarket approval application is submitted, the~~ FDA’s ~~has~~Pre-market 45Clearance ~~days to determine whether the application is sufficiently complete to permit a substantive review~~ and ~~thus~~Approval whether the FDA will file the application for review. The FDA has 180 days of FDA review time to review a filed premarket approval application, although the review of an application generally occurs over a significantly longer period of time due to hold periods during which the submitting sponsor (the Company) gathers information to address FDA requests for additional information. The total review process is highly variable and can take up to several years. During this review period, the FDA may request additional information or clarification of the information already provided. Also, an advisory panel of experts from outside the FDA may be convened to review and evaluate the application and provide recommendations to the FDA as to the approvability of the device.Requirements

23Each medical device we seek to commercially distribute in the United States will require either a prior 510(k) clearance, unless it is exempt, a de novo request or a PMA or HDE approval from the FDA. Generally, if a new device has a predicate that is already on the market under a 510(k) clearance, the FDA will allow that new device to be marketed under a 510(k) clearance; otherwise, a de novo PMA or HDE application (if applicable) is required. Medical devices are classified into one of three classes—Class I, Class II or Class III—depending on the degree of risk associated with each medical device and the extent of control needed to provide reasonable assurance of safety and effectiveness. Class I devices are deemed to be low risk and are subject to the general controls of the Federal Food, Drug, and Cosmetic Act (“FD&C Act”), such as provisions that relate to: adulteration; misbranding; registration and listing; notification, including repair, replacement, or refund; records and reports; and good manufacturing practices. Most Class I devices are classified as exempt from premarket notification under section 510(k) of the FD&C Act, and therefore may be commercially distributed without obtaining 510(k) clearance from the FDA. Class II devices are subject to both general controls and special controls to provide reasonable assurance of safety and effectiveness. Special controls are usually device-specific and may include performance standards, post-market surveillance requirements, patient registries, special labeling requirements, premarket data requirements and guidelines. Most Class II devices require the manufacturer to submit to the FDA a premarket notification requesting permission to commercially distribute the devices. Devices deemed by the FDA to pose the greatest risk, such as life-sustaining, life-supporting or implantable devices, are classified as Class III. In addition, novel devices that have not been previously classified by the FDA or which have been deemed not substantially equivalent to a previously cleared 510(k) device are considered Class III by default, unless and until they are down-classified by the FDA (e.g., via the de novo request process). High risk devices formally classified as Class III by regulation or administrative order cannot be marketed in the U.S. unless the FDA approves the device after submission of a PMA or, if applicable, an HDE. Novel devices that are Class III by default may be eligible for down-classification through the de novo request process, if the device manufacturer can demonstrate that the device is lower risk and should therefore be classified as Class I or Class II. The FDA can also impose post-market sales, marketing, or other restrictions on devices in order to ensure that they are used in a safe and effective manner. The SCD is classified as a Class III medical device and as such is subject to PMA or HDE submission and approval.

~~Although~~Premarket ~~the~~Approval FDA is not bound by the advisory panel decision, the panel’s recommendations are important to the FDA’s overall decision-making process. In addition, the FDA generally conducts a preapproval inspection of the manufacturing facilities to ensure compliance with the Quality System Regulation. The agency also may inspect one or more clinical sites to ensure compliance with FDA’s regulations.Pathway

~~Upon~~A ~~completion of the~~ PMA ~~review,~~application ~~the~~must ~~FDA~~be ~~may:~~submitted ~~(i)~~to ~~approve~~ the ~~PMA~~FDA ~~that~~for ~~authorizes~~Class ~~commercial~~III ~~marketing~~devices ~~with~~for ~~specific~~which ~~prescribing~~the ~~information~~FDA ~~for~~has ~~one~~required ora ~~more~~PMA. ~~indications,~~The ~~which~~PMA ~~can~~application beprocess is more ~~limited~~extensive than ~~those~~the ~~originally sought;~~ 510(iik) ~~issue~~premarket annotification ~~approvable~~and ~~letter~~de ~~that~~novo ~~indicates~~request ~~the~~processes. ~~FDA’s~~A ~~belief that the~~ PMA isapplication ~~approvable and states what additional information the FDA requires, or the post-approval commitments that~~ must be ~~agreed~~supported toby ~~prior~~extensive todata, ~~approval;~~including ~~(iii)~~but ~~issue a~~ not ~~approvable~~limited ~~letter~~to ~~that outlines steps required for approval~~technical, ~~but which are typically more onerous than those in an approvable letter~~preclinical, ~~and may require additional~~ clinical, ~~trials~~manufacturing ~~that are often expensive~~ and ~~time~~labeling ~~consuming~~to ~~and~~demonstrate ~~can~~to ~~delay approval for months or even years; or (iv) deny~~ the ~~application. If the~~ FDA’s ~~issues~~satisfaction anreasonable ~~approvable~~evidence orof ~~not~~safety ~~approvable~~and ~~letter,~~effectiveness ~~the~~of ~~applicant has 180 days to respond, after which~~ the ~~FDA’s review clock is reset~~device.

~~Humanitarian~~After ~~Device~~a ~~Exemption~~PMA ~~Pathway~~application is submitted, the FDA has 45 days to determine whether the application is sufficiently complete to permit a substantive review and thus whether the FDA will file the application for review. The FDA has 180 days of FDA review time to review a filed PMA application, although the review of an application generally occurs over a significantly longer period of time due to hold periods during which the submitting sponsor (the Company) gathers information to address FDA requests for additional information. The total review process is highly variable and can take up to several years. During this review period, the FDA may request additional information or clarification of the information already provided. Also, an advisory panel of experts from outside the FDA may be convened to review and evaluate the application and provide recommendations to the FDA as to the approvability of the device.

In accordance with the Orphan Drug Act of 1984, a rare disease is defined as a disease or condition that affects fewer than 200,000 people in the U.S. Currently, in the U.S., only a portion of the 7,000 known rare diseases have approved treatments. By definition, rare diseases or conditions occur in a small number of patients. As a result, it has been difficult to gather enough clinical evidence to meet the FDA standard of reasonable assurance of safety and effectiveness. 23

In Table ~~order to address the challenge~~ of rare diseases in the medical device realm, Congress included a provision in the Safe Medical Devices Act of 1990 to create a new regulatory pathway for products intended for diseases or conditions that affect small (i.e., rare) populations, which is the Humanitarian Device Exemption program. Contents

AAlthough ~~Humanitarian~~the ~~Use~~FDA ~~Device~~is ~~(“HUD”)~~not isbound aby ~~medical~~the ~~device~~advisory ~~intended~~panel decision, the panel’s recommendations are important to ~~benefit~~the ~~patients~~FDA’s inoverall decision-making process. In addition, the ~~treatment~~FDA orgenerally ~~diagnosis~~conducts a preapproval inspection of athe ~~disease~~manufacturing orfacilities ~~condition~~to ~~that~~ensure ~~affects~~compliance orwith isthe ~~manifested~~Quality inSystem ~~not~~Regulation. The agency also may inspect one or more ~~than~~clinical ~~8,000~~sites ~~individuals~~to inensure ~~the~~compliance ~~U.S.~~with ~~per~~FDA’s ~~year~~regulations.

~~Once~~Upon acompletion ~~Class~~of ~~III~~the ~~medical~~PMA ~~device~~review, ~~has~~the ~~HUD~~FDA ~~designation,~~may: an(i) ~~HDE~~approve ~~application~~the PMA that authorizes commercial marketing with specific prescribing information for one or more indications, which can be ~~submitted~~more ~~per~~limited ~~Section~~than ~~520~~those originally sought; (mii) ofissue an approvable letter that indicates the ~~FD&C~~FDA’s ~~Act.~~belief Anthat ~~HDE~~the ~~application~~PMA ~~has~~is ~~most~~approvable ofand states what additional information the ~~same~~FDA ~~requirements~~requires, asor the post-approval commitments that must be agreed to prior to approval; (iii) issue a ~~PMA~~not ~~application.~~approvable ~~However~~letter that outlines steps required for approval, but which are typically more onerous than those in an ~~HDE~~approvable isletter, ~~exempt~~and ~~from~~may ~~the~~require ~~effectiveness~~additional ~~requirements~~clinical oftrials ~~Sections~~that ~~514~~are often expensive and ~~515~~time ofconsuming and can delay approval for months or even years; or (iv) deny the ~~FD&C~~application. ~~Act~~If ~~and~~the isFDA ~~subject~~issues an approvable or not approvable letter, the applicant has 180 days to ~~certain~~respond, ~~profit~~after ~~and~~which ~~use~~the ~~restrictions.~~FDA’s review clock is reset.

~~Under~~Humanitarian ~~section~~Device ~~520(m)(6)(A)(i)~~Exemption ~~of the FD&C Act, an HUD is only eligible to be sold for profit after receiving an HDE approval if the device is intended for the treatment or diagnosis of a disease or condition that either:~~ Pathway

~~occurs~~In inaccordance ~~pediatric~~with ~~patients~~the Orphan Drug Act of 1984, a rare disease is defined as a disease or condition that affects fewer than 200,000 people in the U.S. Currently, in the U.S., only a ~~pediatric~~portion ~~subpopulation~~of the 7,000 ~~and~~known ~~such~~rare ~~device~~diseases ishave ~~labeled~~approved ~~for~~treatments. ~~use~~By indefinition, ~~pediatric~~rare ~~patients~~diseases or conditions occur in a ~~pediatric~~small ~~subpopulation~~number inof ~~which~~patients. As a result, it has been difficult to gather enough clinical evidence to meet the ~~disease~~FDA orstandard ~~condition~~of ~~occurs;~~reasonable or assurance of safety and effectiveness.

~~occurs~~In inorder ~~adult~~to ~~patients~~address ~~and~~the ~~does~~challenge ~~not~~of ~~occur~~rare diseases in ~~pediatric~~the ~~patients~~medical ordevice ~~occurs~~realm, inCongress ~~pediatric~~included ~~patients~~a provision in ~~such~~the ~~numbers~~Safe ~~that~~Medical ~~the~~Devices ~~development~~Act of ~~the~~1990 ~~device~~to create a new regulatory pathway for ~~such~~products ~~patients~~intended isfor ~~impossible~~diseases or conditions that affect small (i.e., ~~highly~~rare) ~~impracticable~~populations, orwhich ~~unsafe~~is the Humanitarian Device Exemption program.

~~HDE~~A ~~applicants~~Humanitarian ~~whose~~Use ~~devices~~Device ~~meet one of the eligibility criteria above and wish to sell their~~ (“HUD”) ~~for~~is ~~profit~~a ~~should~~medical ~~provide~~device ~~adequate~~intended ~~supporting documentation~~ to ~~FDA~~benefit patients in the ~~original~~treatment ~~HDE~~or ~~application.~~diagnosis ~~HDE~~of ~~holders~~a ~~who~~disease ~~wish~~or tocondition ~~sell~~that ~~their~~affects ~~devices~~or ~~for~~is ~~profit~~manifested ~~and~~in ~~who did~~ not ~~submit~~more ~~the~~than ~~request~~8,000 individuals in the ~~original~~U.S. ~~HDE~~per ~~application may submit a supplement and provide adequate supporting documentation to demonstrate that the HUD meets the eligibility criteria~~year.

~~FDA~~Once ~~approval~~a ofClass anIII ~~HDE~~medical ~~application is predicated on evidence that the~~ device ~~will~~has ~~not~~HUD ~~expose~~designation, ~~patients to~~ an ~~unreasonable~~HDE orapplication ~~significant~~can ~~risk~~be ofsubmitted illness or injury and the probable benefit to health from use of the device outweighs the risk of injury or illness from its use, taking into account the probable risks and benefits of currently available devices or alternative forms of treatment (per Section 520(m)~~(2)(C)~~ of the FD&C Act ~~and 21 CFR 814~~.~~104(b)(3)).~~ InAn ~~addition,~~HDE ~~FDA~~application ~~must~~has ~~determine~~most ~~that~~of the ~~device~~same ~~would~~requirements ~~not~~as ~~be available to~~ a ~~person~~PMA ~~with~~application. ~~the~~However, ~~disease~~an orHDE ~~condition~~is inexempt ~~question~~from ~~without~~ the ~~HDE~~effectiveness ~~application~~requirements ~~approval~~of ~~and~~Sections ~~that~~514 ~~there~~and is515 noof ~~comparable~~the ~~device,~~FD&C ~~other~~Act ~~than~~and ~~another~~is ~~device~~subject ~~under an HDE or IDE, available~~ to ~~treat~~certain orprofit ~~diagnose~~and ~~the~~use ~~disease or condition~~restrictions.

~~HDE~~Under ~~amendments,~~section ~~supplements,~~520(m)(6)(A)(i) ~~and~~of ~~reports~~the ~~are~~FD&C ~~generally~~Act, ~~subject~~an toHUD ~~similar~~is ~~requirements~~only aseligible ~~those~~to ~~for~~be ~~PMAs,~~sold ~~and~~for inprofit ~~fact~~after ~~the~~receiving ~~requirements~~an ~~for~~HDE ~~each~~approval ofif ~~these~~the ~~types~~device ofis ~~HDE~~intended ~~submissions~~for ~~refers~~the ~~back~~treatment toor ~~the~~diagnosis ~~regulatory~~of ~~requirements~~a ~~for~~disease ~~its~~or ~~PMA~~condition ~~counterpart.~~that either:

24• occurs in pediatric patients or in a pediatric subpopulation, and such device is labeled for use in pediatric patients or in a pediatric subpopulation in which the disease or condition occurs; or

~~FDA’s~~• ~~decision~~occurs toin ~~“file”~~adult orpatients ~~“not file” an HDE application will be made within 30 calendar days from the date the HDE application was received. Overall, an HDE must be reviewed~~ and adoes ~~final~~not ~~determination~~occur ~~made~~in bypediatric ~~FDA~~patients ~~within~~or 75occurs ~~days~~in ~~from~~pediatric ~~the~~patients ~~date~~in ofsuch ~~the~~numbers ~~application~~that ~~being filed; however,~~ the ~~review~~development of the ~~application~~device ~~may~~for ~~occur~~such ~~over~~patients ais ~~significantly~~impossible, ~~longer~~highly ~~period~~impracticable, ofor ~~time due to hold periods during which the submitting sponsor (the company) gathers information to address FDA requests for additional information~~unsafe.

~~Upon completion of the~~ HDE ~~review,~~applicants ~~FDA~~whose ~~may:~~devices ~~(i)~~meet ~~issue~~one ~~an Approval Order, which authorizes commercial distribution in accordance with any prescribed conditions~~ of ~~approval; (ii) issue an Approvable Letter that indicates FDA’s belief that~~ the ~~HDE~~eligibility iscriteria ~~approvable~~above and ~~states~~wish ~~what~~to ~~additional~~sell ~~information~~their ~~FDA~~HUD ~~requires~~for ~~(generally~~profit ~~resolution~~should ofprovide ~~minor~~adequate ~~deficiencies~~supporting ordocumentation ~~completion~~to ~~of an~~ FDA ~~inspection);~~in ~~(iii) issue a Major Deficiency Letter to inform~~ the ~~applicant~~original ~~that the~~ HDE application. ~~lacks~~HDE ~~significant~~holders ~~information~~who ~~necessary~~wish ~~for FDA~~ to ~~complete~~sell ~~the~~their ~~review~~devices ~~and that the application must be amended to provide the necessary information (e.g., additional clinical experience, additional non-clinical data, scientific rationale~~ for ~~data~~profit ~~already provided, or new validation data~~ and ~~analyses);~~who ~~(iv)~~did ~~issue a Not Approvable Letter which indicates that FDA does~~ not ~~believe~~submit ~~that~~ the ~~application~~request ~~can~~in bethe ~~approved~~original ~~‘as-is’~~HDE ~~because of significant deficiencies. The letter will, where practical, identify measures to place the~~ application inmay ansubmit ~~approvable form. These measures are typically more onerous than those in~~ a ~~Major~~supplement ~~Deficiency Letter or an Approvable Letter,~~ and ~~may~~provide ~~require~~adequate ~~additional~~supporting ~~clinical~~documentation ~~trials~~to demonstrate that ~~are~~the ~~often~~HUD ~~expensive~~meets ~~and time consuming and can delay approval for months or even years; or (v) deny~~ the ~~application~~eligibility criteria.

If FDA ~~issues~~approval of an ~~Approvable~~HDE ~~Letter,~~application ~~Major~~is ~~Deficiency~~predicated ~~Letter,~~on evidence that the device will not expose patients to an unreasonable or ~~Not~~significant ~~Approvable~~risk ~~letter,~~of illness or injury and the ~~review~~probable ~~clock~~benefit isto ~~stopped~~health from use of the device outweighs the risk of injury or illness from its use, taking into account the probable risks and benefits of currently available devices or alternative forms of treatment (per Section 520(m)(2)(C) of the ~~application~~FD&C isAct ~~placed~~and on21 ~~hold~~CFR 814.104(b)(3)). ~~Once~~In addition, FDA must determine that the ~~applicant~~device ~~submits~~would not be available to a ~~response,~~person with the ~~review~~disease ~~clock~~or condition in question without the HDE application approval and that there is ~~restarted~~no ~~with~~comparable adevice, ~~new~~other ~~75-day~~than ~~FDA~~another ~~response~~device ~~timeframe~~under an HDE or IDE, available to treat or diagnose the disease or condition.

~~Once an~~ HDE ~~application~~amendments, ~~is approved~~supplements, ~~the~~and ~~HUD~~reports ~~may~~are begenerally ~~marketed.~~subject ~~The~~to ~~HDE~~similar ~~holder~~requirements isas ~~responsible~~those for ~~ensuring~~PMAs, ~~that~~and ain ~~HUD~~fact ~~under~~the anrequirements ~~approved~~for ~~HDE~~each isof ~~administered~~these ~~only~~types inof ~~facilities~~HDE ~~having~~submissions ~~IRB~~refers orback ~~appropriate~~to ~~local~~the ~~committee~~regulatory ~~oversight~~requirements infor ~~accordance~~its ~~with~~PMA counterpart. FDA’s ~~regulations~~decision ~~governing~~to ~~IRBs.~~“file” ~~Approval~~or by“not file” an ~~IRB~~HDE orapplication anwill ~~appropriate~~be ~~local~~made ~~committee~~within is30 ~~required~~calendar ~~before~~days afrom ~~HUD~~the ~~under~~date anthe ~~approved~~HDE application was received. Overall, an HDE ~~can~~must be ~~used~~reviewed atand a ~~facility~~final ~~for~~determination ~~clinical~~made ~~care~~by ~~(with~~FDA within 75 days from the ~~exception~~date of ~~emergency~~the ~~use~~application being filed; however, the review of the application may occur over a significantly longer period of time due to hold periods during which the submitting sponsor (the company) gathers information to address FDA requests for additional information.

The number of HDE devices that may be sold for profit is limited to a quantity known as the Annual Distribution Number (“ADN”). If the FDA determines that an HDE holder is eligible to sell the device for profit, the FDA will determine the ADN and notify the HDE holder. 24

~~The~~ Table ~~ADN is calculated by taking the number~~ of devices reasonably necessary to treat or diagnose an individual per year and multiplying it by 8000. For example, if the typical course of treatment using an HDE device, in accordance with its intended use, requires the use of seven devices per patient per year, then the ADN for that HDE device would be 56,000 (i.e., 7 x 8000).Contents

IfUpon completion of the ~~number~~HDE ofreview, ~~devices~~FDA ~~distributed~~may: (i) issue an Approval Order, which authorizes commercial distribution in accordance with any prescribed conditions of approval; (ii) issue an Approvable Letter that indicates FDA’s belief that the HDE is approvable and states what additional information FDA requires (generally resolution of minor deficiencies or completion of an FDA inspection); (iii) issue a ~~year~~Major ~~exceeds~~Deficiency Letter to inform the ~~ADN~~applicant that the HDE application lacks significant information necessary for FDA to complete the review and that the application must be amended to provide the necessary information (e.g., additional clinical experience, additional non-clinical data, scientific rationale for data already provided, or new validation data and analyses); (iv) issue a Not Approvable Letter which indicates that FDA does not believe that the ~~sponsor~~application can ~~continue~~be approved ‘as-is’ because of significant deficiencies. The letter will, where practical, identify measures to ~~sell~~place the ~~device~~application ~~but~~in ~~cannot~~an ~~earn~~approvable form. These measures are typically more onerous than those in a ~~profit~~Major Deficiency Letter or an Approvable Letter, and may require additional clinical trials that are often expensive and time consuming and can delay approval for ~~the~~months ~~remainder~~or ofeven years; or (v) deny the ~~year~~application.

~~The~~If ~~SCD-PED~~FDA ~~(brand~~issues ~~name~~an ~~QUELIMMUNE)~~Approvable isLetter, ~~eligible~~Major toDeficiency ~~sell~~Letter, ~~for~~or ~~profit~~Not asApprovable ~~per~~letter, the ~~Final~~review ~~Approval~~clock ~~Order~~is ~~issued~~stopped, toand usthe application is placed on ~~February~~hold. 21Once the applicant submits a response, ~~2024.~~the review clock is restarted with a new 75-day FDA response timeframe.

~~Clinical~~Once ~~Trials~~an HDE application is approved, the HUD may be marketed. The HDE holder is responsible for ensuring that a HUD under an approved HDE is administered only in facilities having IRB or appropriate local committee oversight in accordance with FDA’s regulations governing IRBs. Approval by an IRB or an appropriate local committee is required before a HUD under an approved HDE can be used at a facility for clinical care (with the exception of emergency use).

~~Clinical~~The ~~trials~~number ~~are~~of ~~almost~~HDE ~~always required to support premarket approval and are sometimes required for 510(k) clearance. In the U.S., for significant risk~~ devices, ~~these~~that ~~trials~~may ~~require~~be ~~submission~~sold ~~of an application~~ for anprofit ~~IDE to the FDA. The IDE application must be supported by appropriate data, such as animal and laboratory testing results, showing it~~ is ~~safe~~limited to ~~test the device in humans and that the testing protocol is scientifically sound. The clinical protocol under an IDE must be approved in advance by the FDA for~~ a ~~specific~~quantity ~~number~~known ofas ~~patients at specified study sites. During~~ the ~~trial,~~Annual ~~the~~Distribution ~~sponsor~~Number must comply with various FDA requirements and regulations. For example, the investigators must obtain patient informed consent, follow the investigational plan, control the disposition of investigational devices and comply with all reporting and recordkeeping requirements. Clinical trials for significant risk devices may not begin until the IDE application is approved by the FDA and the appropriate institutional review boards (“~~IRBs~~ADN”). atIf the ~~clinical~~FDA ~~trial~~determines ~~sites.~~that ~~An IRB is~~ an ~~appropriately~~HDE ~~constituted~~holder ~~group~~is ~~that~~eligible ~~has been formally designated~~ to ~~review~~sell ~~and monitor medical research involving subjects and which has~~ the ~~authority~~device tofor ~~approve~~profit, ~~require~~the ~~modifications~~FDA ~~in,~~will ordetermine ~~disapprove research to protect~~ the ~~rights,~~ADN ~~safety~~ and ~~welfare~~notify ~~of human research subjects. The FDA and/or~~ the ~~IRB~~HDE ~~at each site at which a clinical trial is being performed may withdraw approval of a clinical trial at any time for~~ holder.

25The ADN is calculated by taking the number of devices reasonably necessary to treat or diagnose an individual per year and multiplying it by 8,000. For example, if the typical course of treatment using an HDE device, in accordance with its intended use, requires the use of seven devices per patient per year, then the ADN for that HDE device would be 56,000 (i.e., 7 x 8,000).

~~various~~If ~~reasons, including a belief that~~ the ~~risks~~number toof ~~study~~devices ~~subjects~~distributed ~~outweigh~~in ~~the benefits or~~ a ~~failure~~year toexceeds ~~comply~~the ~~with FDA or IRB requirements. Even if a trial is completed~~ADN, the ~~results~~sponsor ofcan ~~clinical~~continue ~~testing~~to ~~may~~sell ~~not demonstrate~~ the ~~safety and effectiveness of the~~ device, ~~may~~but becannot ~~equivocal~~earn ora ~~may~~profit ~~otherwise~~for ~~not~~the beremainder ~~sufficient to obtain approval or clearance~~ of the ~~product~~year.

~~Ongoing~~We ~~Regulation~~received bythe Final Approval Order on February 21, 2024, to sell QUELIMMUNE, the ~~FDA~~SCD therapy, for profit, to treat critically ill pediatric patients with life-threatening AKI.

~~Even~~Clinical ~~after a device receives clearance or approval and is placed on the market, numerous regulatory requirements may apply. These include:~~Trials

~~Upkeep~~Clinical trials are almost always required to support PMA and are sometimes required for 510(k) clearance. In the U.S., for significant risk devices, these trials require submission of ~~establishment~~an ~~registration~~application for an IDE to the FDA. The IDE application must be supported by appropriate data, such as animal and laboratory testing results, showing it is safe to test the device ~~listing;~~in humans and that the testing protocol is scientifically sound. The clinical protocol under an IDE must be approved in advance by the FDA for a specific number of patients at specified study sites. During the trial, the sponsor must comply with various FDA requirements and regulations. For example, the investigators must obtain patient informed consent, follow the investigational plan, control the disposition of investigational devices and comply with all reporting and recordkeeping requirements. Clinical trials for significant risk devices may not begin until the IDE application is approved by the FDA and the appropriate institutional review boards (“IRBs”) at the clinical trial sites. An IRB is an appropriately constituted group that has been formally designated to review and monitor medical research involving subjects and which has the authority to approve, require modifications in, or disapprove research to protect the rights, safety and welfare of human research subjects. The FDA and/or the IRB at each site at which a clinical trial is being performed may withdraw approval of a clinical trial at any time for various reasons, including a belief that the risks to study subjects outweigh the benefits or a failure to comply with FDA or IRB requirements. Even if a trial is completed, the results of clinical testing may not demonstrate the safety and effectiveness of the device, may be equivocal or may otherwise not be sufficient to obtain approval or clearance of the product.

Adherence to quality system regulations, which requires manufacturers, including third-party manufacturers, to follow stringent design, testing, control, documentation and other quality assurance procedures during all aspects of the manufacturing process; 25

~~Adherence~~ Table ~~to labeling regulations and the FDA prohibitions against the promotion~~ of ~~products for uncleared, unapproved or “off-label” uses and other requirements related to promotional activities;~~Contents

~~Adherence~~Ongoing toRegulation medical device reporting regulations, which require that manufacturers report to the FDA if their device may have caused or contributed to a death or serious injury, or if their device malfunctioned and the device or a similar device marketed by the ~~manufacturer would be likely to cause or contribute to a death or serious injury if the malfunction were to recur; and~~FDA

~~Adherence~~Even toafter ~~corrections and removal reporting regulations, which require that manufacturers report to the FDA field corrections or removals if undertaken to reduce~~ a ~~risk~~device toreceives ~~health~~clearance ~~posed by a device~~ or toapproval ~~remedy~~and ais ~~violation~~placed ofon the ~~FD&C~~market, ~~Act~~numerous ~~that~~regulatory requirements may ~~present a risk to health~~apply. These include:

~~Some~~• ~~changes~~Upkeep toof anestablishment ~~approved~~registration ~~PMA or HDE device, including changes in indications, labeling or manufacturing processes or facilities, require submission~~ and FDA approval of a new PMA/HDE or PMA/HDE supplement, as appropriate, before the change can be implemented. Supplements to a PMA or HDE often require the submission of the same type of information required for an original PMA or HDE, except that the supplement is generally limited to that information needed to support the proposed change from the device covered by the original PMA or HDE. The FDA uses the same procedures and actions in reviewing PMA or HDE supplements as it does in reviewing original PMAs and HDEs. PMA supplements also require the submission of a user fee, which varies depending on the type of supplement.listing;

~~Failure~~• byAdherence usto orquality bysystem ~~our~~regulations, ~~suppliers~~which torequires ~~comply~~manufacturers, ~~with~~including ~~applicable~~third-party ~~regulatory~~manufacturers, ~~requirements~~to ~~can~~follow ~~result~~stringent indesign, ~~enforcement~~testing, ~~action~~control, bydocumentation ~~the~~and ~~FDA~~other orquality ~~state~~assurance ~~authorities,~~procedures ~~which~~during ~~may~~all ~~include~~aspects ~~any~~ of the ~~following~~manufacturing ~~sanctions:~~process;

~~warning~~• orAdherence ~~untitled~~to ~~letters,~~labeling ~~fines,~~regulations ~~injunctions~~and the FDA prohibitions against the promotion of products for uncleared, ~~consent~~unapproved ~~decrees~~or “off-label” uses and ~~civil~~other ~~penalties~~requirements related to promotional activities;

~~customer~~• ~~notifications~~Adherence to medical device reporting regulations, ~~voluntary~~which require that manufacturers report to the FDA if their device may have caused or ~~mandatory~~contributed ~~recall~~to a death or ~~seizure~~serious ofinjury, ~~our~~or ~~products~~if their device malfunctioned and the device or a similar device marketed by the manufacturer would be likely to cause or contribute to a death or serious injury if the malfunction were to recur; and

~~operating~~• ~~restrictions~~Adherence to corrections and removal reporting regulations, ~~partial~~which ~~suspension~~require that manufacturers report to the FDA field corrections or ~~total~~removals ~~shutdown~~if undertaken to reduce a risk to health posed by a device or to remedy a violation of ~~production;~~the FD&C Act that may present a risk to health.

~~delay~~Some changes to an approved PMA or HDE device, including changes in ~~processing~~indications, ~~submissions~~labeling or ~~applications~~manufacturing ~~for~~processes or facilities, require submission and FDA approval of a new ~~products~~PMA/HDE or ~~modifications~~PMA/HDE supplement, as appropriate, before the change can be implemented. Supplements to ~~existing~~a ~~products;~~PMA or HDE often require the submission of the same type of information required for an original PMA or HDE, except that the supplement is generally limited to that information needed to support the proposed change from the device covered by the original PMA or HDE. The FDA uses the same procedures and actions in reviewing PMA or HDE supplements as it does in reviewing original PMAs and HDEs. PMA supplements also require the submission of a user fee, which varies depending on the type of supplement.

~~withdrawing~~Failure ~~approvals~~by ~~that~~us ~~have~~or ~~already~~by ~~been~~our ~~granted;~~suppliers ~~and~~to comply with applicable regulatory requirements can result in enforcement action by the FDA or state authorities, which may include any of the following sanctions:

~~criminal~~• ~~prosecution.~~warning or untitled letters, fines, injunctions, consent decrees and civil penalties;

In• ~~addition,~~customer ~~the FDA imposes requirements on labeling and promotion~~notifications, ~~including~~voluntary ~~requirements~~or ~~that~~mandatory ~~all~~recall ~~statements~~or beseizure truthful, accurate, not misleading, adequately substantiated, and fairly balanced and prohibits an approved device from being marketed for off-label use. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of ~~off-label~~our ~~uses, and a company that is found to have improperly promoted off-label uses may be subject to significant liability, including substantial monetary penalties and criminal prosecution.~~products;

~~Newly~~• ~~discovered~~operating ~~or developed safety or effectiveness data may require changes to a product’s labeling~~restrictions, ~~including~~partial ~~the~~suspension addition of new warnings and contraindications, and also may require the implementation of other risk management measures. Also, new government requirements, including those resulting from new legislation, may be established, or ~~the~~total ~~FDA’s~~shutdown ~~policies may change, which could delay or prevent regulatory clearance or approval~~ of ~~our products under development.~~production;

26• delay in processing submissions or applications for new products or modifications to existing products;

~~Healthcare~~• ~~Regulation~~withdrawing approvals that have already been granted; and

In• ~~addition~~criminal to the FDA’s restrictions on marketing of pharmaceutical products and medical devices, the United States healthcare laws and regulations that may affect our ability to operate include: the federal fraud and abuse laws, including the federal anti-kickback and false claims laws, federal data privacy and security laws, and federal transparency laws related to payments and/or other transfers of value made to physicians and other healthcare professionals and teaching hospitalsprosecution. Many states have similar laws and regulations that may differ from each other and federal law in significant ways, thus complicating compliance efforts. For example, states have anti-kickback and false claims laws that may be broader in scope than analogous federal laws and may apply regardless of payer. In addition, state data privacy laws that protect the security of health information may differ from each other and may not be preempted by federal law. Moreover, several states have enacted legislation requiring pharmaceutical manufacturers to, among other things, establish marketing compliance programs, file periodic reports with the state, make periodic public disclosures on sales and marketing activities, report information related to drug pricing, require the registration of sales representatives, and prohibit certain other sales and marketing practices. These laws may adversely affect our sales, marketing, and other activities with respect to any product candidate for which we receive approval to market in the United States by imposing administrative and compliance burdens on us.

~~Because~~In ofaddition, the ~~breadth~~FDA ofimposes ~~these~~requirements ~~laws~~on ~~and~~labeling ~~the narrowness of available statutory exceptions~~ and ~~regulatory safe harbors~~promotion, itincluding isrequirements ~~possible~~ that ~~some~~all ofstatements ~~our~~be ~~business~~truthful, ~~activities~~accurate, ~~particularly~~not ~~any~~misleading, ~~sales~~adequately substantiated, and ~~marketing~~fairly ~~activities~~balanced ~~after~~and aprohibits ~~product~~an ~~candidate has been~~ approved ~~for~~device ~~marketing~~from inbeing ~~the~~marketed ~~United~~for ~~States,~~off-label ~~could~~use. beThe ~~subject~~FDA ~~to legal challenge~~ and ~~enforcement~~other ~~actions.~~agencies Ifactively ~~our~~enforce ~~operations~~the ~~are~~laws ~~found~~and toregulations beprohibiting inthe ~~violation~~promotion of ~~any~~off-label ofuses, ~~the federal~~ and ~~state~~a ~~laws~~company ~~described~~that ~~above~~is orfound ~~any~~to ~~other~~have ~~governmental~~improperly ~~regulations~~promoted ~~that~~off-label ~~apply~~uses ~~to us, we~~ may be subject to significant ~~civil~~liability, ~~criminal,~~including ~~and~~substantial ~~administrative~~monetary penalties, ~~including, without limitation, damages, fines, imprisonment, exclusion from participation in government healthcare programs, additional reporting obligations~~ and ~~oversight~~criminal 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 operationsprosecution.

~~From~~Newly ~~time~~discovered toor ~~time,~~developed ~~legislation~~safety isor ~~drafted~~effectiveness ~~and~~data ~~introduced~~may inrequire ~~Congress~~changes ~~that~~to ~~could~~a ~~significantly~~product’s ~~change~~labeling, ~~the~~including ~~statutory provisions governing~~ the ~~regulatory~~addition ~~approval, manufacture and marketing~~ of ~~regulated~~new ~~products~~warnings orand ~~the reimbursement thereof. For example~~contraindications, ~~in the U.S., the Patient Protection~~ and ~~Affordable~~also ~~Care~~may ~~Act,~~require ~~as amended by~~ the ~~Health~~implementation ~~Care and Education Reconciliation Act~~ of ~~2010, among~~ other ~~things,~~risk ~~reduced~~management ~~and/or limited Medicare reimbursement to certain providers and imposed an annual excise tax of 2~~measures.3% onAlso, ~~any~~new ~~entity~~government ~~that manufactures or imports medical devices offered for sale in the United States~~requirements, ~~with~~including ~~limited~~those ~~exceptions.~~resulting ~~The~~from ~~Further~~new ~~Consolidated Appropriations Act~~legislation, ~~signed~~may ~~into~~be ~~law on December 20~~established, ~~2019,~~or ~~has now permanently repealed~~ the ~~medical device excise tax. In addition, the Budget Control Act of 2011, as amended by subsequent legislation, further reduces Medicare~~FDA’s ~~payments~~policies ~~to providers by two percent through fiscal year 2027. These reductions~~ may ~~reduce providers’ revenues or profits~~change, which could ~~affect~~delay ~~their~~or ~~ability~~prevent toregulatory ~~purchase~~clearance ~~new~~or ~~technologies.~~approval ~~Furthermore,~~of the healthcare industry in the United States has experienced a trend toward cost containment as government and private insurers seek to control healthcare costs by imposing lower payment rates and negotiating reduced contract rates with service providers. Legislation could be adopted in the future that limits payments for our products ~~from~~under ~~governmental payors~~development.

~~Coverage and Reimbursement~~ 26

In Table ~~both the United States and international markets, the use~~ of medical devices is dependent in part on the availability of reimbursement from third-party payors, such as government and private insurance plans. Healthcare providers that use medical devices generally rely on third-party payors to pay for all or part of the costs and fees associated with the medical procedures being performed or to compensate them for their patient care services. Should our products under development be approved for commercialization by the FDA, any such products may not be considered cost-effective, reimbursement may not be available in the United States or other countries, if approved, and reimbursement may not be sufficient to allow sales of our future products on a profitable basis. The coverage decisions of third-party payors will be significantly influenced by the assessment of our future products by health technology assessment bodies. If approved for use in the United States, we expect that any products that we develop will be purchased primarily by medical institutions, which may in turn bill various third-party payors for the health care services provided to patients at their facility. Payors may include CMS, which administers the Medicare program and works in partnership with state governments to administer Medicaid, other government programs, and private insurance plans. The process involved in applying for coverage and reimbursement from CMS is lengthy and expensive. Further, Medicare coverage is based on our ability to demonstrate that the treatment is “reasonable and necessary” for Medicare beneficiaries. Even if products utilizing our technology receive FDA and other regulatory clearance or approval, they may not be granted coverage and reimbursement by any payor, including by CMS. Many private payors use coverage decisions and payment amounts determined Contents

27Healthcare Regulation

byIn ~~CMS~~addition asto ~~guidelines~~the FDA’s restrictions on marketing of pharmaceutical products and medical devices, the United States healthcare laws and regulations that may affect our ability to operate include: the federal fraud and abuse laws, including the federal anti-kickback and false claims laws, federal data privacy and security laws, and federal transparency laws related to payments and/or other transfers of value made to physicians and other healthcare professionals and teaching hospitals. Many states have similar laws and regulations that may differ from each other and federal law in ~~setting~~significant ~~their~~ways, ~~coverage~~thus complicating compliance efforts. For example, states have anti-kickback and ~~reimbursement~~false ~~policies~~claims laws that may be broader in scope than analogous federal laws and ~~amounts~~may apply regardless of payer. ~~However~~In addition, nostate ~~uniform~~data ~~policy~~privacy ~~for~~laws ~~coverage~~that protect the security of health information may differ from each other and ~~reimbursement~~may ~~for~~not ~~medical~~be ~~devices~~preempted ~~exists~~by federal law. Moreover, several states have enacted legislation requiring pharmaceutical manufacturers to, among ~~third-party~~other ~~payors~~things, inestablish marketing compliance programs, file periodic reports with the ~~United~~state, ~~States~~make periodic public disclosures on sales and marketing activities, report information related to drug pricing, require the registration of sales representatives, and prohibit certain other sales and marketing practices. ~~Therefore~~These laws may adversely affect our sales, ~~coverage~~marketing, and ~~reimbursement~~other ~~can~~activities ~~differ~~with ~~significantly~~respect ~~from~~to ~~payor~~any product candidate for which we receive approval to ~~payor~~market in the United States by imposing administrative and compliance burdens on us.

~~Employees~~Because of the breadth of these laws and the narrowness of available statutory exceptions and regulatory safe harbors, it is possible that some of our business activities, particularly any sales and marketing activities after a product candidate has been approved for marketing in the United States, could be subject to legal challenge and enforcement actions. If our operations are found to be in violation of any of the federal and state laws described above or any other governmental regulations that apply to us, we may be subject to significant civil, criminal, and administrative penalties, including, without limitation, damages, fines, imprisonment, exclusion from participation in government healthcare programs, 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.

AsFrom time to time, legislation is drafted and introduced in Congress that could significantly change the statutory provisions governing the regulatory approval, manufacture and marketing of regulated products or the reimbursement thereof. For example, in the U.S., the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act of 2010, among other things, reduced and/or limited Medicare reimbursement to certain providers and imposed an annual excise tax of 2.3% on any entity that manufactures or imports medical devices offered for sale in the United States, with limited exceptions. The Further Consolidated Appropriations Act, signed into law on December 3120, ~~2024~~2019, wehas ~~had~~now 19permanently ~~full-time~~repealed ~~employees~~the medical device excise tax. ~~None~~In addition, the Budget Control Act of ~~our~~2011, ~~employees~~as ~~are~~amended ~~represented~~by subsequent legislation, further reduces Medicare’s payments to providers by ~~labor~~two ~~unions~~percent through fiscal year 2027. These reductions may reduce providers’ revenues or ~~covered~~profits, which could affect their ability to purchase new technologies. Furthermore, the healthcare industry in the United States has experienced a trend toward cost containment as government and private insurers seek to control healthcare costs by ~~collective~~imposing ~~bargaining~~lower ~~agreements~~payment rates and negotiating reduced contract rates with service providers. Legislation could be adopted in the future that limits payments for our products from governmental payors.

~~Corporate~~Coverage ~~History~~and Reimbursement

WeIn ~~were~~both ~~initially~~the ~~incorporated~~United asStates and international markets, the ~~Predecessor~~use ~~under~~of medical devices is dependent in part on the ~~name~~availability ~~Nephrion~~of reimbursement from third-party payors, ~~Inc~~such as government and private insurance plans. Healthcare providers that use medical devices generally rely on ~~June~~third-party 6,payors ~~2007~~to pay for all or part of the costs and fees associated with the medical procedures being performed or to compensate them for their patient care services. OnShould ~~August~~our 3products under development be approved for commercialization by the FDA, ~~2007~~any such products may not be considered cost-effective, wereimbursement ~~amended~~may ~~our~~not ~~corporate~~be ~~name~~available toin ~~CytoPherx~~the United States or other countries, ~~Inc~~if approved, and reimbursement may not be sufficient to allow sales of our future products on a profitable basis. OnThe ~~June~~coverage ~~19,~~decisions ~~2019~~of third-party payors will be significantly influenced by the assessment of our future products by health technology assessment bodies. If approved for use in the United States, we ~~amended~~expect ~~our~~that ~~corporate~~any ~~name~~products that we develop will be purchased primarily by medical institutions, which may in turn bill various third-party payors for the health care services provided to ~~SeaStar~~patients ~~Medical~~at their facility. Payors may include CMS, ~~Inc~~which administers the Medicare program and works in partnership with state governments to administer Medicaid, other government programs, and private insurance plans. The process involved in applying for coverage and reimbursement from CMS is lengthy and expensive. Further, ~~herein~~Medicare coverage is based on our ability to demonstrate that the ~~Predecessor~~treatment is “reasonable and necessary” for Medicare beneficiaries. Even if products utilizing our technology receive FDA and other regulatory clearance or approval, they may not be granted coverage and reimbursement by any payor, including by CMS. Many private payors use coverage decisions and payment amounts determined by CMS as ~~defined~~guidelines ~~above~~in setting their coverage and reimbursement policies and amounts. However, no uniform policy for coverage and reimbursement for medical devices exists among third-party payors in the United States. Therefore, coverage and reimbursement can differ significantly from payor to payor.

On October 28, 2022, LMF Acquisition Opportunities, Inc. ( as defined above “LMF”), a Delaware special purpose acquisition company, consummated a series of transactions that resulted in the combination of LMF Merger Sub, Inc., a Delaware corporation and a wholly-owned subsidiary of LMF (“Merger Sub”), and the Predecessor, a Delaware corporation, pursuant to an Agreement and Plan of Merger, dated April 21, 2022 (the “Merger Agreement”), by and among LMF, Merger Sub and the Predecessor (the “Transaction”). Pursuant to the terms of the Merger Agreement, Merger Sub merged with and into the Predecessor, with the Predecessor surviving the merger as a wholly-owned subsidiary of LMF (the “Business Combination”). Following the consummation of the Business Combination, LMF was renamed “SeaStar Medical Holding Corporation” (the “Company”). 27

~~Available~~ Table ~~Information~~of Contents

We make available free of charge on or through our website, https://seastarmedical.com, our Annual Reports, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, proxy statements, and all amendments to those filings as soon as reasonably practicable after such material is electronically filed with, or furnished to, the Securities and Exchange Commission (“SEC”). Information contained on, or that may be accessed through our website is not part of, and is not incorporated into this Annual Report.Employees

InAs ~~addition,~~of ~~the~~December ~~SEC maintains a website that contains reports~~31, ~~proxy statements~~2025, ~~and~~we ~~other~~had ~~information~~17 full-time ~~about~~employees. ~~issuers,~~None ~~such~~of asour ~~us,~~employees ~~who~~are ~~file~~represented ~~electronically~~by ~~within~~labor ~~the~~unions ~~SEC.~~or ~~The~~covered ~~address~~by ofcollective ~~the~~bargaining ~~website is www~~agreements.~~sec.gov.~~

28Corporate History

~~Item~~We 1Awere initially incorporated as the Predecessor under the name Nephrion, Inc. ~~Risk~~on ~~Factors~~June 6, 2007. On August 3, 2007, we amended our corporate name to CytoPherx, Inc. On June 19, 2019, we amended our corporate name to SeaStar Medical, Inc., herein the Predecessor as defined above.

~~Investing~~On inOctober ~~our~~28, ~~securities~~2022, ~~involves~~LMF ~~risks.~~Acquisition ~~Before~~Opportunities, ~~you~~Inc. ~~make~~( aas ~~decision~~defined toabove ~~buy our securities~~“LMF”), ina ~~addition~~Delaware tospecial ~~the~~purpose ~~risks~~acquisition ~~and~~company, ~~uncertainties~~consummated ~~discussed~~a ~~above~~series ~~under~~of ~~“Cautionary~~transactions ~~Note~~that ~~Regarding~~resulted ~~Forward-Looking~~in ~~Statements,”~~the ~~you~~combination ~~should~~of ~~carefully~~LMF ~~consider~~Merger ~~the~~Sub, ~~specific~~Inc., ~~risks~~a ~~set~~Delaware ~~forth~~corporation ~~herein.~~and Ifa ~~any~~wholly-owned subsidiary of ~~these~~LMF ~~risks~~(“Merger ~~actually occur~~Sub”), itand ~~may~~the ~~materially~~Predecessor, ~~harm~~a ~~our~~Delaware ~~business~~corporation, ~~financial~~pursuant ~~condition,~~to ~~liquidity~~an Agreement and ~~results~~Plan of ~~operations.~~Merger, Asdated aApril ~~result~~21, 2022 (the ~~market~~“Merger ~~price~~Agreement”), ofby ~~our~~and ~~securities~~among ~~could decline~~LMF, ~~and~~Merger ~~you~~Sub ~~could~~and ~~lose~~the ~~all~~Predecessor or(the ~~part of your investment~~“Transaction”). ~~Additionally,~~Pursuant to the ~~risks~~terms ~~and~~of ~~uncertainties~~the ~~described~~Merger ~~herein~~Agreement, inMerger ~~any~~Sub ~~document~~merged ~~incorporated~~with byand ~~reference~~into ~~herein~~the ~~are~~Predecessor, ~~not~~with the ~~only~~Predecessor ~~risks~~surviving ~~and~~the ~~uncertainties~~merger ~~that~~as wea ~~face.~~wholly-owned ~~Additional~~subsidiary ~~risks~~of ~~and~~LMF ~~uncertainties~~(the ~~not~~“Business ~~presently~~Combination”). ~~known~~Following tothe usconsummation orof ~~that~~the weBusiness ~~currently~~Combination, ~~believe~~LMF towas berenamed ~~immaterial~~“SeaStar ~~may~~Medical ~~become~~Holding ~~material~~Corporation” ~~and~~(the ~~adversely affect our business~~“Company”).

~~Risk~~Available ~~Factor Summary~~Information

We ~~have~~make ~~not~~available ~~generated~~free ~~revenue~~of ~~sufficient~~charge ~~for~~on ~~positive~~or ~~operating~~through ~~cash~~our ~~flows~~website, ~~have~~https://seastarmedical.com, ~~incurred~~our ~~significant~~Annual ~~losses~~Reports, ~~since~~Quarterly ~~our~~Reports ~~inception~~on Form 10-Q, Current Reports on Form 8-K, proxy statements, and ~~may~~all ~~continue~~amendments to ~~incur~~those ~~significant~~filings ~~losses~~as ~~for~~soon as reasonably practicable after such material is electronically filed with, or furnished to, the ~~foreseeable~~Securities ~~future~~and Exchange Commission (“SEC”). Information contained on, or that may be accessed through our website, is not part of, and is not incorporated into this Annual Report.

IfIn weaddition, ~~fail~~the toSEC ~~obtain~~maintains ~~additional~~a ~~financing~~website that contains reports, weproxy ~~would~~statements, beand ~~forced~~other toinformation ~~delay~~about issuers, ~~reduce~~such oras ~~eliminate~~us, ~~our~~who ~~product~~file ~~development~~electronically ~~program~~within the SEC. The address of the website is www.sec.gov.

~~We have a limited operating history.~~ 28

We Table ~~may~~of ~~not be able to use our net operating losses to offset future taxable income.~~Contents

WeItem ~~may~~1A. ~~suffer~~Risk ~~from a lack of availability of future funds~~Factors.

WeInvesting ~~may~~in ~~become~~our securities involves risks. Before you make a ~~defendant~~decision to buy our securities, in ~~one~~addition orto ~~more~~the ~~stockholder~~risks ~~derivative,~~and ~~class~~uncertainties discussed above under “Cautionary Note Regarding Forward-~~action~~Looking Statements,” you should carefully consider the specific risks set forth herein. If any of these risks actually occur, it may materially harm our business, financial condition, liquidity and ~~other~~results ~~litigation~~of operations. As a result, the market price of our securities could decline, and you could lose all or part of your investment. Additionally, the risks and uncertainties described herein in any document incorporated by reference herein are not the only risks and uncertainties that we face. Additional risks and uncertainties not presently known to us or that we currently believe to be immaterial may become material and adversely affect our business.

WeRisk ~~may~~Factor ~~face challenges in obtaining additional FDA approvals to market our product.~~Summary

• We have incurred significant losses since our inception and anticipate that we will continue to incur significant losses for the foreseeable future. • We have not generated substantial revenue to date and we may never be profitable. • We may suffer from lack of availability of additional funds. • There is substantial doubt about our ability to continue as a going concern. • In the event we pursue a restructuring or reorganization under applicable law, we will be subject to the risks and uncertainties associated with such proceedings. • We have a limited operating history, which makes it difficult to forecast our future results of operations. • Our ability to use our net operating losses to offset future taxable income may be subject to certain limitations. • We may become a defendant in one or more stockholder derivative, class-action, and other litigation. • We may face challenges in obtaining additional FDA approvals to market our product. • The United States could change tariff, trade, or tax provisions related to the manufacturing and sales of our products in ways that we currently cannot predict. • We may not be able to manage our growth effectively. • Changing priorities within the U.S. government resulting in the loss of government grant funding could adversely impact our future growth plans. • We will initially depend on revenue generated from a single product. • We may fail to comply with extensive regulations of United States and foreign regulatory agencies. • Delays in successfully completing our planned clinical trials could jeopardize our ability to obtain regulatory approval. • Delays, interruptions, or the cessation of production by our third-party suppliers of important materials or delays in qualifying new materials, may prevent or delay our ability to manufacture or process our SCD device. • Difficulties in manufacturing our SCD could have an adverse effect upon our revenue and expenses. • Our SCD technology may become obsolete. • We face intense competition in the medical device industry. • If our products, or the malfunction of our products, cause or contribute to a death or a serious injury, we will be subject to medical device reporting regulations. • We outsource many of our operational and development activities for which we may not have full control. • A lack of third-party coverage and reimbursement for our devices could delay or limit their adoption. • Adverse changes in reimbursement policies and procedures by payors may impact our ability to market and sell our products. • We may be subject to enforcement action if we engage in improper marketing or promotion of our products. • We are and will be exposed to product liability risks, and clinical and preclinical liability risks, which could place a substantial financial burden upon us should litigation be pursued. • United States legislative or FDA regulatory reforms may make it more difficult and costly for us to obtain regulatory approval of our product candidates and to manufacture, market and distribute our products after approval is obtained.

~~We may not be able to manage our growth effectively.~~ 29

~~Changing~~ Table ~~priorities within the U.S. government resulting in the loss~~ of ~~government grant funding could adversely impact our future growth plans.~~Contents

• We are subject to stringent and changing privacy laws, regulations and standards • Our business operations will ~~initially~~be adversely affected if our security measures, or those maintained on our behalf, are compromised, limited or fails. • We depend on ~~revenue~~key ~~generated~~personnel and our inability to attract and retain qualified personnel could impede our ability to achieve our business objectives. • Our products may in the future be subject to product recalls. • Our forecasted operating and financial results rely upon assumptions and analyses development by us and actual results could be significantly below forecasts. • Our estimates of market opportunity, industry projections and forecasts of operating and financial results and market growth may prove to be inaccurate. • Conflicts, military actions, terrorist attacks, political events, public health crises, changes in regulatory regimes and general instability, could adversely affect our business. • We rely upon exclusively licensed patent rights from third parties which are subject to termination or expiration. • If we are unable to obtain and maintain sufficient patent protection for our products, our ability to commercialize such products successfully may be adversely affected. • We may not be able to obtain protection under the Hatch-Waxman Act and similar non-United States legislation for extending the term of patents covering our products. • We could become involved in intellectual property litigation that could be costly, require us to pay damages, prevent us from selling commercially available products at all or reduce margins we may realize from our products. • Issued patents covering one or more of our products could be found invalid or unenforceable if challenged in patent office proceedings, or in court. • If we are unable to protect the confidentiality of our trade secrets, the value of our technology could be adversely and materially affected, and our business could be harmed. • The United States government may exercise certain rights with regard to our inventions, or licensors’ inventions, developed using federal government funding. • Changes to the patent law in the United States and other jurisdictions could diminish the value of our patents in general, thereby impairing our ability to protect our products. • Intellectual property rights do not necessarily address all potential threats to our competitive advantage. • Obtaining and maintaining our patent protection depends on compliance with various procedural, document submissions, fee payment and other requirements imposed by governmental patent agencies. • We may obtain only limited geographical protection with respect to certain patent rights, • We do not have long-term experience operating as a ~~single~~United ~~product~~States public company. • Our Common Stock may be delisted from Nasdaq if we do not maintain compliance with Nasdaq’s continued listing requirements. If our Common Stock is delisted, it could negatively impact us. • Our inability to develop and maintain an effective system of internal controls of financial reporting could impact ability to accurately report financial results in a timely manner. • The sale of our Common Stock in at-the-market offerings, through our standby equity purchase agreement or through similar arrangements may cause substantial dilution to our existing shareholders. • We may redeem your unexpired warrants prior to their exercise at a time that is disadvantageous to you, thereby making your warrants worthless. • The trading price of our Common Stock has been volatile and is likely to be volatile in the future. • If securities or industry analysts do not publish research or publish inaccurate or unfavorable research about our business, our stock price and trading volume could decline. • Future sales, or the possibility of future sales, of a substantial number of shares of our Common Stock could adversely affect the price of the shares and dilute stockholders. • We have not paid cash dividends in the past and do not expect to pay dividends in the future. • We are an "emerging growth company" and will continue to take advantage of reduced disclosure and governance requirements applicable to emerging growth companies.

~~We may fail to comply with extensive regulations of United States and foreign regulatory agencies.~~ 30

~~Delays~~ Table inof ~~successfully completing our planned clinical trials could jeopardize our ability to obtain regulatory approval.~~Contents

~~Delays,~~Risks ~~interruptions,~~Relating ~~or the cessation of production by our third-party suppliers of important materials or delays in qualifying new materials, may prevent or delay our ability~~ to ~~manufacture~~Our orFinancial ~~process our SCD device.~~Condition

We have ~~limited~~incurred ~~experience~~significant inlosses ~~identifying~~since our inception and ~~working~~anticipate ~~with~~that ~~large-scale~~we ~~contracts~~will ~~with~~continue ~~medical~~to ~~device~~incur ~~manufacturers~~significant losses for the foreseeable future.

~~Difficulties~~We inhave ~~manufacturing~~incurred significant net losses since our ~~SCD~~inception ~~could~~and ~~have~~had an ~~adverse~~accumulated ~~effect~~deficit ~~upon~~of ~~our~~$151.7 million ~~revenue~~and $139.6 million as of December 31, 2025 and ~~expenses~~2024, respectively.

We ~~face~~have ~~intense~~devoted ~~competition~~most inof ~~the~~our ~~medical~~financial ~~device~~resources ~~industry~~to research and development, including clinical trials and non-clinical development activities, and obtaining regulatory approval of our SCD ~~technology~~product ~~may~~candidates. ~~become~~If ~~obsolete~~our product candidates are not successfully developed or commercialized, or if revenues are insufficient following marketing approval, we will not achieve profitability and our business may fail.

IfWe ~~our~~expect ~~products,~~to orcontinue to incur substantial and increased expenses as we expand research and development activities and advance clinical programs through the ~~malfunction~~regulatory approval process. We also expect an increase in our expenses associated with commercialization of our products, ~~cause~~and orcreating ~~contribute~~additional infrastructure to support operations as a ~~death~~public orcompany. As a ~~serious~~result ~~injury~~of the foregoing, we ~~will~~expect beto ~~subject~~continue to ~~medical~~incur ~~device~~significant ~~reporting~~and ~~regulations~~increasing losses and negative cash flows for the foreseeable future.

We ~~outsource~~have ~~many~~not ofgenerated ~~our~~substantial revenue ~~operational~~to date and ~~development activities for which~~ we may ~~not~~never ~~have~~be ~~full control~~profitable.

AOur ~~lack~~ability ofto ~~third-party~~generate ~~coverage~~meaningful ~~and~~future ~~reimbursement~~revenue ~~for~~from ~~our~~product ~~devices~~sales ~~could~~depends ~~delay~~heavily oron ~~limit~~our ~~their~~success ~~adoption.~~with the following items:

~~Adverse~~• ~~changes~~commercializing inQUELIMMUNE, ~~reimbursement~~including ~~policies~~securing ~~and~~adoption ~~procedures by payors may impact our ability to market~~ and ~~sell~~increasing ~~our products.~~awareness;

We• ~~may~~completing bethe ~~subject~~clinical todevelopment ~~enforcement action if we engage in improper marketing or promotion~~ of our ~~products.~~adult SCD;

We• ~~are~~obtaining ~~and~~regulatory ~~will~~approval befor ~~exposed~~our toadult ~~product liability risks~~SCD, ~~and~~including ~~clinical~~the ~~and~~PMA ~~preclinical~~from ~~liability~~the ~~risks, which could place a substantial financial burden upon us should we be sued.~~FDA;

~~United~~• ~~States~~scaling ~~legislative~~our orcommercial ~~FDA~~operations, ~~regulatory~~including ~~reforms~~building ~~may~~a ~~make~~hospital-directed itsales ~~more~~force ~~difficult~~ and ~~costly~~potentially ~~for~~collaborating uswith tothird ~~obtain regulatory approval of our product candidates and to manufacture, market and distribute our products after approval is obtained.~~parties;

29• obtaining third-party reimbursement status from government agencies and insurance carriers; and

We• ~~are~~entering ~~subject~~into tocollaboration ~~stringent~~agreements and ~~changing~~partnerships ~~privacy~~to ~~laws,~~commercialize ~~regulations~~our ~~and standards~~ products.

~~Our~~Because ~~business~~of ~~operations~~the ~~will~~numerous berisks ~~adversely~~and ~~affected~~uncertainties ifassociated ~~our~~with ~~security~~medical ~~measures~~device commercialization and product development, we are unable to predict the timing or ~~those~~amount ~~maintained~~of onexpenses, ~~our~~or ~~behalf~~when, ~~are~~or ~~compromised~~if, ~~limited~~we orwill ~~fails~~be able to achieve profitability. In addition, our expenses could increase beyond expectations if we are required by the FDA to perform additional, unanticipated studies.

WeEven ~~depend~~if onour ~~key~~product ~~personnel~~candidates ~~and~~are approved for commercial sale, we anticipate incurring significant costs associated with commercializing any approved product candidate. In the case of our ~~inability~~SCD totherapy ~~attract~~for ~~and~~the ~~retain~~treatment ~~qualified~~of ~~personnel~~pediatric ~~could~~AKI, ~~impede~~we will be limited in our ability to ~~achieve~~sell ~~our~~and ~~business~~distribute ~~objectives~~QUELIMMUNE due to certain restrictions under the HDE requirements that limit the number of units that can be sold on an annual basis, which will further limit the amount of revenue that could be generated by us.

~~Our products may in the future be subject to product recalls.~~ 31

~~Our~~ Table ~~estimates~~ of ~~market opportunity, industry projections and forecasts of operating and financial results and market growth may prove to be inaccurate.~~Contents

We ~~rely~~may ~~upon~~suffer ~~exclusively licensed patent rights~~ from ~~third~~lack ~~parties~~of ~~which~~availability ~~are~~of ~~subject~~additional ~~to termination or expiration~~funds.

We expect to have ongoing needs for working capital in order to fund our operations and we will need to raise additional funds through equity and debt financings. However, there can be no assurance that we will be successful in securing additional capital on favorable terms, if at all. If we are ~~unable~~successful, whether the terms are favorable or unfavorable, there is a potential that we will fail to ~~obtain~~comply ~~and~~with ~~maintain~~the ~~sufficient~~terms ~~patent~~of ~~protection~~such financing, which could result in liability for ~~our~~us. ~~products~~Further, ~~our~~the ~~ability~~sale of convertible debt securities or additional equity securities could result in additional and potentially substantial dilution to ~~commercialize~~our ~~such~~shareholders. ~~products~~The ~~successfully~~incurrence ~~may~~of beindebtedness ~~adversely~~would ~~affected~~result in additional debt service obligations and could result in operating and financing covenants that would restrict our operations and liquidity.

WeIf ~~may~~we ~~not~~are beunable ~~able~~to raise additional capital in sufficient amounts or on acceptable terms, we will need to ~~obtain~~curtail ~~protection~~development ~~under~~and commercialization efforts, including completing the ~~Hatch-Waxman~~clinical ~~Act~~trials and ~~similar~~regulatory ~~non-United~~approval ~~States~~process ~~legislation~~ for ~~extending~~our ~~the~~SCD ~~term~~product ofcandidates, ~~patents~~which ~~covering~~would have a material adverse impact on our ~~products~~business, results of operations and financial condition.

~~Issued~~In ~~patents~~addition, ~~covering~~if ~~one~~we are unable to generate adequate cash from operations, and if we are unable to find sources of funding, it may be necessary for us to forego business development opportunities, sell all or ~~more~~a portion of our ~~products~~assets, ~~could~~enter beinto ~~found~~a ~~invalid~~business combination, or ~~unenforceable~~reduce ifor ~~challenged~~eliminate inoperations. ~~patent~~These ~~office~~possibilities, ~~proceedings~~to the extent available, may be on terms that result in significant dilution to our shareholders or that result in ~~court~~our shareholders losing all of their investment in us.

IfThere weis ~~are~~substantial ~~unable~~doubt toabout ~~protect~~our ~~the~~ability ~~confidentiality~~to ofcontinue ~~our~~as ~~trade~~a ~~secrets~~going concern, ~~the~~and ~~value~~we ofwill need additional financing to execute our ~~technology~~business ~~could~~plan, beto ~~adversely~~fund our operations and ~~materially~~to ~~affected~~continue as a going concern, and ~~our~~if ~~business~~we ~~could~~are unable to obtain additional financing, we may be ~~harmed~~required to pursue a restructuring of our operations or reorganization proceedings under applicable U.S. bankruptcy or insolvency laws.

~~Competitors~~We ~~may~~expect ~~develop~~our ~~superior~~research ~~products~~and ~~based~~development expenses to substantially increase in connection with our ongoing activities, particularly as we advance our clinical programs. As of December 31, 2025 and December 31, 2024, we had positive working capital of $9.8 million and negative working capital of $3.0 million, respectively. We currently do not have sufficient capital to support our operations and complete our planned regulatory approval process for the adult AKI patient indications. We will need to secure additional capital to continue our operations, and such funding may not be available on ~~new~~acceptable ~~technologies~~terms, or at all.

~~The~~There ~~United~~is ~~States~~substantial ~~government~~doubt ~~may~~regarding ~~exercise~~our ~~certain~~ability ~~rights~~to ~~with~~continue ~~regard~~as a going concern. Our independent registered public accounting firm has expressed in its auditors’ report on our 2025 financial statements, included in our Annual Report on Form 10-K filed on March 26, 2026, an emphasis of matter paragraph relating to our ~~inventions~~ability to continue as a “going concern,” meaning that our recurring losses from operations and negative cash flows from operations raise substantial doubt regarding our ability to continue as a going concern. We have prepared our financial statements on a going concern basis, which contemplates the realization of assets and the satisfaction of liabilities and commitments in the normal course of business. Our financial statements do not include any adjustment to reflect the possible future effects on the recoverability and classification of assets or ~~licensors’~~the ~~inventions~~amounts and classification of liabilities that may result from the outcome of this uncertainty, ~~developed~~with ~~using~~the ~~federal~~exception ~~government~~that ~~funding~~all borrowings are classified as current on the balance sheets.

~~Changes~~In to the ~~patent~~event ~~law~~we inpursue ~~the~~a ~~United~~restructuring ~~States~~or ~~and~~reorganization ~~other~~under ~~jurisdictions~~applicable ~~could~~law, ~~diminish~~we ~~the~~will ~~value~~be ofsubject ~~our~~to ~~patents~~the inrisks ~~general,~~and ~~thereby~~uncertainties ~~impairing~~associated ~~our~~with ~~ability~~such ~~to protect our products~~proceedings.

~~Intellectual~~In ~~property~~the ~~rights~~event dowe ~~not~~seek ~~necessarily~~to ~~address~~pursue ~~all~~a ~~potential~~restructuring, ~~threats~~or if we file for relief under the United States Bankruptcy Code, either Chapter 7, Chapter 11 or other proceedings, our operations, our ability to develop and execute our ~~competitive~~business ~~advantage~~plan and our continuation as a going concern will be subject to the risks and uncertainties associated with bankruptcy proceedings, including, among others: our ability to execute, confirm and consummate a plan of reorganization; the high costs of bankruptcy proceedings and related fees; our ability to obtain sufficient financing to allow us to emerge from bankruptcy and execute our business plan post-emergence, and our ability to comply with terms and conditions of any such financing; our ability to continue our operations in the ordinary course; our ability to maintain our relationships with our customers, business partners, counterparties, employees and other third parties; our ability to obtain, maintain or renew contracts that are critical to our operations on reasonably acceptable terms and conditions; our ability to attract, motivate and retain key employees; the ability of third parties to use certain limited safe harbor provisions to terminate contracts; and the actions and decisions of our stakeholders and other third parties who have interests in our proceedings that may be inconsistent with our operational and strategic plans.

~~Obtaining~~Any ~~and~~delays ~~maintaining~~in our ~~patent~~proceedings ~~protection~~would ~~depends~~increase onthe ~~compliance~~risks of our being unable to reorganize our business and emerge from any such proceedings and may increase our costs associated with ~~various~~the ~~procedural~~process or result in prolonged operational disruption for us. Also, ~~document~~we ~~submissions~~would need the prior approval of a court for transactions outside the ordinary course of business during the course of any such proceedings, ~~fee~~which ~~payment~~may limit our ability to respond timely to certain events or take advantage of certain opportunities. Because of the risks and ~~other~~uncertainties ~~requirements~~associated ~~imposed~~with byany ~~governmental~~such ~~patent~~proceedings, ~~agencies~~we cannot accurately predict or quantify the ultimate impact of events that could occur during any such proceedings. There can be no guarantees that if we seek available protections, we will emerge from protection as a going concern or that holders of our common stock will receive any recovery.

~~We may obtain only limited geographical protection with respect to certain patent rights,~~ 32

We Table doof ~~not have long-term experience operating as a United States public company.~~Contents

~~Our~~We ~~Common~~have ~~Stock~~a ~~may~~limited beoperating ~~delisted~~history, ~~from~~which ~~Nasdaq~~makes ifit wedifficult doto ~~not~~forecast ~~maintain compliance with Nasdaq’s continued listing requirements. If~~ our ~~Common~~future ~~Stock~~results isof ~~delisted, it could negatively impact us~~operations.

We ~~may~~received ~~redeem~~HDE ~~your~~approval ~~unexpired~~from ~~warrants~~the ~~prior~~FDA for our pediatric SCD in February 2024 and shipped our first commercial QUELIMMUNE units in July 2024. As a result, we have a limited commercial operating history, making it difficult to ~~their~~accurately ~~exercise~~forecast atfuture results of our operations and subjecting us to a ~~time~~number ~~that~~of isuncertainties ~~disadvantageous~~and risks, including our ability to ~~you~~plan for and model future growth. Even if we receive regulatory approval to market and sell our other SCD product candidates, ~~thereby~~our ~~making~~revenue ~~your~~growth ~~warrants~~could ~~worthless~~slow in the future, or our revenue could decline or fluctuate for a number of reasons, including slowing demand for our products, increasing competition, changing demand in the markets, new scientific or technological developments, a decrease in the growth of our overall market, our failure to attract more customers, the inability to obtain reimbursement for our products by government agencies and insurers, or our failure, for any reason, to continue to take advantage of growth opportunities. If our assumptions regarding these risks and uncertainties and our future revenue growth are incorrect or change, or if we do not address these risks successfully or forecast our results accurately, our operating and financial results could differ materially from our expectations, and our business could suffer.

~~The~~Our ~~trading~~ability ~~price~~to ofuse our ~~Common~~net ~~Stock~~operating ~~has~~losses ~~been~~to ~~volatile~~offset ~~and~~future istaxable ~~likely~~income tomay be ~~volatile~~subject into ~~the~~certain ~~future~~limitations.

IfAs ~~securities~~of orDecember ~~industry~~31, ~~analysts~~2025, dowe ~~not~~had ~~publish~~net ~~research~~operating orloss ~~publish~~(“NOL”) ~~inaccurate~~carryforwards orfor ~~unfavorable~~federal ~~research~~and ~~about~~state ~~our~~income ~~business~~tax purposes of $117.9 million and $52.5 million, ~~our~~respectively, ~~stock~~which ~~price~~may be available to offset taxable income in the future. Under the Tax Cuts and ~~trading~~Jobs ~~volume~~Act ~~could~~of ~~decline~~2017, as modified by the Coronavirus Aid, Relief, and Economic Security Act, federal NOLs incurred in tax years beginning after December 31, 2017 may be carried forward indefinitely, but the deductibility of such federal net operating losses in tax years beginning after December 31, 2020, is limited to 80 percent of taxable income. Federal NOLs incurred before 2018 may be carried forward 20 years but are not subject to the taxable income limitation. Under current law, California NOLs generally may be carried forward 20 years (with a limited extension for California NOLs incurred in 2020-2021) without a taxable income limitation. Our federal NOLs include $65.0 million that can also be carried forward indefinitely, and the remaining $52.8 million of federal NOLs expire in various years beginning in 2027 for federal purposes. The California NOLs expire beginning in 2039 if not utilized.

~~Future~~In ~~sales~~general, under Section 382 of the Internal Revenue Code of 1986, as amended, or the ~~possibility~~Code, a corporation that undergoes an “ownership change” (as defined in Section 382 of the Code and applicable Treasury Regulations) is subject to limitations on its ability to utilize its pre-change NOLs to offset future ~~sales~~taxable income. We may experience a future ownership change under Section 382 of the Code that could affect our ability to utilize the NOLs to offset our income. We have not completed an ownership change analysis pursuant to IRC Section 382. If ownership changes within the meaning of IRC Section 382 are identified as having occurred, the amount of NOL and research tax credit carryforwards available to offset future taxable income and income tax liabilities in future years may be significantly restricted or eliminated. Further, deferred tax assets associated with such NOLs, and research tax credits could be significantly reduced upon realization of an ownership change within the meaning of IRC Section 382. Furthermore, our ability to utilize NOLs of companies that we may acquire in the future may be subject to limitations. There is also a ~~substantial~~risk ~~number~~that due to legislative or regulatory changes, such as suspensions on the use of ~~shares~~NOLs or other unforeseen reasons, our existing NOLs could expire or otherwise be unavailable to reduce future income tax liabilities, including for state tax purposes. For these reasons, we may not be able to utilize a material portion of the NOLs reflected on our ~~Common~~balance ~~Stock~~sheet, even if we attain profitability, which could potentially result in increased future tax liability to us and could adversely affect ~~the~~our ~~price~~business, results of ~~the~~operations ~~shares~~ and ~~dilute~~financial ~~stockholders~~condition.

30We may become a defendant in one or more stockholder derivative, class-action, and other litigation, and any such lawsuits may adversely affect our business, financial condition, results of operations and cash flows.

~~Risks~~We ~~Relating~~may in the future become defendants in one or more stockholder derivative actions or other class-action lawsuits. For example, certain former directors have threatened litigation for purported harm to ~~Our~~us ~~Financial~~in ~~Condition~~connection with certain allegations made by the former directors against other members of our Board of Directors and management. The former directors have also made demands in connection with certain alleged contractual rights and purported agreements with us. We and the Board of Directors dispute these allegations and believe they are unfounded.

WeIn ~~have~~addition, ~~incurred~~on ~~significant~~July ~~losses~~5, ~~since~~2024, Forrest A K Wells (the “Plaintiff”), a purported stockholder of ours, filed a putative class action complaint in the United States District Court for the State of Colorado (the “Class Action”), alleging that we and our ~~inception~~management members made material misstatements or omissions regarding our business and ~~anticipate~~operations, including disclosures relating to FDA approval of our product candidates, allegedly culminating in the restatement of our consolidated financial statements as disclosed in the Form 8-K filed on March 27, 2024. The Class Action asserts claims under Section 10(b) of the Exchange Act against us, our Chief Executive Officer and former Chief Financial Officer (collectively, the “Defendants”), as well as claims under Section 20(a) of the Exchange Act against the Defendants. Among other remedies, the Class Action seeks to recover compensatory and other damages. On March 4, 2025, the Plaintiff filed an amended complaint. The Defendants moved to dismiss the complaint. The Defendants’ motion to dismiss the complaint was referred to United States District Court Magistrate Judge Timothy P. O’Hara. On February 27, 2026, Magistrate Judge O’Hara issued a written report and recommendation to United States District Judge Regina M. Rodriguez that wethe ~~will~~complaint ~~continue~~be dismissed with leave to ~~incur~~amend ~~significant~~(“R&R”). ~~losses~~Lead ~~for~~Plaintiff filed an objection to the ~~foreseeable~~R&R ~~future~~on March 13, 2026, and Defendants are expected to respond on March 27, 2026. We cannot predict whether the Magistrate Judge’s R&R will be adopted, modified or rejected by the District Court, or whether the Lead Plaintiff will amend the complaint.

~~We have incurred significant net losses since our inception and had an accumulated deficit of $139.6 million and $114.7 million as of December 31, 2024 and 2023, respectively.~~ 33

We Table ~~have devoted most~~ of our financial resources to research and development, including clinical trials and non-clinical development activities, and obtaining regulatory approval of our SCD product candidates. Since the completion of the Business Combination, we relied primarily on the sales of securities to fund our operations and are limited as we need to meet certain conditions before such funding becomes available. The size of our future net losses will depend, in part, on the rate of future expenditures and our ability to generate revenues. If our product candidates are not successfully developed or commercialized, or if revenues are insufficient following marketing approval, it will not achieve profitability and our business may fail. Even if we successfully obtain regulatory approval to market our product candidates in the United States, our revenues are also dependent upon the size of the markets outside of the United States, regulatory approval outside of the United States, and our ability to obtain market approval and achieve commercial success.Contents

WeOn ~~expect~~December to13, ~~continue~~2024, toJose ~~incur~~Lazo, ~~substantial~~a ~~and~~purported ~~increased~~stockholder ~~expenses~~of asours, wefiled ~~expand~~a ~~research~~putative ~~and~~stockholder ~~development~~derivative ~~activities~~action ~~and~~complaint ~~advances~~in ~~clinical programs through~~ the ~~regulatory~~United ~~approval~~States ~~process.~~District WeCourt ~~also~~for ~~expect~~the anDistrict ~~increase~~of inColorado ~~our~~(the ~~expenses~~“Derivative ~~associated~~Action”). ~~with~~The ~~commercialization~~factual allegations of ~~our~~the ~~products~~Derivative ~~and~~Action ~~creating~~are ~~additional~~substantially ~~infrastructure~~similar to ~~support~~the ~~operations~~Class asAction. aOn ~~public~~January ~~company.~~30, As2025, aupon ~~result~~joint motion of the ~~foregoing~~parties, wethe ~~expect~~Court tostayed ~~continue~~the toDerivative ~~incur~~Action ~~significant~~pending ~~and~~the ~~increasing~~Court’s ~~losses~~resolution ~~and~~of ~~negative~~an ~~cash~~anticipated ~~flows~~motion ~~for~~to dismiss to be filed in the ~~foreseeable~~Class ~~future~~Action.

WeSuch ~~have~~lawsuits ~~not~~could ~~generated~~divert ~~any~~our management’s attention and resources from our ordinary business operations, and we would likely incur significant ~~revenue~~expenses associated with their defense (including, without limitation, substantial attorneys’ fees and other fees of professional advisors and potential obligations to indemnify current and former officers and directors who are or may ~~never~~become beparties ~~profitable~~to such actions). The ultimate resolution of these matters and any future matters could have a material adverse effect on our business, financial condition, results of operations and cash flow and, consequently, could negatively impact the trading price of our common stock.

~~Our~~Risks ~~ability~~Related to generate sustainable revenue and achieve profitability depends on our ability, alone or with collaborators, to successfully commercialize our approved pediatric SCD and complete the development, obtain the necessary regulatory approvals of and commercialize our adult SCD. We do not anticipate generating substantial revenue for the foreseeable future. Our ~~ability~~Business ~~to generate meaningful future revenue from product sales depends heavily on our success with the following items:~~ Operations

~~commercializing~~We ~~our~~may ~~pediatric~~face ~~SCD,~~challenges ~~including~~in ~~securing~~obtaining ~~adoption~~additional ~~and~~FDA ~~increasing~~approvals ~~awareness;~~to market our products in the United States or abroad.

~~completing~~We may encounter various challenges and difficulties in our application to seek approval from the ~~clinical~~FDA ~~development~~to ofsell and market our SCD product candidates, including the pivotal trial for adult ~~SCD;~~AKI indication.

~~obtaining~~On ~~regulatory~~April ~~approval~~29, 2022, we received a BDD for the use of our SCD in the treatment of immunomodulatory dysregulation in adult ~~SCD~~patients (18 and older) with AKI, ~~including~~which is expected to accelerate the ~~PMA~~regulatory ~~from~~approval process subsequent to the ~~FDA;~~completion of our ongoing pivotal trial.

~~scaling~~ While ~~our~~we ~~commercial~~expect ~~operations,~~the ~~including~~BDD ~~building~~to aexpedite ~~hospital-directed~~the ~~sales~~clinical ~~force~~development and ~~collaborating~~regulatory ~~with~~review ~~third~~of ~~parties;~~the SCD therapy for use in this patient population, there is no guarantee that we will be able to expedite the clinical development or obtain regulatory approval.

~~obtaining~~While ~~third-party~~we ~~reimbursement~~have obtained ~~status~~approval from ~~government~~the ~~agencies~~FDA to conduct the pivotal trial for SCD therapy in the adult AKI patient population, there is no guarantee that we will be able to complete such trial in a timely manner, or at all, nor can there be any assurance that positive data will be generated from such trials. Even if we are able to generate positive results from this trial, the FDA and ~~insurance~~other ~~carriers;~~regulatory agencies may require us to conduct additional trials to support the study or disagree with the design of the trial and request changes or improvements to such design. We are also subject to numerous other risks relating to the regulatory approval process, which include but are not limited to:

~~entering~~• ~~into~~an ~~collaboration~~inability ~~agreements~~to secure and ~~partnerships~~obtain tosupport ~~commercialize~~and ~~our~~references ~~products.~~from collaborators and suppliers required by the FDA;

~~Because~~• ofa ~~the~~disagreement ~~numerous~~with ~~risks~~the ~~and~~FDA ~~uncertainties~~regarding ~~associated~~the ~~with~~design ~~medical~~of ~~device~~the ~~commercialization and product development~~trial, weincluding ~~are unable to predict~~ the ~~timing~~number ~~or amount~~ of ~~increased~~clinical ~~expenses,~~study ~~when,~~subjects orand ifother data, wewhich ~~will~~may berequire ~~able~~us to ~~achieve~~conduct oradditional ~~maintain~~testing ~~profitability.~~or ~~In addition, our expenses could~~ increase ~~beyond expectations if it is required by~~ the ~~FDA~~size toand ~~perform~~complexity ~~additional,~~of ~~unanticipated~~our ~~studies.~~pivotal study;

~~Even~~• ifa ~~our~~failure product candidates are approved for commercial sale, we anticipate incurring significant costs associated with commercializing any approved product candidate. In the case of our SCD product candidate for the treatment of pediatric AKI, we will be limited in our ability to ~~sell~~obtain ~~and~~a ~~distribute~~sufficient ~~our~~supplies ~~SCD units due~~ to ~~certain~~conduct restrictions under the HDE requirements that limit the number of units that can be sold on an annual basis, which will further limit the amount of revenue that could be generated by us. Even if we successfully expand sales of our ~~products, we may not become profitable and may need to obtain additional funding to continue operations.~~trial;

31• an inability to enroll a sufficient number of subjects;

We• ~~may~~a ~~suffer~~shortage ~~from~~of ~~lack~~necessary ofraw ~~availability~~materials, ofsuch ~~additional~~as ~~funds.~~calcium or IV fluids; and

We• ~~expect~~delays toand ~~have~~failures ~~ongoing needs for working capital in order~~ to ~~fund~~train ~~operations,~~qualified ~~continue to expand our operations and recruit experienced~~ personnel. ~~To that end, we will be required~~ to ~~raise~~operate additional funds through equity or debt financing. However, there can be no assurance that we will be successful in securing additional capital on favorable terms, if at all. If we are successful, whether the ~~terms~~SCD ~~are favorable or unfavorable, there is a potential that we will fail to comply with the terms of such financing, which could result in severe liability for us~~therapy. If we are unsuccessful, we may need to (a) initiate cost reductions; (b) forego business development opportunities; (c) seek extensions of time to fund liabilities, or (d) seek protection from creditors. In addition, any future sale of our equity securities would dilute the ownership and control of your shares and could be at prices substantially below prices at which our shares currently trade. Our inability to raise capital could require us to significantly curtail or terminate our operations altogether. We may seek to increase our cash reserves through the sale of additional equity or debt securities. The sale of convertible debt securities or additional equity securities could result in additional and potentially substantial dilution to our shareholders. The incurrence of indebtedness would result in increased debt service obligations and could result in operating and financing covenants that would restrict our operations and liquidity. In addition, our ability to obtain additional capital on acceptable terms is subject to a variety of uncertainties.

In addition, if we are unable to generate adequate cash from operations, and if we are unable to find sources of funding, it may be necessary for us to sell all or a portion of our assets, enter into a business combination, or reduce or eliminate operations. These possibilities, to the extent available, may be on terms that result in significant dilution to our shareholders or that result in our shareholders losing all of their investment in us. 34

If Table ~~we fail to obtain additional financing, we would be forced to delay, reduce or eliminate our product development program, which may result in the cessation~~ of ~~our operations.~~Contents

~~Developing~~Even ~~medical~~if ~~device~~we ~~products~~obtain approval, ~~including~~the ~~conducting~~FDA ~~preclinical~~or ~~studies~~other ~~and~~regulatory ~~clinical~~authorities ~~trials,~~may isrequire expensive. Weor ~~expect~~burdensome ~~our~~post-market ~~research~~testing ~~and~~or ~~development~~controls. ~~expenses~~Additionally, tothe ~~substantially~~FDA ~~increase~~and inother ~~connection~~regulatory ~~with~~authorities ~~our~~have ~~ongoing~~broad ~~activities,~~enforcement ~~particularly as we advance our clinical programs~~powers. AsRegulatory ofenforcement ~~December~~or 31inquiries, ~~2024~~or ~~and~~other ~~December~~increased ~~31,~~scrutiny ~~2023,~~on ~~we had negative working capital of $3.0 million and $4.2 million~~us, ~~respectively.~~could Wedissuade ~~currently~~some dophysicians ~~not~~from ~~have~~using ~~sufficient capital to support~~ our ~~operations~~products and ~~complete~~adversely ~~our~~affect ~~planned regulatory approval process. We will need to secure additional capital to continue~~ our ~~operations,~~reputation and ~~such~~the ~~funding~~perceived ~~may~~safety ~~not~~and beefficacy ~~available~~of onour ~~acceptable terms, or at all~~products.

~~Even~~Delays ifor werejections ~~receive~~may ~~sufficient~~occur ~~capital~~based inon ~~the~~changes ~~future,~~in wegovernmental ~~will~~policies befor ~~required~~medical todevices ~~raise~~during ~~additional~~the ~~funds~~period toof ~~support~~product ~~our~~development. ~~operations~~The ~~and~~FDA ~~complete~~can ~~our planned regulatory approval process~~delay, ~~and~~limit ~~such funding may not be available in sufficient amounts~~ or ondeny ~~acceptable~~approval ~~terms~~of toa ~~us,~~PMA orapplication atfor ~~all.~~many ~~If we are unable to raise additional capital when required or on acceptable terms~~reasons, ~~we may be required to~~including:

~~significantly~~• ~~delay,~~our ~~scale~~inability ~~back~~to ordemonstrate ~~discontinue~~ the ~~development~~safety or ~~commercialization~~effectiveness of ~~our~~the SCD or any other product ~~candidates~~we develop to the FDA’s satisfaction;

~~seek~~• ~~corporate~~insufficient ~~partners~~data onfrom ~~terms~~our ~~that~~preclinical ~~are~~studies ~~less~~and ~~favorable~~clinical ~~than~~trials, ~~might~~including ~~otherwise~~for beour ~~available~~SCD, to support approval;

~~relinquish~~• orfailure ~~license~~of onthe ~~unfavorable~~facilities ~~terms~~of our ~~rights~~third-party tomanufacturers ~~technologies~~ or ~~product~~suppliers ~~candidates that we otherwise would seek~~ to ~~develop~~meet orapplicable ~~commercialize ourselves~~requirements;

If• weinadequate ~~are~~compliance ~~unable~~with ~~to raise additional capital in sufficient amounts or on acceptable terms~~preclinical, ~~we will be prevented from pursuing development and commercialization efforts, including completing the~~ clinical ~~trials~~or ~~and~~other ~~regulatory approval process for our SCD product candidates, which would have a material adverse impact on our business, results of operations and financial condition.~~regulations;

We• ~~have~~our afailure ~~limited~~to ~~operating~~meet ~~history,~~the ~~which~~FDA’s ~~makes~~statistical itrequirements ~~difficult~~for toapproval; ~~forecast our future results of operations.~~and

We• ~~received~~changes ~~HDE~~in ~~approval from~~ the FDA’s ~~for~~approval ~~our pediatric SCD in February 2024 and shipped our first commercial QUELIMMUNE units in July 2024. As a result~~policies, weor ~~have~~the aadoption ~~limited commercial operating history, making it difficult to accurately forecast future results~~ of ~~our~~new ~~operations~~regulations ~~and~~that ~~subject~~require toadditional adata ~~number~~or ofadditional ~~uncertainties~~clinical ~~and risks, including our ability to plan for and model future growth~~studies. ~~Even if we receive regulatory approval to market and sell our~~

32If we are not able to obtain regulatory approval of our other product candidates in a timely manner or at all, we may not be able to continue to operate our business and may be forced to shut down our operations.

~~other~~The ~~SCD~~United ~~product~~States ~~candidates, our revenue growth~~ could ~~slow~~change ~~in the future~~tariff, ~~or our revenue could decline or fluctuate for a number of reasons~~trade, ~~including slowing demand for our products, increasing competition, changing demand in the markets, new scientific~~ or ~~technological~~tax ~~developments,~~provisions arelated ~~decrease in the growth of our overall market, our failure~~ to ~~attract more customers,~~ the ~~inability~~manufacturing ~~to obtain reimbursement for our products by government agencies~~ and ~~insurers,~~sales ~~or our failure, for any reason, to continue to take advantage~~ of ~~growth opportunities. If~~ our ~~assumptions~~products ~~regarding~~in ~~these~~ways ~~risks~~that ~~and uncertainties and our future revenue growth are incorrect or change, or if~~ we docurrently ~~not~~cannot ~~address these risks successfully or forecast its results accurately, our operating and financial results could differ materially from our expectations, and our business could suffer~~predict.

~~Our~~The ~~ability~~U.S. topresidential ~~use~~administration ~~our~~has ~~net~~instituted ~~operating~~or ~~losses~~proposed changes in trade policies that include the imposition of higher tariffs on imports into the U.S., economic sanctions on individuals, corporations or countries, and other government regulations affecting trade between the U.S. and other countries where we conduct business. The new tariffs and other changes in U.S. trade policy could trigger retaliatory actions by affected countries, and certain foreign governments have instituted or are considering imposing trade sanctions on certain U.S. goods. The U.S. presidential administration has indicated a focus on policy reforms that discourage corporations from outsourcing manufacturing and production activities to ~~offset~~foreign ~~future~~jurisdictions, ~~taxable~~including ~~income~~through tariffs or penalties on goods manufactured outside the U.S., which may berequire ~~subject~~us to change the way we conduct business. These changes in U.S. and foreign laws and policies have the potential to adversely impact the U.S. economy or certain ~~limitations~~sectors thereof, our industry and the demand for our products, and as a result, could have a material adverse effect on our business, financial condition and results of operations. As of December 31, 2025, we do not import materials from Canada or China, but we do source tubing sets from Medtronic that are manufactured in Mexico.

As of December 31, 2024, we had net operating loss (“NOL”) carryforwards for federal and state income tax purposes of $108.2 million and $36.3 million, respectively, which may be available to offset taxable income in the future. Under the Tax Cuts and Jobs Act of 2017, as modified by the Coronavirus Aid, Relief, and Economic Security Act, federal NOLs incurred in tax years beginning after December 31, 2017 may be carried forward indefinitely, but the deductibility of such federal net operating losses in tax years beginning after December 31, 2020, is limited to 80 percent of taxable income. Federal NOLs incurred before 2018 may be carried forward 20 years but are not subject to the taxable income limitation. Under current law, California NOLs generally may be carried forward 20 years (with a limited extension for California NOLs incurred in 2020-2021) without a taxable income limitation. Our federal NOLs include $55.6 million that can also be carried forward indefinitely, and the remaining $52.8 million of federal NOLs expire in various years beginning in 2027 for federal purposes. The California NOLs expire beginning in 2039 if not utilized. A lack of future taxable income would adversely affect our ability to utilize these NOLs before they expire. 35

In Table ~~general, under Section 382~~ of the Internal Revenue Code of 1986, as amended, or the Code, a corporation that undergoes an “ownership change” (as defined in Section 382 of the Code and applicable Treasury Regulations) is subject to limitations on its ability to utilize its pre-change NOLs to offset future taxable income. We may experience a future ownership change under Section 382 of the Code that could affect our ability to utilize the NOLs to offset our income. We have not completed an ownership change analysis pursuant to IRC Section 382. If ownership changes within the meaning of IRC Section 382 are identified as having occurred, the amount of NOL and research tax credit carryforwards available to offset future taxable income and income tax liabilities in future years may be significantly restricted or eliminated. Further, deferred tax assets associated with such NOLs, and research tax credits could be significantly reduced upon realization of an ownership change within the meaning of IRC Section 382. Furthermore, our ability to utilize NOLs of companies that we may acquire in the future may be subject to limitations. There is also a risk that due to legislative or regulatory changes, such as suspensions on the use of NOLs or other unforeseen reasons, our existing NOLs could expire or otherwise be unavailable to reduce future income tax liabilities, including for state tax purposes. For these reasons, we may not be able to utilize a material portion of the NOLs reflected on our balance sheet, even if we attain profitability, which could potentially result in increased future tax liability to us and could adversely affect our business, results of operations and financial condition.Contents

We ~~may~~plan ~~become~~to aexpand ~~defendant~~our inoperations ~~one~~and orwe ~~more~~may ~~stockholder~~not ~~derivative,~~be ~~class-action,~~able ~~and~~to ~~other~~manage ~~litigation,~~our ~~and~~growth ~~any~~effectively, ~~such~~which ~~lawsuits~~could ~~may~~strain ~~adversely~~our ~~affect~~resources ~~our~~and ~~business,~~delay ~~financial~~or ~~condition,~~derail ~~results~~implementation of ~~operations~~our ~~and~~business ~~cash flows~~objectives.

We ~~may~~will inneed to significantly expand our operations to implement our longer-term business plan and growth strategies, including building and expanding our internal organizational infrastructure to complete the ~~future~~regulatory ~~become~~approval ~~defendants~~process inwith ~~one~~the orFDA. ~~more~~We ~~stockholder~~will ~~derivative~~also ~~actions~~be orrequired to manage and form new relationships with various strategic partners, technology licensors, customers, manufacturers and suppliers, consultants and other ~~class-action~~third ~~lawsuits~~parties. ~~For~~This ~~example~~expansion and these new relationships will require us to significantly improve or replace our existing managerial, ~~certain~~operational ~~former~~and ~~directors~~financial ~~have~~systems, ~~threatened~~and ~~litigation~~procedures ~~for~~and ~~purported~~controls; ~~harm~~to improve the coordination between our various corporate functions; and to usmanage, train, motivate and maintain a growing employee base. We cannot assure that we will institute, in ~~connection~~a ~~with~~timely ~~certain~~manner ~~allegations~~or ~~made~~at byall, the ~~former~~improvements ~~directors~~to ~~against~~our ~~other~~managerial, ~~members~~operational ofand financial systems, procedures and controls necessary to support our ~~Board~~anticipated increased levels of ~~Directors~~operations and ~~management.~~to ~~The~~coordinate ~~former~~our ~~directors~~various ~~have~~corporate ~~also~~functions, ~~made~~or ~~demands~~that inwe ~~connection~~will ~~with~~be ~~certain~~able ~~alleged~~to ~~contractual~~properly ~~rights~~manage, train, motivate and ~~purported~~retain ~~agreements~~our ~~with~~anticipated usincreased employee base. WeIf ~~and~~we ~~the~~cannot ~~Board~~manage ofour ~~Directors~~growth ~~dispute~~initiatives, ~~these~~we ~~allegations~~will be unable to commercialize our products on a large scale in a timely manner, if at all, and ~~believe~~our ~~they~~business ~~are~~could ~~unfounded~~fail.

InWe ~~addition,~~may onpursue ~~July~~government 5,funding ~~2024, Forrest A K Wells (the “Plaintiff”), a purported stockholder of ours, filed a putative class action complaint~~ in the ~~United~~future. ~~States~~Changing ~~District~~priorities ~~Court~~within ~~for~~ the ~~State~~U.S. ofgovernment ~~Colorado~~resulting (the “Class Action”), alleging that we and our management members made material misstatements or omissions regarding our business and operations, including disclosures relating to FDA approval of our product candidates, allegedly culminating in the ~~restatement~~loss of ~~our~~government ~~consolidated~~grant ~~financial~~funding ~~statements~~could asadversely ~~disclosed~~impact ~~in the Form 8-K filed on March 27, 2024. The Class Action asserts claims under Section 10(b) of the Exchange Act against us,~~ our ~~Chief~~future ~~Executive~~growth ~~Officer and former Chief Financial Officer (collectively, the “Defendants”), as well as claims under Section 20(a) of the Exchange Act against the~~ plans.

33As a commercial-stage medical device company, there are grants and other funding provided by the U.S. government that we could apply for and receive. However, the current U.S. presidential administration has indicated that there will not only be a pause on government funding, but there will also be a change in who is eligible to receive it and for what purpose. These changes are not predictable and may impact our ability to receive government funding in the future. An inability to receive government funding could adversely impact our future growth plans.

~~Defendants.~~We ~~Among~~currently depend ~~other~~on ~~remedies,~~revenue ~~the~~generated ~~Class~~from ~~Action~~a ~~seeks~~single toproduct ~~recover compensatory~~ and ~~other~~in ~~damages. On March 4, 2025,~~ the ~~Plaintiff~~foreseeable ~~filed~~future anwill ~~amended~~be ~~complaint.~~significantly Wedependent ~~intend~~on toa ~~vigorously~~limited ~~defend~~number ~~the~~of ~~action~~products.

OnWe ~~December~~currently depend ~~13,~~on ~~2024,~~revenue ~~Jose~~generated ~~Lazo,~~from aQUELIMMUNE ~~purported~~and, ~~stockholder~~if ~~of ours~~approved, ~~filed~~our aSCD ~~putative~~product ~~stockholder~~candidate ~~derivative~~for ~~action~~adult ~~complaint~~patients inwith ~~the~~AKI. ~~United~~Given ~~States~~that, ~~District Court~~ for the ~~District~~foreseeable offuture, ~~Colorado~~our ~~(the~~business ~~“Derivative~~will ~~Action”).~~depend ~~The~~on ~~factual~~a ~~allegations~~single ofor ~~the~~limited ~~Derivative~~number ~~Action~~of ~~are~~products, ~~substantially similar~~ to the ~~Class~~extent ~~Action.~~a Onparticular ~~January~~product ~~30,~~is ~~2025,~~not ~~upon~~well-received ~~joint~~by ~~motion of~~ the ~~parties~~market, ~~the~~our ~~Court~~sales ~~stayed~~volume, ~~the~~prospects, ~~Derivative~~business, ~~Action~~results ~~pending the Court’s resolution~~ of anoperations ~~anticipated~~and ~~motion~~financial tocondition ~~dismiss~~could to be ~~filed~~materially inand ~~the~~adversely ~~Class Action~~affected.

~~Any~~If ~~such lawsuit could divert our management’s attention and resources from our ordinary business operations, and~~ we ~~would~~fail ~~likely~~to ~~incur~~comply ~~significant expenses associated~~ with ~~their~~extensive ~~defense~~regulations ~~(including, without limitation, substantial attorneys’ fees and other fees~~ of ~~professional~~United ~~advisors~~States and ~~potential~~foreign ~~obligations~~regulatory ~~to indemnify current and former officers and directors who are or may become parties to such actions). In connection with these lawsuits~~agencies, ~~we may be required to pay material damages, consent to injunctions on future conduct and/or suffer other penalties, remedies or sanctions, or issue additional shares upon~~ the ~~exercise~~commercialization of ~~certain warrants, which may cause additional dilution. In addition, any such future lawsuits could adversely impact~~ our ~~reputation and/or ability to launch and commercialize our~~ products, ~~thereby harming our ability to generate revenue. Accordingly, the ultimate resolution of these matters and any future matters~~ could ~~have~~be adelayed ~~material~~or ~~adverse~~prevented ~~effect on our business, financial condition, results of operations and cash flow and, consequently, could negatively impact the trading price of our common stock~~entirely.

~~Risks~~Our ~~Related~~SCD product candidate and research and development activities are subject to ~~Our~~extensive ~~Business~~government ~~Operations~~regulations related to its development, testing, manufacturing and commercialization in the United States and other countries. We have received FDA approval for our pediatric SCD under the HDE (QUELIMMUNE), but the SCD product has not received regulatory approval from the FDA, or any foreign regulatory agencies, for use with adult patients. The process of obtaining and complying with FDA and other governmental regulatory approvals and regulations in the United States and in foreign countries is costly, time-consuming, uncertain and subject to unanticipated delays. Obtaining such regulatory approvals, if any, can take several years. Despite the time and expense exerted, regulatory approval is never guaranteed. We are also subject to the following risks and obligations, among others:

We• ~~may~~the ~~face~~FDA ~~challenges~~may inrefuse ~~obtaining~~to ~~additional~~approve ~~FDA~~an ~~approvals~~application toif ~~market~~it ~~our~~believes ~~products~~that inapplicable ~~the~~regulatory ~~United~~criteria ~~States~~are ornot ~~abroad.~~satisfied;

We• ~~may encounter various challenges and difficulties in our application to seek approval from~~ the FDA tomay ~~sell~~require ~~and~~additional ~~market~~testing ~~our SCD product candidates, including the pivotal trial~~ for ~~adult~~safety ~~AKI~~and ~~indication.~~ effectiveness;

• Onthe ~~November~~FDA 6,may ~~2024,~~interpret wedata ~~received~~from ~~BDD for our patented and cell~~pre-~~directed SCD to treat chronic systemic inflammation in end-stage renal disease (ESRD) patients who require chronic hemodialysis, also known as chronic dialysis. While we expect the BDD to expedite the~~ clinical ~~development~~testing and ~~regulatory~~clinical ~~review~~trials ~~of the SCD program for use~~ in ~~this~~different ~~patient~~ways ~~population,~~than ~~there is no guarantee that~~ we ~~will~~interpret ~~be able to expedite the clinical development or obtain regulatory approval.~~ them;

~~While~~• weif ~~recently~~regulatory ~~obtained~~ approval ~~from~~of ~~the~~a ~~FDA~~product ~~to conduct the AKI adult pivotal trial for SCD, there~~ is ~~no guarantee that we will be able to complete such trial in a timely manner~~granted, ~~or at all, nor will there be any assurance that positive data will be generated from such trials. Even if we are able to generate positive results from this trial,~~ the ~~FDA~~approval ~~and other regulatory agencies~~ may ~~require~~be uslimited to ~~conduct~~specific ~~additional~~indications ~~trials to support the study~~ or ~~disagree~~limited with ~~the~~respect ~~design of the trial and request changes or improvements~~ to ~~such~~its ~~design.~~distribution; ~~We are also subject to numerous other risks relating to the regulatory approval process, which include but are not limited to:~~and

an• ~~inability~~the toFDA ~~secure~~may ~~and~~change ~~obtain~~its ~~support~~approval ~~and~~policies ~~references from collaborators~~ and/or ~~suppliers~~adopt ~~required~~new ~~by the FDA;~~regulations.

aFailure ~~disagreement~~to comply with ~~the~~these ~~FDA~~or ~~regarding~~other ~~the~~regulatory ~~design~~requirements of the ~~trial,~~FDA ~~including~~may ~~the~~subject ~~number~~us ofto ~~clinical~~administrative ~~study~~or ~~subjects~~judicially ~~and~~imposed ~~other~~sanctions ~~data,~~up ~~which may require us~~ to ~~conduct~~a ~~additional~~total ~~testing~~ or ~~increase~~partial ~~the~~suspension ~~size and complexity~~ of ~~our pivotal study;~~production.

~~a failure to obtain a sufficient supply of cartridges to conduct our trial;~~ 36

an Table ~~inability to enroll a sufficient number~~ of ~~subjects;~~Contents

aDelays ~~shortage~~in ofsuccessfully ~~necessary~~completing ~~raw~~our ~~materials,~~planned ~~such~~clinical astrials ~~calcium;~~could ~~and~~jeopardize our ability to obtain regulatory approval.

~~delays~~Our ~~and~~business ~~failures~~prospects towill ~~train~~depend ~~qualified~~on ~~personnel~~our ability to ~~operate~~complete ~~the~~studies, clinical trials, including our planned pivotal trials of our SCD ~~therapy~~for adult AKI indication, obtain satisfactory results, obtain required regulatory approvals and successfully commercialize our SCD product candidate. The completion of our clinical trials, the announcement of results of the trials and our ability to obtain regulatory approvals could be delayed for a variety of reasons, including:

34• slow patient enrollment;

~~Even~~• ifinsufficient wehospital ~~obtain~~supplies ~~approval, the FDA~~ or other regulatory authorities may require expensive or burdensome post-market testing or controls. Any delay in, or failure to receive or maintain, clearance or approval for our future products could prevent us from generating revenue from these products or achieving profitability. Additionally, the FDA and other regulatory authorities have broad enforcement powers. Regulatory enforcement or inquiries, or other increased scrutiny on us, could dissuade some physicians from using our products and adversely affect our reputation and the perceived safety and efficacy of our products.staffing;

~~Delays~~• orserious ~~rejections~~adverse ~~may~~events ~~occur~~related ~~based~~to onour ~~changes in governmental policies for~~ medical ~~devices~~device ~~during the period of product development. The FDA can delay, limit or deny approval of a PMA application for many reasons, including:~~candidates;

~~our~~• ~~inability~~insufficient funding to ~~demonstrate~~engage ~~the safety~~ or ~~effectiveness~~continue ofto ~~the~~engage ~~SCD~~a orcontract ~~any~~research ~~other~~organization ~~product we develop~~ to execute the ~~FDA’s satisfaction~~trials;

~~insufficient~~• ~~data~~unsatisfactory ~~from~~results ~~our~~of ~~preclinical~~any ~~studies and~~ clinical ~~trials, including for our SCD, to support approval~~trial;

~~failure~~• of the ~~facilities~~failure of ~~our~~principal third-party ~~manufacturers~~investigators orto ~~suppliers~~perform toclinical ~~meet~~trials ~~applicable~~on ~~requirements~~our anticipated schedules; and

~~inadequate~~• ~~compliance~~different ~~with~~interpretations ~~preclinical,~~of our pre-clinical orand ~~other~~clinical ~~regulations;~~data, which could initially lead to inconclusive results.

~~our~~Our ~~failure~~development costs will increase if we have material delays in any clinical trial or if we need to ~~meet~~perform more or larger clinical trials than planned. If the ~~FDA’s~~delays ~~statistical~~are ~~requirements~~significant, ~~for~~or ~~approval;~~if any of our product candidates do not prove to be safe or effective or do not receive regulatory approvals, our financial results and the commercial prospects for our product candidates would be harmed. Furthermore, our inability to complete our clinical trials in a timely manner could jeopardize our ability to obtain regulatory approval.

~~changes~~Delays, ininterruptions, or the ~~FDA’s~~cessation ~~approval~~of ~~policies,~~production orby ~~the~~our ~~adoption~~third-party suppliers of important materials or delays in qualifying new ~~regulations~~materials, ~~that~~may ~~require~~prevent ~~additional~~or ~~data~~delay our ability to manufacture or ~~additional~~process ~~clinical~~our ~~studies~~SCD device.

IfWe wecurrently ~~are~~rely ~~not~~on ~~able~~a tosingle ~~obtain~~supplier ~~regulatory~~for ~~approval~~the ofcartridges ~~our~~and ~~other~~blood ~~product~~tubing ~~candidates~~sets used in athe ~~timely~~SCD ~~manner~~device orfor atthe ~~all~~pediatric and adult AKI indications pursuant to supply agreements. In the event this supplier is unable to meet its obligations under the agreement, we may not be able to ~~continue~~obtain a sufficient number of cartridges or blood tubing sets to ~~operate~~conduct our ~~business~~clinical trials and commercialize our products. FDA review and approval of a new supplier may be ~~forced~~required if these materials become unavailable from our current suppliers. Although there may be other suppliers that have equivalent materials that would be available to ~~shut~~us, ~~down~~FDA review of any alternate suppliers, if required, could take several months or more to obtain, if they are able to be obtained at all. Any delay, interruption, or cessation of production by our ~~operations~~third-party suppliers of important materials, or any delay in qualifying new materials, if necessary, would prevent or delay our ability to manufacture our SCD.

~~The~~Additionally, ~~United~~use ~~States~~of ~~could~~the ~~change~~SCD ~~tariff~~in the hospital setting requires the administration of RCA and calcium replacement into CRRT circuitry for safe and effective use. Both components are IV solutions which are commonly stocked by hospital systems. However, ~~trade~~there are limited manufacturers/suppliers of these IV solutions nationwide, orand ~~tax~~any ~~provisions~~supply ~~related~~chain disruptions may have detrimental effects to the ~~manufacturing~~utilization of CRRT, and ~~sales~~subsequently the commercial use of ~~our~~QUELIMMUNE ~~products~~or inthe ~~ways~~use ~~that~~of weadult ~~currently~~SCD ~~cannot~~in ~~predict~~clinical studies.

Our business benefits from free trade agreements, and we also rely on various U.S. corporate tax provisions related to international commerce as we develop, market and sell our products within the U.S. and globally. The U.S. presidential administration has instituted or proposed changes in trade policies that include the imposition of higher tariffs on imports into the U.S., economic sanctions on individuals, corporations or countries, and other government regulations affecting trade between the U.S. and other countries where we conduct business. The new tariffs and other changes in U.S. trade policy could trigger retaliatory actions by affected countries, and certain foreign governments have instituted or are considering imposing trade sanctions on certain U.S. goods. The U.S. presidential administration has indicated a focus on policy reforms that discourage corporations from outsourcing manufacturing and production activities to foreign jurisdictions, including through tariffs or penalties on goods manufactured outside the U.S., which may require us to change the way we conduct business. These changes in U.S. and foreign laws and policies have the potential to adversely impact the U.S. economy or certain sectors thereof, our industry and the demand for our products, and as a result, could have a material adverse effect on our business, financial condition and results of operations. As of March 27, 2025, we do not import materials from Canada or China, but we do source tubing sets from Medtronic that is manufactured in Mexico. Tariffs and other trade restrictions could adversely affect our ability to obtain such materials on a timely basis or cause such components to become more expensive, which could adversely affect our business. 37

We Table ~~plan to expand our operations and we may not be able to manage our growth effectively, which could strain our resources and delay or derail implementation~~ of ~~our business objectives.~~Contents

WeDifficulties ~~will~~in ~~need~~manufacturing ~~to significantly expand~~ our ~~operations~~SCD tocould ~~implement~~have ~~our~~an ~~longer-term~~adverse ~~business~~effect ~~plan~~upon ~~and growth strategies, including building and expanding~~ our ~~internal~~revenue ~~organizational infrastructure to complete the regulatory approval process with the FDA. We will also be required to manage~~ and ~~form new relationships with various strategic partners, technology licensors, customers, manufacturers and suppliers, consultants and other third parties~~expenses. This expansion and these new relationships will require us to significantly improve or replace our existing managerial, operational and financial systems, and procedures and controls; to improve the coordination between our various corporate functions; and to manage, train, motivate and maintain a growing employee base. The time and costs to

35We outsource the manufacturing of component parts of our SCD and complete final assembly of our SCD kits in-house. The outsourced manufacturing of SCD cartridges is complex and specialized. To support our current clinical trial needs, we comply with and intend to continue to comply with current Good Manufacturing Practice (“cGMP”) for outsourced manufacturing and in-house assembly of our products. Our ability to adequately supply our SCD in a timely manner is dependent on the uninterrupted and efficient operation of our third-party manufacturers, and those of the third parties producing raw materials and supplies upon which we rely on for the manufacturing of our products. The manufacturing of our products may be impacted by:

~~effectuate~~• ~~these steps may place a significant strain on our management personnel, systems and resources, particularly if there are limited financial resources and skilled employees available at~~ the ~~time.~~availability ~~We cannot assure that we will institute, in a timely manner~~ or atcontamination ~~all, the improvements to our managerial, operational and financial systems, procedures and controls necessary to support our anticipated increased levels~~ of ~~operations~~raw ~~and~~materials ~~to coordinate our various corporate functions, or that we will be able to properly manage, train, motivate~~ and ~~retain~~components ~~our~~used ~~anticipated increased employee base. If we cannot manage our growth initiatives, we will be unable to commercialize our products on a large scale~~ in athe ~~timely~~manufacturing ~~manner~~process, ifparticularly atthose ~~all,~~for ~~and~~which ~~our~~we ~~business~~have ~~could~~no ~~fail.~~other supplier;

We• ~~may~~our ~~pursue~~ability ~~government~~to ~~funding~~comply inwith ~~the~~new ~~future.~~regulatory ~~Changing~~requirements ~~priorities~~and ~~within the U.S. government resulting in the loss of government grant funding could adversely impact our future growth plans.~~cGMP;

As• apotential ~~commercial-stage~~facility ~~medical~~contamination ~~device company, there are grants and other funding provided~~ by ~~the~~microorganisms ~~U.S.~~or government that we could apply for and receive. However, the current U.S. presidential administration has indicated that there will not only be a pause on government funding, but there will also be a change in who is eligible to receive it and for what purpose. These changes are not predictable and may impact our ability to receive government funding in the future. An inability to receive government funding could adversely impact our future growth plans. viruses;

We• ~~will~~updating ~~initially~~of ~~depend~~our onmanufacturing ~~revenue generated from a single product and in the foreseeable future will be significantly dependent on a limited number of products.~~specifications;

We• ~~will initially depend on revenue generated from our pediatric SCD and, if approved, our SCD~~ product ~~candidate~~quality ~~for~~success ~~pediatric~~rates and ~~adult~~yields; patients with AKI. Given that, for the foreseeable future, our business will depend on a single or limited number of products, to the extent a particular product is not well-received by the market, our sales volume, prospects, business, results of operations and ~~financial condition could be materially and adversely affected.~~

If• wedisruptions ~~fail~~outside ~~to comply with extensive regulations~~ of ~~United~~our ~~States and foreign regulatory agencies~~control, ~~the~~such ~~commercialization~~as ofglobal ~~our~~viruses ~~products~~and ~~could be delayed or prevented entirely~~pandemics.

~~Our~~If ~~SCD~~efficient ~~product~~manufacture ~~candidate~~ and ~~research~~supply and development activities are subject to extensive government regulations related to its development, testing, manufacturing and commercialization in the United States and other countries. The determination of ~~when and whether a product is ready for large-scale purchase and potential use in~~ the ~~United~~component ~~States~~parts ~~will be made by the United States government through consultation with a number~~ of ~~governmental~~our ~~agencies,~~SCD ~~including~~are ~~the FDA~~interrupted, ~~the~~we ~~National~~may ~~Institutes~~experience ofdelayed ~~Health~~shipments ~~and~~or ~~the~~supply ~~Centers for Disease Control and Prevention~~constraints. WeIf ~~have~~we ~~received~~are ~~approval~~at ~~for our pediatric SCD, but the product has not received regulatory approval from the FDA, or~~ any ~~foreign~~time ~~regulatory~~unable ~~agencies,~~to ~~for~~provide ~~use~~an ~~with~~uninterrupted ~~adult~~supply ~~patients. The process~~ of ~~obtaining~~our ~~and~~SCD, ~~complying~~our ~~with~~ongoing ~~FDA~~clinical ~~and~~trials ~~other governmental regulatory approvals~~ and ~~regulations~~commercialization inof ~~the~~QUELIMMUNE ~~United~~may ~~States~~be ~~and in foreign countries is costly~~delayed, ~~time-consuming,~~which ~~uncertain~~could materially and ~~subject~~adversely toaffect ~~unanticipated~~our ~~delays. Obtaining such regulatory approvals~~business, ifresults ~~any,~~of ~~can~~operations ~~take several years. Despite the time~~ and ~~expense~~financial ~~exerted, regulatory approval is never guaranteed~~condition. ~~We are also subject to the following risks and obligations, among others:~~

~~the FDA may refuse to approve an application if it believes that applicable regulatory criteria are not satisfied;~~ 38

~~the~~ Table ~~FDA~~of ~~may require additional testing for safety and effectiveness;~~Contents

~~the~~Our ~~FDA~~SCD technology may ~~interpret~~become ~~data from pre-clinical testing and clinical trials in different ways than we interpret them;~~obsolete.

ifOur ~~regulatory~~SCD ~~approval~~product ofcandidates amay become obsolete prior to commercialization by new scientific or technological developments, or by others with new treatment modalities that are more efficacious and/or more economical than our products. Further, new technological and scientific developments within the hospital setting could cause our SCD product iscandidates ~~granted~~to become obsolete. For example, the ~~approval~~SCD relies on the existing footprint of CRRT pump systems in ICUs, as well as the growing use and adoption of RCA. Further developments in these areas could require us to reconfigure our SCD product candidates, which may not be ~~limited~~commercially feasible, or cause them to ~~specific~~become ~~indications~~obsolete. orLastly, ~~limited~~our ~~with~~ability ~~respect~~to achieve significant and sustained growth in our key target markets will depend upon our success in hospital penetration, utilization, publication, our SCD’s reimbursement status and medical education. If we fail to ~~its~~sell ~~distribution;~~products that satisfy our customers’ demands or respond effectively to new product announcements by our competitors, then market acceptance of our products could be reduced and our business, results of operations and financial condition could be adversely affected.

~~the~~We ~~FDA~~face ~~may~~intense ~~change~~competition ~~its~~in ~~approval~~the ~~policies~~medical ~~and/or~~device ~~adopt new regulations~~industry.

~~Failure~~We tocompete ~~comply~~ with ~~these~~numerous United States and foreign companies in the medical device industry, and many of our competitors have greater financial, personnel, operational and research and development resources than us. Our commercial opportunities will be reduced or ~~other~~eliminated ~~regulatory~~if ~~requirements~~our competitors develop and market more effective products for any of the ~~FDA~~diseases ~~may~~we ~~subject~~target; ushave fewer or less severe adverse side effects; are better tolerated; are easier to ~~administrative~~administer; or ~~judicially~~are ~~imposed~~less ~~sanctions,~~expensive ~~including:~~than our products or our product candidates.

~~warning~~Even ~~letters~~if we successfully develop the adult SCD and any other future products and obtain FDA and other regulatory approvals necessary for commercializing them, ~~untitled~~our ~~letters~~products ormay not compete effectively with other ~~written~~products. ~~notice~~Our ofcompetitors ~~violations;~~include fully integrated pharmaceutical and medical device companies and biotechnology companies, universities, and public and private research institutions. If our competitors develop more effective treatments for infectious disease or hyperinflammation or bring those treatments to market before we can commercialize the SCD for such uses, we may be unable to obtain any market traction for our products, or the diseases we seek to treat may be substantially addressed by competing treatments. If we are unable to successfully compete against larger companies in the pharmaceutical industry, we may never generate significant revenue or be profitable.

36If our products, or the malfunction of our products, cause or contribute to a death or a serious injury, we will be subject to medical device reporting regulations, which can result in voluntary corrective actions or agency enforcement actions.

~~civil~~Under ~~penalties;~~the FDA medical device reporting regulations, medical device manufacturers are required to report to the FDA that a device has or may have caused or contributed to a death or serious injury or has malfunctioned in a way that would likely cause or contribute to a death or serious injury. If we fail to report these events to the FDA within the required timeframes, or at all, the FDA could take enforcement action against us. Any such adverse event involving our products could also result in future voluntary corrective actions, such as recalls or customer notifications, or agency action, such as inspection or enforcement action. Any corrective action, whether voluntary or involuntary, as well as defending against potential lawsuits, will require the dedication of our time and capital, distract management from operating our business, and may harm our reputation and financial results.

~~criminal penalties;~~ 39

~~injunctions;~~ Table of Contents

~~product~~A ~~seizure~~lack of third-party coverage and reimbursement for our devices could delay or ~~detention;~~limit their adoption.

~~product~~Healthcare ~~recalls;~~providers that use medical devices generally rely on third-party payors to pay for all or part of the costs and fees associated with the medical procedures being performed or to compensate them for their patient care services. Should our products under development be approved for commercialization by the FDA, reimbursement may not be available in the United States or other countries or, even if approved, the amount of reimbursement may not be sufficient to allow sales of our future products, including the SCD, on a profitable basis. The coverage decisions of third-party payors will be significantly influenced by the assessment of our future products by health technology assessment bodies. These assessments are outside our control, and any such evaluations may not be conducted or have a favorable outcome.

~~total~~We expect that any products that we develop, including the SCD, will be purchased primarily by medical institutions through their operations budget. Payors may include the CMS, which administers the Medicare program and works in partnership with state governments to administer Medicaid, other government programs and private insurance plans. The process involved in applying for coverage and incremental reimbursement from CMS is lengthy and expensive. Further, Medicare coverage is based on our ability to demonstrate that the treatment is “reasonable and necessary” for Medicare beneficiaries. Even if products utilizing our SCD technology receive FDA and other regulatory clearance or ~~partial~~approval, ~~suspension~~they may not be granted coverage and reimbursement by any payor, including by CMS. For some governmental programs, such as Medicaid, coverage and adequate reimbursement differ from state to state and some state Medicaid programs may not pay adequate amounts for the procedure products utilizing our technology system, or any payment at all. Moreover, many private payors use coverage decisions and payment amounts determined by CMS as guidelines in setting their coverage and reimbursement policies and amounts. Therefore, coverage and reimbursement can differ significantly from payor to payor. If CMS or other agencies limit coverage or decrease or limit reimbursement payments for doctors and hospitals, this may affect coverage and reimbursement determinations by many private payors for any future products of ~~production~~ours.

~~Delays~~Adverse changes in ~~successfully~~reimbursement ~~completing~~policies ~~our~~and ~~planned~~procedures ~~clinical~~by ~~trials~~payors ~~could~~may ~~jeopardize~~impact our ability to ~~obtain~~market ~~regulatory~~and ~~approval~~sell our products.

~~Our~~Third-party ~~business~~payors ~~prospects~~are ~~will~~increasingly ~~depend~~challenging onthe ~~our~~prices ~~ability~~charged tofor ~~complete~~medical ~~studies,~~products ~~clinical~~and ~~trials,~~services ~~including~~and ~~our~~instituting ~~planned~~cost ~~pivotal~~containment ~~trials~~measures ofto ~~our~~control ~~SCD~~or ~~for~~significantly ~~adult~~influence ~~AKI~~the ~~indication,~~purchase ~~obtain~~of ~~satisfactory~~medical ~~results,~~products ~~obtain required regulatory approvals~~ and ~~successfully~~services. ~~commercialize~~Additionally, ~~our~~executive ~~SCD~~orders ~~product~~have ~~candidate.~~directed ~~The~~governmental ~~completion~~agencies ofto ~~our~~review ~~clinical~~and ~~trials,~~reconsider ~~the~~policies ~~announcement~~that ofaffect ~~results~~healthcare ofaccess ~~the trials~~ and ~~our~~reimbursement, ~~ability~~which ~~to obtain regulatory approvals~~ could belead ~~delayed~~to ~~for~~further achanges ~~variety~~impacting ofour ~~reasons, including:~~business.

~~slow patient enrollment;~~ 40

~~insufficient~~ Table ~~hospital~~of ~~supplies or staffing;~~Contents

~~serious~~In ~~adverse~~addition, ~~events~~Congress ~~related~~is toconsidering additional healthcare reform measures. Legislation could be adopted in the future that limits payments for our products from governmental payors. Furthermore, commercial payors such as insurance companies, could adopt similar policies that limit reimbursement for medical device ~~candidates;~~manufacturers’ products. Therefore, it is possible that our products or the procedures or patient care performed using our products will not be reimbursed at a cost-effective level.

~~insufficient~~We ~~funding~~face similar risks relating to ~~engage~~adverse changes in reimbursement procedures and policies in other countries where we may market our products. Reimbursement and healthcare payment systems vary significantly among international markets. Our inability to obtain international reimbursement approval, or ~~continue~~any adverse changes in the reimbursement policies of foreign payors, could negatively affect our ability to ~~engage~~sell our products in foreign markets and have a ~~contract~~material ~~research~~adverse ~~organization~~effect on our business, results of operations and financial condition. However, we currently have no plans to ~~execute~~expand sales of QUELIMMUNE outside the ~~trials;~~U.S.

~~unsatisfactory~~If ~~results~~we ofor our contractors or service providers fail to comply with laws and regulations, we or they could be subject to regulatory actions, which could affect our ability to develop, market and sell our product candidates and any ~~clinical~~other ~~trial;~~future product candidates and may harm our reputation.

~~the~~If ~~failure~~we ofor ~~principal~~our manufacturers or other third-party ~~investigators~~contractors fail to ~~perform~~comply ~~clinical~~with ~~trials~~applicable onfederal, state or foreign laws or regulations, we could be subject to regulatory actions, which could affect our ~~anticipated~~ability ~~schedules;~~to successfully develop, market and sell our SCD product candidate or any future product candidates under development and could harm our reputation and lead to reduced or non-acceptance of our proposed product candidates by the market. Even technical recommendations or evidence by the FDA through letters, site visits, and overall recommendations to academia or biotechnology companies may make the manufacturing of a clinical product extremely labor intensive or expensive, making the product candidate no longer viable to manufacture in a cost-efficient manner. The mode of administration or the required testing of the product candidate may make that candidate no longer commercially viable. The conduct of clinical trials may be critiqued by the FDA, or a clinical trial site’s Institutional Review Board or Institutional Biosafety Committee, which may delay or make impossible the clinical testing of a product candidate.

~~different~~Even ~~interpretations~~with ofFDA ~~our~~approval, ~~pre-clinical~~we ~~and~~may ~~clinical~~still ~~data,~~be ~~which~~subject ~~could~~to ~~initially~~enforcement ~~lead~~action toif ~~inconclusive~~we ~~results~~engage in improper marketing or promotion of our products.

~~Our~~We ~~development~~are ~~costs~~not ~~will~~permitted ~~increase~~to ifpromote weor ~~have~~market ~~material~~our ~~delays~~product incandidates ~~any~~until ~~clinical~~FDA ~~trial~~approval is obtained. After approval, our promotional materials and training methods must comply with the FDA and other applicable laws and regulations, including the prohibition of the promotion of unapproved or ifoff-label weuse. ~~need~~Practitioners tomay ~~perform~~use ~~more~~our products off-label, as the FDA does not restrict or ~~larger~~regulate ~~clinical~~a ~~trials~~practitioner’s ~~than~~choice ~~planned.~~of Iftreatment within the ~~delays~~practice ~~are~~of ~~significant~~medicine. However, if the FDA determines that our promotional materials or iftraining ~~any~~constitutes promotion of ~~our~~an ~~product~~off-label ~~candidates~~use, doit ~~not~~could ~~prove~~request tothat bewe ~~safe~~modify our training or ~~effective~~promotional materials or dosubject ~~not~~us ~~receive~~to regulatory ~~approvals~~or enforcement actions, including the issuance of an untitled letter, a warning letter, injunction, seizure, civil fine, or criminal penalties. Other federal, state, or foreign enforcement authorities might also take action if they consider our ~~financial~~promotional ~~results~~or ~~and~~training ~~the~~materials ~~commercial~~to ~~prospects~~constitute promotion of an off-label use, which could result in significant fines or penalties under other statutory authorities, such as laws prohibiting false claims for reimbursement. In that event, our reputation could be damaged, which may lead to reduced or non-acceptance of our proposed product candidates ~~would~~by bethe ~~harmed~~market. ~~Furthermore~~In addition, ~~our~~the ~~inability~~off-label touse ~~complete~~of our ~~clinical~~products ~~trials~~may inincrease athe ~~timely~~risk ~~manner~~of product liability claims. Product liability claims are expensive to defend and could ~~jeopardize~~divert the attention of our ~~ability~~management, toresult ~~obtain~~in ~~regulatory~~substantial ~~approval~~damage awards against us, and harm our reputation.

Delays, interruptions, or the cessation of production by our third-party suppliers of important materials or delays in qualifying new materials, may prevent or delay our ability to manufacture or process our SCD device. 41

We Table currently rely on a single supplier for the cartridges and blood tubing sets used in the SCD device for the pediatric and adult AKI indications pursuant to supply agreements. In the event a current supplier is unable to provide cartridges or blood tubing sets for the SCD device or otherwise fails to meet its obligations under the agreement, we may not be able to obtain a sufficient number of cartridges or blood tubing sets to conduct our trials and commercialize our products. In addition, the supplier may decide to discontinue or terminate the specific type of cartridges or blood tubing sets that are required for our SCD for reasons beyond our control, in which case we will be forced to identify and secure an alternative source that may not be available immediately or at all. FDA review and approval of a new supplier may be required if these materials become unavailable from our current suppliers. Although there may be other suppliers that have equivalent materials that would be available to us, FDA review of any alternate suppliers, if required, could take several months or more to obtain, if it is able to be obtained at all. Any delay, interruption, or cessation of production by our third-party suppliers of important materials, or any delay in qualifying new materials, if necessary, would prevent or delay our ability to manufacture our SCD.Contents

We ~~believe~~intend ~~we have sufficient access~~ to ~~the~~outsource ~~SCD~~and ~~inventory~~rely toon ~~conduct~~third ~~our~~parties ~~current~~in part for ~~and~~the ~~near future~~ clinical ~~trials~~development and ~~commercial needs~~manufacture, ~~but~~sales itand ismarketing ~~possible~~of ~~that~~our ~~the~~SCD ~~need~~or ~~for~~any ~~our~~future ~~SCD~~product ~~could~~candidates ~~increase~~that ~~which~~we may ~~require~~develop, usand toour ~~acquire~~future ~~more~~success ~~cartridges~~will ~~than~~be wedependent ~~are~~on ~~currently~~the ~~able~~timeliness toand ~~purchase~~effectiveness ~~under~~of ~~our~~the ~~agreement~~efforts ~~with~~of ~~our~~these ~~supplier~~third parties, ~~and~~for which we ~~may~~will not behave ~~able~~full to control.

37We do not have the required financial and human resources to carry out on our own all the pre-clinical and clinical development for our SCD product candidate or any other or future product candidates that we may develop, and do not have the full capability and resources to manufacture, market or sell our SCD product candidate or any future product candidates that we may develop without the potential reliance on third parties. We rely on third-party consultants, vendors and distributors to manage and implement much of the day-to-day responsibilities of conducting clinical trials and manufacturing and distribution of our current products and product candidates. Our dependence on third parties includes key suppliers and third-party service providers supporting the development, manufacturing, distribution and regulatory approval of our SCD, as well as support for our information technology systems and other infrastructure. While our management team oversees these vendors, the failure of any of these third parties to meet their contractual, regulatory, and other obligations, or the development of factors that materially disrupt the performance of these third parties, could have a material adverse effect on our business, results of operations and financial condition.

~~negotiate~~We aare ~~new~~and ~~supply~~will ~~agreement~~be ~~successfully.~~exposed ~~If we are unable~~ to ~~find~~product ~~alternative~~liability ~~sources of supply in a timely manner~~risks, ~~any such delay could limit our ability to meet demand for the SCD~~ and ~~delay our ongoing~~ clinical ~~trials~~and orpreclinical ~~limit~~liability ~~our sales of QUELIMMUNE~~risks, which ~~would~~could ~~have~~place a ~~material~~substantial ~~adverse~~financial ~~impact~~burden onupon ~~our~~us ~~business,~~should ~~results~~litigation ofbe ~~operations and financial condition~~pursued.

~~Additionally,~~Our ~~use~~business ofexposes ~~the~~us ~~SCD~~to inpotential ~~the~~product ~~hospital~~liability ~~setting~~and ~~requires~~other ~~the~~liability ~~administration~~risks ofthat ~~RCA~~are ~~and~~inherent ~~calcium~~in ~~replacement~~the ~~into~~testing, ~~CRRT~~manufacturing, ~~circuitry~~and ~~for~~marketing ~~safe~~of ~~and~~medical ~~effective use~~devices. ~~Both~~ We ~~components~~may ~~are~~not IVbe ~~solutions~~able ~~which~~to ~~are~~continue ~~commonly~~to ~~stocked~~obtain byor ~~hospital~~maintain ~~systems. However,~~adequate ~~there~~product ~~are~~liability ~~limited~~insurance ~~manufacturers/suppliers~~on ofacceptable ~~these~~terms, IVif ~~solutions~~at ~~nationwide~~all, and ~~any~~such ~~supply~~insurance ~~chain~~may ~~disruptions~~not ~~may~~provide ~~have~~adequate ~~detrimental~~coverage ~~effects~~against topotential ~~the~~liabilities. ~~utilization~~Claims or losses in excess of ~~CRRT,~~any ~~and~~product ~~subsequently~~liability ~~use~~insurance ofcoverage ~~commercial~~that ~~QUELIMMUNE~~we ormay ~~the~~obtain ~~adult~~could ~~SCD~~have ina ~~clinical~~material ~~studies~~adverse effect on our business, results of operations and financial condition.

Our SCD product candidate may be used in connection with medical procedures where those products must function with precision and accuracy. If medical personnel or their patients suffer injury as a result of any failure of our products to function as designed, we may be subject to lawsuits seeking significant compensatory and punitive damages. We have ~~limited~~obtained ~~experience~~general clinical trial liability insurance coverage; however, our insurance coverage may not be adequate or available. In addition, we may not be able to obtain or maintain adequate product liability insurance on acceptable terms, if at all, and such insurance may not provide adequate coverage against potential liabilities. Any product recall or lawsuit in ~~identifying~~excess of any product liability insurance coverage that we may obtain could have a material adverse effect on our business, results of operations and ~~working~~financial ~~with~~condition. ~~large-scale~~Moreover, ~~contracts~~a ~~with~~product ~~medical~~recall ~~device~~could ~~manufacturers~~generate substantial negative publicity about our products and business and inhibit or prevent commercialization of other future product candidates.

To achieve the levels of production necessary to commercialize our SCD and any other future products, we will need to secure large-scale manufacturing agreements with contract manufacturers that comply with the manufacturing standards prescribed by various federal, state, and local regulatory agencies in the United States ~~and~~legislative ~~any~~or ~~other~~FDA ~~country~~regulatory ofreforms ~~use.~~may Wemake ~~have~~it ~~limited~~more ~~experience~~difficult ~~coordinating~~ and ~~overseeing~~costly ~~the~~for ~~manufacturing~~us ~~of medical device products on a large-scale. Manufacturing and control problems could arise as we attempt~~ to ~~commercialize~~obtain ~~our~~regulatory ~~products~~approval ~~and manufacturing may not be completed in a timely manner or at a commercially reasonable cost. In addition, we may not be able to adequately finance the manufacturing and distribution~~ of our ~~products~~product oncandidates ~~terms~~and ~~acceptable~~ to usmanufacture, ifmarket ~~at all. If we cannot successfully oversee~~ and ~~finance~~distribute ~~the manufacturing of~~ our products after ~~receiving regulatory~~ approval, weis ~~may not generate sufficient revenue to become profitable~~obtained.

~~Difficulties~~From intime ~~manufacturing~~to ~~our~~time, ~~SCD~~legislation is drafted and introduced in Congress that could ~~have~~significantly anchange ~~adverse~~the ~~effect~~statutory ~~upon~~provisions governing the regulatory approval, manufacture and marketing of regulated products or the reimbursement thereof. In addition, FDA regulations and guidance are often revised or reinterpreted by the FDA in ways that may significantly affect our ~~revenue~~business and ~~expenses~~our products. Any new regulations or revisions or reinterpretations of existing regulations may impose additional costs or lengthen review times of future products. It is impossible to predict whether legislative changes will be enacted, or FDA regulations, guidance or interpretations will be changed, and what the impact of such changes, if any, may be on our new product development efforts.

We ~~outsource~~are ~~the~~subject ~~manufacturing~~to ofstringent ~~component parts of our SCD~~ and ~~complete~~changing ~~final~~privacy ~~assembly~~laws, ofregulations ~~our SCD kits in-house. The outsourced manufacturing of SCD cartridges is complex~~ and ~~specialized.~~standards Toas ~~support~~well ~~our~~as ~~current clinical trial needs~~policies, wecontracts ~~comply with~~ and ~~intend~~other toobligations ~~continue~~related to ~~comply~~data ~~with~~privacy ~~current Good Manufacturing Practice (“cGMP”) for outsourced manufacturing~~ and ~~in-house assembly of our products~~security. Our ability to adequately supply our SCD in a timely manner is dependent on the uninterrupted and efficient operation of our third-party manufacturers, and those of the third parties producing raw materials and supplies upon which we rely on for the manufacturing of our products. The manufacturing of our products may be impacted by:

~~the~~We ~~availability~~collect, orreceive, ~~contamination~~store, ofprocess, ~~raw~~use, ~~materials~~generate, transfer, disclose, make accessible, protect, and ~~components~~share ~~used~~personal information and other information (“Process” or “Processing”), including information we collect in ~~the~~connection ~~manufacturing~~with clinical ~~process~~trials, ~~particularly~~as ~~those~~necessary to operate our business, for ~~which~~legal weand ~~have~~marketing nopurposes, and for other ~~supplier;~~business-related purposes.

~~our ability to comply with new regulatory requirements and cGMP;~~ 42

~~potential~~ Table ~~facility~~of ~~contamination by microorganisms or viruses;~~Contents

~~updating~~There are numerous federal, state, local and international laws, regulations and guidance regarding privacy, information security and Processing, the number and scope of which is changing, subject to differing applications and interpretations, and which may be inconsistent. We are subject, and may become subject in the future, to certain of these laws, regulations, and guidance, and we are also subject to the terms of our ~~manufacturing~~external ~~specifications;~~and internal privacy and security policies, representations, certifications, standards, publications, frameworks, and contractual obligations to third parties related to privacy, information security and Processing.

~~product~~If ~~quality~~we ~~success~~fail, ~~rates~~or ~~and~~it ~~yields;~~is ~~and~~perceived we have failed, to address or comply with such obligations, it could:

~~global~~• ~~viruses~~increase our compliance and ~~pandemics.~~operational costs;

If• ~~efficient~~expose ~~manufacture~~us ~~and supply of the component parts of our SCD are interrupted, we may experience delayed shipments or supply constraints. If we are at any time unable~~ to ~~provide~~regulatory ~~an uninterrupted supply of our SCD~~scrutiny, ~~our ongoing clinical trials and commercialization of QUELIMMUNE may be delayed~~actions, ~~which~~fines ~~could materially~~ and ~~adversely affect our business, results of operations and financial condition.~~penalties;

~~Our~~• ~~SCD~~result ~~technology~~in ~~may~~reputational ~~become~~harm; ~~obsolete.~~interrupt or stop our clinical trials;

~~Our~~• ~~SCD~~result ~~product~~in ~~candidates~~litigation ~~may~~and ~~become~~liability; ~~obsolete~~result ~~prior~~in toan ~~commercialization~~inability byto ~~new~~process ~~scientific~~personal ordata ~~technological developments,~~ or byto ~~others~~operate ~~with~~in ~~new~~certain ~~treatment~~jurisdictions; ~~modalities that are more efficacious and/~~or more economical than our products. Any one of our competitors could develop a more effective product which would render our technology obsolete. In addition, it is possible that competitors may use similar technologies, equipment or devices, including using

38• harm our business operations or financial results or otherwise result in material harm to our business.

~~certain~~The ~~“off-the-shelf”~~California ~~cartridges~~Consumer ~~unauthorized~~Privacy byAct ~~the~~of ~~FDA,~~2018 to(“CCPA”) ~~attempt~~is toan ~~create~~example aof ~~similar treatment mechanism as~~ the ~~SCD.~~increasingly ~~Further,~~stringent ~~new~~data ~~technological~~protection ~~and~~legislation ~~scientific~~in ~~developments within~~ the ~~hospital~~United ~~setting~~States. ~~could~~The ~~cause~~CCPA ~~our~~gives ~~SCD~~California ~~product~~residents ~~candidates~~expanded rights to ~~become~~access ~~obsolete.~~and ~~For~~require ~~example,~~deletion ~~the~~of ~~SCD~~their ~~relies~~personal oninformation, ~~the~~opt-out ~~existing footprint~~ of ~~CRRT~~certain ~~pump~~personal ~~systems~~information ~~in ICUs~~sharing, asand ~~well~~receive asdetailed ~~the~~information ~~growing~~about ~~use~~how ~~and~~their ~~adoption~~personal ofinformation ~~regional~~is ~~citrate as an anticoagulant~~used. ~~Further~~The ~~developments~~CCPA increated ~~these~~civil ~~areas~~penalties ~~could~~for ~~require~~violations, usas towell ~~reconfigure~~as ~~our~~a ~~SCD~~private ~~product~~right ~~candidates,~~of ~~which~~action ~~may~~for ~~not~~data bebreaches ~~commercially~~and ~~feasible,~~statutory ordamages ~~cause~~ranging ~~them~~from $100 to ~~become~~$750 ~~obsolete.~~per ~~Lastly~~violation, ~~our~~which ~~ability~~is expected to ~~achieve~~increase ~~significant~~data ~~and~~breach ~~sustained~~class ~~growth~~action inlitigation ~~our~~and ~~key~~result ~~target markets will depend upon our success~~ in ~~hospital~~significant ~~penetration,~~exposure ~~utilization,~~to ~~publication,~~costly ~~our~~legal ~~SCD’s~~judgments ~~reimbursement status~~ and ~~medical education~~settlements. ~~Our~~Although ~~products~~there ~~may~~are ~~not~~limited ~~remain~~exemptions ~~competitive~~for ~~with~~clinical ~~products~~trial ~~based~~data onunder ~~new~~the ~~technologies. If we fail to sell products that satisfy our customers’ demands or respond effectively to new product announcements by our competitors~~CCPA, ~~then~~the ~~market~~CCPA ~~acceptance~~and ofother ~~our~~similar ~~products~~laws could beimpact ~~reduced and~~ our business, ~~results~~activities ofdepending ~~operations~~on ~~and~~how ~~financial~~they ~~condition~~are ~~could be adversely affected~~interpreted.

WeOur ~~face~~business ~~intense~~operations ~~competition~~will inbe ~~the~~adversely ~~medical~~affected ~~device~~if ~~industry~~our security measures, or those maintained on our behalf, are compromised, limited or fail.

WeIn ~~compete~~the ~~with~~ordinary ~~numerous~~course ~~United~~of ~~States~~our business, we handle and ~~foreign~~process proprietary, ~~companies~~confidential inand ~~the~~sensitive ~~medical~~information, ~~device~~including ~~industry~~personal data, intellectual property, trade secrets, and ~~many~~proprietary ofbusiness ~~our~~information ~~competitors~~owned ~~have~~or ~~greater~~controlled ~~financial,~~by ~~personnel~~us or other third parties, ~~operational~~or ~~and~~collectively. ~~research~~We may use and ~~development~~share ~~resources~~such ~~than~~sensitive ~~us.~~information Wewith ~~believe~~service ~~that~~providers ~~multiple~~and ~~competitors~~other ~~are~~third orparties. ~~will~~If bewe, ~~developing~~our ~~competing~~service ~~technologies~~providers, topartners, ~~address~~or ~~cytokine~~other ~~storms.~~relevant ~~Progress~~third isparties ~~constant~~have experienced, or in the ~~treatment~~future ofexperience, ~~the~~any ~~immune~~security ~~system,~~incident ~~which~~or ~~may~~incidents ~~reduce~~that ~~opportunities~~result ~~for~~in ~~the~~any ~~SCD.~~data ~~Our~~loss; ~~commercial~~deletion ~~opportunities~~or ~~will~~destruction; beunauthorized ~~reduced~~access to; loss, unauthorized acquisition, disclosure, or ~~eliminated~~exposure ifof, confidential and sensitive information, it may adversely affect our ~~competitors~~business, ~~develop~~results of operations and ~~market~~financial ~~products~~condition, ~~for~~including ~~any~~the diversion of funds to address the ~~diseases~~breach, weand ~~target~~interruptions, ~~that:~~delays, or outages in our operations and development programs.

Cyberattacks, malicious internet-based activity and online and offline fraud are ~~more~~prevalent ~~effective;~~and continue to increase, including the possibility that the ongoing conflict between Russia and Ukraine or other regional conflicts, could result in cyberattacks or cybersecurity incidents that may have a direct or indirect impact on our operations. In addition to threats from traditional computer “hackers,” threat actors, software bugs, malicious code (such as viruses and worms), employee theft or misuse, denial-of-service attacks (such as credential stuffing) and ransomware attacks, sophisticated nation-state and nation-state supported actors now engage in attacks (including advanced persistent threat intrusions). We may also be the subject of phishing attacks, viruses, malware installation, server malfunction, software or hardware failures, loss of data or other computer assets, or other similar issues any of which could have a material and adverse effect on our business, results of operations and financial condition.

~~have fewer or less severe adverse side effects;~~ 43

~~are~~ Table ~~better~~of ~~tolerated;~~Contents

~~are~~We ~~easier~~depend on key personnel and our inability to ~~administer;~~attract orand retain qualified personnel could impede our ability to achieve our business objectives.

Our success depends on the continuing service of key employees, especially our Chief Executive Officer, Eric Schlorff. The loss of any of these individuals could have a material and adverse effect on our business, results of operations and financial condition. We will also be required to hire and recruit highly skilled managerial, scientific, and administrative personnel to fully implement our business plan and growth strategies. Due to the specialized scientific nature of our business, we are ~~less~~highly ~~expensive~~dependent ~~than~~upon our ~~products~~ability to attract and retain qualified scientific, technical and managerial personnel. Competition for these individuals is intense and we may not be able to attract, assimilate or retain additional highly qualified personnel in the future. Also, if we are required to attract personnel from other parts of the United States or abroad, we may have significant difficulty doing so because of the costs associated with moving personnel to the area. If we cannot attract and retain qualified staff and executives, we may be unable to develop our ~~product~~products ~~candidates~~and achieve regulatory clearance, and our business could fail.

Even if we successfully develop the SCD and any other future products and obtain FDA and other regulatory approvals necessary for commercializing them, our products may not compete effectively with other products. Researchers are continually learning more about diseases, which may lead to new technologies for treatment. Our ~~competitors may succeed in developing and marketing~~ products ~~that are either more effective than those that we~~ may develop or that are marketed before any of our products. Our competitors include fully integrated pharmaceutical and medical device companies and biotechnology companies, universities, and public and private research institutions. Many of the organizations competing with us have substantially greater capital resources, larger research and development staffs and facilities, greater experience in product development and in obtaining regulatory approvals, and greater marketing capabilities. If our competitors develop more effective treatments for infectious disease or hyperinflammation or bring those treatments to market before we can commercialize the ~~SCD~~future ~~for such uses, we may~~ be ~~unable~~subject to ~~obtain~~product ~~any market traction for our products, or the diseases we seek to treat may be substantially addressed by competing treatments~~recalls. ~~If we are unable to successfully compete against larger companies in the pharmaceutical industry, we may never generate significant revenue or be profitable.~~

IfThe ~~our~~FDA ~~products,~~and orsimilar foreign governmental authorities have the ~~malfunction~~authority to require the recall of ~~our~~commercialized products, ~~cause~~in the event of material deficiencies or ~~contribute~~defects in their design or manufacture. For the FDA, the authority to require a ~~death~~recall ormust be based on a finding that there is reasonable probability that the device would cause serious injury, weor ~~will~~death. Manufacturers may recall a product if any material deficiency in a device is found. The FDA requires that certain classifications of recalls be ~~subject~~reported to ~~medical~~the ~~device~~FDA ~~reporting~~within ~~regulations~~ten working days after the recall is initiated. A government-mandated or voluntary recall could occur as a result of an unacceptable risk to health, component failures, malfunctions, manufacturing errors, design or labeling defects or other deficiencies and issues. Recalls of any of our products would divert managerial and financial resources and have an adverse effect on our reputation, business, results of operations and financial condition, which ~~can~~could ~~result~~impair our ability to produce our products in ~~voluntary~~a ~~corrective~~cost-effective ~~actions~~and ortimely ~~agency~~manner ~~enforcement~~in ~~actions~~order to meet our customers’ demands.

~~Under~~We ~~the~~may ~~FDA~~also ~~medical~~be ~~device~~subject ~~reporting~~to ~~regulations~~liability claims, ~~medical~~be ~~device manufacturers are~~ required to ~~report~~bear toother ~~the~~costs, ~~FDA~~or ~~that~~take aother ~~device~~actions ~~has~~that or may have ~~caused or contributed to~~ a ~~death~~negative orimpact ~~serious~~on ~~injury~~our orfuture ~~has~~sales ~~malfunctioned~~and inour aability ~~way~~to ~~that~~generate ~~would~~profits. We ~~likely~~may ~~cause~~initiate orvoluntary ~~contribute~~recalls toinvolving aour ~~death~~products orin ~~serious~~the ~~injury.~~future Ifthat we ~~fail~~determine todo ~~report~~not ~~these~~require ~~events~~notification toof the FDA ~~within the required timeframes,~~ or ~~at all,~~ the ~~FDA~~competent ~~could~~authority ~~take~~of ~~enforcement~~another ~~action against us~~country. ~~Any~~If ~~such~~the ~~adverse~~FDA ~~event~~disagrees ~~involving~~with our ~~products~~determinations, they could ~~also~~require ~~result~~us into ~~future~~report ~~voluntary~~those ~~corrective~~ actions, ~~such~~ as recalls. orA ~~customer~~future ~~notifications,~~recall orannouncement ~~agency~~could ~~action,~~harm ~~such~~our asreputation ~~inspection~~with orcustomers ~~enforcement~~and ~~action.~~negatively ~~Any~~affect ~~corrective~~our ~~action,~~sales. ~~whether voluntary or involuntary~~Moreover, asthe ~~well~~FDA ascould ~~defending~~take ~~against~~enforcement ~~potential~~action ~~lawsuits,~~for ~~will~~failing ~~require~~to ~~the~~report ~~dedication~~recalls. ofWe ~~our~~are ~~time~~also ~~and~~required ~~capital,~~to ~~distract~~follow ~~management~~detailed ~~from~~recordkeeping ~~operating~~requirements ~~our~~for ~~business,~~all ~~and~~firm-initiated ~~may~~medical ~~harm~~device ~~our~~corrections ~~reputation~~ and ~~financial results~~removals.

39 44

We Table ~~outsource many~~ of ~~our operational and development activities for which we may not have full control.~~Contents

WeOur ~~rely~~forecasted onoperating ~~third-party consultants, vendors~~ and ~~distributors~~financial toresults ~~manage~~rely ~~and~~in ~~implement~~large ~~much~~part ofupon ~~the~~assumptions ~~day-to-day responsibilities of conducting clinical trials~~ and ~~manufacturing~~analyses ~~and~~developed ~~distribution~~by ~~of our current products and product candidates~~us. ~~Accordingly,~~If wethese ~~are~~assumptions and ~~will~~analyses ~~continue~~prove to be ~~dependent on the timeliness and effectiveness of the efforts of these third parties. Our dependence on third parties includes key suppliers and third-party service providers supporting the development~~incorrect, ~~manufacturing, distribution and regulatory approval of~~ our ~~SCD,~~actual asoperating ~~well as support for our information technology systems~~ and ~~other~~financial ~~infrastructure.~~results ~~While~~may ~~our~~be ~~management~~significantly ~~team~~below oversees these vendors, the failure of any of these third parties to meet their contractual, regulatory, and other obligations, or the development of factors that materially disrupt the performance of these third parties, could have a material adverse effect on our ~~business, results of operations and financial condition~~forecasts.

~~For~~We ~~example,~~have inpreviously ~~December~~provided ~~2022,~~projected wefinancial ~~entered~~and ~~into~~operating ~~the~~information ~~Distribution~~that ~~Agreement~~reflected ~~with Nuwellis, pursuant to which we appointed Nuwellis as~~ our ~~exclusive~~estimates ~~distributor for the sale and distribution~~ of ~~our~~future ~~pediatric~~performance. ~~SCD~~Whether ~~product~~actual ~~throughout~~operating ~~the~~and ~~United~~financial ~~States~~results ~~once~~and webusiness ~~receive~~developments ~~from~~will ~~the~~be ~~FDA~~consistent awith ~~written authorization to market such product for pediatric use pursuant to~~ our ~~HDE~~expectations ~~application.~~and Inassumptions ~~the~~as ~~event~~reflected ~~of a material breach if such breach is not cured within ninety (90) days after written notice, we have the right to terminate the Distribution Agreement~~ in ~~accordance~~our ~~with~~forecast ~~the~~depends ~~terms set forth in the Distribution Agreement. In May 2024, we provided notice to Nuwellis that Nuwellis had breached the Distribution Agreement. Nuwellis disputed the validity of the termination and~~ on ~~October 20, 2024, we entered into~~ a ~~confidential~~number ~~settlement~~of ~~agreement and release with Nuwellis~~factors, ~~pursuant~~many toof which weare ~~paid~~outside ~~Nuwellis~~our ancontrol, ~~aggregate of $900~~including,~~000~~ ~~payable~~but innot ~~three~~limited ~~installments through December 31, 2024.~~to:

A• ~~lack~~whether ofwe ~~third-party~~can ~~coverage~~obtain ~~and~~sufficient ~~reimbursement~~capital ~~for~~to develop and commercialize our ~~devices~~SCD ~~could~~product ~~delay~~candidates orand ~~limit~~grow ~~their~~our ~~adoption.~~business;

In• ~~both~~whether ~~the~~we ~~United~~can ~~States~~manage ~~and~~relationships international markets, the use and success of medical devices is dependent in part on the availability of reimbursement from third-party payors, such as government and private insurance plans. Healthcare providers that use medical devices generally rely on third-party payors to pay for all or part of the costs and fees associated with ~~the~~key ~~medical~~suppliers ~~procedures being performed~~ or tocontract ~~compensate~~research them for their patient care services. Should our products under development be approved for commercialization by the FDA, reimbursement may not be available in the United States or other countries or, even if approved, the amount of reimbursement may not be sufficient to allow sales of our future products, including the SCD, on a profitable basis. The coverage decisions of third-party payors will be significantly influenced by the assessment of our future products by health technology assessment bodies. These assessments are outside our control, and any such evaluations may not be conducted or have a favorable outcome.organizations;

If• ~~approved for use in~~ the United States, we expect that any products that we develop, including the SCD, will be purchased primarily by medical institutions through their operations budget. Payors may include the CMS, which administers the Medicare program and works in partnership with state governments to administer Medicaid, other government programs and private insurance plans. The process involved in applying for coverage and incremental reimbursement from CMS is lengthy and expensive. Further, Medicare coverage is based on our ability to ~~demonstrate~~obtain ~~that the treatment is “reasonable and~~ necessary” ~~for Medicare beneficiaries. Even if products utilizing our SCD technology receive FDA and other~~ regulatory clearance or approval, they may not be granted coverage and reimbursement by any payor, including by CMS. For some governmental programs, such as Medicaid, coverage and adequate reimbursement differ from state to state and some state Medicaid programs may not pay adequate amounts for the procedure products utilizing our technology system, or any payment at all. Moreover, many private payors use coverage decisions and payment amounts determined by CMS as guidelines in setting their coverage and reimbursement policies and amounts. However, no uniform policy for coverage and reimbursement of medical devices exists among third-party payors in the United States. Therefore, coverage and reimbursement can differ significantly from payor to payor. If CMS or other agencies limit coverage or decrease or limit reimbursement payments for doctors and hospitals, this may affect coverage and reimbursement determinations by many private payors for any future products of ours.approvals;

~~Adverse~~• ~~changes~~demand infor ~~reimbursement policies and procedures by payors may impact~~ our ~~ability to market and sell our~~ products.;

~~Healthcare~~• ~~costs have risen significantly over~~ the ~~past~~timing ~~decade,~~ and ~~there~~cost ~~have~~of ~~been~~new and ~~continue~~existing tomarketing ~~be proposals by legislators, regulators~~ and ~~third-party~~promotional ~~payors to decrease costs. Third-party payors are increasingly challenging the~~ efforts;

40• competition, including from established and future competitors;

~~prices~~• ~~charged~~our ~~for~~ability ~~medical products and services and instituting cost containment measures~~ to ~~control~~retain orexisting ~~significantly~~key ~~influence the purchase of medical products and services. Additionally~~management, ~~executive orders have directed governmental agencies~~ to ~~review~~integrate ~~and~~recent ~~reconsider~~hires ~~policies that affect healthcare access~~ and ~~reimbursement, which could lead~~ to ~~further~~attract, ~~changes~~retain ~~impacting~~and ~~our~~motivate ~~business.~~ qualified personnel;

~~Furthermore,~~• the ~~healthcare~~overall ~~industry~~strength inand ~~the~~stability ~~United~~of ~~States~~the ~~has~~economies ~~experienced~~in athe ~~trend~~markets ~~toward~~in ~~cost~~which ~~containment~~we asoperate ~~government~~or ~~and~~intend ~~private insurers seek~~ to ~~control~~operate healthcare costs by imposing lower payment rates and negotiating reduced contract rates with service providers. In addition, Congress is considering additional health reform measures. Legislation could be adopted in the future; that limits payments for our products from governmental payors. Furthermore, commercial payors such as insurance companies, could adopt similar policies that limit reimbursement for medical device manufacturers’ products. Therefore, it is possible that our products or the procedures or patient care performed using our products will not be reimbursed at a cost-effective level.and

We• face similar risks relating to adverse changes in reimbursement procedures and policies in other countries where we may market our products. Reimbursement and healthcare payment systems vary significantly among international markets. Our inability to obtain international reimbursement approvalregulatory, orlegislative ~~any adverse changes in the reimbursement policies of foreign payors, could negatively affect our ability to sell our products in foreign markets~~ and ~~have~~political ~~a material adverse effect on our business, results of operations and financial condition~~changes. ~~However, we currently have no plans to expand sales of QUELIMMUNE outside the U.S.~~

IfUnfavorable wechanges orin ~~our~~any ~~contractors~~of these or ~~service~~other ~~providers~~factors, ~~fail~~most toof ~~comply~~which ~~with~~are ~~laws~~beyond ~~and~~our ~~regulations~~control, ~~we or they~~ could bematerially ~~subject~~and toadversely ~~regulatory actions, which could~~ affect our ~~ability to develop~~business, ~~market~~results ~~and~~of ~~sell~~operations ~~our product candidates~~ and ~~any~~financial ~~other future product candidates and may harm our reputation~~condition.

IfOur weestimates orof ~~our~~market ~~manufacturers or other third-party contractors fail to comply with applicable federal~~opportunity, ~~state~~industry orprojections ~~foreign laws or regulations, we could be subject to regulatory actions, which could affect our ability to successfully develop, market~~ and ~~sell~~forecasts ~~our SCD product candidate or any future product candidates under development and could harm our reputation and lead to reduced or non-acceptance~~ of ~~our proposed product candidates by the~~ market. ~~Even~~growth ~~technical recommendations or evidence by the FDA through letters, site visits, and overall recommendations to academia or biotechnology companies~~ may ~~make~~prove ~~the manufacturing of a clinical product extremely labor intensive or expensive, making the product candidate no longer viable~~ to manufacture in a cost-efficient manner. The mode of administration or the required testing of the product candidate may make that candidate no longer commercially viable. The conduct of clinical trials may be ~~critiqued by the FDA, or a clinical trial site’s Institutional Review Board or Institutional Biosafety Committee, which may delay or make impossible the clinical testing of a product candidate~~inaccurate. For example, the Institutional Review Board for a clinical trial may stop a trial or deem a product candidate unsafe to continue testing. This would have a material adverse effect on the value of the product candidate and our business, results of operations and financial condition.

~~Even~~The ~~with~~market ~~FDA~~opportunity ~~approval~~estimates and growth forecasts included in this Annual Report, including information concerning our industry and the markets in which we ~~may~~intend ~~still~~to beoperate, are obtained from publicly available information released by independent industry and research organizations and other third-party sources. Although we are responsible for the disclosure provided in this Annual Report and believe such third-party information is reliable, we have not independently verified any such third-party information. In addition, projections, assumptions and estimates of the future performance of the industry in which we operate are subject to ~~enforcement~~uncertainty ~~action~~and ifrisk wedue ~~engage~~to a variety of factors. As a result, inaccuracies in ~~improper~~third-party ~~marketing~~information, or ~~promotion~~in ofthe projections, may adversely impact the assumptions that are relied upon for our ~~products~~internal business planning and in the analysis of investors.

We are not permitted to promote or market our product candidates until FDA approval is obtained. After approval, our promotional materials and training methods must comply with the FDA and other applicable laws and regulations, including the prohibition of the promotion of unapproved or off-label use. Practitioners may use our products off-label, as the FDA does not restrict or regulate a practitioner’s choice of treatment within the practice of medicine. However, if the FDA determines that our promotional materials or training constitutes promotion of an off-label use, it could request that we modify our training or promotional materials or subject us to regulatory or enforcement actions, including the issuance of an untitled letter, a warning letter, injunction, seizure, civil fine, or criminal penalties. Other federal, state, or foreign enforcement authorities might also take action if they consider our promotional or training materials to constitute promotion of an off-label use, which could result in significant fines or penalties under other statutory authorities, such as laws prohibiting false claims for reimbursement. In that event, our reputation could be damaged, which may lead to reduced or non-acceptance of our proposed product candidates by the market. In addition, the off-label use of our products may increase the risk of product liability claims. Product liability claims are expensive to defend and could divert the attention of our management, result in substantial damage awards against us, and harm our reputation. 45

41 Table of Contents

WeConflicts, ~~intend~~military toactions, ~~outsource~~terrorist ~~and~~attacks, ~~rely~~political ~~on third parties for the clinical development and manufacture~~events, ~~sales~~public ~~and~~health ~~marketing of our SCD or any future product candidates that we may develop~~crises, ~~and~~changes ~~our~~in ~~future~~regulatory ~~success will be dependent on the timeliness~~ regimes and ~~effectiveness~~general ofinstability, ~~the~~could ~~efforts~~adversely ofaffect ~~these~~our ~~third parties~~business.

WeConflicts, domilitary ~~not~~actions, ~~have~~terrorist ~~the~~attacks, ~~required~~political ~~financial~~events and ~~human~~public ~~resources~~health tocrises ~~carry~~have ~~out~~precipitated oneconomic ~~our~~instability ~~own all the pre-clinical~~ and ~~clinical~~turmoil ~~development~~in ~~for~~international ~~our~~commerce ~~SCD product candidate or any other or future product candidates that we may develop,~~ and ~~do not have~~ the ~~capability~~global ~~and resources to manufacture, market or sell our SCD product candidate or any future product candidates that we may develop~~economy. ~~Our~~The ~~business~~uncertainty ~~model~~and ~~calls~~economic ~~for~~disruption ~~the~~resulting ~~partial~~from ~~or full outsourcing of the clinical development~~hostilities, ~~manufacturing,~~military ~~sales,~~action ~~and~~or ~~marketing~~acts of ~~our~~terrorism ~~product~~may ~~candidates~~impact ~~in order to reduce~~ our ~~capital~~operations ~~and~~or ~~infrastructure~~those ~~costs as a means~~ of ~~potentially improving~~ our ~~financial~~suppliers ~~position.~~or ~~Our success will depend on the performance of these outsourced providers~~customers. IfAccordingly, ~~these~~any ~~providers fail to perform adequately~~conflict, ~~our~~military ~~development~~action ofor ~~product~~terrorist ~~candidates~~attack ~~may~~that beimpacts ~~delayed~~us ~~and~~or any ~~delay in the development~~ of our ~~product~~suppliers ~~candidates~~or ~~may~~customers, could have a material ~~and~~ adverse effect on our business, results of operations, ~~and~~ financial condition and/or liquidity.

WeRisks ~~are~~Relating ~~and will be exposed~~ to ~~product~~Our ~~liability~~Intellectual ~~risks, and clinical and preclinical liability risks, which could place a substantial financial burden upon us should we be sued.~~Property

~~Our~~We ~~business~~rely ~~exposes~~upon usexclusively tolicensed ~~potential~~patent ~~product~~rights ~~liability~~from ~~and~~third ~~other~~parties ~~liability~~which ~~risks that~~ are ~~inherent~~subject into ~~the~~termination ~~testing, manufacturing, and marketing of medical devices. A successful liability claim~~ or ~~series of claims brought against us could have a material adverse effect on our business, results of operations and financial condition~~expiration. WeIf ~~may~~licensors ~~not~~terminate bethe ~~able~~licenses toor ~~continue~~fail to ~~obtain~~maintain or ~~maintain~~enforce ~~adequate~~the ~~product~~underlying ~~liability insurance on acceptable terms~~patents, ifour atcompetitive ~~all,~~position ~~and such insurance may not provide adequate coverage against potential liabilities. Claims or losses in excess of any product liability insurance coverage that we may obtain~~ could ~~have~~be amaterially ~~material adverse effect on our business, results of operations and financial condition~~harmed.

~~Our~~We ~~SCD~~rely ~~product candidate may be used~~ in ~~connection~~part ~~with~~upon ~~medical~~exclusively ~~procedures~~licensed ~~where~~patent ~~those~~rights ~~products~~for ~~must~~the ~~function~~development ~~with precision and accuracy. If medical personnel or their patients suffer injury as a result~~ of ~~any failure of~~ our ~~products~~SCD totechnology. ~~function~~For ~~as designed~~example, orwe ~~our~~co-own ~~products are designed inappropriately~~with, ~~we may be subject to lawsuits seeking significant compensatory~~ and ~~punitive~~exclusively ~~damages. The risk of product liability claims~~licensed from, ~~product~~the ~~recalls~~UOM ~~and~~patents ~~associated~~related ~~adverse~~to ~~publicity is inherent in~~ the ~~testing,~~SCD ~~manufacturing, marketing, and sale of medical products~~technology. WeIf ~~have~~the ~~obtained~~UOM ~~general~~were ~~clinical~~to ~~trial~~terminate ~~liability~~its ~~insurance~~license ~~coverage;~~with ~~however~~us, ~~our~~we ~~insurance~~would ~~coverage~~no ~~may~~longer ~~not~~have beexclusive ~~adequate~~rights ~~or available. In addition, we may not be able~~ to ~~obtain~~the orco-owned ~~maintain~~patents ~~adequate product liability insurance on acceptable terms, if at all,~~ and ~~such~~the ~~insurance~~UOM ~~may~~would ~~not~~be ~~provide~~free ~~adequate~~to ~~coverage~~license ~~against~~the ~~potential~~UOM’s ~~liabilities.~~interest ~~Any product recall or lawsuit~~ in ~~excess~~the ofco-owned ~~any~~patents ~~product~~to ~~liability insurance coverage that we may obtain could have~~ a ~~material~~competitor ~~adverse effect on our business, results~~ of ~~operations and financial condition~~ours. ~~Moreover, a product recall could generate substantial negative publicity about our products and business and inhibit or prevent commercialization of other future product candidates.~~

~~United~~We ~~States~~may ~~legislative~~become orreliant ~~FDA~~in ~~regulatory~~the ~~reforms~~future ~~may~~upon ~~make~~licenses itto ~~more~~certain ~~difficult~~third-party patent rights and ~~costly~~proprietary ~~for~~technologies usnecessary to develop and commercialize our SCD technology or other technologies. If we are unable to timely obtain ~~regulatory~~these ~~approval~~licenses ofon commercially reasonable terms, if at all, our ~~product~~ability ~~candidates~~to ~~and~~commercially exploit such products may be inhibited or prevented. If these licenses do not provide exclusive rights to ~~manufacture,~~use ~~market~~the subject intellectual property in all relevant fields of use and ~~distribute~~all territories in which we choose to develop or commercialize our technology and products, ~~after~~we ~~approval~~may isnot ~~obtained~~be able to prevent competitors from developing and commercializing competitive products in such territories.

~~From~~Should ~~time~~any toof ~~time,~~our ~~legislation~~current isor ~~drafted~~future ~~and~~licenses ~~introduced~~be inprematurely ~~Congress~~terminated ~~that~~for ~~could~~any ~~significantly~~reason, ~~change~~or if the ~~statutory~~patents ~~provisions~~and ~~governing~~intellectual ~~the~~property ~~regulatory~~owned ~~approval,~~by ~~manufacture~~its ~~and~~licensors ~~marketing~~are ofchallenged ~~regulated products~~ or ~~the~~defeated ~~reimbursement~~by ~~thereof.~~third ~~In addition~~parties, ~~FDA~~our ~~regulations~~research and ~~guidance~~commercialization ~~are~~efforts ~~often~~could ~~revised~~be ormaterially ~~reinterpreted~~and byadversely ~~the~~affected. ~~FDA~~Our licenses may not continue in ~~ways~~force ~~that~~for ~~may~~as ~~significantly~~long ~~affect~~as ~~our~~is ~~business~~required to fully develop and market our products. ~~Any~~It ~~new~~is ~~regulations~~possible orthat ~~revisions~~if the licenses are terminated or ~~reinterpretations~~the ofunderlying ~~existing~~patents ~~regulations~~and ~~may~~intellectual ~~impose~~property ~~additional~~are ~~costs~~challenged or ~~lengthen~~defeated, ~~review~~suitable ~~times~~replacements ofmay ~~future~~not ~~products.~~be Itobtained isor ~~impossible~~developed on terms acceptable to ~~predict~~us, ~~whether~~if ~~legislative~~at ~~changes~~all. ~~will~~There beis ~~enacted,~~also orthe ~~FDA~~related ~~regulations,~~risk ~~guidance~~that orwe ~~interpretations~~may ~~will~~not be ~~changed,~~able ~~and~~to ~~what~~make the ~~impact~~required ofpayments ~~such~~under ~~changes,~~any ifpatent ~~any~~license, ~~may~~in bewhich oncase ~~our~~the ~~new~~licensor ~~product~~may ~~development~~terminate ~~efforts~~the license.

WeFurther, ~~are~~our ~~subject~~licensors tomay ~~stringent~~not successfully prosecute the patent applications which it has licensed and ~~changing~~on ~~privacy~~which ~~laws~~our business depends or may prosecute them in a manner not in our best interests. Further, ~~regulations~~licensors ~~and~~may ~~standards~~fail asto ~~well~~maintain aslicensed ~~policies~~patents, ~~contracts~~may ~~and~~decide ~~other~~not ~~obligations~~to ~~related~~pursue litigation against third-party infringers, may fail to ~~data~~prove ~~privacy~~infringement ~~and~~or ~~security~~may fail to defend against counterclaims of patent invalidity or unenforceability.

We collect, receive, store, process, use, generate, transfer, disclose, make accessible, protect, and share personal information and other information (“Process” or “Processing”), including information we collect in connection with 46

42 Table of Contents

~~clinical~~In ~~trials~~addition, asdespite ~~necessary~~our best efforts, a licensor could claim that we have materially breached a license agreement and terminate the license, thereby removing our ability to ~~operate~~obtain regulatory approval for and to market any product covered by such license. If our ~~business~~licenses are terminated, ~~for~~or ~~legal~~if ~~and~~the ~~marketing~~underlying ~~purposes~~patents fail to provide the intended market exclusivity, competitors would have the freedom to seek regulatory approval of, and ~~for~~to ~~other~~market, ~~business-related~~identical ~~purposes~~products.

~~There~~Disputes ~~are~~may ~~numerous~~arise ~~federal, state, local and international laws, regulations and guidance~~ regarding ~~privacy,~~intellectual ~~information~~property ~~security and Processing, the number and scope of which is changing,~~ subject to ~~differing~~a ~~applications~~licensing ~~and interpretations~~agreement, and which may be inconsistent. We are subject, and may become subject in the future, to certain of these laws, regulations, and guidance, and we are also subject to the terms of our external and internal privacy and security policies, representations, certifications, standards, publications, frameworks, and contractual obligations to third parties related to privacy, information security and Processing.including:

If• wethe ~~fail,~~scope orof itrights isgranted ~~perceived~~under wethe ~~have~~license ~~failed,~~agreement toand ~~address~~other orinterpretation ~~comply~~related ~~with such obligations, it could:~~issues;

~~increase~~• the extent to which our ~~compliance~~technology and ~~operational~~processes ~~costs~~infringe on intellectual property of the licensor that is not subject to the licensing agreement;

~~expose~~• usthe tosublicensing ~~regulatory~~of ~~scrutiny,~~patent ~~actions,~~and ~~fines~~other ~~and~~rights ~~penalties~~under any collaboration relationships we might enter into in the future;

~~result~~• inour ~~reputational~~diligence ~~harm;~~obligations ~~interrupt~~under orthe ~~stop~~license ~~our~~agreement ~~clinical~~and ~~trials~~what activities satisfy those diligence obligations;

~~result~~• inthe ~~litigation~~ownership ~~and~~of ~~liability;~~inventions ~~result~~and inknow anhow ~~inability~~resulting tofrom ~~process~~the ~~personal~~joint ~~data~~creation or touse ~~operate~~of inintellectual ~~certain~~property ~~jurisdictions~~by us and our licensors; orand

~~harm~~• ~~our~~the ~~business~~priority ~~operations~~of orinvention ~~financial~~of ~~results~~patented ~~or otherwise result in a material harm to our business~~technology.

~~Additionally,~~If ~~given~~disputes ~~that~~over ~~these~~intellectual ~~obligations~~property ~~impose~~that ~~complex~~we ~~and~~have ~~burdensome~~licensed ~~obligations~~prevents ~~and~~or ~~that~~impairs ~~there~~our isability ~~substantial~~to ~~uncertainty~~maintain ~~over~~our ~~the~~current ~~interpretation~~licensing ~~and~~arrangements ~~application~~on ofacceptable ~~these obligations~~terms, we may be ~~required~~unable to ~~incur~~successfully ~~material~~develop ~~costs, divert management attention,~~ and ~~change~~commercialize ~~our~~the ~~business~~affected ~~operations,~~product ~~including our clinical trials, in an effort to comply, which could materially adversely affect our business, results of operations and financial condition~~candidates.

~~The~~If ~~California~~we ~~Consumer~~are ~~Privacy~~unable ~~Act of 2018 (“CCPA”) is an example of the increasingly stringent data protection legislation in the United States. The CCPA gives California residents expanded rights~~ to ~~access~~obtain and ~~require~~maintain ~~deletion~~sufficient ofpatent ~~their~~protection ~~personal~~for ~~information,~~our ~~opt-out of certain personal information sharing~~products, ~~and~~if ~~receive~~the ~~detailed~~scope ~~information~~of ~~about~~the ~~how~~patent ~~their~~protection ~~personal information~~ is ~~used.~~not ~~The~~sufficiently ~~CCPA created civil penalties for violations~~broad, asor ~~well~~if asthe acombination ~~private right~~ of ~~action~~patents, ~~for~~trade ~~data~~secrets ~~breaches~~ and ~~statutory~~contractual ~~damages~~provisions ~~ranging~~upon ~~from $100 to $750 per violation,~~ which iswe ~~expected~~rely to ~~increase~~protect ~~data~~our ~~breach~~intellectual ~~class~~property ~~action~~are ~~litigation~~inadequate, ~~and~~our ~~result~~competitors incould ~~significant~~develop ~~exposure to costly legal judgments~~ and ~~settlements.~~commercialize ~~Although~~similar ~~there~~or ~~are~~identical ~~limited exemptions for clinical trial data under the CCPA~~products, ~~the CCPA~~ and ~~other~~our ~~similar~~ability ~~laws~~to ~~could~~commercialize ~~impact~~such ~~our~~products ~~business~~successfully ~~activities~~may ~~depending~~be onadversely ~~how they are interpreted~~affected.

Our success depends in large part on our ability to protect our proprietary rights to the technologies incorporated into our products, including our ability to obtain and maintain patent protection in the United States and other countries related to our SCD technology and other technologies that we deem important to our business. ~~operations~~We ~~will~~rely beon ~~adversely~~a ~~affected~~combination ifof patent protection, trade secret laws and nondisclosure, confidentiality, and other contractual restrictions to protect our ~~security~~proprietary ~~measures~~technology. If we do not adequately protect our intellectual property, competitors may be able to erode or ~~those~~negate ~~maintained~~any oncompetitive advantage we may have, which could harm our ~~behalf~~business, result of operations and financial condition. To protect our proprietary technologies, we have pursued patent protection in the United States and abroad related to our SCD technology and other technologies that are ~~compromised~~important to our business. The patent application and approval process are expensive and time-consuming. We may not be able to file and prosecute all necessary or desirable patent applications at a reasonable cost or in a timely manner. Failure to protect, ~~limited~~obtain, maintain, or ~~fail~~extend adequate patent and other intellectual property rights could materially adversely affect our ability to develop and market our products. The enforcement, defense and maintenance of such patents and other intellectual property rights may be challenging and costly.

InWe ~~the~~cannot ~~ordinary~~be ~~course~~certain ofthat ~~our~~any ~~business,~~patents that we ~~handle~~have ~~and~~been ~~processes~~issued ~~proprietary,~~or ~~confidential~~granted ~~and~~will ~~sensitive~~not ~~information,~~later ~~including~~be ~~personal~~found ~~data,~~to ~~intellectual~~be ~~property,~~invalid ~~trade~~and/or ~~secrets,~~unenforceable. ~~and~~We ~~proprietary~~cannot ~~business~~be ~~information~~certain ~~owned~~that orpending ~~controlled~~patent byapplications uswill orbe ~~other~~issued ~~third~~in ~~parties,~~a orform ~~collectively.~~that Weprovides ~~may~~it ~~use~~with ~~and~~adequate ~~share~~protection ~~such~~to ~~sensitive~~prevent ~~information~~competitors ~~with~~from ~~service~~developing ~~providers~~competing ~~and~~products. ~~other~~As ~~third~~a ~~parties.~~medical Ifdevice wetechnology company, our ~~service~~patent ~~providers,~~position ~~partners,~~is oruncertain ~~other~~because ~~relevant~~it ~~third~~involves ~~parties~~complex ~~have~~legal ~~experienced,~~and orfactual inconsiderations. ~~the~~The ~~future~~standards ~~experience,~~applied ~~any~~by ~~security~~United ~~incident~~States orPatent ~~incidents~~and ~~that~~Trademark ~~result~~Office (“USPTO”), and foreign patent offices in ~~any~~granting ~~data~~patents ~~loss;~~are ~~deletion~~not oralways ~~destruction;~~applied ~~unauthorized~~uniformly ~~access~~or ~~to;~~predictably. ~~loss~~For example, ~~unauthorized~~there ~~acquisition,~~is ~~disclosure,~~no uniform worldwide policy regarding patentable subject matter or ~~exposure~~the scope of, ~~confidential~~claims ~~and~~allowable ~~sensitive~~as ~~information~~methods of medical treatment. Consequently, itpatents may ~~adversely~~not ~~affect~~be ~~our~~issued ~~business,~~from ~~results~~any ofapplications ~~operations~~that ~~and~~are ~~financial~~currently ~~condition~~pending or that are filed in the future. As such, ~~including~~we do not know the ~~diversion~~degree of ~~funds~~future toprotection ~~address~~that we will have for our technology. As a result, the ~~breach~~issuance, ~~and~~scope, ~~interruptions~~validity, ~~delays~~enforceability, orand ~~outages~~commercial invalue of our ~~operations~~patent ~~and~~rights ~~development~~are ~~programs~~highly uncertain.

Cyberattacks, malicious internet-based activity and online and offline fraud are prevalent and continue to increase, including the possibility that the ongoing conflict between Russia and Ukraine could result in cyberattacks or cybersecurity incidents that may have a direct or indirect impact on our operations. In addition to threats from traditional computer “hackers,” threat actors, software bugs, malicious code (such as viruses and worms), employee theft or misuse, denial-of-service attacks (such as credential stuffing) and ransomware attacks, sophisticated nation-state and nation-state supported actors now engage in attacks (including advanced persistent threat intrusions). We may also be the subject of phishing attacks, viruses, malware installation, server malfunction, software or hardware failures, loss of data 47

43 Table of Contents

orOnly issued patents can be enforced against third parties practicing the technology claimed in such patents. Pending patent applications cannot be enforced unless and until patents get issued from such applications. Assuming the other ~~computer~~requirements ~~assets~~for patentability are met, orcurrently, ~~other~~patents ~~similar~~are ~~issues~~granted ~~any~~to ofthe ~~which~~party ~~could~~who ~~have~~was the first to file a ~~material~~patent ~~and~~application. ~~adverse~~However, ~~effect~~prior onto ~~our~~March ~~business~~16, ~~results~~2013, in the United States, patents were granted to the party who was the first to invent the claimed subject matter. Publications of ~~operations~~discoveries in the scientific literature often lag behind the actual discoveries, and ~~financial~~patent ~~condition~~applications in the United States and other jurisdictions are typically not published until 18 months after filing, or in some cases not at all. Therefore, we cannot be certain that we were the first to make the inventions claimed in our patents or pending patent applications, or that we were the first to file for patent protection of such inventions.

WeMoreover, ~~depend~~because onthe ~~key~~issuance ~~personnel~~of ~~and~~a patent is not conclusive as to its inventorship, scope, validity or enforceability, our ~~inability~~patents or pending patent applications may be challenged in the courts or by the USPTO or by foreign patent offices. For example, we may be subject to ~~attract~~a ~~and~~third-party ~~retain~~pre-issuance ~~qualified~~submission ~~personnel~~of prior art to the USPTO, or become involved in post-grant review procedures such as oppositions, derivations, reexaminations, inter partes review or interference proceedings, in the United States or elsewhere, challenging our patent rights or the patent rights of third parties. An adverse determination in any such challenges may result in the loss of exclusivity or in patent claims being narrowed, invalidated, or held unenforceable, in whole or in part, which could ~~impede~~limit our ability to ~~achieve~~stop others from using or commercializing similar products, or limit the duration of our ~~business~~patent ~~objectives~~protection. In addition, given the amount of time required for the development, testing and regulatory review of medical devices, our patents might expire before or shortly after such products receive FDA approval and are commercialized, or before we receive approval to market our products in a foreign country.

~~Our~~Changes ~~success~~in ~~depends~~either on the ~~continuing~~patent ~~service~~laws ofor ~~key~~interpretation ~~employees, especially our Chief Executive Officer, Eric Schlorff. The loss~~ of ~~any~~the ofpatent ~~these~~laws ~~individuals~~in ~~could~~the ~~have~~United aStates ~~material~~ and ~~adverse~~other ~~effect~~countries onmay ~~our~~diminish ~~business,~~the ~~results~~value of ~~operations and financial condition. We will also be required to hire and recruit highly skilled managerial, scientific, and administrative personnel to fully implement~~ our ~~business~~patents ~~plan~~or ~~and~~narrow ~~growth strategies. Due to~~ the ~~specialized~~scope ~~scientific nature~~ of our ~~business,~~patent ~~we are highly dependent upon our ability to attract and retain qualified scientific, technical and managerial personnel~~protection. ~~Competition~~In ~~for these individuals is intense and we may not be able to attract~~addition, ~~assimilate~~the orlaws ~~retain~~of ~~additional~~foreign ~~highly~~countries ~~qualified personnel in the future. We~~ may not beprotect ~~able~~our rights to ~~engage~~ the ~~services~~same ofextent ~~qualified personnel at competitive prices~~ or atin ~~all, particularly given~~ the ~~risks~~same ofmanner ~~employment~~as ~~attributable~~the tolaws ~~our limited financial resources and lack~~ of ~~an established track record. Also, if we are required to attract personnel from other parts of~~ the United States. orFor ~~abroad~~example, weEuropean ~~may~~patent ~~have~~law ~~significant~~restricts ~~difficulty~~the ~~doing~~patentability soof ~~because~~methods of ~~the~~treatment ~~costs~~of ~~associated with moving personnel to~~ the ~~area.~~human Ifbody wemore ~~cannot~~than ~~attract~~United ~~and~~States ~~retain~~patent ~~qualified staff and executives, we may be unable to develop our products and achieve regulatory clearance, and our business could fail~~law.

~~Our~~Although ~~products~~we believe that certain of our patents and applications, if they are granted, will help protect the proprietary nature of our SCD technology, this protection may innot be sufficient to protect us during the ~~future~~development of that technology. Our competitors may be ~~subject~~able to ~~product~~circumvent ~~recalls~~our patents by developing similar or alternative technologies or products in a non-infringing manner. Our competitors may also seek approval to market their own products similar to or otherwise competitive with any of our products. Thus, even if we have valid and enforceable patents, these patents still may not provide protection against competing products or technologies sufficient to achieve our business objectives.

~~The~~If ~~FDA~~we ~~and~~do ~~similar~~not ~~foreign~~obtain ~~governmental~~protection authorities have the authority to require the recall of commercialized products in the event of material deficiencies or defects in their design or manufacture. For the FDA, the authority to require a recall must be based on a finding that there is reasonable probability that the device would cause serious injury or death. Manufacturers may, under ~~their own initiative, recall a product if any material deficiency in a device is found. The FDA requires that certain classifications of recalls be reported to~~ the ~~FDA~~Hatch-Waxman ~~within~~Act ~~ten~~and ~~working~~similar ~~days after the recall is initiated. A government~~non-~~mandated~~United orStates ~~voluntary~~legislation ~~recall~~for ~~could~~extending ~~occur~~the asterm ~~a result~~ of anpatents ~~unacceptable~~covering ~~risk to health, component failures, malfunctions, manufacturing errors, design or labeling defects or other deficiencies and issues. Recalls of any of~~ our products, ~~would divert managerial and financial resources and have an adverse effect on~~ our ~~reputation,~~ business, results of operations and financial condition, ~~which~~may ~~could~~be ~~impair~~materially ~~our ability to produce our products in a cost-effective and timely manner in order to meet our customers’ demands~~harmed.

WePatents ~~may~~have ~~also~~a belimited ~~subject~~duration. toIn ~~liability~~the ~~claims~~United States, beif ~~required~~all tomaintenance ~~bear~~fees ~~other~~are ~~costs~~timely paid, orthe ~~take~~natural ~~other~~expiration ~~actions~~of ~~that may have~~ a ~~negative~~patent ~~impact~~is ongenerally ~~our~~20 ~~future~~years ~~sales~~from ~~and~~its ~~our~~earliest ~~ability~~United toStates ~~generate~~non-provisional ~~profits~~filing date. ~~Companies~~Even ~~are~~if ~~required~~patents related to ~~maintain~~our ~~certain records of recalls~~products, ~~even~~or iftheir ~~they~~uses are ~~not~~obtained, ~~reportable~~once to the ~~FDA~~patent orlife ~~the~~has ~~competent~~expired, ~~authority~~we ~~of another country. We~~ may ~~initiate~~be ~~voluntary~~open ~~recalls~~to ~~involving~~competition ~~our~~from competitive products. inGiven the ~~future~~amount ~~that~~of wetime ~~determine~~required dofor ~~not require notification of~~ the ~~FDA~~development, ortesting ~~the~~and ~~competent~~regulatory ~~authority~~review of ~~another~~new ~~country.~~product Ifcandidates, ~~the~~patents ~~FDA~~protecting ~~disagrees with~~ our ~~determinations,~~products ~~they~~might ~~could~~expire ~~require~~before usor toshortly ~~report~~after ~~those~~such ~~actions~~products asreceive ~~recalls.~~FDA Aapproval ~~future recall announcement could harm our reputation with customers~~ and ~~negatively~~are ~~affect~~commercialized. ~~our~~As ~~sales.~~a ~~Moreover~~result, ~~the~~our ~~FDA~~patent ~~could~~portfolio ~~take~~may ~~enforcement~~not ~~action~~provide ~~for~~us ~~failing~~with tosufficient ~~report~~rights ~~recalls. We are also required~~ to ~~follow~~exclude ~~detailed~~others ~~recordkeeping~~from ~~requirements~~commercializing ~~for~~similar ~~all~~or ~~firm-initiated~~identical ~~medical device corrections and removals~~products.

~~Our business is subject to risks arising from future pandemics.~~ 48

~~Worldwide~~ Table ~~pandemics~~of have presented substantial public health and economic challenges and has affected our employees, patients, communities, and business operations, as well as the United States and global economy and financial markets.Contents

ADepending ~~future~~upon ~~pandemic~~the timing, duration and requirements of FDA marketing approval of our product candidates, our United States patents, if issued, may ~~directly~~be eligible for a limited patent term extension under the Hatch-Waxman Act, or ~~indirectly~~under ~~impact~~similar legislation in other countries. However, our patent and patent applications are only eligible for a patent term extension under the ~~timeline~~Hatch Waxman Act if they relate to a medical device classified by the FDA as a Class III device. Therefore, if our product candidates are not classified as Class III devices, we will not be able to apply for an extension of term for any patents covering such approved products. If eligible, the ~~launch~~Hatch-Waxman Act permits a patent term extension of ~~our~~up ~~SCD~~to five years for a patent covering an approved product as compensation for effective patent term lost during product development and the FDA regulatory review process. The patent term extension cannot extend the remaining term of a patent beyond 14 years from the date of product candidate approval, and only one patent related to an approved product candidate may be extended. WeHowever, we may ~~experience~~not ~~disruptions~~receive ~~that~~an ~~could~~extension ~~severely~~if ~~impact~~it ~~our~~fails ~~business,~~to ~~clinical~~apply ~~trials~~within applicable deadlines, ~~and~~fails ~~manufacturing~~to ~~and~~apply ~~supply~~prior ~~chains~~to expiration of relevant patents or otherwise fails to satisfy applicable requirements. Moreover, ~~including:~~the length of the extension could be less than requested.

~~further~~Accordingly, ~~delays~~if we are unable to obtain a patent term extension or ~~difficulties~~the interm ~~enrolling~~of ~~patients~~any insuch extension is less than requested, the period during which we can enforce our ~~clinical~~patent ~~trials;~~rights for that product will be shortened and competitors may obtain approval to market competing products sooner than expected. As a result, our business, results of operations and financial condition could be adversely and materially affected.

~~delays~~We orcould ~~difficulties~~become involved in ~~clinical~~intellectual ~~site~~property ~~initiation,~~litigation ~~including~~that ~~difficulties~~could be costly, result in ~~recruiting~~the ~~clinical~~diversion ~~site~~of ~~investigators~~management’s time and ~~clinical~~efforts, ~~site~~require ~~staff;~~us to pay damages, prevent us from selling our commercially available products and/or reduce the margins we may realize from our products.

44Our commercial success depends, in part, on our ability to develop and market our SCD technology, as well as any future technologies that we develop, without infringing the intellectual property and other proprietary rights of third parties.

~~the~~The ~~diversion~~medical ofdevice ~~healthcare~~industry ~~resources~~is ~~away~~characterized ~~from~~by ~~the~~extensive ~~conduct~~litigation ofand ~~clinical~~administrative ~~trials~~proceedings over patent and other intellectual property rights. Whether a product infringes a patent involves complex legal and factual issues, ~~including~~and the ~~diversion~~determination is often uncertain. There may be existing patents of ~~hospital~~which ~~staff~~we ~~supporting~~are unaware that our products under development may inadvertently infringe. The likelihood that patent infringement claims may be brought against us increases as the ~~conduct~~number of ~~our~~competitors ~~clinical~~increases, ~~trials;~~as it introduces new products and achieves more visibility in the marketplace.

~~the~~Any ~~interruption~~infringement ofclaim ~~key~~against ~~clinical~~us, ~~trial~~even ~~activities~~if without merit, ~~such~~may ascause ~~clinical~~us ~~trial~~to ~~site~~incur ~~monitoring~~substantial costs, ~~due~~and towould ~~limitations~~place a significant strain on ~~travel~~our ~~imposed~~financial resources, divert the attention of management from our core business, and harm our reputation. In some cases, litigation may be threatened or ~~recommended~~brought by ~~federal~~a patent holding company or ~~state~~other ~~governments,~~adverse ~~employers~~patent owner who has no relevant product revenues and ~~others~~against whom our patents may provide little or ~~interruption~~no ofdeterrence. ~~clinical~~If ~~trial~~we ~~subject~~are ~~visits~~found to infringe any patents, we could be required to pay substantial damages. We also could be forced, including by court order, to cease developing, manufacturing, or commercializing infringing products. We also could be required to pay royalties and ~~study~~could ~~procedures~~be prevented from selling our products unless we obtain a license or are able to redesign our products to avoid infringement. We may not be able to obtain a license enabling us to sell our products on reasonable terms, ~~which~~or at all. If we fail to obtain any required licenses or make any necessary changes to our technologies or products, we may ~~impact~~be unable to commercialize one or more of our products or may have to withdraw products from the ~~integrity~~market, either of ~~subject~~which ~~data~~would ~~and~~have ~~clinical~~a ~~study~~material ~~endpoints;~~adverse effect on our business, results of operations and financial condition.

In the ~~interruption~~event a competitor infringes upon any of, our patents or ~~delays~~other inintellectual ~~receiving~~property rights, ~~supplies~~enforcing of our ~~product~~rights ~~candidates~~may be difficult, time consuming and expensive, and would divert management’s attention from managing our ~~contract~~business. ~~manufacturing~~We ~~organizations~~may ~~due~~not tobe ~~staffing~~successful ~~shortages~~on the merits in any enforcement effort. In addition, ~~production~~we ~~slowdowns~~may ornot ~~stoppages~~have ~~and~~sufficient ~~disruptions~~resources into ~~delivery~~litigate, ~~systems;~~enforce or defend our intellectual property rights.

~~delays in clinical sites receiving the supplies and materials needed to conduct our clinical trials and interruptions in global shipping may affect the transport of clinical trial materials;~~ 49

~~limitations~~ Table ~~on employee resources that would otherwise be focused on the conduct~~ of ~~our clinical trials, including because of sickness of employees or their families or the desire of employees to avoid contact with large groups of people;~~Contents

~~delays~~Issued inpatents ~~receiving~~covering ~~feedback~~one or ~~approvals~~more ~~from~~of ~~the~~our ~~FDA~~products orcould ~~other~~be ~~regulatory~~found ~~authorities~~invalid ~~with~~or ~~respect~~unenforceable toif ~~future~~challenged ~~clinical~~in ~~trials~~patent office proceedings, or ~~regulatory~~in ~~submissions;~~court.

~~changes~~Competitors inmay ~~local~~infringe ~~regulations~~our aspatents, ~~part~~trademarks, or other intellectual property. To counter infringement or unauthorized use of aour ~~response~~intellectual property, we may be required to initiate legal proceedings against a ~~future~~third ~~pandemic,~~party ~~which~~to ~~may~~enforce ~~require~~our usintellectual property rights. If we were to ~~change~~file a claim against a third party to enforce a patent covering one of our products, the ~~ways~~defendant incould ~~which~~counterclaim that our ~~clinical~~patent ~~trials~~rights are ~~conducted,~~invalid ~~resulting~~and/or inunenforceable ~~unexpected~~(a ~~costs,~~common orpractice ~~discontinuing~~in the ~~clinical~~United ~~trials altogether;~~States).

~~delays~~Grounds infor ~~necessary~~a ~~interactions~~validity ~~with~~challenge ~~local~~could ~~regulators,~~be ~~ethics~~an ~~committees~~alleged ~~and~~failure ~~other~~to ~~important~~meet ~~agencies~~one ~~and~~or ~~contractors~~more ~~due~~statutory torequirements ~~limitations~~for patentability. Grounds for an unenforceability assertion could be based on ~~employee~~an ~~resources~~allegation orthat ~~the~~someone ~~forced~~connected ~~furlough~~with prosecution of ~~government~~the ~~employees;~~patent intentionally withheld relevant information from the USPTO or made a misleading statement, during prosecution.

In any patent infringement proceeding, there is a risk that a court will decide that a company patent is invalid or unenforceable, in whole or in part. There is also a risk that, even if the ~~refusal~~validity of such patents is upheld, the ~~FDA~~court will construe the patent’s claims narrowly or decide that we do not have the right to ~~accept~~stop ~~data~~the other party from ~~clinical~~using ~~trials~~the invention at issue on the grounds that our patent claims do not cover the invention at issue. An adverse outcome in ~~affected~~a ~~geographies;~~litigation or proceeding involving our patents could limit our ability to assert our patents against those other parties and other competitors, which may curtail or preclude our ability to exclude third parties from selling similar products. Any of these occurrences could adversely and materially affect our business, results of operations and financial condition.

~~difficulties~~Even ~~launching~~if orwe ~~commercializing~~establish ~~products~~infringement, ~~including~~the ~~due~~court tomay ~~reduced~~decide ~~access~~not to ~~doctors~~grant asan 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 ~~result~~risk that some of ~~social~~our ~~distancing~~confidential ~~protocols~~information could be compromised by disclosure during litigation.

~~In addition~~Additionally, third parties are able to challenge the ~~spread~~validity of aissued ~~future~~patents ~~pandemic~~through ~~may~~administrative ~~negatively~~proceedings ~~impact~~in ~~our~~the ~~ability~~patent tooffices ~~raise~~of ~~additional~~certain ~~capital~~countries, onincluding athe ~~timely~~USPTO ~~basis~~and orthe atEuropean ~~all~~Patent Office.

~~The~~With ~~extent~~respect to ~~which~~the avalidity ~~future pandemic may impact our business~~question, ~~including~~for ~~our clinical trials~~example, ~~manufacturing~~we ~~and~~cannot ~~supply~~be ~~chains~~certain ~~and~~that ~~financial~~there ~~condition~~is ~~will~~no ~~depend~~invalidating onprior ~~future developments~~art, of which ~~are~~we ~~highly~~and ~~uncertain~~the ~~and~~patent ~~cannot~~examiner bewere ~~predicted~~unaware ~~with~~of ~~confidence,~~during ~~such~~prosecution. asIf ~~the~~a ~~continued~~defendant ~~geographic~~were ~~spread~~to ofprevail ~~the~~on ~~disease,~~a ~~the~~legal ~~duration~~assertion of ~~the~~invalidity ~~pandemic~~and/or unenforceability, ~~travel~~we ~~restrictions~~would ~~and~~lose ~~social~~some ~~distancing~~or inall of the ~~United~~patent ~~States~~protection ~~and~~for ~~other~~one ~~countries,~~or ~~continued~~more ~~business~~of ~~closures~~our orproducts. ~~business~~Such ~~disruptions~~a ~~and~~loss ~~the~~of ~~effectiveness~~patent ofprotection ~~actions~~could ~~taken~~have ina ~~the~~material ~~United~~adverse ~~States~~impact ~~and~~on ~~other~~its ~~countries~~business, toresults ~~contain~~of operations and ~~treat~~financial ~~the disease~~condition.

~~Our~~Other ~~forecasted~~parties ~~operating~~may ~~and~~challenge ~~financial~~certain ~~results~~of ~~rely~~our foreign patent applications. If any such parties are successful in ~~large~~opposing ~~part~~our foreign ~~upon~~patent ~~assumptions~~applications, ~~and~~we ~~analyses~~may ~~developed~~not gain the protection afforded by ~~us.~~those Ifpatent ~~these~~applications ~~assumptions~~in particular jurisdictions and ~~analyses~~may ~~prove~~face additional proceedings with respect to besimilar ~~incorrect~~patents in other jurisdictions, ~~our~~as ~~actual~~well ~~operating~~as ~~and~~related ~~financial~~patents. ~~results~~The ~~may~~loss beof ~~significantly~~patent ~~below~~protection in one jurisdiction may influence our ~~forecasts~~ability to maintain patent protection for the same technology in other jurisdictions.

WeIn ~~have~~addition, ~~previously~~the ~~provided~~European ~~projected~~Unified ~~financial~~Patent Court, or the UPC, came into force during 2023. The UPC is a common patent court to hear patent infringement and ~~operating~~revocation ~~information~~proceedings ~~that~~effective ~~reflected~~for ~~our~~member ~~estimates~~states of ~~future~~the ~~performance~~European Union. ~~Whether~~Although ~~actual~~we ~~operating~~have decided, and ~~financial~~may ~~results~~continue to decide, to opt out certain of our European patents and ~~business~~patent ~~developments~~applications ~~will~~from the UPC, if certain formalities and requirements are not met, then our European patents and patent applications could be ~~consistent~~challenged ~~with~~for non-compliance and brought under the jurisdiction of the UPC. Thus, we cannot be certain that our ~~expectations~~European patents and ~~assumptions~~patent asapplications ~~reflected~~will inavoid falling under the jurisdiction of the UPC. This could enable third parties to seek revocation of our ~~forecast~~European ~~depends~~patents onin a ~~number~~single ofproceeding ~~factors,~~at ~~many~~the UPC rather than through multiple proceedings in each of the jurisdictions in which ~~are~~the ~~outside~~European patent is validated. Any such revocation and loss of patent protection could have a material adverse impact on our ~~control~~business and our ability to commercialize or license our technology and products. Moreover, ~~including~~the controlling laws and regulations of the UPC will develop over time, ~~but~~and ~~not~~may ~~limited~~adversely affect our ability to: enforce or defend the validity of our European patents.

~~whether we can obtain sufficient capital to develop and commercialize our SCD product candidate and grow our business;~~ 50

~~whether~~ Table weof ~~can manage relationships with key suppliers;~~Contents

Further, disputes may arise regarding the ownership or inventorship of our patents. While we have entered into assignment of intellectual property agreements with our employees, consultants, and collaborators and believe that we own our patents and applications, the assignment and other ownership agreements that we rely on could be challenged. If a court or administrative body determined that we do not own certain of our patents or patent applications, or that inventorship of certain of its patents is incorrect, our title to our patents could be invalidated and our ability to ~~obtain~~develop ~~necessary~~and ~~regulatory~~commercialize ~~approvals;~~our technology could be materially harmed.

~~demand~~If ~~for~~we are unable to protect the confidentiality of our ~~products;~~trade secrets, the value of our technology could be adversely and materially affected, and our business could be harmed.

45We have also entered into non-disclosure and confidentiality agreements with all of our employees, advisors, consultants, contract manufacturers, clinical investigators and other third parties involved in the development and commercialization of our technology in order to protect our intellectual property and other proprietary technologies some of which may not be amenable to patent protection. However, these agreements may not be enforceable or may not provide meaningful protection for our trade secrets or other proprietary information in the event of unauthorized use or disclosure or other breaches of the agreements.

~~the~~Enforcing ~~timing~~a ~~and~~claim ~~costs~~that ofa ~~new~~party ~~and~~illegally ~~existing~~disclosed ~~marketing~~or misappropriated a trade secret is difficult, expensive, time consuming, and ~~promotional~~the ~~efforts;~~outcome is unpredictable. Accordingly, we may not be able to obtain adequate remedies for such breaches, despite any legal action we might take against persons making such unauthorized disclosure.

~~competition~~If any of our trade secrets were to be lawfully obtained or independently developed by a competitor, ~~including~~we would have no right to prevent such third party, or those to whom the third party communicates such technology or information, from ~~established~~using that technology or information to compete with us, and our ~~future~~business, ~~competitors;~~results of operations and financial condition could be adversely affected.

~~our~~Those ~~ability~~with whom we collaborate on research and development related to ~~retain~~current ~~existing~~and ~~key~~future ~~management~~technologies and products may have rights to publish data and other information to which we have rights. In addition, we sometimes engage individuals or entities to ~~integrate~~conduct ~~recent~~research ~~hires~~relevant to our business. The ability of these individuals or entities to publish or otherwise publicly disclose data and other information generated during the course of their research is subject to ~~attract~~certain contractual limitations. But these contractual provisions may be insufficient or inadequate to protect our confidential information. If we do not apply for patent protection prior to such publication, ~~retain~~or if we cannot otherwise maintain the confidentiality of our proprietary technology and ~~motivate~~other ~~qualified~~confidential ~~personnel;~~information, then our ability to obtain patent protection or to protect our trade secret information may be jeopardized.

~~the overall strength and stability of the economies in the markets in which it operates or intends to operate in the future; and~~ 51

~~regulatory,~~ Table ~~legislative~~of ~~and political changes.~~Contents

~~Unfavorable~~The ~~changes~~United inStates ~~any~~government ofmay ~~these~~exercise orcertain ~~other~~rights ~~factors,~~with ~~most~~regard ofto ~~which are beyond~~ our ~~control~~inventions, ~~could~~or ~~materially~~licensors’ ~~and adversely affect our business~~inventions, ~~results~~developed ofusing ~~operations~~federal ~~and~~government ~~financial condition~~funding.

~~Our~~The ~~estimates~~United States federal government retains certain rights in inventions produced with its financial assistance under the Patent and Trademark Law Amendments Act (as amended, the “Bayh-Dole Act”). Certain of ~~market~~our ~~opportunity~~exclusively owned patents and patent applications and those patents and applications that we co-own with and exclusively license from the University of Michigan were developed using federal funding from the National Institutes of Health, ~~industry~~the ~~projections~~U.S. Department of Defense, and/or ~~forecasts~~the U.S. Army Medical Research and Materiel Command. Consequently, pursuant to the Bayh-Dole Act, the U.S. government has certain rights in patents and applications that cover our SCD technology, in particular, to those patents and applications identified in the section of ~~market~~this ~~growth~~Annual ~~may~~Report ~~prove~~titled “Business – Intellectual Property” belonging to bePatent ~~inaccurate~~Families 1-4.

The ~~market~~U.S. ~~opportunity~~federal ~~estimates~~government ~~and~~has ~~growth~~certain ~~forecasts~~rights, ~~included~~including so-called “march-in ~~this~~rights,” ~~Annual~~to ~~Report,~~any ~~including~~patent ~~information~~rights ~~concerning~~that ~~our~~were ~~industry~~funded ~~and~~in part by the ~~markets~~U.S. ingovernment ~~which~~and weany ~~intend~~products toor ~~operate,~~technology developed from such patent rights. When new technologies are ~~obtained~~developed ~~from~~with ~~publicly~~U.S. ~~available~~government ~~information~~funding, ~~released~~the byU.S. ~~independent~~government ~~industry~~generally ~~and~~obtains ~~research~~certain ~~organizations~~rights ~~and~~in ~~other~~any ~~third~~resulting patents, including a non-~~party~~exclusive ~~sources~~license authorizing the U.S. ~~Although~~government weto ~~are~~use ~~responsible~~the invention for non-commercial purposes. These rights may permit the ~~disclosure~~U.S. ~~provided~~government into ~~this~~disclose ~~Annual~~our ~~Report~~confidential information to third parties and ~~believes~~to ~~such~~exercise ~~third~~march-~~party~~in ~~information~~rights isto ~~reliable~~use or to allow third parties to use our licensed patents, weincluding ~~have~~certain ~~not~~patents ~~independently~~relating ~~verified~~to ~~any~~SCD ~~such~~product ~~third-party~~candidates. ~~information~~The U.S. Ingovernment ~~addition,~~can ~~projections,~~exercise ~~assumptions~~its ~~and~~march-in ~~estimates~~rights ofif ~~the~~it ~~future~~determines ~~performance~~that ofaction is necessary because we fail to achieve the ~~industry~~practical inapplication ~~which~~of wegovernment-funded ~~operate~~technology, ~~are~~because ~~subject~~action is necessary to ~~uncertainty~~alleviate ~~and~~health ~~risk~~or ~~due~~safety needs, to ameet ~~variety~~requirements of ~~factors~~federal regulations, or to give preference to U.S. Asindustry. aIn ~~result~~addition, ~~inaccuracies~~our rights in ~~third-party~~such ~~information,~~inventions ormay be subject to certain requirements to manufacture products embodying such inventions in the ~~projections~~United States. Furthermore, ~~may~~the ~~adversely~~U.S. ~~impact~~government may have the ~~assumptions~~right ~~that~~to ~~are~~take ~~relied~~title ~~upon~~to ~~for~~government-funded ~~our~~inventions ~~internal~~if ~~business~~we ~~planning~~fail ~~and~~to indisclose the ~~analysis~~inventions ofto ~~investors~~the government in a timely manner or fails to file a patent application within specified time limits.

~~Risks~~If ~~Relating~~the U.S. government exercises such march-in rights, we may not be able to ~~Our~~develop ~~Intellectual~~or ~~Property~~commercialize our product candidates effectively or profitably, or at all, which could harm our business, results of operations and financial condition. In addition, if any intellectual property owned or licensed by us becomes subject to any of the rights or remedies available to the U.S. government or third parties pursuant to the Bayh-Dole Act, this could impair the value of our intellectual property and could adversely affect our business.

We ~~rely~~also ~~upon~~sometimes ~~exclusively~~collaborate ~~licensed~~with ~~patent~~academic ~~rights~~institutions ~~from~~to ~~third~~accelerate ~~parties~~our research or development. we try to avoid engaging our academic partners in projects in which ~~are~~there ~~subject~~is a risk that federal funds may be co-mingled, we cannot be sure that any co-developed intellectual property will be free from government rights pursuant to ~~termination~~the orBayh-Dole ~~expiration~~Act. If, ~~licensors~~in ~~terminate~~ the ~~licenses~~future, we co-own or ~~fail~~license technology which is critical to ~~maintain~~our business that is developed in whole or ~~enforce~~in part with federal funds subject to the ~~underlying~~Bayh-Dole ~~patents~~Act, our ~~competitive~~ability ~~position~~to ~~could~~enforce or otherwise exploit patents covering such technology may be adversely and materially ~~harmed~~affected.

WeChanges ~~rely~~to inthe ~~part upon exclusively licensed~~ patent ~~rights~~law ~~for~~in the ~~development~~United ofStates ~~our SCD technology. For example, we co-own with,~~ and ~~exclusively~~other ~~licenses~~jurisdictions ~~from,~~could ~~the~~diminish ~~UOM patents related to~~ the ~~SCD~~value ~~technology.~~of Ifpatents ~~the~~in ~~UOM were to terminate its license with us~~general, wethereby ~~would~~impairing noour ~~longer~~ability ~~have exclusive rights~~ to ~~the~~protect ~~co-owned~~our ~~patents and the UOM would be free to license the UOM’s interest in the co-owned patents to a competitor of ours~~products.

WeObtaining ~~may~~and ~~become~~enforcing ~~reliant~~patents in the ~~future~~medical ~~upon~~device ~~licenses~~industry toinvolves ~~certain~~both ~~third-party~~technological ~~patent rights~~ and ~~proprietary~~legal ~~technologies~~complexity ~~necessary to develop~~ and ~~commercialize~~is ~~our~~therefore ~~SCD~~costly, ~~technology~~time orconsuming ~~other~~and ~~technologies~~inherently uncertain. IfPatent wereform ~~are~~legislation ~~unable~~in tothe ~~timely~~United ~~obtain~~States ~~these~~and ~~licenses~~other oncountries could ~~commercially~~increase ~~reasonable~~those ~~terms,~~uncertainties ifand atcosts. The ~~all,~~United ~~our~~States ~~ability~~Supreme toCourt ~~commercially~~has ~~exploit~~ruled ~~such~~on ~~products~~several ~~may~~patent becases, ~~inhibited~~either ornarrowing ~~prevented.~~the Ifscope ~~these~~of ~~licenses~~patent doprotection ~~not~~available ~~provide~~or ~~exclusive~~weakening ~~rights to use~~ the ~~subject~~rights ~~intellectual~~of ~~property~~patent owners in ~~all~~certain ~~relevant~~circumstances. Depending ~~fields~~on offuture ~~use~~actions ~~and~~by ~~all~~Congress, ~~territories~~the inUnited ~~which~~States wecourts, ~~choose~~the toUSPTO ~~develop or commercialize our technology~~ and ~~products,~~the werelevant ~~may~~law-making ~~not~~bodies bein ~~able~~other tocountries, ~~prevent~~the ~~competitors~~laws ~~from~~and ~~developing~~regulations ~~and~~governing ~~commercializing~~patents ~~competitive~~could ~~products~~change in ~~such~~ways ~~territories.~~that ~~Even~~would ifweaken weour ~~are~~ability ~~able~~ to obtain ~~necessary~~new ~~licenses,~~patents weor ~~may be required~~ to ~~pay~~enforce ~~significant~~our ~~licensing~~existing ~~fees~~and infuture ~~order to market our products~~patents.

Should any of our current or future licenses be prematurely terminated for any reason, or if the patents and intellectual property owned by its licensors are challenged or defeated by third parties, our research and commercialization efforts could be materially and adversely affected. Our licenses may not continue in force for as long as is required to fully develop and market our products. It is possible that if the licenses are terminated or the underlying patents and intellectual property are challenged or defeated, suitable replacements may not be obtained or developed on terms acceptable to us, if at all. There is also the related risk that we may not be able to make the required payments under any patent license, in which case the licensor may terminate the license. 52

~~Further,~~ Table ~~our~~of licensors may not successfully prosecute the patent applications which it has licensed and on which our business depends or may prosecute them in a manner not in our best interests. Further, licensors may fail to maintain Contents

46Intellectual property rights do not necessarily address all potential threats to our competitive advantage.

~~licensed~~The ~~patents,~~degree ~~may~~of ~~decide~~future ~~not~~protection toafforded ~~pursue~~by ~~litigation~~our ~~against~~intellectual ~~third-party~~property ~~infringers~~rights is uncertain because intellectual property rights have limitations, and may ~~fail~~not toadequately ~~prove~~protect ~~infringement~~our business, or ~~may~~permit ~~fail~~us to ~~defend~~maintain ~~against~~our ~~counterclaims~~competitive ofadvantage. ~~patent~~The ~~invalidity~~following orexamples ~~unenforceability.~~are illustrative:

In• ~~addition,~~others ~~despite~~may ~~our~~be ~~best~~able ~~efforts,~~to amake ~~licensor~~products ~~could claim~~ that weare ~~have materially breached a license agreement and terminate~~ the ~~license,~~same ~~thereby~~as ~~removing~~or ~~our~~similar ~~ability~~ to ~~obtain~~our ~~regulatory~~products ~~approval~~but ~~for~~that ~~and~~are tonot ~~market any product~~ covered by ~~such~~the ~~license.~~claims Ifof ~~our~~patents ~~licenses~~that ~~are~~we ~~terminated,~~own or ~~if the underlying patents fail to provide the intended market exclusivity, competitors would~~ have ~~the~~rights ~~freedom~~ to ~~seek regulatory approval of, and to market, identical products.~~;

~~Disputes~~• ~~may~~we ~~arise~~or ~~regarding~~our ~~intellectual~~licensors ~~property~~or ~~subject~~any current or future strategic partners might not have been the first to aconceive ~~licensing~~or ~~agreement,~~reduce ~~including:~~to practice the inventions covered by our patents or pending patent applications;

~~the~~• ~~scope~~we ofor ~~rights~~our ~~granted~~licensors ~~under~~or any future strategic partners might not have been the ~~license~~first ~~agreement~~to ~~and~~file ~~other~~patent ~~interpretation~~applications ~~related~~covering ~~issues~~the inventions in our patents or applications;

~~the~~• ~~extent~~others tomay ~~which~~independently ~~our~~develop ~~technology~~similar ~~and~~or ~~processes~~alternative ~~infringe~~technologies onor ~~intellectual~~duplicate ~~property~~any of ~~the~~our ~~licensor~~technologies ~~that~~without isinfringing ~~not~~our ~~subject~~intellectual toproperty ~~the licensing agreement~~rights;

~~the~~• ~~sublicensing~~our ofpending patent ~~and~~rights ~~other~~may ~~rights~~not ~~under~~lead to issued patents, or the patents, if granted, may not provide us with any ~~collaboration~~competitive ~~relationships~~advantage, weor ~~might~~may ~~enter~~be ~~into~~held ininvalid ~~the~~or ~~future~~unenforceable, as a result of legal challenges by our competitors;

• our ~~diligence~~competitors ~~obligations~~might ~~under~~conduct ~~the~~research ~~license~~and ~~agreement~~development activities in countries where we do not have patent rights and ~~what~~then use the information learned from such activities ~~satisfy~~to ~~those~~develop ~~diligence~~competitive ~~obligations~~products for sale in our major commercial markets;

~~the~~• ~~ownership~~third ofparties ~~inventions~~manufacturing ~~and~~or ~~know~~testing ~~how~~our ~~resulting~~products ~~from~~or ~~the~~technologies ~~joint~~could ~~creation or~~ use ofthe intellectual property byof usothers ~~and~~without ~~our~~obtaining ~~licensors;~~proper ~~and~~licenses;

~~the~~• ~~priority~~we ofmay ~~invention~~not ofdevelop ~~patented~~additional ~~technology.~~technologies that are patentable; and

If• ~~disputes~~third ~~over~~parties ~~intellectual~~may ~~property~~allege that weour ~~have~~development ~~licensed~~and ~~prevents~~commercialization orof ~~impairs~~ our ~~ability~~products toinfringe ~~maintain~~their ~~our~~intellectual ~~current~~property ~~licensing~~rights, ~~arrangements~~and onthe ~~acceptable~~outcome ~~terms,~~of weany related litigation may behave ~~unable~~an toadverse ~~successfully~~effect ~~develop~~on ~~and~~our ~~commercialize~~business, ~~the~~results ~~affected~~of ~~product~~operations ~~candidates~~and financial condition.

IfObtaining ~~we are unable to obtain~~ and ~~maintain~~maintaining ~~sufficient~~our patent protection ~~for~~depends ~~our~~on ~~products,~~compliance ifwith ~~the~~various ~~scope of the patent protection is not sufficiently broad~~procedural, ordocument ~~if the combination of patents~~submissions, ~~trade~~fee ~~secrets~~payment and ~~contractual~~other ~~provisions~~requirements ~~upon~~imposed ~~which~~by wegovernmental ~~rely~~patent toagencies, ~~protect~~and our ~~intellectual~~patent ~~property~~protection ~~are inadequate, our competitors~~ could ~~develop~~be ~~and~~reduced ~~commercialize similar~~ or ~~identical~~eliminated ~~products,~~for ~~and~~noncompliance ~~our~~with ~~ability~~these ~~to commercialize such products successfully may be adversely affected~~requirements.

~~Our~~Periodic ~~success~~maintenance ~~depends~~fees ~~in large part~~ on ~~our~~any ~~ability~~issued topatent ~~protect~~are ~~our~~owed ~~proprietary rights~~ to the ~~technologies~~USPTO ~~incorporated into our products, including our ability to obtain~~ and ~~maintain~~foreign patent ~~protection~~agencies in ~~the~~several ~~United~~stages ~~States~~over ~~and~~the ~~other~~lifetime ~~countries~~of ~~related~~the topatent. ~~our~~The ~~SCD~~USPTO ~~technology~~ and ~~other~~various ~~technologies~~foreign ~~that~~governmental wepatent ~~deem~~agencies ~~important~~also torequire ~~our~~compliance ~~business.~~with ~~We rely on~~ a ~~combination~~number of ~~patent~~procedural, ~~protection~~documentary, ~~trade~~fee ~~secret~~payment ~~laws~~ and ~~nondisclosure, confidentiality, and~~ other ~~contractual~~similar ~~restrictions~~provisions toduring ~~protect~~the ~~our~~patent ~~proprietary~~application ~~technology~~process. IfWhile wean doinadvertent ~~not~~lapse ~~adequately~~can ~~protect~~in ~~our~~many ~~intellectual~~cases ~~property,~~be ~~competitors~~cured ~~may~~by bepayment ~~able~~of toa ~~erode~~late fee or ~~negate~~by ~~any~~other ~~competitive~~means ~~advantage~~in weaccordance ~~may~~with ~~have,~~the ~~which~~applicable ~~could~~rules, ~~harm~~there ~~our~~are ~~business,~~situations ~~result~~in ofwhich ~~operations~~noncompliance ~~and~~can ~~financial~~result ~~condition.~~in Toabandonment ~~protect~~or ~~our~~the ~~proprietary~~lapse ~~technologies,~~of wea ~~have~~patent ~~pursued~~or patent ~~protection~~application, resulting in the ~~United~~partial ~~States~~or ~~and~~complete ~~abroad~~loss ~~related~~of topatent ~~our~~rights ~~SCD~~in ~~technology~~the ~~and~~relevant ~~other~~jurisdiction. ~~technologies~~Noncompliance events that ~~are~~could ~~important~~result toin ~~our~~abandonment ~~business.~~or ~~The~~lapse ~~patent~~of ~~application~~a ~~and~~patent ~~approval~~or ~~process~~patent ~~are~~application ~~expensive~~include, ~~and~~but ~~time-consuming.~~are ~~We may~~ not belimited ~~able~~ to, ~~file~~failure ~~and~~to ~~prosecute~~respond ~~all~~to ~~necessary~~official oractions ~~desirable~~within ~~patent~~prescribed ~~applications~~time atlimits, anon-payment ~~reasonable~~of ~~cost~~fees orand infailure ~~a timely manner. Failure~~ to ~~protect,~~properly ~~obtain,~~legalize ~~maintain,~~and orsubmit ~~extend~~formal ~~adequate~~documents. ~~patent~~If ~~and~~we ~~other~~or ~~intellectual~~our ~~property~~licensors ~~rights~~fail ~~could~~to ~~materially~~maintain ~~adversely~~the ~~affect~~patents ~~our~~and ~~ability~~patent toapplications ~~develop~~covering ~~and market~~ our products~~. The enforcement~~, ~~defense~~our ~~and~~competitive ~~maintenance~~position ofwould ~~such patents and other intellectual property rights may~~ be ~~challenging~~adversely ~~and costly~~affected.

We cannot be certain that any patents that we have been issued or granted will not later be found to be invalid and/or unenforceable. We cannot be certain that pending patent applications will be issued in a form that provides it with adequate protection to prevent competitors from developing competing products. As a medical device technology company, our patent position is uncertain because it involves complex legal and factual considerations. The standards applied by United States Patent and Trademark Office (“USPTO”), and foreign patent offices in granting patents are not always applied uniformly or predictably. For example, there is no uniform worldwide policy regarding patentable subject matter or the scope of claims allowable as methods of medical treatment. Consequently, patents may not be issued from any applications that are currently pending or that are filed in the future. As such, we do not know the 53

47 Table of Contents

~~degree~~We ofmay ~~future~~obtain ~~protection~~only ~~that~~limited wegeographical ~~will~~protection ~~have~~with ~~for~~respect ~~our~~to ~~technology.~~certain Aspatent ~~a result~~rights, which may diminish the ~~issuance,~~value ~~scope,~~of ~~validity,~~our ~~enforceability,~~intellectual property rights in those jurisdictions and ~~commercial~~prevent ~~value~~us offrom enforcing our ~~patent~~intellectual property rights ~~are~~throughout ~~highly~~the ~~uncertain~~world.

~~Only~~We ~~issued~~have ~~patents~~not ~~can~~and bein ~~enforced against third parties practicing~~ the ~~technology~~future ~~claimed~~may innot ~~such~~file ~~patents.~~for ~~Pending~~ patent ~~applications~~protection ~~cannot~~in beall ~~enforced~~national ~~unless~~ and ~~until~~regional ~~patents~~jurisdictions ~~get~~where ~~issued from~~ such ~~applications.~~protection ~~Assuming~~may ~~the~~be ~~other~~available ~~requirements~~because ~~for~~it ~~patentability~~is ~~are~~cost ~~met, currently, patents are granted to the party who was the first to file a patent application~~prohibitive. ~~However,~~In ~~prior to March 16~~addition, ~~2013,~~we inmay ~~the~~decide ~~United States, patents were granted~~ to ~~the~~abandon ~~party~~national ~~who was the first to invent the claimed subject matter. Publications of discoveries in the scientific literature often lag behind the actual discoveries,~~ and regional patent applications inbefore ~~the~~grant, ~~United~~or ~~States~~to ~~and other jurisdictions are typically~~ not ~~published~~pay ~~until~~maintenance 18fees ~~months~~on ~~after~~granted ~~filing,~~patents or in ~~some~~certain ~~cases not at all~~jurisdictions. It ~~Therefore,~~is wealso ~~cannot~~quite becommon ~~certain~~ that wedepending ~~were~~on the ~~first~~country, ~~to make~~ the ~~inventions~~scope ~~claimed~~of ~~in our patents or pending~~ patent ~~applications,~~protection ormay ~~that~~vary wefor ~~were~~ the ~~first~~same toproduct ~~file~~candidate ~~for~~or ~~patent protection of such inventions~~technology.

~~Moreover,~~Competitors ~~because~~may ~~the~~use ~~issuance~~our oftechnologies ~~a patent is not conclusive as~~ to ~~its~~develop ~~inventorship,~~their ~~scope,~~own ~~validity~~products ~~or enforceability, our patents or pending patent applications may be challenged~~ in ~~the~~jurisdictions ~~courts~~where orwe byhave ~~the~~not ~~USPTO~~obtained ~~or by foreign~~ patent ~~offices.~~protection ~~For~~and, ~~example~~further, we may beexport ~~subject~~otherwise toinfringing aproducts ~~third-party~~to ~~pre-issuance~~territories ~~submission~~where ofwe ~~prior~~have ~~art~~patent ~~to the USPTO~~protection, orbut ~~become~~where ~~involved~~patent inenforcement ~~post-grant~~is ~~review~~not ~~procedures~~as ~~such~~strong as ~~oppositions,~~that ~~derivations, reexaminations, inter parties review or interference proceedings,~~ in the United States ~~or elsewhere, challenging our patent rights or the patent rights of third parties~~. AnThese ~~adverse~~products ~~determination in any such challenges~~ may ~~result~~also incompete ~~the~~with ~~loss~~our ofproducts ~~exclusivity or~~ in ~~patent~~jurisdictions ~~claims~~where ~~being~~we ~~narrowed,~~do ~~invalidated,~~not orhave ~~held~~any ~~unenforceable,~~issued ~~in whole~~ or inlicensed ~~part,~~patents ~~which could limit our ability to stop others from using~~ or ~~commercializing~~where ~~similar products, or limit the duration of~~ our patent ~~protection. In addition, given the amount of time required for the development, testing and regulatory review of medical devices, our patents might expire before~~ or ~~shortly~~other ~~after~~intellectual ~~such~~property ~~products~~rights ~~receive FDA approval and~~ are ~~commercialized,~~not effective or ~~before~~sufficient ~~we receive approval~~ to ~~market our~~prevent these products infrom acompeting ~~foreign~~with ~~country~~us.

~~Patent~~Additionally, ~~applications~~some ~~may~~countries do not ~~result~~afford inintellectual ~~patents~~property ~~being~~protection ~~issued~~to ~~which~~the ~~protect~~same ~~any~~extent ~~current~~as ~~and~~the ~~future~~laws ~~product~~of ~~candidates,~~the inUnited ~~whole~~States orand inEurope. ~~part,~~Many orcompanies ~~which~~have ~~effectively~~encountered ~~prevent~~significant ~~others~~problems ~~from~~in ~~commercializing~~protecting ~~competitive~~and ~~products.~~defending ~~Changes~~intellectual property rights in ~~either~~certain ~~the~~foreign ~~patent~~jurisdictions. ~~laws~~The orlegal ~~interpretation~~systems of ~~the~~some ~~patent~~countries ~~laws~~do innot favor the ~~United~~enforcement ~~States~~of patents and other ~~countries~~intellectual ~~may~~property ~~diminish~~rights. This could make it difficult for us to stop the ~~value~~infringement of our patents or ~~narrow~~ the ~~scope~~misappropriation of our ~~patent~~other ~~protection.~~intellectual Inproperty ~~addition,~~rights ~~the~~in ~~laws~~these ~~of foreign~~ countries. Competitors may ~~not~~use ~~protect~~ our ~~rights~~technologies to ~~the~~develop ~~same~~their ~~extent~~own orproducts in ~~the~~jurisdictions ~~same~~where ~~manner~~we ashave ~~the~~not ~~laws~~obtained ofpatent ~~the~~protection. ~~United~~Furthermore, ~~States.~~they ~~For~~may ~~example,~~export ~~European~~otherwise infringing products to jurisdictions where we have patent ~~law~~protection, ~~restricts~~if ~~the~~our ~~patentability~~ability ofto ~~methods~~enforce ofour ~~treatment~~patents ofto stop the ~~human~~infringing ~~body~~activities ~~more~~in ~~than~~those ~~United~~jurisdictions ~~States~~is ~~patent law~~inadequate.

~~Although~~Proceedings weto ~~believe~~enforce ~~that~~our ~~certain~~patent ofrights ~~our~~in ~~patents~~foreign ~~and applications~~jurisdictions, ifwhether ~~they~~or ~~are~~not ~~granted~~successful, ~~will~~could ~~help~~result ~~protect~~in ~~the~~substantial ~~proprietary~~costs ~~nature~~and ofdivert our ~~SCD~~efforts ~~technology,~~and ~~this~~resources ~~protection~~from ~~may~~other ~~not~~aspects ~~be sufficient to protect us during the development~~ of ~~that~~our ~~technology~~business. ~~Even~~Furthermore, ifwhile ~~our~~we ~~patent~~intend ~~applications~~to ~~are~~protect ~~issued~~our asintellectual ~~patents,~~property ~~they~~rights ~~may not be issued~~ in amajor ~~form~~markets ~~that~~for ~~will~~our ~~provide it with any meaningful protection~~products, ~~prevent~~we ~~competitors from competing with it or otherwise provide it with any competitive advantage. Our competitors~~ may not be able to ~~circumvent~~initiate ~~our~~or ~~patents~~maintain ~~by developing~~ similar orefforts ~~alternative~~in ~~technologies~~all orjurisdictions ~~products~~ in awhich ~~non-infringing~~we ~~manner.~~wish ~~Our competitors may also seek approval~~ to market ~~their own products similar to or otherwise competitive with any of~~ our products. ~~Thus~~Accordingly, ~~even~~our ifefforts weto ~~have~~protect ~~valid~~our ~~and~~intellectual ~~enforceable~~property ~~patents,~~rights ~~these~~in ~~patents~~such ~~still~~countries may ~~not~~be ~~provide protection against competing products or technologies sufficient to achieve our business objectives~~inadequate.

IfRisks weRelated doto ~~not~~Being ~~obtain~~a ~~protection~~Public under the Hatch-Waxman Act and similar non-United States legislation for extending the term of patents covering our products, our business, results of operations and financial condition may be materially harmed.Company

~~Patents~~We ~~have~~do anot ~~limited~~have ~~duration.~~long-term Inexperience ~~the~~operating ~~United~~as ~~States, if all maintenance fees are timely paid, the natural expiration of~~ a ~~patent is generally 20 years from its earliest~~ United States ~~non-provisional~~public ~~filing~~company ~~date. Various extensions may be available, but the life of a patent,~~ and ~~the protection it affords, is limited. Even if patents related to our products, or their uses are obtained, once the patent life has expired, we~~ may not be ~~open~~able to ~~competition~~adequately ~~from~~implement ~~competitive products. Given~~ the ~~amount of time required for the development~~governance, ~~testing and regulatory review of new product candidates~~compliance, ~~patents~~risk ~~protecting~~management ~~our~~and ~~products~~control ~~might~~infrastructure ~~expire before or shortly after such products receive FDA approval~~ and ~~are~~culture ~~commercialized.~~required Asfor a ~~result~~public company, ~~our~~including ~~patent~~compliance ~~portfolio may not provide us~~ with ~~sufficient~~the ~~rights~~Sarbanes-Oxley ~~to exclude others from commercializing similar or identical products~~Act.

48We are building experience operating as a United States public company and our executive officers have limited experience in managing a United States public company, which makes their ability to comply with applicable laws, rules, and regulations uncertain. Our failure to comply with all laws, rules and regulations applicable to United States public companies could subject us and our management to regulatory scrutiny or sanction, which could harm our reputation and share price. Although we are developing and implementing governance, compliance, risk management and control framework and culture required for a public company, we may not be able to meet the requisite standards expected by the SEC and/or our investors.

Depending upon the timing, duration and requirements of FDA marketing approval of our product candidates, our United States patents, if issued, may be eligible for a limited patent term extension under the Hatch-Waxman Act, or under similar legislation in other countries. However, our patent and patent applications are only eligible for a patent term extension under the Hatch Waxman Act if they relate to a medical device classified by the FDA as a Class III device. Therefore, if our product candidates are not classified as Class III devices, we will not be able to apply for an extension of term for any patents covering such approved products. If eligible, the Hatch-Waxman Act permits a patent term extension of up to five years for a patent covering an approved product as compensation for effective patent term lost during product development and the FDA regulatory review process. The patent term extension cannot extend the remaining term of a patent beyond 14 years from the date of product candidate approval, and only one patent related to an approved product candidate may be extended. However, we may not receive an extension if it fails to apply within applicable deadlines, fails to apply prior to expiration of relevant patents or otherwise fails to satisfy applicable requirements. Moreover, the length of the extension could be less than requested. 54

~~Accordingly,~~ Table ~~if we are unable to obtain a patent term extension or the term~~ of any such extension is less than requested, the period during which we can enforce our patent rights for that product will be shortened and competitors may obtain approval to market competing products sooner than expected. As a result, our business, results of operations and financial condition could be adversely and materially affected.Contents

WeAs ~~could~~a ~~become~~United ~~involved~~States inpublic ~~intellectual~~reporting ~~property~~company, ~~litigation~~we ~~that~~incur ~~could~~significant becosts ~~costly~~for legal, ~~result~~accounting, ininsurance, compliance, and other expenses. We cannot predict or estimate the ~~diversion~~amount of ~~management’s~~additional ~~time~~costs ~~and~~we ~~efforts,~~may ~~require~~incur usor tothe ~~pay~~timing ~~damages~~of such costs. Compliance with reporting, ~~prevent~~internal uscontrol ~~from~~over ~~selling~~financial reporting and corporate governance obligations may require members of our ~~commercially~~management ~~available~~and ~~products~~our finance and~~/or~~ ~~reduce~~accounting ~~the~~staff ~~margins~~to wedivert ~~may~~time ~~realize~~and resources from ~~our~~other ~~products~~responsibilities to ensure these new regulatory requirements are fulfilled.

~~Our~~Other ~~commercial~~challenges ~~success~~in ~~depends,~~complying inwith ~~part,~~these onregulatory ~~our~~requirements ~~ability~~may arise because we may not be able to ~~develop~~complete our evaluation of compliance and ~~market~~any ~~our~~required ~~SCD~~remediation ~~technology,~~in asa ~~well~~timely asfashion. Furthermore, any current or future ~~technologies~~controls ~~that~~may webe ~~develop,~~considered ~~without~~as ~~infringing~~inadequate ~~the~~due ~~intellectual~~to ~~property~~changes ~~and~~or ~~other~~increased ~~proprietary~~complexity ~~rights~~in ofregulations, ~~third~~our ~~parties~~operating environment or other reasons.

~~The~~Due ~~medical~~to ~~device~~inadequate ~~industry~~governance ~~is characterized by extensive litigation~~ and ~~administrative~~internal ~~proceedings~~control ~~over~~policies, ~~patent~~misstatements, ~~and~~or ~~other~~omissions ~~intellectual~~due ~~property~~to ~~rights.~~error ~~Whether~~or afraud ~~product~~may ~~infringes~~occur aand ~~patent~~may ~~involves~~not ~~complex~~be ~~legal~~detected, ~~and~~which ~~factual~~could ~~issues,~~result ~~and~~in ~~the~~failures ~~determination~~to ismake ~~often~~required ~~uncertain.~~filings ~~There~~in ~~may~~a betimely ~~existing~~manner ~~patents~~and ofmake ~~which~~filings wecontaining ~~are~~incorrect ~~unaware~~or ~~that~~misleading ~~our~~information. ~~products~~Any ~~under~~of ~~development~~these ~~may~~outcomes ~~inadvertently~~could ~~infringe.~~result ~~The~~in ~~likelihood~~SEC ~~that~~enforcement ~~patent~~actions, ~~infringement~~monetary ~~claims~~fines, ~~may~~or beother ~~brought~~penalties, ~~against~~as uswell ~~increases~~ as ~~the~~damage ~~number~~to ofour ~~competitors~~reputation, ~~increases~~business, asfinancial itcondition, ~~introduces~~operating ~~new~~results ~~products~~ and ~~achieves~~share ~~more visibility in the marketplace~~price.

~~Any~~Our ~~infringement~~Common ~~claim~~Stock ~~against us, even if without merit,~~ may ~~cause~~be usdelisted ~~to incur substantial costs, and would place a significant strain on our financial resources, divert the attention of management~~ from ~~our~~Nasdaq ~~core business, a~~

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