Spyre Therapeutics Announces Topline SKYWAY‑RA (SPY072) Phase 2 Results

What Happened

• On August 25, 2026 Spyre Therapeutics (SYRE) filed an 8-K and issued a press release reporting topline results from the Phase 2 SKYWAY rheumatoid arthritis (RA) sub‑study of SPY072. The randomized, placebo‑controlled study tested two doses (High, Low) versus placebo in patients with moderate‑to‑severe RA, with the primary endpoint being change from baseline to Week 12 in DAS28‑CRP and a key secondary of ACR20 at Week 12.
• Results: SPY072 Low Dose showed a statistically significant improvement versus placebo on the primary endpoint (ΔDAS28‑CRP at Week 12: High = -1.5; Low = -1.9*; Placebo = -1.3; p<0.05). Nominally significant improvements versus placebo were seen for ACR20 with High Dose (63%* vs placebo 43%) and for ACR50 with Low Dose (38%** vs placebo 19%). Both doses achieved target drug concentrations and complete suppression of free TL1A through Week 12. Safety was generally favorable and consistent with the TL1A class.
• Despite proof‑of‑mechanism in RA, Spyre said these results did not meet its internal bar to prioritize SPY072 as a monotherapy in RA and will focus development priorities across its immunology & inflammation programs.

Key Details

• Filing date: August 25, 2026; press release attached as Exhibit 99.1 to the 8‑K.
• Subject counts: SPY072 High Dose N=48, Low Dose N=48, Placebo N=47.
• Efficacy snapshots at Week 12: ΔDAS28‑CRP High -1.5 / Low -1.9* / Placebo -1.3; ACR20 High 63%, Low 58%, Placebo 43%; ACR50 High 31%, Low 38%, Placebo 19%. (*p<0.05; **nominal p<0.05.)
• Safety: overall TEAEs 27% (active) vs 36% (placebo); infections 14% (active) vs 15% (placebo); one serious TEAE each arm (none drug‑related); one death in placebo arm.

Why It Matters

• The data provide clinical proof‑of‑mechanism for TL1A blockade in RA (target engagement and meaningful activity on key endpoints), which supports further development of the TL1A program in autoimmune diseases and as a combo partner.
• However, Spyre will not prioritize SPY072 as an RA monotherapy based on internal criteria, which may redirect resources to other assets and upcoming readouts (e.g., SKYLINE Part A UC SPY003 expected Sep 2026; SKYWAY PsA/axSpA SPY072 expected 4Q 2026). Investors should view this as a mixed outcome: positive signal and tolerability, but limited near‑term upside for SPY072 as a standalone RA drug.