Spyre Therapeutics, Inc. Announces Potential Best-In-Class SPY001 Induction Results From Skyline Trial In Moderate-To-Severe Ulcerative Colitis Patients

Published: 2026-04-13 15:08:40 ET SYRE

Published on 04/13/2026 at 03:08 pm EDT

Spyre Therapeutics, Inc. announced positive 12-week induction data from Part A of the Phase 2 SKYLINE trial of SPY001, a potential best-in-class anti-a4ß7 being investigated for the treatment of moderate-to-severely active ulcerative colitis (UC). SPY001 met its primary endpoint with a statistically significant reduction of 9.2 points (p. Secondary endpoints included clinical remission by modified Mayo Score of 40% and endoscopic improvement of 51%. SPY001 was well tolerated with a safety profile consistent with the a4ß7 class.

Recruitment for SKYLINE Part A closed, now enrolling Part B monotherapy and combination cohorts. Additionally, Spyre announced that recruitment for Part A of SKYLINE is now closed and enrollment is open for Part B, which includes three monotherapy cohorts (SPY001, SPY002, and SPY003) and three combination cohorts (SPY120, SPY130, and SPY230) into which participants may be randomized versus a shared placebo. Proof-of-concept induction data for the remaining cohorts of Part A are now expected mid-2026 (SPY002) and Third Quarter 2026 (SPY003).

Part B induction data (all cohorts) remain on track for 2027. SKYLINE is a two-part induction and maintenance platform trial of SPY001, SPY002, SPY003, as well as pairwise combinations thereof (six investigational agents total) in patients with moderately to severely active ulcerative colitis. Part A is an open-label assessment of the safety and efficacy of a single dose level of each investigational monotherapy, and Part B is a randomized and placebo-controlled assessment of the safety and efficacy of investigational monotherapies (two dose levels) and combinations.

SPY001 is an extended half-life investigational antibody targeting a4ß7, an integrin central to immune cell trafficking to the gut. Initial 12-week findings from SKYLINE Part A demonstrated that SPY001 met or exceeded all key objectives. Efficacy: SPY001 achieved the primary endpoint, demonstrating a statistically significant reduction in the RHI score of 9.2 points (p<0.0001).

Rates of key secondary endpoints of clinical remission and endoscopic improvement were clinically meaningful and support SPY001?s potential best-in-class profile.Safety: SPY001 was well tolerated with a safety profile consistent with the a4ß7 class. There were six subjects with treatment-emergent adverse events (TEAEs) during the induction treatment period, with one serious adverse event (SAE), deemed not drug-related. The most common AE (occurring in = 2 patients) was back pain (n=2).