Spyre Therapeutics Reports Positive 12-Week Phase 2 SKYLINE Data For SPY001 In Moderate-To-Severe Ulcerative Colitis

Spyre Therapeutics, Inc., a clinical-stage biotechnology company developing long-acting antibodies and antibody combinations to transform the treatment landscape for inflammatory bowel disease (IBD) and rheumatic conditions, announced positive 12-week induction results from Part A of the Phase 2 SKYLINE trial evaluating SPY001. This investigational therapy is designed as a potential best-in-class anti-α4β7 antibody for patients with moderate-to-severely active ulcerative colitis (UC).

According to Deanna Nguyen, M.D., Senior Vice President of Clinical Development and lead for the SKYLINE study, SPY001 was engineered to build on the established activity of vedolizumab. The molecule matches vedolizumab’s epitope and potency while incorporating an extended half-life and enhanced induction dosing to increase target coverage. She noted that the newly released data reinforce the expectation that SPY001 could emerge as a best-in-class therapy when measured across safety, efficacy, and patient convenience. She also emphasized that SPY001’s gut-selective mechanism positions it as a strong foundation for combination regimens with Spyre’s other investigational cytokine-targeting antibodies, including SPY002 (anti-TL1A) and SPY003 (anti-IL23). Enrollment for these global combination studies has already begun, and early proof-of-concept findings are anticipated next year.

Spyre also confirmed that enrollment for Part A of SKYLINE is now complete. Recruitment has opened for Part B, which includes three monotherapy cohorts (SPY001, SPY002, and SPY003) and three combination cohorts (SPY120, SPY130, and SPY230). Participants in Part B may be randomized into these groups or a shared placebo arm. Updated timelines indicate that proof-of-concept induction data for the remaining cohorts in Part A are expected by mid-2026 for SPY002 and in the third quarter of 2026 for SPY003. Induction data from all Part B cohorts remain projected for 2027.

Sheldon Sloan, M.D., MBE, Chief Medical Officer of Spyre Therapeutics, expressed appreciation for the ongoing collaboration from patients and investigators participating in the study. He noted that the rapid completion of Part A enrollment reflects strong execution by the team and sets the stage for an efficient transition into Part B. Sloan added that the encouraging SPY001 results, combined with the low placebo allocation and the chance to evaluate three leading combination therapies, are expected to drive strong investigator engagement as the program advances.