SYRE · Spyre Therapeutics, Inc.

Spyre Therapeutics announced positive initial 12-week induction topline data from Part A of the Phase 2 SKYLINE trial of SPY001 for moderate-to-severely active ulcerative colitis. The data demonstrated that SPY001 met its primary endpoint with a statistically significant reduction of 9.2 points in the Robarts Histopathology Index score at Week 12. Secondary endpoints showed clinically meaningful rates of 40% clinical remission and 51% endoscopic improvement, supporting the company's characterization of SPY001 as having potential best-in-class profile. The safety profile was consistent with the α4β7 class, with 14% of subjects experiencing any adverse event, no drug-related adverse events, and one serious adverse event deemed not drug-related. The company announced that recruitment for Part A is now closed and enrollment is open for Part B, which includes three monotherapy cohorts (SPY001, SPY002, SPY003) and three combination cohorts (SPY120, SPY130, SPY230). Proof-of-concept induction data for the remaining Part A cohorts are expected mid-2026 for SPY002 and Q3 2026 for SPY003, with Part B induction data for all cohorts remaining on track for 2027. Management highlighted that SPY001 was designed to improve upon vedolizumab's proven activity in IBD by matching its epitope and potency while increasing target coverage through extended half-life and greater induction dosing, and that its gut-selective mechanism makes it an ideal backbone for combination therapy.