Spyre Therapeutics, Inc. reported positive topline results from the 12-week induction portion of Part A in its Phase 2 SKYLINE trial for SPY003. The study evaluated SPY003, an extended half-life antibody targeting IL-23, in patients with moderately-to-severely active ulcerative colitis (UC). The study population included 44 subjects with a mean disease duration of 7.1 years and a mean baseline modified Mayo Score of 6.9.
SPY003 met its primary endpoint, demonstrating a statistically significant reduction of 10.0 points in the Robart’s Histopathology Index (RHI) score from baseline at Week 12 (p<0.0001). Secondary endpoints included a clinical remission rate of 20% and an endoscopic improvement rate of 30%. The company noted that the 10.0-point reduction in RHI is comparable to reductions seen in trials for SPY001 and SPY002, which target alpha-4-beta-7 and TL1A, respectively.
Safety data indicated that SPY003 was well tolerated with a profile consistent with the IL-23 class. There were 19 subjects (43%) with treatment-emergent adverse events (TEAEs), and three serious adverse events (SAEs) were reported, all deemed not drug-related. The most common adverse events included arthralgia, nasopharyngitis, and urinary tract infection.
These results establish clinical proof-of-concept for all three components of Spyre’s combination strategy. Part B of the SKYLINE trial, which evaluates pairwise combinations of the assets, is currently enrolling. Topline induction data from Part B are expected in 2027. The company also outlined additional expected topline readouts, including SKYWAY data for Psoriatic Arthritis and Axial Spondyloarthritis in the fourth quarter of 2026.
