Spyre reports positive Phase 2 SPY003 data, completing proof-of-concept for IBD trio

Spyre Therapeutics announced on September 8, 2026 that SPY003 met its primary endpoint with a statistically significant reduction of 10.0 points (p<0.0001) from baseline at Week 12 in Robart's Histopathology Index (RHI) score¹, according to a press release attached to an 8-K filing. Secondary results included clinical remission by modified Mayo Score of 20% and endoscopic improvement of 30%¹.

With this readout, Spyre has now reported positive Part A data for all three mechanisms in its IBD portfolio (α4β7, TL1A, and IL-23), with each component of the pairwise combinations in Part B reaching a clinical proof-of-concept stage¹. The company noted that the 10.0-point RHI reduction for SPY003 lines up with reductions of 9.2 and 10.7 points reported earlier for SPY001 and SPY002¹, and it described these as among the largest such changes reported in ulcerative colitis studies, according to the release.

On safety, SPY003 was well tolerated with a safety profile consistent with the IL-23 class, with 19 subjects reporting treatment-emergent adverse events during induction and three serious adverse events, none deemed drug-related¹. The most common adverse events, each occurring in two patients, were arthralgia, nasopharyngitis, and urinary tract infection¹. Data reflect 44 subjects through Week 12, with a data cut-off of July 27, 2026¹.

Looking ahead, Part B of SKYLINE will test two dose levels of each monotherapy along with three high-dose combination arms, SPY120, SPY130, and SPY230, with topline induction data expected in 2027¹. Spyre also listed SKYWAY topline data for SPY072 in PsA and axSpA expected in the fourth quarter of 2026, and SKYLIGHT data for SPY072 plus an IL-17A/F asset in HS expected in late 2027 or early 2028¹.