Spyre Therapeutics (NASDAQ: SYRE) reported 12-week induction data from Part A of its Phase 2 SKYLINE trial showing that SPY003, an investigational anti-IL-23 antibody, met its primary endpoint in patients with moderately-to-severely active ulcerative colitis (UC).

SPY003 produced a statistically significant 10.0-point reduction from baseline in Robart's Histopathology Index (RHI) score at Week 12 (p<0.0001). Secondary endpoints showed a clinical remission rate of 20% by modified Mayo Score and an endoscopic improvement rate of 30%. The modified Mayo Score declined by 3.5 points.

The trial's study population included 41% advanced therapy-exposed participants, a mean disease duration of 7.1 years, and a mean baseline RHI score of 17.2. The data cut-off was July 27, 2026, with 44 subjects evaluated.

On safety, 19 of 44 subjects (43%) experienced treatment-emergent adverse events. Three serious adverse events were reported, all deemed not drug-related. No deaths or drug-related serious adverse events occurred, and no patients discontinued due to an adverse event.

The SPY003 result follows previously reported Part A data for SPY001 (anti-α4β7) and SPY002 (anti-TL1A), which showed RHI reductions of 9.2 and 10.7 points, respectively. Spyre stated that all three monotherapies have now established clinical proof-of-concept.

Part B of the SKYLINE trial, which evaluates pairwise combinations of the three agents — SPY120, SPY130, and SPY230 — is currently enrolling. Topline induction data from Part B are expected in 2027. Spyre also expects data from its SKYWAY trial in psoriatic arthritis and axial spondyloarthritis in the fourth quarter of 2026, and from the SKYLIGHT trial in hidradenitis suppurativa in late 2027 or early 2028.