SPY001, SPY002, SPY003 - (SKYLINE)

September 8, 2026: Spyre Therapeutics (NASDAQ: SYRE) reported positive 12-week Phase 2 SKYLINE Part A induction data for SPY003 (anti-IL-23) in moderately-to-severely active ulcerative colitis. SPY003 met the primary endpoint with a 10.0-point reduction from baseline in Robarts Histopathology Index score at Week 12 (p<0.0001). Secondary outcomes included 20% clinical remission by modified Mayo Score, 30% endoscopic improvement, and a 3.5-point reduction in modified Mayo Score.

Safety through Week 12 (N=44; data cutoff July 27, 2026) was described as consistent with the IL-23 class: 19 patients (43%) had any AE, 5 (11%) had Grade ≥3 AEs, 1 (2%) had a drug-related AE, 3 (7%) had SAEs, with no drug-related SAEs, no discontinuations due to AEs, and no deaths. Reported SAEs were not drug-related.

The company said it has now reported positive Part A data across all three UC monotherapies in the SKYLINE platform: SPY001 (anti-α4β7), SPY002 (anti-TL1A), and SPY003. SKYLINE Part B, evaluating monotherapies plus combination arms SPY120, SPY130, and SPY230, is actively enrolling, with topline induction data expected in 2027. Other upcoming readouts mentioned: SKYWAY (SPY072 in PsA/axSpA) in 4Q 2026 and SKYLIGHT (SPY072 + IL-17A/F in HS) in late 2027 or early 2028.