Spyre Therapeutics (SYRE) Study result summary

Study background and design

• SKYLINE is a two-part Phase 2 platform study evaluating SPY001 and other agents in moderately to severely active ulcerative colitis, with Part A as an open-label monotherapy induction and Part B as a randomized, placebo-controlled phase including monotherapy and combination cohorts.

• Part A enrolled approximately 130 participants across three cohorts, with standard eligibility criteria and objective measures to minimize placebo response; the patient population was consistent with prior anti-a4β7 trials, with 81% advanced therapy naïve and 42% on steroids.

• The primary endpoint was change from baseline in Robarts Histopathology Index (RHI), with key secondary endpoints including endoscopic improvement, clinical remission, and safety.

• SPY001 is an optimized anti-alpha-4 beta-7 antibody designed for extended half-life and convenient subcutaneous dosing, aiming to improve efficacy, safety, and convenience over existing therapies.

• Enrollment for Part A is complete; Part B is now enrolling globally with multiple monotherapy and combination cohorts, aiming for a balanced naive/refractory population and caps on prior failures.

Efficacy results

• SPY001 met its primary endpoint with a mean RHI change of -9.2 at week 12 (p<0.0001), and -10.6 in a higher baseline RHI subgroup.

• 40% of participants achieved clinical remission and 51% achieved endoscopic improvement at week 12, among the highest rates reported in comparable UC trials.

• Rapid and consistent improvements were observed in symptom scores and biomarkers, including reductions in partial Mayo score and fecal calprotectin, with benefits seen as early as two weeks.

• Robust improvements were observed in endoscopic scores, rectal bleeding, stool frequency, and physician global assessment.

• Efficacy was consistent across geographic regions, advanced therapy naïve and experienced patients, and between naive and refractory subgroups.

Safety and tolerability

• SPY001 was well tolerated, with 14% experiencing any adverse event, 2% severe or serious (not drug-related), and no drug-related discontinuations or deaths.

• Safety profile was consistent with the anti-a4β7 class, with the most common adverse event being back pain.