SPY001, An Anti-α4β7, Shows Promise in Phase 2 SKYLINE Trial for Ulcerative Colitis

Spyre Therapeutics has announced positive 12-week induction data from Part A of the phase 2 SKYLINE trial of SPY001, a potential best-in-class anti-α4β7 being investigated for the treatment of moderate-to-severely active ulcerative colitis (UC).1

In the April 13, 2026, press release, the Company additionally announced that recruitment for Part A of SKYLINE is now closed and enrollment is open for Part B, which includes 3 monotherapy cohorts (SPY001, SPY002, and SPY003) and 3 combination cohorts (SPY120, SPY130, and SPY230) into which participants may be randomized versus a shared placebo. Proof-of-concept induction data for the remaining cohorts of Part A are now expected mid-2026 (SPY002) and Q3 2026 (SPY003), while Part B induction data for all cohorts remain on track for 2027.1

“SPY001 was designed to improve upon vedolizumab’s proven activity in IBD by matching its epitope and potency while increasing target coverage through an extended half-life and greater induction dosing. Our data today support the hypothesis that this approach could lead to a best-in-class anti-α4β7 product across safety, efficacy, and convenience,” said Deanna Nguyen, MD, SVP of Clinical Development and SKYLINE study lead.1 “Beyond SPY001’s potential as a monotherapy, we continue to believe that its gut-selective mechanism makes it an ideal backbone for combination therapy alongside our cytokine-targeting investigational antibodies SPY002 (anti-TL1A) or SPY003 (anti-IL23). We have begun enrolling these combinations globally and look forward to unveiling proof-of-concept data next year.”

SPY001 is an investigational, novel, extended half-life monoclonal antibody targeting α4β7 for the treatment of inflammatory bowel disease (IBD). It targets the same epitope as vedolizumab, which was approved by the US Food and Drug Administration for the treatment of both UC and Crohn’s disease in 2014, and has demonstrated equivalent potency and selectivity as vedolizumab in head-to-head preclinical studies.1,2,3

Interim data from a previous phase 1 trial demonstrated that SPY001 was well tolerated and exhibited a human half-life of ~80 days, approximately 3-fold greater than vedolizumab and supporting potential quarterly or biannual SC maintenance dosing in a single autoinjector compared to vedolizumab's Q2W SC profile.1,2

SKYLINE is a 2-part induction and maintenance platform trial of SPY001, SPY002, SPY003, as well as pairwise combinations thereof, totalling 6 investigational agents, in patients with moderately to severely active UC. Part A is an open-label assessment of the safety and efficacy of a single dose level of each investigational monotherapy, and Part B is a randomized and placebo-controlled assessment of the safety and efficacy of investigational monotherapies (2 dose levels) and combinations.1

Results showed SPY001 achieved the primary endpoint, demonstrating a statistically significant reduction in the Robart’s Histopathology Index score of 9.2 points (P <.0001). Rates of key secondary endpoints of clinical remission and endoscopic improvement were clinically meaningful and support SPY001’s potential best-in-class profile.1

SPY001 was well tolerated with a safety profile consistent with the α4β7 class. There were 6 subjects with treatment-emergent adverse events (TEAEs) during the induction treatment period, with one serious adverse event (SAE) deemed not drug-related. The most common AE (occurring in ≥ 2 patients) was back pain (n = 2).1

“On behalf of the Spyre team, I’d like to thank the patients and investigators whose partnership has made this progress possible as we advance the study with the goal of delivering paradigm-changing combinations for IBD patients,” Sheldon Sloan, MD, MBE, Chief Medical Officer of Spyre Therapeutics, said in a statement.1 “Thanks to our team’s outstanding execution, we enrolled Part A with exceptional speed and now transition to Part B. We expect heightened investigator enthusiasm given these promising results for SPY001, a low placebo allocation for the remainder of the trial, and a unique opportunity to evaluate perhaps the three most promising combinations in development.”

References

1. Spyre Therapeutics. Spyre Announces Potential Best-in-Class SPY001 Part A Induction Results from SKYLINE Trial in Moderate-to-Severe Ulcerative Colitis Patients. April 13, 2026. Accessed April 13, 2026. https://ir.spyre.com/news-releases/news-release-details/spyre-announces-potential-best-class-spy001-part-induction

2. Spyre Therapeutics. Spyre Therapeutics Announces Poster Presentations at Digestive Disease Week (DDW) 2025 Including Up to Eight months of Follow-up from an Ongoing Phase 1 Trial of SPY001. May 5, 2025. Accessed April 13, 2026. https://ir.spyre.com/news-releases/news-release-details/spyre-therapeutics-announces-poster-presentations-digestive

3. Drugs.com. FDA Approves Entyvio (vedolizumab) to treat Ulcerative Colitis and Crohn's Disease. May 20, 2014. Accessed April 13, 2026. https://www.drugs.com/newdrugs/fda-approves-entyvio-vedolizumab-ulcerative-colitis-crohn-s-4040.html