Spyre Therapeutics reports positive Phase 2 SKYLINE (NCT07012395) induction data, with SPY001 showing significant clinical remission and endoscopic improvement in ulcerative colitis.
Written By: Samiksha Jadhav, BPharm
Reviewed By: Pharmacally Editorial Team
Spyre Therapeutics reported positive 12-week induction data from Part A of the Phase 2 SKYLINE trial (NCT07012395) evaluating SPY001, a long-acting anti-α4β7 antibody, in patients with moderate-to-severely active ulcerative colitis. The investigational therapy met the primary endpoint and showed clinically meaningful improvements across remission and endoscopic outcomes, while maintaining a safety profile consistent with the α4β7 class.
SPY001 is designed to improve upon vedolizumab by targeting the same epitope with comparable potency while extending half-life and increasing induction dosing to enhance target coverage. According to Spyre, this strategy aims to deliver stronger efficacy with improved dosing convenience.
Deanna Nguyen, M.D., SVP of Clinical Development and SKYLINE study lead emphasized that the gut-selective mechanism may support combination approaches with cytokine-targeting candidates SPY002 (anti-TL1A) and SPY003 (anti-IL-23), which are now enrolling globally for combination evaluation.
SKYLINE Part A efficacy results
In the open-label Part A cohort (n=43), SPY001 achieved the primary endpoint with a statistically significant reduction in the Robarts Histopathology Index (RHI), showing a mean decrease of 9.2 points (p<0.0001) at Week 12. Secondary endpoints further supported clinical benefit, with a clinical remission rate of 40% and an endoscopic improvement rate of 51%. In addition, the Modified Mayo Score decreased by 3.7 points from baseline. Together, these results indicate meaningful improvements in histologic, endoscopic, and clinical disease activity following induction treatment with SPY001.
Safety profile consistent with class
SPY001 was well tolerated during the induction period. Treatment-emergent adverse events occurred in 14% of participants, with one Grade ≥3 event and one serious adverse event, both considered unrelated to treatment. No drug-related adverse events, discontinuations, or deaths were reported. The most common adverse event was back pain, observed in two patients. The reported serious event involved chest pain in a patient with significant cardiovascular history, without evidence of myocardial infarction.
Trial design and next steps
SKYLINE is a two-part platform study evaluating SPY001, SPY002, SPY003, and their pairwise combinations in ulcerative colitis. Part A assesses safety and efficacy of single-dose monotherapy cohorts, while Part B randomizes patients to monotherapies at two dose levels and combination regimens versus shared placebo.
Recruitment for Part A has closed, and enrollment is now open for Part B. Additional proof-of-concept induction data from remaining Part A cohorts are expected in mid-2026 for SPY002 and in the third quarter of 2026 for SPY003. Part B induction data across all cohorts are anticipated in 2027.
Sheldon Sloan, M.D. MBE, Chief Medical Officer of Spyre Therapeutics. noted that the rapid completion of Part A and the early SPY001 activity support advancing both monotherapy and combination strategies aimed at redefining treatment approaches for inflammatory bowel disease.
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About the Writer
Samiksha Vikram Jadhav is a B.Pharm graduate with a strong academic foundation in pharmaceutical sciences, pharmacology, and drug development. She has a keen interest in healthcare advancements, clinical research, medical writing, and emerging therapies. Her work focuses on presenting developments in the pharmaceutical and healthcare sectors through clear and accurate scientific communication.