Spyre Therapeutics, Inc. (NASDAQ: SYRE) has announced positive interim Phase 1 data for SPY001, a novel, extended half-life monoclonal antibody targeting α4β7 for the treatment of inflammatory bowel disease (IBD). The results support potential quarterly or bi-annual subcutaneous maintenance dosing. The company plans to initiate a Phase 2 platform trial in mid-2025.
Phase 1 Trial Highlights
The Phase 1 trial is a randomized, double-blind, placebo-controlled study evaluating the safety and pharmacokinetics (PK) of SPY001 in healthy volunteers. The trial enrolled 56 healthy adults into single-ascending dose (SAD) and multiple-ascending dose (MAD) cohorts. Doses ranged from 100 mg to 1000 mg SC and IV.
- Safety: SPY001 was well-tolerated across all dose groups, with a safety profile consistent with the anti-α4β7 class. The most common treatment-emergent adverse events (TEAEs) were headache and nasopharyngitis. No Grade 2 or higher TEAEs or serious adverse events (SAEs) were reported.
- Pharmacokinetics: The half-life estimate is >90 days in the 300mg SC cohort and >100 days in the 600mg SC cohort, approximately 4-fold greater than vedolizumab's 25-day half-life. This supports potential maintenance dosing via a single subcutaneous injection every three to six months.
- Pharmacodynamics: A single 300 mg dose of SPY001 saturated α4β7 receptor occupancy up to Day 57, the longest follow-up available for pharmacodynamic data.
Planned Phase 2 Trial in Ulcerative Colitis
Spyre plans to advance SPY001 into a double-blind, randomized, placebo-controlled, Phase 2 platform trial with a master protocol in patients with moderately-to-severely active ulcerative colitis, pending regulatory feedback. The trial is designed to efficiently evaluate each of Spyre's monotherapy and combination therapies against a common placebo control. The trial is also intended to evaluate the contribution of each monotherapy component to the safety and efficacy of Spyre's combination therapies.
This Phase 2 ulcerative colitis trial is expected to initiate in mid-2025 with SPY001 and placebo arms, with SPY002, SPY003, and combination arms to be added following clinical data, nonclinical data, and regulatory feedback. The trial is expected to enroll approximately 500 subjects across treatment arms and consist of a 12-week, placebo-controlled induction period followed by a 38-week maintenance period.
SPY002 and SPY003 Development
Spyre is also advancing two anti-TL1A molecules, SPY002-091 and SPY002-072, into Phase 1 clinical trials. These molecules have demonstrated picomolar potency and the potential for quarterly or twice-yearly dosing in preclinical studies. Interim data from these trials are expected in the second quarter of 2025. Additionally, the first-in-human study for SPY003, Spyre's extended half-life IL-23 antibody, is on track to initiate in the first quarter of 2025.
Market Context
IBD affects an estimated 2.4 million individuals in the United States. SPY001 targets the same epitope as vedolizumab and demonstrates equivalent potency and selectivity in preclinical studies. The extended half-life of SPY001 could offer a significant convenience advantage over vedolizumab, which requires more frequent dosing.
"These interim data exceeded our expectations for SPY001 and support its potential to become both a differentiated monotherapy and an ideal backbone for combination therapy in IBD," said Cameron Turtle, DPhil, Chief Executive Officer of Spyre.
