Spyre Therapeutics reports positive interim Phase 1 results for TL1A antibodies

Spyre Therapeutics (SYRE) announced positive interim Phase 1 results from its first-in-human trials of SPY002 and SPY072, two investigational, novel, extended half-life monoclonal antibodies targeting TL1A. In addition, the company is initiating its SKYLINE-UC platform trial and unveiled its SKYWAY-RD basket trial evaluating anti-TL1A targeted therapy in three rheumatologic indications. Interim results from the Phase 1 trials for SPY002 and SPY072, with data reported as of May 30, 2025, met all Phase 1 objectives, supporting their potential to become next-generation anti-TL1A monotherapies in immune-mediated diseases or as elements of combination therapies. Single doses of up to 1500 mg for SPY002 and SPY072 were well tolerated with no serious adverse events reported, exhibited a prolonged half-life supportive of quarterly or less frequent dosing, and suppressed free TL1A through 20 weeks of follow up available for the lowest dose tested. Building on these Phase 1 results, Spyre is advancing SPY002 into the SKYLINE-UC platform trial – initiated in May 2025 – for ulcerative colitis. SKYLINE-UC is expected to include SPY001, SPY002, SPY003, and combinations thereof under an efficient single master protocol. The SKYWAY-RD study is a Phase 2 basket trial investigating Spyre’s improved anti-TL1A as a treatment for RA, PsA, and axSpA and is expected to initiate in Q3 2025. In 2026 the company expects to readout open-label monotherapy data for its three investigational long-acting antibodies from the SKYLINE-UC trial along with three placebo-controlled readouts for SPY072 in RA, PsA, and axSpA from the SKYWAY-RD trial. In 2027, the company expects to read out placebo-controlled data of its monotherapies and combination therapies from the SKYLINE-UC study.