Spyre Completes SKYWAY Enrollment After Second SKYLINE Hit

The Tip Desk · August 4, 2026 · 3 min read

SPY002 met its ulcerative colitis primary endpoint with a 10.7-point Robart’s Histopathology Index reduction, and all three SKYWAY sub-studies finished enrolling.

Spyre Therapeutics (SYRE), a clinical-stage biotechnology company developing long-acting antibodies for inflammatory bowel disease and rheumatic diseases, announced positive topline induction data for SPY002 from Part A of the Phase 2 SKYLINE trial and completed enrollment in the Phase 2 SKYWAY basket study.

The second-quarter results extended a run of SKYLINE Part A readouts that began with SPY001 in April. SPY002, an investigational anti-TL1A monoclonal antibody, met its primary endpoint in moderately to severely active ulcerative colitis, with a 10.7-point reduction in the Robarts Histopathology Index. Clinical remission was 33% and endoscopic improvement was 42%. The change in modified Mayo Score from baseline at Week 12 was -3.7. SPY001, an α4β7 antibody, had shown a 9.2-point Robarts reduction, 40% clinical remission and 51% endoscopic improvement. Both agents were well tolerated, with safety consistent with in-class comparators.

Chief Executive Officer Cameron Turtle said that, following encouraging Phase 2 results from both SPY001 and SPY002 and competitor results validating combination therapy, the case for Spyre’s approach in IBD had strengthened. He said the company believes its three investigational combinations have the potential to deliver efficacy, safety and convenience beyond today’s therapies.

SKYLINE Part A enrollment has been completed. Topline data for SPY003, an IL-23 p19 antibody, are expected in September 2026. Part B, a randomized, placebo-controlled assessment of monotherapies and combinations designed to provide dose-ranging and proof-of-concept data, is currently enrolling, with induction data expected in 2027. The company is enrolling its combinations SPY120, SPY130 and SPY230 in Part B.

Enrollment also finished for all three sub-studies of SKYWAY, a Phase 2 randomized, placebo-controlled basket trial of SPY072, another anti-TL1A antibody, in rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis. All three sub-studies over-enrolled on or ahead of schedule. Topline proof-of-concept data for the RA sub-study are expected in September 2026; PsA and axSpA readouts are expected in the fourth quarter of 2026. Spyre remains on track for six proof-of-concept Phase 2 readouts in 2026. Turtle said that if the RA data are successful, the company looks forward to initiating pivotal development of SPY072 next year while also exploring combination approaches outside IBD.

Cash, cash equivalents and marketable securities were $1,145.3 million as of June 30, 2026, after $435.2 million of net proceeds from an April public offering of common stock. The company expects runway into the second half of 2029. Net cash used in operating activities was $69.9 million in the second quarter.

Research and development expenses were $65.5 million, up from $40.1 million a year earlier. The increase was primarily driven by higher manufacturing and clinical trial expenses and higher headcount costs. General and administrative expenses were $16.1 million.

Spyre recognized a $40.0 million gain on sale of an in-process research and development asset, tied to an achieved milestone related to the 2023 sale of global rights to pegzilarginase to Immedica Pharma AB, specifically Immedica’s sale of a priority review voucher. Other income was $5.4 million, including $10.1 million of interest income. Net loss was $36.2 million.

The company is studying SPY001, SPY002 and SPY003 as monotherapies and in pairwise combinations in SKYLINE, and SPY072 as a monotherapy in rheumatic diseases. Preclinical data for SPY120 showed that combined TL1A and α4β7 inhibition was superior to either monotherapy in mouse models of colitis, with similar pharmacokinetic profiles for SPY001 and SPY002 in non-human primates whether dosed alone or together. Preclinical data for SPY130 and SPY230 showed enhanced efficacy and pharmacodynamics with SPY003 in combination with SPY001 and SPY002.

The next catalysts are the September SPY003 Part A readout and the September RA proof-of-concept data from SKYWAY, with PsA and axSpA results later in the year and SKYLINE Part B induction data expected in 2027.