WALTHAM, Mass. — September 8, 2026

Spyre Therapeutics announced positive 12-week induction results from Part A of the Phase 2 SKYLINE trial evaluating SPY003, an investigational extended half-life anti-IL-23 antibody, in patients with moderately-to-severely active ulcerative colitis (UC). The company reported that SPY003 achieved the primary endpoint and demonstrated statistically significant improvement in Robart’s Histopathology Index (RHI), supporting continued development of the program. The update represents an important milestone in Spyre’s broader strategy to develop next-generation immunology therapies designed to provide more complete disease control, greater durability and a simpler treatment experience. The company said the latest findings complete clinical proof-of-concept across all three components of its IBD combination strategy, following previously reported results for SPY001, targeting α4β7, and SPY002, targeting TL1A. Spyre is developing these differentiated antibody programs with the objective of creating optimized treatment options for patients with significant unmet needs in inflammatory bowel disease.

SPY003 Strengthens Spyre’s IBD Development Strategy

The positive SPY003 data strengthen Spyre Therapeutics’ strategy of developing multiple complementary mechanisms for inflammatory bowel disease, with the SKYLINE platform designed to evaluate both individual therapies and rational combinations. In Part A, SPY003 demonstrated a 10.0-point reduction in RHI at Week 12 (p<0.0001), while additional assessments showed clinical remission and endoscopic improvement. Rather than positioning SPY003 only as a standalone IL-23 therapy, Spyre is developing the molecule as a potential combination component alongside its α4β7 and TL1A programs. The company believes that optimizing each individual antibody before combining them could create opportunities for stronger disease control and potentially differentiated treatment profiles. SPY003 was also reported to have a safety profile consistent with the IL-23 class, with no drug-related serious adverse events reported through the data cutoff. These findings provide the clinical foundation Spyre needs to advance its broader combination-focused IBD development strategy.

SKYLINE Part B Advances Toward IBD Combination Testing

Spyre is now advancing Part B of the SKYLINE trial, where the company is evaluating pairwise combinations of its three investigational IBD components. The study is designed to assess SPY001, SPY002 and SPY003 individually at multiple dose levels as well as high-dose combination regimens SPY120, SPY130 and SPY230. The combination portion is actively enrolling, with topline induction data expected in 2027. The development approach is central to Spyre’s strategy of using optimized, extended half-life antibodies to potentially improve the durability and convenience of treatment while addressing the complex inflammatory biology underlying UC. The company has now reported positive monotherapy proof-of-concept across α4β7, TL1A and IL-23, giving its combination program a broader clinical foundation. Spyre said the results from SPY003, together with its earlier SPY001 and SPY002 readouts, represent three potential best-in-class IBD clinical milestones delivered within approximately five months and demonstrate progress in its development organization and strategy.

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Spyre Expands Next-Generation Immunology Pipeline

The SPY003 milestone further positions Spyre Therapeutics as an emerging clinical-stage company focused on next-generation immunology and inflammation therapies. Beyond the SKYLINE program in UC, the company expects additional clinical development milestones across its pipeline, including SPY072 in psoriatic arthritis and axial spondyloarthritis through the SKYWAY program, with a readout expected in the fourth quarter of 2026. Spyre is also advancing SKYLIGHT, evaluating SPY072 with an IL-17A/F-targeting component in hidradenitis suppurativa, with topline results anticipated in late 2027 or early 2028. The company’s pipeline is built around extended half-life antibodies targeting α4β7, TL1A, IL-23 and IL-17A/F, alongside rational combination programs intended to address major unmet needs across immune-mediated diseases. With positive proof-of-concept for all three components of its IBD combination strategy and SKYLINE Part B now underway, Spyre is moving its development platform toward the next stage of clinical validation and combination testing.

Source: Spyre Therapeutics press release