Spyre’s Anti-TL1A Antibody SPY072 Misses in Psoriatic Arthritis and Axial Spondyloarthritis, Shifts Focus to Hidradenitis Suppurativa

Spyre Therapeutics’ half-life-extended anti-TL1A antibody SPY072 failed to meet its primary endpoints in psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) in the Phase 2 SKYWAY basket trial, and the company will no longer develop the antibody in rheumatic diseases.¹ Spyre disclosed the results in its third-quarter financial report and said it will instead focus SPY072 on hidradenitis suppurativa (HS).¹

How is SPY072 designed?

SPY072 targets TL1A, a cytokine involved in inflammatory signaling.¹ The antibody is engineered with half-life extension technology and formulated at high concentration, with the goal of infrequent subcutaneous maintenance dosing.¹ TL1A signals through the receptor DR3 and has been linked to both inflammation and fibrosis, and several anti-TL1A antibodies are in late-stage development for inflammatory bowel disease, as BioPharm International® reported when Bionyra launched with two TL1A biologics in June.

What did the SKYWAY trial show?

SKYWAY evaluated SPY072 in separate sub-studies in rheumatoid arthritis (RA), PsA, and axSpA, and Spyre completed enrollment in all three in June.² SPY072 was well tolerated, but neither the PsA nor the axSpA sub-study met its primary endpoint, ACR20 response in PsA or change from baseline in the Ankylosing Spondylitis Disease Activity Score in axSpA.¹ Spyre did not disclose response rates or effect sizes for either sub-study.¹

The results follow a mixed readout in RA in August. In that sub-study of 143 patients, the low dose met the primary endpoint, with a change in DAS28-CRP of −1.9 compared with −1.3 for placebo at Week 12, while the high dose did not reach statistical significance.³ ACR20 response rates were 63% with the high dose and 58% with the low dose, compared with 43% for placebo.³ Spyre said at the time that the effect size did not meet its internal bar for prioritizing SPY072 monotherapy in RA.³

Adverse events in the RA sub-study occurred in 27% of patients receiving SPY072 compared with 36% receiving placebo, and most were mild or moderate.³ Chief executive officer Cameron Turtle, DPhil, cited “the favorable safety profile of TL1A inhibition” as a reason for continued conviction in the program.³

Why is Spyre moving to hidradenitis suppurativa?

Spyre pointed to recent evidence that TL1A blockade works in HS. “We were thrilled to see excellent external proof-of-concept data for TL1A in hidradenitis suppurativa,” Turtle said.¹ In September, Merck reported that its anti-TL1A antibody tulisokibart met its primary endpoint in a phase 2b HS trial, with 72% of patients on the high dose achieving at least a 50% improvement on the Hidradenitis Suppurativa Clinical Response at Week 16, compared with 35% on placebo.⁴

Spyre began the Phase 2 SKYLIGHT trial in September to test SPY072 in combination with bimekizumab, an IL-17A/F inhibitor, in moderate-to-severe HS.¹ The trial is designed to provide proof of concept for dual TL1A and IL-17A/F inhibition, with Week 16 results planned for late 2027 or early 2028.¹ Spyre also plans to advance an anti-TL1A monotherapy into pivotal HS studies in 2027.¹

Combining agents that hit different inflammatory pathways is a growing strategy in immunology. In a BioPharm International interview at BIO 2026, Howard Berman, PhD, chief executive officer of ReAlta Life Sciences, described the value of a multitarget approach in inflammatory disease. “Being able to hit all these targets at once is so critically and verifiably important to ameliorate the disease,” Berman said.

What happens next?

Spyre’s SKYLINE Phase 2 trial in ulcerative colitis is evaluating combinations of its long-acting antibodies, and enrollment in Part B is running ahead of schedule, with induction data expected in the third quarter of 2027.¹ The company reported $1.07 billion in cash, equivalents, and marketable securities as of September 30, plus about $396 million in net proceeds from an October offering and at-the-market sales.¹

References

1. Spyre Therapeutics reports third quarter 2026 financial results and provides corporate update. News release. Spyre Therapeutics. November 3, 2026. Accessed November 4, 2026.
2. Spyre Therapeutics announces completion of enrollment in SKYWAY basket trial evaluating SPY072 (anti-TL1A) in RA, PsA, and axSpA. News release. Spyre Therapeutics. June 3, 2026. Accessed November 4, 2026.
3. Spyre Therapeutics announces topline results from the rheumatoid arthritis sub-study of the SKYWAY Phase 2 trial of SPY072. News release. Spyre Therapeutics. August 25, 2026. Accessed November 4, 2026.
4. Merck’s tulisokibart met primary and key secondary endpoints in Phase 2b study in patients with moderate to severe hidradenitis suppurativa (HS). News release. Merck. September 30, 2026. Accessed November 4, 2026.