SYRE SPY072: Mixed RA Phase 2, Pivots to Psoriasis and UC

Spyre Therapeutics (NASDAQ: SYRE) reported the rheumatoid arthritis readout from its Phase 2 SKYWAY basket trial on August 26, and the verdict is split: the anti-TL1A antibody SPY072 worked, but not well enough to justify developing it as an RA monotherapy. Spyre is deprioritizing the RA program. The stock closed at $107.36 and slid roughly 14% to about $92 in the reaction.

The numbers are genuinely mixed. In the RA sub-study, 143 patients were randomized to a high dose (48), low dose (48), or placebo (47). On the primary endpoint, change in the DAS28-CRP disease-activity score at week 12, the low dose beat placebo with a -1.9 versus -1.3 improvement (p<0.05). The high dose missed, at -1.5. On ACR20, a measure of 20% symptom improvement, the high dose reached 63% versus 43% for placebo. ACR50 responses were 38% for the low dose versus 19% for placebo, while the strictest bar, ACR70, reached just 13% on the high dose versus 2% on placebo. Safety was clean: adverse events in 27% of treated patients versus 36% on placebo, mostly mild or moderate, with no drug-related serious events.

The drug clearly hit its target. TL1A is a cytokine central to T-cell-driven inflammation, and SPY072 is an extended half-life antibody against it. Both doses reached target drug levels and fully suppressed free TL1A through week 12. What missed was the efficacy bar, not the mechanism. Rheumatoid arthritis is the toughest indication in immunology to break into: biosimilars have pushed down prices, and entrenched TNF, JAK, and IL-6 blockers set a high bar. A new biologic has to be dramatically better, not just nominally, to displace them.

Spyre is redirecting the effort where unmet need is higher. Psoriatic arthritis and axial spondyloarthritis data from SKYWAY are due in Q4 2026, the SKYLINE ulcerative colitis readout lands in September, and a hidradenitis suppurativa combination study with an IL-17A/F antibody is underway. TL1A remains one of the most valuable targets in immunology, with Merck’s $10.8 billion Prometheus buy and Roche’s $7.1 billion Telavant deal setting the stakes. Spyre’s role as the pure-play TL1A bet is covered in this IBD and TL1A breakdown.

What to watch: the September SKYLINE Part A ulcerative colitis readout is the near-term catalyst, and it matters more than RA because UC is where a TL1A drug, Merck’s tulisokibart, has already posted a Phase 3 win. A miss there would cut deeper than this RA result. For parsing topline releases like this one, see how to read a clinical trial press release.

Source: Spyre Therapeutics press release, August 26, 2026