Spyre’s rheumatoid arthritis plan toppled by subpar TL1A data

Biotech Spyre’s rheumatoid arthritis plan toppled by subpar TL1A data By Nick Paul Taylor Aug 26, 2026 5:40am Spyre Therapeutics Rheumatoid Arthritis rheumatology autoimmune disease Phase 2 data on Spyre Therapeutics’ anti-TL1A antibody SPY072 in rheumatoid arthritis have fallen short of expectations, prompting the biotech to deprioritize monotherapy development in the indication. Spyre CEO Cameron Turtle set expectations for the study in June at a Goldman Sachs event. Currently, treatments for rheumatoid arthritis patients failed by TNF inhibitors achieve about a one-point reduction on the Disease Activity Score 28 (DAS28-CRP), adjusted for placebo, Turtle said.

Guggenheim Securities analysts cited the same figure when discussing their hopes for the data in a note to investors last week. At Week 12 of a phase 2 trial, Spyre saw DAS28-CRP reductions of 1.5 and 1.9 points, respectively, on the high and low doses of SPY072. DAS28-CRP fell 1.3 points in the control arm, resulting in placebo-adjusted drops that fell well short of the targeted one-point change.

Only the low dose hit statistical significance. The lackluster primary endpoint data were compounded by results from other endpoints looking at the proportion of patients whose condition improved by 20%, 50% or 70%, as assessed by ACR20, ACR50 and ACR70. Turtle and Guggenheim analysts targeted placebo-adjusted improvements on ACR20, ACR50 and ACR70 of about 30 percentage points, 20 percentage points and 10 percentage points, respectively.

ACR20 rates were 63% and 58% on the high and low doses of SPY072, respectively, compared to 43% on placebo. Even the best result for SPY072 fell short of the targeted efficacy. Spyre saw a placebo-adjusted improvement in ACR50 of 19 percentage points on the low dose, as well as an 11-percentage-point gain in ACR70 on the high dose.

But in both cases the other dose underperformed expectations. The biotech’s stock was trading down 12.4% to $93.99 in premarket trading Wednesday from a Tuesday closing price of $107.36. Spyre made the case that, while the results missed its internal bar for prioritizing single-agent SPY072 in rheumatoid arthritis, the dataset provides proof of mechanism for TL1A inhibition in the indication.

That conclusion, coupled to the finding that SPY072 was well tolerated, led Spyre to outline a future for TL1A drugs in other autoimmune diseases and in combination therapies. Readouts in the coming months and years will shape Spyre’s ability to manifest that future. Phase 2 data on single-agent SPY072 in psoriatic arthritis and axial spondyloarthritis are due in the fourth quarter, and a recently initiated study of the asset in combination with UCB’s Bimzelx is scheduled to read out in late 2027 or early 2028.

The studies form the backbone of Spyre’s efforts to expand the use of TL1A inhibitors beyond ulcerative colitis (UC) and Crohn’s disease. Spyre is testing another TL1A inhibitor, SPY002, in UC as a monotherapy and in various combinations. Merck & Co., Roche and Sanofi have chosen UC and Crohn’s as the lead indications for their TL1A drug candidates and are running phase 3 trials in the bowel diseases.

While the lead programs have partly derisked TL1A inhibitors in UC and Crohn’s, there is less evidence of the mechanism’s effect on rheumatic diseases. Last year, Merck started phase 2b trials in several rheumatic indications targeted by Spyre. Roche’s phase 2 program includes trials in rheumatoid arthritis and eczema.

Spyre Therapeutics Rheumatoid Arthritis rheumatology autoimmune disease Clinical Data Biotech