Data Readout

Spyre's SPY072 nears first RA data for an anti-TL1A antibody in Q3 2026

Enrollment in the SKYWAY-RD RA sub-study is complete, and Spyre has no in-class rival past Phase 2, making the DAS28-CRP readout the first human proof-of-concept test for TL1A in rheumatoid arthritis.

By AppliedXLJuly 13, 2026Trial NCT07148414

Executive Summary

Spyre Therapeutics is heading toward the first clinical readout testing an anti-TL1A antibody in rheumatoid arthritis, with topline data expected in the third quarter.
No other anti-TL1A program has advanced past Phase 2 in this indication, so the result will be a first read on whether the mechanism, already active in inflammatory bowel disease, translates to joint disease.
The sponsor finished enrolling the sub-study ahead of its own expectations and moved its readout guidance earlier as a result, a sign of execution rather than strain.
A positive signal would support the sponsor's stated plan to advance into pivotal testing next year, while a weak result would leave the mechanism's case in rheumatic disease unproven even as TL1A programs continue to mature in bowel disease.

The setup

Spyre said enrollment in the rheumatoid arthritis (RA) sub-study of its SKYWAY basket trial (NCT07148414) is complete and that it has moved its expected Week 12 topline readout up to the third quarter of 2026, from a later window. Joshua Friedman, the company's SVP of Clinical Development, said enrollment in the RA sub-study "exceeded our expectations" and reflects both unmet need in the disease and "investigator enthusiasm for the potential of a long-acting anti-TL1A antibody". The trial is a randomized, placebo-controlled Phase 2 study testing SPY072 in patients with moderately to severely active RA, psoriatic arthritis, or axial spondyloarthritis who had an inadequate response to prior therapy. Registry data confirm the RA arm's primary endpoint is change from baseline in DAS28-CRP, a composite score of joint counts and inflammation markers. Spyre+1

Probability of Success

Endpoint Met91%

Completes95%

Clinical Significance19%

Regulatory48%

Trial mechanics

The registry lists NCT07148414 as Active, not recruiting with a target enrollment of 285 patients across the RA, psoriatic arthritis, and axial spondyloarthritis sub-studies, unchanged from its original target. The trial's primary completion date moved from March 2028 to October 2026 shortly after the study was first posted, a change recorded as a single protocol amendment rather than a pattern of drift. The trial has logged one primary-completion-date change and one status change since posting, a change frequency the underlying registry-churn proxy rates as stable. NCT07148414

Where TL1A stands

SPY072 targets TL1A, a cytokine implicated in T-cell-driven inflammation that Spyre and other sponsors are also pursuing in inflammatory bowel disease. Roche's afimkibart and Merck's tulisokibart, the two most advanced anti-TL1A antibodies, are both in Phase 3 testing for Crohn's disease and ulcerative colitis, with completion dates stretching into 2028 through 2037. No industry-sponsored TL1A program has reached beyond Phase 2 in rheumatoid arthritis, which makes SPY072's RA sub-study the only Phase 2 asset for this specific target-indication pairing. The mechanism's clinical validation in bowel disease provides a precedent for T-cell-driven inflammation response, but the RA readout will be the first test of whether that response holds in joint disease. Spyre

What the readout tests

The randomized, placebo-controlled design and a DAS28-CRP primary endpoint give the trial the structure to produce a decision-grade signal on SPY072's activity in RA, though a 285-patient Phase 2 study across three sub-studies is not built to establish comparative efficacy against approved biologics or JAK inhibitors. Given that no anti-TL1A program has generated human RA data before, a DAS28-CRP reduction against placebo that is large enough to support advancing into pivotal testing, as the sponsor has said it intends to pursue, would be the result that distinguishes this readout from a directionally positive but inconclusive signal. NCT07148414+1

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