Spyre reports mixed Phase 2 results for SPY072 in rheumatoid arthritis

Spyre Therapeutics announced on August 25, 2026 topline results from the rheumatoid arthritis sub-study of its Phase 2 SKYWAY basket trial testing SPY072, its TL1A antibody. Both doses of SPY072 demonstrated statistically significant benefits compared to placebo on one or more of the primary endpoint (change from baseline in DAS28-CRP), key secondary endpoint (ACR20), and exploratory endpoint (ACR50).¹

At Week 12, SPY072 Low Dose demonstrated a statistically significant benefit compared to placebo on the primary endpoint (change from baseline in DAS28-CRP)¹. Nominally significant improvements versus placebo were observed on the secondary endpoint (ACR20) with High Dose and on the exploratory endpoint (ACR50) with Low Dose.¹ In the 48-patient high dose and low dose arms versus 47 on placebo, ΔDAS28-CRP was -1.5, -1.9, and -1.3 respectively, with ACR20 rates of 63%, 58%, and 43%, and ACR50 rates of 31%, 38%, and 19%.

Despite the statistical hits, the results provide proof-of-mechanism for TL1A in RA and support its potential in other autoimmune diseases and as a combination component, but did not meet the Company's internal bar to prioritize advancement of SPY072 in RA.¹

On safety, rates of adverse events were comparable between active (27%) and placebo (36%) and generally mild or moderate, with one Serious TEAE on each arm, none deemed drug-related, one death in a placebo recipient, and the most common TEAEs being infections and infestations occurring in 14% of SPY072-treated participants and 15% of placebo-treated participants.¹

Looking ahead, topline data for SPY072 in PsA and axSpA is expected in 4Q 2026, and for SKYLINE Part A in ulcerative colitis with SPY003 in September 2026, SKYLINE Part B in 2027, and SKYLIGHT combining SPY072 with IL-17A/F in HS in late 2027 or early 2028.¹