Spyre Therapeutics, Inc. filed a Form 8-K with the SEC on August 25, 2026, disclosing topline results from the rheumatoid arthritis sub-study of its Phase 2 SKYWAY basket trial evaluating SPY072 in patients with moderate to severely active RA.

Key Highlights

  • Primary endpoint met (Low Dose): SPY072 Low Dose demonstrated a statistically significant benefit versus placebo on the primary endpoint, change from baseline in DAS28-CRP, at Week 12 (ΔDAS28-CRP: -1.9 vs. -1.3 for placebo).
  • ACR20 and ACR50 results: Nominally significant improvements versus placebo were observed on ACR20 with High Dose (63% vs. 43%) and on ACR50 with Low Dose (38% vs. 19%).
  • Safety profile: Rates of adverse events were comparable between active (27%) and placebo (36%) arms; one Serious TEAE occurred on each arm, none deemed drug-related; one death occurred in a participant receiving placebo.
  • Target engagement confirmed: Both doses achieved target drug concentrations and provided complete and durable suppression of free TL1A through Week 12.
  • RA monotherapy advancement not prioritized: According to the filing, results "did not meet the Company's internal bar to prioritize advancement of SPY072 as a monotherapy in RA."
  • Next readouts expected: Topline data from the SKYWAY PsA and axSpA sub-studies are expected in the fourth quarter of 2026; SKYLINE Part A in UC is expected in September 2026.

SPY072 Phase 2 SKYWAY-RA Sub-Study: Efficacy and Safety Details

According to the filing, the SKYWAY-RA sub-study is one of three sub-studies within the SKYWAY basket trial. It is described as a randomized, placebo-controlled study evaluating two doses of SPY072 in patients with moderate to severely active RA who had an inadequate response to conventional or advanced therapies. The study enrolled 48 participants in each of the High Dose and Low Dose arms and 47 in the placebo arm. The primary endpoint was change from baseline to Week 12 in DAS28-CRP, and the secondary endpoint was the proportion of patients achieving an ACR20 response at Week 12.

The filing reported that SPY072 Low Dose achieved a statistically significant improvement on the primary endpoint (ΔDAS28-CRP of -1.9, p<0.05 versus placebo's -1.3). High Dose produced a ΔDAS28-CRP of -1.5. On the ACR20 secondary endpoint, the High Dose arm reached 63% (nominal p<0.05 versus placebo's 43%), while Low Dose reached 58%. On the exploratory ACR50 endpoint, Low Dose reached 38% (nominal p<0.05 versus placebo's 19%). Results were described as "generally comparable between advanced-therapy-naive and advanced-therapy-experienced sub-groups." The company disclosed that the results "provide proof-of-mechanism for TL1A in RA and support its potential in other autoimmune diseases and as a combination component."

On safety, the company reported that SPY072 "was well tolerated, with a safety profile consistent with the TL1A class." The most common treatment-emergent adverse events were infections and infestations, occurring in 14% of SPY072-treated participants and 15% of placebo-treated participants. The filing noted that the forward-looking statements included in the 8-K are the company's own and are subject to the cautionary language and risk factors described therein, including in Spyre's most recent Annual Report on Form 10-K and subsequent quarterly reports.

What Was Disclosed

Spyre Therapeutics disclosed topline efficacy and safety data from the RA sub-study of the Phase 2 SKYWAY trial for SPY072, reported that the results did not meet its internal bar for advancing SPY072 as an RA monotherapy, and outlined expected upcoming clinical readout timelines across its pipeline.