Spyre Therapeutics, Inc. filed a Form 8-K on September 8, 2026, disclosing 12-week induction topline data from Part A of its Phase 2 SKYLINE trial evaluating SPY003 in moderately-to-severely active ulcerative colitis.

Key Highlights

  • Primary endpoint met: SPY003 achieved a statistically significant 10.0-point reduction in Robarts Histopathology Index (RHI) score from baseline (p<0.0001) at Week 12.
  • Clinical remission and endoscopic improvement: The filing reported a 20% clinical remission rate and a 30% endoscopic improvement rate for SPY003 at Week 12.
  • Modified Mayo Score change: SPY003 produced a -3.5 change in modified Mayo Score at Week 12.
  • Study population: 41% of participants had prior advanced therapy exposure, with a mean disease duration of 7.1 years and a mean baseline mMS of 6.9 +/- 1.2 (SD).
  • Safety profile: 19 of 44 subjects (43%) had treatment-emergent adverse events; three SAEs were reported, all deemed not drug-related, and there were no drug-related SAEs or deaths.
  • Part B enrollment active: The SKYLINE Part B trial is actively enrolling, with topline induction data expected in 2027.
  • Data cut-off: SPY003 data pertain to N=44 through Week 12 with a data cut-off of July 27, 2026.

SKYLINE Part A SPY003 Efficacy and Safety Data Detailed by Spyre

According to the filing, Spyre Therapeutics (NASDAQ:SYRE) announced on September 8, 2026 that SPY003, described as an anti-IL-23 being investigated for moderately-to-severely active ulcerative colitis, met all key objectives in the 12-week induction portion of the Phase 2 SKYLINE Part A trial. The study population had a mean baseline RHI score of 17.2 +/- 8.3 (SD), and 59% of participants had a baseline endoscopy score of 3. The company disclosed that the 10.0-point RHI reduction observed with SPY003 "is in line with the 9.2- and 10.7-point reductions observed in participants receiving SPY001 and SPY002, respectively."

On safety, the filing reported that SPY003 was "well tolerated with a safety profile consistent with the IL-23 class." Among the 44 subjects, 19 (43%) experienced treatment-emergent adverse events, 5 (11%) had severe (Grade 3 or higher) adverse events, and 1 (2%) had a drug-related adverse event described as Grade 1 pruritus that "resolved without intervention or treatment interruption." The three SAEs - hospitalization for ulcerative colitis flare, hemorrhoid thrombosis, and acute cholecystitis, each in one subject - were all deemed not drug-related. There were no adverse events of special interest and no deaths.

The filing also outlined next steps in Spyre's pipeline. Part B of the SKYLINE trial, which includes two dose levels of each monotherapy and three high-dose combination arms (SPY120, SPY130, and SPY230), is actively enrolling, with topline induction data expected in 2027. Additional expected readouts include the SKYWAY trial in psoriatic arthritis and axial spondyloarthritis for SPY072 in the fourth quarter of 2026, and the SKYLIGHT trial in hidradenitis suppurativa in late 2027 or early 2028. The filing notes that forward-looking statements, including expected timing of trial results, are subject to the company's cautionary language and risks described in its regulatory filings.

What Was Disclosed

Spyre Therapeutics disclosed 12-week topline induction results from the Phase 2 SKYLINE Part A trial of SPY003 in ulcerative colitis, including primary endpoint achievement, clinical remission, endoscopic improvement, modified Mayo Score changes, and a detailed safety summary for N=44 subjects through a July 27, 2026 data cut-off.