Data Readout

Spyre's SPY003 data will test if SKYLINE's IL-23 arm repeats SPY001's RHI win

Spyre expects induction data for its anti-IL23 antibody SPY003 in the SKYLINE ulcerative colitis trial by the end of Q3 2026, after SPY001 met its primary endpoint in the same platform study.

By AppliedXLJuly 13, 2026Trial NCT07012395

Executive Summary

Spyre Therapeutics is due to report induction data for its anti-IL23 antibody in the same platform trial that already delivered a positive result for its lead antibody, giving the upcoming readout an immediate internal benchmark.
The result will shape how the company's combination cohorts, which pair the two antibodies, are read once they mature, making this less a standalone bet than a link in a broader combination strategy.
The IL-23 mechanism is already validated by multiple approved and late-stage antibodies in ulcerative colitis, so a new entrant's induction data will be read against an established class rather than an open question about whether the target works.
The trial is recruiting on schedule, with no sign of the enrollment or timeline instability that sometimes accompanies platform studies of this design.

The catalyst

Spyre Therapeutics, Inc. said it expects proof-of-concept induction data from the SPY003 monotherapy cohort of the Phase 2 SKYLINE-UC trial (NCT07012395) in the third quarter of 2026, with the guided window running from July 1 through September 30. SPY003 is an antibody targeting IL23 being tested as monotherapy in patients with moderately to severely active ulcerative colitis. The company reaffirmed the same Q3 2026 timing in disclosures published April 13, May 5, and June 15, 2026, giving the guidance three consistent touchpoints ahead of the window's close. Spyre

Probability of Success

Endpoint Met91%

Completes98%

Clinical Significance5%

Regulatory87%

What SPY001 already showed

The comparator for this readout sits inside the same trial. Spyre reported on April 13, 2026 that SPY001, its anti-alpha4beta7 antibody, met the Part A primary endpoint in 43 dosed patients (41 completed), producing a 9.2-point reduction in the Robarts Histopathology Index at Week 12 (p<0.0001). Secondary results showed 40% clinical remission and 51% endoscopic improvement, with a safety profile the company described as consistent with the alpha4beta7 class. That result, not a hypothetical bar, is what a comparable SPY003 signal would need to approach to keep the platform's internal narrative intact. Spyre

The trial's design

SKYLINE-UC is a two-part induction and maintenance study testing SPY001, SPY002, and SPY003 individually and in three pairwise combinations, six investigational regimens in total. Part A is open-label, testing a single dose level of each monotherapy without a placebo control; Part B, now enrolling, is randomized and placebo-controlled across two dose levels and the combination arms. The trial has enrolled toward an anticipated target of 645 across 234 sites in twelve countries, and the registry lists it as Recruiting with a primary completion date of June 1, 2026. An early registry update raised the enrollment target from 35 to 645 patients in June 2025, a change that reflects the platform's build-out from a small Part A cohort to its full combination design and does not read as an operational shortfall. Spyre+1

The competitive frame

IL-23 is not a novel mechanism in ulcerative colitis. Risankizumab, guselkumab, and mirikizumab are Phase 3 or later IL-23-directed antibodies already advancing or approved in the same indication, and Spyre's own SPY003 comparator field showed no other trial pairing the IL23 target with this specific indication in earlier-phase testing. With the mechanism already validated at the class level, the bar for SPY003 is less about proving IL-23 blockade works in ulcerative colitis and more about whether Spyre's molecule produces a histologic and clinical response that supports its role as a combination backbone alongside SPY001, the comparison the company itself set up when it paired the two antibodies in SKYLINE's SPY130 and SPY230 combination cohorts. Spyre

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