Spyre Therapeutics’ monoclonal antibody hit the key goal in a phase 2 study for ulcerative colitis (UC), which the company has touted as proof it can best Takeda’s Entyvio.
The mid-stage trial evaluated the anti-α4β7 antibody, dubbed SPY001, in 43 patients with moderately to severely active UC. At Week 12, SPY001 had demonstrated a statistically significant 9.2-point reduction in patients’ Robarts Histopathology Index—a measure of UC disease activity—from baseline, according to an April 13 release.
The company described a 40% clinical remission rate and a 51% endoscopic improvement rate as “clinically meaningful,” and claimed they supported SPY001’s “potential best-in-class profile.”
SPY001 demonstrated a safety profile consistent with the α4β7 class, according to Spyre. Six participants experienced a treatment-emergent adverse event, with the most common being back pain. However, the only serious adverse event—chest pain in a patient with various other health conditions—was not deemed related to SPY001.
The SPY001 results come from part A of the Skyline trial, which is also assessing Spyre’s anti-TL1A antibody, SPY002 and anti-IL23 antibody, SPY003, both as monotherapies and in various combinations. Initial data from the SPY002 and SPY003 arms are expected in mid-2026 and the third quarter of the year, respectively.
SPY001 targets the same epitope as vedolizumab, the ingredient in Takeda’s UC and Crohn’s disease therapy Entyvio. Spyre has touted SPY001 as exhibiting a half-life three times greater than vedolizumab, while showing similar potency in preclinical tests. The idea is that SPY001 can be administered via autoinjector on a quarterly or biannual basis, whereas Entyvio is administered every two weeks.
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“SPY001 was designed to improve upon vedolizumab’s proven activity in IBD by matching its epitope and potency while increasing target coverage through an extended half-life and greater induction dosing,” Deanna Nguyen, M.D., SVP of clinical development at Sypre, explained in the release.
“Our data today support the hypothesis that this approach could lead to a best-in-class anti-α4β7 product across safety, efficacy and convenience,” Nguyen added.
Analysts at Mizuho said this morning’s data “support the notion” that having around twice the overall exposure of vedolizumab is “translating to improved efficacy.”
“SPY001’s week 12 clinical remission of 40% comfortably exceeds the around 20-25% range we had speculated would be viewed as class-aligned,” the analysts added in an April 13 note. “We see these results as an extremely favorable outcome, particularly for the potential efficacy that could be driven by SPY001-based combination regimens in Skyline Part B.”
