Spyre Therapeutics is fleshing out another pillar in its plan to take on the lucrative ulcerative colitis market with a positive phase 2 readout for its anti-TL1A antibody, SPY002.
The data drop comes from Spyre’s Skyline program, a two-part induction and maintenance platform trial of SPY002 and two other candidates: Spyre’s anti-α4β7 antibody, SPY001, and its anti-IL23 antibody, SPY003.
Part A of the phase 2 study involves a single dose level for each investigational therapy, while Part B will assess the safety and efficacy of two dose levels of the monotherapies and in combinations.
Initial 12-week findings from Skyline Part A showed that SPY002 met all of the study’s key objectives in patients with moderately to severely active ulcerative colitis, Spyre said in a Monday release.
More specifically, the drug prompted a statistically significant reduction of 10.7 points from baseline levels in patients’ Robart’s Histopathology Index (RHI) scores by week 12. RHI is a widely used scoring system that measures histological disease activity in ulcerative colitis.
Additionally, secondary endpoints saw a clinical remission rate of 33% and an endoscopic improvement rate of 42%. The outcomes across SPY002’s endpoints are “among the highest reported” in the disease field, according to Spyre.
The drug’s safety profile was consistent with that of the TL1A class, the company said. In the 48-patient cohort, 20 participants experienced treatment-emergent adverse events during the induction treatment period, with two serious events that were determined not related to the drug.
“SPY002 demonstrated an indication-leading 10.7-point reduction in RHI and meaningful clinical remission and endoscopic outcomes in line with the anti-TL1A class and among the highest across therapeutic classes,” Spyre’s SVP of clinical development and Skyline study lead, Deanna Nguyen, M.D., explained in the release, adding that the findings “build upon our impressive SPY001 results and reinforce our thesis that optimized monotherapy components are the foundation for potentially best-in-class combinations.”
In a note to clients, Mizuho analysts highlighted the efficacy profile of SPY002, arguing the drug could deliver “potentially unprecedented induction clinical remission rates” when combined with SPY001.
Back in April, Spyre announced that its SPY001 demonstrated a statistically significant 9.2-point reduction in patients’ RHI scores from baseline. In that part of the trial, the company reported a 40% clinical remission rate and a 51% endoscopic improvement rate.
The company remains “on track” to report its SPY003 Part A results during the third quarter, Nguyen said, which would round out proof-of-concept results for its monotherapy components before getting into its combination arms in part B. Spyre is currently enrolling patients for part B of the study program.
SPY001 was designed to specifically challenge Takeda’s leading Entyvio as the candidate targets the same epitope as Entyvio’s active ingredient, vedolizumab. SPY002, meanwhile, targets TL1A, which is an upstream cytokine implicated in chronic inflammation and fibrosis in inflammatory bowel disease.