Guselkumab

Spyre Therapeutics' three-pronged approach to inflammatory bowel disease continues to pay off, with the biotech's anti-IL-23 antibody notching a win in a phase 2 ulcerative colitis (UC) study. The therapy, dubbed SPY003, met its primary and secondary endpoints in Part A of the Skyline study of 44 UC patients by demonstrating a significant reduction in disease activity and induction of clinical remission, according to a Sept. 8 release . Specifically, SPY003 induced a 10-point reduction from baseline in Robarts Histopathology Index (RHI) score, a measure of disease activity and remission in UC, by Week 12. Secondary endpoints included clinical remission by modified Mayo Score of 20%, used to measure disease severity and treatment response, and endoscopic improvement of 30%. The Skyline program is a two-part induction and maintenance platform trial for patients with moderately-to-severely active UC that consists of three investigational antibodies: SPY001, an anti-α4β7 antibody, SPY002, an anti-TL1A antibody and SPY003. The win for SPY003 comes after SPY002 scored its own success in June, while a positive readout for SPY001 was announced back in April. “With today’s SPY003 data building upon impressive SPY001 and SPY002 results, we have now delivered three potential best-in-class IBD readouts within a span of five months, demonstrating the quality and efficiency of our development organization and strategy,” Spyre CEO Cameron Turtle said in the release. “We believe that these combinations have the potential to deliver an efficacy, safety and dosing profile that meaningfully surpasses today’s standard of care, and we are excited to unveil those data in 2027,” Turtle added. Part A of the Skyline trial consisted of a single dose level for each investigational monotherapy, while Part B will assess the safety and efficacy of two dose levels of the monotherapies and in combinations. Of the 44 patients enrolled in this part of the study, 19 experienced treatment-related adverse events (AEs), although none led to participants discontinuing their treatment. Three of the AEs were categorized as serious, but none of these were considered related to the drug. SPY003 is a half-life extended monoclonal antibody targeting IL-23 for the potential treatment of UC, Crohn’s disease and other inflammatory conditions. IL-23 is a cytokine that upregulates the expansion of pro-inflammatory T cells and activates inflammatory pathways that drive progression of inflammatory bowel disease. UC is a type of inflammatory bowel disease with no cure and characterized by long-lasting inflammation and ulcers in the colon and rectum. The UC space is pretty crowded with several therapies that have varying mechanisms of action, such as Takeda’s anti-integrin antibody Entyvio, AbbVie’s anti-IL-23 antibody Skyrizi and its JAK inhibitor Rinvoq, as well as Johnson & Johnson’s IL-23 inhibitor Tremfya. Spyre’s SPY001 was designed to compete with Takeda’s Entyvio , as it targets the same epitope, but Spyre has touted SPY001 as exhibiting a half-life three times greater than Takeda’s asset. Merck & Co. also recently reported positive phase 3 data from its anti-TL1A antibody tulisokibart, acquired from the $11 billion buyout of Prometheus Therapeutics in 2023.