Spyre Therapeutics has initiated dosing in a Phase 1 clinical trial of SPY003, its novel half-life extended anti-IL-23 monoclonal antibody designed for the treatment of Inflammatory Bowel Disease (IBD). This milestone represents the company's fourth on-time clinical trial initiation in nine months, underscoring Spyre's commitment to advancing innovative therapies for immune-mediated diseases.
The Phase 1 trial (NCT06873724) is a double-blind, placebo-controlled single-ascending dose study in healthy volunteers. Approximately 56 healthy adult participants are expected to enroll, with safety as the primary endpoint and pharmacokinetics (PK) serving as a secondary endpoint. Interim safety, PK, and anti-drug antibody (ADA) data are anticipated in the second half of 2025.
Potential for Extended Dosing Intervals
Preclinical data suggests SPY003 could offer significant advantages over existing IL-23 inhibitors. The antibody has demonstrated high potency and the potential for quarterly or biannual dosing, which could substantially improve both efficacy and convenience compared to first-generation anti-IL-23 monoclonal antibodies.
In head-to-head preclinical studies, SPY003 showed equivalent potency to risankizumab in inhibiting pSTAT signaling and IL-17 production. More notably, it exhibited a significantly longer half-life in non-human primates, suggesting the potential for dosing as infrequently as once every six months in humans.
"Recent third-party clinical data demonstrate that combination therapies that include an IL-23 antibody can produce superior results for IBD patients," said Deanna Nguyen, M.D., SVP of Clinical Development at Spyre. "We believe SPY003 has the potential to be a best-in-class IL-23 antibody and a compelling combination partner with our α4β7 and TL1A antibodies that can be delivered on a quarterly or bi-annual treatment schedule."
Strategic Role in Combination Therapy Development
Subject to interim results from the Phase 1 trial, Spyre plans to incorporate SPY003 into its planned Phase 2 platform study in ulcerative colitis. This comprehensive trial will explore six investigational therapies: three monotherapies and three combination therapies.
Dr. Nguyen emphasized the strategic importance of this approach: "We look forward to presenting the interim Phase 1 data in the second half of this year before adding SPY003 as the final monotherapy component of our planned Phase 2 platform trial in ulcerative colitis."
Addressing Significant Unmet Needs in IBD
IBD represents a substantial disease burden, affecting approximately 2.4 million individuals in the United States alone. This chronic condition, characterized by inflammation in the gastrointestinal tract, encompasses two main disorders: ulcerative colitis and Crohn's disease.
Current treatment options for IBD often require frequent dosing, which can impact patient adherence and quality of life. By developing a long-acting IL-23 inhibitor, Spyre aims to address these challenges while potentially improving clinical outcomes.
Spyre's Broader Pipeline Strategy
SPY003 is part of Spyre's broader strategy to create next-generation IBD treatments through best-in-class antibody engineering, dose optimization, and rational therapeutic combinations. The company's pipeline includes extended half-life antibodies targeting α4β7, TL1A, and IL-23.
This approach reflects growing evidence that combination therapies may offer superior efficacy in treating complex immune-mediated diseases like IBD. By developing antibodies with extended half-lives, Spyre aims to create more convenient and potentially more effective treatment regimens.
As the Phase 1 trial progresses, the medical and patient communities will be watching closely to see if SPY003 can deliver on its promise of extended dosing intervals while maintaining the efficacy expected from IL-23 inhibition in IBD treatment.
