Spyre Therapeutics Initiates Phase 1 Clinical Trials for Extended Half-Life Therapy for IBD
Spyre Therapeutics, a U.S.-based biotechnology firm, announced the commencement of dosing for the first participants in two Phase 1 studies evaluating its first-generation anti-TL1A antibodies, SPY002-091 and SPY002-072, aimed at treating inflammatory bowel disease (IBD).
IBD is a persistent autoimmune disorder that encompasses primary conditions such as ulcerative colitis and Crohn’s disease. Globally, nearly five million individuals are affected by inflammatory bowel disease, with approximately 2.4 million cases reported in the U.S.
The Phase 1 trials by Spyre will involve healthy adult individuals, focusing on safety as the main objective, with pharmacokinetics serving as a secondary goal. Should the results be favorable, the company anticipates initiating Phase 2 trials in 2025.
SPY002-091 and SPY002-072 are experimental monoclonal antibodies with extended half-lives that target the inflammatory cytokine known as tumor necrosis factor-like cytokine 1A (TL1A). Elevated TL1A levels in IBD are associated with chronic inflammation in the digestive tract that can lead to tissue damage and fibrosis.
“Inhibition of TL1A has shown significant efficacy in patients suffering from ulcerative colitis and Crohn’s disease, and in preclinical IBD models, it provides additive benefits when combined with other targeted therapies,” noted Josh Friedman, SVP of Clinical Development at Spyre, in an official statement.
“Moreover, TL1A is implicated in various inflammatory and fibrotic conditions apart from IBD. Our SPY002 candidates are designed to enhance the advantages of earlier molecules, featuring higher picomolar potencies, prolonged half-lives, and concentrated formulations.”
In preclinical evaluations, Spyre demonstrated that its SPY002 anti-TL1A antibodies possess a longer half-life compared to earlier versions. This may allow for less frequent dosing, potentially on a quarterly or semi-annual basis, leading to improved effectiveness compared to the current regimen of every two to four weeks.
“The initiation of clinical trials with two advanced anti-TL1A molecules marks an exciting phase[…],” expressed Cameron Turtle, CEO of Spyre. “If Phase 1 goes well and we receive positive regulatory response, we aim to launch one of the SPY002 candidates in our innovative Phase 2 study for monotherapies and combination treatments for ulcerative colitis next year and also begin a quick Phase 2 proof-of-concept study in indications outside of IBD…”
Teva and Sanofi are among other companies developing anti-TL1A therapies for IBD. The two have partnered in 2023 to progress Teva’s anti-TL1A treatment into clinical evaluations. In July 2024, they revealed an expedited schedule for their Phase 2 trial, with results expected by year-end.
Additionally, Merck & Co. is exploring its investigational anti-TL1A monoclonal antibody, tulisokibart, through two Phase 3 trials in patients suffering from ulcerative colitis and Crohn’s disease. In September 2024, the company released comprehensive long-term findings indicating that tulisokibart significantly outperformed placebo in inducing remission in patients with moderate to severe active ulcerative colitis.