The U.S. biotech company Spyre Therapeutics announced yesterday that it has dosed the first participants in two Phase 1 trials testing its first-generation anti-TL1A antibodies, SPY002-091 and SPY002-072, for the treatment of inflammatory bowel disease (IBD).
IBD is a chronic autoimmune condition that includes the two main disorders ulcerative colitis and Crohn’s disease. Worldwide, almost five million people have inflammatory bowel disease, with an estimated 2.4 million people affected in the U.S. alone.
Spyre’s two Phase 1 trials will test its therapies in healthy adult participants, with safety as the primary endpoint and pharmacokinetics as the secondary endpoint. Following positive results, Spyre expects to start Phase 2 in 2025.
SPY002-091 and SPY002-072 are two investigational half-life extended monoclonal antibodies targeting the inflammatory cytokine tumor necrosis factor-like cytokine 1A (TL1A). In IBD, TL1A levels are chronically high, resulting in persistent inflammation in the digestive tract, which damages the tissue and can cause fibrosis.
“TL1A inhibition has demonstrated compelling efficacy in ulcerative colitis and Crohn’s disease patients and has been shown in pre-clinical IBD models to provide additive benefit when used in combination with other targeted agents,” explained Josh Friedman, SVP of Clinical Development at Spyre in a press release.
“Further, TL1A is implicated in numerous inflammatory and fibrotic diseases beyond IBD. Our SPY002 molecules were engineered to build upon the evidence from first-generation molecules with optimized properties including picomolar potencies, extended half-lives, and high-concentration formulations.”
In preclinical studies, Spyre was able to show that its SPY002 anti-TL1A molecules have a longer half-life than first-generation anti-TL1As. This means they might be suitable for quarterly or twice-yearly dosing with improved efficacy, as opposed to every two to four weeks.
“Entering the clinic with two optimized anti-TL1A molecules is an exciting next step[...],” said Cameron Turtle, CEO of Spyre. “Pending Phase 1 success and regulatory feedback, we look forward to introducing one of the SPY002 molecules into our groundbreaking Phase 2 platform study of monotherapies and combination therapies in ulcerative colitis next year, as well as initiating an efficient Phase 2 proof-of-concept study outside of IBD…”
Other firms working on anti-TL1A therapies against IBD are Teva and Sanofi, for instance. The two companies joined forces in 2023 to advance Teva’s anti-TL1A therapy into the clinic. In July 2024, they announced an accelerated timeline for their Phase 2 program with topline results expected by the end of this year.
Merck & Co’s investigational anti-TL1A monoclonal antibody, tulisokibart, is currently being investigated in two Phase 3 studies in ulcerative colitis and Crohn’s disease. In September 2024, the company published long-term data showing that tulisokibart was more effective than the placebo in causing remission in patients with moderate to severe active ulcerative colitis.
