Spyre Therapeutics Begins Dosing in Phase 1 Trials of Extended Half-life Anti-TL1A Antibodies

Spyre Therapeutics, Inc., a biotechnology company in Waltham, Mass., has commenced Phase 1 clinical trials for two investigational anti-TL1A monoclonal antibodies aimed at treating inflammatory bowel disease (IBD). These trials will assess the safety and pharmacokinetics of the SPY002 molecules in healthy volunteers. SPY002 molecules are designed to offer significant advantages over first-generation anti-TL1A treatments, including picomolar potency and potential for quarterly or twice-yearly dosing.

Josh Friedman, M.D., Ph.D., the Senior Vice President of Clinical Development at Spyre, emphasized the potential of TL1A inhibition in treating conditions such as ulcerative colitis and Crohn's disease. He noted that their engineered SPY002 molecules build on previous evidence and are optimized for better efficacy and convenience.

The Phase 1 trials (NCT06672718 and NCT06622070) are double-blind and placebo-controlled, involving roughly 56 healthy participants each. The primary focus is on safety, with pharmacokinetics as a secondary endpoint. Interim data from these trials are expected by Q2 2025. Based on the outcomes of these trials, Spyre plans to advance SPY002 into Phase 2 development next year.

Cameron Turtle, D.Phil., CEO of Spyre, highlighted the excitement of progressing with the SPY002 molecules and their strategy to introduce SPY002 into Phase 2 studies for ulcerative colitis. The company is also looking to begin a Phase 2 proof-of-concept study outside of IBD in 2025. These studies are well-funded following a successful $230 million financing, ensuring financial stability for the company until the second half of 2028.

Spyre's extended half-life antibodies, SPY002-091 and SPY002-072, target TL1A to treat inflammatory and fibrotic conditions, including IBD. In the U.S., approximately 2.4 million people suffer from IBD. Preclinical studies indicate that SPY002 candidates may have longer half-lives and superior potency compared to first-generation anti-TL1As, suggesting a potential for less frequent dosing.

The company had a robust financial standing with cash, cash equivalents, and marketable securities totaling approximately $414.2 million as of September 30, 2024. Including the net proceeds from their recent public offering, Spyre's pro forma cash balance stood at around $630.1 million.

Spyre is also preparing to launch its first-in-human study for SPY003, an extended half-life IL-23 antibody, in the first quarter of 2025. This will be the company's fourth antibody to enter clinical trials within nine months, showcasing their aggressive and comprehensive development strategy.

Spyre Therapeutics continues to leverage antibody engineering, rational therapeutic combinations, and precision medicine approaches in the development of next-generation IBD treatments. The company's pipeline includes advanced antibodies targeting α4β7, TL1A, and IL-23, aiming to provide better treatment options for patients suffering from inflammatory and fibrotic diseases.