Xencor, Inc. has commenced dosing in a Phase 1/2 clinical trial evaluating XmAb®942, an investigational anti-TL1A antibody, in healthy volunteers. This study marks a significant step in the development of a novel therapeutic option for patients with inflammatory bowel disease (IBD). The company anticipates initial data from the study in the first half of 2025.
The Phase 1/2 study (NCT06619990) is designed as a randomized, double-blind, placebo-controlled trial. It will proceed in three parts: Phase 1 will assess single-ascending doses (SAD) in Part A, followed by repeat doses in Part B, both in healthy volunteers. Phase 2, Part C, will then enroll patients with ulcerative colitis to receive dosing regimens determined from the earlier phases.
Rationale for XmAb®942 Development
Kenneth Hung, M.D., Ph.D., Senior Vice President, Clinical Development at Xencor, emphasized the potential of XmAb942 to transform IBD treatment. "An anti-TL1A antibody engineered for improved target coverage with long duration of action could transform the clinician’s therapeutic toolbox in inflammatory bowel disease," he stated. He further noted the potential for XmAb942's properties, including potentially class-leading potency, to result in a therapeutic option with improved clinical benefit and a more convenient dosing regimen than other anti-TL1A antibodies currently in clinical development.
XmAb®942 is engineered as a high-potency, extended half-life antibody targeting TL1A (TNF-like cytokine 1A). TL1A interacts with the death receptor 3 (DR3), and blocking this interaction has shown promise in reducing disease activity in ulcerative colitis (UC) and Crohn’s disease (CD) in earlier clinical studies. Xencor's Xtend™ Fc domain technology extends the half-life of XmAb942, potentially supporting an eight- to twelve-week dosing interval in humans.
Preclinical Data
Preclinical characterization data for XmAb942 was presented at the United Europe Gastroenterology Week (UEGW) in October 2024. These findings support the ongoing clinical development of the antibody.
