Xencor reports Phase 1 data for XmAb942 showing 74-day half-life, Phase 2b on track

Xencor disclosed final Phase 1 results for XmAb942, an anti-TL1A antibody for inflammatory bowel disease. The study enrolled 64 healthy participants across single-dose and multiple-dose cohorts testing IV and SC administration. The results support a potential best-in-class profile with an estimated terminal half-life of 74.1 days, enabling a 12-week dosing interval during maintenance treatment.

Xencor announced that enrollment in a first-in-human dose-escalation study of XmAb412, a novel bispecific antibody targeting TL1A and IL23p19, is expected to begin in the third quarter of 2026. The study will evaluate pharmacokinetics and pharmacodynamics in healthy participants to support further development in autoimmune and inflammatory diseases in 2027.

Xencor presented final Phase 1 data for XmAb942, an anti-TL1A antibody for inflammatory bowel disease, at Digestive Disease Week 2026. The study enrolled 64 healthy participants across single- and multiple-ascending-dose cohorts. No serious or severe adverse events occurred, and treatment-emergent adverse events were comparable to placebo. The estimated terminal half-life was 74.1 days, supporting a 12-week dosing interval in the ongoing Phase 2b XENITH-UC study. The immunogenicity profile showed 25% ADA-positive and 0% neutralizing antibody-positive rates in the target dose regimen, lower than first-generation anti-TL1A competitors.

Xencor disclosed preclinical data for XmAb412, a TL1A x IL23p19 bispecific antibody engineered with the new XenLock platform, at DDW 2026. The molecule demonstrated potency comparable to clinical-stage TL1A and approved IL23 antagonists, with a predicted human half-life of 60 to 70 days. Non-human primate studies showed a half-life exceeding 20 days and durable target engagement. The company plans to initiate a first-in-human study in the third quarter of 2026. XmAb412 is designed to deliver dual-pathway inhibition in a single molecule, potentially avoiding the complexity of co-formulation approaches.

Xencor disclosed the design of XENITH-UC, a Phase 2b study of XmAb942 in moderate to severely active ulcerative colitis. The study will enroll approximately 220 patients who have failed at least one conventional or advanced therapy, randomized 4:3:3:3 across three active intravenous induction doses and placebo. The primary endpoint is remission at Week 12 per modified Mayo score. All participants completing induction will receive active subcutaneous maintenance dosing every 12 weeks for 40 weeks. The company expects to report 12-week induction results around year-end 2026.

Xencor outlined a development roadmap for its TL1A portfolio spanning 2026 through 2028 and beyond, integrating decision points for XmAb942 and XmAb412 to define registration-enabling studies in inflammatory bowel disease. The company stated it will assess strategic relationships to accelerate development, referencing precedent transactions including co-development deals, portfolio acquisitions, and early-stage out-licenses. Near-term milestones include initiating the XmAb412 Phase 1 study in 3Q26, a XENITH-UC enrollment update around year-end 2026, XmAb412 interim Phase 1 results in 1H27, and XENITH-UC 12-week induction data in 2H27.

Xencor disclosed a cash position of approximately $611 million as of December 31, 2025, including cash, cash equivalents, and marketable debt securities. This figure was updated as of February 25, 2026. The company highlighted this financial position as supporting its protein engineering capabilities and partnerships.

Xencor disclosed final Phase 1 study results for XmAb942 (tested in healthy participants) and preclinical characterization data for XmAb412. Both are part of the company's TL1A-targeted therapeutic pipeline.