XmAb-942 / Xencor - LARVOL DELTA

XmAb942-01: Study of XmAb942 in Healthy Participants and Participants With Ulcerative Colitis (clinicaltrials.gov) - P1/2 | N=270 | Recruiting | Sponsor: Xencor, Inc. | Trial completion date: Jan 2029 ➔ May 2030 | Trial primary completion date: Apr 2028 ➔ Dec 2027

Trial completion date • Trial primary completion date • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Targeting the TL1A pathway in inflammatory bowel disease: mechanistic insights and emerging therapeutic pipeline. (PubMed, Inflamm Bowel Dis) - "Three anti-TL1A monoclonal antibodies (tulisokibart, afimkibart, and duvakitug) have advanced to phase 3 trials across multiple global programs, with phase 2 clinical remission rates of 26%-48% in ulcerative colitis (placebo-adjusted differences 15-26 percentage points) and endoscopic response rates of 26%-48% in Crohn's disease, alongside favorable safety profiles...The pipeline has expanded to at least 19 development programs, including extended half-life antibodies (XmAb942, SPY002, and BCD-261), bispecifics combining TL1A with IL-23 or α4β7 (RO7837195, XmAb412, LQ080, and ALX001), a first-in-class oral anti-TL1A nanobody, and a first-in-class DR3 receptor antagonist (SL-325). We discuss therapeutic positioning and timing, the opportunity in acute severe UC, and the unusual standing of IBD as the lead indication for this mechanism class."

Journal • Review • Crohn's disease • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Oncology • Ulcerative Colitis • CD40LG • IL23A • TNFA • TNFRSF25 • TNFSF15

XmAb942 (Xtend anti-TL1A), a potential best-in-class, high-potency, extended half-life antibody in development for patients with inflammatory bowel disease (Businesswire) - "Enrollment expectations continue to support a XENITH-UC blinded interim analysis around year-end 2026 and reaching the primary endpoint of the 12-week induction period in 2H27. The primary endpoint of XENITH-UC is the percentage of patients achieving clinical remission defined by the modified Mayo score at week 12."

P2b data • Trial status • Immunology • Ulcerative Colitis

Final results of the Phase 1 study of XmAb942 in healthy participants support a potential best-in-class drug profile in the XENITH-UC study. (Businesswire) - "Induction phase: XmAb942 provides markedly enhanced TL1A inhibition and is predicted to achieve greater than 99% TL1A inhibition in 86% of patients, compared to 31% and 40% for first-generation anti-TL1A antibodies; Maintenance phase: XmAb942 is designed to deliver maximal TL1A inhibition with a single subcutaneous injection every 12 weeks and is predicted to achieve ​greater than 90% TL1A inhibition in 90% of patients, compared to 60% and 68% for first‑generation anti-TL1A antibodies, which are dosed every 4 weeks...Across all XmAb942 doses tested in the Phase 1 study, the incidence of ADA positivity was 57% in healthy participants...PK profile supports the single subcutaneous injection 12-week dosing interval used during the maintenance treatment period in XENITH-UC."

P1 data • PK/PD data • Ulcerative Colitis

Wholly Owned Pipeline Overview:…XmAb942 (Xtend anti-TL1A) (Businesswire) - "Xencor presented final results from the Phase 1 dose-escalation study of XmAb942 in healthy participants at Digestive Disease Week (DDW) in May 2026. All dose levels and routes of administration were well tolerated. XmAb942’s immunogenicity profile supports best-in-class drug exposure, and no impacts of anti-drug antibodies on safety or tolerability or on the population pharmacokinetic model were observed....Enrollment expectations support a XENITH-UC blinded interim analysis around year-end 2026 and reaching the primary endpoint of the 12-week induction period during the second half of 2027."

P1 data • Trial status • Ulcerative Colitis

XmAb942-01: Study of XmAb942 in Healthy Participants and Participants With Ulcerative Colitis (clinicaltrials.gov) - P1/2 | N=270 | Recruiting | Sponsor: Xencor, Inc. | N=148 ➔ 270

Enrollment change • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

XmAb942-01: Study of XmAb942 in Healthy Participants and Participants With Ulcerative Colitis (clinicaltrials.gov) - P1/2 | N=270 | Recruiting | Sponsor: Xencor, Inc. | N=109 ➔ 270

Enrollment change • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

XmAb942-01: Study of XmAb942 in Healthy Participants and Participants With Ulcerative Colitis (clinicaltrials.gov) - P1/2 | N=270 | Recruiting | Sponsor: Xencor, Inc.

New P1/2 trial • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

XmAb942-01 G942-101: A Multi-Stage Study to Test a New Drug in Healthy Adult Volunteers, Then in Adults with Ulcerative Colitis (clinicaltrialsregister.eu) - P1/2 | N=104 | Recruiting | Sponsor: Xencor Inc.

New P1/2 trial • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

Xencor is conducting the global XENITH-UC Study, a Phase 2b study of XmAb942 in ulcerative colitis (UC). (Xencor Press Release) - "Xencor is on-track to present final results from the Phase 1 study of XmAb942 in healthy volunteers in a poster...at Digestive Disease Week (DDW), being held May 2-5, 2026 in Chicago and online, and to provide an update on progress achieved in the XENITH-UC study around year-end 2026."

P1 data • Trial status • Ulcerative Colitis

Phase 1 Interim Results for XmAb942, a Potential Best-in-Class, Long-Acting Anti-TL1A Antibody for the Treatment of Inflammatory Bowel Disease (ECCO-IBD 2026) - "Conclusion Interim results from the Phase 1 portion of the seamless Phase 1/2b XmAb942-01 trial demonstrate that XmAb942 was safe and well-tolerated in single or multiple doses in healthy volunteers, with enhanced target engagement and substantially longer half-life compared to first-generation TL1A inhibitors. The Phase 2b portion of the XmAb942-01 trial in patients with ulcerative colitis, XENITH-UC, is ongoing."

P1 data • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis • TNFA

Two Differentiated, Potentially Best-in-Class Therapeutic Options for Inflammatory Bowel Disease (FinancialContent) - "Present final results from the Phase 1 study of XmAb942 in healthy volunteers in 1H26; Provide an update on progress achieved in the XENITH-UC study near year-end 2026...Present preclinical characterization of XmAb412 in 1H26; Initiate a first-in-human study of XmAb412 in 2H26."

First-in-human • New trial • Preclinical • Trial status • Ulcerative Colitis

Study of XmAb942 in Healthy Participants and Participants With Ulcerative Colitis (clinicaltrials.gov) - P1/2 | N=270 | Recruiting | Sponsor: Xencor, Inc. | Trial completion date: Oct 2027 ➔ Jan 2029 | Trial primary completion date: Oct 2026 ➔ Apr 2028

Trial completion date • Trial primary completion date • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Xencor is conducting the global XENITH-UC Study, a Phase 2b study of XmAb942 in ulcerative colitis (UC) (Businesswire) - "Patient enrollment in the study is ongoing."

Trial status • Ulcerative Colitis

Xencor Reports Second Quarter 2025 Financial Results (Businesswire) - "Clinical Program Updates:...Autoimmune & Inflammatory Diseases:...(i) Xencor is evaluating plamotamab in a Phase 1b/2a proof-of-concept study, for patients with RA have progressed through prior standard-of-care treatment. In June 2025, Xencor received regulatory authorization to proceed with the study...; (ii) Xencor recently initiated the global XENITH-UC Study, a Phase 2b study of XmAb942 in ulcerative colitis (UC). XENITH-UC is a randomized, double-blind, placebo-controlled trial in patients with moderate-to-severe UC, whose disease has progressed after at least one conventional or advanced therapy."

Trial status • Rheumatoid Arthritis • Ulcerative Colitis

XENITH-UC: Phase 2b Study in Ulcerative Colitis (UC) (Businesswire) - "The Phase 2b study of XmAb942 in UC (XENITH-UC) will be a randomized, double-blind, placebo-controlled trial in patients with moderate-to-severely active UC, whose disease has progressed after at least one conventional or advanced therapy. XmAb942 will be administered intravenously during the 12-week induction period and subcutaneously every 12 weeks during the maintenance period. The primary endpoint of the study will be clinical remission based on the modified Mayo score at week 12. The study is designed to enroll approximately 220 patients across three induction dose levels and powered to enable Phase 3 dose selection. XENITH-UC is expected to start in the second half of 2025."

New P2b trial • Ulcerative Colitis

Xencor Announces Positive Interim Results From First-in-Human Healthy Volunteer Study of XmAb942, a High-Potency Extended Half-Life Anti-TL1A Antibody, in Development for Treatment of Inflammatory Bowel Disease (Businesswire) - P1 | N=300 | NCT06619990 | Sponsor: GALE Therapeutics Inc. | "Key Highlights From Phase 1 Study Interim Results: The interim results reflect analyses with subjects in single dose cohorts (IV, n=24; SC, n=24) and in multiple dose cohorts (IV, n=16). Safety: The blinded interim safety analysis indicates that all dose levels and routes of administration of treatment were well tolerated....Pharmacokinetics: The interim analysis of single dose cohorts produced a half-life estimate of greater than 71 days, which is in line with expectations from the 23-day half-life in non-human primates and scaling metrics for half-life extended antibodies. Pharmacodynamics: Consistent with XmAb942’s high-potency and extended exposure design, large and durable dose-dependent increases of total TL1A in circulation were observed in both IV and SC cohorts. Circulating free TL1A was reduced significantly compared to placebo for all cohorts."

P1 data • Inflammatory Bowel Disease • Ulcerative Colitis

Xencor Reports Fourth Quarter and Full Year 2024 Financial Results (Businesswire) - "In the fourth quarter of 2024, Xencor initiated dosing of healthy volunteers in the first-in-human study of XmAb942. In the first half of 2025, Xencor will present initial data from the single-ascending dose portion of the study. In the second half of 2025, Xencor will present data from the multiple-ascending dose portion of the study and plans to initiate a Phase 2 study in participants with ulcerative colitis."

New P2 trial • P1/2 data • Inflammatory Bowel Disease • Ulcerative Colitis

Phase 1/2 study to assess safety, tolerability, and efficacy of XmAb942 (anti-TL1A) in healthy participants and participants with ulcerative colitis (ECCO-IBD 2025) - "This study is currently enrolling in Australia, with Phase 2 to be expanded globally. Interim data are expected in the first half of 2025."

Clinical • P1/2 data • Crohn's disease • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • TNFRSF25

Study of XmAb942 in Healthy Participants and Participants With Ulcerative Colitis (clinicaltrials.gov) - P1/2 | N=300 | Recruiting | Sponsor: GALE Therapeutics Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Xencor Doses First Subject in Phase 1/2 Study of XmAb942 in Development for Patients with Inflammatory Bowel Disease (Businesswire) - "Xencor, Inc...announced that it has initiated dosing of healthy volunteers in the first-in-human study of XmAb942, an investigational high-potency extended half-life anti-TL1A antibody. Xencor continues to expect initial data from the ongoing study during the first half of 2025....The Phase 1/2 randomized, double-blind, placebo-controlled study of XmAb942 will be conducted in three parts. In Phase 1, Part A will enroll healthy volunteers into single-ascending dose (SAD) cohorts, and additional healthy volunteers would receive repeat doses in Part B. In Phase 2, Part C will enroll patients with ulcerative colitis who would receive the dosing determined from Parts A and B."

P1/2 data • Trial status • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Xencor Presents Preclinical Data on XmAb942, a High-Potency Extended Half-Life Anti-TL1A Antibody, to be Developed for Patients with Inflammatory Bowel Diseases (Businesswire) - "Xencor, Inc...announced that preclinical data on XmAb942 were published in a poster to be presented during United European Gastroenterology (UEG) Week on Tuesday, October 15 in Vienna, Austria. XmAb942 is a high-potency, extended half-life, investigational anti-TL1A antibody to be developed for patients with inflammatory bowel diseases, such as ulcerative colitis (UC) and Crohn’s disease (CD). The first generation of anti-TL1A antibodies, designed to block the interaction between the DR3 receptor and its ligand TL1A, have reduced disease activity in patients with UC and CD in multiple clinical studies. Xencor anticipates dosing the first subject in a first-in-human study of XmAb942 in healthy volunteers during the fourth quarter of 2024 and expects to present initial data from the single-ascending dose portion of the study in the first half of 2025."

New P1 trial • P1 data • Preclinical • Crohn's disease • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis