XmAb412 / Xencor - LARVOL DELTA

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

XmAb412 (TL1A x IL23p19), a potential best-in-class, extended half-life bispecific antibody for dual targeting of inflammatory pathways in autoimmune and inflammatory disease, in Phase 1 development and enrolling healthy participants (Businesswire) - "Xencor initiated a first-in-human study of XmAb412 in the third quarter of 2026 and plans to present initial data from the study in 1H27."

Enrollment status • First-in-human • P1 data • Immunology • Inflammation

Study of XmAb412 in Healthy Participants (clinicaltrials.gov) - P1 | N=128 | Recruiting | Sponsor: Xencor, Inc.

First-in-human • New P1 trial

Key Highlights from the Abstract “Discovery and Characterization of XmAb412: A Novel, High-Affinity, Anti-TL1A x Anti-IL23(p19) Native-Like Bispecific Antibody with Extended Half-life for the Treatment of Inflammatory Bowel Disease” (Businesswire) - "XmAb412 robustly suppresses both TL1A and IL23 inflammatory pathways. In cellular assays, XmAb412 demonstrated IC50 values comparable or superior to clinical-stage TL1A antagonist antibodies and approved IL23 antagonist antibodies; XmAb412 is predicted to have a human half-life between 60 and 70 days. In non-human primates, XmAb412 achieved a half-life exceeding 20 days, with similar target engagement to monospecific antibodies; XmAb412 supports high-concentration, low viscosity and citrate-free formulation suitable for subcutaneous dosing....Evaluation of XmAb412 in healthy participants is expected to begin in the third quarter of 2026."

New trial • Preclinical • Immunology • Inflammation

Wholly Owned Pipeline Overview:…XmAb412 (TL1A x IL23p19) (Businesswire) - "(i) Xencor presented preclinical characterization of XmAb412 at DDW in May 2026. XmAb412 robustly suppresses both TL1A and IL-23 inflammatory pathways and is predicted to have a human half-life between 60 and 70 days. XmAb412 supports high-concentration, low viscosity and citrate-free formulation suitable for subcutaneous dosing; (ii) Xencor plans to initiate a first-in-human study of XmAb412 in 3Q26."

First-in-human • New trial • Preclinical • Immunology • Inflammation

Xencor is on track to present the preclinical characterization of XmAb412 in a poster...at DDW in May 2026... (Xencor Press Release) - "...to initiate a first-in-human study of XmAb412 in 2H26."

First-in-human • New trial • Preclinical • Inflammatory Bowel Disease

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

Xencor Reports First Quarter 2025 Financial Results (Businesswire) - "XmAb TL1A x IL23p19: Xencor is conducting lead selection studies and has begun good manufacturing practice (GMP) production campaigns for a TL1A x IL-23p19 bispecific antibody, that is designed to target two important inflammatory pathways for autoimmune and inflammatory disease while avoiding the complexities of dosing and formulary access for two separate TL1A and IL23 targeted drugs. In vitro studies show that several lead candidates match the target inhibition potency of monospecific antibodies to these targets, in a simple IgG bispecific format. Xencor anticipates initiating first-in-human studies during 2026."

New trial • Preclinical • Immunology • Inflammation

Upcoming Clinical Study Initiation Plans (Businesswire) - "XmAb657 (CD19 x CD3), a potent, extended half-life B-cell depleting bispecific T-cell engager for development in autoimmune disease. Xencor plans to initiate a first-in-human study in the second half of 2025; TL1A x IL23 Program: a bispecific antibody for dual targeting of important inflammatory pathways in autoimmune and inflammatory disease, while avoiding the complexities of dosing and formulary access for two separate TL1A and IL23 targeted drugs. Xencor anticipates selecting a lead candidate in 2025 and initiating first-in-human studies during 2026."

New trial • Pipeline update • Immunology • Inflammation