Xencor (XNCR) Digestive Disease Week Conference summary

Key program updates

• Presented Phase I results for XmAb942 and preclinical data for XmAb412, both targeting TL1A for autoimmune and inflammatory diseases.

• XmAb942 is in a global Phase IIb trial (XENITH-UC) for ulcerative colitis, with 12-week induction results expected in 2027.

• XmAb412, a bispecific antibody targeting TL1A and IL-23p19, will enter Phase I in Q3 2026, with Phase II planned for 2027.

• XmAb942 demonstrated high potency, long half-life (74 days), and low immunogenicity in Phase I, supporting infrequent dosing.

• XmAb412 showed sub-picomolar affinity, robust dual pathway inhibition, and favorable formulation for subcutaneous dosing.

Clinical and scientific insights

• XmAb942 achieved durable target engagement and best-in-class immunogenicity profile, with no neutralizing antibodies at target doses.

• QSP modeling predicts XmAb942 will deliver >90% TYK2 inhibition in 90% of patients, outperforming first-generation TL1A antibodies.

• Reduced injection burden with XmAb942 (every 12 weeks) is expected to improve patient experience and adherence.

• XmAb412’s 1+1 bispecific format minimizes immune complex formation, reducing immunogenicity risk compared to traditional bispecifics.

• Preclinical and PK data suggest XmAb412 will enable high, durable exposure and convenient dosing intervals, with a predicted 60–70 day half-life in humans.

Market and development strategy

• TL1A is positioned as a branded anchor for future biologic monotherapy and combination therapies in IBD.

• XmAb942 and XmAb412 are expected to serve complementary roles, with 942 as monotherapy and 412 as a dual-pathway option for refractory or first-line use.

• Data from ongoing and upcoming studies will guide expansion into Crohn’s disease and other autoimmune indications.

• Strategic partnerships and business development will be considered as data matures, with key inflection points in 2027.

• The company’s protein engineering platform enables rapid, high-quality development of next-generation antibodies and bispecifics, including T-cell engagers for oncology and autoimmune diseases.