Main Conference Day 2Tuesday, 16 December 2025 - PT (Pacific Time, GMT-08:00)

PRO-XTEN^TM masked T cell engagers (TCEs) are conditionally active by exploiting the dysregulated protease activity in tumors. Preclinically, PRO-XTEN^TM TCEs demonstrated 1) Strong masking of in vitro cytotoxicity by approximately 4 logs; 2) Potent in vivo efficacy at doses similar to the efficacious doses of unmasked TCE controls; and 3) Increased MTDs in NHP by greater than >100 fold. Clinical trials of PRO-XTEN TCEs targeting HER2, PSMA and EGFR are currently ongoing.

This presentation will cover the discovery and engineering of XmAb942, a potential best in class high-affinity anti-TL1A monoclonal antibody with extended half-life, and a first-in-class bispecific antibody targeting TL1A and IL-23p19. Both candidates are designed for therapeutic use in Ulcerative Colitis and Crohn’s Disease.

Maxion have shown that small cysteine-rich peptides (“knottins”) with ion-channel modulating activity can be inserted into antibody CDR loops while retaining their function. The resulting “KnotBody molecules modulate ion channel activity while benefitting from the optimal drug-like properties of antibodies. This presentation will illustrate the generation and optimisation of KnotBody inhibitors of Kv1.3, an important ion channel affecting function of T effector memory cells.

We present discovery of a novel IgE cleaving protease engineered using our proprietary machine learning enabled IMPACT platform to obtain desired target specificity, potent cleavage, and efficacy in preclinical models with favorable manufacturability properties, low immunogenicity, pharmacokinetics, and pharmacodynamics. IgE cleavers offer a new potential targeted therapy for allergic and atopic diseases.

Therapeutics in inflammatory indications often are limited in their efficacy. Blockade of multiple pathways by targeting multiple cytokines with a single agent is a way to enhance efficacy and benefit to patients. We describe the engineering of trispecific antibodies with high-affinity neutralization of three cytokines simultaneously. Design factors to be discussed include domain arrangement, strategies for driving correct chain pairing, and optimization for expression, stability and developability.