Karsten Sauer

As autoimmune T-cell engager development moves beyond first-generation approaches, the field is increasingly focused on identifying which immune-cell populations and biological pathways will deliver the safest, most selective, and most durable therapeutic responses.

In this interactive roundtable session, attendees will break into smaller discussion groups to evaluate the opportunities, challenges, and translational considerations associated with three of the most important target classes shaping the future of autoimmune T-cell engager development. Each group will discuss one of the following areas:

• Broad B-cell lineage markers, exploring the advantages and limitations of targeting widely expressed B-cell populations to achieve deep immune-cell depletion, rapid disease control, and scalable therapeutic applicability across multiple autoimmune indications
• Plasma cell reservoirs, discussing strategies to eliminate long-lived pathogenic plasma cells that may drive chronic disease persistence and relapse, while balancing infection risk, immune preservation, and long-term safety considerations
• Autoreactive antigen-specific B cells, evaluating emerging precision approaches designed to selectively target diseasedriving immune-cell populations while minimizing off-target immune depletion and preserving broader immune competence

The first generation of autoimmune T-cell engagers has demonstrated the power of broad immune-cell depletion, but questions remain around how to achieve deeper, more durable responses while minimizing infection risk, preserving protective immunity, and addressing disease heterogeneity. The next wave of innovation is focused on identifying diseasedriving immune cells, novel targets, and precision immune modulation strategies capable of delivering more selective and effective therapies. Explore how the field can move beyond conventional approaches by:

• Identifying the optimal pathogenic immune-cell populations to target, evaluating advances in target discovery, immune repertoire profiling, and disease biology to distinguish disease-driving cells from healthy immune populations and improve therapeutic selectivity
• Advancing multi-specific and precision immune modulation strategies, discussing how trispecific, logic-gated, and nextgeneration immune engager platforms can enhance specificity, overcome antigen heterogeneity, and deliver deeper and more durable disease control
• Balancing efficacy, safety, and immune preservation, exploring how novel targeting approaches can achieve potent depletion of pathogenic cells while minimizing off-target toxicity, reducing infection risk, and preserving long-term immune competence