Day Two

• Preclinical development of a dual-targeting T-Cell Engager (TCE) – AMG 305
• Leveraging different techniques in a weight of evidence (WoE) approach to uncover target colocalisation in normal human tissues
• Challenges with relevant species determination for AND-gated targets

• Enhancing translational predictability – Explore how humanized mouse systems can capture key pharmacodynamic changes, immune activation patterns, and tumor microenvironment dynamics to better forecast T-cell engager efficacy in patients
• Bridging the gap to clinical outcomes – Discuss how these models inform dose selection, immune trafficking, and safety readouts, while recognizing current limitations in replicating complex human immune biology
• Toward smarter preclinical workflows – Learn strategies to combine humanized in vivo models with patient-derived ex vivo platforms, advancing more predictive translational frameworks that reduce attrition and accelerate clinical success

• Addressing how TCEs are showing great efficacy in clinic but remain toxic hindering broader patient access and community use
• Showcasing NovalGen’s AutoRegulation (AR) platform: safeguarding potency and efficacy while preventing T cell exhaustion through built-in self-regulation
• Advancing the world’s first AR-enabled TCE toward the clinic by end of 2025

This expert-led discussion will unpack the unique translational challenges and opportunities for T-cell engagers across oncology and autoimmune indications. Panelists will explore how emerging scientific insights, target biology, and mechanistic understanding can inform smarter therapeutic design, combination strategies, and clinical development pathways for both cytotoxic and tolerability-driven indications.

• How does target biology influence format selection, CD3 affinity tuning, and tissue-selective delivery approaches in solid tumours vs autoimmune tissues?
• What translational tools (e.g., biomarkers, PD readouts, in vitro/in vivo models) are proving most predictive for efficacy and safety in both therapeutic areas?
• What combination strategies are most promising e.g., with checkpoint inhibitors, cytokines, or tolerance inducing agents and how do we time them?
• Where are current translational models falling short, and how can we better model immune engagement, off-tumour effects, and chronic exposure?
• How do we de-risk multi-targeting and immune activation in non-lethal diseases where tolerance, durability, and safety thresholds differ from oncology?

• Unlock the potential of masked TCEs with Xilio’s tumor-activation platform, designed to deliver potent, localised T cell activation while minimising systemic toxicities and widening the therapeutic index
• Explore next-generation ATACR bispecifics with masked CD3 domains and SEECR tri-specifics incorporating co-stimulatory signaling engineered to enhance T cell potency, persistence, and anti-tumor activity
• Gain insights into Xilio’s pipeline of wholly-owned masked TCE programs targeting PSMA, CLDN18.2, and STEAP1, advancing toward clinical translation across solid tumor indication

• Selective Tumour Targeting: Conditional Switch-DARPin selectively induces T cell cytotoxicity against dual-TAA expressing tumour cells, sparing single-antigenexpressing cells
• Enhanced T Cell Function: CD2 co-engagement promotes sustained T cell proliferation and prevents T cells dysfunction, supporting durable antitumour responses
• Favorable Safety Profile: In vivo and human whole blood studies show significant tumour regression with minimal cytokine release, highlighting the potential for safe, logic-gated immune activation

• Introduction to the Immuno-STAT™ platform for selective regulation of antigen-specific T cells
• Lead candidate CUE-501 differentiates from pan-TCEs by selectively engaging existing virus-specific T cells to deplete pathogenic B cells while minimising systemic immune activation and CRS risk
• The modularity of the Immuno-STAT™ platform enables opportunities to target additional pathogenic cell types beyond B cells and opens avenues for novel therapeutic approaches in autoimmunity and oncology

• Introduction to the potential of gamma delta T-cells and tackling the challenge of their limited presence in patients by engineering engagers that expand and activate these cells in vivo without relying on CD3 stimulation
• Exploring ways to safely increase levels of rare immune cells like gamma delta T-cells and NK cells inside the body for effective targeting
• Discuss limitations of oncology-based animal models for autoimmune settings and examine strategies with gamma delta T-cells to validate lymphoid tissue targeting, depletion efficacy, and safety in the absence of conventional cytokine-driven biomarkers