Day One

• Tackling key hurdles in TCE development including target discovery, safety concerns, T-cell exhaustion, and limited response rates to improve clinical outcomes despite TCEs being a clinical validated concept
• Overviewing next-generation approaches, such as co-stimulation, TCR mimics, masked TcEs, and engagement of alternative cell types – aim to unlock novel targets, enhance tumour selectivity, and enable differentiated mechanisms of action (MoA)
• Showcasing Boehringer Ingelheim’s progress in advancing TCE technologies toward safer, more effective translation

• Engaging PRAME peptide–HLA complexes

• Optimising TCE format and design for intracellular pHLA targeting to maximise potency, specificity, manufacturability and half-life

• Efficiently translating preclinical findings into clinical results

Kickstart new connections in this speed networking session designed to help you meet a high volume of fellow cell engager experts, exchange insights, and set the stage for deeper conversations throughout the summit.

• Unlocking high tumour specificity with TCR-based bispecifics – exploring how targeting peptide–HLA complexes enables precision beyond surface tumourassociated antigens (TAAs), while addressing the challenge of low epitope density
• Understanding the expression threshold – evaluating how TCR affinity and antigen presentation levels impact engagement, efficacy, and safety, with learnings from TCRengineered therapies like tebentafusp
• Pushing beyond monoclonal limits – discussing the role of TCR-mimetics and dualtargeting strategies to improve on-target precision, reduce off-tumour effects, and broaden addressable patient populations

• Exploring untapped opportunities in both canonical and “dark antigen” spaces to offer substantial new opportunities for cancer patients
• Comparing pHLA epitope targeting with antibody-based surface antigen targeting to assess therapeutic quality and patient benefit
• Enhancing engineering precision in TCR/TCRm affinity and specificity to safely and effectively target pHLA with maximal clinical impact

• Bispecific T-cell engagers (TCEs) have shown promising efficacy in the clinic, especially in the context of hematological malignancies but recently also for small cell lung cancer
• However, these treatments are still associated with significant toxicities, including cytokine release syndrome and ICANS, limiting their therapeutic window and potential for clinical combinations
• We developed a novel TCE format, TITAN (Target Induced T-cell Activating Nanobodies), with the potential for an improved therapeutic index by engineering a first-in-class CD8-guided TCE

• Exploring how MAIT Engagers selectively activate cytotoxic T cells without engaging CD4⁺ regulatory T cells, preventing tumour-localised immune dampening
• Preventing CRS without CD4 binding – discussing how MAIT Engagers are designed to prevent systemic immune overstimulation by avoiding broad T cell activation
• Redefining T cell redirection – as a next-gen alternative to CD3-based approaches, seeing how MAIT Engagers offer a strategic leap in precision, potency, and safety in immune-oncology

This is an informal session to help you connect with your peers in a relaxed atmosphere and forge new and beneficial relationships. With an audience of cell engager experts eager to hear the latest innovations and positive movement, you will have the opportunity to display a poster presenting your own work.

• Evaluating preclinical case studies of NKG2D or NKp30 engaging bispecific antibodies
• Synergy with FcγRIIIA engagement – discussing multispecific molecules and impact of molecule architecture vs combination approaches to improve synapse quality and PK profile
• Exploring opportunities for combination with adoptive NK cell transfer using a novel NK cell expansion technology for enhanced therapeutic impact

• Description of a multifunctional platform using albumin as a scaffold for assembly of functionalised nucleic acid modules or chemical conjugation for combinatorial T-cell engager designs
• The incorporation of albumin sequences with different FcRn affinity for programmable pharmacokinetics of T-cell engagers
• Discussing how these synthetic combinatorial formats approaches may accelerate therapeutic prototyping and allow flexible integration of targeting and effector domains compared to traditional protein engineering

• The use of molecules capable of activating the immune system by targeting costimulatory signals on T cells has not been fully explored yet
• NI-4101 is a FcRH5xCD28 bispecific antibody which has the potential to expand the number of patients who benefit from TCE-based therapies, possibly leading to deeper and more durable responses
• NI-3201, a PD-L1xCD28 bispecific antibody, additionally blocks the PD-L1/PD-1 immune checkpoint pathway, thus overcoming two major immune suppression mechanisms at once

• Applying our proprietary machine learning platform, EMLy, for TCR discovery leading and affinity enhancement, leading to the development of potent and safe TCR-based T-cell engagers
• Leveraging AI to optimise multi-specific modalities, to enhance immune activation and efficacy against solid tumours
• Integrating AI in the design phase to improve solubility, reduce aggregation, and boost protein yield, ensuring candidate molecules are both potent and manufacturable at scale