Day One

• Balancing folding, stability, and affinity across dual binding arms to enable robust and consistent target engagement
• Designing architectures that minimise steric interference while preserving full dual-target functionality
• Accelerating early optimisation and decision-making to shorten timelines from discovery to clinical candidate

• Clinical development of TCEs for solid tumours is often impaired by off-tumour ontarget and cytokine-release syndrome (CRS) triggered toxicities, and limited efficacy due to T-cell exhaustion
• We designed a logic-gated Switch-DARPin TCE (AND-gate) for tumour-localised immune activation targeting MSLN & EpCAM which are highly co-expressed in OC and other solid tumours. In addition, we built CD2 co-engagement into the Switch- DARPin inducing sustained T-cell proliferation and activity
• This approach provides an opportunity for novel cancer treatments through logicgated tumour-directed immune activation with increased efficacy & safety over single TAA-targeting modalities

• Enara’s proprietary EDAPT® platform interrogates the dark genome to discover and validate novel, cancer-specific peptide-HLA and cell surface antigens with hallmarks of optimal cancer targets
• DARKFOXTM is a previously undescribed alternative open reading frame (alt-ORF) contained in the exonic sequence of FOXM1. DARKFOXTM alt-ORF encodes a short polypeptide, from which we identified several Class I HLA peptides on primary tumours by immunopeptidomics. We have designed bispecific T-cell engagers targeting DARKFOX using a rational, fit-for-purpose engineering strategy
• We demonstrate robust in vivo anti-tumour efficacy, showing strong tumour regression and highlighting that DARKFOXTM is an attractive cancer antigen for peptide-HLA targeted bispecific T-cell engagers

Join our speed networking session tailored for Bispecific professionals, like yourselves, to connect with fellow industry peers to facilitate rapid yet meaningful exchanges of insights and expertise. Elevate your networking experience during this session designed for impactful connections within the space

• Combining a CD28-targeting antibody with a complementary non-antibody modality to enable synergistic mechanisms beyond antibody-only approaches and unlock enhanced functional activity
• Applying preclinically driven target selection and a rational combinatorial strategy to increase biological relevance and strengthen translational confidence from bench to patient
• Evaluating early experimental patient data, including emerging complete responses, to provide real-world validation of the therapeutic concept and inform future clinical development

• Which preclinical models have proven most predictive for bispecifics, TCEs, and ADCs- including safety and immunogenicity risk, and which consistently fail to translate?
• How do teams combine in vitro, in vivo, and computational approaches to reduce uncertainty before first-in-human studies?
• What translational signals provide sufficient confidence to advance a program, and how do teams actively manage remaining risk?

• Tuning affinity, valency, and synapse engagement to optimise efficacy while maintaining safety
• Engineering CD8 T-cell selectivity to minimise CRS and ICANS without compromising therapeutic potency
• Presenting pre-clinical data on leading programs entering clinical trials

• This presentation will discuss optimisation strategies for distinct T-cell–targeting modalities, focusing on (i) CD3 affinity modulation in T-cell engagers to improve the benefit–risk profile and (ii) adaptation of dosing frequency for T-cell costimulatory bispecific antibodies to enhance T-cell fitness and durability of antitumour immune responses in the clinic
• For CD3 affinity tuning, comparative in vitro and in vivo studies of two B7-H4– targeting CD3 bispecific antibodies demonstrated that lowering CD3 affinity resulted in reduced potency of tumour cell killing and cytokine secretion. The reduced potency was associated with better tolerability in cynomolgus monkeys
• For conditional T-cell co-stimulation, clinical data with acasunlimab (DuoBody- PD-L1×4-1BB) in combination with pembrolizumab show that a less frequent dosing paradigm results in intermittent target engagement, allowing for periods of T-cell rest and leading to improved magnitude and quality of anti-tumour immune responses

• Aiming to deliver tissue-specific TCR-based therapeutics
• Adapting the ImmTAC platform with a novel effector function to address autoimmune diseases
• Exploring the development of a beta-cell–targeted immune-suppressive PD-1 agonist bispecific to treat type I diabetes

Take this opportunity to showcase your latest research and innovations with your peers and understand the strategies of your fellow Bispecifics experts. Visit the website for the full T&Cs of submitting a poster

• Addressing on-target, off-tumour toxicity in solid-tumour TCEs by exploiting avidity-driven selectivity against tumour-associated antigens such as Nectin-4
• Demonstrating robust translational performance with rich in vitro and in vivo datasets, including dose-response efficacy and complete tumour regression in mouse models
• Advancing next-generation formats by applying multispecific design principles, including logic-gated approaches, to improve therapeutic windows

• Gamma delta T-cells combine innate potency with adaptive durability, enabling rapid and sustained immune responses that are naturally suited to discriminating diseased from healthy cells
• Gamma delta T-cell engagers leverage this unique biology to activate tumour-relevant effector cells while avoiding broad immune activation, supporting effective tumour killing with a lower risk of cytokine-driven toxicity
• Cytospire’s multispecific TCE platform activates all gamma delta T-cell subsets, including tissue-resident populations, overcoming patient heterogeneity to unlock more consistent, scalable efficacy in solid tumours