Emerging clinical validation of costimulatory T-cell engager strategies demonstrates the potential to improve the depth and durability of responses in cancer patients. Therapeutic design considerations will be discussed for integrating TCR and costimulatory receptor activation, selecting alternative costimulatory pathways, and employing single versus multiple-tumor antigen targeting strategies, which together are crucial for maximizing selective tumor engagement and optimizing T cell effector activity to restore anti-tumor immunity in cancer patients.

Bispecific antibodies that engage blood–brain barrier receptors enable systemic delivery of biologics to the CNS, yet limited cell-type specificity constrains efficacy and safety. We are engineering shuttles that couple BBB transport with targeting to neurons, microglia and other brain cell types. These platforms deliver antibodies, cytokines, and antisense oligonucleotides, achieving selective activation, immune modulation, and gene silencing in vivo. We will discuss design principles, PK/PD relationships, and efficacy results to date across different neurological disease models.

NXT007 is a next-generation FVIIIa-mimetic bispecific antibody designed to achieve hemostatic normalisation in people with the bleeding disorder hemophilia A. This presentation details a comprehensive preclinical comparison between NXT007 and emicizumab across multiple in vitro and in vivo models. We demonstrate that NXT007 provides significantly greater potency in thrombin generation, clotting, and bleeding assays, with no evidence of hypercoagulability. Our results support the ongoing clinical development of NXT007 and its potential to improve therapeutic efficacy and patient outcomes by reaching non-hemophilic levels of hemostasis.

Targeting blood–brain barrier proteins such as TfR and CD98hc enables more effective brain delivery of biotherapeutics for neurological diseases. We engineered a human IgG1 Fc domain to bind both receptors, creating a dual transport vehicle (TV) platform that achieves higher brain concentrations than targeting either receptor alone. By tuning affinities to TfR and CD98hc, we can modulate brain uptake kinetics and biodistribution—where stronger TfR binding drives faster uptake and clearance, while stronger CD98hc binding promotes higher, more sustained brain exposure.

The clinical activity of T cell bispecific antibodies (TCBs) in solid tumors remains limited. Insufficient co-stimulatory signals are suspected to be a major factor contributing to the suboptimal efficacy. Tumor-directed co-stimulation offers a promising strategy to deliver localized co-stimulation while minimizing systemic toxicity. While 4-1BB and CD28 are well-characterized co-stimulatory pathways, their relative efficacy in supporting TCBs remains unclear. We systematically compared 4-1BB and CD28 co-stimulation in the context of the HER2xCD3 TCB (runimotamab), using HER2-4-1BBL and HER2-CD28 tumor-targeted co-stimulatory agonists.

Immunotherapy-engineering the immune system to treat diseases such as cancer, neurodegeneration, and autoimmune disorders, has been explored for over a century but is only now transforming medicine. Recent years have brought major clinical successes, driven by advances in genomics, synthetic biology, and machine learning. Single-cell genomics is further revolutionising our understanding of immune-related diseases. I will highlight these insights and discuss emerging technologies shaping the future of immunology and immunotherapy.

T cell engagers (TCEs) are limited by suboptimal pharmacokinetics and safety. We present an mRNA-LNP platform enabling in vivo expression of bispecific and trispecific TCEs with tunable exposure and tissue-directed activity. Through sequence and formulation engineering, this approach achieves potent efficacy with improved safety and reduced cytokine release compared to recombinant formats. Preclinical data highlight its potential to expand the therapeutic window in oncology and beyond.

The precision activated bispecific VHHs comprise albumin-binding and T-cell receptor-binding VHH domains connected via protease-cleavable linkers, remaining masked in healthy tissues but selectively activated in tumors where disease-associated proteases restore T-cell engaging activity. Preclinical data demonstrate >1000-fold increases in T-cell activation and cytotoxicity upon protease cleavage, with significant tumor growth inhibition and improved safety profiles compared to conventional T-cell engagers.