MAIN CONFERENCE DEC. 16Monday, 16 December 2024 - PT (Pacific Time, GMT-08:00)

The talk will focus on our pre-clinical and clinical experience with CD27 monoclonal antibodies and consider how their therapeutic activity might be improved.

A recent clinical trial involving MOv18 IgE, provided tantalising evidence of IgE’s potential for the treatment of cancer. Epsilogen is conducting a phase Ib trial in which translational data will be collated to further understand mechanisms associated with IgE therapy. In addition, Epsilogen has established a pipeline of anti-tumoral IgEs and two novel platforms: bispecific IgE and a hybrid antibody which combines the effector functions of IgE and IgG.

The FORCE™ platform was designed to enhance delivery of oligonucleotide to muscle for the treatment of neuromuscular disorders by conjugating them to an antigen-binding fragment (Fab) that is selective for the human transferrin receptor 1 (TfR1). In this presentation, we introduce the properties and modularity of the FORCE platform and provide evidence of translation between pre-clinical models and clinical proof of concept in myotonic dystrophy type 1 (DM1) with DYNE-101.

The paucity of dendritic cells in the tumor microenvironment is considered to be a limiting factor to immune checkpoint blockade efficacy in patients with cancer. These cells can be expanded in vivo by the growth factor FLT3L, however, used in its native form, FLT3L requires daily dosing up to 14 days, hampering its broader use in the clinic. Here we developed a FLT3L with effectorless NG2LH Fc fusion to improve drug-like properties that allows for sustained expansion of dendritic cells upon a single injection, and stimulation of antitumour immunity when combined with an adjuvant and checkpoint blockade in preclinical models. By easing dosing constraints, FLT3L-Fc NG2LH could facilitate exploration of FLT3L based immunotherapies in cancer patients.

We show unique mechanisms of flexible homodimerization crucial for the inhibitory function of checkpoint receptor PD-1 and LAG-3, and identified a novel cell surface receptor potently modulating myeloid-associated Type-I IFN responses. These efforts laid the foundation for developing novel immunotherapies for cancer and autoimmune diseases.

We present our forward translation strategy for evaluating off-the-shelf T cell engagers in combination with costimulatory agonists, employing advanced humanized mouse models to enhance preclinical insights. Our approach bridges the gap between preclinical and clinical research, showcasing the translational relevance of our findings. Additionally, we will share first-in-human Phase 1 clinical data supporting the predictive value of our preclinical platform and its potential to inform therapeutic development. This integrated strategy underscores the promise of our platform in advancing immunotherapeutic approaches