MAIN CONFERENCE DEC. 17Tuesday, 17 December 2024 - PT (Pacific Time, GMT-08:00)

This presentation will describe pre-clinical data from Regeneron’s clinical approaches to enhancing anti-tumor efficacy of T cells, focusing on the combination of costimulatory bispecific antibodies with checkpoint blockade and T cell redirecting bispecifics. In addition, data from new classes of T cell targeted enhancement strategies in pre-clinical development will be discussed.

T-cell engaging bispecific antibodies have had tremendous success in treating hematologic tumors but have shown limited efficacy in solid tumors. Alternative strategies for engaging the immune system employing safe and tunable bispecific antibodies are needed to overcome the challenges of solid tumors. In this presentation, we describe the bispecific platforms developed at Rondo Therapeutics and highlight progress on our lead program, RNDO-564, a CD28 x Nectin-4 bispecific antibody for treatment of metastatic bladder cancer.

CD3 bispecifics are clinically validated modalities, but none of the 9 approved molecules incorporates a costimulatory signal for optimal T-cell activation. EvolveImmune has integrated natural CD2 costimulation and affinity-tuned CD3 engagement into our EVOLVE platform, which induces sustained T-cell activation and potent redirection against tumor cells, whilst limiting T-cell exhaustion.

IgM-based T-cell engagers (TCEs) exhibit high avidity, specificity and potential safety advantages over other formats due to multivalent architecture and unique position of the CD3 binding domain on J-chain. Having two binding sites on the J chain (for CD3 and CD28), co-stimulatory IgM TCE engages both signal 1 and signal 2 on T-cells, with the goal of optimal T-cell activation and survival for more robust and durable tumor cytotoxicity.

IgA can be a well-suited isotype for therapeutic application in oncology due to its capacity to activate myeloid cells, especially neutrophils. However, therapeutic use is limited through issues with developability, pharmacokinetics, and in vivo translatability. In my talk, I will address the steps we have taken to employ IgA optimally for oncology.

The therapeutic potential of T cell engagers (TCE) has been limited by a narrow safety window, with excess cytokine release and on-target toxicity limiting their clinical usefulness. Our Tumor-Microenvironment Activated Therapeutics (T-MATE™) platform overcomes these challenges by utilizing a pH-dependent conformational switch. This innovative mechanism attenuates TCE activity at physiological pH while preserving full potency within the tumor microenvironment, enabling a new class of safe and effective TCE therapeutics.