Main Conference Day 2Wednesday, 11 June 2025 - BST (British Summer Time, GMT+1)

ImCheck has created a set of bispecific antibodies, exploring different formats and valency to modulate anti-BTN3A agonist potency. Building on these modalities allowed to explore Vγ9Vδ2 T cell stimulation via BTN3A-mediated signal 1, immune checkpoint blocking and cis/trans anchoring to potentiate anti-tumor activity.

HVEM, a member of the TNF receptor superfamily (TNFRSF14), interacts with several molecules, including BTLA, CD160, and LIGHT. HVEM is expressed not only on hematopoietic cells but also on non-hematopoietic cells, which allows it to regulate both the priming phase of T cells in the draining lymph node and the effector phase of the T cell response at the inflamed tissue site. The engagement of HVEM with BTLA provides negative signals, while LIGHT engagement delivers bidirectional positive costimulatory signals, promoting T cell survival and effector functions.

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.

To better harness the anti-tumor activity of T cells on top of immune checkpoint inhibition, we generated a PD-L1/CD28 bispecific antibody using our κλ-body platform to promote antitumor function through a dual mechanism of action, immune checkpoint inhibition and T cell co-stimulation. In this presentation, we provide in vitro and in vivo evidence to confirm the safety and efficient anti-tumor activity of this dual-targeting strategy.

Costimulation of tumor-infiltrating T lymphocytes by anti-4-1BB monoclonal antibodies has shown anti-tumor activity in human trials but can be associated with significant off-tumor toxicities. We designed and validated a tandem Fc-free tumor-specific 4-1BB agonist antibody fused to an engineered albumin sequence with high FcRn binding and favorable pharmacokinetics designed to confine 4-1BB costimulation to the tumor microenvironment. The antibody exhibited prolonged circulating half-life and in vivo tumor inhibition with no evidence of 4-1BB-associated toxicity when administered as purified protein or nucleoside-modified mRNA encoding the antibody.