Immutep Limited announces it has entered into an agreement with the Centre for Human Drug Research (CHDR) to perform a first-in-human clinical study of IMP761. This proprietary LAG-3 agonist antibody has been designed to restore balance to the immune system and address the underlying cause of many autoimmune diseases. Subject to the relevant ethic and regulatory approvals, the single and multiple ascending dose, placebo-controlled, double-blind, Phase I study will enrol approximately 49 healthy volunteers, with the objective of assessing safety, pharmacokinetics (PK) and pharmacodynamics (PD).

The study will implement CHDR?s unique keyhole limpet haemocyanin (KLH) challenge model that allows for the evaluation of immunomodulatory agents? pharmacological activity at the earliest stages of clinical development. Immune checkpoint agonists, including LAG-3, PD-1, and CTLA-4, are increasingly gaining recognition in the healthcare industry for their inherent ability to treat autoimmune diseases.

In numerous scientific publications, LAG-3 has been identified as a promising target for agonist immunotherapy for autoimmune disorders including rheumatoid arthritis, Type 1 diabetes, and multiple sclerosis, among others. IMP761 is uniquely positioned as the world?s first immunosuppressive LAG-3 agonist antibody. It may address numerous autoimmune diseases by silencing self-antigen-specific memory T cells, which accumulate at disease sites, and preventing their overactivation.

This is accomplished through enhancing LAG-3?s natural downregulation of auto-reactive memory T cells. IMP761 remains on target to enter the clinic mid-CY2024 and Immutep looks forward to providing more information as it approaches this important milestone. IMP761, a first-in-class immunosuppressive LAG-3 agonist antibody, has the potential to address the root cause of many autoimmune diseases by specifically silencing autoimmune memory T cells that accumulate at disease sites and restoring balance to the immune system.

As published in the Journal of Immunology, encouraging pre-clinical in vivo and in vitro studies show IMP761 inhibits peptide-induced T cell proliferation, activation of human primary T cells, and an antigen-specific delayed-type hypersensitivity (DTH) reaction. Additional preclinical data in oligoarticular juvenile idiopathic arthritis (o-JIA) published in Pediatric Research details how IMP761 led to a decrease in a broad spectrum of effector cytokines in just 48 hours. This study also showed children with o-JIA have a skewed LAG-3 metabolism and suggested they can benefit from agonistic LAG-3 activity.