Immutep Limited has reported promising early results from its Phase I study of IMP761, a first-in-class LAG-3 agonist antibody designed to treat autoimmune diseases. The placebo-controlled, double-blind trial demonstrated significant T cell suppression with a favorable safety profile at the highest tested dose of 0.9 mg/kg.
Strong Efficacy Signal with Clean Safety Profile
Pharmacodynamic data from the study showed that IMP761 achieved 80% inhibition of T cell infiltration in the skin at day 10 following a neoantigen rechallenge. Notably, no treatment-related adverse events were observed in healthy participants through the highest dosing level tested to date.
The encouraging efficacy and safety results have prompted Immutep to continue dose escalation with single ascending dose levels of 2.5, 7, and 14 mg/kg. The company expects to report additional Phase I data in the second half of 2025.
Novel Mechanism Targets Root Cause of Autoimmune Disease
IMP761 represents the first LAG-3 agonist antibody developed to potentially treat autoimmune disorders. The drug works by enhancing the "brake" function of LAG-3 (lymphocyte-activation gene-3) to silence dysregulated self-antigen-specific memory T cells, targeting what the company describes as the root cause of autoimmune diseases.
"The early pharmacological data showing substantial T cell suppression at the highest dose level of IMP761 are very promising, especially in conjunction with its continued favourable safety profile," said Dr. Frédéric Triebel, Chief Scientific Officer of Immutep. "LAG-3 expression on activated T cells is known to be highly specific to disease sites, and particularly in areas of chronic inflammation. This unique specificity enables the potential for IMP761 to have a more targeted approach with fewer side effects than other therapies."
Broad Therapeutic Potential Across Major Autoimmune Conditions
The LAG-3 immune checkpoint has been identified as a promising therapeutic target for rheumatoid arthritis, Type 1 diabetes, and multiple sclerosis in multiple publications. Each of these conditions represents multi-billion dollar markets, positioning IMP761 to address significant unmet medical needs.
Preclinical studies published in the Journal of Immunology demonstrated that IMP761 inhibits peptide-induced T cell proliferation, activation of human primary T cells, and antigen-specific delayed-type hypersensitivity reactions. Additional preclinical data in oligoarticular juvenile idiopathic arthritis showed the drug led to decreased effector cytokines and suggested children with this condition have skewed LAG-3 metabolism that could benefit from agonistic LAG-3 activity.
Trial Design and Next Steps
The Phase I trial is being conducted by the Centre for Human Drug Research (CHDR) in Leiden, the Netherlands. Beyond safety analysis, CHDR is implementing its keyhole limpet haemocyanin (KLH) challenge model to evaluate IMP761's pharmacological activity in the first-in-human study.
The trial continues as a single ascending dose study, with the company planning to evaluate higher dosing levels to further enhance IMP761's ability to safely silence dysregulated T cells responsible for autoimmune diseases. The study is registered on clinicaltrials.gov under identifier NCT06637865.
