Immutep Gets Approval for Phase I Study of LAG-3 Agonist Antibody for Autoimmune Diseases

Immutep Limited, a biotechnology company known for its innovative LAG-3 immunotherapies, has received official approval to launch the first human trial of its novel drug, IMP761, in the Netherlands. This approval marks a significant advancement in the treatment of autoimmune diseases such as rheumatoid arthritis, Type 1 diabetes, and multiple sclerosis, positioning IMP761 as a potential game-changer in medical science.

IMP761 is the first-ever therapeutic LAG-3 agonist antibody, designed to exploit the immune checkpoint LAG-3, a promising target for agonist immunotherapy. The drug aims to restore immune system balance by enhancing LAG-3's "brake" function to silence unregulated self-antigen-specific memory T cells. These T cells, which accumulate in disease sites, are the primary cause of many autoimmune conditions.

Professor Bent Deleuran of Aarhus University highlighted the critical role that immune checkpoint molecules like LAG-3 play in determining antigen activation outcomes. Preclinical studies have demonstrated the effectiveness of the agonistic LAG-3 antibody IMP761 in suppressing antigen-specific T cell-mediated immune responses and reducing inflammatory cytokines. This has paved the way for its transition to clinical trials, where its potential to address autoimmune diseases will be evaluated.

Dr. Frédéric Triebel, Chief Scientific Officer of Immutep, emphasized the significance of this milestone, noting that the approval of the first-in-human trial for IMP761 marks an important step in the development of new treatments for autoimmune diseases. According to Dr. Triebel, blocking LAG-3 with an antagonist antibody in cancer patients can unleash anti-tumor T cell responses but may also lead to autoimmunity in some patients. This observation has placed LAG-3 at the center of autoimmune disorder research. By using IMP761, an agonist LAG-3 antibody, to reinforce the physiological control of the T cell response, Immutep aims to silence the aggressive T cells responsible for autoimmune diseases.

The Phase I study of IMP761 is designed as a single and multiple ascending dose, placebo-controlled, double-blind trial. It will be conducted by the Centre for Human Drug Research (CHDR) in Leiden, the Netherlands, a leading institute specializing in early-stage clinical drug research. The study plans to enroll 49 healthy volunteers to assess the drug's safety, pharmacokinetics, and pharmacodynamics. CHDR will utilize its unique keyhole limpet haemocyanin (KLH) challenge model to evaluate IMP761's pharmacological activity in the earliest stages of clinical development. Immutep expects the first participants to be enrolled in Q3 of 2024, with initial data anticipated by the end of the year.

IMP761 represents a pioneering approach in the realm of immunosuppressive therapies. The drug has the potential to address the root causes of many autoimmune diseases by specifically targeting and silencing autoimmune memory T cells at the disease sites, thereby restoring immune system balance. Preclinical studies published in the Journal of Immunology have shown that IMP761 inhibits peptide-induced T cell proliferation, activation of human primary T cells, and antigen-specific delayed-type hypersensitivity reactions. Additional data published in Pediatric Research on oligoarticular juvenile idiopathic arthritis (o-JIA) revealed that IMP761 reduced a broad spectrum of effector cytokines within 48 hours. The study also indicated that children with o-JIA exhibit a skewed LAG-3 metabolism, suggesting they could benefit from agonistic LAG-3 activity.

Immutep, a clinical-stage biotechnology company, is at the forefront of developing novel LAG-3 immunotherapies for both cancer and autoimmune diseases. The company is committed to advancing the understanding and application of LAG-3-related therapeutics to bring innovative treatment options to patients and maximize shareholder value.