Innovative LAG-3 Immunotherapy in Oncology and Autoimmune Diseases

When our Chief Scientific Officer, Dr. Frédéric Triebel, first discovered Lymphocyte Activation Gene-3 (LAG-3), he realized there was a novel pathway that could lead to valuable therapeutics for patients by harnessing the power of their own immune systems. This view centered on his findings around the interaction of LAG-3 and one of the central components of how our bodies respond to cancer, autoimmune diseases, and infection - the major histocompatibility complex class II (MHC II) - found on antigen-presenting cells.

Since those discoveries, Immutep has been a pioneer in developing therapeutics that are distinctly designed around the interplay of LAG-3 and MHC II to either stimulate or suppress the immune system to fight cancer or eradicate autoimmune diseases. Today, we have a diversified portfolio of cutting-edge immuno-oncology and targeted LAG-3 immunotherapy including three clinical stage candidates, one pre-clinical candidate, and one candidate that is early-stage.

Oncology Portfolio

• Igniting the Immune Response via Antigen Presenting Cells (APC)
  Our lead clinical candidate, eftilagimod alpha (efti / IMP321), is a first-in-class soluble LAG-3 protein delivered subcutaneously that uniquely activates APCs (e.g., dendritic cells, monocytes) via a specific subset of MHC II ligands, stimulating both the adaptive & innate immune systems to fight cancer. The broad immune response elicited by efti includes significant increases of various anti-tumor cells and serum biomarkers that corresponds with encouraging outcomes in numerous clinical trials.
  
  
• Blocking LAG-3 On T Cells to Boost an Immune Response
  As a co-inhibitory receptor, LAG-3’s expression on T cells has a negative feedback mechanism that cancer utilizes to hide from the immune system. Immutep designed the world’s first anti-LAG-3 antibody to block LAG-3 and remove the brakes on the immune system to better respond to cancer. Our subsequent efforts led to LAG525 (ieramilimab), the anti-LAG-3 clinical candidate we have out-licensed to Novartis. Today, Immutep continues to innovate in blocking LAG-3 on T cells through a novel, small molecule anti-LAG-3 candidate at the early development stage.

Autoimmune Diseases Portfolio

• Agonist LAG-3 Antibody
  Immutep has developed the world’s first LAG-3 agonist antibody for autoimmune diseases, called IMP761, which acts upstream on activated T cells to target the root cause of self-antigen-specific T cell induced disease and restore balance to the immune system. This clinical candidate is a potential game-changer in how autoimmune diseases are treated.
  
  
• Depleting LAG-3 Antibody
  IMP731 is Immutep's depleting LAG-3 antibody that removes T cells involved in autoimmune diseases. This clinical-stage asset was evaluated by GSK in a Phase I/Ib trial in psoriasis with encouraging early evidence of clinical efficacy. GSK then commenced a Phase II in patients with active ulcerative colitis. While the ulcerative colitis trial was ultimately discontinued, it concluded IMP731 may have potential efficacy in other non-gastrointestinal inflammatory conditions.

For more on the Company’s technology and LAG-3 product portfolio, please see Our Science and our Clinical Pipeline.