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LAG-3, a validated immune checkpoint molecule.

Lymphocyte Activation Gene-3 or LAG-3 is an immune checkpoint molecule involved in the regulation of the immune system that was discovered by Professor Frédéric Triebel, M.D., Ph.D., our Chief Scientific Officer.

Dr. Triebel is a pioneer in the understanding and advancement of therapeutics related to LAG-3, and our diversified product portfolio exploits this molecule’s unique ability to stimulate or suppress the immune response. With immunotherapies distinctly designed around the interaction of LAG-3 and major histocompatibility complex class II (MHC II) on antigen-presenting cells (APC) and T cells, we aim to harness the power of the body’s immune system to fight cancer and autoimmune diseases.

In oncology, LAG-3 is unique among the three immune checkpoints with approved therapeutics (PD-1, LAG-3, CTLA-4), in that both its inhibition on T cells and its activation of dendritic cells can, in different ways, stimulate the immune system against cancer.

Eftilagimod alpha is Immutep’s leading clinical candidate in oncology. This first-in-class soluble LAG-3 protein and MHC Class II agonist has been designed to uniquely activate antigen-presenting cells (e.g., dendritic cells, monocytes) that elicit both adaptive and innate immunity to fight cancer. Efti acts as a key to unlock a broad immune response through its high-affinity binding to a specific subset of MHC II ligands on APCs leading to the expansion and proliferation of CD8+ (cytotoxic) T cells, CD4+ (helper) T cells, dendritic cells, NK cells, and monocytes. It also upregulates the expression of key biological molecules like IFN-ƴ and CXCL10 that further boost the immune system’s ability to fight cancer.

Immutep is investigating its novel efti immunotherapy and its distinctive mechanism of action across numerous solid tumor indications in combination with anti-PD-(L)1 therapies, chemotherapy, and as part of a triple combination approach with standard-of-care anti-PD-1 therapy & chemotherapy. These combinations aim to capitalize on efti’s favourable safety profile and synergies with anti-PD-(L)1 therapies and chemotherapy, as has been seen across numerous clinical trials to date, to drive superior outcomes for patients.

In autoimmune diseases, Immutep’s experienced research team under the guidance of Dr. Triebel has designed the world’s first LAG-3 agonist antibody, IMP761, that is mechanistically distinct from any of the known LAG-3 antibodies.

Inhibitory receptor agonists represent a significant, untapped opportunity for the treatment of autoimmune disease, and IMP761 is the first candidate created for fine tuning the immune response to the LAG-3 immune checkpoint. Using an agonist antibody to target the LAG-3 receptor on the surface of activated T cells is expected to result in a stronger inhibitory signal being delivered directly into the T cell; thereby stopping it from continuing to proliferate and react against a patient’s own tissues. By suppressing self-antigen overactive T cells through LAG-3 inhibitory signaling, IMP761 is uniquely positioned to address the root cause of autoimmune diseases.

For more on Immutep’s pioneering immuno-oncology and immunotherapy LAG-3 portfolio, including ieramilimab (LAG525) and GSK’781, please see our Clinical Pipeline and Clinical Trials.