Wednesday, July 22 Company Company Presentations 2–Biotech
Name /Immutep Limited
Address /Level 12, 95 Pitt Street, Sydney, NSW 2000, Australia
Name /Marc Voigt
Title /Chief Executive Officer
Telephone /(Work) +61 2 8315 7003
Fax /+61 2 8569 1880
Immutep is a globally active biotechnology company that is the leader in LAG-3 related development of immunotherapeutic products for the treatment of cancer and autoimmune disease. Immutep is dedicated to leveraging its technology and expertise to bring innovative treatment options to market for patients and to maximize value to shareholders. Immutep is listed on the Australian Securities Exchange (IMM), and on the NASDAQ (IMMP) in the United States.
For further information visit www.immutep.com
Lymphocyte Activation Gene-3 (LAG-3 or CD223) is an emerging immune checkpoint that is attracting significant interest in the biotech and pharmaceutical industries.
LAG-3 was discovered in 1990 by our Chief Scientific and Chief Medical Officer, Professor Frederic Triebel. Today Immutep is the global leader in LAG-3 with more product candidates in clinical development, including our partnered programs, than any other company in the industry.
Our lead product candidate is eftilagimod alpha (efti or IMP321) which is in late-stage clinical development for the treatment of cancer.
We are also developing IMP761 for the treatment of autoimmune diseases, and our big pharma partners are developing IMP731 for the treatment of autoimmune diseases and IMP701 for the treatment of cancer (further details of our pipeline are available here).
A brief description of the LAG-3 immune checkpoint
Like CTLA-4 and PD-1, LAG-3 is a cell surface receptor with a negative regulatory function. LAG-3 is widely expressed on CD4+ T cells, CD8+ T cells, Tregs, B cells and NK cells and its main ligand is MHC class II molecules on antigen presenting cells (APCs) such as dendritic cells, monocytes and macrophages.
On T cells, LAG-3 is physically associated with the T cell receptor (TCR). When LAG-3 expressed on an activated CD8+ T cell binds to MHC class II molecules on an APC at the same time as the TCR binds to MHC class I, calcium signaling is inhibited which leads to a reduction in cytokine production and a decline in the immune response. This negative feedback mechanism is necessary to actively switch off an immune response when it is no longer required and thus prevent autoimmunity.
Thus, the LAG-3 immune checkpoint is emerging as a promising target for drug development in cancer and autoimmune disease. Immutep is developing four product candidates that target different aspects of the LAG-3 immune control mechanism.
Eftilagimod alpha (IMP321) - an APC activator for cancer
Eftilagimod alpha (efti or IMP321) is a first-in-class antigen presenting cell (APC) activator, which has been shown to induce sustained immune responses in cancer patients when used at low dose (i.e. as a cancer vaccine adjuvant) or at higher doses to achieve a systemic effect (i.e. general APC activation). Other examples of APC activators include toll like receptor (TLR) agonists, STING agonists, or anti-CD40 agonists.
In addition, efti has been shown to be safe and well tolerated, thus making it an ideal combination partner for other drugs or drug candidates. Combining different therapeutic approaches is the most promising way to fight cancer and is attracting considerable industry investment. Our Phase I, Phase II, and Phase II(b) clinical trials are evaluating efti with either chemotherapy or immunotherapy in a number of different cancer settings (further details of these trials are available here).
IMP731 - a depleting anti-LAG-3 antibody for autoimmune diseases
IMP731 (or GSK2831781) is in clinical development by our partner GSK for the treatment of autoimmune disease. IMP731 is a first-in-class cytotoxic (depleting) monoclonal antibody that aims to kill the few LAG-3+ activated T cells that infiltrate autoimmune disease sites. It belongs to the next wave of innovative products that target the underlying cause of autoimmune diseases, rather than merely treat the symptoms such as inflammation. IMP731 is currently in a Phase II clinical trial in ulcerative colitis.
IMP701 - a blocking anti-LAG-3 antibody for cancer
IMP701 (or LAG525) is in clinical development by our partner Novartis for the treatment of cancer.
IMP701 is an antagonist monoclonal antibody which blocks the LAG-3-mediated inhibitory (suppressive) signal given to tumor infiltrating T cells. This allows the CD8+ T cell to generate a better cytotoxic response against cancer cells. LAG-3 is a prime target for immune checkpoint blockade in immuno-oncology as it is readily expressed at high levels on tumor infiltrating lymphocytes in many human tumors.
IMP701 is currently in five Phase I and/or Phase II clinical trials in various cancer settings.
IMP761 - an agonist LAG-3 antibody for autoimmune diseases
IMP761 is a first-in-class agonist antibody of LAG-3 being developed for the treatment of autoimmune diseases. It is a humanised IgG4 monoclonal antibody and is mechanistically distinct from any of the known LAG-3 antibodies.
IMP761 represents the first potential opportunity for fine tuning the immune response to an immune checkpoint target such as LAG-3. It is mechanistically different from the approach used with IMP731 which is a cytotoxic (depleting) anti-LAG-3 antibody. Using an agonist antibody that targets 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 to stop it from continuing to proliferate and react against a patient’s own tissues. Our aim for the clinical development of IMP761 is to address the root cause of autoimmune diseases by suppressing the few self-antigen overactive T cells though a physiological mechanism (LAG-3 inhibitory signalling into activated T cells), rather than just treating the consequences of this overactivation, such as by reducing inflammation.
IMP761 is currently in preclinical development by Immutep.
Name /Amanda Tang
Phone /+61 2 8315 7003