Technology Platforms
Immutep S.A. is a biopharmaceutical company developing immunotherapeutics in oncology. Our products include a T cell immunostimulatory factor (APC activator) for cancer chemo-immunotherapy and a therapeutic antibody for immune response modulation in cancer. The Company's technologies are based on the LAG-3 immune control mechanism which plays a vital role in the regulation of the T cell immune response.
ImmuFact IMP321 is an APC (antigen presenting cell) activator. Repeated IMP321 injections lead to strong anti-tumor T cell responses in cancer patients. In synergistic combination with first-line chemotherapy for metastatic disease, IMP321 doubles the clinical response rate.
ImmuTune IMP701 is an antagonist anti-LAG-3 antibody. It gives rise to T cell proliferation in a similar manner to anti-CTLA-4 and anti-PD-1 antibodies in cancer patients.
ImmuTune IMP731 is a depleting anti-LAG-3 antibody. It depletes activated T cells in autoimmune disease leading to long-term immunosuppression.
Immunostimulatory Factors:
ImmuFact® IMP321- Immunostimulatory Factor for amplifying the T cell response.
The induction of the T cell response depends on the ability of specialised "antigen presenting cells" (APC) to present the antigen to the receptors on T-cells ("antigen presentation"). This both stimulates the T-cells and enables them to recognise the cancer cell. LAG-3 plays a central role in this process.
The lead product, ImmuFact® IMP321 is a highly potent APC activator derived from a soluble form of LAG-3 that binds to MHC class II molecules expressed by dendritic cells (DC). This leads to DC maturation, migration to the lymph nodes and enhanced cross-presentation of antigens to T cells. As a result, strong and sustained anti-tumor cytotoxic T cell responses are obtained with repeated IMP321 injections. in cancer patients. In synergistic combination with chemotherapy, IMP321 doubles the clinical response rate. This new type of therapeutic strategy is called 'chemo-immunotherapy'. In a Phase Ib trial in metastatic renal cell cancer IMP321 showed an excellent safety profile with no drug-related adverse events and a statistically significant increase in progression-free survival. In a Phase I/II trial in metastatic breast cancer treated with first-line chemotherapy (weekly paclitaxel) IMP321 induced a strong immune and clinical responses (doubling of objective response rate).
IMP321 has two intended clinical settings:
– low dose (e.g. 250 µg) as adjuvant to cancer vaccines
– high dose (e.g. 12 injections 6 mg s.c.) combined with standard chemotherapy (first-line chemo-immunotherapy).
ImmuCcine®: Vectorisation of T-Cell Antigens: "one molecule, two functions"
Covalently linking an antigen to IMP321 in a fusion protein results in both vectorisation of the antigen to dendritic cells as well as the immunostimulatory effect described above. Vectorised therapeutic vaccines have been obtained by Immutep’s researchers by genetically coupling antigens to IMP321 leading to rapid capture and internalisation of the antigen into dendritic cells with increased efficacy and lower dose of vaccine to be used per injection. This second technology thereby combines the T-cell immunostimulatory effect with a powerful vectorisation effect (i.e. one molecule, two functions).
Therapeutic Antibodies:
ImmuTune®: Fine Tuning of the Immune Response
This technology comprises antibodies against LAG-3 in its natural membrane-bound form on the surface of T cells:
- ImmuTune antagonist antibodies. ImmuTune IMP701 is a therapeutic monoclonal antibody targeting LAG-3. This antagonist antibody modulates the signaling pathways in effector T cells and regulatory T cells (Tregs) leading to increased Th1 response and T-cell proliferation in cancer. Very few molecules have been identified as negative regulators of T cell function. CTLA-4 mAbs like ipilimumab do enhance T cell activation. However, it has since become clear that ipilimumab is only activating effector T cells, and not inhibiting Treg activity. The same applies to anti-PD-1 antibodies. Thus, LAG-3 may now be the only target available for a therapeutic antagonistic mAb to both activate T effector cells (by downregulating the LAG-3 inhibiting signal into pre-activated LAG-3+ cells) and inhibit induced (i.e. antigen-specific) Treg suppressive activity. This means that LAG-3 has become a sought-after target for enhancing T cell proliferation against cancer and infectious disease. ImmuTune antagonist antibodies inhibit the role of LAG-3 as a down-regulator of the T cell response. LAG-3 down-regulates the T cell response either directly by inhibiting effector T cells or indirectly through the suppressive activity of the LAG-3+ Tregs. Thus antagonist antibodies lead to enhanced T cell proliferation. Accordingly, Immutep has initiated a preclinical development program which could lead ultimately to cGMP production and clinical testing of an antagonist LAG-3 antibody (IMP701).
- ImmuTune depleting antibodies. This application is based on the fact that LAG-3 is, by definition, a marker of activated T cells enabling depleting antibodies to suppress unwanted T cell activity in autoimmune diseases or transplantation. The lead product, IMP731, will enter the clinic in 2012.
