Over the last decade or so, immuno-oncology has gained a reputation as one of the most exciting areas in medicine. Referring to treatments that harness the immune system in the fight against cancer, it has grown from a niche and somewhat speculative field into a vibrant area of drug discovery. It is no surprise, then, that a large number of biotech companies have jumped into this area, intent on finding the next magic bullet for cancer.
Amphivena Therapeutics, Inc. is one such clinical-stage, immuno-oncology company with a novel platform of T cell engagers (Amphivena ReSTORE™) that directly targets myeloid derived suppressor cells (MDSC), thus relieving cancer-induced immune suppression while controlling cytokine release syndrome (CRS). AMV564, Amphivena’s lead molecule, is a clinical stage T cell engager that is highly potent and selectively binds to MDSC while sparing other myeloid cells such as monocytes and neutrophils, activating and expanding anti-tumor T cells in cancer patients. Other platform molecules are trispecific and target tumor antigens in addition to MDSC, providing direct tumor cell killing while combatting immune suppression and restoring anti-tumor immunity.
Targeting the Immune Suppression Cycle in Cancer
Established data have demonstrated that tumor associated immune suppressive cells, such as MDSC, actively inhibit T cell responses and promote immune suppression in solid tumors. Multiple studies across a broad spectrum of malignancies have shown that the accumulation of MDSC within tumors is associated with poor clinical outcomes and poor response to immunotherapy including checkpoint blockade. Recent evidence also revealed that T cell activation in cancer further induces myelopoiesis and immune suppression, via a process known as compensatory or emergency myelopoiesis. Together these processes make up an immune suppression cycle in cancer.
Amphivena Therapeutic’s lead candidate AMV564 drives selective depletion of MDSC in patients based on results from the on-going first-in human clinical trials in solid tumors and AML. In parallel, AMV564 promotes T cell activation and repolarization, producing a cytokine milieu to promote tumor antigen presentation and restore anti-cancer immunity. Consistent with this observed restoration of immune function, AMV564 has demonstrated monotherapy activity in solid tumor and hematologic cancer patients with an excellent clinical safety profile and combinability with checkpoint inhibition. These early signals of clinical activity support its goal to bring new treatment options to cancer patients underserved by immunotherapy.
AMV564 induced T cell mediated killing of MDSC and T cell activation
AMV564 harnesses the patient’s own T-cells to both relieve immune suppression and restore anti-cancer T cell function systemically and in the tumor microenvironment. AMV564 induces T cell mediated killing of myeloid derived suppressor cells (MDSC) and AML leukemic blasts, while sparing differentiated myeloid cells (e.g., neutrophils and monocytes) and drives activation and repolarization of T cells and improved T effector function.
To date, over 80 patients have received AMV564 across three Phase 1 clinical trials for solid tumors, acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), and AMV564 has demonstrated monotherapy activity in solid tumor and hematologic cancer patients with an excellent safety profile as well as combinability with checkpoint inhibition. The company is uniquely positioned to leverage the simultaneous relief of immune suppression and enhanced T cell effector function to restore anti-cancer immunity in patients.
The Relentlessly Reliable Leader
Curtis Ruegg, Ph.D. is the President and Chief Executive Officer of Amphivena Therapeutics, Inc. He has over 25 years of experience in the biopharmaceutical industry, and has built and managed several successful novel biologics development programs, from research through clinical development and resulting in health authority approval and commercialization. Prior to joining Amphivena, Curtis was President and CEO at Parvus Therapeutics developing a novel biologics platform targeting regulatory T cells for the treatment of autoimmune disease. Prior to Parvus, Curtis was Executive Vice President, Technical Operations at Revance where he established and managed the biologics development program to support the Company’s first IND spanning through Phase 3.
Dr. Ruegg earned his Ph.D. degree from Johns Hopkins University School of Medicine for research on retroviral mediated immunosuppression and performed research in immunology as a Cancer Research Institute Fellow at Stanford University School of Medicine.