Cancer-associated immune suppression and CRS are major limiting factors in current immunotherapy. MDSC actively inhibit T cell responses in cancer patients and promote immune suppression in solid tumors. They are also significant producers of pathologic CRS-promoting myeloid cytokines, such as IL6.
Our molecules deplete MDSC resulting in the activation and expansion of anti-tumor T cells, without causing CRS, in both immune sensitive and insensitive cancers.
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.
ReSTORE molecules have prolonged pharmacodynamic activity and are delivered subcutaneously (SC) at home via pre-filled syringe. The dosing route and regimen of these molecules is patient-friendly and highly compatible with other therapies (e.g. checkpoint blockade, CAR-T, vaccines).
SC administration serves as a mechanism for effective delivery of our molecules to the lymphatics, the brain center of the immune system, where T cell education and metastatic spread occur. MDSC accumulate in the lymphatic system where they suppress the generation of anti-tumor T cells. By removing MDSC with ReSTORE molecules, the anti-tumor T cells are relieved from their immune suppressed status, allowing them to migrate to tumors and kill tumor cells.
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 (1). 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 (2,3).
Recent evidence (4) 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.
Our goal is to therapeutically disrupt this cycle and restore anti-cancer immunity in patients.
Our lead candidate AMV564 drives selective depletion of MDSC in patients based on results from our 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 our goal to bring new treatment options to cancer patients underserved by immunotherapy.
(1) Gabrilovich DI. Myeloid-derived suppressor cells. Cancer Immunol Res. 2017 Jan;5(1):3-8.
(2) Solito S, Marigo I, Pinton L, Damuzzo V, Mandruzzato S, Bronte V. Myeloid-derived suppressor cell heterogeneity in human cancers. Ann N Y Acad Sci. 2014; 1319:47–65.
(3) Meyer Cet al. Frequencies of circulating MDSC correlate with clinical outcome of melanoma patients treated with ipilimumab. Cancer Immunol Immunother. 2014; 63(3): 247–257.
(4) Sayed et al. T-cell-Secreted TNFα Induces Emergency Myelopoiesis and Myeloid-Derived Suppressor Cell Differentiation in Cancer. Cancer Research 2019;79(2):346-359.