The fundamental challenge in immuno-oncology is that a majority of patients do not respond to immunotherapies. Cancer patients exhibit tumor-induced immune suppression mediated by immune cell types such as myeloid derived suppressor cells (MDSC). T cell activating therapies can also trigger autoregulatory immune modulation, via MDSC recruitment.
Our proprietary ReSTORE platform is designed to potently and selectively deplete MDSC and to drive the activation and repolarization of T cells to relieve immune suppression and restore anti-cancer immunity in patients. Through subcutaneous delivery, we optimize immune activation by targeting the lymphoid tissues where immunoregulation occurs.
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.