Cleave Therapeutics is a clinical stage biopharmaceutical company focused on valosin-containing protein (VCP)/p97 as a novel target in cellular stress pathways essential to cancer cell growth and survival such as the DNA damage response (DDR) and the response to proteotoxic stress. These pathways are attractive targets for therapeutic use in cancer, and have potential in other disease areas like neurodegeneration and some rare disease indications. There is a growing body of evidence around inhibiting VCP to target cancer stress pathways with known biological relevance in cancer. Cleave has ongoing collaborations with industry partners and leading academic institutions, as well as strategic investment from Astellas and Bristol Myers Squibb. The company is leveraging this combined expertise to advance VCP/p97 inhibitors for use in cancer and other diseases.
VCP is a critical enzyme in the AAA (ATPases Associated with diverse cellular Activities) family of ATPases and is a key regulator of various aspects of protein homeostasis and cellular stress that are critical for cancer cell growth and survival. In neurodegenerative diseases, VCP/p97 has been shown to be important for the health and function of mitochondria, and Cleave’s research has demonstrated the potential for therapeutic benefit for patients with limited treatment options with those devastating diseases.
Cleave’s oncology drug discovery pipeline exploits molecular features that are dependent on VCP/p97 and are key to the growth and survival of cancers cells. Cleave’s investigational drug, CB-5339, is a potent, oral, selective, second-generation inhibitor of VCP/p97, which addresses the limitations of earlier compounds, including exposure and selectivity to the target. The company is conducting a Phase 1 clinical study in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), for which there is compelling preclinical data and a significant unmet medical need.