Cleave Therapeutics is a biopharmaceutical company focused on valosin-containing protein (VCP)/p97 as a novel target in protein homeostasis and cellular stress pathways for therapeutic use in cancer and neurodegenerative diseases. 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 the National Cancer Institute (NCI) and leading academic institutions. The company is leveraging this combined expertise to advance VCP/p97 inhibitors for cancer and neurodegenerative disease. 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 lead drug development candidate, 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 launching a Phase 1 clinical study in acute myeloid leukemia (AML), for which there is compelling preclinical data and a significant unmet medical need. The National Cancer Institute has a decades long interest in VCP/p97 as a target and is planning to sponsor a Phase I trial with CB-5339 in solid tumors.