Cleave Therapeutics

Cleave Therapeutics, initially known as Cleave Biosciences, was a clinical-stage biopharmaceutical company founded in 2011 by scientific co-founders Raymond Deshaies, PhD, Seth Cohen, PhD, and Francesco Parlati, PhD. The company focused on developing novel treatments for cancer and neurodegenerative diseases by targeting protein homeostasis pathways, specifically the Valosin-Containing Protein (VCP)/p97 enzyme.

The company's core strategy revolved around developing small-molecule inhibitors for VCP/p97, a critical enzyme that regulates cellular stress and protein degradation, processes upon which cancer cells are highly dependent for survival. Its pipeline was also exploring VCP/p97's role in mitochondrial health for potential application in neurodegenerative diseases. After an initial drug candidate, CB-5083, was terminated in Phase 1 trials due to adverse effects, the company developed a second-generation candidate, CB-5339. CB-5339 is an oral, selective inhibitor designed to overcome the limitations of earlier compounds. In July 2020, Cleave initiated a Phase 1 clinical study of CB-5339 for patients with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS). The trial was conducted in collaboration with the National Cancer Institute (NCI), which also sponsored a separate Phase 1 trial for solid tumors and lymphomas.

Cleave Therapeutics operated as a venture-backed private entity, securing significant funding to advance its research. Over its lifetime, the company raised approximately $103 million from prominent investors including Orbimed, 5AM Ventures, U.S. Venture Partners, Celgene, and Astellas Venture Management. In March 2021, the company entered into a licensing agreement with CASI Pharmaceuticals to develop and commercialize CB-5339 in Greater China, which included a $5.5 million upfront payment and a $5.5 million investment in Cleave via a convertible note. However, by July 2023, Cleave Therapeutics ceased operations and sold its assets. CASI Pharmaceuticals acquired the global rights to the clinical asset CB-5339, while Eikon Therapeutics acquired the preclinical assets and chemical library. Keywords: VCP/p97 inhibitor, protein homeostasis, CB-5339, acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), oncology drug development, cellular stress pathways, AAA ATPases, neurodegenerative disease, small molecule therapeutics, CASI Pharmaceuticals, Eikon Therapeutics, Raymond Deshaies, Seth Cohen, Francesco Parlati, Laura Shawver, clinical trial, biopharmaceutical, cancer research, solid tumors, drug discovery, venture capital, OrbiMed, 5AM Ventures.