Burlingame, CA (Press Release) - Cleave Biosciences today announced that it has begun a Phase 1 clin­i­cal trial to eval­u­ate its lead drug can­di­date, CB-5083, in patients with re­lapsed and refractory multiple myeloma. CB-5083 is a first-in-class, oral inhibitor of p97, a critical enzyme that controls various aspects of protein homeo­stasis.

The open-label, Phase 1 dose escalation/dose expansion trial will eval­u­ate the safety, phar­ma­co­ki­netics, pharmacodynamics and anti-tumor activity of CB-5083 in multiple myeloma patients who have re­lapsed/​refractory or refractory disease after receiving two or more lines of ther­apy, in­­clud­ing an immuno­modu­la­tory agent (IMiD) and a pro­te­a­some inhibitor. Cleave ex­pec­ts to enroll up to 60 patients at multiple U.S. cancer centers that are part of the Multiple Myeloma Research Consortium. More in­for­ma­tion about the trial, in­­clud­ing enrolling centers, is avail­able by visiting www.clinicaltrials.gov (ID # NCT02223598) or www.cleavebio.com.

"Patients with multiple myeloma whose disease is resistant to existing ther­a­pies have run out of options. We are eager to assess CB-5083 in this trial and to further under­stand which tumors are dependent on the p97 path­way for their growth and survival so we can focus our future clin­i­cal pro­gram on the patients most likely to benefit from this poten­tial treat­ment," said Laura Shawver, Ph.D., Chief Executive Officer of Cleave Biosciences.

Cleave Biosciences discovered CB-5083 through a targeted screen­ing and medicinal chemistry effort. CB-5083 is a potent, specific and orally bioavailable inhibitor of p97 for which anti-tumor activity has been char­ac­ter­ized in vivo in tumor-bearing mice. It has robust activity in multiple hema­to­logical models as well as in solid tumor xenograft models that are resistant to pro­te­a­some inhibitors. Pharmacologic inter­fer­ence with p97 function in tumors generates irresolvable endoplasmic reticulum stress that induces a lethal unfolded protein response, which in turn leads to apop­tosis and profound antitumor activity.

"Targeting protein homeo­stasis is a well-established ap­proach for the treat­ment of patients with multiple myeloma, but eventually many patients relapse or no longer respond to ther­apy. By disrupting protein homeo­stasis using a com­pletely novel target, we hope to val­i­date CB-5083's mech­a­nism and estab­lish­ its path forward for patients with myeloma," said Sagar Lonial, M.D., Director of Translational Research, B-cell Malignancy Program and Professor of Hematology and Medical Oncology at the Winship Cancer Institute of Emory University.

Preclincial studies also dem­onstrate sig­nif­i­cant promise for CB-5083 in solid tumors. Cleave is cur­rently planning to ini­ti­ate a Phase 1 trial in solid tumors later this year.

CB-5083 is derived from a com­pound initially synthesized by the Specialized Chemistry Center at the University of Kansas, which is part of the National Institutes of Health's Molecular Libraries Program. Cleave's discovery partners also in­clude Tsui-Fen Chou, Ph.D. from the laboratory of Raymond J. Deshaies, Ph.D., who is Professor of Biology, California Institute of Technology, a Howard Hughes Medical Institute Investigator and a Scientific Founder of Cleave Biosciences; and The Scripps Research Institute, also a member of the Molecular Libraries Program.

About Multiple Myeloma

Multiple myeloma, also known as myeloma, is a hema­to­logic cancer, or cancer of the blood, that develops in the plasma cells in bone marrow. It is the second most common blood cancer, after non-Hodgkin's lym­phoma. The National Cancer Institute esti­mates that in the U.S., approx­i­mately 70,000 people are living with multiple myeloma and approx­i­mately 24,050 new cases will be diag­nosed this year. Worldwide, nearly 230,000 people are living with the disease and approx­i­mately 114,000 new cases are diag­nosed annually.

About Cleave Biosciences

Biopharmaceutical com­pany Cleave Biosciences is a pioneer in the discovery and devel­op­ment of drugs that target protein homeo­stasis systems and have the poten­tial to transform the treat­ment of people with dif­fi­cult to treat solid tumors and hema­to­logic malig­nan­cies. The com­pany is privately held and located in Burlingame, California. For addi­tional in­for­ma­tion, visit www.cleavebio.com.

Source: Cleave Biosciences.