Hepion Pharmaceuticals, Inc. announced that its research collaborator, Carlos Perez-Stable, PhD, from the University of Miami Miller School of Medicine and Miami Veterans Affairs/Research, presented new findings from a preclinical study on the Company’s lead drug candidate, rencofilstat, a potent inhibitor of cyclophilins, in a presentation at the 2023 State of Florida Cancer Symposium in Tampa, Florida. The presentation, entitled “A New Strategy to Increase Proteotoxic Stress in Prostate Cancer,” highlighted a preclinical study which investigated the killing of cultured prostate cancer cells by rencofilstat in combination with a proteasome inhibitor, ixazomib. Proteosome inhibitors are a class of anti-cancer agents that are used for the treatment of multiple myeloma and other blood cancers.

They kill cancer cells by inducing a process called proteotoxic stress. There has been long-standing interest in expanding the use of proteosome inhibitors for solid tumors, but clinical trials to date have not shown durable anti-tumor efficacy. The present study showed that rencofilstat could synergistically increase the proteotoxic stress and in vitro cancer killing properties of ixazomib.

These results suggest that the addition of rencofilstat could expand the use of proteosome inhibitors for existing applications, or possibly for other cancers, such as prostate cancer. In this preclinical study, rencofilstat and ixazomib were applied at low concentrations to several types of prostate cancer cell lines, and also to non-cancerous prostate cells. Neither drug alone at low concentrations caused proteotoxic stress or killed the cells.

However, in combination they induced sustained proteotoxic stress and killed 70% - 90% of the cancer cells (4 different cell lines) over two days. In contrast, the drug combination caused only mild, transient stress and no killing of the non-cancer cells.