EDISON, N.J., Jan. 10, 2023 — Hepion Pharmaceuticals, Inc. (NASDAQ:HEPA), a clinical stage biopharmaceutical company focused on Artificial Intelligence (“AI”)-driven therapeutic drug development for the treatment of non-alcoholic steatohepatitis (“NASH”), hepatocellular carcinoma (“HCC”), and other chronic liver diseases, announced that its research collaborator, Carlos Perez-Stable, PhD, from the University of Miami Miller School of Medicine and Miami Veterans Affairs/Research, today 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.
“The selective killing of several cancer cell lines by this drug combination without killing the non-cancer cells occurred because cancer cells are especially susceptible to proteotoxic stress due to their aggressive growth and high demand for proteins,” said Dr. Perez-Stable. “Certain isoforms of cyclophilins participate in the efficient synthesis and function of proteins and contribute significantly to cancer cell growth. Inhibiting those cyclophilins with rencofilstat and impairing protein turnover with ixazomib together stressed the cells beyond a threshold and triggered their death.”
“Dr. Perez-Stable’s findings open up new opportunities, in addition to our Phase 2 trials in NASH, for investigation of potential cancer treatments and therapeutic use of rencofilstat,” said Daren Ure, PhD, Hepion’s Chief Scientific Officer. “The findings are similar to those of a previous, independent study in which cyclophilin inhibition in combination with the proteosome inhibitor, carfilzomib, synergistically killed multiple myeloma cells.1 A synergistic anti-cancer effect also has been observed in a liver cancer study in mice with a combination of rencofilstat and a checkpoint inhibitor, anti-PD1 antibody. Thus, evidence is accumulating that rencofilstat could potentiate the anti-cancer activities of multiple agents, through multiple mechanisms, and across a variety of cancer types. This makes us very optimistic that rencofilstat will have tremendous versatility as an anti-cancer agent.”
1Nature Medicine, 2021 27(3):491-503. doi: 10.1038/s41591-021-01232-w
About Hepion Pharmaceuticals
The Company’s lead drug candidate, rencofilstat, is a potent inhibitor of cyclophilins, which are involved in many disease processes. Rencofilstat is currently in clinical-phase development for the treatment of NASH, with the potential to play an important role in the overall treatment of liver disease – from triggering events through to end-stage disease. Rencofilstat has been shown to reduce liver fibrosis and hepatocellular carcinoma tumor burden in experimental models of NASH, and has demonstrated antiviral activities towards HBV, HCV, and HDV through several mechanisms, in nonclinical studies. In November 2021, the U.S. Food and Drug Administration (“FDA”) granted Fast Track designation for rencofilstat for the treatment of NASH. That was followed in June 2022 by the FDA’s granting of Orphan Drug designation to rencofilstat for the treatment of HCC.
Hepion has created a proprietary AI platform, called AI-POWR™, which stands for Artificial Intelligence – Precision Medicine; Omics (including genomics, proteomics, metabolomics, transcriptomics, and lipidomics); World database access; and Response and clinical outcomes. Hepion intends to use AI-POWR™ to help identify which NASH patients will best respond to rencofilstat, potentially shortening development timelines and increasing the delta between placebo and treatment groups. In addition to using AI-POWR™ to drive its ongoing NASH clinical development program, Hepion intends to use the platform to identify additional potential indications for rencofilstat to expand the company’s footprint in the cyclophilin inhibition therapeutic space.
Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimated,” and “intend,” among others. These forward-looking statements are based on Hepion Pharmaceuticals’ current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, substantial competition; our ability to continue as a going concern; our need for additional financing; uncertainties of patent protection and litigation; risks associated with delays, increased costs and funding shortages caused by the COVID-19 pandemic; uncertainties with respect to lengthy and expensive clinical trials, that results of earlier studies and trials may not be predictive of future trial results; uncertainties of government or third party payer reimbursement; limited sales and marketing efforts and dependence upon third parties; and risks related to failure to obtain FDA clearances or approvals and noncompliance with FDA regulations. As with any drug candidates under development, there are significant risks in the development, regulatory approval, and commercialization of new products. There are no guarantees that future clinical trials discussed in this press release will be completed or successful, or that any product will receive regulatory approval for any indication or prove to be commercially successful. Hepion Pharmaceuticals does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in Hepion Pharmaceuticals’ Form 10-K for the year ended December 31, 2021, and other periodic reports filed with the Securities and Exchange Commission.
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Hepion Pharmaceuticals Investor Relations
Direct: (646) 274-3580