Hepion Pharmaceuticals Stock

Hepion Pharmaceuticals, Inc., a biopharmaceutical company, focuses primarily on the development of drug therapy for the treatment of chronic liver diseases.

This therapeutic approach targets fibrosis, inflammation, and shows potential for the treatment of hepatocellular carcinoma (HCC) associated with non-alcoholic steatohepatitis (NASH), viral hepatitis, and other liver diseases. The company's cyclophilin inhibitor, rencofilstat is being developed to offer benefits to address multiple complex pathologies related to advanced liver disease. Rencofilstat is a cyclophilin inhibitor that targets multiple pathologic pathways involved in the progression of liver disease. Preclinical studies with rencofilstat in NASH models demonstrated consistent reductions in liver fibrosis and additional reductions in inflammation and cancerous tumors in some studies. Rencofilstat additionally showed in vitro antiviral activity towards hepatitis B, C, and D viruses which also trigger liver disease. Preclinical studies also have shown potentially therapeutic activities of rencofilstat in experimental models of acute lung injury, kidney injury, platelet activation, and SARS-CoV-2 replication.

The company is developing rencofilstat as its lead molecule. Rencofilstat is a compound that binds and inhibits the function of a specific class of isomerase enzymes called cyclophilins that regulate protein folding.

The company has completed a Phase 1 program with rencofilstat in healthy subjects demonstrating safety, tolerability, and pharmacokinetics (PK). This Phase 1 program consisted of four different clinical trials with rencofilstat, administered orally once daily, includinga Single Ascending Dose (SAD) study; a Multiple Ascending Dose (MAD) study; a Drug-Drug Interaction (DDI) study; and a Food Effect Study. The SAD, MAD, DDI and Food Effect studies comprised 32, 25, 18 and 44 healthy subjects, respectively. Additionally, in the SAD study, 8 of the 32 subjects received placebo (24 received rencofilstat).

Rencofilstat was well-tolerated in the Phase 1 program, and there were no serious adverse events (SAEs) reported. The few adverse events (AEs) observed were mild to moderate and mostly unrelated to study drug. The PK profile of each subject was characterized and rencofilstat blood exposures were similar to those levels needed to elicit efficacy in the preclinical studies.

The company has also completed a Phase 2a, multi-center, single-blind, placebo-controlled study in NASH F2/F3 subjects dosed orally with rencofilstat once daily. All of the primary objectives for the study were met, including safety, tolerability, and PK endpoints. In addition, a number of NASH biomarkers, collagen degradation proteins, and transcriptomics were also collected, and these results indicate early evidence of rencofilstat efficacy in NASH subjects. Based on screening procedures, including laboratory (aspartate aminotransferase [AST]), imaging (FibroScan), and biomarkers (Pro-C3, ELF score), 47 presumed NASH F2/F3 subjects were enrolled into the trial and included in the safety date set.

Building on the results of the Phase 2a study in NASH subjects, two separate Phase 2 NASH trials were initiated in 2022. The first trial, a Phase 2b, randomized, multi-center, double-blind, placebo-controlled study to evaluate the efficacy and safety of rencofilstat in adult subjects with NASH and advanced liver fibrosis was initiated in August 2022. This Phase 2b clinical study is anticipated to enroll up to 336 biopsy confirmed F2/F3 NASH subjects to gain a better understanding of histologic changes in liver fibrosis and steatosis for three different dosing levels of rencofilstat, as well as evaluate multiple clinically relevant endpoints and biomarkers related to improvements in or halting the progression of NASH. The trial design will closely follow U.S. Food and Drug Administration (FDA) guidance on the development of NASH therapeutic agents, as the primary endpoint will be based on changes in paired liver biopsy samples after one year of three active drug dosing levels versus a matching placebo group. The second trial, a Phase 2, randomized, multi-center, open-label study to evaluate changes in hepatic function of rencofilstat in adult subjects with advanced F3 NASH was initiated in Q3 of 2022, which the company expects to complete in Q2 of 2023. This phase 2 clinical trial enrolled 70 subjects with advanced NASH, and included a HepQuant Shunt procedure as the primary endpoint to allow a sensitive measure of each subject's hepatic function from baseline to the end of 120 days dosing with rencofilstat. In addition to the HepQuant procedure, numerous NASH biomarkers are being collected to evaluate changes over the 120 days for each subject.

The company uses contract manufacturers to produce clinical trial material for use in the clinical trials of rencofilstat.

Rencofilstat

The company is developing rencofilstat as its lead molecule. Rencofilstat is a therapeutic drug candidate that binds and inhibits the function of a specific class of isomerase enzymes called cyclophilins that mainly regulate protein folding. In preclinical in vitro and/or in vivo experiments conducted to date rencofilstat decreased liver fibrosis, liver inflammation, liver tumor burden, and titers of HBV, HCV, HDV, and HIV-1. Importantly, reduction in liver fibrosis by rencofilstat was observed in vivo in several experimental models and studies of NASH and liver fibrosis.

As of December 31, 2022, the company completed a number of separate preclinical animal efficacy studies of rencofilstat to assess antifibrotic activity. These studies were conducted by independent laboratory collaborations at, for example, The Scripps Research Institute (San Diego, CA), SMC Corporation (Tokyo, Japan), and Physiogenex S.A.S. (France). Each of these studies demonstrated consistent and significant reductions in fibrosis in mice and rats. Rencofilstat was also tested in ex vivo Precision Cut Liver Slices and in Precision Cut Lung Slices obtained from human donors. Again, rencofilstat demonstrated an antifibrotic effect in human tissue that was consistent with the animal study findings. These studies provide support of advancing rencofilstat into clinical trials for NASH, and potentially additional indications where fibrosis plays a role.

On May 10, 2018, the company submitted an Investigational New Drug (IND) Application to the U.S. Food and Drug Administration (FDA) to support initiation of its rencofilstat HBV clinical development program in the United States and received approval in June 2018. The company successfully completed the first segment of its Phase 1 clinical activities for rencofilstat in October 2018.

On June 17, 2019, the company submitted an IND to the FDA to support initiation of a rencofilstat clinical development program for NASH in the United States and received approval in July 2019. It completed dosing of rencofilstat in its multiple ascending dose (MAD) clinical trial in September 2020.

On November 20, 2020, the company submitted an IND to the FDA to support initiation of a rencofilstat clinical development program in the United States for COVID-19. It received approval December 17, 2020, to conduct a COVID-19 clinical trial and are investigating potential sources of collaboration and/or funding for the trial.

On November 19, 2021, the company submitted an Investigational New Drug Application (IND) to the FDA to support initiation of a rencofilstat clinical development program in the United States for the treatment of HCC and received approval on December 17, 2021.

On November 30, 2021, the FDA granted Fast Track designation for the company's lead drug candidate, rencofilstat, for the treatment of NASH.

On June 20, 2022, the FDA granted Orphan Drug Designation to rencofilstat, a liver-targeting, orally administered, novel cyclophilin inhibitor, for the treatment of HCC.

Artificial Intelligence (AI)

The company has created a proprietary AI tool called, AI-POWR to optimize the outcomes of its clinical programs and to potentially identify novel indications for rencofilstat and possibly identify new targets and new drug molecules to broaden its pipeline.

AI-POWR is the company's acronym for Artificial Intelligence - Precision Medicine; Omics that include, proteomics, metabolomics, transcriptomics, and lipidomics and patient specific clinical traits; World database access; and Response and clinical outcomes. AI-POWR allows for the selection of novel drug targets, biomarkers, and appropriate patient populations. AI-POWR is used to identify responders from big data sources using the company's multi-omics approach, while modelling inputs and scenarios to increase response rates. The components of AI-POWR include access to publicly available databases, and in-house genomic and multi-omic big data, processed via machine learning algorithms.

The company intends to use AI-POWR to help identify which NASH patients will best respond to rencofilstat. It is anticipated that applying this proprietary platform to the company's drug development program will ultimately save time, resources, and money. In so doing, AI-POWR is a risk-mitigation strategy that should reap benefits all the way through from clinical trials to commercialization. The AI-POWRplatform is continually updated with in-house and published data to further refine the accuracy of the neural network.

AI-POWR is designed to address many of the typical challenges in drug development, as the company can use its proprietary platform to shorten development timelines and increase the delta between placebo and treatment groups. AI-POWRwill be used to drive the company's ongoing Phase 2b NASH program and identify additional potential indications for rencofilstat to expand its footprint in the cyclophilin inhibition therapeutic space. The AI-POWR platform is now planned to provide clinical dosing strategies after a successful NDA for web or cloud-based dosing.

Research and Development

For the year ended December 31, 2022, the company’s research and development expenses were $33.3 million.

Regulations

Pursuant to FDA regulations, the company is required to successfully undertake a long and rigorous development process before its product candidate can be marketed or sold in the U.S.

The company must submit the results of these preclinical studies, together with other information, including manufacturing records, analytical data and proposed clinical trial protocols, to the FDA as part of an IND, which must be reviewed and become effective before the company may begin any human clinical trials.

Any FDA-approved products manufactured or distributed by the company are subject to continuing regulation by the FDA, including record-keeping requirements and reporting of adverse events or experiences.

If the FDA approves the company's product candidate, it, or its collaborators if applicable, and its contract manufacturers must provide the FDA with certain updated safety, efficacy, and manufacturing information.

History

The company was founded in 2013. It was incorporated under the laws of the state of Delaware in 2013. It was formerly known as ContraVir Pharmaceuticals, Inc. and changed its name to Hepion Pharmaceuticals, Inc. in 2019.