Hepion Pharmaceuticals Inc Lead Therapy, Rencofilstat Approved for FDA Orphan Drug Designation

Some of the leading causes of liver cancer, which is called Hepatocellular Carcinoma, we call it. Oftentimes, just because HCC is a bit of a multiple, we just refer to it as HCC. You hear me talking about the treatment of Hepatocellular Carcinoma (HCC), one of the leading causes of HCC development. In the Western world, particularly if we look at the US or look at parts of Europe, the leading cause would be something called NASH.

What is NASH?

NASH is another liver disease. NASH stands for nonalcoholic steatohepatitis. Again, another mouthful. There are lots of acronyms in this world that we live in. NASH is a serious disease and is characterized by a number of different findings, namely fatty liver, as well as liver fibrosis, and also inflammation. And so, it's kind of a perfect storm of those things that can ultimately lead to HCC. And I guess one of the things that I, we're probably familiar with the terminology or the term called cirrhosis, or some people say cirrhosis liver, which is a little bit redundant, but anyway, cirrhosis. This is probably one of the most powerful risk factors that can lead to HCC. This is all intertwined, and so what Hepion has done is developed a drug called Rencofilstat, and Rencofilstat is a drug that has multiple modes of action, or multiple things that it can do. And along the pathway of addressing the disease of liver disease, we can address fatty liver, NASH, and the HCC components. We're trying to hit all three of these things with one molecule. So that really lays out what I was trying to do here. And then a relative of HCC.

Key Statistics for Rencofilstat in Patients With HCC

• Hepatocellular carcinoma is the most common form of liver cancer, accounting for 85% to 90% of all cases.

• The randomization of the NASH F3 subjects will be performed in a 1:1:1 ratio between rencofilstat 75 mg, rencofilstat 150 mg, and rencofilstat 225 mg.

• Prior to dosing, subjects can have a light breakfast, avoiding high-fat meals. In the follow-up phase, the investigational product (IP) will be discontinued, followed by 14 days of safety follow-up.

• DSI change from baseline score of subjects taking rencofilstat (75 mg, 150 mg, 225 mg), determined using the HepQuant SHUNT Test, on Day 60 and Day 120.

• The percent of subjects taking rencofilstat (75 mg, 150 mg, 225 mg) that have experienced treatment-emergent adverse events, serious adverse events, adverse events of special interest, and physical and laboratory abnormalities.

• Rencofilstat binds to Cyclophilin A, which blocks the binding of Cyclophilin A to specific receptors on inflammatory cells, decreasing the infiltration of the cells into the tissue and production of harmful inflammatory molecules, resulting in reduced inflammatory damage to the liver.

• Rencofilstat blocks the actions of Cyclophilin B, an important regulator of collagen production in stellate cells. This leads to a reduction in collagen secretions and fibrotic scarring, a primary goal in the treatment of NASH.

• Rencofilstat binds to Cyclophilin D, which prevents or reverses the formation of pores in the mitochondrial membrane that cause mitochondria to rupture, allowing mitochondria to resume normal energy production and enabling the survival of liver cells.

FDA Orphan Approval of Rencofilstat

Having orphan drug approval by the FDA is a big deal for us. It's big for a lot of companies that have a drug that addresses an unmet medical need. And you'll hear a lot of companies talk about how they have a drug to meet an unmet medical need. There are certain diseases like Hepatocellular Carcinoma (HCC), which is one of those diseases. There truly is an unmet medical need. There's not a lot out there. That satisfactorily addresses the disease. And the other part of that equation when it comes to orphan drug status is that it's a disease that doesn't occur that frequently. Hence the name, orphan. According to the FDA, it must be a disease that afflicts 200,000 or fewer people in the population, and HCC falls into that category. Having an orphan drug approval for Rencofilstat and HCC is a big thing for us because it allows us to have a constant line of communication with the FDA. It can also give us some tax incentives. We could also look at getting some market exclusivity because once the drug gets approved, we'll have some protection on the commercial. And it allows us to have interaction with the FDA when it comes to protocol development. There are a lot of advantages to having this orphan drug approval and future clinical trials.

Hepion Pharmaceuticals: Hepion intends to use the FDA Status Designation for Rencofilstat (formerly CRV431) for the Treatment of HCC Clinical Trials

Hepion Pharmaceuticals, Inc., a clinical mid-stage biopharmaceutical company focused on AI-driven therapeutic drug development for the overall treatment of non-alcoholic steatohepatitis ("NASH") and HCC, announced today that the U.S. Food and Drug Administration ("FDA") has granted Orphan Drug Designation to rencofilstat, a liver-targeting, orally administered, novel cyclophilin inhibitor.

The most frequent type of liver cancer, accounting for 85-90 percent of all occurrences, is HCC. HCC is caused by NASH, viral hepatitis infection, and alcohol intake. Over 800,000 individuals died from liver cancer worldwide in 2020, ranking second only to lung cancer among all cancer-related deaths. 1 The high mortality rate is partly owing to the fact that only about half of all people diagnosed with HCC in affluent nations receive a diagnosis early enough to benefit from treatment intervention. Furthermore, recurrence rates are significant, and effective treatment choices are scarce.

From Hepion Pharmaceuticals on Rencofilstat

“Orphan Drug Designation for Rencofilstat in HCC represents a significant milestone for Hepion and its recognition by the FDA of the potential for rencofilstat to address a significant unmet medical need for patients suffering from this aggressive cancer,” “In addition to two Phase 2 studies in patients with NASH, we remain on track to initiate patient enrollment in a Phase 2a study of rencofilstat in HCC in the third quarter of 2022.” said Robert Foster, PharmD, PhD, Hepion’s CEO.

The FDA's Orphan Drug Designation program grants orphan designation to medicines or biologics used to prevent, diagnose, or cure diseases that afflict fewer than 200,000 people in the United States. Orphan Drug Designation entitles sponsors of medications to specific benefits, including tax subsidies for eligible clinical trials, prescription drug user-fee exemptions, and potential seven-year marketing exclusivity upon FDA approval.

Robert Foster, PharmD, Phd - Hepion Pharmaceuticals

Dr. Foster is the CEO of Hepion Pharmaceuticals, which has offices in Edison, New Jersey, and Edmonton, Canada. He is also an Adjunct Professor at the University of Alberta's Faculty of Pharmacy and Pharmaceutical Sciences and a Board member of Transcriptome Sciences Inc. He previously served on the Alberta Economic Development Authority's Board of Directors, as a member of the Alberta Premier's Advisory Council on Health, as an Advisory Board Member of the University of Alberta's Industry Liaison Office, as Co-Chair and Board Member of BioAlberta, and as a member of the Alberta Science and Research Authority's Board of Management.

Dr. Foster started working on cyclophilin medication development in 1988 and has over 30 years of pharmaceutical and biotech experience. He was the CEO and Founder of Ciclofilin Pharmaceuticals Inc. before joining Hepion in 2016. Prior to that, he formed Isotechnika Pharma Inc. (TSX:ISA) in 1993 and served as its Chairman and CEO for nearly two decades. Dr. Foster discovered voclosporin, an immunosuppressive medication used to treat autoimmune illnesses while working at Isotechnika.

Dr. Foster negotiated a USD $215 million licence agreement for voclosporin for kidney transplant immunosuppression with Hoffman-La Roche in 2002, which was Canada's largest at the time (Basel, Switzerland). Later, once Isotechnika bought Aurinia Pharma (NASDAQ:AUPH), he became its founding CEO and then CSO. In January 2021, the FDA authorized voclosporin (LupkynisTM) for the treatment of lupus nephritis. Voclosporin has been licensed for the treatment of lupus nephritis in the EU, Japan, the United Kingdom, Russia, Switzerland, Norway, Belarus, Iceland, Liechtenstein, and Ukraine by Otsuka Pharmaceutical Co., Ltd.

In addition to pharmaceutical discovery and development, Dr. Foster created and received regulatory approval for Helikit, a commercially accessible 13C urea breath test for the detection of H. pylori, a bacteria that can cause peptic ulcers. In 2009, Dr. Foster sold Helikit. It still generates multimillion-dollar annual sales in Canada and other nations today.

Dr. Foster has undergraduate degrees in Science (Chemistry) and Pharmacy, as well as a PharmD and a Ph.D. in Pharmaceutical Sciences. From 1988 to 1997, Dr. Foster was a tenured Associate Professor in the Faculty of Pharmacy and Pharmaceutical Sciences at the University of Alberta. Dr. Foster worked as a Medical Staff, Scientific and Research Associate in the Department of Laboratory Medicine at the Walter C. Mackenzie Health Sciences Centre from 1990 to 1994.

Dr. Foster (Hepion's CEO) has over 200 papers, abstracts, and book chapters on drug analysis, development, and pharmacokinetics to his credit, and he has received numerous accolades for both pharmaceutical research and education. In 2002, he was awarded one of Alberta's 50 Most Influential People, and in 2003, Isotechnika was designated both Alberta Venture's third fastest growing company and Profit Magazine's top 100 fastest growing Canadian company. Dr. Foster previously held the position of Division Chairman of Pharmacy Practice at the University of Alberta and has worked as a consultant for a number of pharmaceutical companies. Dr. Foster is listed as an inventor on about 170 patents.

Hepion Pharmaceuticals: Current Expectations

The company's lead drug candidate is a potent inhibitor of cyclophilins, which are implicated in numerous disease processes. Rencofilstat is now in clinical trials for the treatment of NASH, with the potential to play a significant role in the whole treatment of liver disease, from triggering events to end-stage disease. It has been proven in nonclinical investigations to reduce liver fibrosis and hepatocellular carcinoma tumor burden in experimental models of NASH, as well as antiviral activity against HBV, HCV, and HDV via many mechanisms. Rencofilstat was given Fast Track status by the US Food and Drug Administration ("FDA") in November 2021 for the treatment of NASH. In December 2021, the FDA approved Hepion's investigational new drug (IND) application for rencofilstat for the treatment of HCC. Rencofilstat was designated an orphan drug in June 2022 for the treatment of HCC.

AI-POWRTM stands for Artificial Intelligence - Precision Medicine; Omics (including genomes, proteomics, metabolomics, transcriptomics, and lipidomics); World Database Access; and Response and clinical outcomes. Hepion intends to apply AI-POWRTM to assist in determining which NASH patients may respond best to Rencofilstat, potentially decreasing development timelines and boosting the delta between placebo and treatment groups. Hepion hopes to use AI-POWRTM to find other potential indications for rencofilstat to expand the company's footprint in the cyclophilin inhibition therapeutic arena, in addition to driving its ongoing NASH clinical development program.

Liver Disease

Liver fibrosis is the abnormal accumulation of extracellular matrix proteins, such as collagen, that occurs in the majority of chronic liver disorders.

References

1. Hepion Pharmaceuticals press release - Hepion Pharmaceuticals Receives FDA Orphan Drug Status Designation for Rencofilstat for the Treatment of Hepatocellular Carcinoma - Hepion Pharmaceuticals Press Release, June 20, 2022

2. Hepion Pharmaceuticals - Robert Foster, B.Sc. (Pharm), Pharm.D., Ph.D., Chief Executive Officer - Hepion Pharmaceuticals Biography, 2022