HEPA Hepion Pharmaceuticals Inc

Hepion Pharmaceuticals, Inc. (NASDAQ:HEPA), a clinical stage biopharmaceutical company focused on Artificial Intelligence (“AI”)-driven therapeutic drug development for the treatment of metabolic dysfunction-associated steatohepatitis (“MASH”; previously referred to as “NASH”), fibrotic diseases, hepatocellular carcinoma (“HCC”), and other chronic diseases, today announced additional efficacy data for rencofilstat, its lead drug candidate.

Additional rencofilstat efficacy data from Hepion’s ‘ALTITUDE-NASH’ clinical trial was presented earlier this afternoon by Dr. Mayo in a late-breaker poster presentation at the Liver Meeting® 2023, hosted by the American Association for the Study of Liver Diseases (“AASLD”). Dr. Mayo’s presentation indicated that 17 weeks of rencofilstat treatment was associated with significant reduction in liver stiffness (FibroScan®) in MASH subjects with advanced F3, an outcome suggesting reduction in hepatic fibro-inflammation.  

Ongoing hepatic fibro-inflammation leads to progressive accumulation of collagen or fibrosis, increasing liver stiffness, and functional deterioration. Determination of liver stiffness often utilizes an ultrasound-based imaging technique called vibration-controlled transient elastography (“VCTE”) of which FibroScan® is the most common platform. Physicians rely on liver stiffness measurements as a diagnostic tool to help determine whether liver health is worsening or improving, as the measurements correlate well with the extent of fibrosis in liver biopsies and are predictive of the course of disease. The predictive power of liver stiffness measurements on the course of disease is further enhanced when taken together with blood-based markers of liver disease. Liver stiffness measurements are expressed in kilopascals (kPa), and Fibroscan® scores higher than 12 kPa usually represent advanced forms of fibrosis (F3 or F4 in biopsies). Reduction in liver stiffness by rencofilstat likely indicates reduction in fibroinflammation, and reduction in risk for subsequent clinical outcome.

Patients who participated in the study and received a once-daily oral dose of 225 mg rencofilstat experienced an average decline of 6.02 kPa (LSMean) from their baseline measurement. When expressed as a percentage, rencofilstat treatment decreased liver stiffness by a mean of 28.8 (95% CI, -44.3, -13.4) percent from baseline over 17 weeks (p=0.001). This change from baseline was among the highest reductions ever measured in F2-F3 MASH studies (see table below).

The ALTITUDE-NASH study was a multi-center, open label study in F3 MASH subjects identified by historical biopsy or having AGILE 3+ screening score of 0.53 or higher. Subjects were randomized to one of three rencofilstat treatment groups receiving either 75 mg, 150 mg, or 225 mg soft gelatin capsules once daily for a period of 17 weeks. The objective of this study was to collect a wide range of information on rencofilstat dosing levels, safety, and efficacy to optimize designs of subsequent studies.

As previously announced, ALTITUDE-NASH achieved its primary and secondary endpoints, with rencofilstat demonstrating statistically significant improvements in DSI (Drug Severity Index), hepatic reserve, risk ACE (annual risk of adverse clinical outcomes) score, liver transaminases (ALT, AST), ProC3 (procollagen C 3-terminal peptide, a measure of fibrogenesis), PIIINP (procollagen 3 N-terminal peptide), TIMP1 (tissue inhibitor of metalloproteinase), hyaluronic acid, and ELF (enhanced liver fibrosis) score. The benefits of rencofilstat administration were more pronounced in subjects with more severe disease, defined as having baseline ProC3 ≥ 37.5 ng/mL.

The aforementioned blood tests, combined with the additional FibroScan® results released today, demonstrated that rencofilstat improved several key indicators of liver health and function.

Comparison of rencofilstat FibroScan® results to other F2-F3 MASH studies in which the study endpoint of reduction in biopsy-assessed liver fibrosis was successfully achieved

Drug Candidate	Baseline Fibroscan® (KPa) LSM	Absolute Change FibroScan®(KPa) LSM	Reference
Rencofilstat (Cyclophilin)225 mg qd, oral17 weeks (N=21)NCT05461105	14.74	-6.02 (p=0.0001)	1
Efruxifermin (FGF21)50 mg qw, sc96 weeks (n=35)NCT04767529	14.8	-4.3 (p=0.005)	2
Efruxifermin (FGF21)28 mg qw, sc96 weeks (n=37)NCT04767529	14.8	-2.6 (p=0.131)	2
Efruxifermin (FGF21)50 mg qw, sc16 weeks (n=20)NCT03976401	22.1	-5.7 (p=0.0036)Placebo -1.1; ns	3
Pegozafermin (FGF21)15 mg qw, sc24 weeks (n=14)NCT04929483	13.0	-1.4Placebo 0.8	4
Pegozafermin (FGF21)30 mg qw, sc24 weeks (n=66)NCT04929483	13.0	-3.1	4
Pegozafermin (FGF21)44 mg q2w, sc24 weeks (n=51)NCT04929483	13.0	-2.4	4
Resmetirom (THR-β)80 mg qd, oral36 weeks (n=19)NCT02912260	10.3	-1.8 (p=0.007)	5
Resmetirom (THR-β)100 mg qd, oral36 weeks (n=5)NCT02912260	10.3	-3.4 (p=0.008)	5
Obeticholic Acid (FXR)10 mg qd, oral72 weeks (n=69)NCT02548351	12.5	-1.51	6
Obeticholic Acid (FXR)25 mg qd, oral72 weeks (n=91)NCT02548351	12.5	-1.76In subjects with at least a 1-point reduction in fibrosis score	6

Note: Some studies did not report statistical significance on LSMeans

RCF=Rencofilstat, EFX=Efruxifermin, PEG=Pegozafermin, RES=Resmetirom, OCA=Obeticholic Acid PLB=Placebo, CFB=Change from Baseline, QD=Every Day, QW=Every Week, Q2W=Every Two Weeks

“These latest results were presented today as a late-breaker at the annual AASLD The Liver Meeting® in Boston,” commented Dr. Mayo. “These data combined with the novel liver function, multi-omic and traditional clinical data increase our ability to predict clinical outcomes in MASH patients. Both completed Phase 2 studies in MASH subjects, the 28-day Phase 2a AMBITION-NASH trial and the 17-week ALTITUDE-NASH trial, provided exponentially more information to inform our proprietary AI and risk-mitigate the on-going 1-year Phase 2b ASCEND-NASH trial. Moving forward, the demonstrated improvement in hepatic function, decrease in liver stiffness, and multi-omics at 17-weeks in the ALTITUDE-NASH trial, predict that rencofilstat is anticipated to achieve biopsy endpoints in the ASCEND-NASH trial. The ultimate goal is to determine the optimal dose of rencofilstat in individual MASH subjects to improve both quality and quantity of life in this patient population.”

Stephen Harrison, MD, Hepion’s Consultant Medical Director, added, “The encouraging results of this Phase 2 study with rencofilstat bodes well for the ongoing success of Hepion’s drive to bring clinical benefits to individuals suffering from this serious medical condition. The initial results in the ALTITUDE-NASH study that were announced this past May indicated a significant improvement in liver function using the HepQuant diagnostic of liver function. Now, with the new non-invasive efficacy data announced today, I am further encouraged that Hepion continues to move in the right direction, and look forward to continuing with the ongoing Phase 2b ASCEND-NASH study. MASH is an incredibly tough disease to tackle, and we are always looking for predictive clinical signs of success. The results released today along with the HepQuant results indicates to me that Hepion is on the right track.”

Conference Call Details

Hepion is pleased to invite all interested parties to participate in a conference call at 4:30 p.m. ET today, during which the additional rencofilstat efficacy data will be discussed. To participate in this conference call, please (800) 715-9871 (U.S.) or (646) 307-1963 (international), conference ID 8619177, approximately 10 minutes prior to the start time. The call will also be broadcast live and archived on the Company’s website at www.hepionpharma.com under “Events” in the Investors section.

References

1. Harrison, S.; Mayo, P.; Hobbs, T.; Zhao, C.; Canizares, C.; Foster, R.; McRae, M.; Helmke, S.; Everson, G. Hepatic Functional Improvement detected by HepQuant DuO within 120 days of treatment with Rencofilstat (RCF) in MASH subjects with ≥F3 fibrosis. (2023): AASLD late breaker.
2. Harrison, Stephen A., et al. Safety and efficacy of once-weekly efruxifermin versus placebo in non-alcoholic steatohepatitis (HARMONY): a multicentre, randomised, double-blind, placebo-controlled, phase 2b trial. The Lancet Gastroenterology & Hepatology (2023): 8(12):1080-1093.
3. Harrison, Stephen A., et al. A randomized, double-blind, placebo-controlled phase IIa trial of efruxifermin for patients with compensated NASH cirrhosis. JHEP Reports (2022): 5(1):100563.
4. Loomba, Rohit, et al. Randomized, Controlled Trial of the FGF21 Analogue Pegozafermin in NASH. New England Journal of Medicine (2023): 389(11):998-1008.
5. Harrison, Stephen A., et al. Effects of resmetirom on noninvasive endpoints in a 36‐week phase 2 active treatment extension study in patients with NASH. Hepatology Communications (2021): 5(4):573-588.
6. Sanyal, Arun J., et al. Results from a new efficacy and safety analysis of the REGENERATE trial of obeticholic acid for treatment of pre-cirrhotic fibrosis due to non-alcoholic steatohepatitis. Journal of Hepatology (2023): 79(5):1110-1120.

About Hepion Pharmaceuticals

The Company's lead drug candidate, rencofilstat, is a potent inhibitor of cyclophilins, which are involved in many disease processes. Rencofilstat has been shown to reduce liver fibrosis and hepatocellular carcinoma tumor burden in experimental disease models and is currently in Phase 2 clinical development for the treatment of NASH. 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 Artificial Intelligence deep machine learning (“AI/ML”) platform designed to better understand disease processes and identify patients that are rencofilstat responders. This AI/ML has the potential to shorten development timelines and increase the observable differences between placebo and treatment groups. In addition, Hepion’s AI/ML can be used to drive its ongoing NASH and HCC clinical development programs and identify other potential therapeutic indications for cyclophilin inhibition with rencofilstat.

Forward-Looking Statements

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, 2022, and other periodic reports filed with the Securities and Exchange Commission.

For further information, please contact:

Stephen KilmerHepion Pharmaceuticals Investor RelationsDirect: (646) 274-3580skilmer@hepionpharma.com  

A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/c1c02b71-d7ce-4516-9148-18b3e83bf99a