Demonstrated improvements among best reported of fibrosis-reducing compounds -

- Liver stiffness results complemented by positive changes in disease biomarkers and HepQuant Duo liver function test -

“These findings presented today at AASLD The Liver Meeting^® confirm that rencofilstat’s novel mechanism of action represents a fresh approach to the treatment of severe liver disease.” (Patrick Mayo, PhD, Hepion’s Senior VP, Clinical Pharmacology & Analytics)

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

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  along with the HepQuant results indicates to me that Hepion is on the right track.”