Hepion Pharmaceuticals, Inc. · OTC:HEPA
Hepion Pharmaceuticals — Investor Presentation (October 2022)
34 slides from Hepion Pharmaceuticals's investor presentation, Oct 17, 2022
Slide 1: Rencofilstat (CRV431): A Novel Drug Candidate for NASH, Fibrosis, and HCC
1 1 Rencofilstat (CRV431): A Novel Drug Candidate for NASH, Fibrosis, and HCC October 2022 Creating a Therapeutic Ecosystem NASDAQ: HEPA
Slide 2: Forward-Looking Statements
2 This presentation may contain forward - looking statements within the meaning of Section 27 A of the Securities Act of 1933 and Section 21 E of the Securities Exchange Act of 1934 . Such forward - looking statements are characterized by future or conditional verbs such as “may,” “will,” “expect,”
Slide 3: Rencofilstat Highlights
3 Rencofilstat Anti - Fibrotic Drug Candidate • Novel mechanism - cyclophilin inhibition • Once - daily, oral medication – soft gel capsules • Collagen - specific anti - fibrotic • Targets key pathologies including fibrosis, inflammation, cell injury • All clinical trials to date show rencofilstat t
Slide 4: Landscape of Clinical Antifibrotic Drug Development
4 Physiol Rev 2022 Apr 1;102(2):605 - 652. Development of antifibrotic therapy for stricturing Crohn's disease: lessons from randomized trials in other fibrotic diseases • Despite ≈300 clinical trials, the only approved antifibrotic drugs are pirfenidone and nintedanib • Most anti - fibrotic agents
Slide 5: Collagen – Core To Fibrotic Diseases
5 Collagen – Core To Fibrotic Diseases Excessive Collagen Production – Universal to Every Fibrotic Disease • Fibrosis is an exaggerated “scarring” of tissue in response to many types of cellular injuries, chronic inflammation, & other tissue insults • Fibrosis impairs normal organ structure & functi
Slide 6: Fibrotic Collagen Production
6 Am J Respir Cell Mol Biol 2022 Apr;66(4):363 - 381. Fighting the Fiber: Targeting Collagen in Lung Fibrosis. Claudia A Staab - Weijnitz Denotes CypB participation Fibrotic Collagen Production Cyclophilin B ( Cyp B; PPIB) – Participant in several stages of collagen synthesis and fibrotic scar forma
Slide 7: Rencofilstat Inhibits Three Primary Cyclophilins
7 Rencofilstat Inhibits Three Primary Cyclophilins Hitting the Right Targets – Fibrosis, Inflammation, and Cell Injury/Death Rencofilstat blocks Cyclophilin D activation of mitochondrial membrane pores and thereby decreases cell death in injured livers CYTOPROTECTIVE 7 Rencofilstat blocks Cyclophili
Slide 8: Preclinical Models Consistent Antifibrotic Findings
8 Preclinical Models Consistent Antifibrotic Findings Antifibrotic Activity Observed in Every Preclinical Model Liver • 8 NASH - related models • Human liver slices Lung • Chronic fibrosis • Acute injury • Human lung slices Kidney • Acute injury Heart Skin
Slide 9: Summary of Rencofilstat Programs – Pipeline within a Product
9 Program Pre - Clinical Phase 1 * Phase 2 Phase 3 NASH Fast Track Designation Hepatocellular Carcinoma Orphan Drug Designation Multiple Myeloma Idiopathic Pulmonary Fibrosis Renal Fibrosis Cardiac Fibrosis Biopsy Summary of Rencofilstat Programs – ‘Pipeline within a Product’ Liver Function
Slide 10: NASH Fibrotic Liver Disease
10 NASH Fibrotic Liver Disease
Slide 11: The Need and Opportunity: NASH is Driving a Healthcare Crisis
11 Image adapted from “From NASH to HCC: current concepts and future challenges”, Anstee et al. (2019) The Need and Opportunity NASH is Driving a Healthcare Crisis NAFLD n on - a lcoholic f atty l iver d isease Approx. 25% of global population Up to 100 million in U.S. “Fatty liver” disease associat
Slide 12: Challenges to Achieve Development and Commercial Success
12 Challenges to Achieve Development and Commercial Success A Comprehensive Approach to Provide Solutions NASH • No FDA drugs approved • Traditional metabolism - regulating drugs largely not efficacious • Multifactorial disease processes – metabolism, inflammation, fibrosis Need for Disease Modifyin
Slide 13: Overview of Phase 1 Studies (completed)
13 Overview of Phase 1 Studies (completed)
Slide 14: Phase 1 Studies Completed – Safe and Well Tolerated
14 Phase 1 Studies Completed – Safe and Well Tolerated Key Findings • No serious adverse events • No adverse events with dose response • Effective t1/2 ~ 30 hours • Tmax ss ~ 1 – 2 hours • Ketoconazole increased rencofilstat concentrations ~ 5 - fold • Rencofilstat had no effect on midazolam exposur
Slide 15: Overview of Phase 2a 'AMBITION' NASH Trial (completed)
15 Overview of Phase 2a ‘AMBITION’ NASH Trial (completed)
Slide 16: Phase 2a 'AMBITION' NASH Study
16 F2/F3 NASH Subjects (N=43) Rencofilstat 225 mg (n=17) Placebo (n=8) Placebo (n=6) Rencofilstat 75 mg (n=12) OFF - TREATMENT OFF - TREATMENT OFF - TREATMENT OFF - TREATMENT DAYS FASTED ONCE DAILY ORAL DOSING Phase 2a ‘AMBITION’ NASH Study Safety, Tolerability, and Pharmacokinetics Conducted at 10
Slide 17: Phase 2a 'AMBITION' NASH Study: All Primary Endpoints Met
17 Rencofilstat is safe and well - tolerated Efficacy signals were observed in only 28 days including: • Reduction in ALT (marker of inflammation & fibrosis) • Reduction in Pro - C3 (marker of fibrosis) • Downregulation of collagen genes • Upregulation of genes associated with liver recovery and fav
Slide 18: Hepion's Proprietary Artificial Intelligence
18 Hepion’s Proprietary Artificial Intelligence
Slide 19: Hepion's Proprietary State-of-the-Art Artificial Intelligence
19 Hepion’s Proprietary State - of - the - Art Artificial Intelligence Developing a Panel for Clinical Development and Commercialization AI - POWR Œ MACHINE LEARNING DEEP LEARNING ARTIFICIAL INTELLIGENCE F acilitates: • I mproved drug target selection • Clinical study design • a priori responder ana
Slide 20: AI-POWR Applied to the Phase 2a Program
20 AI - POWR TM Applied to the Phase 2a Program Guiding Hepion’s Future Development CPK Baso Glu Conc Trigs Age BMI Sex Creat PLT WBC Chol AST ALT A1c Responders Non - Responders Using machine learning on data from the Phase 2a, Hepion was able to identify subjects more likely to respond to rencofil
Slide 21: Fibrosis-Associated Gene Network Observed in Phase 2a Blood Samples
21 A1B G SDC 2 MM P23 B FBN 2 EMID1 LOXL1 SERP INB8 ORM1 ICAM1 VCAN CLEC3B PXDN HTRA1 F13A1 COCH COL9A2 COL4A3 EMILIN2 MMRN1 LAMB1 COL6AE LAMA5 ADAM9 LTBP1 TIMP2 COL 26A1 HRNR COLQ HSPG2 C1QB CLU ADAM 19 BCAM MXRA7 PLSCR1 PCSK6 BCHE N1D1 F5 FN1 FBN1 HGF PKLR NID2 COL3A1 LAMB2 LAMC1 IL2RA EGFL7 PLSCR
Slide 22: Phase 2b 'ASCEND-NASH' Trial (in progress)
22 Phase 2b ‘ASCEND - NASH’ Trial (in progress)
Slide 23: Phase 2b ASCEND-NASH (Biopsy Trial)
23 Phase 2b ASCEND - NASH (Biopsy Trial) Rencofilstat 225 mg qd (n=84) Placebo (n=84) Rencofilstat 75 mg qd (n=84) Rencofilstat 150 mg qd (n=84) RANDOMIZED 1:1:1:1 OFF - TREATMENT OFF - TREATMENT OFF - TREATMENT OFF - TREATMENT MONTHS 1 12 13 | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Slide 24: Phase 2b ASCEND-NASH Endpoints
24 Phase 2b ASCEND - NASH Primary Efficacy Endpoint: Superiority of rencofilstat compared to placebo on liver histology at month 12 relative to the screening biopsy, by assessing the proportion of subjects with improvement in fibrosis by at least 1 stage (NASH CRN system) OR NASH resolution without
Slide 25: Phase 2 'ALTITUDE-NASH' Trial (in progress)
25 Phase 2 ‘ALTITUDE - NASH’ Trial (in progress)
Slide 26: Phase 2 'ALTITUDE-NASH' (Liver Function Trial)
26 • Subjects identified from historical biopsy or by meeting AGILE 3+ criteria for F3 • Subjects who complete study will be considered for enrollment into ASCEND - NASH 2b Phase 2 ‘ALTITUDE - NASH’ (Liver Function Trial) Primary Objective: Evaluate the change in hepatic function with once daily (QD
Slide 27: Phase 2 'ALTITUDE-NASH' Endpoints
27 Primary Efficacy Endpoint: Change from baseline in DSI score of subjects taking rencofilstat using HepQuant SHUNT Test, on Day - 1, Day 60, and Day 120 Secondary Efficacy Endpoints: • Percent of subjects with a reduction in DSI score of >2 • Change from baseline in portal and systemic Hepatic Fil
Slide 28: Phase 2a HCC Trial (upcoming)
28 Phase 2a HCC Trial (upcoming)
Slide 29: Phase 2a: Advanced Hepatocellular Carcinoma (HCC)
29 Objectives: • Safety & tolerability • Efficacy: - Disease Control Rate - Duration of response - Overall survival - Objective response rate - 4 - month progression free survival • Pharmacokinetics PHASE 2a: Advanced Hepatocellular Carcinoma (HCC) Safety, Tolerability, Pharmacokinetics, and Efficac
Slide 30: Summary
30 Summary
Slide 31: Hepion's Approach to Developing an Ecosystem
31 Hepion’s Approach to Developing an Ecosystem Creating a Bundle to Support Rencofilstat’s Success Strategy: • Rencofilstat (disease modifying), efficacious, safe and well - tolerated • Companion Point - of - Care Diagnostic (e.g., Blood Panel) • A.I. and Multiomic Analyses Identify Responders (Off
Slide 32: Financials: Two Value Drivers Tackling Fibrotic Diseases
32 $71.7 M Cash as of 6/30/22 Financials Two Value Drivers Tackling Fibrotic Diseases • Rencofilstat , once - daily oral, targeting key drivers of pathology, tested in over 200 subjects • Two Phase 2 NASH trials underway • Upcoming Phase 2 for HCC • Developing companion A.I. for clinical development
Slide 33: Experienced Team
33 Launa Aspeslet , PhD COO Formerly COO of Isotechnika ( Aurinia ) from 1996 - 2013. Was CEO of an oncology CRO from 2013 until joining HEPA in 2022. Core R&D team has collectively > 120 yrs of experience with cyclophilin inhibition drug development, most notably voclosporin ( Lupkynis ®) for lupus
Slide 34: Contact Us
CONTACT US Hepion Pharmaceuticals Inc. 399 Thornall Street, First Floor Edison, New Jersey, USA, 08837 Email: info@hepionpharma.com Phone: 732 - 902 - 4000 www.hepionpharma.com
Hepion Pharmaceuticals — Investor Presentation (October 2022) on 6ix