Hepion Pharmaceuticals, Inc. · OTC:HEPA
Hepion Pharmaceuticals — Investor Presentation (September 2022)
40 slides from Hepion Pharmaceuticals's investor presentation, September 2022
Slide 1: Rencofilstat (CRV431): A liver-targeting drug candidate for NASH and HCC
N A S D A Q : HE PA Rencofilstat (CRV431): A liver-targeting drug candidate for NASH and HCC Creating a Therapeutic Ecosystem S e p t e mb e r 2 0 2 2 1 1
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation may contain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Such forward-looking statements are characterized by future or conditional verbs such as “may,”
Slide 3: The Need and Opportunity: NASH and HCC are driving a Healthcare Crisis
The Need and Opportunity NASH and HCC are driving a Healthcare Crisis NAFLD NASH HCC non-alcoholic fatty liver disease non-alcoholic steatohepatitis hepatocellular carcinoma “Fatty liver” disease A more severe form of NAFLD, Most prevalent type (90%) of liver associated with obesity, with inflammati
Slide 4: Challenges to Achieve Development and Commercial Success
Challenges to Achieve Development and Commercial Success A Comprehensive Approach For Solutions NASH 1. Need for Disease Modifying Drugs • Many molecules in development, majority • No FDA drugs approved targeting metabolic disease (liver fat) • Traditional metabolism-regulating • Need to address adv
Slide 5: Hepion's Development Strategy
Hepion’s Development Strategy Rencofilstat Characteristics Offer Numerous Opportunities for Success Targets KEY disease Safe, Oral Oral medication with few side Disease Modifying pathologies including fibrosis, Once Daily effects derived from proven Properties inflammation, cell injury & Dosing drug
Slide 6: Hepion's Proprietary State-of-the-Art Artificial Intelligence
Hepion’s Proprietary State-of-the-Art Artificial Intelligence Developing a Panel for Clinical Development and Commercialization NEURAL MACHINE Understand disease mechanisms NETWORK LEARNING Identify biomarkers NASH BIG AI-POWR™ Track disease progression and DATA regression Predict drug responders MU
Slide 7: Rencofilstat Snapshot
Rencofilstat Snapshot • Cyclophilin inhibitor – novel approach to treating liver disease • Once-daily, oral medication – soft gel capsules • No serious adverse events to date Rencofilstat • Liver targeting: [liver] > [blood] Drug Candidate for • Targets key pathologies including fibrosis, inflammati
Slide 8: Rencofilstat Clinical Programs Advancing in 2022
Rencofilstat Clinical Programs Advancing in 2022 Program Pre-Clinical Phase 1* Phase 2 Phase 3 Phase 2B (Biopsy) NASH 2022 Phase 2 Fast Track Designation (Liver Function) 2022 HCC Phase 2 Orphan Drug Designation 2022 8 *The Phase 1 program was comprised of Single and Multiple Ascending Doses, a Drug
Slide 9: Cyclophilins – Modulators of Diverse Biological Functions
Cyclophilins –Modulators of Diverse Biological Functions Participants in Many Disease Processes Cyclophilins: • enzymes that regulate the functions of target Proline Peptide Bond cis-trans Isomerization proteins through alterations in protein conformation Cyclophilin Modulatory Roles: • protein synt
Slide 10: Rencofilstat Inhibits Three Primary Cyclophilins
Rencofilstat Inhibits Three Primary Cyclophilins Hitting the Right Targets – Inflammation, Fibrosis, and Cell Injury/Death Rencofilstat blocks Cyclophilin A binding to CD147 receptors ANTI-INFLAMMATORY and thereby decreases pro- inflammatory signaling Rencofilstat blocks Cyclophilin B binding to pro
Slide 11: Preclinical NASH: Antifibrotic and Anti-inflammatory Effects
Preclinical NASH: Antifibrotic and Anti-inflammatory Effects Extensive Preclinical Testing ANIMAL MODELS (mice and rats) • 8 NASH-related studies - diet and/or chemical-induced liver disease • Consistent antifibrotic effects up to 80% • Chronic lung fibrosis study • Acute lung injury study • Decreas
Slide 12: Preclinical HCC: Multi-modal and Drug Combination Effects
Preclinical HCC: Multi-modal and Drug Combination Effects Diverse Experimental Models and Analyses EXPERIMENTAL MODELS • Murine syngeneic Hep53.4 transplant into normal and fatty livers • Monotherapy and drug combination anti- • Murine NASH-induced HCC (STAM) tumor effects • 12 human HCC cell lines
Slide 13: Cyclophilins in Cancer
Cyclophilins in Cancer 13 Numerous Cancer Processes Regulated by Cyclophilins CYCLOPHILIN-REGULATED PROCESSES IN CANCER Cyp A Cyp B Cyp D Cyp E, G, H, L1, L3 Proteostasis (synthesis, folding, ubiquitin-proteosome) Signal transduction • MDM2-p53-p21 • ERK1/2, p38, PI3K/Akt, CrkII, STAT3, Ja
Slide 14: Overview of Phase 1 Studies
Overview of Phase 1 Studies (completed) 14
Slide 15: Phase 1 Studies Completed – Safe and Well Tolerated
Phase 1 Studies Completed – Safe and Well Tolerated Key Findings Single Ascending Dose: 75 mg – 525 mg • No SAEs • No AEs with Dose Response Multiple Ascending Dose: 75 mg – 375 mg • No SAEs • No AEs with Dose Response • Effective t1/2 ~ 30 hours, Tmaxss ~ 1 – 2 hours Drug-Drug Interaction: Midazola
Slide 16: Overview of Phase 2a 'AMBITION' NASH Trial
Overview of Phase 2a ‘AMBITION’ NASH Trial (completed) 16
Slide 17: Phase 2a 'AMBITION' NASH Study
Phase 2a ‘AMBITION’ NASH Study Safety, Tolerability, and Pharmacokinetics AMBITION: A Phase 2a, Multi-center, Single-Blind, Placebo-Controlled, Proof of Concept Study to Evaluate the Safety & Tolerability of Rencofilstat Dosed Once Daily in NASH Induced F2 & F3 Subjects Placebo (n=6) OFF-TREATMENT P
Slide 18: Phase 2a: All Primary Endpoints Met
Phase 2a: All Primary Endpoints Met Adequate Exposures Anticipated for Efficacy • No Serious Adverse Events • Rencofilstat concentrations not significantly altered by NASH • 225 mg QD achieves effective concentrations after the first dose* *Response analysis suggests concentrations > 800 ng/mL by Da
Slide 19: Phase 2a: Clinical Efficacy Biomarkers
Phase 2a: Clinical Efficacy Biomarkers ALT Change from Baseline Pro-C3 Change from Baseline ≥ 17.5 ng/mL - ALT has a high efficiency for screening NASH drug effects but low effectiveness as a sole marker - ProC3 emerging as biomarker indicative of fibrosis2 for NASH Fibrosis Response1 19 1 Loomba, R
Slide 20: Machine Learning and A.I. Applied to Phase 2a Program
Machine Learning and A.I. Applied to Phase 2a Program 20
Slide 21: Phase 2a: PK-PD - Changes in ALT and Pro-C3 are Predictable
Phase 2a: PK-PD - Changes in ALT and Pro-C3 are Predictable Early Evidence of a Concentration-effect Relationship • Higher drug concentrations required to decrease Pro-C3 as compared to ALT • Forecasting expected efficacy biomarker movements can be made early and accurately IC50 PD SE RSE (%) (ng/mL
Slide 22: Phase 2a: Responder Analysis Illustration Using ALT
Phase 2a: Responder Analysis Illustration Using ALT Used to Enrich Future Trials for Greater Success By using multiple variable machine learning, Hepion can accurately identify patients that are more likely to respond to rencofilstat ALT Responder Analysis 1 = Non-responder 2 = Responder 3 = No base
Slide 23: Phase 2a: Responder Analysis Illustration Using Pro-C3
Phase 2a: Responder Analysis Illustration Using Pro-C3 Used to Enrich Future Trials for Greater Success By using multiple variable machine learning, Hepion can accurately identify patients that are more likely to respond to rencofilstat Pro-C3 Responder Analysis 1 = Non-responder 2 = Responder 23 Ci
Slide 24: Phase 2a: Genomic Analysis Generates a Responder Panel
Phase 2a: Genomic Analysis of Subjects (75mg) Generates a Responder Panel AI-POWRTM (n=6 out of 12 total subjects) • Assessed patient demographics and baseline labs • 12/12 Active Subjects • AST/ALT, C6M, TIMPs, MMP Responders • Rencofilstat Day 14, Time 0 concentration > 800 ng/mL AI-machine Potent
Slide 25: Phase 2a: Gene Ontology Collagen Regulatory Network
Phase 2a: Gene Ontology MMP 23B Collagen Regulatory Network A1BG SDC2 COCH FBN2 SERP Consistent antifibrotic ACHE EMID1 F5 INB8 LOXL1 effects observed with BCHE N1D1 ICAM1 rencofilstat in all preclinical COL9A2 MMP8 F13A1 HTRA1 PXDN ORM1 and clinical models EMILIN2 LAMC1 VCAN COL4A3 FBN1 USH2A FN1 L
Slide 26: Phase 2a 'AMBITION' NASH Study Summary
Phase 2a ‘AMBITION’ NASH Study Summary • Rencofilstat is safe and well-tolerated while showing efficacy signals 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 asso
Slide 27: Phase 2b 'ASCEND-NASH' Trial
Phase 2b ‘ASCEND-NASH’ Trial (in progress) 27
Slide 28: 2b ASCEND-NASH (Biopsy Trial)
Phase 2b ASCEND-NASH (Biopsy Trial) Primary Objective: Evaluate the efficacy and safety of once-daily 75mg, 150 mg, and 225 mg doses of Rencofilstat compared to placebo in subjects with biopsy proven NASH and stage 2 liver fibrosis (F2) / stage 3 liver fibrosis (F3) Rencofilstat 75 mg qd (n=84) OFF-
Slide 29: Developing a Strategy to Monitor Clinical Outcomes
Developing a Strategy to Monitor Clinical Outcomes Exploring Meaningful Diagnostic Value Alongside Rencofilstat (supplemental to biopsy) Machine Learning & A.I. Exploratory Diagnostics Other Diagnostics • Develop panel of • Require high diagnostic • Biopsy biomarkers value and accessibility • Fibros
Slide 30: 2b ASCEND-NASH Endpoints
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 worse
Slide 31: 'ALTITUDE-NASH' Trial
Phase 2 ‘ALTITUDE-NASH’ Trial (in progress) 31
Slide 32: 'ALTITUDE-NASH' (Liver Function Trial)
Phase 2 ‘ALTITUDE-NASH’ (Liver Function Trial) Primary Objective: Evaluate the change in hepatic function with once daily (QD) 75 mg, 150 mg, and 225 mg doses of rencofilstat in subjects with NASH F3 fibrosis using the HepQuant SHUNT test. Rencofilstat 75 mg qd (n=20) OFF- Endpoints: RANDOMIZED 1:1:
Slide 33: 'ALTITUDE-NASH' Endpoints
Phase 2 ‘ALTITUDE-NASH’ (Liver Function Trial) 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
Slide 34: Phase 2a HCC Trial
Phase 2a HCC Trial (upcoming) 34
Slide 35: Phase 2a: Advanced Hepatocellular Carcinoma (HCC)
PHASE 2a: Advanced Hepatocellular Carcinoma (HCC) Simon 2 Stage - Safety, Tolerability, Pharmacokinetics, and Efficacy A Phase 2a, Open-Label, Multi-Center, Simon 2-Stage Clinical Study to Assess the Preliminary Efficacy, Safety, and Pharmacokinetics of 2 Dosage Levels of Rencofilstat in Advanced Me
Slide 36: Phase 2a HCC: Objectives
Phase 2a HCC: Objectives Primary Objectives: • Assess disease control rate (DCR) • Assess the safety and tolerability of CRV431 Secondary Objectives: • Assess the effect of rencofilstat on: • Duration of response (DoR) measured from the time measurement criteria are first met for CR/PR (whichever is
Slide 37: Summary
2° VEPION Summary
Slide 38: Hepion's Approach to Developing an Ecosystem
Hepion’s Approach to Developing an Ecosystem Creating a Bundle to Support Rencofilstat’s Success Disease Modifying Drug Strategy: • Rencofilstat (disease modifying), efficacious, safe and well-tolerated • Companion Point-of-Care Diagnostic (e.g., Blood Panel, TAEUS) • Identify Responders, Hepion’s P
Slide 39: Two Value Drivers
Tackling Chronic Liver Disease Two • Rencofilstat, once-daily oral, targeting key drivers of Value Drivers pathology • Two Phase 2b NASH trials underway • Upcoming Phase 2a for HCC • Developing companion proprietary A.I. for clinical A Potential AI-Driven, development and commercialization strategy
Slide 40: 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
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