Hepion Pharmaceuticals, Inc. · OTC:HEPA
Hepion Pharmaceuticals — Investor Presentation (March 2020)
22 slides from Hepion Pharmaceuticals's investor presentation, March 2020
Slide 1: Corporate Presentation 2020
1 C O R P O R AT E P R E S E N TAT I O N • 2 0 2 0 Nasdaq: HEPA Nasdaq: HEPA
Slide 2: Forward-Looking Statements
Forward-Looking Statements 2 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: Corporate Overview
Corporate Overview 3 Lead Asset CRV431: Novel, high-potency, cyclophilin inhibitor that targets multiple stages of liver disease, including NASH Anti-fibrotic, anti-viral, and anti-cancer properties (pleiotropic) Strong preclinical proof of concept Strong safety profile in preclinical and phas
Slide 4: Development Phase
Development Phase 4 Discovery Phase 1 Phase 3 Projected Launch CRV431 2026 Preclinical Phase 2 Phase 1 Phase 2 Phase 1 Multiple Ascending Single Ascending Proof of Concept Dosing in Progress, Preparation Ongoing, Dosing Completed Completion in H1, 2020 Initiation in H1, 2020 Nasdaq: HEPA
Slide 5: CRV431 in NASH
CRV431 in NASH 5 Cyclophilin Inhibitors Target Multiple Liver Disease Stages Injury/Steatosis Inflammation Fibrosis Cirrhosis/Cancer Antiviral activity Suppress pro-inflammatory Reduce collagen production Block cancer cell (HBV, HCV, HDV, HIV-1) pathways mediated by from hepatic stellate cells adapt
Slide 6: Anti-Fibrotic Activity in NASH Models
Anti-Fibrotic Activity in NASH Models 6 STAM Mouse Model “Friedman” Mouse Model (High fat diet + streptozotocin) (Western diet + CCl4) 3 - 11 weeks oral CRV431 treatment 6 weeks oral CRV431 treatment P≤0.0001 p < 0 .0 1 p = 0 .0 3 p = 0 .0 1 10 4 6 Sirius Red (% of area) S ir iu s r e d - p o s itiv
Slide 7: Anti-Fibrotic Activity in Liver Toxin Models
Anti-Fibrotic Activity in Liver Toxin Models 7 Rat Thioacetamide Model Carbon Tetrachloride Mouse Model 9 weeks thioacetamide 6 weeks CCL4 9 weeks vehicle or CRV431 6 weeks vehicle, CRV431, or obeticholic acid (OCA) Fibrosis (% Sirius Red) Fibrosis (% Sirius Red) Fibrosis score P = 0.008 15 P=0.008
Slide 8: Anti-Cancer Activity in Late-Stage NASH Model
Anti-Cancer Activity in Late-Stage NASH Model 8 STAM Mouse Model Number of Tumor Nodules (Streptozotocin + High Fat Diet) 15 p = 0.05 Number of nodules per liver 10 Score 0 5 10 weeks oral CRV431 treatment 0 Vehicle CRV431 p = 0.014 44% reduction in tumor number 5 Sirius red-positive fibrosis Score
Slide 9: CRV431 on Human Liver Explant Tissue
CRV431 on Human Liver Explant Tissue (FibroFind, UK) 9 CRV431 Decreases Inflammation and Fibrosis Markers in Diseased Human Liver Tissue Picrosirius Red Staining of Fibrotic Collagen Summary Precision cut liver slices from 4 human donors had baseline 1.3 - % Normalized to Nonstimulated and Stimula
Slide 10: CRV431 on Human IPF Lung Explant Tissue
CRV431 on Human IPF Lung Explant Tissue (FibroFind, UK) 10 CRV431 Decreases Inflammation and Fibrosis Markers in Diseased Human Lung Tissue Gene Expression Secreted Protein Markers (Daily Average Change) 600 25 outlier excluded from mean Col1α1 Col1α1 400 % change vs vehicle 200 αSMA 0 Hyaluronic ac
Slide 11: Anti-Fibrotic Mechanisms of Action
Anti-Fibrotic Mechanisms of Action 11 CRV431 is proposed to decrease fibrosis by affecting two processes in hepatic stellate cells, the primary, collagen-producing cell type in hepatic fibrosis: • decrease expression of fibrosis-related genes • decrease cyclophilin B-dependent collagen synthesis and
Slide 12: Summary of Nonclinical Anti-fibrotic Activities
Summary of Nonclinical Anti-fibrotic Activities 12 Treatment Fibrosis Reduction Species Model Location Other CRV431 Effects Duration (% Sirius Red)* Friedman NASH model Mice Scripps (USA) 6 weeks 82% Weight gain (CCl4 + Western diet) STAM NASH model Mice Stelic (Japan) 3 weeks 57% None (strept
Slide 13: Clinical Pharmacology: Single Ascending Dose Study
Clinical Pharmacology 13 Single Ascending Dose (SAD) Study: (CRV431-101) → To evaluate the safety and tolerability of single oral doses of CRV431 at increasing dose levels Objectives → To evaluate the pharmacokinetics of CRV431 Design → Randomized, Partially blinded, Placebo-controlled, sequential S
Slide 14: Clinical Pharmacology: CRV431
Clinical Pharmacology: CRV431 14 Mean Pharmacokinetic Parameters: Non-Compartment Model AUC0-inf, Tmax, h Cmax, ng/mL t½, h Dose (range) (SD) ng*h/mL (SD) (SD) 75 mg 4 (2-10) 334±106 20,917±3,780 73.6±15.2 225 mg 1.3 (1-2) 1,368±221 84,422±32,373 97.3±18.4 375 mg 1.5 (1-3) 1,488±176 103,833±30,916 1
Slide 15: Clinical Pharmacology: SAD Safety Profile and Conclusions
Clinical Pharmacology 15 Safety Profile and Conclusions: SAD Study → No SAEs were reported in the SAD study Safety Profile → AEs from the SAD study have been mild to moderate and mostly unrelated to study drug → There were no Grade 3 or Grade 4 laboratory abnormalities → Vital signs and ECGs were un
Slide 16: Clinical Pharmacology: Multiple Ascending Dose Study
Clinical Pharmacology 16 Multiple Ascending Dose (MAD) Study (CRV431-101) → To evaluate the safety and tolerability of multiple oral doses of CRV431 at increasing dose levels over 28 days Objectives → To evaluate maximum tolerated dose → To evaluate the pharmacokinetics of CRV431 at steady state Des
Slide 17: Phase 2A Proof-of-Concept AMBITION Trial
Clinical Pharmacology 17 Phase 2A Proof-of-Concept (CRV431-201, ‘AMBITION’ Trial) To evaluate the safety and tolerability of once daily (qd) 150 mg dose of CRV431 in presumed Objectives nonalcoholic steatohepatitis (NASH) fibrosis stage 2 (F2)/fibrosis stage 3 (F3) subjects compared to Placebo con
Slide 18: Clinical Pharmacology: Where does the Drug Work?
Clinical Pharmacology: Where does the Drug Work? 18 Physiological Based PK Modeling Bioinformatics: Gene-Gene Interactions Extensive liver partitioning Favors the use of CRV431 in liver diseases Confirms once daily dosing at drug target sites CRV431 Receptor Gene – NASH Interactions Evaluate
Slide 19: Bioinformatics: AI Predicting Clinical Outcomes
Bioinformatics: Artificial Intelligence (AI) Predicting Clinical Outcomes 19 NASH Clinical Outcome: AI STEP 1: Shallow Neural Net: A Simple Example STEP 2: Deep Neural Net: In-Training with Enhanced Proprietary Methods Neural Network Architecture B1 B2 Drug I1 Black lines indicate positive weights
Slide 20: Clinical Timelines
Clinical Timelines 20 2020 H1 • Data from Clinical 28-day study, oral CRV431 Multiple Ascending Dose (MAD), once daily dosing • Initiate Phase 2 NASH biomarker pilot trial (‘AMBITION’), 28-day CRV431 once daily dosing Q3 • Bioinformatic biomarker analysis, genomic analysis: NASH + CRV431 • AI Analys
Slide 21: Non-Clinical Events
Non-Clinical Events 21 2020 Q1 Data from Precision Cut Liver Slices, UK • Initiate chronic toxicology in rat and monkey • Continue fibrosis studies Q2 • Data from kidney fibrosis model • Bioinformatic analyses of previous animal models H2 • Data from chronic toxicology, rat and monkey • Data from
Slide 22: Thank You
22 THANK YOU Corporate Contact: Investor Relations: Robert Foster Stephen Kilmer rfoster@hepionpharma.com skilmer@hepionpharma.com Tel: 646.274.3580 Nasdaq: HEPA
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