Hepion Pharmaceuticals, Inc. · OTC:HEPA
Hepion Pharmaceuticals — Investor Presentation (March 2020)
21 slides from Hepion Pharmaceuticals's investor presentation, Mar 11, 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 Precision Cut Liver Slices
CRV431 on Human Precision Cut Liver Slices (FibroFind, UK) 9 CRV431 Decreases Tissue Fibrosis in Human Liver Samples Picrosirius Red Staining of Fibrotic Collagen Summary Precision cut liver slices from 4 human donors had baseline 1.3 - % Normalized to Nonstimulated and Stimulated 9.5% Sirius red
Slide 10: Anti-Fibrotic Mechanisms of Action
Anti-Fibrotic Mechanisms of Action 10 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 11: Summary of Nonclinical Anti-fibrotic Activities
Summary of Nonclinical Anti-fibrotic Activities 11 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 (strepto
Slide 12: Clinical Pharmacology: Single Ascending Dose Study
Clinical Pharmacology 12 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 13: Clinical Pharmacology: CRV431
Clinical Pharmacology: CRV431 13 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 14: Clinical Pharmacology: Safety Profile and Conclusions
Clinical Pharmacology 14 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 15: Clinical Pharmacology: Multiple Ascending Dose Study
Clinical Pharmacology 15 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 16: Phase 2A Proof-of-Concept AMBITION Trial
Clinical Pharmacology 16 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 17: Clinical Pharmacology: Where does the Drug Work?
Clinical Pharmacology: Where does the Drug Work? 17 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 18: Bioinformatics: AI Predicting Clinical Outcomes
Bioinformatics: Artificial Intelligence (AI) Predicting Clinical Outcomes 18 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 19: Clinical Timelines
Clinical Timelines 19 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 20: Non-Clinical Events
Non-Clinical Events 20 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 21: Thank You
21 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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