Hepion Pharmaceuticals, Inc. · OTC:HEPA
Hepion Pharmaceuticals — Investor Presentation (February 2020)
21 slides from Hepion Pharmaceuticals's investor presentation, February 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 2 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: 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 CRV431 LAUNCH 2026 Preclinical Phase 2 • IND for HBV – Phase 1 Single Ascending Dose completed • IND for HBV – Multiple Ascending Dose in progress, Q3-2019 • IND for NASH – Approved, Q3-2019 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 adaptation (HBV, HCV, HDV, HIV-1) pathways mediated by from hepatic s
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 .0 1 P≤0.0001 p = 0 .0 3 p = 0 .0 1 10 4 6 S ir iu s r e d - p o s itiv e fib r o s is S ir iu
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 p = 0.05 (streptozotocin + high fat diet) 15 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) 9 CRV431 Decreases Tissue Fibrosis in Human Liver Samples Picrosirius Red Staining of Fibrotic Collagen SUMMARY % Normalized to Nonstimulated and Stimulated • Precision cut liver slices from 4 human donors had baseline 1.3 - 9.5% Sirius red stai
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 (SAD) Study
Clinical Pharmacology Single Ascending Dose (SAD) Study 12 (CTRV-CRV431-101) Objectives • To evaluate the safety and tolerability of single oral doses of CRV431 at increasing dose levels • To evaluate the pharmacokinetics of CRV431 Design • Randomized, Partially blinded, Placebo-controlled, sequenti
Slide 13: Clinical Pharmacology: Safety Profile and Conclusions
Clinical Pharmacology: Safety Profile and Conclusions 13 SAD Study Safety Profile • No SAE’s were reported in the SAD Study • AE’s 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
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 Multiple Ascending Dose (MAD) Study
Clinical Pharmacology Multiple Ascending Dose (MAD) Study 15 (CTRV-CRV431-101) Objectives • To evaluate the safety and tolerability of multiple oral doses of CRV431 at increasing dose levels over 28 days • To evaluate maximum tolerated dose • To evaluate the pharmacokinetics of CRV431 at steady stat
Slide 16: Clinical Pharmacology Phase 2A Proof-of-Concept
Clinical Pharmacology Phase 2A Proof-of-Concept 16 (CTRV-CRV431-201) Objectives • To evaluate the safety and tolerability of a once daily (QD) 150 mg dose of CRV431 in presumed nonalcoholic steatohepatitis (NASH) fibrosis stage 2 (F2)/fibrosis stage 3 (F3) subjects compared to placebo control over 2
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: Artificial Intelligence Predicting Clinical Outcomes
Bioinformatics: Artificial Intelligence Predicting Clinical Outcomes 18 NASH Clinical Outcome: AI Step 1: Shallow Neural Net: A Simple Example Neural Network architecture. Black lines indicate positive weights and grey lines indicate negative weights. B1 B2 Line thickness is in proportion to the
Slide 19: Clinical Timelines
Clinical Timelines 19 2020 H1 • Data from Clinical 28-day study, oral CRV431 Multiple Ascending Dose (MAD), once daily • Initiate Phase 2 NASH biomarker pilot study, 1-month CRV431 repeat dose Q3 • Data from Phase 2 NASH pilot study, 1 month, CRV431 repeat dose • Bioinformatic Biomarker analysis, Ge
Slide 20: Non-Clinical Events
Non-Clinical Events 20 2020 Q1 Data from Precision Cut Liver Slices, UK • Initiate chronic dosing safety, animals (rat and monkey) fibrosis study Q2 • Data from UUO kidney fibrosis model • Bioinformatic analyses of previous animal models H2 • Data from chronic dosing safety, animals (rat and monkey
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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