Hepion Pharmaceuticals, Inc. · OTC:HEPA
Hepion Pharmaceuticals — Investor Presentation (June 2020)
25 slides from Hepion Pharmaceuticals's investor presentation, Jun 12, 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, a cyclophilin inhibitor Novel molecule 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 phase 1
Slide 4: Development Phase
Development Phase 4 CRV431 Discovery Preclinical Phase 1 Phase 2 Phase 3 Synthesized and Efficacy Models: Single ascending May 2020 Projected Launch screened ~200 molecules 5 in vivo 5 in vitro fibroblast 2 human explants - dosing completed Multiple ascending Announced advancement to Phase 2a Trial
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: Anti-Fibrotic Activity in Human Liver Explant Tissue
Anti-Fibrotic Activity in Human Liver Explant Tissue (FibroFind, UK) 9 Picrosirius Red Staining of Fibrotic Collagen % Normalized to Nonstimulated and Stimulated 150 Sirius Red (normalized %) 100 Precision cut liver slices (PCLS), 4 human donors 50 3 days pro-fibrotic stimulation (TGFβ + PDGF-BB
Slide 10: Anti-Fibrotic Activity in Human Liver Explant Tissue
Anti-Fibrotic Activity in Human Liver Explant Tissue (FibroFind, UK) 10 Gene Expression Secreted Protein Markers (Daily Average Change) 150 25 Col1α1 Col1α1 % change vs vehicle αSMA 0 Fibronectin % vs vehicle 100 Timp1 Timp1 -25 IL-6 Hyaluronic Acid MCP-1 -50 IL-6 50 MCP-1 -75 -48% -11% -23% -9% -14
Slide 11: Anti-Fibrotic Activity in Human IPF Lung Explant Tissue
Anti-Fibrotic Activity in Human IPF Lung Explant Tissue (FibroFind, UK) 11 Gene Expression Secreted Protein Markers (Daily Average Change) 600 25 outlier excluded from mean Col1α1 Col1α1 400 % change vs vehicle 200 αSMA 0 Hyaluronic acid % vs vehicle 150 Timp1 Timp1 -25 TGF-ß1 MMP-7 100 IL-6 -50 IL-
Slide 12: Renal Fibrosis Model in Mice (SMC Labs, Japan)
Renal Fibrosis Model in Mice (SMC Labs, Japan) 12 Unilateral ureter obstruction (UUO) Day 14 Analyses • 14 days of treatment (n = 8 per group) • Vehicle or CRV431 50 mg/kg/day Vehicle CRV431 vs • Left ureter ligation vs SHAM Vehicle Kidney weight 3-fold increase No difference (ligated kidney) Time 0
Slide 13: Anti-Fibrotic Mechanisms of Action
Anti-Fibrotic Mechanisms of Action 13 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 14: Consistent Nonclinical Anti-Fibrotic Activities
Consistent Nonclinical Anti-Fibrotic Activities 14 Species Model Location CRV431 Fibrosis Reduction* Other CRV431 Effects Friedman NASH model Mice Scripps (USA) 6 weeks 82% Weight gain (CCl4 + Western diet) STAM NASH model Mice Stelic (Japan) 3 weeks 57% None (streptozotocin + HFD) STAM NASH m
Slide 15: Clinical Pharmacology: Single Ascending Dose Study
Clinical Pharmacology 15 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 16: Clinical Pharmacology: CRV431
Clinical Pharmacology: CRV431 16 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 17: Clinical Pharmacology: Safety Profile and Conclusions
Clinical Pharmacology 17 Safety Profile and Conclusions: SAD Study → No SAEs Safety Profile → AEs were mild to moderate, and mostly unrelated to study drug → No Grade 3 or Grade 4 laboratory abnormalities → Vital signs and ECGs were unremarkable → Doses were tested up to 525 mg with no concerns Conc
Slide 18: Clinical Pharmacology: Multiple Ascending Dose Study
Clinical Pharmacology 18 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 19: Clinical Pharmacology: Phase 2A AMBITION Trial
Clinical Pharmacology 19 Phase 2A Pilot Study (CRV431-201, the ‘AMBITION’ Trial) To evaluate the safety and tolerability of once daily (qd) 75 mg dose of CRV431 in presumed Objectives nonalcoholic steatohepatitis (NASH) fibrosis stage 2 (F2)/fibrosis stage 3 (F3) subjects compared to placebo contr
Slide 20: Bioinformatics of CRV431 in NASH/NAFLD Human Liver Slices
The Bioinformatics of CRV431 in NASH/NAFLD Human Liver Slices 20 Early Analysis of Key NASH Genetics After 3-Days CRV431 • NASH/NAFLD is heterogenous Gene Implications for NASH Fold p-value (Down-regulation, loss-of- Change • Genetic analysis of the effects of CRV431 on function, polymorphism) 28,27
Slide 21: CRV431 and the Genetics of NASH
Clinical Pharmacology: CRV431 and the Genetics of NASH 21 Bioinformatics: Gene-Gene Network Interactions • CRV431 inhibits all cyclophilins • Cyclophilin B (PPIB) and G (PPIG) have direct regulatory effects on NAFLD/NASH genes • Network analysis demonstrates the genetic role of CRV431 in NASH • Pros
Slide 22: Bioinformatics: AI Predicting Clinical Outcomes
Bioinformatics: Artificial Intelligence (AI) Predicting Clinical Outcomes 22 STEP 1: Create Shallow Neural Net STEP 2: Create Deep Neural Net: In-Training with Enhanced Proprietary Methods B1 B2 Neural Network Architecture Drug I1 Inputs: Drug Type, Drug Dose, Mechanism of Action, Number of Patien
Slide 23: Clinical Timelines
Clinical Timelines 23 2020 H1 • Initiate Phase 2 NASH biomarker pilot trial (‘AMBITION’), 28-day CRV431 once daily dosing Q3 • Data from Clinical 28-day study, oral CRV431 Multiple Ascending Dose (MAD), once daily dosing* • Bioinformatic biomarker analysis, genomic analysis: NASH + CRV431 • AI Analy
Slide 24: Non-Clinical Events
Non-Clinical Events 24 2020 Q1 • 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 Diamond NASH mice • Data from cyclophilin knockouts 2021 H1 • Data from chronic toxi
Slide 25: Thank You
25 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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