Hepion Pharmaceuticals, Inc. · OTC:HEPA
Hepion Pharmaceuticals — Investor Presentation (October 2021)
28 slides from Hepion Pharmaceuticals's investor presentation, October 2021
Slide 1: A Better Approach to Drug Development for Liver Diseases
A BETTER APPROACH TO DRUG DEVELOPMENT FOR LIVER DISEASES October 2021 | I N V E S T O R P R E S E N TAT I O N smart drug smart technology smart development
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: NASH is a Healthcare Crisis
The Need and Opportunity NAFLD non-alcoholic fatty liver disease NASH is a “Fatty liver” disease associated with Healthcare Crisis obesity, diabetes, hypertension, etc. NASH leads to cirrhosis, 1 liver cancer (HCC), end stage Approx. 25% of global population liver disease, and death Up to 100 millio
Slide 4: The Challenges of NASH Drug Development
The Challenges Nash Drug Development NASH Resolution 14% 27% Regulatory agencies require improvement in several Simtuzamab Simtuzamab Placebo indices of NASH by analysis of liver biopsies: Selonsertib Low dose Obeticholic acid Cenicriviroc Aramchol Medium dose • Fatty deposits, cell death, inflammat
Slide 5: Multiple Therapeutic Actions Through Cyclophilin Inhibition – A Novel Class
Multiple Therapeutic Actions Through Cyclophilin Inhibition – A Novel Class Cyclophilin A CD147 pro-inflammatory receptors CRV431 (cytosol and secreted) Pan-Cyclophilin Inhibitor (Ki ≈ 1 nM) Secreted from injured cells and acts as proinflammatory cytokine x x INFLAMMATION Cyp A by binding to CD147 P
Slide 6: Genesis of CRV431
Genesis of Theory Prediction and Experimentation Findings Modifications that increase calcineurin binding and immunosuppression Modifying Cyclosporine A can (voclosporin) Inhibition of each cyclophilin greatly change its binding and isoform may produce distinct functional properties Modifications th
Slide 7: IND Approvals
IND Approvals Program Pre-Clinical Phase 1* Phase 2 Phase 3 NDA Submission Phase 2B Projected Initiation NDA filing NASH IND 142904 Q1 2022 2028 Will not proceed COVID-19 IND 151344 unless externally funded/licensed Open to HBV IND 1376787 partnerships *Separate Phase 1 programs were not conducted f
Slide 8: Non-clinical Evidence of Strong and Consistent Beneficial Activities for CRV431
Non-clinical Evidence of Strong and Consistent Beneficial Activities for CRV431 Human Cell Cultures CRV431 Effects Hepatic stellate cells, TGFβ or endogenous stimulation ▼fibrotic gene expression fibroblasts (multiple organs) ▼procollagen and fibronectin secretion Blood platelets Collagen and thromb
Slide 9: Overview of Phase 2a 'AMBITION' Trial
Overview of PHASE 2A ‘AMBITION’ TRIAL 9
Slide 10: Phase 2a 'AMBITION' Study
PHASE 2a ‘AMBITION’ Study NASH Subjects - Safety, Tolerability, and Pharmacokinetics AMBITION: A Phase 2a, Multi-center, Single-Blind, Placebo-Controlled, Proof of Concept Study to Evaluate the Safety & Tolerability of CRV431 Dosed Once Daily in NASH Induced F2 & F3 Subjects Placebo (n=6) OFF-TREATM
Slide 11: Phase 2a: 'AMBITION' Study Baseline Demographics
Phase 2a: ‘AMBITION’ Study Baseline Demographics CRV431 75 mg CRV431 225 mg Pooled Placebo (n = 12) (n = 17)* (n = 14) Age (years) Mean (SD) 61.9 (8.0) 54.0 (13.3) 61.1 (12.0) Range 48-72 27-71 27-72 Gender Male n (%) 7 (58.3) 7 (41.2) 9 (64.3) Female n (%) 5 (41.7) 10 (58.8) 5 (35.7) Race White n (
Slide 12: All Primary Endpoints Met – Safety, Tolerability, & Pharmacokinetics
All Primary Endpoints Met – Safety, Tolerability, & Pharmacokinetics (‘PK’) Adequate Exposures Anticipated for Efficacy Biomarker response Slides demonstrate Cohort C (225 mg) achieves Cohort A (75 mg) achieves analysis suggests 225 mg accumulation of maximum concentrations > maximum concentrations
Slide 13: ALT, Area Under the Curve (AUC) – Pharmacodynamics
ALT, Area Under the Curve (AUC) – Pharmacodynamics (‘PD’) Change From Baseline (FOUR Weeks) Placebo 75 mg 225 mg Mean ± SD (%) -6.1 ± 13.3 -18.4 ± 25.8 -21.1 ± 21.0 Median (%) -5.2 -15.9 -20.0 (Range) (-23.8 – 13.8) (-58.3 – 17.2) (-81.5 – 11.1) N (%) Reduction 7/14 (50%) 8/12 (67%) 13/15 (87%) ALT
Slide 14: 'PK-PD' Model Successfully Predicts ALT Effects
‘PK-PD’ Model Successfully Predicts ALT Effects (Responder & Non-Responder) Observed vs Predicted: ALT PK PD Inhibitory Imax Absorption Model Ka (h-1) Volume (L) -Baseline (ALT) IC50:Half-Maximal Inhibition Elimination (k h-1) Assess patient Final Covariate Model: characteristics Confirms Allows sim
Slide 15: ALT Responder Analysis
ALT Responder Analysis ALT Responder Analysis 1 = Non-responder 2 = Responder 3 = No baseline By Flexible Discriminate Analysis: Misclassification Error = 0.04255 Discriminant analysis evaluates Step 1: Identify Responders vs Non-Responders: Means of Non- the ability of multiple variables Responders
Slide 16: Pro-C3: Collagen Formation – Pharmacodynamics
Pro-C3: Collagen Formation – Pharmacodynamics (’PD’) Released N-terminal Pro-Peptide of Type III Collagen ProC3 indicates ACTIVE FIBROSIS 16 Source: HEPA:CRV431-201: Phase2A Trial on NASH
Slide 17: PK-PD Model Successfully Predicts Pro-C3
PK-PD Model Successfully Predicts Pro-C3 Observed vs Predicted: Pro-C3 PK PD Inhibitory Imax Absorption Model Ka (h-1) Volume (L) -Baseline (Pro-C3) IC50:Half-Maximal Inhibition Elimination (k h-1) No Covariates were Final Covariate Model: Quantitative Allows simulation required to predict - PK 1-Co
Slide 18: Pro-C3 CRV431 Responder Analysis
Pro-C3 CRV431 Responder Analysis Pro-C3 Responder Analysis 1 = Non-responder 2 = Responder By Mixture Discriminate Analysis: Misclassification Error = 0.02128 Discriminant analysis evaluates Step 1: Identify Responders vs Non-Responders: Means of Non- the ability of multiple variables Responders vs
Slide 19: Hepion's Artificial Intelligence
Hepion’s Artificial Intelligence CRV431: Multiple Beneficial Properties and State-of-the-Art Artificial Intelligence NEURAL MACHINE Understand disease mechanisms NETWORK LEARNING Identify biomarkers BIG NASH AI-POWR™ Track disease progression and DATA regression Predict drug responders MULTI-OMICS D
Slide 20: Phase 2a: Transcriptomics & AI
Phase 2a: Transcriptomics & AI Standard Differentially Expressed Genes - DESEq2 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 • CRV431 concentration > 800 ng/mL AI-machine Potential learning ha
Slide 21: Clinical Collagen-Related Gene Regulatory Network
Clinical Collagen-Related MMP 23B A1BG Gene Regulatory Network SDC2 COCH FBN2 SERP Consistent antifibrotic ACHE EMID1 F5 LOXL1 INB8 effects observed in all BCHE N1D1 ICAM1 COL9A2 preclinical and clinical F13A1 HTRA1 PXDN MMP8 ORM1 models COL4A3 EMILIN2 LAMC1 VCAN FBN1 USH2A FN1 LAMB2 HGF CLEC3B LAMB
Slide 22: Conclusions Phase 2a Study
Conclusions Phase 2a Study Phase 2a study provided Phase 2a study demonstrated signals safety and exposure of efficacy (reduced inflammation and data in NASH subjects fibrosis) within 4 weeks Phase 2a study provided post-hoc Data from the Phase 2a was utilized to responder analysis data to further a
Slide 23: Phase 2b 'ASCEND-NASH' Trial
PHASE 2B ‘ASCEND-NASH’ TRIAL 23
Slide 24: Phase 2b 'ASCEND-NASH'
Phase 2b ‘ASCEND-NASH’ Primary Objective: Evaluate the efficacy and safety of once-daily 75mg, 150 mg, and 225 mg doses of CRV431 compared to placebo in subjects with biopsy proven NASH and stage 2 liver fibrosis (F2) / stage 3 liver fibrosis (F3) Off-treatment follow-up CRV431 75 mg qd (n=84) RANDO
Slide 25: Phase 2b Endpoints
Phase 2b Endpoints Primary Efficacy Endpoint: Secondary Efficacy Endpoints: Superiority of CRV431 (75mg, 150 mg, 225 mg) Superiority of CRV431 (75mg, 150 mg, 225 mg) compared to placebo on liver histology at month compared to placebo on histology at month 12 12 relative to the screening biopsy, by a
Slide 26: 2021 Anticipated Events
2021 ANTICIPATED EVENTS CRV431 Complete Ongoing Phase 2a NASH program by Q1-Q2, 2021 Complete long-term animal toxicology (Q2, 2021) Continue to optimize and scale-up chemistry and manufacturing Complete additional clinical Drug-Drug Interaction study (Q2, 2021) NASH Phase 2b preparation (H2, 2021)
Slide 27: Summary: Two Value Drivers
Summary Two • CRV431, once-daily oral, multi-modal Value Drivers • Cyclophilin inhibition allows for several benefits, including anti-fibrotic, anti-inflammatory, cytoprotective • Phase 2a NASH trial completed with success - Safe, well-tolerated, PK defined A Therapy for AI-Driven, NASH with Bioinfo
Slide 28: Contact Us
CONTACT US Robert T. Foster, PharmD, Ph.D. Chief Executive Officer Hepion Pharmaceuticals Inc. 399 Thornall Street, First Floor Edison, New Jersey, USA, 08837 Email: rfoster@hepionpharma.com www.hepionpharma.com
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