Hepion Pharmaceuticals, Inc. · OTC:HEPA
Hepion Pharmaceuticals — Investor Presentation (January 2022)
28 slides from Hepion Pharmaceuticals's investor presentation, January 2022
Slide 1: Rencofilstat (CRV431): A liver-targeting drug candidate for NASH and HCC
Rencofilstat (CRV431): A liver-targeting drug candidate for NASH and HCC January 2022 | I N V E S T O R P R E S E N TAT I O N smart drug smart technology smart development 1 1
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: The Need and Opportunity: NASH and HCC Healthcare Crisis
The Need and Opportunity NASH and HCC are driving a Healthcare Crisis NAFLD NASH HCC non-alcoholic fatty liver disease non-alcoholic steatohepatitis hepatocellular carcinoma “Fatty liver” disease associated with A more severe form of NAFLD, with Most prevalent type (90%) of liver cancer, obesity, di
Slide 4: The Challenges: Complex and Diverse Diseases
The Challenges Complex and Diverse Diseases • No FDA drugs approved NASH • Many disappointments amongst drug classes – FXR, PPAR, FGF, GLP, etc. • Industry focus on metabolism-regulating therapeutics may be “missing the mark” (need for direct acting anti-fibrotics) • Tyrosine kinase inhibitors and i
Slide 5: Hepion's Strategy: Cornerstones of Drug Development for Complex Diseases
Hepion’s Strategy Cornerstones of Drug Development For Complex Diseases Targeting multiple disease mechanisms Oral medications with few side effects and derived from maximizes the opportunity to reverse proven drug classes offer several complex diseases such as advantages as stand-alone NASH and HCC
Slide 6: Rencofilstat
Rencofilstat • Cyclophilin inhibitor – new drug class • Once-daily, oral medication – soft gel capsules Rencofilstat • No serious adverse effects Drug Candidate for • Liver targeting: [liver] > [blood] NASH and HCC • Pleiotropic activities in preclinical models of NASH, liver fibrosis, and hepatocel
Slide 7: Rencofilstat IND Approvals
Rencofilstat IND Approvals Program Pre-Clinical Phase 1* Phase 2 Phase 3 Phase 2B NASH IND 142904 2022 HCC IND 158432 Open to HBV IND 1376787 partnerships Will not proceed unless externally COVID-19 IND 151344 funded/licensed *Separate Phase 1 programs were not conducted for each separate indication
Slide 8: Cyclophilin Isomerases - Rencofilstat Target
Cyclophilin Isomerases - Rencofilstat Target Protein Foldases and Participants in Diverse Molecular Activities Cyclophilins: • enzymes that regulate geometry of Proline Peptide Bond cis-trans Isomerization proline-peptide bonds – cis-trans conformations Cyclophilin Key Roles: • protein synthesis and
Slide 9: Cyclophilins in NASH and HCC
Cyclophilins in NASH and HCC Cyclophilins Propagate Diverse Pathologic Activities CYCLOPHILIN A (Gene PPIA) Examples: dysregulated cell proliferation, viral replication (hepatitis and corona- viruses, proinflammatory signaling) CYCLOPHILIN B (Gene PPIB) Examples: multi-organ fibrosis (excess collage
Slide 10: Preclinical Studies: Extensive Testing in Disease Models
Preclinical Studies Extensive Testing in Disease Models ANIMAL MODELS (mice and rats) RENCOFILSTAT EFFECTS • 8 NASH-related studies • Anti-inflammatory and anti-fibrotic effects - diet and/or chemical-induced liver disease across all animal and translational • 4 HCC-related studies models -spontaneo
Slide 11: Overview of Phase 2a 'AMBITION' NASH Trial
Overview of PHASE 2A ‘AMBITION’ NASH TRIAL 11
Slide 12: Phase 2a 'AMBITION' NASH Study
PHASE 2a ‘AMBITION’ NASH 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 Rencofilstat Dosed Once Daily in NASH Induced F2 & F3 Subjects Placebo (n=6)
Slide 13: Summary Phase 2a Study
Summary Phase 2a Study • Rencofilstat, safe and well-tolerated, while showing efficacy signals in only 28 days dosing, including: • Reduction in ALT (marker of inflammation) • Reduction in Pro-C3 (marker of fibrosis) • Blood exposures in subjects with NASH similar to healthy subjects • Data to suppo
Slide 14: All Primary Endpoints Met – Safety, Tolerability, & Pharmacokinetics
All Primary Endpoints Met – Safety, Tolerability, & Pharmacokinetics (‘PK’) Adequate Exposures Anticipated for Efficacy No Serious Adverse Cohort A (75 mg) achieves Cohort C (225 mg) achieves Response analysis suggests Events maximum concentrations ~ maximum concentrations > 225 mg QD achieves effec
Slide 15: Efficacy Endpoints
Efficacy Endpoints ALT Change from Baseline Pro-C3 Change from Baseline ≥ 17.5 ng/mL 15
Slide 16: PK-PD: Changes in ALT and Pro-C3 are Predictable
PK-PD: Changes in ALT and Pro-C3 are Predictable * Arithmetic Mean ** Bootstrap (n=500) 16
Slide 17: 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 18: Pro-C3 Responder Analysis
Pro-C3 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 Respond
Slide 19: Hepion's Artificial Intelligence
Hepion’s Artificial Intelligence Rencofilstat: Multiple Beneficial Properties and State-of-the-Art Artificial Intelligence NEURAL MACHINE Understand disease mechanisms NETWORK LEARNING Identify biomarkers NASH BIG AI-POWR™ Track disease progression and DATA regression Predict drug responders MULTI-O
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 • Rencofilstat concentration > 800 ng/mL AI-machine Potential learn
Slide 21: Clinical Collagen-Related Gene Regulatory Network
Clinical Collagen-Related MMP 23B Gene Regulatory Network A1BG SDC2 COCH FBN2 Consistent antifibrotic ACHE EMID1 F5 LOXL1 SERP INB8 effects observed in all BCHE N1D1 ICAM1 preclinical and clinical COL9A2 F13A1 HTRA1 PXDN MMP8 ORM1 models COL4A3 EMILIN2 LAMC1 VCAN FBN1 USH2A FN1 LAMB2 HGF CLEC3B LAMB
Slide 22: Phase 2b 'ASCEND-NASH' Trial
PHASE 2B ‘ASCEND-NASH’ TRIAL 22
Slide 23: 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 rencofilstat compared to placebo in subjects with biopsy proven NASH and stage 2 liver fibrosis (F2) / stage 3 liver fibrosis (F3) Off-treatment follow-up Rencofilstat 75 mg qd
Slide 24: Phase 2a HCC Trial
2I* HEPION PHASE 2A HCC TRIAL
Slide 25: Phase 2a: HEPA-RENCOFILSTAT-209, Simon 2 Stage Design
PHASE 2a: HEPA-RENCOFILSTAT-209, Simon 2 Stage Design Advanced HCC Subjects - Safety, Tolerability, Pharmacokinetics, and Efficacy HEPA-RENCOFILSTAT-209: A Phase 2a, Open-Label, Multi-Center, Simon 2-Stage Clinical Study to Assess the Preliminary Efficacy, Safety, and Pharmacokinetics of 2 Dosage Le
Slide 26: HEPA-CRV431-209 Efficacy Endpoints
HEPA-CRV431-209 Efficacy Endpoints Primary Objectives Endpoints • Assess disease control rate (DCR) • DCR = sum of subjects achieving complete response (CR), partial response (PR) and stable disease (SD) per Response Evaluation Criteria in Solid Tumors (RECIST) after 16 weeks observation Secondary O
Slide 27: Summary: Two Value Drivers and Financials
Summary Two • Rencofilstat, once-daily oral, multi-modal Value Drivers • Phase 2a NASH trial completed with success • Phase 2b activities initiated for NASH • Phase 2a activities initiated for HCC A Potential AI-Driven, • Hepion’s Proprietary Artificial Intelligence Platform Therapy for Bioinformati
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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