Hepion Pharmaceuticals, Inc. · OTC:HEPA
Hepion Pharmaceuticals — Investor Presentation (May 2022)
36 slides from Hepion Pharmaceuticals's investor presentation, May 2022
Slide 1: Rencofilstat (CRV431): A liver-targeting drug candidate for NASH and HCC
N A S D A Q : HE PA Rencofilstat (CRV431): A liver-targeting drug candidate for NASH and HCC smart drug smart technology smart development May 2022 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 are driving a 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 A more severe form of NAFLD, Most prevalent type (90%) of liver associated with obesity, with inflammati
Slide 4: The Challenges: New approaches to developing NASH and HCC therapeutics needed
The Challenges Complex and Associated Diseases New approaches NASH HCC to developing • No FDA drugs approved • Poor prognosis and rising • Traditional metabolism- incidence from NASH NASH and HCC regulating drugs largely not • Tyrosine kinase inhibitors therapeutics are efficacious and immune checkp
Slide 5: Hepion's Strategy
Hepion’s Strategy Cornerstones of Drug Development For Complex Diseases Targeting multiple disease Pleiotropic Safe, Oral Oral medications with few side mechanisms maximizes the Drug Once Daily effects and derived from proven opportunity to reverse Actions Dosing drug classes offer several complex d
Slide 6: Rencofilstat
Rencofilstat • Cyclophilin inhibitor – new drug class • Once-daily, oral medication – soft gel capsules Rencofilstat • No serious adverse effects • Liver targeting: [liver] > [blood] Drug Candidate for NASH and HCC • Pleiotropic activities in preclinical models of NASH, liver fibrosis, and hepatocel
Slide 7: Rencofilstat Clinical Programs Advancing in 2022
Rencofilstat Clinical Programs Advancing in 2022 Program Pre-Clinical Phase 1* Phase 2 Phase 3 NASH Phase 2B IND 142904 2022 (biopsy) Phase 2 HCC IND 158432 2022 NASH IND 142904 Phase 2 (liver function) 2022 • HBV and COVID-19 INDs open to partnerships 7 *The Phase 1 program was comprised of Single
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: signal transduction; proinflammatory signaling; cell proliferation; viral replication (hepatitis and corona-viruses) CYCLOPHILIN B (Gene PPIB) Examples: multi-organ fibrosis (excess
Slide 10: Rencofilstat Inhibition of Three Primary Cyclophilins in NASH
Rencofilstat Inhibition of Three Primary Cyclophilins in NASH ANTI-INFLAMMATORY Rencofilstat blocks Cyclophilin A binding to CD147 receptors and thereby decreases pro-inflammatory signaling ANTI-FIBROTIC Rencofilstat blocks Cyclophilin B binding to pro-collagen fibrils and thereby decreases formatio
Slide 11: 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 models • 4 HCC-related studies • Consiste
Slide 12: Overview of Phase 1 Studies (completed)
Overview of Phase 1 Studies (completed) 12
Slide 13: Phase 1 Studies Completed: Key Findings
Phase 1 Studies Completed Key Findings Single Ascending Dose: 75 mg – 525 mg • No SAEs • No AEs with Dose Response Multiple Ascending Dose: 75 mg – 375 mg • No SAEs • No AEs with Dose Response • Effective t1/2 ~ 30 hours, Tmaxss ~ 1 – 2 hours Drug-Drug Interaction: Midazolam & Ketoconazole • 4.9-fol
Slide 14: Overview of Phase 2a 'AMBITION' NASH Trial (completed)
Overview of Phase 2a ‘AMBITION’ NASH Trial (completed) 14
Slide 15: 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 16: 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 & fibrosis) • Reduction in Pro-C3 (marker of fibrosis) • Downregulation of collagen genes • Upregulation of genes associated wi
Slide 17: All Primary Endpoints Met – Safety, Tolerability, & Pharmacokinetics
All Primary Endpoints Met – Safety, Tolerability, & Pharmacokinetics (‘PK’) Adequate Exposures Anticipated for Efficacy No Serious Adverse Events NASH does not significantly alter Rencofilstat Concentrations 75 mg QD achieves maximum concentrations > 1000 ng/mL on Day 28 225 mg QD achieves maximum c
Slide 18: Clinical Efficacy Endpoints
Clinical Efficacy Endpoints ALT Change from Baseline Pro-C3 Change from Baseline ≥ 17.5 ng/mL - High Efficiency for screening NASH drug effects - ProC3 emerging as biomarker indicative of fibrosis - Low Effectiveness as a sole marker for NASH Fibrosis Response Boyle, Marie, et al. "Performance of th
Slide 19: PK-PD: Changes in ALT and Pro-C3 are Predictable
PK-PD: Changes in ALT and Pro-C3 are Predictable Early evidence of a concentration-effect relationship * Arithmetic Mean ** Bootstrap (n=500) 19
Slide 20: 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 the ability of multiple variables Non-Responders
Slide 21: 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 the ability of multiple variables Non-Responders vs Responde
Slide 22: 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 BIG NASH AI-POWR™ Track disease progression and DATA regression Predict drug responders MULTI-O
Slide 23: 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 24: 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 25: Phase 2b 'ASCEND-NASH' Trial (Q3, 2022 start)
Phase 2b ‘ASCEND-NASH’ Trial (Q3, 2022 start) 25
Slide 26: Phase 2b ASCEND-NASH (Biopsy Trial)
Phase 2b ASCEND-NASH (Biopsy Trial) 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) Rencofilstat 75 mg qd (n=84) Off-
Slide 27: Phase 2b ASCEND-NASH Endpoints
Phase 2b ASCEND-NASH Primary Efficacy Endpoint: Superiority of Rencofilstat (75mg, 150 mg, 225 mg) compared to placebo on liver histology at month 12 relative to the screening biopsy, by assessing the proportion of subjects with improvement in fibrosis by at least 1 stage (NASH CRN system) OR NASH r
Slide 28: Phase 2 'ALTITUDE-NASH' Trial (Q3, 2022 start)
Phase 2 ‘ALTITUDE-NASH’ Trial (Q3, 2022 start) 28
Slide 29: Phase 2 'ALTITUDE-NASH' (Liver Function Trial)
Phase 2 ‘ALTITUDE-NASH’ (Liver Function Trial) Primary Objective: Evaluate the change in hepatic function with once daily (QD) 75 mg, 150 mg, and 225 mg doses of rencofilstat in subjects with NASH F3 fibrosis using the HepQuant SHUNT test. Off-treatment follow-up Endpoints: RANDOMIZED 1:1:1 Rencofil
Slide 30: Phase 2 'ALTITUDE-NASH' (Liver Function Trial) Endpoints
Phase 2 ‘ALTITUDE-NASH’ (Liver Function Trial) Primary Efficacy Endpoint: Change from baseline in DSI score of subjects taking rencofilstat (75 mg, 150 mg, 225 mg), determined using HepQuant SHUNT Test, on Day -1, Day 60, and Day 120 Secondary Efficacy Endpoints: • Percent of subjects in each treatm
Slide 31: Phase 2a HCC Trial (Q3, 2022 start)
Phase 2a HCC Trial (Q3, 2022 start) 31
Slide 32: Phase 2a: HEPA-CRV431-209, Simon 2-Stage Design
PHASE 2a: HEPA-CRV431-209, Simon 2 Stage Design Advanced HCC Subjects - Safety, Tolerability, Pharmacokinetics, and Efficacy HEPA-CRV431-209: A Phase 2a, Open-Label, Multi-Center, Simon 2-Stage Clinical Study to Assess the Preliminary Efficacy, Safety, and Pharmacokinetics of 2 Dosage Levels of Renc
Slide 33: HEPA-CRV431-209: Objectives
HEPA-CRV431-209: Objectives Primary Objectives: • Assess disease control rate (DCR) • Assess the safety and tolerability of CRV431 Secondary Objectives: • Assess the effect of CRV431 on duration of response (DoR) measured from the time measurement criteria are first met for CR/PR (whichever is first
Slide 34: Summary
#6 EEN Summary
Slide 35: Two Value Drivers
Tackling Chronic Liver Disease Two • Rencofilstat, once-daily oral, multi-modal Value Drivers • Phase 2a NASH trial completed with success • Phase 2 activities initiated for NASH • 12-month paired biopsy Phase 2b study A Potential AI-Driven, • 4-month hepatic function Phase 2 study Therapy for Bioin
Slide 36: 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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