Hepion Pharmaceuticals, Inc. · OTC:HEPA
Hepion Pharmaceuticals — Investor Presentation (April 2023)
38 slides from Hepion Pharmaceuticals's investor presentation, April 2023
Slide 1: Rencofilstat (CRV431): A Novel Drug Candidate for NASH, Fibrosis, and HCC
N A S D A Q : H E PA Rencofilstat (CRV431): A Novel Drug Candidate for NASH, Fibrosis, and HCC Creating a Therapeutic Ecosystem A pri l 2023 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: Rencofilstat Highlights
Rencofilstat Highlights • Novel mechanism - cyclophilin inhibition • Once-daily, oral medication – soft gel capsules Rencofilstat • Collagen-specific anti-fibrotic Anti-Fibrotic Drug • Targets key pathologies including fibrosis, inflammation, Candidate cell injury • All clinical trials to date show
Slide 4: NASH
NASH Fibrotic Liver Disease Leading Indication for Rencofilstat 4
Slide 5: Summary of Rencofilstat Programs – 'Pipeline within a Product'
Summary of Rencofilstat Programs – ‘Pipeline within a Product’ Program Pre-Clinical Phase 1 Phase 2 Phase 3 Biopsy NASH Fast Track Designation Liver Function Hepatocellular Carcinoma Orphan Drug Designation Multiple Myeloma Prostate Cancer Idiopathic Pulmonary Fibrosis Renal Fibrosis Cardiac Fibrosi
Slide 6: The Need and Opportunity: NASH is Driving a Healthcare Crisis
The Need and Opportunity NASH is 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 inflammation and li
Slide 7: Why Develop a Drug for NASH?
Why Develop a Drug for NASH? • No currently approved drugs for the treatment of NASH • Market for NASH is extremely large (estimated as ~20 million adults in U.S. alone) • NAFLD/NASH may be asymptomatic with no convenient diagnostic to identify subjects early in disease progression • Symptoms may on
Slide 8: NASH Therapeutic Strategies
NASH Therapeutic Strategies Multiple therapeutic agents targeting multiple stages of disease likely required WHY? • Generally poor response rates with drugs in development • Many pathologic mechanisms contribute to disease normal liver cells Most failed drugs and drugs in development are "metabolic"
Slide 9: Rencofilstat Mode of Action
Rencofilstat Mode of Action 9
Slide 10: Collagen - Core To Fibrotic Diseases
Collagen - Core To Fibrotic Diseases Excessive collagen production – universal to every fibrotic disease Fibrosis is an exaggerated “scarring” of tissue in response to many types of cellular injuries, chronic inflammation, & other tissue insults Fibrosis impairs normal organ structure & function
Slide 11: Landscape of Clinical Antifibrotic Drug Development
Landscape of Clinical Antifibrotic Drug Development Opportunity for Collagen-Targeting Therapeutics • Despite ≈300 clinical trials, the only approved antifibrotic drugs are pirfenidone and nintedanib • Most anti-fibrotic agents have targeted upstream drivers of fibrogenesis (e.g., TGFβ) or disease-s
Slide 12: Rencofilstat Attenuates Collagen Synthesis by Inhibiting Cyclophilin B
Rencofilstat Attenuates Collagen Synthesis by Inhibiting Cyclophilin B Enzyme Activity - "normalizing" disease-associated fibrosis Cyclophilin B is one of the most active enzymes involved in the proper folding, synthesis, secretion, and eventual crosslinking of collagen that forms the fibrotic matri
Slide 13: Antifibrotic Activity Observed in Preclinical Models: Proof of Concept
Preclinical Models: Proof of Concept Cyclophilin Inhibition Produces Consistent Antifibrotic Effects Liver: 8 NASH-related models Human liver slices Antifibrotic Lung Chronic fibrosis Activity Acute injury Observed in Human lung slices Every Preclinical Kidney Model Acute injury Heart Skin
Slide 14: Rencofilstat Inhibits Three Primary Cyclophilins
Rencofilstat Inhibits Three Primary Cyclophilins Hitting the Right Targets – Fibrosis, Inflammation, and Cell Injury/Death Rencofilstat blocks Cyclophilin B binding to pro-collagen fibrils ANTI-FIBROTIC and thereby decreases formation and secretion of fibrotic collagen Rencofilstat blocks Cyclophili
Slide 15: Overview of Phase 1 Studies
Overview of Phase 1 Studies (completed) 15
Slide 16: Phase 1 Studies Completed – Safe and Well Tolerated
Phase 1 Studies Completed – Safe and Well Tolerated Key Findings No serious adverse events No adverse events with dose response Effective t1/2 ~ 30 hours Single Multiple Drug-Drug Tmaxss ~ 1 – 2 hours Ascending Ascending Interaction Food Effect Dose Dose (midazolam & (high fat meal) Ketoco
Slide 17: Overview of Phase 2a 'AMBITION' NASH Trial
Overview of Phase 2a ‘AMBITION’ NASH Trial (completed) 17
Slide 18: Phase 2a 'AMBITION' NASH Study: Safety, Tolerability, and Pharmacokinetics
Phase 2a ‘AMBITION’ NASH Study 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) OFF-TREATMENT P
Slide 19: Phase 2a 'AMBITION' NASH Study: All Primary Endpoints Met
Phase 2a ‘AMBITION’ NASH Study All Primary Endpoints Met Rencofilstat is safe and well-tolerated Efficacy signals were observed in only 28 days including: • Reduction in ALT (marker of inflammation & fibrosis) • Reduction in Pro-C3 (marker of fibrosis) • Downregulation of collagen genes • Upregulati
Slide 20: Hepion's Proprietary Artificial Intelligence
Hepion’s Proprietary Artificial Intelligence 20
Slide 21: The Hepion AI-POWR Proprietary Clinical Process
The Hepion AI-POWR Proprietary Clinical Process Right Patient All Data Right Dose Generative Neural Net INPUT OUTPUT Deep Convoluted Neural Net 21
Slide 22: The Hepion AI-POWR Proprietary Clinical Process
The Hepion AI-POWR Proprietary Clinical Process AI-POWR • Biomarkers • Responder Identification PKPD/QSP/PBPK • Digital Biomarkers • Patient Selection • Phase III Enrichment + Multi-omics Pre-Clinical Data • Eliminate Biopsy • Simulation • Predict Clinical Outcome + QoL Informs AI/ML • Patient Spe
Slide 23: Illustration of Hepion's AI-POWR for Rencofilstat (RCF)
Illustration of Hepion’s AI-POWR™ for Rencofilstat (RCF) *Genes (number) Predictive Genes (number) AUROC Comment 1733 Statistically Highly Predictive for 25 0.97 Significant ProC3 Response *Key genes identified demonstrate RCF – CypA and B interaction in NASH subjects Lipids (number) Predictive Lipi
Slide 24: Phase 2 'ALTITUDE-NASH' Trial
Phase 2 ‘ALTITUDE-NASH’ Trial (Fully Enrolled) 24
Slide 25: 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. Rencofilstat 75 mg qd (n=20) OFF- Endpoints: RANDOMIZED 1:1:
Slide 26: Phase 2 'ALTITUDE-NASH' Endpoints
Phase 2 ‘ALTITUDE-NASH’ (Liver Function Trial) Primary Efficacy Endpoint: Change from baseline in DSI score of subjects taking rencofilstat using HepQuant SHUNT Test, on Day -1, Day 60, and Day 120 Secondary Efficacy Endpoints: • Percent of subjects with a reduction in DSI score of >2 • Change from
Slide 27: Phase 2b 'ASCEND-NASH' Trial
Phase 2b ‘ASCEND-NASH’ Trial (Enrolling) 27
Slide 28: 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 29: Phase 2b ASCEND-NASH Endpoints
Phase 2b ASCEND-NASH Primary Efficacy Endpoint: Superiority of rencofilstat 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 resolution without worse
Slide 30: Phase 2a HCC Trial
Phase 2a HCC Trial (pending) 30
Slide 31: Phase 2a: Advanced Hepatocellular Carcinoma (HCC)
PHASE 2a: Advanced Hepatocellular Carcinoma (HCC) Safety, Tolerability, Pharmacokinetics, and Efficacy A Phase 2a, Open-Label, Multi-Center, Simon 2-Stage Study to Assess Preliminary Efficacy, Safety, and Pharmacokinetics of 2 Dosage Levels in Advanced Metastatic Resistant or Refractory HCC Subjects
Slide 32: Intellectual Property
Intellectual Property 32
Slide 33: Intellectual Property Position
Intellectual Property Position Long Patent Life with Patent Term Extensions (PTE) Family Status Notes December 2031 Expiry Composition of Matter 54 US & International Issued Patents (December 2036 Expiry with PTE) Assuming 2028 and 2029 NDA submission and approval Composition of Matter Provisional (
Slide 34: Summary
Summary 34
Slide 35: Hepion's Approach to Developing an Ecosystem
Hepion’s Approach to Developing an Ecosystem Creating a Bundle to Support Rencofilstat’s Success Disease Modifying Drug Strategy: • Rencofilstat (disease modifying), efficacious, safe and well-tolerated • Companion Point-of-Care Diagnostic (e.g., Blood Panel) • A.I. and Multiomic Analyses Identify R
Slide 36: Two Value Drivers
Two Tackling Fibrotic Diseases Value Drivers • Rencofilstat, once-daily oral, targeting key drivers of pathology, tested in over 325 subjects • Two Phase 2 NASH trials ongoing • Upcoming Phase 2 for HCC • Developing companion A.I. for clinical development and commercialization strategy • Core scient
Slide 37: Experienced Team
Experienced Team Core R&D team has collectively > 120 yrs of experience with cyclophilin inhibition drug development, most notably voclosporin (Lupkynis®) for lupus nephritis while at Isotechnika (Aurinia, NASDAQ:AUPH) Robert Foster, PharmD, PhD Launa Aspeslet, PhD CEO COO Founded Isotechnika (Aurin
Slide 38: Contact Us
CONTACT US Hepion Pharmaceuticals Inc. 399 Thornall Street, First Floor Edison, New Jersey, USA, 08837 Email: info@hepionpharma.com Phone: 732-902-4000 www.hepionpharma.com
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