Hepion Pharmaceuticals, Inc. · OTC:HEPA
Hepion Pharmaceuticals — Investor Presentation (August 2023)
38 slides from Hepion Pharmaceuticals's investor presentation, August 2023
Slide 1: Rencofilstat (CRV431): A Novel Drug Candidate for NASH, Fibrosis, and HCC
N A S D A Q : HE PA Rencofilstat (CRV431): A Novel Drug Candidate for NASH, Fibrosis, and HCC Creating a Therapeutic Ecosystem August 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: NASH Drug Development Landscape
NASH Drug Development Landscape Phase 2b and 3 THRβ agonist CCR2/5 inhibitor Enhanced SCD1 inhibitor Resmetirom1 omega-3 fatty ASC411 Cenicriviroc1 Aramchol1 VK2809 1 acids ASK1 inhibitor Icosabutate1 FASN inhibitor DGAT2 inhibitor cyclophilin inhibitor Selonsertib1 Denifanstat1 ION2242 Rencofilstat
Slide 10: Rencofilstat Mode of Action
Rencofilstat Mode of Action 10
Slide 11: 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 12: Rencofilstat Attenuates Collagen Synthesis by Inhibiting Cyclophilin B Enzyme Activity
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 (Completed)
Overview of Phase 1 Studies (Completed) 15
Slide 16: Phase 1 Studies Completed – Demonstrated a Favorable Safety Profile
Phase 1 Studies Completed – Demonstrated a Favorable Safety Profile 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 fa
Slide 17: Overview of Phase 2a 'AMBITION' NASH Trial (Completed)
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 demonstrated a favorable safety profile 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
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 + QoL • Simulation • Predict Clinical Outcome 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 (Clinically Complete)
Phase 2 ‘ALTITUDE-NASH’ Trial (Clinically Complete) 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' HepQuant SHUNT Test Results
Phase 2 ‘ALTITUDE-NASH’ HepQuant SHUNT Test Results Functionally Impaired Subjects# All Subjects with Paired Data (n=61) with Paired Data (n=34) All Doses 75 mg 150 mg 225 mg All Doses 75 mg 150 mg 225 mg % of Subjects with a greater than 2-point Decrease in DSI % of Subjects with a greater than 2-p
Slide 27: Phase 2 'ALTITUDE-NASH' Key NASH Non-Invasive Markers Results
Phase 2 ‘ALTITUDE-NASH’ Key NASH Non-Invasive Markers (NIMs) Results All Subjects Subjects with Baseline ProC3 ≥ 37.5 ng/ml % Change From Baseline % Change From Baseline 75 mg 150 mg 225 mg 75 mg 150 mg 225 mg rencofilstat rencofilstat rencofilstat rencofilstat rencofilstat rencofilstat n=23 n=21 n=
Slide 28: Phase 2b 'ASCEND-NASH' Trial (Enrolling)
Phase 2b ‘ASCEND-NASH’ Trial (Enrolling) 28
Slide 29: 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 30: 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 31: Phase 2a HCC Trial (Pending)
Phase 2a HCC Trial (Pending) 31
Slide 32: 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 33: Intellectual Property
2° VEPION Intellectual Property
Slide 34: Intellectual Property Position: Long Patent Life with Patent Term Extensions
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 Filed (Solid
Slide 35: Summary
2° VEPION Summary
Slide 36: Two Value Drivers and Financials
Two Tackling Fibrotic Diseases Value Drivers • Rencofilstat, once-daily oral, targeting key drivers of pathology, tested in over 425 subjects • Two Phase 2 NASH trials: • ALTITUDE-NASH – Clinically Complete • ASCEND-NASH Phase 2b – Recruiting • Upcoming Phase 2 for HCC • Developing companion A.I. fo
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
Hepion Pharmaceuticals — Investor Presentation (August 2023) on 6ix