Hepion Pharmaceuticals, Inc. · OTC:HEPA
Hepion Pharmaceuticals — Investor Presentation (July 2023)
38 slides from Hepion Pharmaceuticals's investor presentation, Jul 24, 2023
Slide 1: Rencofilstat (CRV431): A Novel Drug Candidate for NASH, Fibrosis, and HCC
1 1 Rencofilstat (CRV431): A Novel Drug Candidate for NASH, Fibrosis, and HCC July 2023 Creating a Therapeutic Ecosystem NASDAQ: HEPA
Slide 2: Forward-Looking Statements
2 This presentation may contain forward - looking statements within the meaning of Section 27 A of the Securities Act of 1933 and Section 21 E of the Securities Exchange Act of 1934 . Such forward - looking statements are characterized by future or conditional verbs such as “may,” “will,” “expect,”
Slide 3: Rencofilstat Highlights
3 Rencofilstat Anti - Fibrotic Drug Candidate • Novel mechanism - cyclophilin inhibition • Once - daily, oral medication – soft gel capsules • Collagen - specific anti - fibrotic • Targets key pathologies including fibrosis, inflammation, cell injury • All clinical trials to date show rencofilstat t
Slide 4: NASH Fibrotic Liver Disease Leading Indication for Rencofilstat
4 NASH Fibrotic Liver Disease Leading Indication for Rencofilstat
Slide 5: Summary of Rencofilstat Programs – Pipeline within a Product
5 Program Pre - Clinical Phase 1 Phase 2 Phase 3 NASH Fast Track Designation Hepatocellular Carcinoma Orphan Drug Designation Multiple Myeloma Prostate Cancer Idiopathic Pulmonary Fibrosis Renal Fibrosis Cardiac Fibrosis Biopsy Summary of Rencofilstat Programs – ‘Pipeline within a Product’ Liver Fun
Slide 6: NASH is Driving a Healthcare Crisis
6 Image adapted from “From NASH to HCC: current concepts and future challenges”, Anstee et al. (2019) NASH is Driving a Healthcare Crisis The Need and Opportunity NAFLD n on - a lcoholic f atty l iver d isease Approx. 25% of global population Up to 100 million in U.S. “Fatty liver” disease associate
Slide 7: Why Develop a Drug for NASH?
7 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
Slide 8: NASH Therapeutic Strategies
8 NASH DISEASE PROGRESSION normal liver cells fatty liver cells inflammation, cell injury, and activation of fibrotic cells production of fibrotic matrix WHY? • Generally poor response rates with drugs in development • Many pathologic mechanisms contribute to disease Most failed drugs and drugs in d
Slide 9: Phase 2b and NASH Drug Development Landscape
9 Phase 2b and 3 NASH Drug Development Landscape ASK1 inhibitor Galectin - 3 inhibitor LOXL2 inhibitor FASN inhibitor FXR agonist CCR2/5 inhibitor THR β agonist SCD1 inhibitor PPAR agonist FGF21 analog Pegbelfermin 2 Pegozafermin 2 Efruxifermin 2 Lanifibranor 1 Elafibranor 1 Seladelpar 1 Saroglitaza
Slide 10: Rencofilstat Mode of Action
10 Rencofilstat Mode of Action
Slide 11: Collagen - Core To Fibrotic Diseases
11 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 & funct
Slide 12: Rencofilstat Attenuates Collagen Synthesis by Inhibiting Cyclophilin B
12 Rencofilstat Attenuates Collagen Synthesis by Inhibiting Cyclophilin B Enzyme Activity - "normalizing" disease - associated fibrosis Denotes CypB participation Am J Respir Cell Mol Biol 2022 Apr;66(4):363 - 381. Fighting the Fiber: Targeting Collagen in Lung Fibrosis. Claudia A Staab - Weijnitz C
Slide 13: Cyclophilin Inhibition Produces Consistent Antifibrotic Effects
13 Cyclophilin Inhibition Produces Consistent Antifibrotic Effects Preclinical Models: Proof of Concept » Liver: 8 NASH - related models Human liver slices » Lung Chronic fibrosis Acute injury Human lung slices » Kidney Acute injury » Heart » Skin Antifibrotic Activity Observed in Every Preclinical
Slide 14: Hitting the Right Targets – Fibrosis, Inflammation, and Cell Injury/Death
14 Hitting the Right Targets – Fibrosis, Inflammation, and Cell Injury/Death Rencofilstat Inhibits Three Primary Cyclophilins Rencofilstat blocks Cyclophilin D activation of mitochondrial membrane pores and thereby decreases cell death in injured livers CYTOPROTECTIVE 14 Rencofilstat blocks Cyclophi
Slide 15: Overview of Phase 1 Studies (Completed)
15 Overview of Phase 1 Studies (Completed)
Slide 16: Key Findings Phase 1 Studies Completed
16 Key Findings Phase 1 Studies Completed – D emonstrated a Favorable S afety P rofile » No serious adverse events » No adverse events with dose response » Effective t 1/2 ~ 30 hours » Tmax ss ~ 1 – 2 hours » Ketoconazole increased rencofilstat concentrations ~ 5 - fold » Rencofilstat had no effect
Slide 17: Overview of Phase 2a AMBITION NASH Trial (Completed)
17 Overview of Phase 2a ‘AMBITION’ NASH Trial (Completed)
Slide 18: Phase 2a AMBITION NASH Study Design
18 F2/F3 NASH Subjects (N=43) Rencofilstat 225 mg (n=17) Placebo (n=8) Placebo (n=6) Rencofilstat 75 mg (n=12) OFF - TREATMENT OFF - TREATMENT OFF - TREATMENT OFF - TREATMENT DAYS FASTED ONCE DAILY ORAL DOSING Safety, Tolerability, and Pharmacokinetics Phase 2a ‘AMBITION’ NASH Study Conducted at 10
Slide 19: Phase 2a AMBITION NASH Study: All Primary Endpoints Met
19 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 • Upregulation of genes associated with liver recov
Slide 20: Hepion's Proprietary Artificial Intelligence
20 Hepion’s Proprietary Artificial Intelligence
Slide 21: The Hepion AI-POWR Proprietary Clinical Process
21 Right Patient Right Dose The Hepion AI - POWR Proprietary Clinical Process All Data Generative Neural Net Deep Convoluted Neural Net INPUT OUTPUT
Slide 22: Pre-Clinical Data Informs AI/ML for Clinical Development
22 The Hepion AI - POWR Proprietary Clinical Process Pre - Clinical Data Informs AI/ML for Clinical Development • Biomarkers • Patient Selection • Simulation 1. AI/ML pop PKPD 2. AI/ML QSP 3. AI/ML PBPK AI - POWR PKPD/QSP/PBPK + Multi - omics + QoL + Safety + Deep Learning AI = Digital Biomarkers Re
Slide 23: Illustration of Hepion's AI-POWR for Rencofilstat
23 Illustration of Hepion’s AI - POWR w for Rencofilstat (RCF) * Genes (number) Predictive Genes (number) AUROC Comment 1733 Statistically Significant 25 0.97 Highly Predictive for ProC3 Response Lipids (number) Predictive Lipids (number) AUROC Comment 443 Statistically Significant 25 0.74 Highly Pr
Slide 24: Phase 2 ALTITUDE-NASH Trial (Clinically Complete)
24 Phase 2 ‘ALTITUDE - NASH’ Trial (Clinically Complete)
Slide 25: Phase 2 ALTITUDE-NASH (Liver Function Trial)
25 • Subjects identified from historical biopsy or by meeting AGILE 3+ criteria for F3 • Subjects who complete study will be considered for enrollment into ASCEND - NASH 2b Phase 2 ‘ALTITUDE - NASH’ (Liver Function Trial) Primary Objective: Evaluate the change in hepatic function with once daily (QD
Slide 26: HepQuant SHUNT Test Results Phase ALTITUDE-NASH
26 HepQuant SHUNT Test Results Phase 2 ‘ALTITUDE - NASH’ All Doses 75 mg 150 mg 225 mg % of Subjects with a greater than 2 - point Decrease in DSI 32.8 (20/61) 26.1 (6/23) 15.0 (3/20) 61.1 (11/18) • Absolute Change from Baseline to Day 120 BMI (kg.m - 2 ) - 0.04 0.21 - 0.09 - 0.31 DSI (score) - 0.55
Slide 27: Key NASH Non-Invasive Markers Results
27 All Subjects % Change From Baseline Subjects with Baseline ProC3 ≥ 37.5 ng/ml % Change From Baseline 75 mg rencofilstat n=23 150 mg rencofilstat n=21 225 mg rencofilstat n=21 75 mg rencofilstat n=10 150 mg rencofilstat n=7 225 mg rencofilstat n=6 ALT - 3.37 *,**** - 13.01 *,** - 21.63 *,** - 13.2
Slide 28: Phase 2b ASCEND-NASH Trial (Enrolling)
28 Phase 2b ‘ASCEND - NASH’ Trial (Enrolling)
Slide 29: Phase 2b ASCEND-NASH (Biopsy Trial)
29 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 225 mg qd (n=
Slide 30: Phase 2b ASCEND-NASH Efficacy Endpoints
30 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
Slide 31: Phase 2a HCC Trial (Pending)
31 Phase 2a HCC Trial (Pending)
Slide 32: Phase 2a Advanced Hepatocellular Carcinoma Trial
32 Objectives: » Safety & tolerability » Efficacy: » Disease Control Rate » Duration of response » Overall survival » Objective response rate » 4 - month progression free survival » Pharmacokinetics Safety, Tolerability, Pharmacokinetics, and Efficacy PHASE 2a: Advanced Hepatocellular Carcinoma (HCC
Slide 33: Intellectual Property
2 SSE EIN) Intellectual Property
Slide 34: Intellectual Property Position
34 Long Patent Life with Patent Term Extensions (PTE) Intellectual Property Position Family Status Notes Composition of Matter 54 US & International Issued Patents December 2031 Expiry (December 2036 Expiry with PTE) Assuming 2028 and 2029 NDA submission and approval Composition of Matter (Solid Sta
Slide 35: Summary
2 SSE EIN) Summary
Slide 36: Two Value Drivers Tackling Fibrotic Diseases
36 $ 43.0 M Cash as of 03/31/23 Financials Two Value Drivers Tackling Fibrotic Diseases • 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 • Upcom
Slide 37: Management Team
37 Patrick Mayo, PhD SVP, Clinical Pharmacology and Analytics Joined Isotechnika ( Aurinia ) in 2002 and joined HEPA in 2019. Robert Foster, PharmD, PhD CEO Founded Isotechnika ( Aurinia ) in 1993, and served mostly as CEO & Chairman, until 2014. Joined HEPA in 2016 as CSO and became CEO in 2018. Jo
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 (July 2023) on 6ix