Hepion Pharmaceuticals, Inc. · OTC:HEPA
Hepion Pharmaceuticals — Corporate Update (May 2022)
31 slides from Hepion Pharmaceuticals's corporate update, May 27, 2022
Slide 1: Rencofilstat (CRV431): A liver-targeting drug candidate for NASH and HCC
1 1 Rencofilstat (CRV431): A liver-targeting drug candidate for NASH and HCC Todd M. Hobbs MD – CMO May 27, 2022 smart drug smart technology smart development
Slide 2: Complex and Associated Diseases: The Challenges
2 Complex and Associated Diseases The Challenges New approaches to developing NASH and HCC therapeutics are needed NASH • No FDA drugs approved • Traditional metabolism-regulating drugs largely not efficacious • Multifactorial disease processes – metabolism, inflammation, fibrosis HCC • Poor prognos
Slide 3: Cornerstones of Drug Development for Complex Diseases: Hepion's Strategy
3 Cornerstones of Drug Development For Complex Diseases Hepion’s Strategy PLEIOTROPIC DRUG ACTIONS SAFE, ORAL ONCE DAILY DOSING EXTENSIVE PRECLINICAL TESTING BIOINFORMATICS / AI Targeting multiple disease mechanisms maximizes the opportunity to reverse complex diseases such as NASH and HCC Oral medi
Slide 4: Rencofilstat Drug Candidate for NASH and HCC
4 Rencofilstat Drug Candidate for NASH and HCC • Non-Immunosuppressive Cyclophilin inhibitor – new drug class • Once-daily, oral medication – soft gel capsules • No serious adverse effects • Liver targeting: [liver] > [blood] • Pleiotropic activities in preclinical models of NASH, liver fibrosis, an
Slide 5: Rencofilstat Inhibition of Three Primary Cyclophilins in NASH
5 Rencofilstat Inhibition of Three Primary Cyclophilins in NASH Rencofilstat blocks Cyclophilin A binding to CD147 receptors and thereby decreases pro-inflammatory signaling Rencofilstat blocks Cyclophilin B binding to pro-collagen fibrils and thereby decreases formation and secretion of fibrotic co
Slide 6: Extensive Testing in Disease Models: Preclinical Studies
6 Extensive Testing in Disease Models Preclinical Studies ANIMAL MODELS (mice and rats) TRANSLATIONAL RESEARCH • 8 NASH-related studies - diet and/or chemical-induced liver disease • 4 HCC-related studies - spontaneous tumors and transplant tumor models • 2 diabetes-related studies • 1 acute renal i
Slide 7: Rencofilstat: Multiple Beneficial Properties and State-of-the-Art Artificial Intelligence
7 AI-POWR™ NEURAL NETWORK MACHINE LEARNING BIG DATA DEEP LEARNING MULTI-OMICS NASH Rencofilstat: Multiple Beneficial Properties and State-of-the-Art Artificial Intelligence Hepion’s Artificial Intelligence Understand disease mechanisms Identify biomarkers Track disease progression and regression Pre
Slide 8: Rencofilstat Clinical Programs Advancing in 2022
8 Phase 2B 2022 Program Pre-Clinical Phase 1* Phase 2 Phase 3 NASH (biopsy) IND 142904 HCC IND 158432 NASH (liver function) IND 142904 Rencofilstat Clinical Programs Advancing in 2022 *The Phase 1 program was comprised of Single and Multiple Ascending Doses, and a Drug-Drug Interaction study. Phase
Slide 9: Phase 2a 'AMBITION' NASH Trial (completed)
9 PHASE 2A ‘AMBITION’ NASH TRIAL (completed)
Slide 10: Phase 2a AMBITION NASH Study Design
10 OFF-TREATMENT OFF-TREATMENT OFF-TREATMENT OFF-TREATMENT NASH Subjects - Safety, Tolerability, and Pharmacokinetics PHASE 2a ‘AMBITION’ NASH Study Primary Endpoints: • Safety • Tolerability • Pharmacokinetics Day 1 RANDOMIZATION Day 28 END OF TREATMENT Day 42 END OF TRIAL Rencofilstat 225 mg (n=17
Slide 11: Baseline Characteristics: Phase 2a AMBITION NASH Study
11 Baseline Characteristics PHASE 2a ‘AMBITION’ NASH Study Click to add text Treatment 75mg Placebo 225mg Placebo All subjects N 15 6 17 9 47 Age, years 59.1 (9.9) 61.8 (8.7) 54 (13.3) 61.1 (13.8) 58.0 (11.94) Sex Female 8 53.33% 3 50% 10 58.82% 2 22.22% 23 48.94% Male 7 46.67% 3 50% 7 41.18% 7 77.7
Slide 12: All Primary Endpoints Met: Safety, Tolerability, Pharmacokinetics
12 No Serious Adverse Events Adequate Exposures Anticipated for Efficacy All Primary Endpoints Met – Safety, Tolerability, & Pharmacokinetics (‘PK’) 225 mg QD achieves maximum concentrations > 1000 ng/mL on Day 1 75 mg QD achieves maximum concentrations > 1000 ng/mL on Day 28 Response analysis sugge
Slide 13: Clinical Efficacy Endpoints
13 Clinical Efficacy Endpoints ALT Change from Baseline Pro-C3 Change from Baseline ≥ 17.5 ng/mL -Changes in ALT may indicate drug activity but alone not linked to fibrosis response Loomba, Rohit. "Serum alanine aminotransferase as a biomarker of treatment response in nonalcoholic steatohepatitis."
Slide 14: Additional Exploratory Endpoints Collected
14 • Analysis limited by study duration and number of subjects Addition Exploratory Endpoints Collected: • ELF Score • No significant changes over 28 days • Fibroscan • Small reductions in both Fibrosis (kPa) and Steatosis (dB/m) endpoints for all groups over 28 days – not significant vs. placebo •
Slide 15: Consistent antifibrotic effects observed in all preclinical and clinical models
15 A1BG SDC2 MMP 23B FBN2 EMID1 LOXL1 SERP INB8 ORM1 ICAM1 VCAN CLEC3B PXDN HTRA1 F13A1 COCH COL9A2 COL4A3 EMILIN2 MMRN1 LAMB1 COL6AE LAMA5 ADAM9 LTBP1 TIMP2 COL 26A1 HRNR COLQ HSPG2 C1QB CLU ADAM 19 BCAM MXRA7 PLSCR1 PCSK6 BCHE N1D1 F5 FN1 FBN1 HGF PKLR NID2 COL3A1 LAMB2 LAMC1 IL2RA EGFL7 PLSCR4 US
Slide 16: Phase 2b 'ASCEND-NASH' Trial (Q3 2022)
16 PHASE 2B ‘ASCEND-NASH’ TRIAL (Q3 2022)
Slide 17: Phase 2b ASCEND-NASH Study Design
17 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) Phase 2b ASCEND-NASH F2/F3 NASH Patients (N=336) RANDOMIZED 1:1:1:
Slide 18: Primary and Secondary Efficacy Endpoints
18 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 resolution without
Slide 19: ASCEND-NASH: Many Ongoing Activities Ahead of FPFV
19 • CRO selected with deep NASH experience • Design finalized with 336 subjects • Three rencofilstat doses and matched placebo arm (84 subjects/arm) • 125 sites selected to target a 12-14 month recruitment • Final country selection: US, Germany, France, Italy, Spain, Mexico, Hungary • F4 cohort wil
Slide 20: ASCEND-NASH Interim Analysis Plans
20 • DSMB with extensive NASH experience in place • Hepion blinded from results until DBL • Safety review for any signals and at each of two planned interim analyses • First Efficacy Interim Analysis – After 34 subjects in each cohort (136) pass day 180 visit and have Non-invasive Measures (NIM) ava
Slide 21: Key Considerations Addressed in Phase 2B Design
21 Number of Subjects: • Larger subject numbers allow for higher power for all three doses to better inform selection of a single dose in phase 3 Trial Length: • For fibrosis endpoint, minimum of 12 months is required by FDA • Shorter study may not allow enough time to observe drug effect on fibrosi
Slide 22: Key Considerations Addressed in Phase 2B Design (cont.)
22 Biopsy Procedures: • Numerous trials impacted by high placebo rates and inconsistent reads from single pathologist • Hepion will employ a 2 pathologist read with a 3rd pathologist to resolve any differences • Additional H & E stained slides will be obtained to allow for increased review of tissue
Slide 23: Phase 'ALTITUDE-NASH' Trial (Q3 2022)
23 PHASE 2 ‘ALTITUDE-NASH’ TRIAL (Q3 2022)
Slide 24: ALTITUDE-NASH (Liver Function Trial)
24 Nasdaq: HEPA Phase 2 ‘ALTITUDE-NASH’ (Liver Function Trial) F3 NASH Patients (N=60) RANDOMIZED 1:1:1 Day 1 (Shunt + Labs) Day 120 End of treatment (Shunt + Labs) Rencofilstat 225 mg qd (n=20) Rencofilstat 150 mg qd (n=20) Off - treatment Rencofilstat 75 mg qd (n=20) Day 134 Follow-Up Endpoints: •
Slide 25: HepQuant Shunt Test: An Accurate Measure of Liver Function
25 Nasdaq: HEPA HepQuant Shunt Test: An Accurate Measure of Liver Function
Slide 26: HepQuant DSI Links Liver Dysfunction to Risk for Clinical Outcome
26 Nasdaq: HEPA HepQuant’s products are not FDA-approved and are for investigational use only in clinical trials under FDA IDE guidelines. 26 HepQuant DSI Links Liver Dysfunction to Risk for Clinical Outcome DSI, HepQuant’s proprietary disease severity index HepQuant Research suggests that As Liver
Slide 27: Baseline Results for 1089 Subjects Tested in Studies
27 Nasdaq: HEPA 27 Baseline Results for 1089 Subjects Tested in 26 Studies Lean Controls All Controls Controls/NPKD PLD minimal PSC Slow Progressors PLD massive HCV F0-F2 Mixed NonCirrh Port Hyp NASH & HCV F0-F2 NonCirrh HCV FONTAN NU Obese wo Liver Disease FONTAN PENN Mixed CP A NASH F3 NonCirrh HC
Slide 28: Phase 2a HCC Trial (Q2 2022)
28 PHASE 2A HCC TRIAL (Q2 2022)
Slide 29: Phase 2a HCC Trial: Interim Analysis & Safety Review
29 Interim Analysis & Safety Review If ≤ 1 subject achieves DCR: May stop for futility OR If ≥ 2 subjects achieves DCR: Stage 2 Advanced HCC Subjects - Safety, Tolerability, Pharmacokinetics, and Efficacy PHASE 2a: HEPA-CRV431-209, Simon 2 Stage Design Day 1 RANDOMIZATION Week 16* END of STAGE 1 Wee
Slide 30: Summary: Two Value Drivers
30 Two Value Drivers A Potential Therapy for NASH and HCC AI-Driven, Bioinformatic Platform Summary • Rencofilstat, once-daily oral, multi-modal • Phase 2a NASH trial completed with success • Phase 2 activities initiated for NASH • 12 - month paired biopsy 2B study • 4 - month hepatic function study
Slide 31: Contact Info
CONTACT INFO: Todd M. Hobbs MD Chief Medical Officer Hepion Pharmaceuticals Inc. 399 Thornall Street, First Floor Edison, New Jersey, USA, 08837 Email: thobbs@hepionpharma.com www.hepionpharma.com