8-K
Hepion Pharmaceuticals, Inc. (HEPA)
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, DC 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported):
September 13, 2021
Hepion
Pharmaceuticals, Inc.
(Exact name of registrant as specified in its charter)
| Delaware | 001-36856 | 46-2783806 |
|---|---|---|
| (State or other jurisdiction | (Commission | IRS Employer |
| of incorporation or organization) | File Number) | Identification No.) |
399 Thornall Street, First Floor
Edison, NJ 08837
(Address of principal executive offices)
Registrant’s telephone number, including
area code: (732) 902-4000
(Former name or former address, if changed since last report)
Securities registered pursuant to Section 12(b) of the Act:
| Title of each class: | Trading Symbol(s) | Name of each exchange on which registered: |
|---|---|---|
| Common Stock | HEPA | Nasdaq Capital Market |
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
¨ Written communication pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
¨ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
¨ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
¨ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))
Indicate by check mark whether the registrant is an emerging growth company as defined in as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter). Emerging growth company x
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. x
| Item 7.01 | Regulation FD Disclosure |
|---|
On September 13, 2021, Hepion Pharmaceuticals, Inc. (the “Company”) issued a press release announcing additional efficacy data from its Phase 2a AMBITION clinical trial. . A copy of the press release is furnished as Exhibit 99.1 to this Form 8-K. In addition, the Company plans to make a presentation to investors at 8:30 am ET on September 13, 2021 with the Corporate Presentation furnished as Exhibit 99.2 to this Form 8-K.
In accordance with General Instruction B.2 of Form 8-K, the information in this Current Report on Form 8-K is being furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liabilities of that Section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended.
| Item 9.01<br><br><br><br>****<br><br><br><br>(d) Exhibits | Financial Statements and Exhibits |
|---|---|
| 99.1 | Hepion Pharmaceuticals, Inc. Press Release dated September 13, 2021 |
| 99.2 | Corporate Presentation |
| 104 | Cover Page Interactive Data File (formatted as inline XBRL and contained<br>in Exhibit 101 |
SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, the Registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
Dated: September 13, 2021
| HEPION PHARMACEUTICALS, INC. | |
|---|---|
| By: | /s/ Robert Foster |
| Robert Foster | |
| Chief Executive Officer |
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Exhibit 99.1
Additional Data from HepionPharmaceuticals’ Phase 2a ‘AMBITION’ Trial Further Strengthens CRV431 Clinical Profile and Paves Way for Initiationof Phase 2b ‘ASCEND-NASH’ Clinical Program
| · | Pro-C3 and ALT reductions point to anti-inflammatory and antifibroticeffects of CRV431 |
|---|---|
| · | PK-PD models successfully predict early reductions in Pro-C3 and ALT |
| --- | --- |
| · | Hepion’s proprietary AI-POWR™ and machine learning accuratelypredict CRV431 responders |
| --- | --- |
| · | Anti-fibrotic gene expression signature revealed in bioinformatic analyses |
| --- | --- |
| · | Phase 2b activities initiated |
| --- | --- |
EDISON,N.J.****, September 13 ,2021 - Hepion Pharmaceuticals, Inc. (NASDAQ:HEPA), a clinical stage biopharmaceutical company focused on Artificial Intelligence (“AI”)-driven therapeutic drug development for the treatment of non-alcoholic steatohepatitis (“NASH”) and liver disease, today announced additional efficacy data from its Phase 2a AMBITION clinical trial.
AMBITION, a multicenter, randomized, placebo controlled, single-blind Phase 2a trial, enrolled 43 NASH patients. The trial was designed to investigate once daily oral administration of CRV431 at doses of 75 mg (n=12) and 225 mg (n=17) administered as soft gelatin capsules to presumed F2 and F3 NASH subjects for 28 days, followed by a 14-day observation period for safety.
As previously reported, all primary endpoints of the AMBITION NASH trial (safety, tolerability and pharmacokinetics) were met.
Today, Hepion reports additional data on biomarkers, alanine aminotransferase (“ALT”) and N-terminal type III collagen pro-peptide (“Pro-C3”), as well as advanced pharmacologic and bioinformatic analyses that indicate CRV431 efficacy in treating NASH patients.
Once-daily 225 mg dosing of CRV431 decreased mean Pro-C3 levels by 7.9% (-2.1 ng/ml) and 22.4% (-11.6 ng/ml) at days 28 and 42, respectively, in subjects stratified for baseline Pro-C3 levels greater than 17.5 ng/mL (n=7). Pro-C3 levels greater than 15-20 ng/ml are generally accepted to represent active NASH disease activity and the primary patient population for treatment by many NASH drug candidates. In contrast to the 225 mg CRV431 cohort, placebo treatment similarly stratified by baseline Pro-C3 greater than 17.5 ng/mL (n=9) resulted in a mean increase of 3.5% (0.7 ng/ml) and a mean decrease of 4.7% (-1.6 ng/ml) at days 28 and 42, respectively. The same Pro-C3 baseline stratification for the 75 mg CRV431 dose (n = 11) resulted in a mean decrease in Pro-C3 of 9.1% by Day 42, indicating a dose-dependent effect. When stratified for baseline Pro-C3 levels greater than 15.0 ng/mL, 225 mg once daily CRV431 (n=9) reduced mean levels by 4.1% and 14.3% at days 14 and 28 days, respectively, compared to a mean increase of 1.5% and a decrease of 8.8% in the placebo group (n=9) at days 28 and 42, respectively. The reductions in Pro-C3 produced by CRV431 treatment mirror the previously reported dose-dependent declines in ALT.
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Importantly, more detailed analyses of the AMBITION trial data using Hepion’s proprietary AI-POWR™ platform provided further evidence of CRV431 efficacy in the treatment of NASH. First, pharmacokinetic-pharmacodynamic (“PK-PD”) analyses were able to generate robust models that could predict whether individual patients would show reductions in ALT and Pro-C3 based on CRV431 exposure, baseline ALT, Pro-C3, and other demographic and clinical measurements. Second, analysis of full-genome, ribonucleic acid (RNA) sequencing data (“transcriptomics”) from the patients revealed that CRV431 treatment produced changes in gene expression that were consistent with anti-fibrotic effects. Labelled as a collagen-related gene regulatory network, the CRV431-induced changes in gene expression included six key collagen isoforms, and many other structural and enzymatic constituents of the fibrotic matrix. In similarity to the PK-PD models for ALT and Pro-C3, supervised machine learning analyses were able to categorize patients as responders or non-responders based on their transcriptome responses to CRV431 treatment.
“The decline in Pro-C3 that was observed in the AMBITION trial puts us well within the range of NASH data published by other companies with later-stage NASH drug candidates,” said Hepion’s Chief Medical Officer, Todd Hobbs MD. “But notably, these declines in Pro-C3 with CRV431 occurred in only 4 weeks, compared to declines with other agents, where the changes occurred over several months.”
“These biomarker findings offer us two important insights. First, CRV431 has sustained effects, as evidenced by the Pro-C3 changes at day 42. The long terminal half-life of CRV431 can explain these findings and, in fact, circulating blood concentrations of CRV431 are present at day 42, even though drug administration stopped on day 28,” said Hepion’s Senior VP, Clinical Pharmacology & Analytics, Patrick Mayo, PhD.
“Second, the most recent data generated from our AMBITION trial has allowed us to put our machine learning and proprietary AI-POWR™ to work,” continued Dr. Mayo. “We have been able to construct models that may predict a priori who will respond to CRV431. In this context, we believe that we can predict how much of a reduction in ALT and Pro-C3 may be expected in any given subject, even as early as the first administered dose of CRV431. Indeed, we demonstrated that this works very elegantly in predicting ALT and Pro-C3 responses of subjects in the AMBITION trial with a high degree of accuracy. The PK-PD modeling also demonstrated great accuracy in predicting clinical response, as indicated by modeling diagnostics including predicted versus observed plots. Moreover, we have used our transcriptomics to investigate and construct a network of genes that gave us a very consistent picture of antifibrotic effects when CRV431 was tested in the latest clinical program. Interestingly, we also looked at these same genes in our preclinical animal models, our cellular assays, and our studies of human liver slices, and we observed the same findings with the collagen-related gene network.”
“These powerful tools allow us to investigate CRV431 in silico which should allow us to simulate future trials before conducting them in the clinic. The more data we feed into our AI, the more the AI will learn. This, in turn, should enable us to be very precise in this very heterogenous NASH disease. Our AI, therefore, is a very powerful and important tool. The Phase 2a study provided a treasure-trove of information that has allowed us to fine-tune our AI and adjust the design of our planned Phase 2b study,” concluded Dr. Mayo.
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Robert Foster, PharmD, PhD, Hepion’s CEO, commented, “Dr. Mayo and his team are conducting truly ground-breaking work. Many of us at Hepion have been working on cyclophilin inhibitor drug development for the better part of three decades. But, any kind of drug development is inherently risky, especially when relying solely on traditional tools. We believe we may now be able to mitigate a great deal of development risk with the AI and machine learning tools developed and utilized by our clinical pharmacology group. The fact that our team has been able to identify early changes in important biomarkers and in collagen genes, while developing predictive responder analyses, should help propel us in the NASH drug development space. Ultimately, our goal is to employ our models to optimize trial design, efficiency, cost, and outcomes, while mitigating development risk. In many ways, we believe that what we are doing is unprecedented in NASH drug development. We are confident that the AMBITION trial and our detailed analyses set the stage for success in the upcoming and larger Phase 2b program called, “ASCEND-NASH”.”
The full AMBITION analysis will be presented by Dr. Stephen Harrison at the upcoming AASLD “The Liver Meeting”, in early November 2021.
Conference Call &Webcast Details
Hepion is pleased to invite all interested parties to participate in a conference call today at 8:30 a.m. ET, during which both the Phase 2a AMBITION trial data and the design of the planned Phase 2b ASCEND- will be discussed. To participate telephonically, please dial (855) 493-3481 (U.S.) or (929) 517-0949 (international), conference ID 3568976, approximately 10 minutes prior to the start time. A live, listen-only webcast of the conference call, which will include accompanying slides, can be accessed by visiting the “Events” page of the “Investors” section at www.hepionpharma.com. An archive of the webcast will be available for approximately 90 days following the conclusion of the conference call.
About Hepion Pharmaceuticals
The Company's lead drug candidate, CRV431, is a potent inhibitor of cyclophilins, which are involved in many disease processes. CRV431 is currently in clinical-phase development for the treatment of NASH, with the potential to play an important role in the overall treatment of liver disease - from triggering events through to end-stage disease. CRV431 has been shown to reduce liver fibrosis and hepatocellular carcinoma tumor burden in experimental models of NASH; and has demonstrated antiviral activities towards HBV, HCV, and HDV through several mechanisms, in nonclinical studies.
Hepion has created a proprietary AI platform, called AI-POWR™, which stands for Artificial Intelligence - Precision Medicine; Omics (including genomics, proteomics, metabolomics, transcriptomics, and lipidomics); World database access; and Response and clinical outcomes. Hepion intends to use AI-POWR™ to help identify which NASH patients will best respond to CRV431, potentially shortening development timelines and increasing the delta between placebo and treatment groups. In addition to using AI-POWR™ to drive its ongoing NASH clinical development program, Hepion will use the platform to identify additional potential indications for CRV431 to expand the company's footprint in the cyclophilin inhibition therapeutic space.
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Forward Looking Statements
Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimated,” and “intend,” among others. These forward-looking statements are based on Hepion Pharmaceuticals’ current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, substantial competition; our ability to continue as a going concern; our need for additional financing; uncertainties of patent protection and litigation; risks associated with delays, increased costs and funding shortages caused by the COVID-19 pandemic; uncertainties with respect to lengthy and expensive clinical trials, that results of earlier studies and trials may not be predictive of future trial results; uncertainties of government or third party payer reimbursement; limited sales and marketing efforts and dependence upon third parties; and risks related to failure to obtain FDA clearances or approvals and noncompliance with FDA regulations. As with any drug candidates under development, there are significant risks in the development, regulatory approval, and commercialization of new products. There are no guarantees that future clinical trials discussed in this press release will be completed or successful, or that any product will receive regulatory approval for any indication or prove to be commercially successful. Hepion Pharmaceuticals does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in Hepion Pharmaceuticals’ Form 10-K for the year ended December 31, 2020 and other periodic reports filed with the Securities and Exchange Commission.
For further information, please contact:
Stephen Kilmer
Hepion Pharmaceuticals Investor Relations
Direct: (646) 274-3580
skilmer@hepionpharma.com
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Exhibit 99.2
INVESTOR UPDATE September 13 , 2021 Nasdaq: HEPA
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,” “intend,” “anticipate,” believe,” “estimate” and “continue” or similar words . You should read statements that contain these words carefully because they discuss future expectations and plans, which contain projections of future results of operations or financial condition or state other forward - looking information . Such statements are only predictions and our actual results may differ materially from those anticipated in these forward - looking statements . We believe that it is important to communicate future expectations to investors . However, there may be events in the future that we are not able to accurately predict or control . Factors that may cause such differences include, but are not limited to, those discussed under Risk Factors in our periodic reports filed with the Securities and Exchange Commission, including the uncertainties associated with product development, the risk that products that appeared promising in early clinical trials do not demonstrate safety and efficacy in larger - scale clinical trials, the risk that we will not obtain approval to market our products, risks associated with delays, increased costs and funding shortages caused by the COVID - 19 pandemic ; the risks associated with dependence upon key personnel and the need for additional financing . We do not assume any obligation to update forward - looking statements as circumstances change . This presentation does not constitute an offer or invitation for the sale or purchase of securities or to engage in any other transaction with Hepion Pharmaceuticals or its affiliates . The information in this presentation is not targeted at the residents of any particular country or jurisdiction and is not intended for distribution to, or use by, any person in any jurisdiction or country where such distribution or use would be contrary to local law or regulation . Statements Forward - Looking
3 Executive Management Introduction to • Dr. Robert Foster, Chief Executive Officer • Dr. Todd Hobbs, Chief Medical Officer • Dr. Daren Ure , Chief Scientific Officer • Dr. Patrick Mayo, Senior Vice President, Clinical Pharmacology & Analytics • Mr. John Cavan , Chief Financial Officer
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5 NAFLD n on - a lcoholic f atty l iver d isease • “Fatty liver” disease associated with obesity, diabetes, hypertension, etc. • Approx. 25% of global population (up to 100 million in U.S.) NASH leads to cirrhosis, liver cancer (HCC), end stage liver disease, and death NASH n on - a lcoholic s teato h epatitis • A more severe form of NAFLD, with inflammation and liver scarring (fibrosis) • 1.5 – 6.5% globally (up to 17 million in U.S.) NASH is a Healthcare Crisis Large cost to healthcare system No drugs are approved for treating NASH Soon to be lead reason for liver transplantation NASH Drug Development The Need and Opportunity -
6 Through Cyclophilin Inhibition Multiple Therapeutic Actions Cyclophilin A (cytosol and secreted) Secreted from injured cells and acts as proinflammatory cytokine by binding to CD147 Cyclophilin B (endoplasmic reticulum) Promotes fibrotic scarring by controlling collagen production CRV431 Non - immunosuppressive analog of cyclosporine A Pan - Cyclophilin Inhibitor (Ki ≈ 1 nM ) Cyclophilin D (mitochondria) Regulates mitochondrial metabolism Promotes mitochondrial pore opening leading to mitochondrial and necrotic cell death INFLAMMATION x CD147 pro - inflammatory receptors x Procollagen x x FIBROTIC SCARRING Cyp A Cyp B Cyp D Mitochondrial pores (mPT) x NECROTIC CELL DEATH x
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8 SAFETY TOLERABILITY PHARMACOKINETICS FIBROSCAN BIOMARKERS Day 1 Randomization * Day 28 End of treatment Day 42 End of trial CRV431 225 mg (n=17) Placebo (n=8) O ff - treatment O ff - treatment F2/F3 NASH Patients (N=43) Fasted Oral Dosing Day 29 Placebo (n=6) O ff - treatment CRV431 75 mg (n=12) O ff - treatment NASH Subjects - Safety, Tolerability, and Pharmacokinetics PHASE 2a AMBITION Study * Randomized assignment 2:1 CRV431. AMBITION: A Phase 2a, M ulti - center, Single - B l i nd, Placebo - Controlled, Proof of Concept Study to Evaluate the Safety & T olerab i lity of CRV431 Dosed O nce Daily in N ASH Induced F2 & F3 Subjects
9 Baseline Demographics Phase 2a: AMBITION Study CRV431 75 mg (n = 12) CRV431 225 mg (n = 17)* Pooled Placebo (n = 14) Age (years) Mean (SD) 61.9 (8.0) 54.0 (13.3) 61.1 (12.0) Range 48 - 72 27 - 71 27 - 72 Gender Male n (%) 7 (58.3) 7 (41.2) 9 (64.3) Female n (%) 5 (41.7) 10 (58.8) 5 (35.7) Race White n (%) 11 (91.7) 17 (100) 13 (92.9) Hispanic n (%) 1 (8.3) 1 (7.1) 2 (4.7) BMI ( kg/m 2 ) Mean (SD) 35.0 (8.0) 37.7 (6.4) 38.9 (8.8) Range 25 - 53 28 - 53 29 - 57 *1 - Covid Patient
10 Dose AE Term Severity Outcome Relation to Study Drug Placebo Body Aches Moderate Ongoing Possible 75 mg Sensation of Heart Beating Strongly Moderate Resolved Probable 75 mg Constipation Mild Resolved Probable 225 mg Diarrhea Mild Resolved Probable 225 mg Constipation Severe Resolved Probable 225 mg Fatigue Mild Resolved Probable 225 mg Lips Tingling Mild Resolved Probable 225 mg Constipation Mild Ongoing Probable 225 mg Increased Weight Mild Ongoing Probable 225 mg Headache Mild Ongoing Probable 225 mg Diarrhea Mild Ongoing Probable Well Tolerated Primary Endpoint: Safety – No Serious Adverse Events Note: all events we categorized as not serious.
11 Adequate Exposures Anticipated for Efficacy Primary Endpoint: Pharmacokinetics –
IMPORTANCE OF BASELINE ALT & PRO - C3 1. NASH subjects may have advanced disease (F3 or higher), but have ‘NORMAL’ ALT or Pro - C3 2. Elevation of ALT suggests active inflammation in the liver 3. Elevation of ProC3 suggests active formation of collagen 4. Elevated baseline biomarkers suggest ACTIVE disease compared to CHRONIC disease 5. For evaluation of pharmacodynamic effect, it is preferable to have ACTIVE disease Verma, Siddharth, et al. "Predictive value of ALT levels for non - alcoholic steatohepatitis (NASH) and advanced fibrosis in non - alcoholic fatty liver disease (NAFLD)." Liver International 33.9 (2013): 1398 - 1405.
13 ALT, Area Under the Curve (AUC) p = 0.0493 ANOVA % Change From Baseline Dose Placebo 75 mg 225 mg Mean ± SD - 6.1 ± 13.3 - 18.4 ± 25.8 - 21.1 ± 21.0 Median (Range) - 5.2 ( - 23.8 – 13.8) - 15.9 ( - 58.3 – 17.2) - 20.0 ( - 81.5 – 11.1) N (%) Reduction ALT 7/14 (50%) 8/12 (67%) 13/15 (87%) AUC of ALT (IU*D/L) 1465.1 ± 810.9 1190.5 ± 712.1 859.9 ± 387.0* *p < 0.05 versus placebo
14 Volume (L) Absorption Ka (h - 1 ) Elimination (k h - 1 ) Inhibitory Imax Model - Baseline (ALT) IC50:Half - Maximal Inhibition • Assess patient characteristics (COVARIATES) that help refine prediction of both PK and PD • Final Covariate Model: ↑Cholesterol ~ ↓Absorption ↑Baseline AST ~ ↑Effect ↑Lean Body Weight ~ ↓ IC50 • Confirms Concentration - Effect for ALT • Allows simulations for Phase 2b and Phase 3 PK PD Observed vs Predicted: ALT PK - PD Model Successfully Predicts ALT
15 ALT Responder Analysis By Flexible Discriminate Analysis: Misclassification Error = 0.04255 ALT Non - Responder Responder Unknown Age 61.6 57.2 60.6 BMI 40.2 36.1 36.1 Sex > Male > Female 2.0 Day 1, 2h 284.2 596.5 264.8 Day 14, 0h 483.4 882.5 667.9 Day 28, 0h 557.9 1040.7 706.0 Day 28, 2h 724.0 1243.0 870.1 BASO 0.0677 0.0741 0.0540 CPK 128.8 100.0 114.4 CREAT 0.700 0.683 0.700 GLUCOSE 117.3 134.8 109.4 PLT 228.5 235.7 237.8 TRIGs 164.5 174.6 169.0 WBC 7.2 7.6 6.5 CHOL 160.5 176.5 188.2 AST 42.8 50.4 75.6 ALT 51.8 59.8 79.6 A1C 6.7 6.9 6.5 DX_Y = Day X, Y - Hour CRV431 Concentration
16 FDA:ALT Responder Analysis 1 = non - responder 2 = responder 3 = no baseline
17 Note stratification by Baseline Example: Resmetirom Harrison, Stephen A., et al . Lancet 2019; published online Nov 11. http:// dx.doi.org /10.1016/S0140 - 6736(19)32517 - 6. Note stratification by Baseline
18 Released N - terminal Pro - Peptide of Type III Collagen Pro - C3: Collagen Formation ProC3 indicates ACTIVE FIBROSIS and pharmacodynamic modulation Source: HEPA:CRV431 - 201: Phase2A Trial on NASH FUNCTION: ACTIVE FIBROSIS
19 Volume (L) Absorption Ka (h - 1 ) • No Covariates were required to predict both PK and PD. • Final Covariate Model: PK 1 - Compartment PD: Inhibitory Imax Model with Baseline Pro - C3 • Quantitative Concentration - Effect for Pro - C3 • Allows simulation of Phase 2b and Phase 3 trials PK PD Observed vs Predicted: Pro - C3 PK - PD Model Successfully Predicts Pro - C3 Elimination (k h - 1 ) Inhibitory Imax Model - Baseline (Pro - C3) IC50:Half - Maximal Inhibition
20 Pro - C3 Responder Analysis By Mixture Discriminate Analysis: Misclassification Error = 0.02128 Pro - C3 Non - Responder Responder Sex >Male >Female Age 60.4 55.4 BMI 36.3 39.1 CHOL 177.9 163.5 TRIGs 181.0 150.1 AST 45.6 62.5 ALT 55.3 69.0 PLT 239.8 221.3 Day 1, 2h 449.8 528.2 Day 14, 0h 732.3 785.5 Day 28, 0h 828.1 964.2 Day 28, 2h 1012.8 1160.0 BASO 0.0697 0.0713 WBC 7.6 7.1 GLUCOSE 128.3 124.9 A1C 6.9 6.5 CPK 105.5 118.1 CREAT 0.666 0.740 DX_Y = Day X, Y - Hour CRV431 Concentration
21 PRO - C3 CRV431 Responder Analysis 1=Non - Responder 2=Responder 1 = non - responder 2 = responder
AI - POWR TM (n=6 out of 12 total subjects) • Assessed patient demographics and baseline labs • AST/ALT, C6M, TIMPs, MMP Responders • CRV431 concentration > 800 ng / mL Potential Genomic Biomarke r Responder Panel • 12/12 Active Subjects AI - machine learning has selected responders The AI is still training to decrease heterogeneity and predict a priori who will respond to CRV431 22 Standard Differentially Expressed Genes - DESEq2 Phase 2a: Transcriptomics & AI
23 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 USH2A MMP8 CLUL1 TMEM256 - PLSCR3 PKM ACHE Clinical Collagen - Related Gene Regulatory Network collagen - containing extracellular matrix collagen binding collagen type IV trimer collagen type IX trimer collagen fibril organization collagen catabolic process Consistent antifibrotic effects observed in all preclinical and clinical models
24 Phase 2a Study Conclusions • Phase 2a study provided safety and exposure data in NASH subjects • Phase 2a study demonstrated signals of efficacy (inflammation and fibrosis) within 4 weeks • Phase 2a study provided post - hoc responder analysis data to further train AI - POWR for a priori responder analysis • Data from the Phase 2a was utilized to add a 150 mg dose cohort for the Phase 2b protocol and to adjust inclusion criteria (Pro - C3 > 14 ng/mL).
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26 Primary Objective: Evaluate the efficacy and safety of once - daily 75mg, 150 mg, and 225 mg doses of CRV431 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 1:1:1:1 Day 1 12 Months End of treatment CRV431 225 mg qd (n=84) Placebo (n=84) CRV431 150 mg qd (n=84) 13 Months End of trial Data to inform phase 3 trial patient selection and biomarkers for analysis. AI - POWR identification of biomarkers of CRV431 response Off - treatment follow - up CRV431 75 mg qd (n=84) Interim Analysis Interim Analysis • Targeted 12 – 14 - month recruitment period will include 86 US sites and 39 ex - US sites (Canada, France, UK, Spain, Germany, Italy, Belgium, Australia) • Up to 20 additional F4 subjects discovered during screening will be enrolled in an open label cohort dosed with 225mg CRV431 • Power = 90% to distinguish each dose level
27 Primary Efficacy Endpoint: Superiority of CRV431 (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 worsening of fibrosis Secondary Efficacy Endpoints: Superiority of CRV431 (75mg, 150 mg, 225 mg) compared to placebo on histology at month 12 relative to screening by assessing: • Proportion of subjects with improvement in fibrosis by at least 1 stage (NASH CRN system), regardless of effect on NASH • Proportion of subjects with improvement in fibrosis by at least 2 stages (NASH CRN system), regardless of effect on NASH • Proportion of subjects with improvement in fibrosis by at least 2 stages (NASH CRN system) AND no worsening of NASH. By at least 1 stage regardless of the effect on NASH Endpoints
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29 Financial Position as of June 30, 2021 Cash - $110.1 MM Working Capital - $106.6 MM No Debt Common Shares Outstanding - 76,225,245
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31 • CRV431, once - daily oral, multi - modal • Cyclophilin inhibition allows for several benefits, including anti - fibrotic, anti - inflammatory, cytoprotective • Phase 2a NASH trial completed with success • Safe, well - tolerated, PK defined • Efficacy signals in only 4 weeks • Phase 2b activities initiated • Hepion’s Proprietary Artificial Intelligence Platform (AI - POWR Ρ ) • Core scientific team with >100 years collective cyclophilin expertise • Core scientific team discovered and developed voclosporin (currently marketed) • Robust IP $ 110.1 M as of 6/30/21 CASH TWO VALUE DRIVERS A Therapy for NASH with indications for several other conditions AI - Driven, Bioinformatic Platform Summary 31 76.2 M common shares outstanding