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): June 11, 2019

 

ContraVir 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

 

CTRV

 

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:

 

o  Written communication pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

 

o  Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

 

o  Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

 

o  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.

 

ContraVir Pharmaceuticals, Inc. (the “Company”) is furnishing this Current Report on Form 8-K in connection with the disclosure of information, in the form of the textual information from a PowerPoint presentation (the “Presentation”) to be used by the Company in various investor meetings. This information may be amended or updated at any time and from time to time through another Current Report on Form 8-K, a later company filing or other means. A copy of the Presentation is furnished herewith as Exhibit 99.1 and is incorporated into this Item 7.01 by reference.

 

The information furnished in this Item 7.01, including Exhibit 99.1, is being furnished and shall not be deemed to be “filed” for the 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 to be incorporated by reference into any registration statement or other document filed pursuant to the Securities Act of 1933, as amended, except as shall be expressly set forth by specific reference in such filing.

 

The Company does not have, and expressly disclaims, any obligation to release publicly any updates or any changes in our expectations or any change in events, conditions, or circumstances on which any forward-looking statement in the Presentation is based.

 

Item 9.01. Financial Statements and Exhibits.

 

(d)         Exhibits

 

Exhibit
Number

 

Description

 

 

 

99.1

 

ContraVir Pharmaceuticals, Inc. Presentation, dated June 2019

 

2


 

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: June 11, 2019

 

 

CONTRAVIR PHARMACEUTICALS, INC.

 

 

 

By:

/s/ Robert Foster

 

 

Robert Foster

 

 

Chief Executive Officer

 

3


Exhibit 99.1

1 Corporate Presentation • 2019 Nasdaq: CTRV Nasdaq: CTRV

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Forward-Looking Statements 2 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,” “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, 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 ContraVir 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. Nasdaq: CTRV

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Snapshot A Liver Disease Company Committed to developing pleiotropic drug therapy for treatment of chronic liver diseases, including NASH (non-alcoholic steatohepatitis) and other liver diseases (HBV, HCV, HDV) 3 “…Nearly 45% of all deaths in the developed world are attributed to some type of chronic fibroproliferative disease. Therefore, the demand for antifibrotic drugs that are both safe and effective is likely to be enormous...” – J Clin Invest. 2007 Mar;117(3):524-9. Common and unique mechanisms regulate fibrosis in various fibroproliferative diseases. Wynn TA https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1804380/ Nasdaq: CTRV

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Corporate Overview Product CRV431: Novel, high-potency, cyclophilin inhibitor that targets multiple stages of liver disease, including NASH 4 • • • • • • Anti-fibrotic, anti-viral, and anti-cancer properties (pleiotropic) Strong preclinical proof of concept Strong safety profile in preclinical and Phase 1 clinical studies Orally active, once daily Robust IP Built upon 30 years' experience in this very specific field of chemistry • Core team that founded Aurinia Pharmaceuticals, and discovered and developed voclosporin (phase 3), and other autoimmune indications (Nasdaq:AUPH) is same core team that has discovered and is developing CRV431 Nasdaq: CTRV

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CRV431 Structure 5 A cyclic undecapeptide, built off our voclosporin experience AA1 chemical modification decreases immunosuppression R1 HO AA3 chemical modification enhances cyclophilin binding O O H N N R2 N N N O O O O O O N H N H N AA1 chemical modification increases immunosuppression N CH2 N H N O O O CRV431 HO O O H N N N N N O O O O O O N H N H N N N H N O O O Voclosporin Nasdaq: CTRV

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Development Phase 6 Discovery Phase 1 Phase 3 CRV431 Preclinical Phase 2 • • IND for HBV – Phase 1 Single Ascending Dose completed IND for HBV – Multiple Ascending Dose initiation expected, Q2, 2019 in patients IND for NASH – Expected approval, Q3, 2019 • “In our large combined tertiary center cohorts, patients with concomitant NASH and CHB (chronic hepatitis B) had more advanced fibrosis, and shorter time to development of liver-related outcomes of death, compared to patients with CHB alone. Among patients with advanced fibrosis, superimposed NASH predicted poorer clinical outcomes in our cohort” H.S.J. Choi et al., Hepatology, 68(1, suppl.), 2018 Nasdaq: CTRV

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CRV431 in NASH Cyclophilin Inhibitors 7 Target Multiple Liver Disease Stages INJURY/STEATOSIS INFLAMMATION Suppress pro-inflammatory pathways mediated by extracellular cyclophilin A binding to CD147 FIBROSIS Reduce collagen production from hepatic stellate cells Reduce collagen hydroxyl-ation and crosslinking Increase collagenase CIRRHOSIS/CANCER • • Antiviral activity (HBV, HCV, HDV, HIV-1) Suppress cell death by inhibiting mitochondrial pore regulator, cyclophilin D • • Block cancer cell adaptation to hypoxia Suppress metastasis-related gene expression Reduce cell proliferation • • • • • NAFLD/ NASH Stellate cell activation Collagen deposition (scarring) Cellular transformation and metastasis Cell injury/death Alcohol Viral Hepatitis (HBV/HCV/HDV) Inflammatory cell infiltration/activation Nasdaq: CTRV

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CRV431 Anti-Inflammatory/Steatosis 8 Efficacy in STAM Murine NASH Model 3, 6, or 11 weeks oral CRV431 treatment p = 0. 0 3 10 10 10 8 8 8 6 6 6 4 4 4 2 2 2 0 0 0 20 m g / k g / da y C R V 431 V e h ic le 5 m g / k g / da y C R V 431 V e h ic le 50 m g / k g / da y C R V 431 V e h ic l e 50 m g / k g / da y C R V 431 STUDY #1: Stelic Institute (Japan) STUDY #2: Scripps Institute (USA) STUDY #3: Scripps Institute (USA) 3-week, oral CRV431 treatment 6-week, oral CRV431 treatment 11-week, oral CRV431 treatment Nasdaq: CTRV N A FLD S c or e ( s t ea t o s is + i nf lam m a t i on + ba ll ooni ng ) N A FLD S c or e ( s t ea t o s is + i nf lam m a t i on + ba ll ooni ng ) N A FLD S c or e ( s t ea t o s is + i nf lam m a t i on + ba ll ooni ng )

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CRV431 Anti-Fibrotic 9 Efficacy in STAM Murine NASH Model 3, 6, or 11 weeks oral CRV431 treatment p < 0. 0 1 p = 0.014 p = 0. 0 3 p = 0. 0 1 2 . 5 5 4 6 2 . 0 4 3 4 1 . 5 3 2 1 . 0 2 2 1 0 . 5 1 0 . 0 0 0 0 20 m g / k g / da y C R V 431 V e h ic le 5 m g / k g / da y C R V 431 Vehicle 50 mg/ kg/day CRV431 50 m g / k g / da y C R V 431 50 m g / k g / da y C R V 431 V e h ic l e V e h ic l e STUDY #1: Stelic Institute STUDY #2: Scripps Institute STUDY #3: Scripps Institute STUDY #4: Scripps Institute 3-week, oral CRV431 6-week, oral CRV431 11-week, oral CRV431 10-week, oral CRV431 (late disease stage) Nasdaq: CTRV S ir i u s r e d - p o s i t iv e f ib r o s is ( % o f s am p l ed ar ea ) S ir i u s r e d - p o s i t iv e f ib r o s is ( % o f s am p l ed ar ea ) S ir i u s r e d - p o s i t iv e f ib r o s is ( % o f s am p l ed ar ea ) Sirius red-positive fibrosis (%of sampled area) n s

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CRV431 Anti-Fibrotic 10 Efficacy in Carbon Tetrachloride Murine Model P = 0.008 6 weeks carbon tetrachloride (i.p.) + drug treatment (oral): P = 0.32 • • • • Vehicle CRV431 50 mg/kg/day Obeticholic acid (OCA) 10 mg/kg/day CRV431 50 mg/kg/day + OCA 10 mg/kg/day 4 3 Assess liver fibrosis by Sirius Red staining of liver sections 2 RESULTS • 1 Second model showing reduction in liver fibrosis by CRV431 (43% decrease versus vehicle) Lead late-stage NASH drug candidate, OCA, did not demonstrate a statistically significant antifibrotic effect in this CCl4 murine model conducted by us • 0 Nasdaq: CTRV Sirius red-positive fibrosis (%of sampled area) P = 0.005 P = 0.03 P = 0.05

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CRV431 for Liver Disease 11 Liver morphology in NASH Mice Vehicle treatment, 11 weeks (enlarged fatty liver) CRV431 treatment, 50 mg/kg, PO, 11 weeks (normalized liver) Nasdaq: CTRV

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Putative Anti-Fibrotic Mechanism of Action 12 Collagen reduction Nasdaq: CTRV R e la tiv e ex p r es s ion v s D M S O L ysyl O x i d ase ( L O X ) G en e E xp r ess i o n 2 .5 2 .0 1 .5 1 .0 0 .5 0 .0 •Role of cyclophilins in formation of collagen involved in at least two ways: 1.Peptidyl prolyl isomerase (cyclophilin) activity confers CIS-TRANS geometry of procollagen (protein folding) 2.Hydroxylation of proline and lysine in procollagen are necessary steps for covalent intermolecular cross-linking resulting in formation of the triple helix of collagen •In vitro studies demonstrated that CRV431 reduced expression of lysyl oxidase (LOX) genes involved in fibrotic collagen formation •Reduction in LOX gene expression observed with CRV431 is dose-dependent •As a comparison, obeticholic acid (OCA), a farnesoid X receptor agonist has no effect on LOX gene expression

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CRV431 Anti-Cancer 13 Activity in NASH Mice 10 weeks oral CRV431 treatment T u m o r S c o r e ( n u m b er x p = 0. 02 si z e ) N um be r of Tum or N odu l e s p = 0. 05 15 Score = 0 (no nodules) 7 6 5 10 4 3 Score = 7 (many large nodules) 5 2 1 0 0 V e h ic le C R V 431 V e h ic le C R V 431 STUDY: Scripps Research Institute (USA) • • 10-week, oral CRV431 treatment 44% reduction in tumor number; 52% reduction in tumor score, reflecting number and size of tumors Nasdaq: CTRV N um be r o f n od ul es p er liv er H C C nod ul e s c or e

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Single Ascending Dose (SAD) Study (CTRV-CRV431-101) Objectives 14 • • To evaluate the safety and tolerability of single oral doses of CRV431 at increasing dose levels To evaluate the pharmacokinetics of CRV431 Design • Randomized, Partially blinded, Placebo-controlled, sequential SAD Study in healthy volunteers CRV431375 mg CRV431225 Healthy Subjects CRV43175 mg Nasdaq: CTRV SAD CRV431525 mg 2 (24 CRV431; 8 Placebo) mg N = 3

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CRV431 15 Mean Pharmacokinetic Parameters (SD) • • Drug exposure is linear up to 375mg (r2=0.914) Pharmacokinetic profile supports once daily dosing. Nasdaq: CTRV Dose Tmax, h (range) Cmax, ng/mL (SD) AUC0-inf, ng*h/mL (SD) t½, h 75 mg 4 (2-10)334±10620,917±3,78073.6±15.2 225 mg 1.3 (1-2)1,368±22184,422±32,37397.3±18.4 375 mg 1.5 (1-3)1,488±176103,833±30,916110.8±36.2 525 mg 1 (1-1)1,655±250102,087±43,61298.5±24.1

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Safety Profile and Conclusions SAD Study 16 Safety Profile • • • • No SAE’s were reported in the SAD Study AE’s from the SAD study have been mild to moderate and mostly unrelated to study drug There were no Grade 3 or Grade 4 laboratory abnormalities Vital signs and ECGs were unremarkable Conclusions • • In the SAD doses were tested up to 525 mg with no concerns The collective data from the SAD demonstrate a favorable pharmacological, pharmacokinetic, and safety profile for CRV431 with acceptable safety margins that support the proposed clinical development program Nasdaq: CTRV

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CRV431 Advantages in Treating Liver Disease 17 • • • • First-in-class cyclophilin inhibitor (inhibits peptidyl prolyl isomerase) Broad range of liver-protective mechanisms (pleiotropic) due to targeting multiple cyclophilins The only investigational drug targeting both viral hepatitis and liver disease Later-stage disease focus (fibrosis, HCC) differentiates CRV431 from many NASH compounds in development Accumulates to 5-fold higher concentrations in the liver compared to blood Excellent safety profile in preclinical and clinical studies is backed up by approximately 35 years of cyclosporine A experience • • Of the histologic features of NASH, fibrosis is considered the strongest predictor of adverse clinical outcomes, including liver-related death. … the FDA encourages sponsors to focus drug development on the area of greatest need and potential effect on health (i.e., non-cirrhotic NASH with liver fibrosis). Steatohepatitis With Liver Fibrosis: Developing Drugs for Treatment FDA Guidance for Industry December 2018 Nasdaq: CTRV

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Viral Hepatitis Anti-HBV and HCV Activities 18 CRV431 anti-viral activities toward hepatitis B virus (HBV) and hepatitis C virus (HCV) expected to reduce liver disease arising from viral hepatitis HBV CRV431 decreases several HBV markers in cell culture and an animal model, including HBV DNA, HBsAg, HBeAg, cccDNA, pgRNA, and inhibits NTCP-mediated HBV uptake. HCV CRV431 inhibits HCV replication by blocking cyclophilin A - NS5A binding. PLoS One. 2015 Aug 11;10(8):e0134707. The Novel Cyclophilin Inhibitor CPI-431-32 Concurrently Blocks HCV and HIV-1 Infections via a Similar Mechanism of Action. Gallay PA, Bobardt MD, Chatterji U, Trepanier DJ, Ure D, Ordonez C, Foster R Nasdaq: CTRV

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CRV431 Planned Next Steps 19 • Clinical 28-day study, oral CRV431 escalating dose, once daily. Initiate Q2, 2019 with data Q4, 2019 • HBV patients with <F2, administered escalating doses of CRV431 (75, 150, 225, 375 mg), plus 300 mg tenofovir disoproxil fumarate (TDF). One additional fibrosis F2/F3 cohort, given 225 mg CRV431 once daily for 28-days • • Scripps Research Institute (in vivo): • • Friedman NASH model, fibrosis and HCC, data Q3 and Q4/2019 Xenograft, data in Q3, 2019 • • • • • In-house in vitro, stellate cell, data available H1, 2019 NASH IND approval, Q3, 2019 (currently IND is for HBV) IND opening study, human hepatic impairment study, initiate Q3, 2019 with read-out Q1, 2020 Phase 2 NASH, approx. 100 subjects, CRV431 orally, once daily for 24 weeks, initiate Q4/Q1, 2020/21 Chronic dosing safety, animals (rat and monkey), initiate Q4, 2019 and read-out H2, 2020 • Safety study to support longer term NASH studies (24-week studies in humans) • API manufacturing • Currently, enough finished product (capsules) for 28-day study and for hepatic impairment study (NASH opening study), and all preclinical in-house and external collaborations Additional API for chronic rat and monkey studies, and further NASH phase 2 clinical study (24-weeks) • Nasdaq: CTRV

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20 Thank You Corporate Contact: Robert Foster rfoster@contravir.com Investor Relations: Stephen Kilmer skilmer@contravir.com Tel: 646.274.3580 Nasdaq: CTRV

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