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MarketScreener Homepage  >  Equities  >  Nasdaq  >  Hepion Pharmaceuticals, Inc.    HEPA

HEPION PHARMACEUTICALS, INC.

(HEPA)
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Hepion Pharmaceuticals : Download Corporate Presentation

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12/03/2019 | 02:03pm EST

C O R P O R AT E P R E S E N TAT I O N • 2 0 1 9

Nasdaq: HEPA

Forward-Looking

2

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," "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 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.

Nasdaq: HEPA

Snapshot

3

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)

"…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: HEPA

Corporate Overview

4

Lead Asset

CRV431: Novel, high-potency, cyclophilin inhibitor that targets multiple stages of liver disease, including NASH

  • 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: HEPA

Development Phase

5

Discovery

Phase 1

Phase 3

CRV431

Preclinical

Phase 2

  • IND for HBV - Phase 1 Single Ascending Dose completed
  • IND for HBV - Multiple Ascending Dose in progress, Q3-2019
  • IND for NASH - Approved, 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: HEPA

CRV431 in NASH

6

Cyclophilin Inhibitors Target Multiple Liver Disease Stages

INJURY/STEATOSIS

  • Antiviral activity
    (HBV, HCV, HDV, HIV-1)
  • Suppress cell death by inhibiting mitochondrial pore regulator, cyclophilin D

INFLAMMATION

FIBROSIS

Suppress pro-inflammatory

Reduce collagen production

pathways mediated by

from hepatic stellate cells

extracellular cyclophilin A

Reduce collagen hydroxyl-

binding to CD147

ation and crosslinking

CIRRHOSIS/CANCER

  • Block cancer cell adaptation to hypoxia
  • Suppress metastasis-related gene expression
  • Suppress cell proliferation
  • Sensitize to cell death

NAFLD/

NASH

Alcohol

Viral Hepatitis (HBV/HCV/HDV)

Cell injury/death

Stellate cell

Collagen

Cellular

activation

deposition

transformation

(scarring)

and metastasis

Inflammatory cell infiltration/activation

Nasdaq: HEPA

Anti-Fibrotic Activity in NASH Models

STAM Mouse Model

(High fat diet + streptozotocin)

3 - 11 weeks oral CRV431 treatment

p < 0 . 0 1

srofibeitivsop-dreis )areadlepmasfo

4

p = 0 . 0 3

6

p = 0 . 0 1

issrofibeitivsop-dre )areadlepmasfo

2 .5

n s

1

issrofibeitivsop-dre )areadlepmasfo

2 .0

3

4

1 .5

2

1 .0

2

iriu s

(%

0 .5

iriu s (%

iriu s

(%

0 .0

0

S

S

S

0

V e h i c l e

5 m g /

2 0 m g /

V e h i c l e

5 0 m g /

V e h i c l e

5 0 m g /

k g /d a y

k g /d a y

k g /d a y

k g /d a y

C R V 4 3 1 C R V 4 3 1

C R V 4 3 1

C R V 4 3 1

3 weeks treatment

6 weeks treatment

11 weeks treatment

57%reduction in fibrosis

46%reduction in fibrosis

37%reduction in fibrosis

Nasdaq: HEPA

7

"Friedman" Mouse Model

(Western diet + CCl4)

6 weeks oral CRV431 treatment

10

P0.0001

of area)

8

6

(%

Red

4

Sirius

2

0

Vehicle

CRV431

OCA

CRV431

Normal

50 mg/kg

10 mg/kg

+ OCA

Western Diet + CCl4

6 weeks treatment: 82%reduction in fibrosis

Anti-Fibrotic Activity in Liver Toxin Models

8

Rat Thioacetamide Model

9 weeks thioacetamide

9 weeks vehicle or CRV431

Carbon Tetrachloride Mouse Model

6 weeks CCl4

6 weeks vehicle, CRV431, or obeticholic acid (OCA)

Fibrosis (% Sirius Red)

Fibrosis (% Sirius Red)

15

P=0.008

area)

10

red (% of

5

Sirius

0

Vehicle CRV431

40 mg/kg

9 weeks treatment

48%reduction in fibrosis

Fibrosis score

score

Cirrhotic

4

histologic

3

2

Fibrosis

1

0

Vehicle CRV431

40 mg/kg

No cirrhotic livers

in CRV431 treatment group

P = 0.008

Sirius red-positive fibrosis

4

P = 0.32

P = 0.005

P = 0.03

P = 0.05

(%of sampled area)

3

2

1

0

Non-CCl4

Vehicle

CRV431

OCA

CRV431

50 mg/kg

10 mg/kg

+ OCA

Carbon tetrachloride (CCl4)

Nasdaq: HEPA

6 weeks treatment: 43%reduction in fibrosis

Anti-Cancer Activity in Late-Stage NASH Model

9

STAM Mouse Model

(streptozotocin + high fat diet)

10 weeks oral CRV431 treatment

Sirius red-positive fibrosis

5

p = 0.014

(%of sampled area)

4

3

2

1

0

Vehicle

50 mg/

kg/day

CRV431

Number of Tumor Nodules

p = 0.05

per liver

15

10

of nodules

5

Number

0

CRV431

Vehicle

44%reduction in tumor number

Tumor Score (number x size)

p = 0.02

score

7

6

5

nodule

4

3

HCC

2

1

0

CRV431

Vehicle

Score 0

Score 2

Score 5

10 weeks treatment

52%reduction in tumor

44%reduction in fibrosis

composite score

Nasdaq: HEPA

Score 7

CRV431 on Human Precision Cut Liver Slices

10

CRV431 Decreases Inflammation and Fibrosis (UK Study Group)

Picrosirius Red Staining of Fibrotic Collagen

(%)

12

Time 0 (baseline)

stained

10

Vehicle

11

Control (non-stimulated)

area

9

ALK5i (TBGβR inhibitor)

Percentage

8

CVR431 1 M

0Time

Control

Vehicle

ALK5i

1CVR431

5CVR431

10OCA

20ELF

7

CVR431 5 M

Obeticholic acid 10 M

6

Elifibranor 20 M

+ TGFβ 1 + PDGFβ β

CONCLUSIONS

  • TGFβ +PDGF stimulation increased inflammation and fibrosis

markers, and TGFβ/PDGF receptor inhibition (Alk5i) blocked the effects

  • CRV431 decreased all markers of inflammation and fibrosis:
    • GENE EXPRESSION - e.g. collagen, IL-6
    • SECRETED CYTOKINES AND EXTRACELLULAR MATRIX PROTEINS
    • FIBROTIC TISSUE COLLAGEN
  • CRV431 had similar or better efficacy than OCA (FXR agonist) and elafibranor (PPAR agonist)
  • CRV431 5 µM completely prevented the Day 0-4 increase in fibrosis in similarity to TGFβ receptor inhibition (Alk5i)
  • CRV431 was more efficacious than OCA and elafibranor

Nasdaq: HEPA

Anti-Fibrotic Mechanisms of Action

11

CRV431 is proposed to decrease fibrosis by affecting two processes in hepatic stellate cells, the primary, collagen-producing cell type in hepatic fibrosis:

  • decrease expression of fibrosis-related genes
  • decrease cyclophilin B-dependent collagen synthesis and secretion

Representative Experiments on LX-2 Hepatic Stellate Cells

Fibrosis-related gene expression reduced by CRV431

Procollagen secretion reduced by CRV431 or Cyp B knockdown

Collagen-1α 1

DMSO

8

6

vs

expression

4

2

Relative

0

CRV431

CRV431

CRV431

OCA

DMSO

DMSO

M

β

+

M

M

M

1

TGF

. 2

1

5

β

+

0

+

+

TGF

+

TGF

β

TGF

β

TGF

β

LOX (crosslinking enzyme)

DMSO

2.5

2.0

vs

expression

1.5

1.0

Relative

0.5

0.0

DMSO

+

DMSO

CRV431

CRV431

CRV431

M

OCA

TGF

β

. 2

M

1

M

5

M

β

+

1

+

0

β

+

β

+

TGF

β

TGF

TGF

TGF

(normalized)

Procollagen

40

30

ng/well

20

Procollagen

10

0

CRV431

CRV431

CRV431

CRV431

Untreated

CRV431

Untreated

CRV431

M

M

M

M

M

M

2

5

2

5

.

1

.

1

0

0

+ 0.1 ng/ml TGFβ

(normalized)

Procollagen

40

30

ng/well

20

Procollagen

10

0

siRNA

siRNA

siRNA

siRNA

siRNA

siRNA

siRNA

siRNA

siRNA

siRNA

Control

A

B

C

D

Control

A

B

C

D

Cyp

Cyp

Cyp

Cyp

Cyp

Cyp

Cyp

Cyp

+ 0.1 ng/ml TGFβ

Nasdaq: HEPA

Summary of Nonclinical Anti-fibrotic Activities

12

Species

Model

Location

Treatment

Fibrosis Reduction

Other CRV431 Effects

Duration

(% Sirius Red)

Mice

Friedman NASH model

Scripps (USA)

6 weeks

82%

Weight gain

(CCl4 + Western diet)

Mice

STAM NASH model

Stelic (Japan)

3 weeks

57%

none

(streptozotocin + HFD)

Mice

STAM NASH model

Scripps (USA)

6 weeks

46%

none

(streptozotocin + HFD)

Mice

STAM NASH model

Scripps (USA)

11 weeks

37%

Weight gain

(streptozotocin + HFD)

NAS score

Mice

STAM NASH model

Scripps (USA)

10 weeks

44%

Liver tumor number and size 52%

(streptozotocin + HFD)

(late disease)

Liver weight

Mice

Carbon tetrachloride (CCl4)

Scripps (USA)

6 weeks

44%

none

Rats

Thioacetamide

Physiogenex

9 weeks

48%

Prevented progression to cirrhosis

(France)

Human

Precision cut liver slice (PCLS)

FibroFind (UK)

4 days

100%

RNA levels and secretion of

cultures with TGFβ+PDGF-BB

inflammatory/fibrotic proteins

Human

LX-2 hepatic stellate cell

Hepion

1-2 days

30-50%

Fibronectin secretion

cultures (± TGFβ)

collagen secretion

Fibrotic gene expression

Nasdaq: HEPA

Single Ascending Dose (SAD) Study

13

(CTRV-CRV431-101)

Objectives

  • 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
    SAD

CRV431 525 mg

CRV431 375 mg

Healthy

CRV431 225 mg

Subjects

CRV431 75 mg

Nasdaq: HEPA

N = 32 (24 CRV431; 8 Placebo)

CRV431

14

Mean Pharmacokinetic Parameters

Tmax, h

Cmax, ng/mL

AUC0-inf,

t½, h

Dose

ng*h/mL

(range)

(SD)

(SD)

(SD)

75 mg

4 (2-10)

334±106

20,917±3,780

73.6±15.2

225 mg

1.3 (1-2)

1,368±221

84,422±32,373

97.3±18.4

375 mg

1.5 (1-3)

1,488±176

103,833±30,916

110.8±36.2

525 mg

1 (1-1)

1,655±250

102,087±43,612

98.5±24.1

  • Drug exposure is linear up to 375mg (r2=0.914)
  • Pharmacokinetic profile supports once daily dosing.

Nasdaq: HEPA

Safety Profile and Conclusions

15

SAD Study

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: HEPA

CRV431 Advantages

16

in Treating Liver Disease

  • Cyclophilin inhibitor (inhibits peptidyl prolyl isomerase)
  • Broad range of liver-protective mechanisms (pleiotropic) due to targeting multiple cyclophilins
  • The only investigational drug targeting bothviral hepatitis and liver disease
  • Later-stagedisease 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: HEPA

Clinical Timelines/Events

2020

2020/2021

Nasdaq: HEPA

2019

17

  • NASH IND, authorization to proceed
  • Initiated Clinical 28-day study, oral CRV431 escalating dose, once daily repeat doses

H1

  • Data from Clinical 28-day study, oral CRV431 Multiple Ascending Dose (MAD), once daily
  • Initiate Phase 2 NASH biomarker pilot study, 1-month CRV431 repeat dose

Q3

  • Data from Phase 2 NASH pilot study, 1 month, CRV431 repeat dose

Q4/Q1

  • Initiate Phase 2 NASH, approx. 100 subjects, CRV431 orally, once daily for 24 weeks

Non-Clinical Events

2019

2020

Nasdaq: HEPA

2019

18

  • Data from Human Precision Cut Liver Slice culture

H2

  • Data from In-housein vitro - stellate cells
  • Ongoing Mode of Action studies, ongoing and collaborations

Q4

  • Data from rat thioacetamide, fibrosis study
  • Data from NASH Western Diet, fibrosis study
  • Data from Precision Cut Liver Slices (PCLS, Part B), UK, fibrosis study

Q1

  • Initiate chronic dosing safety, animals (rat and monkey),

Q2

  • Data from NASH Western Diet, in vivo model, TSRI, HCC
  • Data from HCC xenograft model

H2

  • Data from chronic dosing safety, animals (rat and monkey),
  • Data from Diamond NASH mice
  • Data from cyclophilin knockout animal models for
    NASH/HCC

Thank You

Corporate Contact:

Investor Relations:

Robert Foster

Stephen Kilmer

rfoster@hepionpharma.com

skilmer@hepionpharma.com

Tel: 646.274.3580

Nasdaq: HEPA

Disclaimer

Hepion Pharmaceuticals Inc. published this content on 03 December 2019 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 03 December 2019 19:02:01 UTC

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Financials (USD)
Sales 2019 -
EBIT 2019 -7,53 M
Net income 2019 -7,53 M
Debt 2019 -
Yield 2019 -
P/E ratio 2019 -4,36x
P/E ratio 2020 -3,65x
Capi. / Sales2019 infx
Capi. / Sales2020 infx
Capitalization 17,9 M
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Number of Analysts 2
Average target price 10,50  $
Last Close Price 5,19  $
Spread / Highest target 131%
Spread / Average Target 102%
Spread / Lowest Target 73,4%
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Managers
NameTitle
Robert T. Foster President, Chief Executive Officer & Director
Gary S. Jacob Chairman
John T. Cavan Chief Financial & Accounting Officer
Daren Ure Chief Scientific Officer
John P. Brancaccio Independent Director
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