Raymond F Schinazi Chairman Raymond F. Schinazi, Chairman Jeffrey A - - PowerPoint PPT Presentation

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Raymond F Schinazi Chairman Raymond F. Schinazi, Chairman Jeffrey A Meckler Interim CEO Jeffrey A. Meckler, Interim CEO Jefferies Healthcare Conference June 4, 2015 Developing the next generation of antiviral therapies 1 Forward-looking

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Raymond F Schinazi Chairman Raymond F. Schinazi, Chairman Jeffrey A Meckler Interim CEO Jeffrey A. Meckler, Interim CEO Jefferies Healthcare Conference June 4, 2015

Developing the next generation of antiviral therapies

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Forward-looking Statements

This presentation contains forward-looking statements, including the timing of our drug development programs. Risks include delays in manufacturing created by third parties and the ability of clinical research organizations to recruit patients. Forward looking statements also are prefaced by words such as "expect " "plan " Forward-looking statements also are prefaced by words such as "expect," "plan," "intend," "anticipate," and similar words. Forward-looking statements are based on

  • ur current expectations and assumptions regarding our business, the economy

and other future conditions. Because forward-looking statements relate to the g future, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict. Our actual results may differ materially from those contemplated by the forward-looking statements for a variety of reasons including those contained in our Form 10 K as amended for the year reasons, including those contained in our Form 10-K, as amended, for the year ended December 31, 2014. We caution you, therefore, against relying on any of these forward-looking statements. They are neither statements of historical fact nor guarantees or assurances of future performance. We do not undertake any duty to update these forward-looking statements.

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Cocrystal Pharma Today

A leading antiviral company developing therapies that inhibit the essential replication functions of a virus.

  • World renowned scientific leadership
  • Dr. Roger Kornberg (2006 Nobel Prize winner in Chemistry)
  • Dr. Raymond Schinazi (founder of Pharmasset, Idenix, Triangle)
  • Proprietary technologies
  • Structure-based drug design platform
  • Proprietary nucleoside chemistry
  • Preclinical assets - HCV

Preclinical assets HCV

  • CC-1845 (Nuc)
  • CC-2068 (NS5A)
  • CDI-31244 (NNI)

CC 31326 (H li )

  • CC-31326 (Helicase)
  • Other Therapeutic targets
  • Influenza, Norovirus

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SLIDE 4

Opportunity

There exists significant unmet medical needs across a large variety of viral infections….

  • HCV
  • HCV
  • 80-170 million chronic infections, >350,000 deaths/year
  • Growing consensus large market opportunity post-2020
  • Influenza
  • 3-5 million severe cases/year, >250,000 deaths/year
  • Constantly mutating virus evades current therapeutic and vaccine

approaches approaches

  • Estimated economic impact of seasonal influenza in U.S. varies from

~$50B to ~$150B (CDC & other research estimates)

  • Norovirus
  • >250 million acute cases, 3-5 million deaths/year
  • Large immunocompromised patient population as well as stockpile

markets markets

  • Economic cost in US alone estimated >$5B (University of Michigan)

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SLIDE 5

Technology Platform

Structure-Based Drug Discovery Approach – Cocrystal’s integrated suite of drug discovery and design technologies platform with enhanced target selection process - higher probability of yielding successful drug candidates from the start.

Example of HCV fragment hits Advantages I hibit C

Provides 3D structure of inhibitor complexes at near-atomic resolution ith i di t i i ht t id SAR

Inhibitor B Inhibitor C

with immediate insight to guide SAR Identifies novel binding sites

Inhibitor A

Allows rapid turnaround of structural information through highly automated X-ray data processing and refinement X-ray data processing and refinement

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SLIDE 6

Cocrystal Pharma Evolution

Cocrystal Pharma

Founded in 2008

RFS Pharma

Founded in 2004

  • High throughput cocrystal

evaluation and structure- based drug design N b l i i i ti

  • World class nucleoside

discovery/development team HCV N l l id

  • Nobel prize winning expertise
  • HCV: NNI & first-in-class

Helicase inhibitor

  • Active discovery programs in
  • HCV: Novel nucleosides

(Nuc) and prodrugs

  • HCV: NS5A Inhibitors
  • Norovirus: Strong &

y p g

  • ther viruses including:

influenza and noroviruses g broad Nuc IP Merger in Nov 2014

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SLIDE 7

Pipeline

Viral Disease Lead Discovery Lead Optimization Preclinical IND Phase I/II Hepatitis C CC-1845 (Nuc) CC 2068 (NS5A) CC-2068 (NS5A) CDI-31244 (NNI) CC-31326 (Helicase) Norovirus Influenza CC-1845 (Nuc)

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HCV Approach

Four different classes of drugs: Expect a pan-genotypic, shorter therapy duration and high SVR

CC‐1845

Nuc

Cocrystal’s HCV

NS5A NNI

CC 2068 CDI 31244 HCV regimens

NS5A NNI

CC‐2068 CDI‐31244

Helicase

CC‐31326

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Nucleoside Prodrug Inhibitors

HCV Treatment

  • One of the best classes of anti-HCV direct acting antiviral agents (DAA)
  • Excellent safety and potency, pan-genotypic and high barrier to resistance

Excellent safety and potency, pan genotypic and high barrier to resistance

  • Must be metabolized to active nucleoside triphosphate form
  • Prodrugs: bypass non-productive first phosphorylation step and target the liver

nucleus

Liver cell

prodrug

Activation

NTP HCV

✖

Chain‐termination No virus replication

NS5B viral polymerase

CC CG GGAUAUAA★

Activation (host kinases)

rNTP

viral RNA genome

CCUAUAUUACGAAU

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CC-1845: Pan-Genotypic Nucleoside

  • Novel pan-genotypic nucleoside
  • CC-1845-based combination regimen

Compelling potential drug properties

Novel pan genotypic nucleoside prodrug: delivers three active nucleoside 5’-triphosphates – One IND needed CC 1845 based combination regimen expects a shorter duration than Harvoni

  • Single dose (max tolerated dose):
  • 2 of the 3 active metabolites of

showed comparable potency to sofosbuvir

  • Single dose (max. tolerated dose):

1,000 mg/kg in both rats and dogs

  • 7-day toxicity: *NOAEL in rats (500

mg/kg/day) and in dogs (50

  • Equivalent NTP potency compared to

sofosbuvir in human hepatocytes No cytotoxicity observed including mg/kg/day) and in dogs (50 mg/kg/day)

  • Anticipate QD dosing based on t1/2 in

primary human hepatocytes (two of

  • No cytotoxicity observed, including

mitochondrial assays

  • No resistant virus selected (3

tt t ) primary human hepatocytes (two of the NTPs have T1/2 greater than 20 hr etc.) IND bli t di (70% l t ) attempts)

* NOAEL = no observable adverse effect level

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  • IND-enabling studies (70% complete)
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CC-1845: Nucleoside Profile

Objective: Develop novel nucleoside analog inhibitors that are: Potent

Cascade of rNTP metabolite generation

Non‐toxic High barrier to resistance No drug‐drug interactions

g Half‐lives of rNTP (two NTPs >20 h and one NTP: 5.9 h) will support

  • nce‐a‐day dosing.

Pan‐genotypic activity Cytotoxicity

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CC-2068: Pan-Genotypic NS5A

  • Novel highly potent, pan-genotypic, NS5A inhibitor

(GT1b EC50, < 10 pM) (

50

p )

  • CC-2068 produces an active metabolite (also a pM HCV inhibitor)
  • Single dose (max tolerated) in rats & dogs: 1,000 mg/kg
  • 7-day oral toxicology in rats: NOAEL 800 mg/kg/day
  • Potentially an excellent combination drug candidate with Nuc and/or

NNI

  • IND-enabling studies in progress

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* NOAEL = no observable adverse effect level

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SLIDE 13

CC-2068: Pan-Genotypic NS5A

  • CC-2068 showed excellent potency against NS5A drug resistant

variants variants

  • CC-2068 showed no cytotoxicity
  • Large therapeutic index

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CDI-31244: Pan-Genotypic NNI

  • Highly potent (nM) and active against all genotypes (1 – 6)

g y p ( ) g g yp ( )

  • No cytotoxicity across cell systems
  • Favorable PK and liver targeting (>2,000‐fold above EC50)
  • Potential Best‐in‐Class NNI based on pan‐genotypic activity

and high barrier to resistance

  • IND‐enabling studies in progress

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CDI-31244: Pan-Genotypic NNI

Cocrystal’s NNIs show a high barrier to drug resistance

1600 1800

nge

HCV‐796 (Viropharma) Drug resistance variants

800 1000 1200 1400

fold cha

Cocrystal’s NNI‐4 Leads Cocrystal’s Backup Leads S365T (NNI‐4) N316Y (NNI‐4) L419M (NNI 2)

200 400 600 800

IC50 f

L419M (NNI‐2) S282T (Nuc)

1 2 3 4 5

31228 31244 959 985 HCV‐796

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Hepatitis C Helicase Program

Provides unique opportunities for ideal drug combinations

  • Creates a new option for HCV combination therapy
  • Creates a new option for HCV combination therapy
  • First-in-class pan-genotypic inhibitors (new mechanism of action)
  • Highly conserved drug binding mode demonstrated in all

genotype crystals developed (1-6)

  • Potentially an ideal combination candidate with HCV NNI, Nuc

prodrug, NS5A, and/or protease inhibitors

  • Inhibits essential viral RNA unwinding process
  • No cytotoxicity due to lack of ATPase inhibition

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Norovirus Program

Norovirus polymerase leads: nucleoside and NNI

  • Norovirus replicon and enzyme assays available
  • Novel anti-norovirus Nuc prodrug developed: confirmed activity

based on replicon and enzyme assay; also active against HCV

  • Favorable PK properties of Nuc demonstrated
  • Drug resistance evaluation for Norovirus (in progress)
  • Structure based NNI lead discovery (in progress)
  • Structure-based NNI lead discovery (in progress)
  • Expect to be used as prophylaxis and for acute and chronic

norovirus infections; especially in immunocompromised patients norovirus infections; especially in immunocompromised patients

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Norovirus Program

  • Norovirus nucleoside inhibitors with good antiviral activity
  • Above norovirus inhibitors exhibited no cytotoxicity

Above norovirus inhibitors exhibited no cytotoxicity

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Influenza Replication Inhibitor Program

  • Novel antiviral agents targeting highly conserved essential site

Influenza endonuclease inhibitors: g g g g y

  • Expect broad spectrum anti-influenza activity
  • High barrier to resistance
  • Structure-based lead discovery in progress

T‐705 (Nuc), Phase 3(US) Approved in Japan

Cocrystal Pharma

pp p Toyama/Fujifilm EC50, 0.1 ‐5 μM

Cocrystal Pharma VX‐787, Phase 2

Janssen

EC50, 0.3‐2.8 nM

50,

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2015 Goals

De elopment Accelerate transition into a full-scale, clinical biopharmaceutical company

  • Development
  • Progress regulatory filings as soon as possible
  • CC-1845 is first priority, followed closely by CC-2068 and

CDI-31244 CDI-31244

  • Research
  • Identify preclinical leads for Influenza

Identify preclinical leads for Influenza

  • Initiate IND enabling studies in the Norovirus NNI program
  • Operations
  • Continue transition to fully-listed, Nasdaq company
  • Enhance leadership team and technical capabilities

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SLIDE 21

Leadership

Raymond Schinazi (Chairman) Board of Directors and Key Management Raymond Schinazi (Chairman) Phil Frost David Block Jane Hsaio Steven Rubin Gary Wilcox Jeffrey Meckler Sam Lee Sam Lee

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Summary

  • World renowned scientific and business leadership
  • Innovative and proprietary technologies for unmet medical needs
  • HCV assets currently in preparation for regulatory filings
  • Next step: human trials (anticipate initial filing in 2015)
  • Additional therapeutic areas of high economic potential
  • Influenza, Norovirus

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Summary

  • World renowned scientific and business leadership
  • Innovative and proprietary technologies for unmet medical needs
  • HCV assets currently in preparation for regulatory filings
  • Next step: human trials (anticipate initial filing in 2015)
  • Additional therapeutic areas of high economic potential
  • Influenza, Norovirus

Thank You

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