Raymond F Schinazi ChairmanRaymond F. Schinazi, Chairman

Jeffrey A Meckler Interim CEOJeffrey A. Meckler, Interim CEO

Jefferies Healthcare ConferenceJune 4, 2015

Developing the next generation of antiviral therapies1

Forward-looking StatementsThis presentation contains forward-looking statements, including the timing of ourdrug development programs. Risks include delays in manufacturing created bythird 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 onour current expectations and assumptions regarding our business, the economyand other future conditions. Because forward-looking statements relate to thegfuture, they are subject to inherent uncertainties, risks and changes incircumstances that are difficult to predict. Our actual results may differ materiallyfrom those contemplated by the forward-looking statements for a variety ofreasons including those contained in our Form 10 K as amended for the yearreasons, including those contained in our Form 10-K, as amended, for the yearended December 31, 2014. We caution you, therefore, against relying on any ofthese forward-looking statements. They are neither statements of historical factnor guarantees or assurances of future performance. We do not undertake anyduty 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 - HCVPreclinical 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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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

approachesapproaches • 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

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

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Technology PlatformStructure-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 AdvantagesI hibit C

Provides 3D structure of inhibitor complexes at near-atomic resolution

ith i di t i i ht t id SAR

Inhibitor BInhibitor 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 refinementX-ray data processing and refinement

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Cocrystal Pharma Evolution

Cocrystal PharmaFounded in 2008

RFS PharmaFounded in 2004

• High throughput cocrystal evaluation and structure-based drug designN b l i i i ti

• World class nucleoside discovery/development teamHCV 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

other viruses including: influenza and noroviruses

gbroad Nuc IP

Merger inNov 2014

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Pipeline

Viral DiseaseLead

DiscoveryLead

Optimization Preclinical IND Phase I/II

Hepatitis CCC-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’sHCV NS5ANNI CC 2068CDI 31244 HCV

regimensNS5ANNI CC‐2068CDI‐31244

Helicase

CC‐313268

Nucleoside Prodrug InhibitorsHCV Treatment• One of the best classes of anti-HCV direct acting antiviral agents (DAA)

• Excellent safety and potency, pan-genotypic and high barrier to resistanceExcellent 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 cellprodrug

Activation NTP

HCV✖Chain‐terminationNo virus replication

NS5B viral polymerase

CC CGGGAUAUAA★Activation

(host kinases)rNTP

viral RNA genomeCCUAUAUUACGAAU

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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)

CC-1845: Nucleoside ProfileObjective: Develop novel nucleoside analog inhibitors that are:

PotentCascade of rNTP metabolite generation 

Non‐toxicHigh barrier to resistanceNo drug‐drug interactions

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

CC-2068: Pan-Genotypic NS5A

CC-2068 showed excellent potency against NS5A drug resistant variantsvariants

CC-2068 showed no cytotoxicityLarge 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 LeadsCocrystal’s

Backup Leads

S365T (NNI‐4)

N316Y (NNI‐4)

L419M (NNI 2)

200

400

600

800

IC50f L419M (NNI‐2)

S282T (Nuc)

01 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 patientsnorovirus infections; especially in immunocompromised patients

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Norovirus Program

• Norovirus nucleoside inhibitors with good antiviral activity

• Above norovirus inhibitors exhibited no cytotoxicityAbove 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 pToyama/FujifilmEC50, 0.1 ‐5 μMCocrystal Pharma

VX‐787, Phase 2Janssen

EC50, 0.3‐2.8 nM50,

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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-31244CDI-31244

• Research• Identify preclinical leads for InfluenzaIdentify 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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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 LeeSam 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 You23