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Item 1. Business

2022-03-23 compared with 2021-03-17 · 423 added, 352 removed, 67 unchanged (92% of the section changed)

(the “Company”

or “Cocrystal”) is a biotechnology company seeking to discover and develop

novel antiviral therapeutics as treatments for serious and/or chronic viral diseases.

We employ unique structure-based technologies

and Nobel Prize winning expertise to create first- and best-in-class antiviral drugs.

These technologies are designed to efficiently

deliver small molecule therapeutics that are safe, effective, and convenient to administer.

We have identified promising discovery,

preclinical and clinical stage antiviral compounds for unmet medical needs caused by influenza virus, coronavirus, hepatitis C

virus (“HCV”), and norovirus infections.

(the “Company” or “Cocrystal”) is a biotechnology company seeking to discover and develop novel

antiviral therapeutics as treatments for serious and/or chronic viral diseases.

We employ unique structure-based technologies and Nobel

Prize winning expertise to create first- and best-in-class antiviral drugs.

These technologies are designed to efficiently deliver small

molecule therapeutics that are safe, effective, and convenient to administer.

We have identified promising discovery, preclinical and

clinical stage antiviral compounds for unmet medical needs caused by coronavirus, influenza virus, hepatitis C virus (“HCV”),

and norovirus infections.

Company operates in one segment.

Management uses cash flows as the primary measure to manage its business and does not segment

its business for internal reporting or decision-making.

Management uses cash flows as the primary measure to manage its business and does not segment its business

for internal reporting or decision-making.

are developing antiviral therapeutics that inhibit the essential viral replication function of RNA viruses causing acute and chronic

viral diseases.

Our goals include treating influenza virus, coronavirus, and norovirus infections by discovering and developing

drug candidates targeting the viral replication process.

Additionally, one of our goals is to decrease the duration of HCV therapy

by advancing our drug candidate targeting the HCV RNA-dependent RNA polymerase enzyme through partnerships and/or licensing activities.

In the case of coronavirus, we target a major protease enzyme that produces the active form of the viral replication enzyme.

To discover and design these inhibitors, we use a proprietary platform comprising computation, medicinal

chemistry, X-ray crystallography, and our extensive know-how.

We determine the structures of cocrystals containing the inhibitors

bound to the enzyme or protein to guide our structure-based drug design.

We also use advanced computational methods to screen

and design product candidates using proprietary cocrystal structural information.

In designing the candidates, we seek to anticipate

and avert potential viral mutations leading to resistance.

By designing and selecting drug candidates that interrupt the viral

replication process and also have specific binding characteristics, we seek to develop drugs that are not only effective against

both the virus and possible mutants of the virus, but which also have reduced off-target interactions that cause undesirable clinical

side effects.

The successful application of our approach requires an extensive knowledge of viruses and drug targets.

knowledge and experience in the fields of structural biology, and enzymology are required.

We developed our proprietary structure-based

drug design under the guidance of Dr.

Roger Kornberg, our Chief Scientist, Chairman of our Scientific Advisory Board and recipient

of the Nobel Prize in Chemistry in 2006.

Our drug discovery process focuses on the highly conserved regions of the viral enzymes

and inhibitor-enzyme interactions at the atomic level.

Additionally, we have developed proprietary chemical libraries consisting

of non-nucleoside inhibitors, metal-binding inhibitors, and drug-like fragments.

Our drug discovery process is different from

traditional, empirical, medicinal chemistry approaches that often require iterative high-throughput compound screening and lengthy

hit-to-lead processes.

We will continue developing preclinical and clinical drug candidates using our proprietary drug discovery

Company’s proprietary technology integrates several powerful and specialized techniques:

of viral drug targets amenable to broad-spectrum antiviral drug development and essential for viral genome replication;

resolution 3-D structure determination of drug binding pockets;

computational analysis of conservation of drug-binding pockets and critical molecular interactions between antiviral inhibitors

and amino acid residues of the target molecule’s drug-binding pocket;

structure determinations to inform hit identification, hit-to-lead, and lead optimization processes;

modeling and computer-guided lead discovery to support rational chemical modifications based on structure-activity relationships,

or SAR, of candidate inhibitor compounds;

of enzymatic mechanisms to guide the design of drugs with exceptional affinity, specificity, and broad-spectrum activity;

for rapid identification of antiviral enzyme inhibitors showing broad-spectrum antiviral activity.

Our goals include treating influenza virus, coronavirus, and norovirus infections by discovering and developing drug

candidates targeting the viral replication process.

Additionally, one of our goals is to decrease the duration of HCV therapy by advancing

our drug candidate targeting the HCV RNA-dependent RNA polymerase enzyme through partnerships and/or licensing activities.

of coronavirus antiviral therapeutics, we target replication enzymes and proteases that are required for the viral replication and transcription.

To discover and design these inhibitors, we use a proprietary platform comprising computational chemistry, medicinal chemistry, X-ray

crystallography and our extensive know-how.

We determine the structures of cocrystals containing the inhibitors bound to the enzyme or

protein to guide our structure-based drug design.

We also use advanced computational methods to screen and design product candidates

using proprietary cocrystal structural information.

In designing the candidates, we seek to anticipate and avert potential viral mutations

leading to resistance.

By designing and selecting drug candidates that interrupt the viral replication process and also have specific

binding characteristics, we seek to develop drugs that are not only effective against both the virus and possible mutants of the virus,

but which also have reduced off-target interactions that may cause undesirable clinical side effects.

The successful application of our

approach requires an extensive knowledge of viruses and drug targets.

In addition, knowledge and experience in the fields of structural

biology, and enzymology are required.

We developed our proprietary structure-based drug design under the guidance of Dr.

Roger Kornberg,

our Chief Scientist and Chairman of both our Scientific Advisory Board and Board of Directors, in addition to a recipient of the

Nobel Prize in Chemistry in 2006.

Our drug discovery process focuses on the highly conserved regions of the viral enzymes and inhibitor-enzyme

interactions at the atomic level.

Additionally, we have developed proprietary chemical libraries consisting of non-nucleoside inhibitors,

metal-binding inhibitors, and drug-like fragments.

Our drug discovery process is different from traditional, empirical, medicinal chemistry

approaches that often require iterative high-throughput compound screening and lengthy hit-to-lead processes.

We will continue developing

preclinical and clinical drug candidates using our proprietary drug discovery technology.

Company’s proprietary technology integrates several powerful and specialized techniques:

Selection of viral drug

targets amenable to broad-spectrum antiviral drug development and essential for viral genome replication;

Atomic resolution 3-D structure

determination of drug binding pockets;

In-depth computational

analysis of conservation of drug-binding pockets and critical molecular interactions between antiviral inhibitors and amino acid

residues of the target molecule’s drug-binding pocket;

Cocrystal structure determinations

to inform hit identification, hit-to-lead, and lead optimization processes;

Molecular modeling and

computer-guided lead discovery to support rational chemical modifications based on structure-activity relationships, or SAR, of candidate

inhibitor compounds;

Knowledge of enzymatic

mechanisms to guide the design of drugs with exceptional affinity, specificity, and broad-spectrum activity;

Platforms for rapid identification

of antiviral enzyme inhibitors showing broad-spectrum antiviral activity.

have applied these techniques to develop antiviral inhibitors of four important viruses:

influenza virus, coronavirus, HCV and

influenza virus, coronavirus, HCV and norovirus.

Market-Driven

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all of our programs our goal is to develop best-in-class broad-spectrum antiviral drugs with high-barrier-to-drug resistance.

An ideal product for an antiviral therapy would have at least the following characteristics:

barrier to viral resistance;

against all viral subtypes that cause disease;

onset of action and/or shortened therapeutic time;

safety and tolerability profile;

routes of administration including oral, inhalation, and/or injection.

product for an antiviral therapy would have at least the following characteristics:

High barrier to viral resistance;

Effective against all viral

subtypes that cause disease;

Fast onset of action and/or

shortened therapeutic time;

Good safety and tolerability

Multiple routes of administration

including oral, inhalation, and/or injection.

at the discovery stage of drug development, we select compounds with these factors in mind.

Furthermore, we believe our

technology is capable of delivering therapies that satisfy all of these key factors, as detailed below.

Furthermore, we believe our technology is

capable of delivering therapies that satisfy all of these key factors, as detailed below.

barrier to drug resistance :

2 unchanged sentences

rapidly and in enormous quantities in infected human cells.

During viral replication, random changes in the viral genome, called

mutations, develop.

If such a mutation occurs in a region of the viral genome that is targeted by a given antiviral therapy, that

therapy may no longer be effective against the mutated virus.

These mutated or “resistant”

viruses can freely infect

and multiply even in individuals who have received drug treatment.

During viral replication, random changes in the viral genome, called mutations,

If such a mutation occurs in a region of the viral genome that is targeted by a given antiviral therapy, that therapy may no

longer be effective against the mutated virus.

These mutated or “resistant” viruses can freely infect and multiply even in

individuals who have received drug treatment.

In some cases, resistant virus strains may even predominate.

For example, in the 2009 swine influenza pandemic, the predominant strain was resistant to the best available therapies.

the current COVID-19 pandemic mutated viruses have been identified and sequenced demonstrating that the potential for resistance

to current drugs and reduced effectiveness of vaccines is already present.

Company’s focus on viral replication proteins can overcome the obstacle of viral resistance.

We identify and target critical

components of viral replication proteins that are essential for function, and therefore, sensitive to change.

A mutation in these

critical components is likely to inactivate the replication protein and, in turn, render the virus incapable of replicating.

such mutations cannot propagate, the virus cannot effectively develop resistance to the enzyme inhibitors we employ.

effectiveness of our compounds against potential viral mutations and select compounds with the highest barrier to resistance.

For example, in the 2009 swine

influenza pandemic, the predominant strain was resistant to the best available therapies.

In the COVID-19 pandemic mutated viruses have

been identified and sequenced demonstrating that the potential for resistance to current drugs and reduced effectiveness of vaccines

is already present.

For example, the Omicron variant which arose as the dominant strain of COVID-19 in late 2021 until it diminished

in the winter of 2022 has displayed increased resistance to available vaccines and treatments, resulting in the limitation or suspension

of emergency use authorizations by the FDA for certain therapeutic products.

Company’s focus on viral replication proteins can overcome the obstacle of viral resistance.

We identify and target critical components

of viral replication proteins that are essential for function, and therefore, sensitive to change.

A mutation in these critical components

is likely to inactivate the replication protein and, in turn, render the virus incapable of replicating.

Because such mutations cannot

propagate, the virus cannot effectively develop resistance to the enzyme inhibitors we employ.

We test the effectiveness of our compounds

against potential viral mutations and select compounds with the highest barrier to resistance.

effective against major strains responsible for a viral disease :

For any given viral disease, there are different strains

of viruses that cause the disease.

For any given viral disease, there are different strains of viruses

that cause the disease.

For example, there are three types of influenza viruses, A, B, and C.

Influenza A and B viruses

are significant human respiratory pathogens that cause seasonal flu.

Influenza A and B viruses are significant

human respiratory pathogens that cause seasonal flu.

Influenza A viruses can also cause an influenza pandemic.

Influenza C is a subtype of the influenza virus that tends to cause only mild illness and is not responsible for seasonal or pandemic

Our goal is to design and develop drug candidates that will be effective on the broadest possible range of viruses

causing the disease.

antiviral drugs available today are effective only against certain strains of a given virus and less effective or not effective

at all against other strains.

To address this problem, we are developing drug candidates that specifically target viral proteins

involved in viral replication.

Despite the various strains of virus that may exist, these enzymes required for viral replication

are essentially similar (highly conserved) among all strains of a given virus.

By targeting these highly conserved regions of

the replication enzymes, our antiviral compounds are designed and tested to be effective against major virus strains.

enzymes are generally conserved not only among subtypes of a given virus but also among many different viruses, creating an opportunity

for the development of broad-spectrum antiviral drugs.

Influenza C is a subtype

of the influenza virus that tends to cause only mild illness and is not responsible for seasonal or pandemic infections.

to design and develop drug candidates that will be effective on the broadest possible range of viruses causing the disease.

antiviral drugs available today are effective only against certain strains of a given virus and less effective or not effective at all

against other strains.

To address this problem, we are developing drug candidates that specifically target viral proteins involved in

viral replication.

Despite the various strains of virus that may exist, these enzymes required for viral replication are essentially

similar (highly conserved) among all strains of a given virus.

By targeting these highly conserved regions of the replication enzymes,

our antiviral compounds are designed and tested to be effective against major virus strains.

Replication enzymes are generally conserved

not only among subtypes of a given virus but also among many different viruses, creating an opportunity for the development of broad-spectrum

antiviral drugs.

onset of action:

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All drugs have side effects, also referred to as adverse effects.

These usually result from a drug’s

ability to bind to human molecules (usually proteins).

When this interaction is intentional (i.e., part of the drug’s mechanism

of action), the adverse effects are classified as on-target effects.

When this interaction is unintentional (i.e., resulting from

the drug’s interaction with an unintended human molecule), the effects are called off-target effects.

Our inhibitors target

viral replication enzymes, which are generally unique to viruses.

Because the targets are viral, not human, minimal adverse effects

may be the result.

During the discovery phase, we evaluate candidate compounds for potential cross-reactivity with human replication

enzymes and attempt to eliminate those compounds that are cross-reactive with human homologous proteins.

These usually result from a drug’s ability

to bind to human molecules (usually proteins).

When this interaction is intentional (i.e., part of the drug’s mechanism of action),

the adverse effects are classified as on-target effects.

When this interaction is unintentional (i.e., resulting from the drug’s

interaction with an unintended human molecule), the effects are called off-target effects.

Our inhibitors target viral replication enzymes,

which are generally unique to viruses.

Because the targets are viral, not human, minimal adverse effects may be the result.

discovery phase, we evaluate candidate compounds for potential cross-reactivity with human replication enzymes and attempt to eliminate

those compounds that are cross-reactive with human homologous proteins.

of administration:

We select compounds for development that can be administered orally, preferably once daily in pill-form,

or by inhalation or injection.

We select compounds for development that can be administered orally, preferably once daily in pill-form, or by

inhalation or injection.

and Development Update

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have several preclinical candidates under development for the treatment of influenza infection.

CC-42344, a novel PB2 inhibitor,

has been selected as a preclinical lead.

This candidate binds to a highly conserved PB2 site of influenza polymerase complex (PB1:

CC-42344, a novel PB2 inhibitor, was

selected as a preclinical lead for influenza A.

This candidate binds to a highly conserved PB2 site of influenza polymerase

complex (PB1:

PA) and exhibits a novel mechanism of action.

CC-42344 showed excellent antiviral activity against influenza A strains, including

avian pandemic strains and Tamiflu resistant strains, and has favorable pharmacokinetic and drug resistance profiles.

We are currently

conducting additional preclinical IND enabling studies and plan to initiate a Phase 1 study in the third quarter of 2021.

CC-42344 showed excellent antiviral activity against influenza A strains,

including avian pandemic strains and Tamiflu resistant strains, and has favorable pharmacokinetic and drug resistance profiles.

have received regulatory clearance to initiate a Phase 1 clinical trial for this product candidate in Australia, and began enrollment

of subjects in March 2022.

addition, novel inhibitors effective against both influenza strains A and B have been identified and are in the preclinical stage.

Several of these have potencies approaching single digit nanomolar.

On January 2, 2019, the Company entered into an Exclusive

License and Research Collaboration Agreement (the “Collaboration Agreement”) with Merck Sharp & Dohme Corp.

(“Merck”)

to discover and develop certain proprietary influenza A/B antiviral agents.

See “Item 1 –

Business –

Collaborations

Merck Collaboration”

for more information.

January 2021, we announced that we completed all research obligations under the Merck exclusive worldwide license and collaboration

agreement, and that Merck is now solely responsible for further development of the influenza A/B antiviral compounds that were

discovered using Cocrystal’s unique structure-based technologies and Nobel Prize-winning expertise.

Merck is continuing

development of the compounds under the terms of our Collaboration Agreement.

December 2020 we announced the selection of CDI-45205 as the lead compound for further development against coronaviruses including

SARS-CoV-2, that causes COVID-19.

was one of the broad-spectrum protease inhibitors that were obtained from Kansas State University Research Foundation (“KSURF”)

of these have potencies approaching single digit nanomolar.

On January 2, 2019, the Company entered into an Exclusive License and Research

Collaboration Agreement (the “Collaboration Agreement”) with Merck Sharp & Dohme Corp.

(“Merck”) to discover

and develop certain proprietary influenza A/B antiviral agents.

See “Item 1 – Business – Collaborations – Merck

Collaboration” for more information.

January 2021, we announced that we completed all research obligations under the Merck exclusive worldwide license and collaboration agreement,

and that Merck is now solely responsible for further development of the influenza A/B antiviral compounds that were discovered using

Cocrystal’s unique structure-based technologies and Nobel Prize-winning expertise.

Merck is continuing development of the compounds

under the terms of our Collaboration Agreement.

December 2020 we announced the selection of CDI-45205 as the lead compound for further development against coronaviruses including SARS-CoV-2,

that causes COVID-19.

was one of the broad-spectrum protease inhibitors that were obtained from Kansas State University Research Foundation (“KSURF”)

under an exclusive license agreement announced in April 2020.

That agreement provides Cocrystal with an exclusive, royalty-bearing

license to develop and commercialize therapeutic, diagnostic and prophylactic products against coronaviruses, caliciviruses and

picornaviruses based on antivirals discovered by KSURF.

See “Collaborations –

Kansas State University Research Foundation.”

The Company believes these protease inhibitors have the ability to convert the inactive SARS-CoV-2 polymerase replication enzymes

into an active form.

We are working toward pre-IND status with CDI-45205.

are also developing COVID-19 replication inhibitors using our drug discovery platform and expect to develop such additional

COVID-19 inhibitors with novel mechanism of action in 2021.

continue to identify and develop non-nucleoside polymerase and protease inhibitors using the Company’s proprietary structure-based

That agreement provides Cocrystal with an exclusive, royalty-bearing license

to develop and commercialize therapeutic, diagnostic and prophylactic products against coronaviruses, caliciviruses and picornaviruses

based on antivirals discovered by KSURF.

See “Collaborations – Kansas State University Research Foundation.” The Company

believes these protease inhibitors have the ability to convert the inactive SARS-CoV-2 polymerase replication enzymes into an active

We are working toward pre-Investigational New Drug application (“IND”) status with CDI-45205 with the goal of commencing

a Phase 1 clinical study in 2022.

To this end, in January 2022 we received guidance from the U.S.

Food and Drug Administration (the “FDA”)

for further development of CDI-45205 in response to the Company’s pre-IND briefing package that was submitted in 2021.

are also developing COVID-19 replication inhibitors using our drug discovery platform and continued to work towards developing such

additional COVID-19 inhibitors with novel mechanism of action in 2021.

In January 2022 we announced the selection of two investigational

novel antiviral drug candidates, CDI-988 and CDI-873, for further development as oral treatments for SARS-CoV-2.

The Company intends

to initiate a first-in-human trial with one selected candidate as soon as possible in 2022.

Although CDI-988 and CDI-873 are chemically

differentiated, both exhibited superior in vitro potency against SARS-CoV-2 with activity maintained against recent variants of concern,

including Omicron.

In preclinical studies, both candidates demonstrated a favorable safety profile and pharmacokinetic properties supportive

of daily oral dosing.

continue to identify and develop non-nucleoside polymerase and protease inhibitors using the Company’s proprietary structure-based

drug design technology platform.

In addition, we now have exclusive rights to norovirus protease inhibitors for use in humans

obtained in the license from Kansas State University Research Foundation (see under Collaborations below).

We expect to complete

proof-of-concept animal study in the first half of 2021.

In addition, we now have exclusive rights to norovirus protease inhibitors for use in humans obtained

in the license from KSURF (see under Collaborations below).

We expect to complete proof-of-concept animal study in the first half

A worldwide public health problem, including the potential for pandemic disease .

is a severe respiratory illness, caused primarily by influenza A or B virus.

The Centers for Disease Control and Prevention (the

“CDC”) estimates that influenza was linked to approximately 79,000 deaths and 960,000 hospitalizations in the United

States during the 2017-2018 flu season.

According to the report published by BCC Research in May 2018, the global influenza market

was valued at approximately $5.6 billion in 2017 and is expected to reach nearly $6.5 billion by 2022, increasing at a compound

annual growth rate (CAGR) of 3.0% from 2017 through 2022.

The Centers for Disease Control and Prevention (the “CDC”)

estimates that influenza was linked to approximately 79,000 deaths and 960,000 hospitalizations in the United States during the 2017-2018

According to the report published by BCC Research in May 2018, the global influenza market was valued at approximately $5.6

billion in 2017 and is expected to reach nearly $6.5 billion by 2022, increasing at a compound annual growth rate (CAGR) of 3.0% from

2017 through 2022.

approved antiviral treatments for influenza are effective, but burdened with significant viral resistance.

Strains of influenza

virus that are resistant to the approved treatments osteltamivir phosphate (Tamiflu(R)) and zanamavir (Relenza(R)) have appeared,

and in some cases predominate.

For example, the predominant strain of the 2009 swine influenza pandemic was resistant to Tamiflu.

Strains of influenza virus

that are resistant to the approved treatments osteltamivir phosphate (Tamiflu(R)) and zanamavir (Relenza(R)), baloxavir marboxil (Xofluza®)

have appeared, and in some cases predominate.

For example, the predominant strain of the 2009 swine influenza pandemic was resistant

These drugs target viral neuraminidase enzymes, which are not highly conserved between viral strains.

In fact, different influenza

virus strains such as H1N1 and H5N1 are named according to their respective differences in hemagglutinin (H) and neuraminidase

In fact, different

influenza virus strains such as H1N1 and H5N1 are named according to their respective differences in hemagglutinin (H) and neuraminidase

Company has several preclinical candidates under development for the treatment of influenza infection.

CC-42344, a novel PB2 inhibitor,

has been selected as a preclinical lead.

This candidate binds to a highly conserved PB2 site of the influenza polymerase (PB1:

was selected as a preclinical lead and our Phase 1 study is currently ongoing.

This candidate binds to a highly conserved

PB2 site of the influenza polymerase (PB1:

PA), and exhibits a novel mechanism of action.

CC-42344 showed excellent antiviral activity against influenza A strains,

including avian pandemic strains, and Tamiflu-resistant, Xofluza-resistant strains, and has a favorable pharmacokinetic profile.

In addition to Tamiflu, an approved antiviral product candidate that is a competitor for the Company’s influenza programs,

S-033188, being developed by Shionogi/Roche.

S-033188 was approved as Xofluza in Japan on February 23, 2018, and in the US as

baloxavir marboxil (trade name Xofluza ®

) on October 24, 2018.

See “Item 1 –

Business –

and Development Update –

Influenza”

for more information.

CC-42344 showed excellent antiviral activity

against influenza A strains, including avian pandemic strains, and Tamiflu-resistant, Xofluza-resistant strains, and has a favorable

pharmacokinetic profile.

In addition to Tamiflu, an approved antiviral product candidate that is a competitor for the Company’s

influenza programs, S-033188, being developed by Shionogi/Roche.

S-033188 was approved as Xofluza in Japan on February 23, 2018, and

in the US as baloxavir marboxil (trade name Xofluza ® ) on October 24, 2018.

See “Item 1 – Business –

Research and Development Update – Influenza” for more information.

Xofluza-resistant strains emerged in both the US and Japan

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COVID-19 continues to be a global pandemic fueled by an emergence of new strains .

continues to be a global pandemic with 117,332,262 confirmed cases globally, including 2,605,356 deaths, as of March 10, 2021,

according to the data reported by the World Health Organization.

The COVID-19 pandemic and the measures taken by the federal,

state and foreign governments to stop the spread of the virus have caused a significant disruption to the U.S.

As a global pandemic with 402,044,502

COVID-19 confirmed cases globally, including 5,770,023 deaths, as of February 10, 2022, according to the data reported by the World Health

Organization (“WHO”).

The COVID-19 pandemic and the measures taken by the federal, state and foreign governments to stop

the spread of the virus have caused a significant disruption to the U.S.

and global economy.

Coronaviruses

(CoV) are a large family of viruses that historically have been associated with illness ranging from mild symptoms similar to

the common cold to more severe respiratory disease.

Infection with the novel SARS-CoV-2 has been associated with a wide range

of responses, from no symptoms to more severe disease that has included pneumonia, severe acute respiratory syndrome, kidney failure,

The incubation period for SARS-CoV-2 is believed to be within 14 days after exposure, with most illness occurring within

about 5 days after exposure.

The ability of someone with no symptoms to transmit infection to another person has heightened the

public health challenge of COVID-19.

(CoV) are a large family of RNA viruses that historically have been associated with illness ranging from mild symptoms similar to the

common cold to more severe respiratory disease.

Infection with the novel SARS-CoV-2 has been associated with a wide range of responses,

from no symptoms to more severe disease that has included pneumonia, severe acute respiratory syndrome, kidney failure, and death.

incubation period for SARS-CoV-2 is believed to be within 14 days after exposure, with most illness occurring within about 5 days after

SARS-CoV-2, like other RNA viruses, is prone to mutate over time, resulting in the emergence of multiple variants.

mutations in the viral genome can alter the virus’s pathogenic potential.

Even a single amino acid exchange can drastically affect

a virus’s ability to evade the immune system and complicate the vaccine and antibody therapeutics development against the virus.

Based on the recent epidemiological update by the WHO, five SARS-CoV-2 VOCs (variants of concern) have been identified since the

beginning of the pandemic.

Also, as demonstrated in Delta and Omicron variants, some variations allow the virus to spread more

easily and make it resistant to the treatments and vaccines.

October 22, 2020, FDA approved the antiviral drug Veklury (remdesivir) for the treatment of COVID-19 requiring hospitalization.

Remdesivir is a nucleotide prodrug that inhibits viral replication and was previously evaluated in clinical trials for Ebola treatment

We are aggressively pursuing the development of novel antiviral compounds for the treatment of coronavirus infections

using our established proprietary drug discovery platform.

By targeting the viral replication enzymes and protease, we believe

it is possible to develop an effective treatment for all coronavirus diseases including COVID-19, Severe Acute Respiratory Syndrome

(SARS), and Middle East Respiratory Syndrome (MERS) - coronaviruses.

is a nucleotide prodrug that inhibits viral replication and was previously evaluated in clinical trials for Ebola treatment in 2014.

In addition to Veklury, the FDA has recently issued emergency authorization use on several antibody and antiviral therapeutics.

We are aggressively pursuing the development of novel antiviral compounds for the treatment of coronavirus infections using our established

proprietary drug discovery platform.

By targeting the viral replication enzymes and protease, we believe it is possible to develop an

effective treatment for all coronavirus diseases including COVID-19, Severe Acute Respiratory Syndrome (SARS), and Middle East Respiratory

Syndrome (MERS) - coronaviruses.

A large competitive market with opportunity for shorter treatment regimens .

1 unchanged sentence

Currently, the standard treatment varies with the genotype of the HCV infection.

Prior to late 2013, treatment included peginterferon alpha and ribavirin, along with a protease inhibitor (either telaprevir,

boceprevir, or simeprevir).

In late 2013, sofosbuvir, a drug belonging to a new class of drugs called “nucleoside analogs”

or “Nucs,”

was approved to treat HCV.

In patients infected with HCV genotype 1 (the most common HCV genotype in the

US), sofosbuvir was administered in combination with peginterferon alpha and ribavirin.

In patients with HCV genotypes 2 and 3,

however, sofosbuvir could be effectively administered in combination with ribavirin, without the need for peginterferon alpha.

Since 2014, several new combinations of direct-acting antiviral agents (“DAAs”) have been approved for the treatment

of HCV infection.

These include Harvoni (sofosbuvir/ledipasvir) 12 weeks of treatment, Viekira Pak (ombitasvir/paritaprevir/ritonavir,

dasabuvir) 12 weeks of treatment, Epclusa (sofosbuvir/velpatasvir) 12 weeks of treatment, Zepatier (elbasvir/grazoprevir) 12 weeks

of treatment and Mavyret (glecaprevir/pibrentasvir) 8 weeks of treatment.

We believe the next improvements in HCV treatment will

be ultra-short treatments of four to six weeks, the goal of our program.

anticipate a significant global HCV market opportunity that will persist through at least 2036, given the large prevalence of

HCV infection worldwide.

The 2017 World Health Organization Global Hepatitis Report estimates that 71 million people worldwide

have chronic HCV infections.

are targeting the viral NS5B polymerase with an NNI, which could be developed as part of an all-oral, pan-genotypic combination

late 2013, treatment included peginterferon alpha and ribavirin, along with a protease inhibitor (either telaprevir, boceprevir, or simeprevir).

In late 2013, sofosbuvir, a drug belonging to a new class of drugs called “nucleoside analogs” or “Nucs,” was

approved to treat HCV.

In patients infected with HCV genotype 1 (the most common HCV genotype in the US), sofosbuvir was administered

in combination with peginterferon alpha and ribavirin.

In patients with HCV genotypes 2 and 3, however, sofosbuvir could be effectively

administered in combination with ribavirin, without the need for peginterferon alpha.

Since 2014, several new combinations of direct-acting

antiviral agents (“DAAs”) have been approved for the treatment of HCV infection.

These include Harvoni (sofosbuvir/ledipasvir)

12 weeks of treatment, Viekira Pak (ombitasvir/paritaprevir/ritonavir, dasabuvir) 12 weeks of treatment, Epclusa (sofosbuvir/velpatasvir)

12 weeks of treatment, Zepatier (elbasvir/grazoprevir) 12 weeks of treatment and Mavyret (glecaprevir/pibrentasvir) 8 weeks of treatment.

We believe the next improvements in HCV treatment will be ultra-short combination oral treatments of four to six weeks, the goal of our

anticipate a significant global HCV market opportunity that will persist through at least 2036, given the large prevalence of HCV infection

The 2017 World Health Organization Global Hepatitis Report estimates that 71 million people worldwide have chronic HCV infections.

are targeting the viral NS5B polymerase with an NNI, which could be developed as part of an all-oral, pan-genotypic combination regimen.

Our focus is on developing what is now called ultrashort treatment regimens from 4 to 6 weeks in length.

Such a combination

treatment CC-31244 with different classes of approved DAAs has the potential to change the paradigm of treatment for HCV with

a shorter duration of treatment.

Combination strategies with approved drugs could allow us to expand CC-31244 into the HCV antiviral

therapeutic area globally and could lead to a high and fast cure rate, to improved compliance, and to reduced treatment duration.

To our knowledge no competing company has yet developed a short HCV treatment of less than 8 weeks with a high (>95%) sustained

virologic response (SVR) at week 12.

Such a combination treatment

CC-31244 with different classes of approved DAAs has the potential to change the paradigm of treatment for HCV with a shorter duration

of treatment.

Combination strategies with approved drugs could allow us to expand CC-31244 into the HCV antiviral therapeutic area globally

and could lead to a high and fast cure rate, to improved compliance, and to reduced treatment duration.

To our knowledge no competing

company has yet developed a short HCV treatment of less than 8 weeks with a high (>95%) sustained virologic response (SVR) at week

an HCV NNI, is a potential best in class pan-genotypic inhibitor of NS5B polymerase for the treatment of HCV.

The Company completed

a Phase 1a/b study in Canada in September 2016, with favorable safety results in a randomized, double-blinded, Phase 1a/b study

in healthy volunteers and HCV-infected subjects.

The Company has completed a Phase 2a study in HCV genotype 1 subjects in the

United States.

Cocrystal presented the interim results from the Phase1a/b study at the APASL in February 2017.

HCV-infected subjects

treated with CC-31244 had a rapid and marked decline in HCV RNA levels, and slow viral rebound after treatment.

Results of this

study suggest that CC-31244 could be an important component in a shortened duration all-oral HCV combination therapy.

enrollment has been completed in the Phase 2b and the final study report filed with the FDA.

See “Item 1 –

Research and Development Update –

Hepatitis C”

for more information.

The Company completed a

Phase 1a/b study in Canada in September 2016, with favorable safety results in a randomized, double-blinded, Phase 1a/b study in healthy

volunteers and HCV-infected subjects.

The Company completed a Phase 2a study in HCV genotype 1 subjects in the United States.

presented the interim results from the Phase1a/b study at the APASL in February 2017.

HCV-infected subjects treated with CC-31244 had

a rapid and marked decline in HCV RNA levels, and slow viral rebound after treatment.

Results of this study suggest that CC-31244 could

be an important component in a shortened duration all-oral HCV combination therapy.

Patient enrollment has been completed in the Phase

2b and the final study report filed with the FDA.

See “Item 1 – Business – Research and Development Update –

Hepatitis C” for more information.

Company has been seeking a partner for further clinical development of CC-31244 since completing Phase 2a trials.

A worldwide public health problem responsible for close to 90% of epidemic, non-bacterial outbreaks of gastroenteritis around

is a very common and highly contagious virus that causes symptoms of acute gastroenteritis including nausea, vomiting, stomach

pain and diarrhea.

A worldwide public health problem responsible for close to 90% of epidemic, non-bacterial outbreaks of gastroenteritis around the world .

is a very common and highly contagious virus that causes symptoms of acute gastroenteritis including nausea, vomiting, stomach pain and

Other symptoms include fatigue, fever and dehydration.

Noroviruses are a major cause of gastrointestinal illness

in closed and crowded environments, having become notorious for their common occurrence in hospitals, nursing homes, child care

facilities, and cruise ships.

In the United States alone, noroviruses are the most common cause of acute gastroenteritis, and

are estimated to cause 20 million illnesses each year and contribute to 70,000 hospitalizations and 800 deaths.

Noroviruses are

responsible for up to 1.1 million hospitalizations and 218,000 deaths annually in children in the developing world.

In immunosuppressed

patients, chronic norovirus infection can lead to a debilitating illness with extended periods of nausea, vomiting and diarrhea.

There is currently no effective treatment or effective vaccine for norovirus, and the ability to curtail outbreaks is limited.

A few companies, including Chimerix, are developing antiviral treatments for this disease and three candidate vaccines are currently

in early stages of clinical testing by GlaxoSmithKline, Ligocyte and Takeda Pharmaceuticals.

targeting viral replication enzymes and a viral protease, we believe it is possible to develop an effective treatment for all

genogroups of norovirus.

Also, because of the significant unmet medical need and the possibility of chronic norovirus infection

in immunocompromised individuals, new antiviral therapeutic approaches may warrant an accelerated path to market.

is developing inhibitors of the RNA-dependent RNA polymerase and protease of norovirus.

Similar to the HCV polymerases, these

enzymes are essential to viral replication and is highly conserved between all noroviral genogroups.

Therefore, an inhibitor of

these enzymes might be an effective treatment or short-term prophylactic agent, when administered during a cruise or nursing home

stay, for example.

We have developed X-ray quality norovirus polymerase and protease crystals and have identified promising inhibitors.

We are implementing the platform and approaches that have proven successful in our other antiviral programs.

Noroviruses are a major cause of gastrointestinal illness in closed

and crowded environments, having become notorious for their common occurrence in hospitals, nursing homes, child care facilities, and

cruise ships.

In the United States alone, noroviruses are the most common cause of acute gastroenteritis, and are estimated to cause

20 million illnesses each year and contribute to 70,000 hospitalizations and 800 deaths.

Noroviruses are responsible for up to 1.1 million

hospitalizations and 218,000 deaths annually in children in the developing world.

In immunosuppressed patients, chronic norovirus infection

can lead to a debilitating illness with extended periods of nausea, vomiting and diarrhea.

There is currently no effective treatment

or effective vaccine for norovirus, and the ability to curtail outbreaks is limited.

A few companies, including Chimerix, are developing

antiviral treatments for this disease and three candidate vaccines are currently in early stages of clinical testing by GlaxoSmithKline,

Ligocyte and Takeda Pharmaceuticals.

targeting viral replication enzymes and a viral protease, we believe it is possible to develop an effective treatment for all genogroups

of norovirus.

Also, because of the significant unmet medical need and the possibility of chronic norovirus infection in immunocompromised

individuals, new antiviral therapeutic approaches may warrant an accelerated path to market.

The Company is developing inhibitors of

the RNA-dependent RNA polymerase and protease of norovirus.

Similar to the HCV polymerases, these enzymes are essential to viral replication

and is highly conserved between all noroviral genogroups.

Therefore, an inhibitor of these enzymes might be an effective treatment or

short-term prophylactic agent, when administered during a cruise or nursing home stay, for example.

We have developed X-ray quality norovirus

polymerase and protease crystals and have identified promising inhibitors.

We are implementing the platform and approaches that have

proven successful in our other antiviral programs.

success depends, in part, upon our ability to protect our core technology.

To establish and protect our proprietary rights, we

rely on a combination of patents, patent applications, trademarks, copyrights, trade secrets and know-how, license agreements,

confidentiality procedures, non-disclosure agreements with third parties, employee disclosure and invention assignment agreements,

and other contractual rights.

patent portfolio consists of issued patents and pending applications in the areas primarily related to the treatment of disease

associated with HCV, Influenza A, Influenza B, and Norovirus/Coronavirus.

our HCV program, our patent portfolio consists of four patent families, with granted patents in the U.S.

and Europe, as well as

China, Canada, Eurasia, Japan, and Singapore.

To establish and protect our proprietary rights, we rely on

a combination of patents, patent applications, trademarks, copyrights, trade secrets and know-how, license agreements, confidentiality

procedures, non-disclosure agreements with third parties, employee disclosure and invention assignment agreements, and other contractual

patent portfolio consists of issued patents and pending applications in the areas primarily related to the treatment of disease associated

with HCV, Influenza A, Influenza B, and norovirus/coronavirus.

our HCV program, our patent portfolio consists of several patent families, with granted patents in the U.S.

and Europe, as well as China,

Canada, Eurasia, Japan, and Singapore.

Applications are pending in numerous other jurisdictions.

our Influenza A program, our patent portfolio consists of four patent families, including two pending international (PCT) applications

our Influenza A program, our patent portfolio consists of several patent families, including two pending international (PCT) applications

and two families of pending applications in the U.S.

and various foreign countries.

our Influenza A/B program, our patent portfolio consists of a number of patent families pending, variously, as international (PCT)

applications and in Taiwan.

Aspects of this program are developed in collaboration with Merck.

our Norovirus and Coronavirus programs, our patent portfolio consists of three pending families of U.S.

provisional applications,

and a portfolio of patent families licensed through KSURF.

In our Influenza A/B program, our patent portfolio

consists of a number of patent families pending, variously, as international (PCT) applications and in Taiwan.

Aspects of this program

are developed in collaboration with Merck.

In our norovirus and coronavirus programs, our

patent portfolio consists of three pending families of U.S.

provisional applications, and a portfolio of patent families licensed through

Collaborations

Collaboration

January 2, 2019, we entered into an Exclusive License and Research Collaboration Agreement (the “Collaboration Agreement”)

with Merck to discover and develop certain proprietary influenza A/B antiviral agents.

1 unchanged sentence

clinical development at Merck, and Merck is responsible for worldwide commercialization of any products derived from the collaboration.

The Company received an upfront payment of $4,000,000 in January 2019 and is eligible to receive milestone payments related to

designated development, regulatory and sales milestones with the potential to earn up to $156,000,000, as well as royalties on

product sales.

The Collaboration Agreement operates under a Research Operating Plan (ROP) which includes goals for both organizations.

In January 2021, the Company announced it had completed all research obligations under the Merck exclusive worldwide license and

collaboration agreement, and that Merck is now solely responsible for further development of the influenza A/B antiviral compounds

that were discovered in the collaboration using Cocrystal’s unique structure-based technologies and Nobel Prize-winning

The Company received an upfront payment of $4,000,000 in January 2019 and is eligible to receive milestone payments related to designated

development, regulatory and sales milestones with the potential to earn up to $156,000,000, as well as royalties on product sales.

than the initial upfront payment, to date we have not received any payments under this Collaboration Agreement.

The Collaboration

Agreement operates under a Research Operating Plan (ROP) which includes goals for both organizations.

In January 2021, the Company announced

it had completed all research obligations under the Collaboration Agreement, and that Merck is now solely responsible for further

development of the influenza A/B antiviral compounds that were discovered in the collaboration using Cocrystal’s unique structure-based

technologies and Nobel Prize-winning expertise.

State University Research Foundation

entered into a License Agreement with KSURF on February 18, 2020 to further develop certain proprietary broad-spectrum antiviral

compounds for the treatment of Norovirus and Coronavirus infections.

to the terms of the License Agreement, KSURF granted the Company an exclusive royalty bearing license to practice under certain

patent rights, under patent applications covering antivirals against coronaviruses, caliciviruses, and picornaviruses, and related

know-how, including to make and sell therapeutic, diagnostic and prophylactic products.

Company agreed to pay KSURF a one-time non-refundable license initiation fee of $80,000 under the License Agreement, and annual

license maintenance fees.

The Company also agreed to make certain future milestone payments of up to approximately $3.1 million,

dependent upon the progress of clinical trials, regulatory approvals, and initiation of commercial sales in the United States

and certain countries outside the United States.

April 19, 2020, the Company entered into a second License Agreement with KSURF in addition to the License Agreement entered into

in February 2020.

to the terms of the second License Agreement, KSURF granted the Company an exclusive royalty bearing license to practice under

certain patent rights under patent applications covering antivirals against coronaviruses, caliciviruses, and picornaviruses,

and related know-how, including to make and sell therapeutic, diagnostic and prophylactic products.

entered into a License Agreement with KSURF on February 18, 2020 to further develop certain proprietary broad-spectrum antiviral compounds

for the treatment of norovirus and coronavirus infections.

to the terms of the License Agreement, KSURF granted the Company an exclusive royalty bearing license to practice under certain patent

rights, under patent applications covering antivirals against coronaviruses, caliciviruses, and picornaviruses, and related know-how,

including to make and sell therapeutic, diagnostic and prophylactic products.

Company agreed to pay KSURF a one-time non-refundable license initiation fee of $80,000 under the License Agreement, and annual license

maintenance fees.

The Company also agreed to make certain future milestone payments of up to approximately $3.1 million, dependent upon

the progress of clinical trials, regulatory approvals, and initiation of commercial sales in the United States and certain countries

outside the United States.

April 19, 2020, the Company entered into a second License Agreement with KSURF in addition to the License Agreement entered into in February

to the terms of the second License Agreement, KSURF granted the Company an exclusive royalty bearing license to practice under certain

patent rights under patent applications covering antivirals against coronaviruses, caliciviruses, and picornaviruses, and related know-how,

including to make and sell therapeutic, diagnostic and prophylactic products.

Company agreed to pay KSURF a one-time non-refundable license initiation fee and annual license maintenance fees.

also agreed to make certain future milestone payments of up to approximately $4.2 million, dependent upon the progress of clinical

trials, regulatory approvals, and initiation of commercial sales in the United States and certain countries outside the United

The Company also agreed

to make certain future milestone payments of up to approximately $4.2 million, dependent upon the progress of clinical trials, regulatory

approvals, and initiation of commercial sales in the United States and certain countries outside the United States.

Discovery Collaboration with HitGen and InterX

has a drug discovery collaboration with HitGen, a biotech company with an innovative DNA Encoded Library technology, and InterX

Inc., a computer software company with a biomolecular simulation for drug discovery.

The collaboration was initiated in September

2017 and has a term through August 2023.

this collaboration, Cocrystal, HitGen and InterX scientists are applying HitGen’s DNA-encoded library (DEL) technology platform,

Cocrystal’s structure-based drug discovery platform technology, and InterX’s computational science to develop novel

antiviral lead candidates.

The DEL technology combines the power of molecular biology, combinatorial chemistry, high throughput

sequencing and advanced informatics to identify potential drug candidates.

Cocrystal applies its technology to determine the cocrystal

structures of the potential drug candidates identified from the DEL library.

This structural information is then combined with

InterX’s advanced computer algorithms to predict inhibitor-target interactions.

A Joint Steering Committee comprised of

representatives from all three companies is overseeing the collaboration.

biotechnology and pharmaceutical industries are subject to intense and rapidly changing competition as companies seek to develop

new technologies and proprietary products.

We know of several companies that have marketed or are developing products for the

treatment of influenza, coronavirus and HCV, including Roche, Gilead Sciences, Inc.

(“Gilead”), Merck, Janssen Pharmaceuticals,

Inc., Bristol-Myers Squibb, Toyama Chemical Co., Shionogi/Roche and Abbvie, Inc.

has a drug discovery collaboration with HitGen, a biotech company with an innovative DNA Encoded Library technology, and InterX Inc.,

a computer software company with a biomolecular simulation for drug discovery.

The collaboration was initiated in September 2017 and

has a term through August 2023.

this collaboration, Cocrystal, HitGen and InterX scientists are applying HitGen’s DNA-encoded library (DEL) technology platform,

Cocrystal’s structure-based drug discovery platform technology, and InterX’s computational science to develop novel antiviral

lead candidates.

The DEL technology combines the power of molecular biology, combinatorial chemistry, high throughput sequencing and

advanced informatics to identify potential drug candidates.

Cocrystal applies its technology to determine the cocrystal structures of

the potential drug candidates identified from the DEL library.

This structural information is then combined with InterX’s advanced

computer algorithms to predict inhibitor-target interactions.

A Joint Steering Committee comprised of representatives from all three

companies is overseeing the collaboration.

The biotechnology and pharmaceutical industries

are subject to intense and rapidly changing competition as companies seek to develop new technologies and proprietary products.

worldwide competition from larger biotechnology and pharmaceutical companies, universities and other academic or research institutions

and government agencies that are developing and commercializing pharmaceutical products similar to our product candidates that target

the viruses we are seeking to treat.

We know of several companies that have marketed or are developing products for the treatment of

influenza, coronavirus and HCV, including Roche, Gilead Sciences, Inc.

(“Gilead”), Merck, Janssen Pharmaceuticals, Inc.,

Bristol-Myers Squibb, Toyama Chemical Co., Shionogi/Roche and Abbvie, Inc.

Their products are widely considered effective.

Further, in the wake of the global COVID-19 pandemic a number of third parties, including large biotechnology and pharmaceutical

companies such as Pfizer Inc., Moderna, Inc., Janssen Pharmaceuticals, Inc., and academic institutions have been conducting research

aimed at development of an effective treatment for, or a vaccine against, COVID-19.

Many of the companies developing products

for the viral diseases that are the focus of our programs have substantially greater financial resources, including government

funding, expertise and capabilities than we do and have existing products in significantly more advanced stages of development.

the wake of the global COVID-19 pandemic a number of third parties, including large biotechnology and pharmaceutical companies such as

Pfizer Inc., Moderna, Inc., Janssen Pharmaceuticals, Inc., and academic institutions have been conducting research aimed at development

of an effective treatment for, or a vaccine against, COVID-19.

A number of vaccines and treatments for COVID-19 have been commercialized

under the FDA’s emergency use authorization.

At least one treatment and two vaccines for COVID-19 have also received FDA approval.

Many of the companies developing products for the viral diseases that are the focus of our programs have substantially greater financial

resources, including government funding, expertise and capabilities than we do and have existing products in significantly more advanced

stages of development.

Additionally, viral mutations can lead to new strains or variants of a virus that may be more resistant to products

we develop when compared to those of competitors.

See “Risk Factors” for more information on the risks we face with respect

to our competition.

To date, we have not fully developed, received

regulatory approval for or commercialized any of our product candidates.

Our ability to compete will depend, to a great extent, on the

speed in which we and our collaborators can develop safe and effective product candidates, complete clinical testing and regulatory approval

processes, and coordinate with third parties to produce and distribute the resulting products in sufficient commercial quantities to

create and maintain a market for such products at favorable costs and prices.

If we do complete development of and obtain regulatory

approval to market any product candidate, we anticipate that the competition we would face with respect to such product would be based

on a combination of a number of factors including efficacy, safety, reliability, availability, price, patent position, and other factors.

authorities extensively regulate the research, development, testing, manufacturing and commercialization of drug products.

product candidates we develop must be approved by the U.S.

Food and Drug Administration (“FDA”) before they may be

legally marketed in the U.S., and by the appropriate foreign regulatory agencies before they may be legally marketed in other

The clinical testing of product candidates to establish their safety and efficacy in humans is subject to substantial

statutory and regulatory requirements with which we must comply.

of December 31, 2020, we employed 13 full-time employees.

Of these full-time employees, eight are engaged in research and development

In addition, we have contracts with Clinical Research Organizations (“CROs”), Contract Manufacturing Organizations

(“CMOs”) and consultants to provide chemistry, toxicology, preclinical, clinical, and regulatory work on our programs.

candidates we develop must be approved by the U.S.

Food and Drug Administration (“FDA”) before they may be legally marketed

in the U.S., and by the appropriate foreign regulatory agencies before they may be legally marketed in other countries.

testing of product candidates to establish their safety and efficacy in humans is subject to substantial statutory and regulatory requirements

with which we must comply.

In addition to the U.S.

requirements such as those

enforced by the FDA with respect to safety and efficacy of research, testing, development and production, we also must comply with applicable

laws and regulations of any foreign jurisdictions in which we operate.

For example, our Phase 1 trial currently underway in Australia

in 2022 for CC-42344, our lead Influenza A product candidate, causes us to be subject to the Australian government’s laws and regulations

pertaining to the research and development, including clinical testing on human subjects, of therapeutic product candidates.

in Australia will also subject us to more general laws applicable to operations abroad, such as the U.S.

Foreign Corrupt Practices Act

(the “FCPA”) and comparable legislation and regulation in foreign jurisdictions.

Generally speaking, the FCPA prohibits U.S.

corporations and their representatives from offering, promising, authorizing or making payments to any foreign government official, government

staff member, political party or political candidate to obtain or retain business abroad.

The scope of the FCPA includes interactions

with certain healthcare professionals in many countries.

Other countries have enacted similar anti-corruption laws and/or regulations.

Further, because of our anticipated reliance on one or more CROs and CMOs with respect to our research and development activities both

and in foreign jurisdictions, we may have limited control over compliance with such requirements in certain instances.

With respect to coronavirus-related products as

of the date of this Report, with the exception of Veklury (remdesivir), an antiviral drug commercialized by Gilead, no treatment has

been approved by the FDA for COVID-19 symptoms.

Instead, most existing treatments for COVID-19 that are or have been offered by competing

companies have been made available under the FDA’s emergency use authorization.

The FDA has, however, reduced or removed many of

these authorizations, including for treatments using monoclonal antibodies such as the REGEN-COV treatment commercialized by Regeneron

Pharmaceuticals, Inc., due to waning efficacy against symptoms caused by the Omicron variant of the virus which until recently was the

dominant strain.

As the foregoing description demonstrates, our coronavirus programs and any product candidates that we may develop therefrom

are subject to uncertainty as to the FDA’s actions, which are in turn inherently unpredictable given the unpredictable nature of

the virus and its mutations, as well as their effects on treatment compounds.

As of December 31, 2021, we employed 13 full-time

Of these full-time employees, ten are engaged in research and development activities.

In addition, we have contracts with

CROs, CMOs and consultants to provide chemistry, toxicology, preclinical, clinical, and regulatory work on our programs, including in

both pre-clinical and clinical studies for our product candidates.

Company was formerly incorporated in Nevada under the name Biozone Pharmaceuticals, Inc.

(“Biozone”).

On January 2, 2014,

2014, Biozone sold substantially all of its assets to MusclePharm Corporation, and, on the same day, merged with Cocrystal Discovery,

(“Discovery”) in a transaction accounted for as a reverse merger.

Following the merger, the Company assumed Discovery’s

Biozone sold substantially all of its assets to MusclePharm Corporation, and, on the same day, merged with Cocrystal Discovery, Inc.

(“Discovery”) in a transaction accounted for as a reverse merger.

Following the merger, the Company assumed Discovery’s

business plan and operations.

On March 18, 2014, the Company reincorporated in Delaware under the name Cocrystal Pharma, Inc.

November 25, 2014, a subsidiary of the Company and affiliated entities completed a series of merger transactions.

a subsidiary of the Company merged with RFS Pharma, LLC, a Georgia limited liability company (RFS Pharma”).

corporate website is www.cocrystalpharma.com.

We make available on our website under “Investors –

SEC Filings”

access to our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, Proxy Statements on Schedule

14A and amendments to those materials filed or furnished pursuant to Section 13(a) or 15(d) of the Securities Exchange Act of

1934, as amended (the “Exchange Act”), free of charge.

We make available on our website under “Investors – SEC Filings” access

to our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, Proxy Statements on Schedule 14A and

amendments to those materials filed or furnished pursuant to Section 13(a) or 15(d) of the Securities Exchange Act of 1934, as amended

(the “Exchange Act”), free of charge.

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business