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Item 1. Business

2023-03-29 compared with 2022-03-23 · 208 added, 240 removed, 250 unchanged (64% 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 coronavirus, influenza virus, hepatitis C virus (“HCV”),

and norovirus infections.

(the “Company” or “Cocrystal”) is a clinical-stage 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, norovirus, and hepatitis C virus

(“HCV”) infections.

Company operates in one segment.

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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.

our Chief Scientist and Chairman of both our Scientific Advisory Board and Board of Directors (the “Board”), 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.

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.

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

influenza virus, coronavirus, HCV and norovirus.

influenza virus, coronavirus, norovirus and

Market-Driven

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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.

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.

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

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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

in the winter of 2022 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.

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onset of action:

Antiviral drugs are needed with faster onset of viral load reduction resulting in shorter treatment time.

As viruses can reproduce rapidly and in enormous quantities in human cells, antiviral drugs are needed with faster

onset of viral load reduction resulting in shorter treatment time.

and tolerability :

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

In December 2022, we reported favorable safety and tolerability

results from a Phase 1 study of our oral antiviral CC-42344 developed for the treatment of both pandemic and seasonal influenza A.

of administration:

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the year ended December 31, 2022 the Company focused its research and development efforts primarily in three areas:

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

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.

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.

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

CC-42344, a novel oral PB2 inhibitor, was selected

as a preclinical lead for the treatment of pandemic and seasonal influenza A, and was advanced to a Phase 1 clinical trial in 2022 as

described in more detail below.

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

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.

March 2022 enrollment was initiated in a randomized, double-blind, placebo-controlled Phase 1 study of CC-42344, which was conducted

in Australia.

In April 2022 we announced preliminary results from the first two cohorts of the single-ascending dose portion of the study

in which CC-42344 demonstrated a favorable safety and pharmacokinetic profile.

In December 2022, we reported favorable safety and tolerability

results from a Phase 1 study of CC-42344 for the treatment of both pandemic and seasonal influenza A.

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

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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

and that Merck would be 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

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.

Merck is continuing development of the influenza

A/B antiviral compounds under the terms of our Collaboration Agreement and is legally protecting the intellectual property of the collaboration

October 2022 we announced the selection of a novel, broad-spectrum antiviral drug candidate CDI-988 for clinical development as an oral

treatment for SARS-CoV-2, the virus that causes COVID-19.

CDI-988 targets a highly conserved region in the active site of SARS-CoV-2

main (3CL) protease required for viral replication and was specifically designed and developed as an oral antiviral candidate for COVID-19

using Cocrystal’s proprietary structure-based drug discovery platform technology.

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 coronaviruses, including SARS-CoV-2, the virus that causes COVID-19.

Both compounds exhibited

superior in vitro potency against SARS-CoV-2 with activity maintained against recent variants of concern.

In preclinical studies,

both candidates demonstrated a favorable safety profile and pharmacokinetic properties supportive of daily oral dosing.

begin a randomized, double-blind, placebo-controlled Phase 1 study of CDI-988 during the first half of 2023.

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

CDI-45205 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.”

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

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

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

We expect to select a preclinical lead in the first half of 2023.

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

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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

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

2017 through 2022.

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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

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

(Xofluza®) have appeared, and in some cases predominated.

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

was resistant to Tamiflu.

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

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

CC-42344, a novel PB2 inhibitor,

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 –

Research and Development Update – Influenza” for more information.

Xofluza-resistant strains emerged in both the US and Japan

within several months of Xofluza being on the market.

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

neuraminidase (N).

Company selected CC-42344, a novel PB2 inhibitor, as a lead candidate and has clinically completed a Phase 1 study.

In December 2022,

the Company reported on the favorable safety and tolerability results of the CC-42344 Phase 1 study and plan to initiate a Phase 2a study

in the first half of 2023.

CC-42344 binds to a highly conserved PB2 site of the influenza polymerase (PB1:

PA), and exhibits a novel

mechanism of action.

CC-42344 has shown 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.

was approved as Xofluza in Japan on February 23, 2018, and in the US as baloxavir marboxil (trade name Xofluza ® ) on October

See “Item 1 – Business – Research and Development Update – Influenza” for more information.

Xofluza-resistant

strains emerged in both the US and Japan within several months of Xofluza being on the market.

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

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.

a global pandemic with 760,360,956 COVID-19 confirmed cases globally, including 6,873,477 deaths, as of March 16, 2023, 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.

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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.

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.

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.

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

(nirmatrelvir and ritonavir) and Lagevrio (molpiravir).

We continue 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 .

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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

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

cruise ships.

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19-21 million illnesses each year and contribute to 109,000 hospitalizations and 900 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.

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 have been developing antiviral

treatments for this disease and four candidate vaccines are in stages of clinical testing by Vaxart Pharmaceutical, Takeda Pharmaceuticals,

Anhui Zhifei Longcom Biopharmaceutical (China) and National Vaccine and Serum Institute (China).

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

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

and is highly conserved between all noroviral genogroups.

and are highly conserved between all noroviral genogroups.

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

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and various foreign countries.

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

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, which is legally protecting the intellectual property

of the collaboration compounds.

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.

Collaborations

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the terms of the Collaboration Agreement, Merck is funding research and development for the program at Cocrystal and Merck, including

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.

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.

clinical development at Merck, protecting intellectual property 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.

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

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

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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.

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.

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.

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

technologies and proprietary products.

We face 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

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.

A number of vaccines and treatments for COVID-19

have been commercialized under the FDA’s emergency use authorization.

At least one treatment and four vaccines for COVID-19 have

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.

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.

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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.

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 in Australia in 2022 for CC-42344, our lead Influenza

A product candidate, caused 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.

Our presence in Australia has also subjected

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.

In general, 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.

On January 2, 2014,

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.

Further, because of our reliance on one or more CROs and

CMOs with respect to our research and development activities both in the U.S.

and in foreign jurisdictions, we may have limited control

over compliance with such requirements in certain instances.

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.

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.

of March 21, 2023, we employed 12 full-time employees.

Of these full-time employees, nine 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 preclinical and clinical studies for our product candidates.

corporate website is www.cocrystalpharma.com.

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What changed 10-K

Item 1. Business