COCP US Equity☆

Item 1A. Risk Factors. 10

Item 1B. Unresolved Staff Comments. 37

Item 1C. Cybersecurity. 38

Item 2. Properties. 38

Item 3. Legal Proceedings. 38

Item 4. Mine Safety Disclosures. 38

Part II. 38

Item 6. [Reserved] 39

Item 7A. Quantitative and Qualitative Disclosures About Market Risk. 42

Item 8. Financial Statements. 42

Item 9A. Controls and Procedures. 43

Item 9B. Other Information. 43

Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections. 43

Part III. 44

Item 10. Directors, Executive Officers and Corporate Governance. 44

Item 11. Executive Compensation. 49

Item 14. Principal Accounting Fees and Services. 54

Part IV. 55

Item 15. Exhibits, Financial Statement Schedules. 55

SIGNATURES 57

PART

I

Item

1. Business.

Overview

Cocrystal

Pharma, Inc. (the “Company” or “Cocrystal”) is a clinical-stage biotechnology company discovering and developing

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 RNA viruses including influenza virus, coronaviruses (including

SARS-CoV-2 & MERS-CoV), norovirus, respiratory virus infections and hepatitis C virus (“HCV”) infections.

The

Company operates as one business entity.

Cocrystal

Technology

We

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

and chronic viral diseases. Our goals include treating and preventing influenza virus, coronavirus, and norovirus infections by discovering

and developing direct-acting antiviral drug candidates targeting required steps in the viral replication process. To discover and design

these direct-acting antiviral drug candidates, 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 viral

enzyme or protein to guide our structure-based drug design. We also use advanced computational methods to screen and design product candidates

using proprietary high-resolution 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 specific

binding characteristics, we seek to develop drugs that are effective against both the virus and possible mutants of the virus and 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, pharmacology, virology, 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 (“SAB”)

and Board of Directors (the “Board”), who received the Nobel Prize in Chemistry in 2006. Our drug discovery process focuses

on the highly conserved regions of the viral drug target 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.

The

Company’s proprietary technology integrates several powerful and specialized computational techniques for drug design:

(2) Atomic resolution 3-D structure determination of drug-binding pockets;

We

have applied these techniques to develop antiviral inhibitors of four important viruses: influenza virus, coronavirus, norovirus and

HCV.

Market-Driven

Product Profiles

In

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:

(1) High barrier to viral resistance;

(2) Effective against all viral subtypes that cause disease;

(3) Novel mechanism of action for therapeutic and/or prophylactic treatments;

(4) Favorable safety and tolerability profile; and

Even

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.

High

barrier to drug resistance: Drug resistance is a major obstacle to developing effective antiviral therapies. Viruses can

reproduce 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. 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. During the COVID-19 pandemic outbreak newly emergent mutated coronaviruses were identified, resulting in the

ineffectiveness of some vaccines and therapeutics. For example, the Omicron variant that arose as the dominant strain of COVID-19 in

late 2021 until COVID-19 diminished 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. In early

2024, a new strain of COVID-19 named JN.1 became the predominant strain of the virus in circulation and was believed to be either

more transmissible or better at evading the immune system than other circulating variants. As of early 2025, the prevalent variants

of COVID-19 were XEC and LP.8.1, each of which emerged in 2024. These two variants are variants under monitoring (VUM) by the World

Health Organization as of February 2025 due to their increasing prevalence globally.

The

Company’s focus on viral drug targets inhibiting replication proteins can potentially overcome the obstacle of viral resistance.

We identify and target critical residues of viral drug targets that are essential for function, and therefore, sensitive to change. A

mutation in these critical residues is likely to inactivate or slow down the replication processes 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 existing drug-resistant variants and select compounds with the highest barrier

to resistance.

Broadly

effective against major strains responsible for a viral disease and multiple indications: 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 and hospitalizations, with influenza A viruses being

solely responsible for past influenza pandemics. 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. Our goal is to design and develop drug candidates that will be effective

on the broadest possible range of viruses causing the disease.

Many

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 enzymes involved in

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

is essentially highly conserved among all strains of a given virus. By targeting these highly conserved regions of the replication enzymes

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

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 and pan-viral drugs.

Fast

onset of action: 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.

Safety

and tolerability: All drugs potentially have side effects, also referred to as adverse effects. These usually result from a drug’s

ability to interact and/or interfere the physiological functions of human proteins, causing undesirable effects. 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.

Ease

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

inhalation or injection.

Research

and Development Update

During

the twelve months ended December 31, 2024 the Company continued to focus its research and development efforts primarily in three areas.

Influenza

Program

We

have several candidates under development for the treatment of influenza infection. CC-42344, a novel PB2 inhibitor, was selected as

a preclinical lead as an oral or inhaled treatment of pandemic and seasonal influenza A. This candidate binds to a highly conserved PB2

site of influenza polymerase complex (PB1: PB2: PA) and exhibits a novel mechanism of action. CC-42344 showed excellent in vitro

antiviral activity against influenza A strains, including avian pandemic strains and Tamiflu® and Xofluza® resistant strains,

and has favorable pharmacokinetic and drug resistance profiles.

In

addition to the oral candidate of CC-42344, the inhaled CC-42344 is being developed for the potential prophylactic treatment of pandemic

and seasonal influenza infections. Dry powder inhalation development and toxicology studies have been evaluated.

We

received authorization from the United Kingdom Medicines and Healthcare Products Regulatory Agency (MHRA) to conduct a Phase 2a human

challenge study with oral CC-42344 as a potential treatment for pandemic and seasonal influenza A. This randomized, double-blind, placebo-controlled

study is designed to evaluate the safety, tolerability, viral and clinical measurements of influenza A infection in subjects dosed with

oral CC-42344 treatment. In May 2024 we announced completion of enrollment of 78 subjects. In December 2024, the Company announced plans

to extend enrollment for the oral CDI-42344 Phase 2a study due to unexpectedly low influenza infection among study participants. Specifically,

management determined that an extension of the study is necessary due to low infectivity rate of the challenge influenza strain used

in this study, as the establishment of robust influenza infection in healthy, uninfected study subjects is critical to determine clinical

endpoints for evaluating antiviral molecule, and the low infectivity obtained in this study hindered antiviral data analysis. The Company

is currently in continuing discussions with the clinical research organization to address this study and determine a course forward with

respect thereto, including potentially by preparing a protocol amendment or a resubmission for approval by the United Kingdom Medicines

and Healthcare Products Regulatory Agency (“MHRA”) in order to seek enrollment to study and to ensure necessary infection

rates among enrolled study subjects in the study. CC-42344 has demonstrated favorable safety and tolerability profile from the Phase

2a study to date, with no SAEs and no drug-related discontinuations by study participants.

In

June 2024 we reported the potential efficacy of CC-42344 against the new Texas avian flu strain from in vitro studies with the

recently published genome sequence for H5N1. Using our proprietary structure-based platform technology, the Company reported a high-resolution

cocrystal structure of this avian PB2 protein complexed with CC-42344 and confirmed that CC-42344 binds to its highly conserved PB2 region.

The in vitro data using purified Texas avian H5N1 PB2 protein further showed in vitro affinity of CC-42344 similar to that of

previous data using pandemic avian and seasonal influenza A PB proteins.

We

also continue developing novel broad-spectrum influenza antivirals targeting replication enzymes of seasonal and pandemic influenza A

and B strains.

Norovirus

and Coronavirus Programs

We

developed the novel protease inhibitor CDI-988 as an oral pan-viral treatment of noroviruses and coronaviruses, including SARS-CoV-2

and its variants. CDI-988 was specifically designed and developed using our proprietary structure-based drug discovery platform technology

as a broad-spectrum antiviral inhibitor to a highly conserved region in the active site of noroviruses, coronaviruses and other 3CL viral

proteases. We believe CDI-988 represents a first-in-class pan-viral antiviral for the treatment of viral gastroenteritis caused by noroviruses

and coronaviruses, including SARS-CoV-2 and its variants.

Oral

CDI-988 is being clinically evaluated for safety, tolerability and pharmacokinetics including a food-effect cohort in healthy volunteers

in a single-center, randomized, double-blind, placebo-controlled Phase 1 study being conducted in Australia. We expect that the oral

CDI-988 Phase 1 data will support future norovirus and coronavirus Phase 2 and Phase 3 studies.

In

July 2024 we announced favorable safety and tolerability results from the single-ascending dose (SAD) cohorts of the Phase 1 study with

CDI-988. Study participants in the SAD cohorts received CDI-988 in doses ranging from 100 mg to 600 mg. All participants completed the

study with no discontinuations. There were no serious adverse events or severe treatment-emergent adverse events. No clinically significant

observations were noted in laboratory assessments, physical exams or electrocardiograms.

In

September 2024 we initiated dosing of the first subjects in the multiple-ascending dose (MAD) portion of the Phase 1 study with CDI-988

and topline Phase 1 study safety and tolerability SAD results and testing of 800 mg for 10 consecutive days were reported in January

2025 indicating favorable safety and tolerability results. The topline data of the MAD cohorts, including based on an additional cohort

with a higher dose of 1200 mg and a shorter treatment duration of five consecutive days, is expected to be released in the first half

of 2025.

Therapeutic

Targets

Influenza:

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

Influenza

is a severe respiratory illness, caused primarily by influenza A or B virus. Influenza A viruses are the only influenza viruses known

to cause influenza pandemics. Each year there are approximately 1 billion cases of seasonal influenza worldwide, with 3-5 million severe

illnesses and up to 650,000 deaths, according to the World Health Organization (“WHO”). On average about 8% of the U.S. population

contracts influenza each season, according to the Centers for Disease Control and Prevention (“CDC”). In addition to the

health risk, influenza is responsible for approximately $10.4 billion in direct medical costs in the U.S. annually, according to the

National Institutes of Health (“NIH”).

Currently

approved antiviral treatments for influenza are effective but burdened with significant viral resistance. Strains of influenza virus

resistant to the approved treatments oseltamivir phosphate (Tamiflu®), zanamavir (Relenza®) and baloxavir marboxil (Xofluza®)

have appeared and in some cases are predominant. For example, the predominant strain of the 2009 swine influenza pandemic was resistant

to oseltamivir. Oseltamivir inhibits influenza neuraminidase enzymes, which are not highly conserved between viral strains. According

to the WHO, approximately 15% of the H1N1 isolates circulating worldwide were oseltamivir resistant. Also, treatment-emergent resistance

to recently approved baloxavir has been observed during clinical trials and the potential transmission of resistant influenza variants

could significantly diminish baloxavir effectiveness.

Coronavirus:

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

COVID-19

is a global health concern responsible for more than 777 million reported cases globally, including more than 7 million deaths, as of

March 2025, according to data reported by the WHO.

Coronaviruses

(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. The

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

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

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 the Delta, Omicron and other variants, some variations allow the virus to spread more easily

and make it resistant to the treatments and vaccines.

On

October 22, 2020, the U.S. Food and Drug Administration (“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 in 2014. On May 25, 2023, the FDA approved PaxlovidTM (nirmatrelvir tablets and

ritonavir tablets, co-packaged for oral use) for the treatment of mild-to-moderate COVID-19 in adults who are at high risk for progression

to severe COVID-19, including hospitalization or death. For certain hospitalized adults with COVID-19, the FDA has also approved Olumiant®

(baricitinib) and Actemra® (tocilizumab). In addition, the FDA issued emergency use authorization (EUA) for several antibody and

antiviral therapeutics, including and LagevrioTM (molnupiravir).

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).

Norovirus:

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

no effective treatment or vaccine.

Norovirus

is a very common and highly contagious virus that causes symptoms of acute gastroenteritis among people of all ages including nausea,

vomiting, stomach pain and diarrhea as well as fatigue, fever and dehydration. Norovirus infection can be significantly more severe and

prolonged in specific risk groups including infants, children, the elderly and people with immunodeficiency. In immunosuppressed patients,

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

occur most commonly in semi-closed communities and have become notorious for their occurrence in hospitals, nursing homes, childcare

facilities, cruise ships, schools, disaster relief sites and military settings. In the U.S. alone, noroviruses are responsible for an

estimated 21 million cases annually, including 109,000 hospitalizations, 465,000 emergency department visits and an estimated 900 deaths,

according to the CDC. The NIH estimates the annual burden to the United States at $10.6 billion. Noroviruses are responsible for up to

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

There

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

a novel norovirus antiviral candidate for the prophylactic and therapeutic treatment of norovirus infection that is currently in a Phase

1 clinical study. A few companies have been developing vaccines and are in stages of clinical testing, including Vaxart Pharmaceutical,

Moderna, Hillevax, Takeda Pharmaceuticals, Anhui Zhifei Longcom Biopharmaceutical (China) and National Vaccine and Serum Institute (China).

By

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 and prophylactic approaches may warrant an accelerated path to market. We are developing inhibitors

of the RNA-dependent RNA polymerase and protease of norovirus. These enzymes are essential to viral replication and are 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 our proprietary drug discovery platform technology and

approaches that have proven successful in our other antiviral programs.

Hepatitis

C: A large competitive market with opportunity for shorter treatment regimens.

HCV

is a highly competitive and changing market. Since 2014, several 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

PakTM (ombitasvir/paritaprevir/ritonavir, dasabuvir) 12 weeks of treatment, Epclusa® (sofosbuvir/velpatasvir) 12 weeks of treatment,

ZepatierTM (elbasvir/grazoprevir) 12 weeks of treatment and Mavyret® (glecaprevir/pibrentasvir) eight weeks of treatment. We

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

of our program.

We

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

worldwide. The 2024 World Health Organization Global Hepatitis Report estimates that 50 million people worldwide have chronic HCV infections

with about 1 million new infections occurring per year and an estimated 3.2 million adolescents and children with chronic HCV infection.

We

are targeting the viral NS5B polymerase with a non-nucleoside inhibitor (“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 four to six weeks

in length. Combining CC-31244 with different classes of approved direct-acting antivirals (“DAAs”) has the potential to change

the paradigm of treatment for HCV by shortening the 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.

CC-31244,

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

double-blinded Phase 1a/b study in healthy volunteers and HCV-infected subjects in Canada in September 2016, with favorable safety results.

We completed a Phase 2a study in HCV genotype 1 subjects in the U.S. in 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. In 2017, we completed the Phase 2a final study report as

filed with the FDA.

We

have been seeking a partner for further clinical development of CC-31244 since completing a Phase 2a study.

Intellectual

Property

Our

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.

Our

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

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

In

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.

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 were developed in collaboration with Merck, which is legally protecting the intellectual property

of the collaboration compounds.

In

our norovirus and coronavirus programs, our patent portfolio consists of three pending families of U.S. provisional applications.

In

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.

Collaborations

Merck

On

December 15, 2023, we received written notice from Merck of Merck’s election to terminate the Collaboration Agreement, dated January

2, 2019, by and between the Company and Merck, with respect to the collaboration with Merck on the development of influenza A/B antiviral

compounds. The termination of the Agreement took effect on March 14, 2024. The termination resulted from the inability to develop the

compounds to meet a specific aspect of Merck’s program.

Kansas

State University Research Foundation

Cocrystal

entered into two License Agreement with KSURF (the “Foundation”) on February 18, 2020 to further develop certain proprietary

broad-spectrum antiviral compounds for the treatment of norovirus and coronavirus infections.

On

February 28, 2024, the Company provided notice to the Foundation of the Company’s election to terminate the 2020 License Agreements.

The terminations, which were made due to the Company’s determination that further development efforts under the License Agreements

would be futile, took effect on March 29, 2024.

Business-Competition

The

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, norovirus 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 began conducting

research aimed at development of an effective treatment for, or a vaccine against, COVID-19. As a result of these efforts, a number of

vaccines and treatments for COVID-19 have been commercialized under FDA approval, or under the FDA’s emergency use authorization,

although certain of these approvals or authorizations are limited to specified circumstances. At least four treatments and five 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.

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

effective clinical testing and advance through 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.

Government

Regulation

Government

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

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,

as a result of our Phase 1 trial in Australia for CDI-988, our lead norovirus and coronavirus product candidate, we are 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. Further, our Phase 2a study for in the United Kingdom for CC-42344 subjects us to similar laws and

regulations in the United Kingdom. Our presence in foreign countries 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 reliance on one or more CROs and clinical manufacturing organizations

(“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.

Human

Capital

As

of December 31, 2024, we employed 11 full-time employees. Of these full-time employees, eight are engaged in clinical advancement and

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.

Available

Information

Our

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.

ITEM

1A. RISK FACTORS

You

should carefully consider the risks described below, as well as other information contained in this Annual Report on Form 10-K (this

“Report”), including the consolidated financial statements and the notes thereto and “Management’s Discussion

and Analysis of Financial Condition and Results of Operations.” The occurrence of any of the events discussed below could significantly

and adversely affect our business, prospects, results of operations, financial condition, and cash flow.

Summary

Risk Factors

Our

business is subject to numerous risks and uncertainties that you should consider before investing in our common stock. The following

is a summary of the principal risk factors we face:

● our financial statements are qualified on a going concern basis;

● our ability to manage our growth and our expanded operations;

● failure to maintain the security of patient-related information;

● our ability to attract and retain key scientific and management personnel;

RISK

FACTORS

RISK

RELATED TO OUR FINANCIAL CONDITION

Because

there is substantial doubt as to the Company’s ability to continue as a going concern, we may not be successful and our ability

to continue our operations is in doubt unless we can access sufficient working capital within the timeframe needed.

The

Company has limited capital and substantial accumulated deficit as of the date of this Report. We do not have sufficient working capital

and cash flows for continued operations for at least the next 12 months, which raises a risk of our potential inability to continue as

a going concern. Our continued existence is dependent upon our obtaining the necessary capital to meet our expenditures, and we can provide

no assurance that we will be able to raise adequate capital to meet our future working capital needs.

RISKS

RELATED TO OUR BUSINESS

We

have never generated revenue from product sales and all of our product candidates are currently in the preclinical and early clinical

stage, and we may continue to incur significant losses for the foreseeable future and never generate revenue from product sales.

We

are still in the process of researching and developing product candidates, and to-date have not completed development of, obtained regulatory

approval for or commercialized any products. Because of the need to complete clinical trials, establish safety and efficacy and obtain

regulatory approval, which is an expensive and time-consuming process, we do not anticipate generating revenue from product sales for

at least four years and will continue to sustain considerable losses. We may develop a partnership that could generate income sooner,

but there is no guarantee that will be achievable.

We

had an accumulated deficit of $333,418,000 from inception through December 31, 2024 and expect to continue losing money in the future.

We may never achieve income from operations or have positive cash flow from operations.

As

an early-stage drug development company, our focus is on developing product candidates, obtaining regulatory approvals and commercializing

pharmaceutical products. As a result, we have accumulated losses of $333,418,000 from inception through December 31, 2024, expect losses

to continue, and have never generated revenue from product sales. We will need to raise additional capital in the near future to fund

our operations and research and development programs for the next 12 months. There can be no assurance that we will ever generate income

from operations or have positive cash flow from operations.

Because

we have yet to generate any revenue from product sales on which to evaluate our potential for future success and to determine if we will

be able to execute our business plan, it is difficult to evaluate our prospects and the likelihood of success or failure of our business.

Our

ability to generate revenue from product sales and achieve profitability depends on our ability, alone or with partners, to successfully

complete the development of, obtain the regulatory approvals for and commercialize pharmaceutical product candidates. We have no pharmaceutical

product candidates that have generated any commercial revenue, do not expect to generate revenues from the commercial sale of pharmaceutical

products for foreseeable future, and might never generate revenues from the sale of pharmaceutical products. Our ability to generate

revenue and achieve profitability will depend on, among other things, the following:

● identifying and validating new therapeutic strategies;

● attracting, hiring and retaining qualified personnel.

Because

of the numerous risks and uncertainties associated with pharmaceutical product development, we cannot predict the timing or amount of

increased expenses and when we will be able to achieve or maintain profitability, if ever. Our expenses could increase beyond expectations

if we are required by regulatory agencies to perform additional unanticipated studies and trials.

Even

if one or more pharmaceutical product candidates we independently develop is approved for commercial sale, we anticipate incurring significant

costs associated with commercializing any approved pharmaceutical product candidate. Moreover, even if we can generate revenues from

the sale of any approved pharmaceutical products, we may not become profitable and may need to obtain additional funding to continue

operations.

Because

early-stage drug development requires major capital investment and is subject to various challenges, as we continue to incur operating

losses, we will need to raise additional capital or form strategic partnerships to support our research and development activities in

the future, which activities may not result in the results desired or further our business.

We

are still in the early stages of preclinical and clinical development of our product candidates and have no products approved for commercial

sale or presently in clinical trials. However, our ability to conduct clinical trials in a cost-effective manner and within the desired

timeframes remains subject to uncertainties, supply chain shortages, and potential difficulties in obtaining adequate participant enrollments,

infection rates or other study criteria. For example, in December 2024, the Company announced plans to extend enrollment for the oral

CDI-42344 Phase 2a study due to unexpectedly low influenza infection among study participants. Specifically, management determined that

the low infectivity obtained in this study hindered antiviral data analysis. The Company is currently in continuing discussions with

the CRO to address this study and determine a course forward with respect thereto, including potentially by preparing a protocol amendment

for approval by the United Kingdom MHRA in order to seek to extend enrollment in this study and to ensure necessary infection rates among

enrolled study subjects in the study. While we cannot predict the ultimate outcome of these developments, we expect that we will need

to incur additional expenses to proceed with trial and obtain data that can be used to continue our development of our CDI-42344 Influenza

candidate, which development will also be delayed as a result. Further, our investments in the initial Phase 2s trial process could prove

to be all or partially lost as a result. These and other challenges or events that may arise in the future with respect to our research

and development efforts could materially adversely effect our operations and financial position, cause reputational harm or damage our

relationships with key or prospective collaborators or have other adverse consequences on us and our business.

Further,

developing pharmaceutical products, including conducting preclinical studies and clinical trials, is capital-intensive. As a rule, research

and development expenses increase substantially as we advance our product candidates toward clinical programs. As we seek to advance

our products through clinical trials, we will need to raise additional capital to support our operations and/or form partnerships, in

addition to our existing collaborative alliances, which may give substantial rights to a partner. Such funding or partnerships may not

be available to us on acceptable terms, or at all. Moreover, any future financing may be very dilutive to our existing stockholders.

As

we move lead compounds through toxicology and other preclinical studies, also referred to as nonclinical studies, we have and we will

be required to file an IND or its equivalent in foreign countries, and as we conduct clinical development of product candidates, we may

have adverse results that may cause us to consume additional capital. Our partners may not elect to pursue the development and commercialization

of our product candidates subject to our respective agreements with them. These events may increase our development costs more than we

expect. We may need to raise additional capital or otherwise obtain funding through strategic alliances if we initiate clinical trials

for new product candidates other than programs currently partnered. We will require additional capital to obtain regulatory approval

for, and to commercialize, product candidates.

In

securing additional financing, such additional fundraising efforts may divert our management’s attention from our day-to-day activities,

which may adversely affect our ability to develop and commercialize product candidates. We cannot guarantee that future financing will

be available in sufficient amounts or on terms acceptable to us, if at all. If we cannot raise additional capital when required or on

acceptable terms, we may be required to:

If

we are unable to raise additional capital in sufficient amounts or on terms acceptable to us, we will be prevented from pursuing development

and commercialization efforts, which will have a material adverse effect on our business, operating results and prospects or may render

the Company unable to continue operations.

RISKS

RELATED TO THE DISCOVERY, DEVELOPMENT AND COMMERCIALIZATION OF PRODUCT CANDIDATES

Our

programs are in the early clinical stage and we face significant competition from major companies who have developed vaccines or treatments.

If we fail to gain market share because our competitors develop and successfully commercialize effective vaccines or therapies or if

we fail to obtain or maintain FDA authorization or to otherwise account for uncertainties surrounding the virus, our business and future

prospects could be materially and adversely affected.

We

have committed substantial financial and other resources to our influenza A, norovirus and coronaviruses programs. While the approval

or authorization of certain of these competitive offerings are limited to specified circumstances or patients, given the uncertainties

in our ability to fully develop a viable therapeutic product, the substantial amount of time and resources that would be necessary to

complete development and obtain regulatory approval, and the growing number of competitive offerings, we may ultimately be unable to

produce a product that is commercially viable or is able to generate material revenue.

Even

if we do obtain FDA authorization for a therapeutic product, the FDA may subsequently rescind or limit such authorization as more information

about the product, including its efficacy and side effects, becomes available. Further, this virus is highly mutative and a number of

variants have already arisen, and any treatment we are able to develop and commercialize will therefore remain subject to the risk that

a mutation will occur that produces a strain or strains of the virus to which such treatment has a diminished effect or is ineffective.

For example, newer variants of the virus can be more resistant to treatments that were effective against prior variants of the virus.

If we do develop a treatment that is effective against a current variant, a later variant may arise that reduces or eliminates the product’s

efficacy before we are able to commercialize it. Further, if this occurs, one or more competitors’ products may be more effective

against new variants than ours, resulting in a diminished market for our products. If we are unable to timely advance our programs, or

if we fail to gain or maintain a market share as a result of our competitors developing and successfully commercializing vaccines and

effective therapies more quickly than we do, our business and future prospects could be materially and adversely affected.

If

we form strategic alliances which are unsuccessful or are terminated, we may be unable to develop or commercialize certain product candidates

and we may be unable to generate revenues from our development programs.

We

will likely need to use third-party alliance partners for financial, scientific, manufacturing, marketing and sales resources for the

clinical development and commercialization of certain of our product candidates. These strategic alliances, if we are able to enter into

them, will likely constrain our control over development and commercialization of our product candidates, especially once a candidate

has reached the stage of clinical development. Our ability to recognize revenues from successful strategic alliances may be impaired

by several factors including:

We

expect to rely on third parties to conduct some or all aspects of our compound formulation, research and preclinical testing, if those

third parties do not perform satisfactorily our business and future prospects would be materially and adversely affected.

We

do not expect to independently conduct all aspects of our drug discovery activities, compound formulation research or preclinical testing

of product candidates. We rely and expect to continue to rely on third parties to conduct some aspects of our preclinical testing and

on third-party CROs to conduct clinical trials. This reliance can materially delay our research and developments efforts, and increase

the costs of undertaking them. For example, beginning in 2021, certain of our CROs began experiencing staffing shortages and other issues

due to the outbreak of Omicron cases, resulting in delays and increased costs in researching our product candidates. We have also experienced

material delays and cost increases in general throughout the pandemic caused by pandemic-related difficulties faced by our CROs and CMOs.

Further, any disputes that may arise from our arrangements with CROs or CMOs may result in additional unexpected expenses and force our

management to allocate their limited time to seeking a resolution to the problem, which could materially adversely affect our operations.

If

these third parties terminate their engagements, we will need to enter into alternative arrangements which would delay our product development

activities. Our reliance on these third parties for research and development activities will reduce our control over these activities

but will not relieve us of our responsibilities. If in the future, we elect to develop and commercialize any product candidates on our

own, we will remain responsible for ensuring that each of our IND-enabling preclinical studies and clinical trials are conducted under

the respective study plans and trial protocols. If these third parties do not successfully carry out their contractual duties, meet expected

deadlines or conduct our studies under regulatory requirements or our stated study plans and protocols, we will not be able to complete,

or may experience delays in completing, the necessary clinical trials and preclinical studies to enable us or our partners to select

viable product candidates for IND submissions and will not be able to, or may be delayed in our efforts to, successfully develop and

commercialize such product candidates.

Because

we intend to rely on third-party manufacturers to produce our preclinical and clinical supplies, and commercial supplies of any approved

product candidates, we will be subject to a variety of risks.

Our

reliance on third-party manufacturers to develop products and our anticipated reliance on third-party manufacturers to produce products

we may develop in the future entail risks to which we would not be subject if we supplied the materials needed to develop and manufacture

our product candidates ourselves, including:

● supply chain shortages which were prevalent during the COVID-19 pandemic;

● a delay or inability to procure or expand sufficient manufacturing capacity;

● manufacturing and product quality issues related to scale-up of manufacturing;

● costs and validation of new equipment and facilities required for scale-up;

● a failure to comply with cGMP and similar foreign standards;

● carrier disruptions or increased costs beyond our control;

These

events could lead to clinical study delays or failure to obtain regulatory approval or impact our ability to successfully commercialize

future products. Some of these events could be the basis for regulatory actions, including injunction, recall, seizure or total or partial

suspension of production.

Because

we expect to rely on limited sources of supply for the drug substance and drug product of product candidates, any disruption in the chain

of supply may cause a delay in developing and commercializing these product candidates.

Part

of our business plan envisions establishing manufacturing relationships with a limited number of suppliers to manufacture raw materials,

drug substances, and the drug product of any product candidate for which we are responsible for preclinical or clinical development.

Each supplier may require licenses to manufacture such components if such processes are not owned by the supplier or in the public domain.

As part of any marketing approval, a manufacturer and its processes must be qualified by the FDA or foreign regulatory authorities prior

to commercialization. If supply from the approved vendor is interrupted, there could be a significant disruption in commercial supply.

An alternative vendor would need to be qualified through a New Drug Application (“NDA”) or marketing authorization supplement,

which could cause further delay. The FDA or other regulatory agencies outside of the United States may also require additional studies

if a new supplier is relied upon for commercial production.

These

factors could cause the delay of clinical trials, regulatory submissions, required approvals or commercialization of our product candidates,

cause us to incur higher costs and prevent us from commercializing our products successfully. Furthermore, if our suppliers fail to deliver

the required commercial quantities of drug substance or drug product on a timely basis and at commercially reasonable prices, and we

are unable to secure one or more replacement suppliers capable of production at a substantially equivalent cost, our clinical trials

may be delayed, or we could lose potential revenue.

If

third party manufacturing issues arise, it could increase product and regulatory approval costs or delay commercialization.

As

third parties scale up manufacturing of product candidates and conduct required stability testing, product, packaging, equipment and

process-related issues may require refinement or resolution to proceed with any clinical trials and obtain regulatory approval for commercial

marketing. We or the manufacturers may identify significant impurities or stability problems, which could cause discontinuation or recall

by us or our manufacturers, increased scrutiny by regulatory agencies, delays in clinical programs and regulatory approval, significant

increases in our operating expenses, or failure to obtain or maintain approval for product candidates or any approved products.

Since

we expect to continue to rely on third parties to conduct, supervise and monitor our clinical trials, if those third parties fail to