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On track to begin a Phase 2a trial in the second half of 2023with CC-42344 for the treatment ofpandemic and seasonal influenza A Selected the novel protease inhibitor CDI-988 as development lead inthe oral norovirus program CDI-988, the first potential dual coronavirus-norovirus oral antiviral, was cleared by the Australian regulatory agency for evaluation in healthy volunteers BOTHELL, Wash., Aug. 14, 2023 (GLOBE NEWSWIRE) -- CoCrystal Pharma, Inc. (Nasdaq: COCP) (Cocrystal or the Company) reports financial results for the three and six months ended June 30, 2023, and provides updates on its antiviral pipeline, upcoming milestones and business activities. “This is an eventful time for Cocrystal with notable advancements in developing our pipeline of highly promising antivirals,” said Sam Lee, Ph.D., President and co-CEO of Cocrystal. “With our novel oral PB2 inhibitor CC-42344 for the treatment of pandemic and seasonal influenza A, we are building on the favorable data from our Phase 1 trial with the submission of an application for UK MHRA (Medicine and Healthcare Products Regulatory Agency) approval to begin a Phase 2a human challenge trial later this year. “In our COVID-19 program, we received approval from the Australian regulatory agency in late May to begin a first-in-human trial with our novel, broad-spectrum oral protease inhibitor CDI-988. Earlier this month we announced the selection of CDI-988 as our lead oral norovirus candidate. This Phase I study is designed to access the safety, tolerability, and pharmacokinetics of CDI-988 for both our COVID-19 and our norovirus programs. We expect to report top-line data of CDI-988 Phase 1 study in 2024.” “We have a number of significant near-term inflection points with our three leading antiviral programs including the commencement of multiple clinical trials,” said James Martin, CFO and co-CEO. “I’m pleased to report that under our cost-efficient business model, we believe our current cash position is sufficient to fund our planned operations for the next 12 months.” Antiviral Product Pipeline Overview We are developing therapeutics that inhibit the viral replication function of RNA viruses that cause acute and chronic diseases. Our drug discovery process focuses on the highly conserved regions of the viral enzymes and inhibitor-enzyme interactions at the atomic level. It differs from traditional, empirical medicinal chemistry approaches that often require iterative high-throughput compound screening and lengthy hit-to-lead processes. By designing and selecting antiviral drug candidates that interrupt the viral replication process and have specific binding characteristics, we seek to develop drugs that are effective against both the virus and mutants of the virus, and also have reduced off-target interactions that may cause undesirable clinical side effects. Influenza Programs Influenza is a severe respiratory illness caused by the influenza A or B virus that results in disease outbreaks mainly during the winter months. The global seasonal influenza market including diagnostics, treatments and vaccines is projected to reach up to $27.95 billion by 2029, according to Data Bridge Market Research. Pandemic and Seasonal Influenza A Our novel oral PB2 inhibitor CC-42344 has shown excellent antiviral activity against influenza A strains including pandemic and seasonal strains, as well as strains that are resistant to Tamiflu® and Xofluza®. In March 2022 we initiated enrollment in a randomized, double-controlled, dose-escalating Phase 1 trial to evaluate the safety, tolerability and pharmacokinetics (PK) of orally administered CC-42344 in healthy adults. In April 2022 we announced preliminary Phase 1 trial data demonstrating a favorable safety and PK pro the first two cohorts in the single-ascending-dose portion of the study. In July 2022 we reported PK results from the single-ascending-dose portion of the study that support once-daily dosing. In December 2022 we reported favorable safety and tolerability results from the CC-42344 Phase 1 trial. We entered into an agreement with a UK-based clinical research organization to conduct a Phase 2a human challenge study to evaluate safety, and viral and clinical measures of orally administered CC-42344 in influenza A-infected subjects. We submitted an application to the United Kingdom Medicines and Healthcare Products Regulatory Agency to conduct the Phase 2a human challenge study and, pending clearance, we expect to initiate the study in the second half of 2023. Preclinical development is underway with an inhaled formulation of CC-42344 as a potential treatment and prophylaxis for influenza A. We expect to complete active pharmaceutical ingredient (API) manufacturing in preparation for toxicity studies, and to begin the Phase 1 clinical trial in the first half of 2024. Pandemic and Seasonal Influenza A/B Program In January 2019 we entered into an Exclusive License and Research Collaboration Agreement with Merck Sharp & Dohme Corp. (Merck) to discover and develop certain proprietary influenza antiviral agents that are effective against both influenza A and B strains. This agreement includes milestone payments of up to $156 million plus royalties on sales of products discovered under the agreement. In January 2021 we announced completion of all research obligations under the agreement, making Merck solely responsible for further preclinical and clinical development of these compounds. In early 2023 Merck notified us of its intent to continue development of the proprietary compounds discovered under this agreement and of their filing on behalf of both companies of multiple U.S. and international patent applications associated with these compounds. Merck continues to be responsible for managing the patents. COVID-19 and Other Coronavirus Programs By targeting viral replication enzymes and protease, we believe it is possible to develop effective treatments for all diseases caused by coronaviruses including COVID-19, Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). Our main SARS-CoV-2 protease inhibitors showed potent in vitro pan-viral activity against common human coronaviruses, rhinoviruses and respiratory enteroviruses that cause the common cold, as well as against noroviruses that can cause symptoms of acute gastroenteritis. Oral Protease Inhibitor CDI-988 In August 2023 we announced the selection of CDI-988 as our lead candidate for development as a potential oral treatment for SARS-CoV-2. Designed and developed using our proprietary structure-based drug discovery platform technology, CDI-988 targets a highly conserved region in the active site of SARS-CoV-2 3CL (main) protease required for viral RNA replication. CDI-988 exhibited superior in vitro potency against SARS-CoV-2 with activity maintained against variants of concern, and demonstrated a safety pro PK properties that are supportive of once-daily dosing. In May 2023 we announced approval of our application to the Australian regulatory agency for a planned randomized, double-blind, placebo-controlled Phase 1 trial in healthy volunteers. We believe the FDA’s guidance for further development of our antiviral candidate CDI-45205 (described below) assists us in designing a subsequent Phase 2 trial for CDI-988. Intranasal/Pulmonary Protease Inhibitor CDI-45205 CDI-45205 is our novel SARS-CoV-2 3CL (main) protease inhibitor and was among the broad-spectrum viral protease inhibitors we obtained from Kansas State University Research Foundation (KSURF) under an exclusive license agreement announced in April 2020. We believe the protease inhibitors obtained from KSURF have the ability to inhibit the inactive SARS-CoV-2 polymerase replication enzymes into an active form. CDI-45205 and several analogs showed potent in vitro activity against the main SARS-CoV-2 variants, surpassing the activity observed with the original Wuhan strain of the virus. CDI-45205 demonstrated good bioavailability in mouse and rat PK studies via intraperitoneal injection, and no cytotoxicity against a variety of human cell lines. CDI-45205 also demonstrated a strong synergistic effect with the FDA-approved COVID-19 medicine remdesivir. In January 2022 we received guidance from the FDA regarding further preclinical and clinical development of CDI-45205, which provides a clearer pathway for future development. An IND-enabling study is ongoing with CDI-45205. Replication Inhibitors We are using our proprietary structure-based drug discovery platform technology to discover replication inhibitors for orally administered therapeutic and prophylactic treatments for SARS-CoV-2. Replication inhibitors hold potential to work with protease inhibitors in combination therapy regimens. Norovirus Program In August 2023 we announced our selection of the novel broad-spectrum 3CL protease inhibitor CDI-988 as our lead potential oral treatment for norovirus. CDI-988 is approved for evaluation in a first-in-human trial in healthy volunteers in Australia, and that trial is expected to serve as the Phase 1 trial for both our norovirus and our coronavirus programs. With no approved treatments or vaccines, norovirus represents a significant unmet medical need. It is a highly contagious infection and is the most common cause of acute gastroenteritis, accounting for nearly one in five cases. According to the Centers for Disease Control and Prevention (CDC), an estimated 685 million cases and an estimated 200,000 deaths are attributed to norovirus each year worldwide, with an estimated societal cost of $60 billion. Hepatitis C Program We are seeking a partner to advance development of CC-31244 following the successful completion of a Phase 2a trial. This compound has shown favorable safety and preliminary efficacy in a triple-regimen Phase 2a trial in combination with Epclusa (sofosbuvir/velpatasvir) for the ultra-short duration treatment of individuals infected with the hepatitis C virus (HCV). HCV is a viral infection of the liver that causes both acute and chronic infection. The World Health Organization estimated that 58 million people worldwide had chronic HCV infection in 2019. Corporate Updates In April we announced the appointment of Fred Hassan to our Board of Directors. Mr. Hassan’s distinguished 40-year career includes serving in senior executive and director positions at global pharmaceutical companies and leading investment firms. He currently is Chairman of the investment firm Caret Group and a Director of Warburg Pincus LLC, a global private equity firm. In April we completed a $4.0 million private placement offering of common stock with Mr. Hassan and Phillip Frost, M.D., a Company co-founder and director, who currently is Chairman and CEO of OPKO Health. Second QuarterFinancial Results Research and development (R&D) expenses for the second quarter of 2023 were $2.8 million, compared with $2.4 million for the second quarter of 2022. The increase was primarily due to preparations for a Phase 2a clinical trial with CC-42344 for pandemic and seasonal influenza A, and preparations for advancing CDI-988’s COVID-19 and norovirus programs toward a Phase 1 clinical trial. General and administrative (G&A) expenses for the second quarter of 2023 were $1.5 million, compared with $1.4 million for the second quarter of 2022, with the increase primarily due to professional fees and general corporate cost increases. The net loss for the second quarter of 2023 was $4.2 million, or $0.41 per share, compared with the net loss for the second quarter of 2022 of $24.4 million, or $3.00 per share. The second quarter of 2022 included a legal settlement of $1.6 million, which was returned to the Company in the third quarter of 2023 following a successful appeal of the trial court’s summary judgment ruling. In the second quarter of 2022, the Company also recorded a non-cash goodwill impairment of $19.1 million. Six Month Financial Results R&D expenses for the six months ended June 30, 2023 were $6.7 million, compared with $5.2 million for the first six months of 2022. G&A expenses for the six months ended June 30, 2023 and 2022 were unchanged at $2.7 million. During the first six months of 2022, the Company recorded a $19.1 million non-cash goodwill impairment. There was no comparable impairment charge during the first six months of 2023. The net loss for the six months ended June 30, 2023 was $9.4 million, or $1.03 per share. The net loss for the six months ended June 30, 2022 was $28.6 million, or $3.48 per share, and reflected the litigation expense and non-cash impairment charge described above. Cocrystal reported unrestricted cash as of June 30, 2023 of $32.4 million, compared with $37.1 million as of December 31, 2022. Net cash used in operating activities for the first six months of 2023 was $8.7 million. The Company had working capital of $34.1 million and 10.2 million common shares outstanding as of June 30, 2023. During the second quarter of 2023, the Company raised $4.0 million in a private placement offering of common stock that was priced “at-the-market” under Nasdaq Listing Rules. About Cocrystal Pharma, Inc. Cocrystal Pharma, Inc. is a clinical-stage biotechnology company discovering and developing novel antiviral therapeutics that target the replication process of influenza viruses, coronaviruses (including SARS-CoV-2), noroviruses and hepatitis C viruses. Cocrystal employs unique structure-based technologies and Nobel Prize-winning expertise to create first- and best-in-class antiviral drugs. For further information about Cocrystal, please visit . Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding our plans for the future development of preclinical and clinical drug candidates, our expectations regarding future characteristics of the product candidates we develop, the expected time of achieving certain value-driving milestones in our programs, including, preparation, commencement and advancement of clinical studies for certain product candidates in 2023 and beyond, the viability and efficacy of potential treatments for coronavirus and other diseases, expectations for the markets for certain therapeutics, our ability to execute our clinical and regulatory goals and deploy regulatory guidance towards future studies, the expected sufficiency of our cash balance to advance our programs and fund our planned operations, and our liquidity. The words "believe," "may," "estimate," "continue," "anticipate," "intend," "should," "plan," "could," "target," "potential," "is likely," "will," "expect" and similar expressions, as they relate to us, are intended to identify forward-looking statements. We have based these forward-looking statements largely on our current expectations and projections about future events. Some or all of the events anticipated by these forward-looking statements may not occur. Important factors that could cause actual results to differ from those in the forward-looking statements include, but are not limited to, the risks and uncertainties arising from the risks arising from interest rate increases in response to inflation, uncertainty in the financial markets, the possibility of a recession and the Ukraine war on our Company, our collaboration partners, and on the U.S., U.K., Australia and global economies, including manufacturing and research delays arising from raw materials and labor shortages, supply chain disruptions and other business interruptions including any adverse impacts on our ability to obtain raw materials and test animals as well as similar problems with our vendors and our current and any future CROs and contract manufacturing organizations (CMOs), the ability of our CROs to recruit volunteers for, and to proceed with, clinical studies, our reliance on Merck for further development in the influenza A/B program under the license and collaboration agreement, our and our collaboration partners’ technology and software performing as expected, financial difficulties experienced by certain partners, the results of any current and future preclinical and clinical trials, general risks arising from clinical trials, receipt of regulatory approvals, regulatory changes, development of effective treatments and/or vaccines by competitors, including as part of the programs financed by the U.S. government, potential mutations in a virus we are targeting which may result in variants that are resistant to a product candidate we develop, and the outcome of the ongoing litigation with the insurance company. Further information on our risk factors is contained in our filings with the SEC, including our Annual Report on Form 10-K for the year ended December 31, 2022. Any forward-looking statement made by us herein speaks only as of the date on which it is made. Factors or events that could cause our actual results to differ may emerge from time to time, and it is not possible for us to predict all of them. We undertake no obligation to publicly update any forward-looking statement, whether as a result of new information, future developments or otherwise, except as may be required by law. Investor Contact: LHA Investor Relations Jody Cain 310-691-7100 jcain@lhai.com Media Contact: JQA Partners Jules Abraham 917-885-7378 Jabraham@jqapartners.com Financial Tables to follow COCRYSTAL PHARMA, INC. CONSOLIDATED BALANCE SHEETS (in thousands) June 30, 2023 December 31, 2022 (unaudited) Assets Current assets: Cash $ 32,419 $ 37,144 Restricted cash 75 75 Tax credit receivable 1,207 716 Prepaid expenses and other current assets 1,200 2,243 Total current assets 34,901 40,178 Property and equipment, net 305 342 Deposits 46 46 Operating lease right-of-use assets, net (including $72 and $99 respectively, to related party) 167 274 Total assets $ 35,419 $ 40,840 Liabilities and stockholders’ equity Current liabilities: Accounts payable and accrued expenses $ 1,421 $ 976 Current maturities of finance lease liabilities - 7 Current maturities of operating lease liabilities (including $62 and $59 respectively, to related party) 166 233 Total current liabilities 1,587 1,216 Long-term liabilities: Operating lease liabilities (including $10 and $42 respectively, to related party) 10 57 Total liabilities 1,597 1,273 Commitments and contingencies Stockholders’ equity: Common stock, $0.001 par value; 150,000 shares authorized as of June 30, 2023, and December 31, 2022; 10,174 and 8,143 shares issued and outstanding as of June 30, 2023 and December 31, 2022 10 8 Additional paid-in capital 341,957 337,489 Accumulated deficit (308,145 ) (297,930 ) Total stockholders’ equity 33,822 39,567 Total liabilities and stockholders’ equity $ 35,419 $ 40,840 COCRYSTAL PHARMA, INC. CONSOLIDATED STATEMENTS OF OPERATIONS (unaudited) (in thousands, except per share data) Three months ended June 30, Six months ended June 30, 2023 2022 2023 2022 Operating expenses: Research and development 3,661 2,361 7,568 5,233 General and administrative 1,538 1,375 2,742 2,708 Legal settlement - 1,600 - 1,600 Impairments - 19,092 - 19,092 Total operating expenses 5,199 24,428 10,310 28,633 Loss from operations (5,199 ) (24,428 ) (10,310 ) (28,633 ) Other income (expense): Interest income (expense), net 140 - 140 (1 ) Foreign exchange loss 33 (1 ) (45 ) (14 ) Change in fair value of derivative liabilities - 1 - 12 Total other expense, net 173 - 95 (3 ) Net loss $ (5,026 ) $ (24,428 ) (10,215 ) (28,636 ) Net loss per common share, basic and diluted $ (0.50 ) $ (3.00 ) (1.12 ) (3.48 ) Weighted average number of common shares outstanding, basic and diluted 10,065 8,143 9,109 8,143 # # #

PAXLOVID is the first FDA-approved oral treatment for COVID-19; has been authorized for emergency use since December 2021 Approval is based on the totality of scientific evidence submitted, including efficacy data from the Phase 2/3 EPIC-HR study showing an 86% reduction in risk of COVID-19-related hospitalization or death from any cause in patients who took PAXLOVID within five days of symptom onset PAXLOVID remains available to eligible patients via prescription at no charge* NEW YORK--(BUSINESS WIRE)-- Pfizer Inc. (NYSE: PFE) announced today that the U.S. Food and Drug Administration (FDA) approved PAXLOVID™ (nirmatrelvir tablets and ritonavir tablets) 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. PAXLOVID has been available in the U.S. since December 2021 under Emergency Use Authorization (EUA), and the overall benefit/risk pro indication for use in eligible adults remain consistent with the EUA. More than 11.6 million treatment courses of PAXLOVID have been prescribed in the U.S. to date.1 “Great advancements have been made in the fight against COVID-19, yet the virus remains a present and unpredictable concern. This is especially true for the hundreds of millions of American adults who are age 50 or older or are otherwise at high risk for progression to severe illness, even if symptoms are initially mild,” said Albert Bourla, Chairman and Chief Executive Officer, Pfizer. “Today marks a monumental milestone as PAXLOVID became the first COVID-19 oral treatment to be approved by the U.S. FDA, underscoring the value it brings to patients, providers, and health systems alike.” COVID-19 continues to cause significant burden in the U.S. with approximately 14,500 reported cases each week as of the end of April 2023;2 but the majority of cases are not reported.3 In addition, data show that the impact of COVID-19 extends beyond an acute infection; an estimated 10-31 million Americans may experience persisting, recurring or new symptoms after the acute phase of COVID-19 infection.4,5 The FDA approval of PAXLOVID is based on the totality of scientific evidence shared by Pfizer, including safety and efficacy data from the EPIC (Evaluation of Protease Inhibition for COVID-19) clinical development program. This included results from the Phase 2/3 EPIC-HR (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients) study, which enrolled unvaccinated, non-hospitalized adults, aged 18 years and older, with confirmed COVID-19 who were at increased risk of progressing to severe disease. The data showed an 86% reduction in risk of COVID-19-related hospitalization or death from any cause through Day 28 in patients who initiated treatment with PAXLOVID within five days of symptoms onset, compared to placebo. The FDA approval was further supported by the results from a secondary endpoint of the Phase 2/3 EPIC-SR (Evaluation of Protease Inhibition for COVID-19 in Standard-Risk Patients) study, which showed a numerical reduction in COVID-19-related hospitalizations or death from any cause through Day 28 in a sub-group of non-hospitalized adults, aged 18 years and older, with confirmed COVID-19 who had at least one risk factor for progression to severe disease and who were fully vaccinated. Available safety data have been consistent in participants across the EPIC clinical program, as well as across reported post-authorization safety experience in millions of patients prescribed PAXLOVID to date. Recent real-world studies of PAXLOVID support the efficacy conclusions from Pfizer’s EPIC clinical program, providing additional data on the use of PAXLOVID in the post-authorization setting of Omicron sub-lineage predominance and where high levels of pre-existing immunity occur. These real-world studies also have shown that PAXLOVID is effective amongst both vaccinated and unvaccinated high-risk patients.6,7,8,9,10 Based on the relative risk reduction seen across both clinical and real-world data, the FDA provided an estimate in March 2023 that more than 1,500 lives could be saved, and 13,000 hospitalizations avoided each week with PAXLOVID use in eligible patients.11 At this time, the U.S. government will continue to oversee the distribution of PAXLOVID, and U.S. residents eligible for PAXLOVID will continue to receive the medicine at no charge.* PAXLOVID remains available for eligible children, 12 to 17 years of age (and weighing at least 40 kg), under the existing EUA. Pfizer continues to gather pediatric data from the ongoing clinical trial, EPIC-Peds (Evaluation of Protease Inhibition for COVID-19 in Pediatric Patients) and intends to submit a supplemental New Drug Application (sNDA) to support the FDA approval of PAXLOVID in children at a future date. PAXLOVID is currently approved or authorized for conditional or emergency use in more than 70 countries across the globe to treat COVID-19 patients who are at increased risk for progressing to severe illness. *Other administrative fees may apply About PAXLOVID™ (nirmatrelvir tablets and ritonavir tablets) PAXLOVID is a SARS-CoV-2 main protease (Mpro) inhibitor (also known as SARS-CoV-2 3CL protease inhibitor) therapy. It was developed to be administered orally so that it can be prescribed early after infection, potentially helping patients avoid severe illness (which can lead to hospitalization and death). Nirmatrelvir, which originated in Pfizer laboratories, is designed to block the activity of the Mpro, an enzyme that the coronavirus needs to replicate. Co-administration with a low dose of ritonavir helps slow the metabolism, or breakdown, of nirmatrelvir in order for it to remain active in the body for longer periods of time at higher concentrations to help combat the virus. Nirmatrelvir is designed to inhibit viral replication at a stage known as proteolysis, which occurs before viral RNA replication. In preclinical studies, nirmatrelvir did not demonstrate evidence of mutagenic DNA interactions. Current variants of concern can be resistant to treatments that work by binding to the spike protein found on the surface of the SARS-CoV-2 virus. PAXLOVID, however, works intracellularly by binding to the highly conserved Mpro (3CL protease) of the SARS-CoV-2 virus to inhibit viral replication. Nirmatrelvir has consistently shown in vitro antiviral activity against the variants Alpha, Beta, Delta, Gamma, Lambda, Mu, and Omicron BA.1, BA.2, BA.2.12.1, BA.4, BA.4.6, BA.5, BF.7, BQ.1.11, BQ.1 and XBB.1.5. Work is ongoing to evaluate activity against recently identified variants as they become available for testing. PAXLOVID is generally administered at a standard dose of 300 mg (two 150 mg tablets) of nirmatrelvir with one 100 mg tablet of ritonavir, given twice-daily for five days. One standard dose carton contains blister packs of PAXLOVID, as co-packaged nirmatrelvir tablets with ritonavir tablets, providing all required doses for a full five-day treatment course. The modified dose for patients with moderate renal impairment (eGFR ≥30 to <60 mL/min) is reduced to 150 mg nirmatrelvir (one 150 mg tablet) with 100 mg ritonavir (one 100 mg tablet), with both tablets taken together twice daily for five days (PAXLOVID is not recommended in patients with severe renal impairment [eGFR <30 mL/min]). For more information, please visit . Our Commitment to Access Pfizer is committed to working toward equitable access to our oral COVID-19 treatment, PAXLOVID, for high-risk patients in need. Pfizer has established a comprehensive strategy in close partnership with worldwide governments, international global health leaders, including WHO’s Access to COVID-19 Tools Accelerator (ACT-A), and global manufacturers to optimize supply and access of PAXLOVID all around the world. This includes: Multilateral Supply Agreements: Signed agreement with UNICEF to supply up to 4 million treatment courses of PAXLOVID to 137 low- and middle-income countries; Signed letter of intent with Global Fund for up to 6 million PAXLOVID treatment courses for supply to 132 Global-Fund eligible countries. Expanding Access to Patent-Protected Medicines in Lower-Income Countries: Launched An Accord for a Healthier World, to support access for PAXLOVID and many other medicines and vaccines in lower-income countries. In addition to offering the full portfolio of medicines and vaccines for which we hold global rights on a not-for-profit-bases to 45 lower-income countries, through the Accord, Pfizer has committed to collaborate with country governments and global health organizations to help address barriers to access for these medicines and vaccines – like diagnostics, training, storage and more – to get PAXLOVID and other medicines to patients who need them in these countries. Voluntary Licensing: Signed a voluntary license agreement with Medicines Patent Pool (MPP) for the oral COVID-19 treatment to help expand access, pending country regulatory authorization or approval, for approximately 53% of the world’s population. The 35 generics manufacturers will develop generic versions of Pfizer’s COVID-19 oral treatment for distribution to 95 low- and lower-middle-income countries and some upper-middle-income countries in Sub-Saharan Africa as well as countries that have transitioned from lower-middle to upper-middle-income status in the past five years, subject to approval or authorization. U.S. Indication PAXLOVID is indicated for the treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in adults who are at high risk for progression to severe COVID-19, including hospitalization or death. Limitations of Use PAXLOVID is not approved for use as pre-exposure or post-exposure prophylaxis for prevention of COVID-19. U.S. FDA Emergency Use Authorization Statement The U.S. Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the emergency use of mild- to‑moderate coronavirus disease 2019 (COVID-19) and who are at high risk for progression to severe COVID‑19, including hospitalization or death. PAXLOVID has not been approved, but has been authorized for emergency use by FDA under an EUA, for the treatment of mild-to-moderate COVID-19 in pediatric patients (12 years of age and older weighing at least 40 kg) who are at high risk for progression to severe COVID-19, including hospitalization or death. The emergency use of PAXLOVID is only authorized for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of drugs and biological products during the COVID-19 pandemic under Section 564(b)(1) of the Act, 21 U.S.C. § 360bbb-3(b)(1), unless the declaration is terminated or authorization revoked sooner. IMPORTANT SAFETY INFORMATION WARNING: SIGNIFICANT DRUG INTERACTIONS WITH PAXLOVID PAXLOVID includes ritonavir, a strong CYP3A inhibitor, which may lead to greater exposure of certain concomitant medications, resulting in potentially severe, life-threatening, or fatal events Prior to prescribing PAXLOVID: 1) Review all medications taken by the patient to assess potential drug-drug interactions with a strong CYP3A inhibitor like PAXLOVID and 2) Determine if concomitant medications require a dose adjustment, interruption, and/or additional monitoring Consider the benefit of PAXLOVID treatment in reducing hospitalization and death, and whether the risk of potential drug-drug interactions for an individual patient can be appropriately managed PAXLOVID is contraindicated in patients with a history of clinically significant hypersensitivity reactions (eg, toxic epidermal necrolysis or Stevens-Johnson syndrome) to its active ingredients (nirmatrelvir or ritonavir) or any other components of the product. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue PAXLOVID and initiate appropriate medications and/or supportive care. PAXLOVID is contraindicated with drugs that are primarily metabolized by CYP3A and for which elevated concentrations are associated with serious and/or life-threatening reactions and drugs that are strong CYP3A inducers where significantly reduced nirmatrelvir or ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance. There are certain other drugs for which concomitant use with PAXLOVID should be avoided and/or dose adjustment, interruption, or therapeutic monitoring is recommended. Drugs listed here are a guide and not considered a comprehensive list of all drugs that may be contraindicated with PAXLOVID. The healthcare provider should consult other appropriate resources such as the prescribing information for the interacting drug for comprehensive information on dosing or monitoring with concomitant use of a strong CYP3A inhibitor like PAXLOVID. Drugs that are primarily metabolized by CYP3A for which elevated concentrations are associated with serious and/or life-threatening reactions: Alpha 1-adrenoreceptor antagonist: alfuzosin Antianginal: ranolazine Antiarrhythmic: amiodarone, dronedarone, flecainide, propafenone, quinidine Anti-gout: colchicine (in patients with renal and/or hepatic impairment) Antipsychotics: lurasidone, pimozide Benign prostatic hyperplasia agents: silodosin Cardiovascular agents: eplerenone, ivabradine Ergot derivatives: dihydroergotamine, ergotamine, methylergonovine HMG-CoA reductase inhibitors: lovastatin, simvastatin (these drugs can be temporarily discontinued to allow PAXLOVID use) Immunosuppressants: voclosporin Microsomal triglyceride transfer protein inhibitor: lomitapide Migraine medications: eletriptan, ubrogepant Mineralocorticoid receptor antagonists: finerenone Opioid antagonists: naloxegol PDE5 inhibitor: sildenafil (Revatio®) when used for pulmonary arterial hypertension Sedative/hypnotics: triazolam, oral midazolam Serotonin receptor 1A agonist/serotonin receptor 2A antagonist: flibanserin Vasopressin receptor antagonists: tolvaptan Drugs that are strong CYP3A inducers: PAXLOVID cannot be started immediately after discontinuation of any of the following medications due to the delayed offset of the recently discontinued CYP3A inducer: Anticancer drugs: apalutamide Anticonvulsant: carbamazepine, phenobarbital, primidone, phenytoin Antimycobacterials: rifampin, rifapentine Cystic fibrosis transmembrane conductance regulator potentiators: lumacaftor/ivacaftor Herbal Products: St. John’s Wort (hypericum perforatum) Risk of Serious Adverse Reactions Due to Drug Interactions: Initiation of PAXLOVID, which contains ritonavir, a strong CYP3A inhibitor, in patients receiving medications metabolized by CYP3A or initiation of medications metabolized by CYP3A in patients already receiving PAXLOVID, may increase plasma concentrations of medications metabolized by CYP3A. Medications that induce CYP3A may decrease concentrations of PAXLOVID. These interactions may lead to: Clinically significant adverse reactions, potentially leading to severe, life-threatening, or fatal events from greater exposures of concomitant medications Loss of therapeutic effect of PAXLOVID and possible development of viral resistance Severe, life-threatening, and/or fatal adverse reactions due to drug interactions have been reported in patients treated with PAXLOVID. The most commonly reported concomitant medications resulting in serious adverse reactions were calcineurin inhibitors (eg, tacrolimus, cyclosporine), followed by calcium channel blockers. Hepatotoxicity: Hepatic transaminase elevations, clinical hepatitis, and jaundice have occurred in patients receiving ritonavir. Therefore, caution should be exercised when administering PAXLOVID to patients with pre-existing liver diseases, liver enzyme abnormalities, or hepatitis. Because nirmatrelvir is coadministered with ritonavir, there may be a risk of HIV-1 developing resistance to HIV protease inhibitors in individuals with uncontrolled or undiagnosed HIV-1 infection. The most common adverse reactions in the PAXLOVID group (≥1%) that occurred at a greater frequency than in the placebo group were dysgeusia (5% and <1%, respectively) and diarrhea (3% and 2%, respectively). The following adverse reactions have been identified during use of PAXLOVID under Emergency Use Authorization: Immune System Disorders: Anaphylaxis, hypersensitivity reactions Skin and Subcutaneous Tissue Disorders: Toxic epidermal necrolysis, Stevens-Johnson syndrome Nervous System Disorders: Headache Vascular Disorders: Hypertension Gastrointestinal Disorders: Abdominal pain, nausea, vomiting General Disorders and Administration Site Conditions: Malaise PAXLOVID is a strong inhibitor of CYP3A, and an inhibitor of CYP2D6, P-gp, and OATP1B1. Coadministration of PAXLOVID with drugs that are primarily metabolized by CYP3A and CYP2D6 or are transported by P-gp or OATP1B1 may result in increased plasma concentrations of such drugs and increase the risk of adverse events. Coadministration with other CYP3A substrates may require a dose adjustment or additional monitoring. Pregnancy: Available data on the use of nirmatrelvir during pregnancy are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Published observational studies on ritonavir use in pregnant women have not identified an increase in the risk of major birth defects. Published studies with ritonavir are insufficient to identify a drug-associated risk of miscarriage. There are maternal and fetal risks associated with untreated COVID-19 in pregnancy. Lactation: There are no available data on the presence of nirmatrelvir in human or animal milk, the effects on the breastfed infant, or the effects on milk production. A transient decrease in body weight was observed in the nursing offspring of rats administered nirmatrelvir. Limited published data report that ritonavir is present in human milk. There is no information on the effects of ritonavir on the breastfed infant or the effects of the drug on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for PAXLOVID and any potential adverse effects on the breastfed infant from PAXLOVID or from the underlying maternal condition. Contraception: Use of ritonavir may reduce the efficacy of combined hormonal contraceptives. Advise patients using combined hormonal contraceptives to use an effective alternative contraceptive method or an additional barrier method of contraception. Pediatrics: The optimal dose of PAXLOVID has not been established in pediatric patients. Systemic exposure of nirmatrelvir increases in renally impaired patients with increase in the severity of renal impairment. No dosage adjustment is recommended in patients with mild renal impairment. Reduce the dose of PAXLOVID in patients with moderate renal impairment (eGFR ≥30 to <60 mL/min). PAXLOVID is not recommended in patients with severe renal impairment (eGFR <30 mL/min) or in patients with end-stage renal disease (eGFR <15 mL/min). PAXLOVID is not recommended for use in patients with severe hepatic impairment (Child-Pugh Class C). Please see Full Prescribing Information, including BOXED WARNING and Patient Information Click for Fact Sheets: There may be a delay as the documents are updated with the latest information. It will be available as soon as possible. Please check back for the updated full information shortly. For Consumers: EUA Fact sheet for Patients, Parents, and Caregivers For Healthcare Professionals: EUA Fact Sheet for HCPs About Pfizer: Breakthroughs That Change Patients’ Lives At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 170 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at . In addition, to learn more, please visit us on and follow us on Twitter at @Pfizer and @Pfizer News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer. Disclosure Notice The information contained in this release is as of May 25, 2023. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments. This release contains forward-looking information about Pfizer’s efforts to combat COVID-19 and PAXLOVID (including an approval in the U.S. of PAXLOVID 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, intention to submit a supplemental New Drug Application to support the FDA approval of PAXLOVID in children at a future date, the transition to a more traditional U.S. commercial model, efforts toward equitable access, the anticipated timing of data readouts, regulatory submissions, regulatory approvals or authorizations, and anticipated manufacturing, distribution and supply), involving substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as risks associated with preclinical and clinical data, including the possibility of unfavorable new preclinical, clinical or safety data and further analyses of existing preclinical, clinical or safety data; the ability to produce comparable clinical or other results including efficacy, safety and tolerability pro to date, in additional studies or in larger, more diverse populations following commercialization; uncertainties regarding the commercial impact of the results of the EPIC-SR and EPIC-PEP trials; the ability of PAXLOVID to maintain efficacy against emerging virus variants; the risk that serious and unexpected adverse events may occur that have not been previously reported with PAXLOVID use; the risk that preclinical and clinical trial data are subject to differing interpretations and assessments, including during the peer review/publication process, in the scientific community generally, and by regulatory authorities; whether regulatory authorities will be satisfied with the design of and results from these and any future preclinical and clinical studies; whether and when any drug applications or submissions to request emergency use or conditional marketing authorization for any potential indications for PAXLOVID or any of Pfizer’s other products or product candidates may be filed in particular jurisdictions and if obtained, whether or when such emergency use authorization or licenses will expire or terminate; whether and when regulatory authorities in any jurisdictions may approve any applications or submissions for PAXLOVID or any of Pfizer’s other products or product candidates that may be pending or which will depend on myriad factors, including making a determination as to whether the product’s benefits outweigh its known risks and determination of the product’s efficacy and, if approved, whether it will be commercially successful; decisions by regulatory authorities impacting labeling or marketing, manufacturing processes, safety and/or other matters that could affect the availability or commercial potential of PAXLOVID or any of Pfizer’s other products or product candidates, including the authorization or approval of products or therapies developed by other companies; the risk that other companies may produce superior or competitive products; risks related to the availability of raw materials to manufacture or test PAXLOVID; manufacturing capabilities or capacity; the risk that we may not be able to maintain manufacturing capacity or access to logistics or supply channels commensurate with global demand, which would negatively impact our ability to supply the estimated numbers of courses of PAXLOVID within the projected time periods; whether and when additional purchase agreements will be reached or existing agreements will be completed or re-negotiated; challenges related to a transition to the commercial market for PAXLOVID; the risk that demand for any products may be reduced, no longer exist or not meet expectations, which may lead to excess inventory on-hand and/or in the channel or reduced revenues; uncertainties regarding the impact of COVID-19 on Pfizer’s business, operations and financial results; and competitive developments. A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2022 and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors” and “Forward-Looking Information and Factors That May Affect Future Results”, as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at and . __________________________ 1 IQVIA National Prescription Audit data through May 05, 2023, containing retail pharmacy, mail order and long-term care channels; U.S. Department of Health and Human Services data through February 2023, for non-retail channels. Note: This information is an estimate derived from the use of information under license from the following IQVIA information service: National Prescription Audit, for the period January 1, 2022-May 05, 2023. IQVIA expressly reserves all rights, including rights of copying, distribution and republication. 2 Covid Data Tracker Weekly Review. Centers for Disease Control and Prevention. (2023, April 14). Retrieved April 27, 2023, from 3 Estimated COVID-19 burden. (2022). Retrieved from . 4 Davis HE, McCorkell L, Vogel JM, et al. Long COVID: major findings, mechanisms and recommendations. Nature Reviews Microbiology. 2023;21(3):133-46. 5 Bull-Otterson L, Baca S, Saydah S, et al. Post–COVID conditions among adult COVID-19 survivors aged 18–64 and≥ 65 years—United States, March 2020–November 2021. Morbidity and Mortality Weekly Report. 2022;71(21):713-17. 6 Lewnard JA, McLaughlin JM, Malden D, et al. Effectiveness of nirmatrelvir-ritonavir against hospital admission or death: a cohort study in a large US healthcare system. Lancet ID: (23)00118-4 7 Ganatra S, Dani SS, Ahmad J, et al. Oral Nirmatrelvir and Ritonavir in Non-hospitalized Vaccinated Patients with Covid-19 [published online ahead of print, 2022 Aug 20]. Clin Infect Dis. 2022;ciac673. doi:10.1093/cid/ciac673 8 Aggarwal NR, Molina KC, Beaty LE, et al. Real-world use of nirmatrelvir–ritonavir in outpatients with COVID-19 during the era of omicron variants including BA.4 and BA.5 in Colorado, USA: a retrospective cohort study. The Lancet Infectious Diseases 2023. DOI: (23)00011-7. 9 Shah MM, Joyce B, Plumb ID, et al. Paxlovid Associated with Decreased Hospitalization Rate Among Adults with COVID-19 — United States, April–September 2022. MMWR Morb Mortal Wkly Rep 2022;71:1531–1537. DOI: . 10 Dryden-Peterson S, Kim A, Kim AY, Caniglia EC, Lennes IT, Patel R, Gainer L, Dutton L, Donahue E, Gandhi RT, Baden LR, Woolley AE. Nirmatrelvir Plus Ritonavir for Early COVID-19 in a Large U.S. Health System : A Population-Based Cohort Study. Ann Intern Med. 2023 Jan;176(1):77-84. doi: 10.7326/M22-2141. Epub 2022 Dec 13. PMID: 36508742; PMCID: PMC9753458. 11 U.S. Food and Drug Administration. Treatment of mild-to-moderate COVID-19 in adults who are at high risk for progression to severe COVID-19, including hospitalization or death Antimicrobial Drugs Advisory Committee Meeting. Briefing Document. Reference data as of January 2023. Available at: March 16, 2023 Meeting of the Antimicrobial Drugs Advisory Committee Meeting (fda.gov). Accessed: May 4, 2023.