Baloxavir Marboxil

BOTHELL, Wash., March 31, 2025 (GLOBE NEWSWIRE) -- Cocrystal Pharma, Inc. (Nasdaq: COCP) (“Cocrystal” or the “Company”) reports financial results for the 12 months ended December 31, 2024, and provides updates on its antiviral product pipeline, upcoming milestones and business activities. “Our novel, potent antiviral compounds for norovirus, influenza and coronavirus address critical gaps in global health where effective treatments or vaccines are currently lacking,” said Sam Lee, Ph.D., President and co-CEO of Cocrystal. “We plan to initiate a norovirus human challenge study in the U.S. later this year to evaluate our pan-viral protease inhibitor CDI-988 for the potential treatment and prevention of norovirus infection. The big surge in reported norovirus outbreaks is possibly due to norovirus variants switching from GII.4 to GII.17, as well as increased social gathering after the COVID-19 pandemic. Norovirus is the most common cause of acute gastroenteritis and there are no approved therapeutics or vaccines, making it a compelling target. “We are optimistic that our oral PB2 inhibitor CC-42344 will have potential as a treatment for seasonal influenza A infection and pandemic avian influenza,” he added. “Following the unexpected low infection rate from the Phase 2a challenge study that precluded us from obtaining meaningful human efficacy data, we plan to continue the influenza challenge study.” “News coverage in recent months of norovirus and avian flu outbreaks underscore the urgent need for new antiviral solutions,” said James Martin, CFO and co-CEO of Cocrystal. “We are advancing our first- and best-in-class antiviral drug compounds that were designed using our Nobel Prize-winning structure-based technologies for these high-value viral targets that address multibillion-dollar markets.” Antiviral Product Pipeline Overview We apply our proprietary structure-based drug discovery platform technology for developing broad-spectrum antivirals that inhibit viral replication. By designing and selecting candidates that target highly conserved regions of the viral enzymes, we seek to develop drugs that are effective against the virus and mutations of the virus, while reducing off-target interactions that may cause undesirable side effects. Our drug discovery process differs from traditional, empirical medicinal chemistry approaches that often require iterative high-throughput compound screening and lengthy hit-to-lead processes. Influenza Programs Influenza is a major global health threat that may become more challenging to treat due to the emergence of highly pathogenic avian influenza viruses and resistance to approved influenza antivirals. Each year there are approximately 1 billion cases of seasonal influenza worldwide, 3-5 million severe illnesses and up to 650,000 deaths. On average, about 8% of the U.S. population contracts influenza each season. In addition to the health risk, influenza is responsible for an estimated $11.2 billion in direct and indirect costs in the U.S. annually. Oral CC-42344 for the treatment of pandemic and seasonal influenza A Our novel PB2 inhibitor CC-42344 showed excellent in vitro antiviral activity against pandemic and seasonal influenza A strains, as well as strains that are resistant to Tamiflu® and Xofluza®.In December 2022 we reported favorable safety and tolerability results from the oral CC-42344 Phase 1 study.In December 2023 we began a randomized, double-blind, placebo-controlled Phase 2a human challenge study to evaluate the safety, tolerability, viral and clinical measurements of CC-42344 in influenza A-infected subjects in the United Kingdom, following authorization from the UK Medicines and Healthcare Products Regulatory Agency (MHRA).In May 2024 we completed enrollment in the Phase 2a human challenge study.In June 2024 we reported that in vitro studies demonstrated CC-42344 inhibits the activity of the highly pathogenic avian influenza A (H5N1) PB2 protein identified in humans exposed to infected dairy cows.In December 2024 we announced a plan to extend the CC-42344 human challenge study due to unexpectedly low influenza infection among study participants. Inhaled CC-42344 as prophylaxis and treatment for pandemic and seasonal influenza A Our preclinical testing showed superior pulmonary pharmacology with CC-42344 including high exposure to drug and a long half-life.We have completed CC-42344 inhalation formulation development and GLP toxicology studies. Influenza A/B program Our efforts to develop a preclinical lead of novel influenza replication inhibitors are ongoing. Norovirus Program Norovirus symptoms can include severe nausea, vomiting and diarrhea. An estimated 685 million cases and an estimated 50,000 child deaths worldwide are attributed to norovirus each year, with an estimated societal cost of $60 billion. By targeting viral replication, we believe it is possible to develop an effective treatment and/or prophylaxis for closed environments for all genogroups of norovirus. Oral pan-viral protease inhibitor CDI-988 for the treatment of noroviruses and coronaviruses Our novel, broad-spectrum protease inhibitor CDI-988 is being evaluated as a potential oral treatment for noroviruses and coronaviruses.CDI-988 has shown in vitro pan-viral activity against multiple norovirus strains.In May 2023 we announced approval of our application to the Australian regulatory agency for a randomized, double-blind, placebo-controlled Phase 1 study to evaluate the safety, tolerability and pharmacokinetics (PK) of oral CDI-988 in healthy volunteers.In August 2023 we announced our selection of CDI-988 as our lead compound for the oral treatment for noroviruses, in addition to coronaviruses.In July 2024 we reported favorable safety and tolerability results from the single-ascending dose cohorts in the Phase 1 study.In December 2024 we reported favorable safety and tolerability results from the multiple-ascending dose cohorts of the Phase 1 study and the addition of a higher-dose cohort.We expect to report topline results from the high-dose healthy volunteer cohort with CDI-988 in the second quarter of 2025.We plan to initiate a human challenge study in the U.S. in 2025 to evaluate CDI-988 as a norovirus treatment and prophylaxis. SARS-CoV-2 and Other Coronavirus Programs By targeting viral replication enzymes and proteases, we believe it is possible to develop effective treatments for all diseases caused by coronaviruses including SARS-CoV-2 and its variants, Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). CDI-988 showed potent in vitro pan-viral activity against common human coronaviruses, rhinoviruses and respiratory enteroviruses, as well as against noroviruses. The global COVID-19 therapeutics market is estimated to exceed $16 billion annually by the end of 2031. Oral pan-viral protease inhibitor CDI-988 for the treatment of coronaviruses and noroviruses CDI-988 exhibited superior in vitro potency against SARS-CoV-2 and demonstrated a favorable safety profile and PK properties.In September 2023 we dosed the first healthy subject in our dual pan-norovirus/pan-coronavirus oral CDI-988 study, which is expected to serve as a Phase 1 study for both indications.In July 2024 we reported favorable safety and tolerability results from the single-ascending dose cohort in the Phase 1 study.In December 2024 we reported favorable safety and tolerability results from the multiple-ascending dose cohorts of the Phase 1 study and the addition of a higher-dose cohort.We expect to report topline results from the higher dose cohort in the CDI-988 Phase 1 study in the second quarter of 2025. 2024 Financial Results Research and development (R&D) expenses for 2024 were $12.5 million, compared with $15.2 million for 2023. The decrease was primarily due to the timing of clinical study costs. General and administrative (G&A) expenses for 2024 were $5.3 million, compared with $6.0 million for 2023, with the $0.7 million decrease primarily due to a reduction of insurance costs and other expenses. During 2023 the Company received $2.6 million related to litigation with an insurer. The net loss for 2024 was $17.5 million, or $1.72 per share, compared with the net loss for 2023 of $18.0 million, or $1.87 per share. For 2024 the year over-year-net loss was reduced by $3.1 million exclusive of the $2.6 million received in 2023 noted above. Cocrystal reported unrestricted cash as of December 31, 2024 of $9.9 million, compared with $26.4 million as of December 31, 2023. Net cash used in operating activities for 2024 was $16.5 million, compared with $14.7 million for 2023. The Company had working capital of $9.2 million and 10.2 million common shares outstanding as of December 31, 2024. 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. For further information about Cocrystal, please visit www.cocrystalpharma.com. 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 product 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 2025, our plans regarding further clinical development of such product candidates, and the viability and efficacy of potential treatments for diseases our product candidates are designed to treat, and expectations for the markets for certain therapeutics. 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 our need for additional capital to fund our operations over the next 12 months, inflation, the possibility of a recession, interest rate increases, imposed and threated tariffs, and geopolitical conflicts including those in Ukraine and Israel on our Company, our collaboration partners, and on the U.S., UK, 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 for and otherwise proceed with studies as well as similar problems with our vendors and our current and any future clinical research organization (CROs) and contract manufacturing organizations (CMOs), the progress and results of the studies for CC-42344 and CDI-988 including the delay of the Phase 2a study for CC-42344 which may require us to incur substantial additional costs, the ability of us and our CROs to recruit volunteers for, and to otherwise proceed with, clinical studies, 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 studies, general risks arising from clinical studies, receipt of regulatory approvals, regulatory changes including potential downward pressure on government spending on the biopharmaceutical and healthcare industry based on policies and actions taken by the Trump Administration in the U.S., the impact of the Trump Administration’s policies and actions on regulation affecting the FDA and other healthcare agencies and potential staffing issues resulting therefrom, potential mutations in a virus we are targeting that may result in variants that are resistant to a product candidate we develop, and the potential for the development of effective treatments by competitors which could reduce or eliminate a prospective future market share commercializing any product candidates we may develop in the future. Further information on our risk factors is contained in our filings with the SEC, including the “Risk Factors” in Item 1A of our Annual Report on Form 10-K for the year ended December 31, 2024. 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:Alliance Advisors IRJody Cain310-691-7100jcain@allianceadvisors.com Financial Tables to follow COCRYSTAL PHARMA, INC. CONSOLIDATED BALANCE SHEETS(in thousands) December 31, 2024 December 31, 2023 Assets Current assets: Cash $9,860 $26,353 Restricted cash 75 75 Tax credit receivable 1,215 890 Prepaid expenses and other current assets 430 1,773 Total current assets 11,580 29,091 Property and equipment, net 153 271 Deposits 29 46 Operating lease right-of-use assets, net (including $152 and $42 to related party) 1,694 1,851 Total assets $13,456 $31,259 Liabilities and stockholders’ equity Current liabilities: Accounts payable and accrued expenses $2,127 $3,022 Current maturities of operating lease liabilities (including $49 and $42 to related party) 301 240 Total current liabilities 2,428 3,262 Long-term liabilities: Operating lease liabilities (including $104 and $0 to related party) 1,505 1,613 Total long-term liabilities 1,505 1,613 Total liabilities 3,933 4,875 Commitments and contingencies Stockholders’ equity: Common stock $0.001 par value; 100,000 and 150,000 shares authorized as of December 31, 2024 and 2023, respectively; 10,174 shares issued and outstanding as of December 31, 2024 and 2023, respectively 10 10 Additional paid-in capital 342,931 342,288 Accumulated deficit (333,418) (315,914)Total stockholders’ equity 9,523 26,384 Total liabilities and stockholders’ equity $13,456 $31,259 COCRYSTAL PHARMA, INC. CONSOLIDATED STATEMENTS OF OPERATIONS(unaudited)(in thousands, except per share data) December 31, 2024 2023 Operating expenses: Research and development $12,537 $15,169 General and administrative 5,341 5,990 Legal settlement - (2,600)Total operating expenses 17,878 18,559 Loss from operations (17,878) (18,559) Other income (expense): Interest income, net 537 640 Foreign exchange loss (163) (65)Total other income, net 374 575 Net loss $(17,504) $(17,984) Net loss per common share, basic and diluted $(1.72) $(1.87)Weighted average number of common shares outstanding, basic and diluted 10,174 9,651 # # #

今年3月，很多人出现发烧的现象，体温有时能超过40度，这正是2025年春季甲流病毒正在施展威力。多位临床专家向健识局表示：流行性感冒看似是小病，实则对人体健康带来极大伤害，一旦确诊应及时用药控制，以免引起重症肺炎或相关脑病。甲流高发让抗病毒药物销量迎来大幅增长，诸如“居家囤药指南”等内容的帖子在社交平台上刷屏。而根据1药网、美团买药、叮当快药的销售数据来看，玛巴洛沙韦和奥司他韦（商品名：速福达、达菲）两款产品的销量增幅最大。鲜为人知的是，这两款跨越20年的流感特效药背后，站着同一个巨人：全球制药巨头——罗氏制药。研发接续创新罗氏两款明星产品接力全球流感治疗史上，奥司他韦（达菲）是一个绕不开的名字。这款经典药物是由罗氏制药研发的，2002年的时候进入中国。很多人都记得它的名字叫“达菲”。多年下来，“达菲”疗效确切、安全性好，是许多家庭的常备药。奥司他韦的作用机制，其实是将流感病毒“囚禁”在人体细胞内部，不让这些病毒直接复制和转录，等于说“困住”病毒，等待人体的免疫系统把病毒清除掉。奥司他韦是上世纪九十年代开发的，药品上市后临床反馈很好。当时所有抗病毒药物的研发集中在如何彻底消灭病毒本身上，奥司他韦的研发思路让全球学术界耳目一新：原来“抗病毒”最好的方式就是“困病毒”。这一思路启发了之后不少抗病毒药物的研究。不过，奥司他韦毕竟上市20多年了，有一定的局限性：其活性代谢物的半衰期约为6至10小时。这意味着，患者早上服用一剂奥司他韦，药物浓度会在10小时之后下降，药效减弱，所以晚上还得再吃一粒，连续服用5天医药界很快就把关注点集中到“如何延长药效时间”这个关键话题上。罗氏以战略眼光锁定新一代抗病毒方向，推出了玛巴洛沙韦（速福达）。流感病毒本身不能合成/不具有5'-帽状结构引物。其聚合酶中的PA亚基中的帽依赖性核酸内切酶可识别宿主细胞的前体mRNA，并将宿主前体mRNA中的帽状结构剪切掉并“抢来”，拼接到病毒mRNA上，如此一来，病毒mRNA就具有了完整的功能。从流感病毒的感染过程来看，“抢帽”是病毒转录/翻译起始所必须的，只要阻断“抢帽”过程，病毒就无法顺利复制。玛巴洛沙韦正是直击流感病毒复制“命门”：通过抑制流感病毒“抢帽”机制，一次性阻断mRNA功能化。因此，2018年“速福达”一经在中国上市，单次服药方案很快引发市场轰动，被冠以“流感神药”的称号。最新真实世界研究数据也进一步验证了“流感神药”的临床优势。根据一项日本健康保险数据库分析显示，5-11岁流感患儿使用玛巴洛沙韦较奥司他韦等神经氨酸酶抑制剂可降低53%的重症住院风险。【1】另一项中国多中心研究证实其可将中位症状缓解时间缩短20小时（28h vs. 48h），发热持续时间减少近1天，【2】且儿童胃肠道不良反应发生率仅为奥司他韦的1/5（2.38% vs. 12.13%）。【3】针对乙型流感的一项超万人研究更显示，玛巴洛沙韦组住院率低至0.15%，显著优于奥司他韦组0.37%，使用玛巴洛沙韦治疗可有效降低流感引发严重肺炎等住院重症率和其他抗流感治疗的发生率。【4】截至2025年，全球已经有超过2500万患者使用玛巴洛沙韦用于治疗流感，其中六成来自日本。从达菲到速福达可以看出：一款成熟的药物要想取得市场认可，不仅需要薪火相传的科研精神、长时间大规模的研发投入、也需要灵感和巧思，更需要从患者角度出发的人文考虑，这些缺一不可。考虑患者需求原研药仍是治疗基石玛巴洛沙韦能在中国的热销，最初的关键卖点肯定是“仅一次服药，一天就好”。中国和欧美发达国家在人口结构上的最大差别就是儿童数量多，孩子又特别容易感染流感。得了病不仅孩子遭罪，大人跟着也焦心，就算吃上了特效药，如果居家治疗期间孩子和孩子之间、孩子和大人之间相互感染，可能就会越弄越糟。“仅一次服药”、一天就见好，这些特点让玛巴洛沙韦成为众多家长给孩子抗病毒治疗药物的首选。罗氏敏锐地注意到这点，迅速开发了推出干混悬剂型。根据权威数据显示，中国平均每年约有1亿人感染流感，其中30%是儿童，比例上孩子染病率远高于成人。根据相关研究，在临床中有43%的儿童有不同程度的用药困难，片剂及口味不佳占多数。有35%的家长会通过牛奶、果汁、或糖水送药，还有48%的家长会在儿童病情好转后自行停药。想要控制好流感病毒，就必须从娃娃抓起。相比于传统的治疗方案，奥司他韦需每日多次服用，而玛巴洛沙韦仅需单次口服即可见效，显著提升了患者的依从性。2023年12月，国家药监局批准玛巴洛沙韦干混悬剂上市申请，干混悬剂在片剂基础上，给了低龄儿童可以根据体重精准用药的新选择。相比于片剂，干混悬剂在胃肠道的吸收更迅速、更完全。中国专门针对儿童的专用剂型只占所有药品的1.7%，罗氏专门考虑到了这一庞大患者群体的需求，而且干混悬剂的玛巴洛沙韦还是草莓口味的，孩子用药会容易得多。今年1月，玛巴洛沙韦干混悬剂进入医保，家长给孩子买药就可以享受医保报销了。巨人的使命仍在镇守病毒的前沿阵地人类与病毒的博弈一直没有停歇。过去二十年间，光是流感病毒就已历经十二次变异。从本世纪初的SARS病毒、08年席卷非洲的埃博拉病毒、到几年之前在全球肆虐的新冠病毒，每一次疫情都是对医药行业的严峻考验。罗氏制药等一批制药企业不求回报地投入新药研发之中，这才有了今天人类能够组建起对抗病毒的最基本防线。在这个过程中，所有医药企业第一位所想的都是治病救人，而不是追逐利益。对罗氏制药来说，“先患者之需”是公司的核心价值观，把所有患者的利益放在首位，是罗氏的企业使命。去年11月，罗氏在上海实现了玛巴洛沙韦的本土化生产，让中国患者可以更快使用到“流感神药”。同时，罗氏的奥司他韦、玛巴洛沙韦开发了片剂、干混悬剂等多个剂型，便于不同年龄患者使用，满足各年龄段的用药需求，又兼顾了临床疗效和安全性。在抗流感病毒的漫漫征途中，奥司他韦、玛巴洛沙韦经过二十多年全球验证，始终受到广大医务人员和家长、患儿的认可。生物医药的创新研发难度越来越大，抗病毒药物又是最吃力不讨好的品种，想想曾经“一药难求”的新冠口服药就知道。即便如此，罗氏依然保持着高昂的研发热情，这才有了奥司他韦和玛巴洛沙韦的迭代升级。未来，抗流感病毒药物还会进步，诚然这场与病毒的赛跑之中，罗氏可能不会永远是领先者，会有更多的企业站到巨人的肩膀上。不过，相信二十年前率先吹响抗疫号角的医药巨人，仍然会战斗在对抗病毒的前线，守护人类的健康防线。【参考文献】1. Miyairi, I., et al. (2025). Comparative effectiveness of baloxavir and neuraminidase inhibitors in preventing severe influenza outcomes: Analysis of Japanese health insurance claims database. The Lancet Regional Health – Western Pacific.2. Cai, X., et al. (2024). Ambispective observational study on baloxavir marboxil versus oseltamivir in Chinese influenza outpatients. Journal of Medical Virology3. Ge, L., et al. (2024). Real-world tolerance and efficacy of baloxavir in pediatric influenza patients: A cohort study at Children's Hospital of Fudan University. Pediatric Infectious Disease Journal4. Takazono, T., et al. (2024). Baloxavir versus oseltamivir for influenza B: Retrospective cohort study on hospitalization risk using nationwide insurance data. Influenza and Other Respiratory Viruses撰稿丨雷公编辑丨江芸 贾亭运营｜雾纪插图｜视觉中国声明：健识局原创内容，未经许可请勿转载儿科爆满，身高焦虑让药企年入百亿上岸了，但200亿拿什么实现？信达生物请回答！营收净利双双爆雷，投资也亏了5亿，泰格医药路在何方？