Baloxavir Marboxil

BOTHELL, Wash., Nov. 13, 2024 (GLOBE NEWSWIRE) -- Cocrystal Pharma, Inc. (Nasdaq: COCP) (“Cocrystal” or the “Company”) reports financial results for the three and nine months ended September 30, 2024, and provides updates on its antiviral product pipeline, upcoming milestones and business activities. “The coming months are critically important to Cocrystal as we expect to report topline results from two ongoing clinical studies with our best-in-class antiviral candidates in major medical indications,” said Sam Lee, Ph.D., President and co-CEO of Cocrystal. “In the Phase 2a influenza A challenge study with our oral PB2 inhibitor CC-42344, we expect to report topline results before year end. Earlier this year, we received feedback from the U.S. Food and Drug Administration (FDA) on a Pre-IND package that improves our clarity on the regulatory path and requirements for the late-stage influenza A clinical study we plan to conduct in the U.S. “The multiple-ascending dose portion in our Phase 1 pan-norovirus/pan-coronavirus study with oral protease inhibitor CDI-988 is underway and we are on track to report topline results in late 2024 or early 2025,” he added. “We view the development of an effective antiviral for norovirus as a significant opportunity for Cocrystal. There is no approved vaccine or antiviral for norovirus, which is highly contagious and the most common cause of acute gastroenteritis. In in vitro studies, CDI-988 exhibited pan-viral activity against multiple norovirus strains, including the strain that is responsible for major outbreaks.” “Our significant clinical progress so far this year puts us on track for an active 2025,” said James Martin, CFO and co-CEO of Cocrystal. “I’m pleased to report that based on our currently projected expenditures and our cost-efficient business model, we expect our cash will be sufficient to fund the advancement of our planned development programs through the coming 12 months.” 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 antiviral drug candidates that target the highly conserved regions of the viral enzymes, we seek to develop drugs that are effective against the virus and mutations of the virus, and also reduce 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 infections 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 new highly pathogenic avian influenza A (H5N1) PB2 protein recently identified in humans exposed to infected dairy cows.We expect to report topline results from the Phase 2a human challenge study by yearend and plan to file an IND application in 2025 to conduct a late-stage study in the U.S. Inhaled CC-42344 for the therapeutic and prophylactic treatment of pandemic and seasonal Influenza A infections Our preclinical testing showed superior pulmonary pharmacology with CC-42344 including high exposure to drug and a long half-life.We completed CC-42344 inhalation formulation development.We initiated GLP toxicology studies. Influenza A/B Program Our work to develop a preclinical lead of novel influenza replication inhibitors is underway. Norovirus Program Norovirus is a highly contagious infection and is the most common cause of acute gastroenteritis. Worldwide, norovirus causes about one out of five cases of acute gastroenteritis that leads to diarrhea and vomiting. An estimated 685 million cases and an estimated 50,000 child deaths are attributed to norovirus each year worldwide, with an estimated societal cost of $60 billion. By targeting viral replication, we believe it is possible to develop an effective treatment and/or short-term prophylactic for closed environments for all genogroups of norovirus. Oral pan-viral protease inhibitor CDI-988 for the treatment of norovirus and coronavirus infections 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, including the genogroup II, genotype 4 (GII.4) norovirus strain that is responsible for major norovirus outbreaks.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 for the oral treatment for norovirus, in addition to coronavirus.In September 2023 we began dosing subjects in a first-in-human study in healthy volunteers with oral CDI-988. In July 2024 we reported favorable safety and tolerability results from the single-ascending dose cohort in the Phase 1 study.In September 2024 we advanced CDI-988 into the multiple-ascending dose cohort of the Phase 1 study.We expect to report topline results from the CDI-988 Phase 1 study in late 2024 or early 2025. COVID-19 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 COVID-19 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 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 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 September 2024 we advanced CDI-988 into the multiple-ascending dose cohort of the Phase 1 study.We expect to report topline results from the CDI-988 Phase 1 study in late 2024 or early 2025. Third Quarter Financial Results Research and development (R&D) expenses for the third quarter of 2024 were $3.2 million, compared with $4.2 million for the third quarter of 2023, with the decrease primarily due to lower clinical study expenses. General and administrative (G&A) expenses for the third quarters of 2024 and 2023 remained relatively stable at $1.8 million. The net loss for the third quarter of 2024 was $4.9 million, or $0.49 per share, compared with a net loss for the third quarter of 2023 of $4.2 million, or $0.41 per share, that included a $1.6 million payment to the Company in 2023 for a legal settlement. Nine Month Financial Results R&D expenses for the first nine months of 2024 were $10.5 million, compared with $10.9 million for the first nine months of 2023. G&A expenses for the first nine months of 2024 were $4.1 million, compared with $4.6 million for the first nine months of 2023. The net loss for the first nine months of 2024 was $14.2 million, or $1.40 per share, compared with a net loss for the first nine months of 2023 of $13.5 million, or $1.43 per share. Cocrystal reported unrestricted cash as of September 30, 2024 of $13.0 million, compared with $26.4 million as of December 31, 2023. Net cash used in operating activities for the first nine months of 2024 was $13.3 million, compared with $11.3 million for the first nine months of 2023. The Company had working capital of $12.3 million and 10.2 million common shares outstanding as of September 30, 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. 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 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 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 2024 and 2025, the viability and efficacy of potential treatments for diseases our product candidates are designed to treat, expectations for the markets for certain therapeutics, our ability to execute our clinical and regulatory goals and deploy regulatory guidance towards future studies, and the expected sufficiency of our cash balance to advance our programs and fund our planned operations. 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 future inflation, potential future increases in interest rates uncertainty in the financial markets, the possibility of a recession, and geopolitical conflict including 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 on our ability to 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 ability of our CROs to recruit volunteers for, and to 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 healthcare in the wake of the recent presidential election in the U.S., the impact of the recent U.S. presidential election on regulation affecting the FDA and other healthcare agencies and potential staffing issues, potential mutations in a virus we are targeting that may result in variants that are resistant to a product candidate we develop. 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, 2023. 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 Media Contact:JQA PartnersJules Abraham917-885-7378Jabraham@jqapartners.com Financial Tables to follow COCRYSTAL PHARMA, INC. CONSOLIDATED BALANCE SHEETS(in thousands) September 30, 2024 December 31, 2023 (unaudited) Assets Current assets: Cash $13,020 $26,353 Restricted cash 75 75 Tax credit receivable 652 890 Prepaid expenses and other current assets 509 1,773 Total current assets 14,256 29,091 Property and equipment, net 181 271 Deposits 29 46 Operating lease right-of-use assets, net (including $163 and $42 respectively, to related party) 1,767 1,851 Total assets $16,233 $31,259 Liabilities and stockholders’ equity Current liabilities: Accounts payable and accrued expenses $1,655 $3,022 Current maturities of operating lease liabilities (including $55 and $42 respectively, to related party) 293 240 Total current liabilities 1,948 3,262 Long-term liabilities: Operating lease liabilities (including $163 and $0 respectively, to related party) 1,582 1,613 Total liabilities 3,530 4,875 Commitments and contingencies Stockholders’ equity: Common stock, $0.001 par value 100,000 and 150,000 shares authorized as of September 30, 2024, and December 31, 2023; 10,174 shares issued and outstanding as of September 30, 2024 and December 31, 2023 10 10 Additional paid-in capital 342,845 342,288 Accumulated deficit (330,152) (315,914)Total stockholders’ equity 12,703 26,384 Total liabilities and stockholders’ equity $16,233 $31,259 COCRYSTAL PHARMA, INC. CONSOLIDATED STATEMENTS OF OPERATIONS(unaudited)(in thousands, except per share data) Three months ended September 30, Nine months ended September 30, 2024 2023 2024 2023 Operating expenses: Research and development 3,242 4,194 10,500 10,902 General and administrative 1,800 1,849 4,148 4,591 Legal settlement - (1,600) - (1,600) Total operating expenses 5,042 4,443 14,648 13,893 Loss from operations (5,042) (4,443) (14,648) (13,893)Other income (expense): Interest income (expense), net 111 320 482 460 Foreign exchange loss (8) (42) (72) (87)Total other expense, net 103 278 410 373 Net loss $(4,939) $(4,165) (14,238) (13,520)Net loss per common share, basic and diluted $(0.49) $(0.41) (1.40) (1.43)Weighted average number of common shares, basic and diluted 10,174 10,153 10,174 9,461 # # #

近年来，以流感为典型代表的秋冬季呼吸道感染性疾病带来的考验依然严峻。为更有效地应对流感挑战，罗氏制药中国在第七届中国国际进口博览会上，召开了一场以“全心守护 福泽万家”为主题的新闻发布会。流感创新药速福达®（通用名：玛巴洛沙韦）携最新CENTERSTONE研究成果再度亮相四叶草舞台，展现其快速抑制病毒，切断流感传播链条，守护家庭健康方面的全新突破。现场，罗氏携手医疗健康领域专家与医疗健康新零售领域负责人以多元解读共探共讨流感防治的新武器、新模式、新生态，一同为公众筑起一道坚实的流感防护屏障，为守护全民健康贡献力量。 秋冬流感防治行动启动仪式 ▌多方携手，提高公众流感疾病认知 每年的10月到次年3年，都是季节性流感高发时期。每年流感病毒仍然会在全球导致300万到500万例重症病例、29万到65万人死亡1。 流感疫苗接种是预防流感最有效的方式。目前在中国，流感疫苗的接种率依然不高，国家疾控中心数据显示，中国2022年到2023年流感季接种率为3.84%，与欧美有很大的的差异。此外，还有相当多的民众对流感和普通感冒的区别认识不够，对及时接受流感检测以及规范化流感抗病毒治疗的意识不高。 活动现场，复旦大学附属华山医院张文宏教授就流感防控策略的议题展开分享，他表示，作为一种可引起重症肺炎的急性传染病，流感不仅会对个人健康构成威胁，也会给公共卫生系统带来巨大压力。他强调：“我们今天所面对的问题不是流感的治疗，而是大众认为流感不用治疗。流感是一个可以治疗、可以预防的疾病，我们强烈建议一老、一少与身体状况欠佳的人群，一旦出现发热症状，应尽早诊断、及时治疗，避免重症的出现。” 复旦大学附属华山医院张文宏教授致辞 世界冠军、中国游泳运动员汪顺也作为“流感防治公益项目”爱心宣传大使跨界亮相会场，分享流感防治心得，他积极呼吁大众在流感高发季正确地看待流感，科学地应对流感，建立起流感预防与规范化流感治疗理念，吸引了社会各界的广泛关注。 “流感防治公益项目”爱心宣传大使汪顺致辞 ▌助力阻断病毒传播，防治一体守护家庭健康 速福达®作为治疗流感的全球首个全程单次口服药物，一次口服即可在24小时内停止病毒排毒，缩短传染期并快速缓解发热等流感症状2，为流感患者提供了突破性的治疗方案。发布会现场，罗氏制药中国特药领域副总裁陈顗娟女士为大家分享了速福达®最新突破性成果。III期临床试验CENTERSTONE达到主要研究终点，流感患者单次口服速福达®后，可减少向其家庭成员传播流感病毒的可能性3。“这意味着，速福达既是‘矛’，也是‘盾’：它不仅能够抑制病毒，迅速缓解患者症状，还能为患者的家人，尤其是免疫力较弱的儿童和老人，提供一层有效的保护屏障。”陈顗娟解释。 “共筑防线，守护万家”圆桌讨论 作为CENTERSTONE中国的研究者，复旦大学附属中山医院呼吸与危重症医学科张静教授分享了该研究带来的深远意义：“玛巴洛沙韦在早期抑制病毒复制方面具有显著优势，其第一天的病毒载量降低速度是奥司他韦的40倍左右，24小时就可以停止病毒排毒，进而切断病毒传播链。CENTERSTONE研究是全球首个证实抗呼吸道病毒感染药物可以减少流感病毒传播的III期研究，对比安慰剂，流感患者单次口服玛巴洛沙韦后，家庭成员感染病毒的发生率降低了29%，一项真实世界研究数据也表明，玛巴洛沙韦阻断病毒传播的效力是奥司他韦的2倍，明确了抗病毒治疗药物在阻断病毒传播中的临床价值。” 对此，中国医学科学院北京协和医学院群医学及公共卫生学院副院长冯录召教授也从公共卫生的视角进行了展望：“流感给医疗卫生系统和社会带来巨大压力，每年感染流感人数约占总人口的10%，并导致约9万例超额死亡。然而，疫苗作为有效的预防方式，在我国接种率却不到4%。抗病毒药物为流感的主动预防提供了新的选择，流感创新药物玛巴洛沙韦不仅能有效治流感，还能预防其在家庭和集体单位中的传播。我们希望能基于此积累更多中国本土证据，探索更有效的流感预防策略，为政策调整提供支持，推动防治结合和医防协同。” ▌双剂保护克服儿童用药难题，各界力量共倡流感防治新生态 本次进博会上，速福达今年刚刚上市的，专门为儿童设计的新剂型——速福达干混悬剂也与片剂一同亮相罗氏展台。现场，各位专家也针对儿童流感防治用药展开讨论。 “全速‘宝’护，福佑未来”圆桌讨论 据南京医科大学附属儿童医院呼吸内科田曼教授介绍，儿童是流感的高发人群，一旦在秋冬季小孩出现高热等流感典型症状，一定要尽早诊断是否为流感，并进行抗病毒治疗；早期的明确诊断可以助力合理用药，减少抗菌药物不合理应用。同时，复旦大学附属儿科医院院长王艺教授指出，目前我国的儿童专用剂型仅占1.7%，家长在儿童给药时常面临“剂量靠猜，用药靠掰”的局面。“速福达干混悬剂是专门为儿童设计的草莓味干混悬剂，家长可以根据儿童体重精准给药，且全病程只需一次服药，儿童也不易呕吐，大幅改善儿童用药体验，并提高儿童服药的依从性。”上海交通大学医学院附属新华医院儿急危重症医学科朱晓东教授补充介绍到。 “全渠速达，共创生态”圆桌讨论及启动仪式 发布会上，罗氏也与阿里健康、华润医药等共同启动流感防治新生态的共建。多方从监测预警、疾病预防、疾病诊断、疾病治疗方面携手，把握流感流行趋势，提升公众对流感的科学认知，打通从居家检测到药物配送的“最后一公里”，构建一个全流程全体系的大健康生态圈，降低流感带来的威胁，持续为公众健康提供强有力的支持。 罗氏制药中国特药领域副总裁陈顗娟女士致辞 罗氏制药中国特药领域副总裁陈顗娟女士表示：“秉承‘先患者之需而行’的理念，未来，罗氏将持续携手各方力量，共同探索流感防治一体化创新解决方案，切实做好流感季抗病毒药物的供药保障，实现‘尽早治疗，阻断传播’，勾勒流感防治全新图景，助力筑牢公共卫生护城河。” 关于速福达®(玛巴洛沙韦) 玛巴洛沙韦是一款创新的RNA聚合酶抑制剂，已证明对多种流感病毒有效，包括对奥司他韦耐药株和非临床研究中禽流感病毒的体外活性株（H7N9、H5N1）245。玛巴洛沙韦全程仅需单次口服用药，就能在24小时内停止病毒排毒，缩短传染期，快速退热并大幅减少流感症状持续时间。对无基础疾病的既往健康流感患者和流感并发症高风险患者均有治疗获益1。 玛巴洛沙韦目前已在70多个国家被批准用于治疗甲型和乙型流感。在中国，速福达®（玛巴洛沙韦）已于被批准用于治疗5 周岁及以上单纯性甲型和乙型流感患者并被纳入《国家医保目录》。 强有力的临床证据证明速福达®在不同人群（包括健康、并发症高风险和儿童等人群）中的临床获益2,6,7,8。  玛巴洛沙韦已被欧盟、日本、韩国、瑞士等多国批准用于1岁及以上儿童、青少年和成人的单纯性流感的治疗以及上述人群的流感暴露后预防。 关于速福达®在中国已上市药品规格 速福达®片剂2片*20mg，为白色至浅黄色、椭圆形、薄膜包衣片剂，一侧凹陷有“BXM20”。 速福达®片剂1片*40mg，为白色至浅黄色、椭圆形、薄膜包衣片剂，一侧凹陷有“BXM40”。 速福达®干混悬剂40mg为白色至浅黄色颗粒，装在带有儿童安全盖的琥珀色玻璃瓶中。当用20ml常温饮用水进行配置，悬浮液的可用体积为20ml，相当于40mg(2mg/ml)玛巴洛沙韦。玛巴洛沙韦干混悬剂具有草莓口味。 关于CENTERSTONE CENTERSTONE（NCT03969212）是一项全球性、多中心、随机、双盲、安慰剂对照研究，评估了在症状出现48小时内服用单剂量玛巴洛沙韦减少家庭内流感传播的效果。该研究在全球295个地区进行，计划纳入1130名5至64岁的健康患者，这些患者通过聚合酶链反应（PCR）诊断检测确诊为流感阳性患者（称为指示病例，IP）及其家庭成员（称为家庭接触者，HHC）。主要终点是IP接受玛巴洛沙韦或安慰剂治疗后第5天HHC中病毒学检测出流感阳性的比例，且病毒亚型与IP人群一致；次要终点是第5天出现流感症状的HHC比例。研究最终纳入 1457 例流感病毒阳性患者（IPs），被随机分至安慰剂组（731 例）和玛巴洛沙韦组（726例）；安慰剂组和玛巴洛沙韦组分别有1336例和1345例家庭接触者。两组的IPs及HHC 的人口统计学特征与基线情况总体相当。最终结果显示：与安慰剂相比，玛巴洛沙韦组第5天时的流感病毒传播率显著降低29%。同时，玛巴洛沙韦的耐受性良好，试验过程中未发现新的安全信号。 - 上下滑动查看参考资料 -  [1]World Health Organization. Influenza (seasonal). [Internet; cited December 2022]. Available from: https://www-who-int.libproxy1.nus.edu.sg/news-room/fact-sheets/detail/influenza-(seasonal). [2]Hayden F, et al. N Engl J Med 2018;379:913–923. [3]https://mp.weixin.qq.com/s/GjCpcHpWGWxn1oZ9WOfYtg [4]Noshi T, et al. Antiviral Res. 2018;160:109-117. [5]Taniguchi K, et al. Sci Rep. 2019;9:3466. [6]Baker J, et al. Pediatr Infect Dis J. 2020;39(8):700-705. [7]Ikematsu H, et al. N Engl J Med. 2020;383:309-320. [8]Ison, et al. Lancet Infect Dis 2020;20(10):1204–14.