Calcifediol

活性维生素D已有近50年的使用历史，在全球各个国家已被广泛应用于骨科疾病、内分泌疾病、皮肤类疾病等治疗领域，并在国内外多项临床研究中展现出积极可靠的疗效以及安全性。近年来，活性维生素D所靶向的维生素D受体（VDR）相关研发热度不断，多项分子研究和动物实验已证实活性维生素D在肿瘤、罕见病、心血管疾病治疗等方面具有巨大的发展潜力。弗若斯特沙利文（Frost & Sullivan，简称“沙利文”）于2024年1月29日正式发布《活性维生素D（骨化醇）产业现状与未来发展报告》（以下简称“《报告》”），对活性维生素D领域进行深入分析，从技术发展、应用领域、市场现状、临床进展、行业挑战、企业竞争格局和未来趋势等多维度进行系统阐述，追踪行业和技术发展脉络，挖掘行业增长潜力，揭示市场发展背后的驱动因素，展望活性维生素D的广阔市场前景。1活性维生素D概览 维生素D概览维生素D是一种脂溶性的开环固醇类物质，主要由维生素D3以及维生素D2构成。其中，维生素D3为人体能够经日照自然合成的自源性物质；而维生素D2通常只能从食物或补充剂中获取。维生素D在人体中经代谢后不仅参与骨骼神经肌肉系统正常功能的维持；近年来的大量研究证实维生素D还具有骨骼外健康效应，参与组织细胞的分化、增殖和活性调节，对机体免疫功能具有调节作用，对人体各项机能的正常运转都起着至关重要的作用。 来源：文献检索，沙利文分析由于维生素D合成及获取的渠道有限，许多因素都可能导致人体维生素D含量不足。其中，最为重要的便是饮食和日照。《报告》详细梳理了维生素D对人体的重要性、维生素D不足的风险因素和流行病学分析，更多详细内容可参见完整版报告。活性维生素D概览维生素D3本身不具备生理活性，需要在人体先后经过肝脏由25-羟化酶羟化生成25(OH)D，即骨化二醇, 再由肾脏中的1α-羟化酶羟化生成1,25-(OH)2D3，即骨化三醇，才能发挥生理调节功能。因此，骨化二醇以及骨化三醇被称为维生素D的活性形式，即：活性维生素D。维生素D2的代谢原理与此相同。相比起口服普通维生素D，活性维生素可到达肠壁细胞或其他组织的细胞直接起作用。来源：文献检索，沙利文分析目前全球共有约十款活性维生素D产品在不同国家或地区获批上市，主要被分为天然活性维生素D以及新型活性维生素D两类。其区别在于，天然活性维生素D为维生素D经人体代谢转化后能够天然生成的化学物质；而新型活性维生素D则为药物化学家通过对天然活性维生素D的化学结构进行修饰后所得的活性物质。《报告》详细梳理了活性维生素D发展历史、代谢机制、天然和新型活性维生素D产品以及其应用领域，更多详细内容可参见完整版报告。2活性维生素D市场发展现状与未来以销售量的口径来看，虽然全球活性维生素D制剂的销量在近五年间受到COVID-19的影响略有波动，整体表现较为稳定。2022年全球活性维生素D的销售仍集中在日本、中国以及美国市场，合计占据超过56%的市场份额。在全球其他国家中，活性维生素D制剂的销量分布较为分散。来源：IMS医药数据库，沙利文分析目前中国处于销售状态的活性维生素D产品有骨化三醇、阿法骨化醇、卡泊三醇、他卡西醇、帕立骨化醇以及艾地骨化醇共6个品种。虽然2020年和2022年受到COVID-19的影响，活性维生素D的市场在这两年略有波动，整体中国活性维生素D的市场在2018至2022年间总体呈现增长的趋势，2022年中国活性维生素D市场规模超过60亿元。来源：沙利文分析《报告》对全球、日本和中国活性维生素D市场概况、中国的上市产品和市场规模、维生素D受体临床在研管线、未来发展趋势进行了分析，更多详细内容可参考完整版报告。3活性维生素D临床使用场景分析应用场景一——佝偻病维生素D缺乏性佝偻病，又称营养性佝偻病，主要由于患儿体内维生素D不足因而引起全身性钙、磷代谢失常以致钙盐不能正常沉着在骨骼的生长部分，最终发生骨骼畸形。维生素D缺乏性佝偻病的病因主要有日照不足，维生素D或钙摄入不足，生长过速，疾病和药物带来的影响。来源：文献检索，沙利文分析根据《营养性佝偻病预防和管理的全球共识建议》，维生素D缺乏性佝偻病的主要治疗方案包括以下口服维生素D或活性维生素D、增加钙的摄入和改善生活方式三种，其中口服活性维生素D是目前最常用的治疗手段及治疗基础。来源：文献检索，沙利文分析应用场景二——骨质疏松症骨质疏松症是一种随着患者骨骼中含有的钙和无机物的流失，致使骨组织显微结构破坏或骨强度下降所导致骨脆性增加的慢性代谢性疾病。患病人数较多，最新数据表明，全球骨质疏松症患病人数已达2亿人，患病率高达18.3%。来源：文献检索，沙利文分析目前全球共有三种能够用于治疗骨质疏松症的活性维生素D产品上市，包括：骨化三醇、阿法骨化醇以及艾地骨化醇。这三种产品的原研药目前皆已进入中国，且已有对应仿制药上市并销售。在这三类活性维生素D中，骨化三醇以及阿法骨化醇已在中国有了悠长的使用历史；尽管艾地骨化醇于10余年前就在日本上市，但并没有在全球（尤其是欧美）广泛上市，中国是第二个上市应用的国家。 注：终端价格指的是该药物在2023年的最小制剂单位于中国中标或挂网价格来源：文献检索，沙利文分析应用场景三——继发性甲状旁腺功能亢进继发性甲状旁腺功能亢进症 (SHPT) 是指慢性肾脏病患者在各种因素引起的高血磷或低血钙长期刺激下，甲状旁腺细胞分泌过多的甲状旁腺激素（PTH）所引起的疾病，超过85%的终末期慢性肾脏病患者患有该疾病，并发症较多，营养状况较差，一旦发生心脑血管意外、脓毒症等不良事件时，预后较差。来源：文献检索，沙利文分析目前全球共有七款适应症获批用于治疗继发性甲状旁腺功能亢进的活性维生素D及其衍生物的药物，其中仅有骨化三醇、阿法骨化醇以及帕立骨化醇这三种药物在中国上市，其余在中国皆处于临床试验阶段或临床前阶段。骨化三醇是最经典的用于治疗SHPT的药物。此外，由于新型活性维生素D药物的安全性更高，在国内外都有着广泛的患者使用群体。应用场景四——银屑病银屑病，俗称“牛皮癣”，是一种慢性炎症性皮肤病，会导致皮肤出现片状斑块并形成鳞屑，最常见于膝盖、肘部、躯干和头皮，多在冬季加重。目前全球已有超过1.25亿人正受扰于银屑病。我国银屑病患病率稳定在0.86%~3.29%之间。来源：文献检索，沙利文分析局部应用活性维生素D及其衍生物制剂后能够促进表皮的增殖或分化，是目前银屑病患者的一线治疗方式。现在全球主要获批用于治疗银屑病的活性维生素D衍生物包括他卡西醇、卡泊三醇以及马沙骨化醇三款。注：终端价格指的是该药物在2023年的最小制剂单位于中国中标或挂网价格来源：文献检索，沙利文分析《报告》详细梳理了活性维生素D的四个应用场景，并对每个应采用场景的致病因素、疾病分类、疾病分期、流行病学、疾病负担、治疗方式和活性维生素D药物应用对比进行了分析，更多详细内容可参考完整版报告。4活性维生素D行业壁垒分析虽然活性维生素D已在中国使用多年，但是由于其原料药合成难度大、使用剂量低以及化学结构不稳定，给原料药的生产、制剂以及质量控制方面皆带来诸多挑战，因此国内少有公司能够同时自主生产活性维生素D的原料药及制剂，且口服制剂以软胶囊和胶丸这类较为容易实现大规模生产的剂型为主。目前活性维生素D行业中，能够实现自研、自产活性维生素D原料药及其相关制剂的厂商主要包括：海融制药、正大制药青岛（中国生物制药）以及国为医药等。行业壁垒一——原料药合成由于活性维生素D及其衍生物的甾醇骨架中含有共轭双烯结构，该结构在光、热、氧条件下结构不稳定，容易发生化学变化生成杂质，给提纯带来难度，因此在工业生产活性维生素D的上游合成以及下游纯化分离环节皆有较大的难度。《报告》详细梳理了活性维生素D上游合成壁垒、下游纯化分离难点与SFC超临界流体色谱优势，更多详细内容可参考完整版报告。行业壁垒二——制剂生产目前活性维生素D已上市的剂型包括口服固体制剂、注射剂和半固体外用制剂等剂型均有相应产品上市。然而，这些制剂在生产工艺上都有相应的难点。其中，低剂量的口服固体制剂制备尤为值得关注，由于活性维生素D容易引发高钙血症等副反应，因此单剂量产品中活性维生素D的含量通常不超过1mg或载药量＜0.01% (w/w)，相对于常规口服剂型而言，低剂量制剂往往会由于原料药与药用辅料混合不均匀导致低效力以及稳定性不佳等问题。《报告》详细梳理了低剂量口服固体制剂制备难点、工艺、专利和双螺杆湿法制粒工艺优势，更多详细内容可参考完整版报告。行业壁垒三——质量控制对于活性维生素D制剂而言，鉴于其低剂量药物制剂属性，因此除了其处方研究、工艺开发及放大生产以外，其制剂的质量控制与分析方法的建立也较常规制剂相比难度更高，也更具有挑战性。对于活性维生素D制剂而言，最主要的质量控制检查项目包括反映其均匀性的含量均匀度、表征其稳定性的有关物质（杂质）和含量、反映其晶型等可能变化的溶出度试验等，这些关键质量属性皆会直接影响药物的安全性、有效性和质量可控性。《报告》详细梳理了活性维生素D制剂质量控制的三大难点，更多详细内容可参考完整版报告。5活性维生素D公司介绍海融医药海融医药（NQ：870070），是一家坚持创新驱动和研发产品差异化竞争的制药企业，最早于2013年成立。公司拥有全球领先的活性维生素D衍生物类药物研发技术，并基于该技术已开发多条活性维生素D制剂产品管线，覆盖艾地骨化醇、度骨化醇等新型及天然活性维生素D，是目前我国覆盖活性维生素D最广的生产厂商。截至最新，海融医药在活性维生素D领域已申请专利24项；授权14件，其中发明专利10件，实用新型专利2件，外观设计专利2件。海融医药在活性维生素D产业做到上、下游全链条覆盖，是目前国内唯一一家开展全系列活性维生素D衍生物类原料药及制剂的医药企业。帝人制药帝人制药株式会社（简称：帝人制药，英文名：Teijin Pharma）于1970年代由帝人集团（TSE: 3401）的高分子化学业务发展而来，是帝人集团的核心子公司之一。此后经过半个世纪持续培育研究开发能力，融合了集团的材料、IT业务的不同的技术能力，不断深化预防/增进健康、治疗、康复/护理，为整个医疗服务周期做出贡献的综合性健康医疗解决方案，其拥有2款原研活性维生素D产品，分别是阿法骨化醇片剂和他卡西醇软膏。利奥制药利奥制药（英文名：LEO Pharma）是一家成立于1908年，总部坐落于丹麦的全球首屈一指的制药公司，产品销售覆盖全球100多个国家。利奥中国在中国专攻与皮肤领域疾病，目前已拥有银屑病、特异性皮炎和痤疮等治疗领域的共7个外用药物产品组。其开发的三款活性维生素D制剂分别为针对银屑病的单方及复方制剂。罗氏制药罗氏集团（英文名：Roche）成立于1896年，总部位于瑞士巴塞尔，拥有125年的历史, 是全球领先的生物技术、体外诊断公司和工业化生产原研药的企业之一。目前，罗氏制药在华共计25款产品，覆盖抗感染、抗肿瘤、血友病、风湿免疫、移植、骨质疏松、神经科学和贫血8大治疗领域。罗氏集团及其联盟企业分别推出了骨化三醇软胶囊、艾地骨化醇软胶囊以及艾地骨化醇片剂。四川国为成都国为生物医药有限公司（简称：国为医药）成立于2005年，总部位于成都高新区，是一家集研发、生产、销售于一体的综合性医药企业。公司产品主要集中在心脑血管、消化系统、抗感染、泌尿系统等领域，已获得28个药品生产批件，3个保健品生产批件，拥有授权专利41项，注册商标176项。国为医药目前拥有包括艾地骨化醇软胶囊、骨化三醇软胶囊以及帕立骨化醇注射液三款上市产品。正大天晴正大天晴药业集团股份有限公司（简称：正大天晴）是一家从事医药创新和高品质药品的研发、生产与销售的创新型医药集团，为中国生物制药（01177.HK）的核心子公司之一，致力于为患者提供更佳的健康解决方案和优质可负担的医药资源，是国内知名的抗肿瘤、肝病药物研发和生产基地。公司共有三款产品处临床阶段，分别为艾地骨化醇软胶囊、度骨化醇注射液以及度骨化醇软胶囊。正大青岛正大制药（青岛）有限公司（简称：正大青岛）是由正大制药集团投资设立的外商独资新型高新技术制药企业，公司产品分为海洋药物、中药、化学药和保健食品四大门类。公司自主研发上市的国家级新药——盖三醇（骨化三醇软胶囊）填补了国内空白，获山东省轻工业科技进步一等奖。公司目前拥有四款活性维生素D领域的上市产品，包括骨化三醇软胶囊和口服液、阿法骨化醇胶囊以及帕立骨化醇注射液。更多详细内容请扫描以下二维码获取完整报告↓↓长按扫描下方二维码获取↓↓撰写团队李诗嘉沙利文大中华区生命科学事业部项目经理、scarlett.li@frostchina.com程叶馨沙利文大中华区生命科学事业部咨询顾问vanni.cheng@frostchina.com沙利文生命科学事业部联系方式：李谦 咨询总监 18917935734（同微信）李诗嘉 项目经理 15821373719（同微信）联系邮箱：hcknowledgecenter@frostchina.com“关于沙利文生命科学事业部沙利文生命科学事业部在生命科学领域拥有专业的分析能力和丰富的项目经验。依托沙利文全球智库资源和大中华区跨行业业务发展平台，沙利文生命科学事业部在生命科学产业投融资服务有着独特核心优势。沙利文生命科学事业部在中国拥有广泛的企业客户，并在过去20年里建立了庞大的客户网络，积累大量生命科学各细分领域的项目经验。项目类型包括知识中心项目（深度内容、宣传活动），Pre-IPO项目（DCF估值、商业计划书服务），IPO上市项目（行业顾问、临床稽查、募投撰写），市场调研，市值管理及战略咨询等，并与国内外知名的资讯平台及投融资机构合作，为企业提供医药及医疗器械等专业细分领域行业一站式解决方案，受到投资者的广泛关注。”点击获取完整报告！

Conference call begins at 4:30 p.m. Eastern time todayMIAMI, Nov. 06, 2023 (GLOBE NEWSWIRE) -- OPKO Health, Inc. (NASDAQ: OPK) reports business highlights and financial results for the three and nine months ended September 30, 2023. Business highlights from the third quarter and subsequent weeks included the following: ModeX Therapeutics Inc. (ModeX) was awarded a contract from the Biomedical Advanced Research and Development Authority (BARDA) to develop novel multispecific antibodies against viral infectious disease threats. BARDA awarded a contract to ModeX to advance a platform and specific therapeutic candidates designed to address a range of public health threats in viral infectious diseases. The BARDA contract includes an initial $59 million award for the development, manufacturing and execution of a Phase 1 clinical trial for a next-generation MSTAR multispecific antibody with broad neutralizing activity against known variants of SARS-CoV-2. ModeX may be eligible to receive up to an additional $109 million from BARDA upon achieving milestones to develop multispecific antibodies targeting other viral pathogens, such as influenza.ModeX advanced its antiviral and immune-oncology product pipeline. ModeX advanced its pipeline of antiviral and immune-oncology programs utilizing its next-generation multispecific antibodies. ModeX’s oncology programs are in the preclinical stage and at least one program is expected to enter the clinic in 2024. ModeX’s collaboration with Merck to develop MDX-2201, its vaccine for Epstein-Barr virus, is advancing. ModeX’s antiviral program is focused on developing multiple indications, including HIV, as well as other potential viral pathogens funded by BARDA.NGENLA has now been approved in 48 markets including the U.S., Japan, EU Member States, Canada and Australia; sales are underway by Pfizer in over 23 countries including all priority global markets. NGENLA is the first once-weekly product approved for the treatment of pediatric growth hormone deficiency in Japan, Canada, Australia, the United Kingdom, Taiwan, United Arab Emirates and Brazil. OPKO is entitled to gross profit sharing in all global markets based on regional, tiered gross profit for both NGENLA and Genotropin. The U.S. region commenced gross profit sharing in August 2023.New clinical data on RAYALDEE® presented at Kidney Week 2023. OPKO Health presented late-breaking clinical data on RAYALDEE extended-release calcifediol in a poster presentation at the American Society of Nephrology Kidney Week. The data indicate that early, sustained and effective treatment of secondary hyperparathyroidism (SHPT) with RAYALDEE is associated with significantly slower progression of chronic kidney disease (CKD) in pre-dialysis patients. Data presented in an additional poster demonstrated that effective control of SHPT was achieved with RAYALDEE in both randomized clinical trials and in a real-world clinical experience trial.OPKO Biologics entered into a research collaboration agreement with Entera Bio Ltd. to develop oral peptide tablet formulations for obesity and intestinal malabsorption syndromes. Under the agreement, OPKO will supply its long-acting GLP-2 peptide and certain oxyntomodulin (OXM) analogs for the development of oral tablet formulations using Entera’s proprietary oral delivery technology. Treatment with glucagon-like peptide-2 (GLP-2) analogs has been shown to improve the absorption of nutrients in patients with short bowel syndrome and to reduce parenteral support requirements. OXM is a naturally occurring peptide hormone found in the colon, with glucagon-like peptide-1 (GLP-1) and glucagon dual agonist activity that suppresses appetite and induces weight loss. OPKO has developed several proprietary, modified OXM analogs as potential candidates for treating obesity, including an injectable pegylated peptide that demonstrated significant reductions in weight loss and decreased plasma triglyceride levels in a 420-patient Phase 2b study.BioReference Health continued executing its plan to improve operational efficiencies and enhance productivity, and is on track to return to profitability. BioReference continued to implement initiatives to reduce costs and rationalize its business in line with current testing volumes. Additionally, BioReference is focused on improving productivity and enhancing innovation of its higher-value specialty testing segments. Other efforts to return this business to profitability include expanding into new market segments, such as providing information for the pharmaceutical market. Third Quarter Financial Results Pharmaceuticals: Revenue from products in the third quarter of 2023 increased to $40.7 million from $32.4 million in the third quarter of 2022, driven by higher sales in OPKO’s international operating companies positively impacted by foreign currency exchange fluctuations of $2.9 million, and by an increase in sales of RAYALDEE to $7.3 million from $6.9 million in the prior-year period. Revenue from the transfer of intellectual property was $6.2 million in the third quarter of 2023 compared with $4.5 million in the 2022 period, which included revenue of $4.9 million and $1.4 million, respectively, of gross profit share for NGENLA in Europe and Japan and does not include an estimate from gross profit in the U.S. as our partner has not yet provided details post their launch in August 2023. Total costs and expenses were $72.3 million in the third quarter of 2023, up from $65.2 million in the prior-year period. The increase was mainly from the cost of revenue due to higher sales in OPKO’s international operating companies, higher inventory costs compared with the 2022 third quarter and unfavorable foreign currency exchange fluctuations of $2.2 million. Operating loss was $25.4 million in the third quarter of 2023 compared with $28.3 million in the third quarter of 2022.Diagnostics: Revenue from services in the third quarter of 2023 was $131.7 million compared with $142.9 million in the prior-year period. Revenue decreased $10.0 million due to lower COVID-19 testing volume and reimbursement. Furthermore, clinical test reimbursement decreased by $6.6 million due to the mix of testing ordered, partially offset by a $5.4 million increase in clinical test volume. Total costs and expenses were $160.8 million in the third quarter of 2023 compared with $192.3 million in the third quarter of 2022, resulting in an operating loss of $29.1 million compared with an operating loss of $49.5 million in the 2022 period, an improvement of 41%. Operating loss improved primarily due to continued cost-reduction initiatives at BioReference as we strive to return to profitability.Consolidated: Consolidated total revenues for the third quarter of 2023 were $178.6 million compared with $179.7 million for the comparable 2022 period. Operating loss for the third quarter of 2023 was $64.4 million compared with an operating loss of $87.8 million for the 2022 quarter. Net loss for the third quarter of 2023 included a mark-to-market adjustment of $8.3 million compared with $30.6 million in the 2022 period related to the decrease in the share price of GeneDx, resulting in a net loss of $84.5 million, or $0.11 per share, compared with a net loss of $86.1 million, or $0.11 per share, for the 2022 quarter.Cash and cash equivalents: Cash and cash equivalents were $138.6 million as of September 30, 2023. Conference Call and Webcast Information OPKO’s senior management will provide a business update, discuss third quarter financial results, provide financial guidance and answer questions during a conference call and audio webcast today beginning at 4:30 p.m. Eastern time. Participants are encouraged to pre-register for the conference call using this link. Callers who pre-register will receive a unique PIN to gain immediate access to the call and bypass the live operator. Participants may register at any time, including up to and after the call start time. Those unable to pre-register can participate by dialing 833-630-0584 (U.S.) or 412-317-1815 (International). A webcast of the call can also be accessed at OPKO’s Investor Relations page and here. A telephone replay will be available until November 13, 2023 by dialing 877-344-7529 (U.S.) or 412-317-0088 (International) and providing the passcode 8299382. A webcast replay will be available beginning approximately one hour after the completion of the live conference call here. About OPKO Health OPKO Health is a multinational biopharmaceutical and diagnostics company that seeks to establish industry-leading positions in large, rapidly growing markets by leveraging its discovery, development and commercialization expertise, and its novel and proprietary technologies. For more information, visit www.opko.com. Cautionary Statement Regarding Forward Looking Statements This press release contains "forward-looking statements," as that term is defined under the Private Securities Litigation Reform Act of 1995 (PSLRA), which statements may be identified by words such as "expects," "plans," "projects," "will," "may," "anticipates," "believes," "should," "intends," "estimates," and other words of similar meaning, including statements regarding expected financial performance and expectations regarding the market for and sales of our products, whether our products will launch in all the territories in which they have been approved for sale, the timing of such launches, our product development efforts and the expected benefits of our products, whether the relationship with our commercial and strategic partners will be successful, whether our commercial and strategic partners will be able to commercialize our products and successfully utilize our technologies, our ability to attract new commercial and strategic partners, our ability to market and sell any of our products in development, whether we will continue to successfully advance products in our pipeline and whether they can be commercialized, our expectations about RAYALDEE, the therapeutic benefits or effectiveness of RAYALDEE or whether early initiation of SHPT treatment with RAYALDEE would delay disease progression, whether BioReference’s cost-cutting initiatives and attempts at returning to its core business will be successful, as well as other non-historical statements about our expectations, beliefs or intentions regarding our business, technologies and products, financial condition, strategies or prospects. Many factors could cause our actual activities or results to differ materially from the activities and results anticipated in forward-looking statements. These factors include those described in our Annual Reports on Form 10-K filed and to be filed with the Securities and Exchange Commission and under the heading “Risk Factors” in our other filings with the Securities and Exchange Commission, as well as the continuation and success of our relationship with our commercial partners, liquidity issues and the risks inherent in funding, developing and obtaining regulatory approvals of new, commercially-viable and competitive products and treatments. In addition, forward-looking statements may also be adversely affected by general market factors, competitive product development, product availability, federal and state regulations and legislation, the regulatory process for new products and indications, manufacturing issues that may arise, patent positions and litigation, among other factors. The forward-looking statements contained in this press release speak only as of the date the statements were made, and we do not undertake any obligation to update forward-looking statements. We intend that all forward-looking statements be subject to the safe-harbor provisions of the PSLRA. Contacts:LHA Investor RelationsYvonne Briggs, 310-691-7100ybriggs@lhai.com orBruce Voss, 310-691-7100 bvoss@lhai.com —Tables to Follow— OPKO Health, Inc. and SubsidiariesCondensed Consolidated Balance Sheets(in millions)Unaudited As of September 30, 2023 December 31, 2022Assets: Cash and cash equivalents$138.6 $153.2 Other current assets 218.6 241.3 Total current assets 357.2 394.5 In-process research and development and goodwill 789.5 790.9 Other assets 910.0 981.9 Total Assets$2,056.7 $2,167.3 Liabilities and Equity: Accounts payable$66.8 $67.0 Accrued expenses 92.4 98.3 Current portion of convertible notes 0.0 3.1 Other current liabilities 41.4 45.1 Total current liabilities 200.6 213.5 Long-term portion of convertible notes 213.3 210.4 Deferred tax liabilities, net 138.0 126.4 Other long-term liabilities, principally contract liabilities,leases, contingent consideration and lines of credit 0.2 55.4 Total Liabilities 612.1 605.7 Equity 1,444.6 1,561.6 Total Liabilities and Equity$2,056.7 $2,167.3 OPKO Health, Inc. and SubsidiariesCondensed Consolidated Statements of Operations(in millions, except share and per share data)Unaudited For the three months endedSeptember 30, For the nine months endedSeptember 30, 2023 2022 2023 2022 Revenues Revenue from services$131.7 $142.8 $391.1 $616.3 Revenue from products 40.7 32.4 124.6 104.9 Revenue from transfer of intellectual property and other 6.2 4.5 165.9 97.7 Total revenues 178.6 179.7 681.6 818.9 Costs and expenses Cost of service revenues 106.4 128.2 333.5 521.3 Cost of product revenues 24.5 20.2 74.7 65.4 Selling, general and administrative 72.3 79.7 227.7 298.7 Research and development 19.4 18.8 70.2 54.4 Contingent consideration (1.1) (0.8) (1.0) (0.7)Amortization of intangible assets 21.5 21.4 64.5 66.2 Gain on sale of assets 0.0 0.0 0.0 (15.4)Total costs and expenses 243.0 267.5 769.6 989.9 Operating loss (64.4) (87.8) (88.0) (171.0)Other expense, net (14.0) (38.6) (23.8) (118.3)Loss before income taxes and investment losses (78.4) (126.4) (111.8) (289.3)Income tax benefit (provision) (6.1) 40.3 (10.5) 46.5 Loss before investment losses (84.5) (86.1) (122.3) (242.8)Loss from investments in investees (0.0) (0.0) (0.1) (0.4)Net loss$(84.5) $(86.1) $(122.4) $(243.2)Loss per share, basic and diluted$(0.11) $(0.11) $(0.16) $(0.34)Weighted average common shares outstanding, basic and diluted 751,525,007 750,396,263 751,716,692 708,121,980