SanBio Co., Ltd.

中美至今未批准任何一款干细胞药物。 干细胞高端局在国内风起云涌，疗程一次标价7.8万元至20万元，2022年7月，有人在江西九江被骗450余万元。干细胞在医学界被称为万用细胞，被套利群体演绎成包治百病、返老还童的神药。只有当合规产品正常供给之后，这一领域才有可能河清海晏。 干细胞合规市场明年初迎来开天辟地时刻。Mesoblast于2024年7月向FDA重新提交remestemcel-L上市申请，PDUFA日期为2025年1月7日，有望成为美国首个获批的干细胞创新药。2024 年6月，铂生卓越生物的艾米迈托赛注射液成为国内首款获得国家药监局新药上市申请正式受理并纳入优先审评的干细胞新药。 成药性解决后，巨大的临床需求将在合规产品上集中释放。 从2018年到2024年7月，国内干细胞新药 IND获批83个，进入临床60个。据医药魔方数据不完全统计，国内干细胞创新药处于III期临床试验4项，II期临床试验11项。 等待一支穿云箭。 01  黎明降至 干细胞是人体中具有自我更新能力、多功能性和再分化能力的细胞，具有分化成各种组织和器官的潜能。作为重要的再生医学产品，干细胞进入人体，哪里有损伤、老化、病变，就在哪里聚集，可能应用到几乎涉及人体所有重要组织器官的修复及研究，攻克人类诸多医学医美难题，根治糖尿病、帕金森综合征、阿尔兹海默症，抗衰除皱，疤痕修复。 可见干细胞疗法是一种乌托邦药物，戳中富裕老人的每一个痛点，具有浓郁的老钱风，一度成为高端定制坑。 干细胞疗法面临着伦理和成药挑战。胚胎干细胞（ESC)效果最佳，却需要破坏人类胚胎，存在伦理争议。诱导性多能干细胞（iPSC）的发现克服这一担忧，却面临着另一场伦理争议，其无限的分化能力有朝一日可能应用于人类克隆，并且在临床治疗中仍具有高风险，这些细胞经移植可能会诱导肿瘤形成。虽然间充质干细胞被普遍认为是安全的，在当前临床应用中最多，从组织中分离获得并在体外培养和扩增，具有增殖能力强、分化潜力广泛的优点，但其持续监测和长期随访将是未来研究重点，需观察、避免治疗后形成肿瘤。间充质干细胞规模化生产需要突破，供体单次取材难以满足大规模商业化生产需求，而不同供体来源的细胞存在生物特性差异，只有保证细胞批次间产量和质量的稳定性才有可能提高制剂生产效率，获得可重复的临床疗效。 缓慢的进步始终在发生，FDA也快要动心。Mesoblast今年以来股价已上涨353%。 今年7月23日，FDA接受Mesoblast公司细胞疗法remestemcel-L的生物制品许可申请重新提交，用于治疗类固醇难治性急性移植物抗宿主病（SR-aGVHD）儿童，如果获得批准，将成为美国首个同种异体现货型细胞疗法，早于通用CAR-T取得突破。 remestemcel-L是一种同种异基因间充质干细胞疗法，其细胞来源于无关供体的骨髓，通过抑制T细胞增殖，和下调促炎细胞因子和干扰素的产生，来调节T细胞介导的炎症反应。此前已公开的一项III期试验结果显示，患者接受治疗后第28天的客观缓解率（ORR）为69％，与45%历史控制率相比，有统计学意义的显著增加。在接受至少一次输注治疗且随访100天的患者中，患者的死亡率为22％，而接受初始类固醇治疗无效的患者第100天死亡率高达70%。 即使Mesoblast遇挫，后面还有大将福泰制药为干细胞疗法托底。 一名叫Amanda Smith的35岁护士患有1型糖尿病，一直依赖胰岛素维持生命。直到2023年情人节，她接受一项开创性干细胞疗法。医生将实验室中从胚胎干细胞中培养出来的替代胰岛细胞移植到为Amanda Smith的肝脏供血的血管中。到8月，她不再需要胰岛素了，新细胞正在大量生产胰岛素。 Amanda Smith接受的干细胞疗法，是福泰制药的VX-880，正向关键临床阶段迈进。 VX-880是一种研究性同种异体干细胞衍生、完全分化、产生胰岛素的胰岛细胞疗法，其Ⅰ/Ⅱ期临床试验数据显示，所有接受全剂量单次输注的12名患者在第90天时均展现出胰岛细胞移植成功及对葡萄糖有反应的胰岛素生成，均达到HbA1c水平低于7.0%的目标水平。并有超过70%的时间血糖值处于正常范围(70-180 mg/dL)，其中11位患者减少外源性胰岛素使用或完全停用。 VX-880临床试验中2名患者死亡，后经独立监督委员会审查数据并确定死亡与试验治疗无关，临床试验恢复。福泰制药还有VX-880的升级版，将与VX880相同的同种异体干细胞衍生的胰岛细胞封装在类似于“海蜇”的装置中，大小约为一枚硬币，可通过手术植入患者体内，且无需使用免疫抑制疗法。 现在轮到中国药企上场了。 2024年5月30日，北京市药监局核发全国第一张干细胞《药品生产许可证》，获得者正是铂生卓越，引起轰动，预示着合规干细胞药物即将进入产业化阶段。 6月，铂生卓越自主研发的艾米迈托赛注射液（人脐带间充质干细胞）上市申请获得受理，适应症为激素失败的急性移植物抗宿主病（aGVHD），有望成为全国首款干细胞新药。 国内临床II期后干细胞创新药研发情况（不完全统计） 02  群起撞线 在铂生卓越身后，还有3款干细胞创新药也即将撞线，分别来自爱萨尔生物（膝骨关节炎，III期）、麦迪森再生医学（移植物抗宿主病，III期）、赛比曼/ 西比曼（膝骨关节炎，III期），行业渐呈汹涌澎湃之势。 中源协和布局干细胞全产业链，参股公司牙髓干细胞药物有望成为大单品。 公司主导或参与的11个干细胞临床研究项目完成备案，全资子公司武汉光谷药业核心产品VUM02共开发8个适应症，为自研的冷冻保存型细胞制剂，是由经筛选的健康新生儿脐带组织通过体外分离、扩增、收获、冻存后制备的人脐带源间充质干/基质细胞（UC-MSC）新药，其中用于治疗特发性肺纤维化（IPF）2023年8月获得FDA授予的孤儿药资格认定。 参股的北京三有利和泽生物与首都医科大学共同申报的人牙髓间充质干细胞注射液治疗慢性牙周炎是国内首个获得IND 受理的干细胞新药，于2023年5月进入II期临床试验，目前已有受试者入组给药。 传统牙周炎治疗聚焦炎症控制，阻止或延缓疾病进程，难以获得满意的牙周组织再生，目前临床常用的植骨术依赖手术方式实施。国内外尚无与“人牙髓间充质干细胞注射液”局部注射治疗类似的非侵入式的牙周组织再生引导技术。 牙周炎发病率高，危害大，是导致成年人牙齿缺失的最主要原因。据民生证券测算，2023年我国中重度牙周炎患者约10087万人，三有利牙髓干细胞预计2027年获批上市销售，至少在2031年前享有市场独占期，2033年销售额有望达到约77亿元。 天士力引进的remestemcel-L暂停研究，是悲是喜？ 2018 年7月，天士力与前文所述干细胞明星Mesoblast签署MPC-150-IM（rexlemestrocel-L）产品开发商业化协议。2023 年1月，公司公告决定暂停rexlemestrocel-L研究工作，主要是在美国审评审批遇到波折，是否倒在黎明前的黑暗？然而，2024 年3月，FDA支持Rexlemestrocel-L用于终末期射血分数降低（ HFrEF ）和植入左心室辅助装置（ LVAD ）心衰患者的加速批准申请。 在前沿领域的创新需要坚持的勇气。 不过，天士力从东方医院引进的人脐带间充质干细胞注射液（B2278注射液），今年1月获批开展心衰适应症的临床试验。 国内骨关节适应症干细胞创新药研发情况 干细胞疗法围攻关节炎大适应症。 骨关节炎( osteoarthritis，OA) 是一种严重影响患者生活质量的关节退行性疾病，随着我国人口老龄化程度的不断加剧，OA的患病率有逐渐上升的趋势。据《中国骨关节炎诊疗指南（2021年版）》，我国40岁及以上人群不同年龄段原发性 OA 患病率分别为：30.1%（40~49 岁）、48.7%（50~59岁）、62.2%（60~69岁）和62.1%（70岁以上）；由此估算我国OA患病人数约有3.59 亿。 2021 年9月6日，发表于《The Knee》的一项荟萃分析通过对 79 项（包含 8761名膝骨关节炎患者）的随机对照临床试验进行系统总结证实：在长达一年的随访中，干细胞注射对膝骨关节炎患者的疼痛和功能有最大的改善作用，优于其他骨关节炎治疗方式。 我武生物子公司我武干细胞持续开展干细胞领域的研究开发，完成自研完全培养基、分化培养基（成脂、成骨、成软骨）的开发，相关培养基已应用于干细胞治疗骨关节炎项目中，正全力推进干细胞治疗药物的临床前研究。 Biotech进度更快，西比曼与爱萨尔两家均已开展III期临床。新三板上市公司赛莱拉人脐带间充质干细胞注射液治疗膝骨关节炎新药I 期临床试验完成首例患者给药。 针对缺血性脑卒中后偏瘫是新兴热点。 ST 九芝堂子公司北京美科同种异体骨髓间充质干细胞治疗缺血性脑卒中处于I/ II期临床。据医药魔方数据，国内另有5家公司也在布局缺血性卒中干细胞产品。 成药性在日本得到验证。由于脑细胞不可再生，针对慢性运动功能障碍及其他后遗症一直缺乏有效的治疗手段，2024年7月，SanBio 开发的AKUUGO在日本获批成为全球首款用于此适应症的同种异体间充质干细胞。 首家干细胞Biotech上市公司能成吗？ 泽辉生物向港交所递表，将申请主板挂牌上市。 核心产品ZH901处于临床II期阶段，是国内首个也是唯一一个源自hESC（人胚干细胞）的干细胞来源细胞治疗在研产品，为可用现货细胞制剂，且可于气相液氮中稳定保存至少3年。 如前文所述胚胎干细胞存在伦理争议。用于新hESC系来源的胚胎是在父母双方知情同意的情况下通过体外受精诊所获得。只有无法用于不孕治疗的多余胚胎才能用于获取hESC。然而，这种获取通常需要破坏子宫外胚胎，此举会引起伦理问题，在诸多国家为法律所禁止。 泽辉生物还折射出一级市场Biotech的现金流危机。 2023年末，泽辉生物的现金及现金等价物为1.67亿元，而到今年8月底，已降至0.67亿元，这意味着历轮融资累计获得的6.88亿元已快烧完。 在另外一面，泽辉生物计划10亿元建设中山工厂，预计2024年底开工，2026年下半年完成，年产能约为500000支细胞疗法产品注射液。 奇迹会发生吗？

作为生物制药的一大前沿，细胞疗法越来越受业界重视，也成为不少国家抢占的高地，日本就是这样的代表。 2012年，因发现诱导多能干细胞（iPSC）技术，日本京都大学教授山中伸弥获得诺贝尔奖。此后，日本政府开始积极在细胞治疗领域布局。 通过建立《再生医学促进法》《再生医学安全法》等特殊法规监管途径，十多年来，日本不遗余力地鼓励细胞疗法的开发和商业化，批准了许多产品。它们大部分是由日本公司推出的，但也包括来自欧美MNC的CAR-T疗法。 然而，由于某些产品的疗效缺乏可预测性，日本近期修改了该领域的法规，谨慎地缩小附条件批准范围，降低价格补贴。 商业探索喜忧参半，一些细胞产品已退出日本市场。对于其他国家，能从日本的处境看到多少自己的影子？ 1 18种获批细胞疗法 到目前为止，日本已经批准了18种细胞疗法，包括两款基于附条件批准框架的产品。 适应症分布上，用于治疗血液瘤的产品最多，共计6种。在神经、眼科、骨科等其他疾病领域，也都有疗法覆盖。 从地域看，12种疗法来自日本，占比近七成。其中，光是J-TEC就推出5种。2015年之前，J-TEC的Jace（自体培养表皮）和Jacc（自体培养软骨）是日本仅有的两款获批细胞产品。 改变日本细胞疗法产业环境的关键之年是2012年，山中伸弥因相关研究获得诺贝尔奖。此后，被视为具有广阔前景的iPSC领域，也开始受到日本政府层面的支持。 很多适应症都是在那之后获得批准的。最近一款上市产品，是由日本公司SanBio开发的同种异体间充质干细胞疗法Akuugo，用于改善与创伤性脑损伤相关的慢性运动性麻痹。7月底，Akuugo首次获得附条件批准。 2 安倍“十年战略” 2013年，时任日本首相安倍晋三在其经济政策中指出，政府应牵头推动创新医疗研发的全国性举措，并承诺到2022年这10年间，投资1100亿日元（约合7.53亿美元）支持再生医学发展。 到2014年，安倍政府通过内阁府推动《健康医疗战略推进法》出台，并于2015年成立了专门负责协调和支持国内药物研发项目（不仅仅是细胞疗法）的日本医学研究开发机构（AMED）。 AMED旨在通过横跨厚生劳动省（MHLW）、经济产业省（METI）以及文部科学省（MEXT）三个部门，架起政府、公司和学术机构的桥梁。 从2015年到2020年，AMED每年提供约140亿到160亿日元（约合0.97亿到1.11亿美元）用于支持国内药物研发，其中近一半（65亿日元）用于iPSC领域。 3 附条件批准框架 大约在安倍政府提供资金支持的同一时间，日本颁布了《再生医学促进法》，对《药品和医疗器械法案》进行修订，引入细胞和基因疗法等再生医学产品的附条件批准框架。 改革前，小分子药物等疗法必须经过昂贵且繁琐的三个阶段临床试验，才能获得日本药品和医疗器械管理局（PMDA）的批准。 为了缩短上市时间，该方案允许在若干条件下，提前批准已证实安全性和具备“潜在”疗效的疗法。之后，这些产品需要开展上市后的试验以确认疗效，并在附条件批准期内提交申请以获得全面批准。 Nature刊登的一篇文章介绍，基于这个框架，再生医学疗法开发商将不必按照阶段推进临床，而是在一项试验研究中证明疗效。如果变化足够显著，则一次试验中至少要有10名患者；如果改善幅度较小，则要有几百名患者。 2014年11月，PMDA在一份解释性文件中表示，对iPSC相关产品的高期望和解决潜在安全风险的监管方法是该方案的关键。 从2017年开始，附条件批准框架扩大到包括非再生创新药物。 4 分化的商业市场 得益于这些转变，监管部门自2015年以来越来越频繁地对细胞和基因疗法产品点头。然而，日本也不得不的面临随之而来的问题，例如，产品附条件批准后的疗效不及预期，日本国民健康保险（NHI）计划中的成本与效益平衡压力。 2015年，JCR Pharmaceuticals申报的同种异体骨髓源间充质干细胞（MSC）产品Temcell、Terumo申报的自体成骨肌源性细胞片产品HeartSheet，分别获得附条件批准。 Temcell基于2003年由Osiris Therapeutics授权的MSC技术开发，被批准用于移植物抗宿主病，这是一种发生在同种异体骨髓移植患者中的严重并发症。Temcell每次治疗价格约为1400万日元，并成为日本最成功的细胞疗法之一，在2023年创造32亿日元（2210万美元）的收入。 不过，HeartSheet就没那么幸运了。最初，HeartSheet获得治疗严重心力衰竭的5年有条件批准，但由于其适应症小等诸多限制，后来在上市后试验中招募患者时遇到困难。 附条件批准期延长至8年后，Terumo在2023年申请全面批准，但未能证明其有效性。最终，Terumo决定在今年将HeartSheet撤出市场。 另一个与之相似的案例，是日本公司Nipro开发的自体骨髓来源MSC产品Stemirac，附条件批准期间从2018年到2025年，用于改善与创伤性脊髓损伤相关的神经症状和功能障碍。 自COVID-19以来，Nipro在Stemirac商业化方面受阻。最近该公司表示，它的目标是在2025年申请全面批准，并扩大与医疗机构的合作，以获得收入。 5月，Nipro披露的最新财务报告说：“COVID-19的两年中，由于优先考虑重症患者，对Stemirac的管理一直很困难，其收入未能达到最初的预测。” 5 收窄加速通道 附条件批准框架施行十年后，今年3月，MHLW发布一项新指南，以说明如何通过上市后的研究计划来认定细胞疗法的有效性。 指南提到，药企和监管机构应事先明确附条件批准后所开展试验的适当性，应涉及病例数、开展试验的地点数、参数的客观性、病例的随机化、评价的盲法、对照组的建立等方面。为此，指南还提出了统计学上可推测有效性的参考基准。 MHLW此举的背景是，2020年到2023年，日本政府根据此前“十年战略”的框架，对未来的创新药品政策进行一系列讨论。 6月，因为附条件批准期限届满，AnGes撤回了日本首款基因疗法Collategene的制造和营销批准申请。随着Collategene、HeartSheet等几款产品证明其疗效的失败，MHLW认为，通过哪种类型的数据，并以怎样的准确性“推测”疗效，成为日本的关键挑战之一。 “重要的是要有某种指导方针来推定有条件批准的效力。”去年，MHLW在就这一问题撰写的最终报告里写道。 截至2024年，没有任何附条件批准的细胞治疗产品在日本成功获得全面批准。 6 国家医保“砍价” 日本细胞疗法开发商面临的另一个挑战是，NHI降低了报销价格。有几种产品由于价格昂贵，已根据成本效益评估（CEA）框架进行了审查。 CEA框架自2019年推出，旨在通过增加另一种价格评估选项，来“补充日本的药品定价体系”，帮助维持NHI报销费率内的财务平衡。CEA导致的最大降价幅度为15%。MHLW指出，如果产品在初始定价中获得的溢价低于25%，则降价幅度将限制在10%以内；如果溢价超过25%，则降幅最高不超过15%。 数种CAR-T细胞疗法——包括吉利德的Yescarta，BMS的Breyanzi和Abecma，诺华的Kymriah——已在日本获得了报销价格。 MHLW最初通过成本计算方法，在2019年将Kymriah的报销价格定为约3411.37万日元（约合23.43万美元）。这是在诺华的基因疗法Luxturna于2023年登陆日本市场前，在NHI获得的最高价格。 2021年，通过CEA审查，和安进的Blyncito、辉瑞的Besponsa等其他几种疗法进行比较后，MHLW将Kymriah的价格下调了4.3%，至3264.78万日元。该机构指出，Kymriah在首次定价时的生产成本缺乏透明度（低于50%）。 Yescarta、Breyanzi和Abecma预计也将在日本的CEA框架下接受审查。 7 本土尚有后来者 尽管监管立场日趋谨慎，日本目前还有其他细胞疗法处于临床开发当中。 Healios K.K.的同种异体骨髓来源的多能祖细胞候选药物HLCM051，目前正处于治疗急性呼吸窘迫综合征的III期研究。1月，在美国开展的另一项治疗缺血性卒中的III期项目中，HLCM051错过了主要终点。 另一家专注于CAR-T疗法的日本公司Noile-Immune，旗下NIB101、NIB102已处于I期临床，分别靶向GM2和GPC3。 2023年6月，Noile-Immune在本土IPO，但目前股价跌幅超过70%。 Noile-Immune遭遇了几次挫折，包括终止与武田就NIB102的研发合作。不过，该公司近期表示，它仍将继续推进NIB102。 参考资料： 1.Progress Or Hype? Looking At A Decade Of Cell Therapy In Japan；Pink Sheet 2.Japan to offer fast-track approval path for stem cell therapies；Nature 3.医薬品医療機器総合機構（PMDA）のウェブサイト；PMDA 4.BRIEF—Collategene sales rights deal terminated in Japan and the USA；Pharma Letter 5.Japan’s CEA Scheme: How It Works And Impact So Far；Pink Sheet 6.Cell Therapy HLCM051 Fails to Improve Stroke Outcomes Despite Safe Profile；NeurologyLive 同写意媒体矩阵，欢迎关注↓↓↓

Revenue improved sequentially across all businesses Commercial Cell & Gene Therapy revenue increased 51% year-over-year and 20% sequentially A record total of 684 global clinical trials supported as of June 30, 2024 Cost reduction initiatives anticipated to result in approximately $22 million of annualized cost savings and drive Cryoport towards its goal of profitable growth, as well as a return to positive Adjusted EBITDA in 2025 Company provides updated 2024 full-year revenue guidance of $225 to $235 million NASHVILLE, Tenn., Aug. 6, 2024 /PRNewswire/ -- Cryoport, Inc. (NASDAQ: CYRX) (Cryoport), a global leader in supply chain solutions for the life sciences, today announced financial results for its second quarter (Q2) and first half (H1) of 2024. Jerrell Shelton, CEO of Cryoport, commented, "During our second quarter, we saw continued progress across all businesses as all revenue lines improved sequentially. Our revenue from the support of commercial Cell & Gene Therapies stood out, with an increase of 51% year-over-year and 20% sequentially, reflecting a strong demand for these life-saving treatment therapies. "MVE Biological Solutions, our primary Life Sciences Products business, showed a modest sequential improvement for the quarter, as we continued to experience overall lower demand compared to previous years. We anticipate continued softness in demand in our Life Sciences Products business, as customers continue to delay capital expenditures and leverage their existing footprint of cryogenic systems. We have executed cost management initiatives across our manufacturing facilities and aligned the direct workforce with the current market demand to help enable continuing positive cash flow contribution. Longer term, we expect demand to improve as excess freezer capacity is absorbed. "Based on our anticipated sequential revenue growth in our Life Sciences Services, coupled with the expected continued softness in demand for our Life Sciences Products, we are revising our full year 2024 revenue guidance to the range of $225 million to $235 million, with revenue expected to continue to improve progressively during the course of the remainder of this year. "As previously disclosed, we have been implementing cost reduction and capital realignment measures as well as pacing the build-out of our global capabilities and infrastructure to be more in line with the current market environment. We anticipate our cost reduction initiatives will be fully implemented by the end of 2024 and will positively impact Cryoport's financial results for the second half of 2024 with approximately $22 million in annualized cost savings for 2025, driving the Company towards its goal of profitable growth, as well as a return to positive adjusted EBITDA in 2025. "We believe our cost reduction and capital realignment plan will enable us to continue to successfully service our customers and execute on our key growth initiatives as we optimize our operational efficiencies by reducing operating costs across our global organization. We intend to drive profitable growth in our key markets, enhance operating performance, and generate positive cash flow. Examples of some of the cost reduction actions taken to date are outlined below: Life Sciences Services Reduced global Full Time Equivalents (FTE) by 101 Reduction of external contractors and consultants CAPEX reduction/deferrals, including New facilities delayed, and Consolidation of engineering and R&D initiatives Prioritizing resource allocation for the support of anticipated commercial launches and the ongoing global ramps of approved therapies Life Sciences Products Reduced global FTE by 46 Reduced variable manufacturing labor and material costs CAPEX reductions and deferrals, including Deferral of expansion plans Reprioritization of engineering and R&D projects "We remain confident in a broad-based market recovery for the life sciences industry except for China, which we think will remain challenged through 2025. Our current full year 2024 revenue outlook includes expected sequential improvements across our Life Sciences Services offerings driven in part by the ramp of clinical and commercial Cell & Gene therapies we currently support, as well as anticipated new product and service launches later this year that will further diversify and enhance our revenue streams. We therefore expect a return to year-over-year revenue growth for Cryoport in the second half of 2024," concluded Mr. Shelton. In tabular form, Q2 2024 and H1 2024 revenue compared to Q2 2023 and H1 2023, respectively, were as follows: BioStorage/Bioservices revenue continues to grow double digits year-over-year as we continue to add new customers into our global network and as more allogeneic clinical and commercial therapies progress in the number of patients treated. Revenue from commercial approved Cell & Gene therapies increased 51% year-over-year. One new therapy received U.S. Food and Drug Administration (FDA) approval during Q2 2024, one new therapy was approved by the Pharmaceuticals and Medical Devices Agency (PMDA) of Japan in July, and last week the FDA approved the first cell therapy targeting a solid tumor. This brings our current total commercial count to seventeen (17) as of August 1, 2024. The FDA approval in the second quarter was ImmunityBio's Anktiva for BCG-unresponsive non-muscle invasive bladder cancer. The FDA approval on August 1st, 2024 was Adaptimmune's Tecelra for the treatment of adults with unresectable or metastatic synovial sarcoma. The therapy approved by the PMDA in July was SanBio's AKUUGO, an allogeneic treatment for the indication of improving chronic motor paralysis resulting from traumatic brain injury. Moreover, in the second quarter two other previously approved Cryoport supported therapies received new approvals to move to earlier lines of treatment, which increased the addressable market for both therapies. Separately, two other Cryoport supported therapies received expanded label approvals in the second quarter. As of June 30, 2024, Cryoport supported a total of 684 global clinical trials, a net increase of 16 clinical trials over June 30, 2023, with 76 of these clinical trials in Phase 3 . The number of trials by phase and region are as follows: During the second quarter five (5) BLA/MAA filings occurred, one BLA filing occurred in July. For the remainder of 2024, we anticipate up to an additional seven (7) application filings, two (2) new therapy approvals and an additional one (1) approval for label/geographic expansion. BioLogistics Solutions growth in the second quarter also benefited from the ramp in temperature-controlled logistics revenue outside of the Cell & Gene market, including biosimilars, antibodies, API's and a growing number of Direct-to-Patient shipments. Financial Highlights Revenue Total revenue for Q2 2024 was $57.6 million compared to $57.0 million for Q2 2023, a year-over-year increase of 1.0% or $0.6 million and up $3.0 million or 5.5% sequentially. Life Sciences Services revenue for Q2 2024 was $38.0 million compared to $35.2 million for Q2 2023, up 8.1% year-over-year and 3.4% sequentially, including BioStorage/BioServices revenue of $3.5 million, up 10.1% year-over-year and down 0.2% sequentially. Life Sciences Products revenue for Q2 2024 was $19.6 million compared to $21.8 million for Q2 2023, down 10.4% year-over-year and up 9.8% sequentially. Total revenue for H1 2024 was $112.2 million compared to $119.8 million for H1 2023. Life Sciences Services revenue for H1 2024 was $74.8 million compared to $71.0 million for H1 2023, including BioStorage/BioServices revenue of $7.1 million for H1 2024 compared to $6.4 million for H1 2023. Life Sciences Products revenue for H1 2024 was $37.4 million compared to $48.8 million for H1 2023. Gross Margin Total gross margin was 43.7% for Q2 2024 compared to 43.4% for Q2 2023. Gross margin for Life Sciences Services was 44.5% for Q2 2024 compared to 43.2% for Q2 2023. Gross margin for Life Sciences Products was 42.2% for Q2 2024 compared to 43.7% for Q2 2023. Total gross margin was 41.9% for H1 2024 compared to 43.2% for H1 2023. Gross margin for Life Sciences Services was 42.9% for H1 2024 compared to 45.0% for H1 2023. Gross margin for Life Sciences Products was 39.7% for H1 2024 compared to 40.7% for H1 2023. Operating Costs and Expenses Operating costs and expenses were $104.4 million for Q2 2024 compared to operating cost and expenses of $43.1 million for Q2 2023. The increase for Q2 2024 was primarily the result of an impairment loss of $63.8 million, which is primarily related to the write off of remaining goodwill for MVE Biological Solutions. Operating costs and expenses for H1 2024 including the write off were $147.5 million compared to $80.2 million for H1 2023. Operating costs and expenses, excluding the impairment loss for Q2 2024 were $40.6 million, down year-over-year and sequentially, compared to operating costs and expenses of $43.1 million for both Q2 2023 and Q1 2024, respectively. The decrease is primarily attributable to the Company's recent implementation of cost alignment and reprioritization initiatives. The Company expects these initiatives to further positively impact its results of operations during the second half of 2024. Operating costs and expenses include the start-up cost of services planned to be introduced during the fourth quarter and the first half of 2025 and are expected, as a percentage, to decline as these introductions are made and ramp. Excluding the impairment charge, operating costs and expenses for H1 2024 were $83.7 million, compared to $80.2 million for H1 2023. Net Loss Net loss for Q2 2024 and H1 2024 was $78.0 million and $96.9 million, respectively, compared to a net loss of $18.4 million and $23.9 million for the same periods in 2023, respectively. The increase in net loss was primarily a result of the impairment loss of $63.8 million. Net loss, excluding the impairment loss for Q2 2024 and H1 2024 was $14.2 million and $33.1 million, respectively, compared to a net loss of $18.4 million and $23.9 million for the same periods in 2023, respectively. Net loss attributable to common stockholders was $80.0 million, or $1.62 per share, and $100.9 million, or $2.05 per share, for Q2 2024 and H1 2024, respectively. This compares to a net loss attributable to common stockholders of $20.4 million, or $0.42 per share, and $27.9 million, or $0.58 per share, for Q2 2023 and H1 2023, respectively. Adjusted EBITDA Adjusted EBITDA was a negative $3.8 million for Q2 2024, compared to negative $1.3 million for Q2 2023. Adjusted EBITDA for H1 2024 was a negative $11.5 million compared to $1.6 million for H1 2023. Cash, Cash equivalents, and Short-Term Investments Cryoport held $427.1 million in cash, cash equivalents, and short-term investments as of June 30, 2024. Convertible Debt repurchases During Q2 2024 and in July 2024, the Company repurchased $10.0 million and $15.0 million in aggregate principal amount of its Convertible Senior Notes due in 2026 for an aggregate repurchase price of $8.7 million and $12.9 million, respectively. On August 6, 2024, the Company announced that its Board of Directors had authorized a repurchase program to purchase up to $200 million of the Company's common stock and/or convertible senior notes (the "2024 Repurchase Program"). The 2024 Repurchase Program became effective on August 1, 2024 and remains in effect through December 31, 2027. It further announced that it has entered into agreements with certain of the holders of its 0.75% Convertible Senior Notes due in 2026 (the "2026 Notes") to repurchase $160 million in aggregate principal amount of the 2026 Notes for an aggregate repurchase price of $141.6 million, plus accrued and unpaid interest. The repurchase was made under the 2024 Repurchase Program. Note: All reconciliations of GAAP to adjusted (non-GAAP) figures above are detailed in the reconciliation tables included later in the press release. Outlook We now expect full year 2024 revenue in the range of $225 million - $235 million. The Company's 2024 guidance is dependent on its current business and expectations, which may be further impacted by, among other things, factors that are outside of our control, such as the global macroeconomic and geopolitical environment, supply chain constraints, inflationary pressures, and the effects of foreign currency fluctuations, as well as the other factors described in the Company's filings with the Securities and Exchange Commission ("SEC"), including in the "Risk Factors" section of its most recently filed periodic reports on Form 10-K and Form 10-Q, as well as in its subsequent filings with the SEC. Additional Information Further information on Cryoport's financial results is included in the attached condensed consolidated balance sheets and statements of operations, and additional explanations of Cryoport's financial performance are provided in the Company's Quarterly Report on Form 10-Q for the three months ended June 30, 2024, which is expected to be filed with the SEC on August 6, 2024. Additionally, the full report will be available in the SEC Filings section of the Investor Relations section of Cryoport's website at . Earnings Conference Call Information IMPORTANT INFORMATION: In addition to the earnings release, a document titled "Cryoport Second Quarter 2024 in Review", providing a review of Cryoport's financial and operational performance and a general business update, will be issued at 4:05 p.m. ET on Tuesday, August 6, 2024. The document is designed to be read in advance of the questions and answers conference call and will be accessible at . Cryoport management will host a conference call at 5:00 p.m. ET on August 6, 2024. The conference call will be in the format of a questions and answers session and will address any queries investors have regarding the Company's reported results. A slide deck will accompany the call. Conference Call Information The questions and answers call will be recorded and available approximately three hours after completion of the live event in the Investor Relations section of the Company's website at for a limited time. To access the replay of the questions and answers click here. A dial-in replay of the call will also be available to those interested, until August 13, 2024. To access the replay, dial 1-844-512-2921 (United States) or 1-412-317-6671 (International) and enter replay entry code: 1157932#. About Cryoport, Inc. Cryoport, Inc. (Nasdaq: CYRX), is a global leader in supply chain solutions for the Life Sciences with an emphasis on cell & gene therapies. Cryoport enables manufacturers, contract manufacturers (CDMO's), contract research organizations (CRO's), developers, and researchers to carry out their respective business with products and services that are designed to derisk services and provide certainty. We provide a broad array of supply chain solutions for the life sciences industry. Through our platform of critical products and solutions including advanced temperature-controlled packaging, informatics, specialized bio-logistics services, bio-storage, bio-services, and cryogenic systems, we are "Enabling the Future of Medicine™" worldwide, through our innovative systems, compliant procedures, and agile approach to superior supply chain management. Our corporate headquarters, located in Nashville, Tennessee, is complemented by over 50 global locations in 17 countries, with key sites in the United States, United Kingdom, France, the Netherlands, Belgium, Portugal, Germany, Japan, Australia, India, and China. For more information, visit or follow via LinkedIn at or @cryoport on X, formerly known as Twitter at for live updates. Forward-Looking Statements Statements in this press release which are not purely historical, including statements regarding Cryoport's intentions, hopes, beliefs, expectations, representations, projections, plans or predictions of the future, are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, but are not limited to, those related to Cryoport's industry, business, long-term growth prospects, plans, strategies, acquisitions, future financial results and financial condition, such as Cryoport's outlook and updated guidance for full year 2024 revenue and the related assumptions and factors expected to drive revenue, projected growth trends in the markets in which the Cryoport operates, Cryoport's plans and expectations regarding the launch of new products and services, such as the expected timing and benefits of such products and services launches, Cryoport's expectations about future benefits of its acquisitions, and anticipated regulatory filings, approvals, label/geographic expansions or moves to earlier lines of treatment approved with respect to the products of Cryoport's clients. Forward-looking statements also include those related to Cryoport's plans and expectations relating to its recently announced cost reduction and capital realignment measures, including that such measures will be fully implemented by the end of 2024 and will positively impact Cryoport's financial results for the second half of 2024 with approximately $22 million in annualized cost savings, driving Cryoport towards its goal of profitability, as well as a return to positive adjusted EBITDA in 2025; Cryoport's expectations of continued softness in demand in its Life Sciences Products business with demand to improve over the longer term as excess freezer capacity is absorbed; Cryoport's expectations that its revenue will continue to improve progressively during the course of the remainder of 2024, along with a return to year-over-year revenue growth in the second half of 2024; Cryoport's beliefs about a broad-based market recovery for the life sciences industry except for China, which it believes will remain challenged through 2025; Cryoport's expectations of sequential improvements across its Life Sciences Services offerings driven in part by the ramp of clinical and commercial Cell & Gene therapies its currently supports, as well as anticipated new product and service launches later this year that will further diversify and enhance its revenue streams; and Cryoport's belief that operating costs and expenses, which include the start-up cost of services planned to be introduced during the fourth quarter and the first half of 2025, are expected to, as a percentage, decline as these introductions are made and ramped up. It is important to note that Cryoport's actual results could differ materially from those in any such forward-looking statements. Factors that could cause actual results to differ materially include, but are not limited to, risks and uncertainties associated with the effect of changing economic and geopolitical conditions, supply chain constraints, inflationary pressures, the effects of foreign currency fluctuations, trends in the products markets, variations in Cryoport's cash flow, market acceptance risks, and technical development risks. Additional risks and uncertainties include difficulties, delays or Cryoport's inability to successfully complete its planned cost reduction and capital realignment measures, which could reduce the benefits realized from such activities within the time periods currently anticipated. Cryoport's business could be affected by other factors discussed in Cryoport's SEC reports, including in the "Risk Factors" section of its most recently filed periodic reports on Form 10-K and Form 10-Q, as well as in its subsequent filings with the SEC. The forward-looking statements contained in this press release speak only as of the date hereof and Cryoport cautions investors not to place undue reliance on these forward-looking statements. Except as required by law, Cryoport disclaims any obligation, and does not undertake to update or revise any forward-looking statements in this press release. Note Regarding Use of Non-GAAP Financial Measures To supplement our financial statements, which are presented on the basis of U.S. generally accepted accounting principles (GAAP), the following non-GAAP measures of financial performance as defined in Regulation G of the Securities Exchange Act of 1934 are included in this release: revenue at constant currency, revenue growth rate at constant currency, operating costs and expenses, excluding impairment loss, net income, excluding impairment loss, and adjusted EBITDA. Non-GAAP financial measures are not calculated in accordance with GAAP, are not based on any comprehensive set of accounting rules or principles and may be different from non-GAAP financial measures presented by other companies. Non-GAAP financial measures, including revenue at constant currency, revenue growth rate at constant currency and adjusted EBITDA, should not be considered as a substitute for, or superior to, measures of financial performance prepared in accordance with GAAP. We believe that revenue growth is a key indicator of how Cryoport is progressing from period to period and we believe that the non-GAAP financial measures, revenue at constant currency and revenue growth rate at constant currency, are useful to investors in analyzing the underlying trends in revenue. Under GAAP, revenue received in local (non-U.S. dollar) currency is translated into U.S. dollars at the average exchange rate for the period presented. As a result, fluctuations in foreign currency exchange rates affect the results of our operations and the value of our foreign assets and liabilities, which in turn may adversely affect results of operations and cash flows and the comparability of period-to-period results of operations. When we use the term "constant currency," it means that we have translated local currency revenue for the current reporting period into U.S. dollars using the same average foreign currency exchange rates for the conversion of revenue into U.S. dollars that we used to translate local currency revenue for the comparable reporting period of the prior year. Revenue growth rate at constant currency refers to the measure of comparing the current reporting period revenue at constant currency with the reported GAAP revenue for the comparable reporting period of the prior year. However, we also believe that data on constant currency period-over-period changes have limitations, particularly as the currency effects that are eliminated could constitute a significant element of our revenue and could significantly impact our performance. We therefore limit our use of constant currency period-over-period changes to a measure for the impact of currency fluctuations on the translation of local currency revenue into U.S. dollars. We do not evaluate our results and performance without considering both period-over-period changes in non-GAAP constant currency revenue on the one hand and changes in revenue prepared in accordance with GAAP on the other. We caution the readers of this press release to follow a similar approach by considering revenue on constant currency period-over-period changes only in addition to, and not as a substitute for, or superior to, changes in revenue prepared in accordance with GAAP. Operating costs and expenses, excluding impairment loss, is defined as operating costs and expenses, excluding impairment losses, if any. Net loss, excluding impairment loss, is defined as net loss, excluding impairment losses, if any. Management believes these measures, when read in conjunction with, and as supplemental to, the corresponding GAAP financial measures, provide a useful measure of Cryoport's expenses and operating results, a meaningful comparison with historical results, and insight into Cryoport's operating performance. Adjusted EBITDA is defined as net loss adjusted for interest expense, income taxes, depreciation and amortization expense, stock-based compensation expense, acquisition and integration costs, restructuring costs, investment income, unrealized (gain)/loss on investments, foreign currency (gain)/loss, gain on insurance claim, net gain on extinguishment of debt, impairment loss, changes in fair value of contingent consideration and charges or gains resulting from non-recurring events, as applicable. Management believes that adjusted EBITDA provides a useful measure of Cryoport's operating results, a meaningful comparison with historical results and with the results of other companies, and insight into Cryoport's ongoing operating performance. Further, management and the Company's board of directors utilize adjusted EBITDA to gain a better understanding of Cryoport's comparative operating performance from period to period and as a basis for planning and forecasting future periods. Adjusted EBITDA is also a significant performance measure used by Cryoport in connection with its incentive compensation programs. Management believes adjusted EBITDA, when read in conjunction with Cryoport's GAAP financials, is useful to investors because it provides a basis for meaningful period-to-period comparisons of Cryoport's ongoing operating results, including results of operations, against investor and analyst financial models, helps identify trends in Cryoport's underlying business and in performing related trend analyses, and it provides a better understanding of how management plans and measures Cryoport's underlying business. SOURCE Cryoport, Inc.