EryDel SpA

导读 长久以来，医用红细胞主要来源于人体血液捐献。合成红细胞技术改变了这样一种局面，它是一种革命性的方法，能解决血液短缺的问题。 这项技术包括体外培养或扩增人类红细胞，作为药物的载体。人工合成的红细胞有几个优点，包括没有致癌的DNA和RNA，在体内的半衰期长，能够携带高浓度的药物。 这项技术在制药行业越来越受欢迎，那么这项技术有哪些优点、类别，以及主要做这项技术的公司有哪些，本文进行初步的剖析。 值得一提的是，这个领域的明星公司、红细胞药物先驱 Rubius 2023年年初宣布解散，20亿美元市值蒸发殆尽，可以说这令红细胞药物发展前途未卜，这一技术仍有待完善。 红细胞是人体中数量最多的细胞，其占全部细胞数量的84%左右。长久以来，来源于捐献的血液都是人类医用红细胞的最主要来源。而合成红细胞技术，顾名思义，就是利用新型技术，以在体外培养或者扩增的方式，得到人体红细胞。更重要的是，以合成红细胞为载体，可以建立一个药物开发、制造和体内递送的通用平台，具有发展潜力。 合成红细胞技术起源于美国军方的“一个都不能少”政策。战场创伤引起的大量失血是战地死亡的一大原因，及时输血能挽救这些战地死亡。血液保存期仅仅为六周，而血液从美国本土收集到运输至战地需要四周，这造成战地血液保存期仅为两周，为战地后勤带来巨大的压力。因此，美国国防高级研究计划局（简称DARPA）在2008年向全世界召集在战地生产红细胞的建议。 最终，美国新基制药（Celgene）获得了DARPA的合同，并在人类历史上第一次成功利用造血干细胞，在体外培养出了正常的人红细胞。虽然这条路在理论上可行、可以实现试验，但是由于培养体系较为昂贵，美国国防高级研究计划局认为与其以高昂价格提供输血原料，还不如按照传统献血采集红细胞更为划算。 合成红细胞作为药物开发、制造和递送的载体具有以下几个优点： 1、红细胞没有细胞核、线粒体和核糖体，也就没有任何DNA和长链RNA。 红细胞药物没有致癌性，具有所见即所得的特性； 2、红细胞在人体内存活120天。因此，在红细胞内和表面的蛋白药物也能在体内存活120天，这可以极大延长蛋白药物在体内的半衰期； 3、红细胞具有极好的延伸性，能达到极小的毛细血管； 4、红细胞具有很大的表面积和体积。 比如说，一个红细胞表面可以放360万个抗体，红细胞内可以放2.8亿血红蛋白分子，这种特性可以保障药物的浓度； 5、红细胞特殊的结构使单位体积内红细胞数量很高，人血液中，每微升含有500万个红细胞； 6、输血已经是一种标准的临床医疗操作，因此红细胞药物可以作为货架化的细胞药物。 在制药行业中流行的被称为红细胞药物可以分成三类： 第一类是合成红细胞技术，也就是综合红细胞本身的天然特性和药用蛋白来治疗疾病。 这种类型还可以分为以下两种：一种是先合成造血干细胞，再在体外分化成的合成红细胞来治疗疾病，代表公司有Rubius Therapeutics和Plasti cell。另一种是修改体内成熟的红细胞用来治疗疾病，代表公司为Anokion。而另外两类也同样被称为红细胞药物，但是基本原理就与合成红细胞完全不同了，基本与合成红细胞并无关联。在此，我们只做简要介绍。 第二类是利用红细胞包裹药用蛋白或者小分子药物，提高药用蛋白或者小分子药物的体内半衰期，代表公司是EryDel和Erytech。 这类红细胞药物利用的是传统红细胞破膜及载药功能，基本没有核心专利技术，但对于药用蛋白和小分子药物的体内半衰期提高不多，市场影响力不大。 第三类是利用红细胞以提供大规模细胞膜，和不同的纳米分子、脂质体或固体脂质纳米粒等结合，来递送不同药物分子，包括蛋白、核酸、小分子等，代表公司为Arytha Biosciences、Cello、Nano blood和RxMP。 在这类红细胞药物中，红细胞仅仅是一类生物膜提供者，核心技术专利还是在于纳米分子、脂质体或固体脂质纳米粒。这类药物的优缺点和现有的纳米分子、脂质体或固体脂质纳米粒类似。 Rubius Therapeutics Harvey Lodish教授、Hidde Ploegh教授和Flagship Venture的Noubar Afeyan博士合作以Venture labs模式在2014年初成立Rubius Therapeutics。然后，公司入驻波士顿Lab Central生物孵化器，并于2018年7月在纳斯达克上市。Rubius Therapeutics的合成红细胞药物管线开始有三个方向，肿瘤免疫治疗、自身免疫性疾病和代谢酶缺乏型罕见病。后来，治疗代谢酶缺乏型罕见病的合成红细胞的临床试验不理想，这个研究方向被暂时搁置。 合成红细胞治疗肿瘤是通过肿瘤免疫方式，这包括两种方法，系统性提高免疫细胞数量和抗原特异性免疫细胞扩增。系统性提高免疫细胞数量是在合成红细胞表面表达4-1BBL和IL-15TP（RTX-240），这样的合成红细胞能启动NK细胞的扩增和活化，CD4和CD8T细胞的扩增和活化，同时还能启动CD8记忆细胞的扩增和生存。因此RTX-240主要是作为免疫力提升的疗法，可以和其他靶向性的肿瘤疗法联用。 而抗原特异性免疫细胞扩增则类似一种体内抗原特异T细胞启动的方法。合成红细胞在表面上表达IL-12、4-1BBL和携带特定肿瘤抗原的MHC1（RTX-321）。RTX-321能和拮抗特定肿瘤抗原的T细胞结合，并刺激这类T细胞扩增和启动。这类合成红细胞能在体内启动抗原特定的T细胞，有潜力成为通用的CAR-T疗法的替代品，而且由于合成红细胞上可以冰冻，并大规模生产，这也解决了CAR-T疗法的产量、储存和运输的问题。 合成红细胞治疗自身免疫性疾病则是基于2012年Jeffray Hubbell教授的研究，他发现依附在红细胞上的蛋白抗原能诱导T细胞程式性死亡，Hubbell教授后来成立了Anokion公司。Rubius Therapeutics利用蛋白融合的方法把抗原蛋白表达在合成红细胞表面，同样发现这样的合成红细胞能诱导抗原特异性的T细胞程式性死亡。这就称为了一种潜在的治疗自身免疫性疾病的手段，目前出于开发阶段。 Plasticell Plasticell是一家欧洲公司，法国和英国的科学家在体外培养造血干细胞和前体细胞制造红细胞在2011年以前处于世界领先，法国也是第一个实现体外合成红细胞在人体内存活的临床试验的国家。但是他们并不拥有合成红细胞药物相关的专利，因此虽然Plasticell具有完善的体外红细胞制造系统，却没有办法利用这些红细胞治疗除贫血外的疾病。 注：本文节选自由香港商务印书馆出版的《生命科技投资启示录·捕捉下一只独角兽》，文章已获出版社及作者授权，略有修改。 识别微信二维码，添加生物制品圈小编，符合条件者即可加入 生物制品微信群！ 请注明：姓名+研究方向！ 版 权 声 明 本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Quince Therapeutics, Inc. (Nasdaq: QNCX), a late-stage biotechnology company developing an innovative drug delivery technology designed to leverage a patient’s own biology to deliver rare disease therapeutics, today announced that the first patient has been dosed in the company’s Phase 3 NEAT (Neurologic Effects of EryDex on Subjects with A-T) clinical trial to evaluate the neurological effects of EryDex in patients with Ataxia-Telangiectasia (A-T). This pivotal Phase 3 study will be conducted under a Special Protocol Assessment (SPA) agreement with the U.S. Food & Drug Administration (FDA). “The initiation of our pivotal Phase 3 NEAT study is a major milestone for Quince, and an opportunity for patients living with the devastating effects of Ataxia-Telangiectasia to participate in research seeking to identify a beneficial therapeutic solution,” said Dirk Thye, M.D., Quince’s Chief Executive Officer and Chief Medical Officer. “There are currently no approved therapeutic treatments in any global market for this rare pediatric disease, and our primary corporate objective is to change that for patients with A-T and their families.” The Phase 3 NEAT clinical trial (#IEDAT-04-2022/NCT06193200) is an international, multi-center, randomized, double-blind, placebo-controlled clinical trial to evaluate the neurological effects of EryDex in patients with A-T. The study plans to enroll approximately 86 patients with A-T ages six to nine years old (primary analysis population) and approximately 20 patients with A-T ages 10 years or older. Participants will be randomized (1:1) between EryDex or placebo and treatment will consist of six infusions scheduled every 21 to 30 days. The primary efficacy endpoint will be measured by the change from baseline to last visit completion in rescored modified International Cooperative Ataxia Rating Scale (RmICARS). Participants who complete the full treatment period, complete the study assessments, and provide informed consent will be eligible to transition to an open label extension (OLE) study. Quince expects to report Phase 3 NEAT topline results in the second half of 2025 with a potential New Drug Application (NDA) submission in 2026, assuming positive study results. With the achievement of the first patient enrolled in this study, Quince will make a cash milestone payment of $5 million to the former EryDel shareholders. The company owes no further development related milestones to EryDel shareholders. About Ataxia-Telangiectasia A-T is an inherited autosomal recessive neurodegenerative and immunodeficiency disorder caused by mutations in the ATM gene, which is responsible for cell homeostatic and cell division functions including but not limited to double-stranded DNA repair. Typically, A-T is first diagnosed before the age of five as children begin to develop an altered gait and fall with greater frequency. Neurological symptoms worsen and patients with A-T frequently become wheelchair-bound by adolescence. Teenage years for patients with A-T are typically marked by repeated infections, pulmonary impairment, and malignancies. The median lifespan is approximately 25 to 30 years old with mortality due to infections and malignancy. Based on IQVIA Medical Claims (Dx), PharmetricsPlus (P+), and IQVIA Analytics information, there are approximately 4,600 diagnosed patients with A-T in the U.S. Quince estimates that there are approximately 5,000 patients with A-T in the U.K. and EU4 countries. There are currently no approved therapeutic treatments in any global market for A-T. About EryDex for A-T EryDex is comprised of dexamethasone sodium phosphate (DSP) encapsulated in a patient’s own red blood cells. DSP is a corticosteroid well known for its anti-inflammatory properties as well as its dose-limiting toxicity due to adrenal suppression. EryDex is designed to provide the efficacy of corticosteroids and to reduce or eliminate the significant adverse effects that accompany chronic use of corticosteroid treatment. EryDex leverages Quince’s proprietary Autologous Intracellular Drug Encapsulation, or AIDE, technology platform, which is a novel drug/device combination that uses an automated process designed to encapsulate a drug into the patient’s own red blood cells. Red blood cells have several characteristics that make them a potentially effective vehicle for drug delivery, including potentially better tolerability, enhanced tissue distribution, reduced immunogenicity, and prolongation of circulating half-life. Quince’s AIDE technology is designed to harness these benefits to allow for the chronic administration of drugs that have limitations due to toxicity, poor biodistribution, suboptimal pharmacokinetics, or immune response. About Quince Therapeutics Quince Therapeutics (Nasdaq: QNCX) is a late-stage biotechnology company dedicated to unlocking the potential of a patient’s own biology to deliver innovative and life-changing therapeutics to those living with rare diseases. For more information on the company and its latest news, visit and follow Quince Therapeutics on social media platforms LinkedIn, Facebook, and Twitter/X. Forward-looking Statements Statements in this news release contain “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 as contained in Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, which are subject to the “safe harbor” created by those sections. All statements, other than statements of historical facts, may be forward-looking statements. Forward-looking statements contained in this news release may be identified by the use of words such as “believe,” “may,” “should,” “expect,” “anticipate,” “plan,” “believe,” “estimated,” “potential,” “intend,” “will,” “can,” “seek,” or other similar words. Examples of forward-looking statements include, among others, statements relating to current and future clinical development of EryDex, including a pivotal trial for Ataxia-Telangiectasia, potential commercial-stage inflection point for EryDex, and expansion of the company’s proprietary Autologous Intracellular Drug Encapsulation (AIDE) technology for treatment of other rare diseases; the strategic development path for EryDex; planned regulatory agency submissions and clinical trials and timeline, prospects, and milestone expectations; the timing and success of the clinical trials and related data, including plans and the ability to initiate, conduct, and/or complete current and additional studies; the company’s future development plans and related timing; the company’s focus, objectives, plans, and strategies; and the company’s market opportunity. Forward-looking statements are based on Quince’s current expectations and are subject to inherent uncertainties, risks, and assumptions that are difficult to predict and could cause actual results to differ materially from what the company expects. Further, certain forward-looking statements are based on assumptions as to future events that may not prove to be accurate. Factors that could cause actual results to differ include, but are not limited to, the risks and uncertainties described in the section titled “Risk Factors” in the company’s Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) on April 1, 2024, and other reports as filed with the SEC. Forward-looking statements contained in this news release are made as of this date, and Quince undertakes no duty to update such information except as required under applicable law.

The FDA has granted fast track designation to Quince Therapeutics’ Phase III drug candidate EryDex to treat rare disease ataxia-telangiectasia. Credit: grandbrothers via Shutterstock. California-based biotech Quince Therapeutics has won fast track designation from the US Food and Drug Administration (FDA) for its ataxia-telangiectasia (A-T) drug EryDex. Recommended Buyer's Guides Buyer's Guide Leading Guide to Packaging Materials, Containers and Containment Services for the Pharmaceutical Industry Buyer's Guide Leading Guide to Clinical Packaging Companies in contract Manufacturing for the Pharmaceutical Industry According to the 3 June announcement, fast track designation was awarded to address a high unmet medical need for patients with A-T. The status allows for earlier interactions with the FDA as Quince seeks accelerated approval, and also the possibility to undergo rolling reviews. A-T is a rare disease of the nervous and immune systems, affecting motor movement and speech. EryDex utilises autologous intracellular drug encapsulation (AIDE) technology to administer dexamethasone sodium phosphate (DSP) into a patient’s red blood cells. Red blood cells filled with DSP are then reinfused into the patient, allowing for the slow release of steroids over several weeks, without the long-term toxicity commonly associated with chronic administration. The FDA lifted a partial clinical hold that was on the drug in October 2023, advancing it into the Phase III NEAT study (NCT06193200). The FDA removed the partial clinical hold after requesting additional information on plastics used in the single-use EryKit, which is part of EryDex. Changes were made to comply with recent European regulations. The NEAT study will enrol approximately 86 six- to nine-year-old patients with A-T as the primary analysis population, as well as 20 patients over the age of ten years. Participants will be randomised between EryDex or placebo and treatment will involve six infusions once every 21 to 30 days. The primary efficacy endpoint will be measured by the change from baseline to last visit completion in the rescored modified International Cooperative Ataxia Rating Scale (RmICARS). See Also: FDA hearing set to discuss advisory committee members’ conflicts and more Be Bio’s haemophilia B treatment gains FDA orphan drug status Quince shared in an April 2024 business update that it anticipates topline results in H2 2025 with a potential NDA submission in 2026. Quince inherited EryDex in July 2023 when it acquired biotech EryDel in a $485m deal in October 2023. Formerly known as Cortexyme, Quince changed its name in 2022 and focused on rare diseases following several setbacks, including a clinical hold on its Alzheimer’s disease drug atuzaginstat. In the announcement accompanying the fast track, Quince CEO Dirk Thye said: “The granting of fast track status for EryDex System marks another important milestone in our endeavour to identify a beneficial therapeutic solution for patients with A-T. “We have initiated our pivotal Phase III NEAT clinical trial, which is being conducted in the US, UK, and the European Union.”