Antheia, Inc.

在全球化的今天，药物供应链的稳定性对公共卫生至关重要。然而，这一链条面临着多种挑战，导致药品短缺问题时有发生。 为解决这一问题，合成生物学通过重新设计和构建微生物的遗传物质，提供了一种高效、可持续的药物生产方法。这种方法能够简化生产流程，减少生产步骤，从而提高生产效率和产品质量。 合成生物学技术同样可以推动原料药产业的创新，使得一些以前难以合成或成本过高的药物成分得以经济有效地生产。比如，利用合成生物学技术改造微生物，使其能够生产特定的药物成分，从而提高全球基本药物的可及性，解决药物短缺问题。 在解决药物供应短缺问题上，美国公司Antheia很具有代表性，这是一家利用合成生物学技术来生产药物成分的公司，其目标是改变基本药物供应链，以消除药物短缺的问题。Antheia的合成生物学制造平台能够在酵母细胞中重建复杂的生物合成路径，并将发酵规模化扩展到商业水平。这种方法可以实现关键药物成分的按需、敏捷和弹性生物制造，取代无法支持现代医疗需求的传统合成方法。 全球超过20亿人 无法获得基础药物 当前的药品生产方式，往往导致人们无法公平地获得基本药物。世界卫生组织估计，全世界有超过 20 亿人无法获得基本药物。 药品供应链的短缺问题可能由多种因素引起，包括生产中断、原料药供应不足、市场需求的急剧变化、价格因素、政策和法规变化，以及自然灾害和地缘政治等不可预测的因素。 受到原材料供应不稳定、价格上涨、生产过程中的环境和安全问题的影响，原料药供应不足常常是导致成品药短缺的主要原因。除此之外，工厂设备老化、技术落后或生产线升级改造导致的生产中断，季节性流行疾病导致的市场需求急剧变化，一些基本药物价格低廉导致企业缺乏生产动力等，都同样会影响药品的供应。 为了应对这些挑战，各国政府和制药企业都在采取措施提高药品供应链的稳定性和韧性。提高监测和及时响应的灵敏度，通过建立多源信息采集平台和协同监测机制，实现原料药和制剂在注册、生产、采购、价格等方面的信息联通共享，是提高供应链稳定性的重要手段。 其中，合成生物学的应用有助于解决药物短缺问题，因为它能够快速响应市场需求，通过生物发酵的方式大量生产药物成分，同时降低成本，提高原料药的可获得性。 Antheia便是这一领域的领头羊，Antheia 成立于 2015 年，由斯坦福大学 Smolke 实验室创立，其理念是酵母可以通过编程高效生产复杂的药物成分。他们希望致力于利用合成生物学，建立更有效的解决方案，以可持续和负责任的方式生产药品，并推动世界各地更加公平的健康结果。 Antheia的联合创始人兼首席执行官Christina Smolke博士是斯坦福大学的生物工程教授，她通过拼接起23个不同的来自植物、哺乳动物、细菌和酵母的基因，合成了阿片类化合物，并因此成为Nature 2015年度“十大值得关注人物”。 迄今为止，Antheia已经从 Viking Global、Sherpalo Ventures 和亿万富翁 Eric Schmidt 的投资公司 Hillspire 等投资者手中筹集了超过 1.41 亿美元资金。而Antheia在2021年完成了B轮融资，筹集了7300万美元，用于将公司的首批药用化合物推向市场、扩大其产品管道以及提升生产规模供全球市场。 设计酵母中最复杂的生物合成途径，聚焦KSM与API生产短缺问题 通过合成生物学技术，Antheia希望以更高效、更灵活、更可持续的方式，生产生物合成的基本药物关键起始材料 （Key Starting Material，KSM）和活性药物成分（Active Pharmaceutical Ingredient，API）。 KSM关键起始材料是指在原料药合成过程中，第一个引入活性药物成分最终结构的重要结构片段的化合物。KSM是原料药合成的起点，通常是一个相对复杂的有机分子，它在合成过程中会通过一系列的化学反应转化为API。 合成生物学技术可以用于生产KSM，通过基因编辑和生物发酵的方法，以求更加高效和可持续地生产这些关键起始物料。据Antheia介绍，如今，40% 的 KSM 和 API 都来自大自然。种植用于药物的农作物是一个缓慢、低效且充满风险的过程，使医药供应链变得脆弱，并经常导致关键和基本药物短缺。 为此，Antheia建立了传统方法的革命性替代方案，并打造了聚焦KSM和API的全链条生产体系。 首先，Antheia的平台能够通过发酵方式制造一些最复杂的小分子药物。利用全细胞工程方法，Antheia团队在酵母细胞中重建了前所未有的复杂度和长度的生物合成途径，大大扩展了可通过发酵生产的化合物种类。利用这些经过工程改造的酵母细胞，Antheia可将糖转化为复杂的分子。 接下来，便是Antheia的微生物工厂工程装配线，通过收集自然界中各种生物的基因组信息，Antheia可以应用先进的生物信息学工具来搜索、分析和识别编码酶的基因，这些酶可催化有价值且复杂的天然产物的生产。然后，Antheia用生产复杂、高效药用小分子的蓝图对酵母的 DNA 进行编码。这样，公司就达到了在酵母中设计分子工厂装配线的目的，并精确控制酶如何协同作用以构建生物合成途径。  在构建这些工程微生物后，Antheia致力于完善发酵及下游加工。通过采用高通量工作流程，公司能够每月对数万种菌株设计进行小规模定量性能表征，并开发发酵和下游化学工艺来生产和纯化目标分子。 不过，对于合成生物学企业来说，规模化生产才是最重要的瓶颈。使研发适应产业规模，是Antheia的终极目标。据介绍，在筛选菌株和开发工艺的同时，公司开始确定全面生产能力并扩大到商业规模。虽然许多菌株在实验室规模下表现良好，但将这些相同的工艺过渡到中试规模（高达 500 升）并最终过渡到工业规模（>100000 升）非常复杂，需要深入整合研发、制造、工艺工程、供应链、质量保证、质量控制和监管事务。Antheia的工艺及其多次迭代，为过渡到中试和全面生产提供了最佳路径。 而为了让这些简化的工作流程为产品转向工业制造铺平了清晰的道路。Antheia开发了先进的分析和建模工具，来优化、简化和系统化技术平台的发现和设计流程。凭借通过研发流程积累的大量内部数据集，公司利用数据驱动的方法显著改进了生物制造平台。 在这样的平台技术支持下，Antheia能够优化总体成本与生产效率，还能够大幅缩短生产时间，实现按需、快速响应生产。 目前，Antheia的产品线已经完全符合美国FDA和世界卫生组织的基本药物清单，其技术为改善全球基本药物可及性的努力提供支持。公司的产品线涵盖多种治疗领域，包括神经学、呼吸系统、抗感染药物和肿瘤学。 约5天内生产116立方米蒂巴因，Antheia已完成首次规模商业化生产 经过8年的发展，2023年8月，Antheia宣布完成首次商业化规模生产。 Antheia的首个商业规模发酵产品是蒂巴因（thebaine），这是羟考酮、丁丙诺啡、纳络酮、纳布啡、羟吗啡酮和埃托啡等止痛和戒毒药物的关键成分。在合成生物学领域，蒂巴因可以通过基因改造的微生物如酵母进行生物合成，这为生产提供了一种替代传统提取方法的途径。 根据新闻信息， Antheia 利用高度工程化微生物（具有 25-30 个复杂异源生物合成步骤及 20 多种酶）来生产植物来源的药物活性成分，提高此类药物制造的规模和效率。公司在大约五天内生产出116000升蒂巴因，并达到了可盈利水平的发酵产品浓度，这一成就标志着公司在合成生物学领域的商业化突破。 "我们首次全规模发酵生产标志着规模化制造复杂性小分子药物的技术成就，以及商业化突破的重要进展。 凭借 Antheia的技术，客户可以获得对其药物生产供应链的更好地控制性和可预见度，"Antheia首席执行官兼联合创始人Christina Smolke博士曾说道，"看到我们的商业进步与改变药品供应链、实现更公平获得药物的使命相结合，这着实令人兴奋。" 根据公司官网公布的研发目标，除了蒂巴因（thebaine）外，他们的产品还包括东罂粟碱（oripavine）和东莨菪碱（scopolamine），这些都是用于生产小分子药物的关键起始原料（KSM）或活性药物成分（API）。其产品管线则包括由东罂粟碱可制得可待因、氢可酮和纳洛酮等止痛和戒毒药物；由东莨菪碱可制得抗恶心和抗痉挛药物。 目前，Antheia 管线覆盖的治疗领域包括神经病学、呼吸系统、抗感染药物、肿瘤学、胃肠道、内分泌学和血液学。而在未来，随着重要的商业化突破已经达成，Antheia将在这两年向市场推出首批产品，利用合成生物学实现其改变医药行业供应问题的承诺。  *封面图片来源：123rf 如果您想对接文章中提到的项目，或您的项目想被动脉网报道，或者发布融资新闻，请与我们联系；也可加入动脉网行业社群，结交更多志同道合的好友。 近 期 推 荐 声明：动脉网所刊载内容之知识产权为动脉网及相关权利人专属所有或持有。未经许可，禁止进行转载、摘编、复制及建立镜像等任何使用。 动脉网，未来医疗服务平台

Company awarded government project agreement to onshore key pharmaceutical supply chains, alongside strategic investment from In-Q-Tel and Echo MENLO PARK, Calif., July 19, 2024 /PRNewswire / -- Antheia, the pharmaceutical ingredient manufacturer transforming essential medicine supply chains, today announced $17 million in new funding via a government project agreement through the Biopharmaceutical Manufacturing Preparedness Consortium (BioMaP-Consortium), alongside matching support from new strategic investors. The combined funding will support onshoring the production of critical pharmaceutical ingredients to the U.S. and accelerating the company's commercialization strategy. The funding includes a non-dilutive two-year project agreement up to $11 million through the BioMaP Consortium and additional investment from In-Q-Tel, Inc. (IQT), Echo Investment Capital (Echo), and several existing investors, including Viking Global Investors. "Biotechnology has a critical role to play in U.S. national and economic security," said Dr. Christina Smolke, Antheia CEO and co-founder. "With the support of both the public and private sectors, we can leverage this technology to bolster essential medicine production in the U.S., with an agile, scalable biomanufacturing approach that leapfrogs existing pharmaceutical manufacturing practices." The BioMaP-Consortium is a multiple-purpose acquisition vehicle supporting the Biomedical Advanced Research and Development Authority (BARDA) and is composed of pharmaceutical, medical, academic, and scientific organizations. This project has been funded in whole or in part with federal funds from the U.S. Department of Health and Human Services; Administration for Strategic Preparedness and Response (ASPR); Office of Industrial Base Manufacturing and Supply Chain (IBMSC), under OT number #75A50123D00003. The BioMaP-Consortium aims to meet the U.S. public health preparedness and response requirements by expanding the industrial and manufacturing base for medical countermeasures. As part of the BioMaP-Consortium award, Antheia will demonstrate the domestic production of three critical pharmaceutical ingredients at population scale using advanced biomanufacturing processes. In addition to the BioMaP-Consortium project agreement, Antheia brought in matching support from new strategic investors – including IQT and Echo – that represent the intersection of innovation, national security, and domestic manufacturing. IQT connects cutting edge innovation from the private sector to the U.S. government and its allies to advance national security in the 21st century. Echo is a multi-strategy investment firm that connects overlooked domestic resources and infrastructure with world-class founders, ideas, and capital to generate exceptional financial and social returns. "The U.S. is a leader in biomanufacturing, synthetic biology, and computational biology, but there is more we must do to scale these advanced technologies to solve global problems like essential medicine shortages," said Eugene Chiu, Senior Partner, IQT. "We are excited to support Antheia in advancing the U.S. bioeconomy and building resilient pharmaceutical supply chains." "Antheia's disruptive innovation is dramatically changing the outlook for security and resiliency of our biopharmaceutical supply chains," said Christian Kanady, Founding Partner & CEO, Echo. "We are proud to partner in advancing Antheia's groundbreaking technologies and importantly renewing the domestic bioeconomy in the process." Today's financing news comes on the heels of significant 2024 momentum, including the company's validated process for its first product , thebaine, and the opportunity to host U.S. Secretary of State, Antony J. Blinken at its labs for a discussion on the importance of a robust domestic bioeconomy. Antheia continues to deliver on its commercial strategy and plans to ship its first orders to customers later this year. About Antheia Antheia is the next-generation pharmaceutical ingredient producer transforming essential medicine supply chains to end drug shortages. Using its novel whole-cell engineering approach, Antheia's biomanufacturing platform enables the reconstruction of biosynthetic pathways of unprecedented complexity in yeast cells and the scaling of fermentation processes to commercial levels. This highly flexible approach enables on-demand, agile, and resilient biomanufacturing of critical pharmaceutical ingredients, replacing legacy approaches that cannot support the needs of modern healthcare. For more information, visit . MEDIA CONTACT: Mission North for Antheia [email protected] SOURCE Antheia

Olon to support Antheia’s continued scale up and commercialization of early productsMENLO PARK, Calif. and MILAN, Italy, March 13, 2024 (GLOBE NEWSWIRE) -- Antheia, the pharmaceutical ingredient manufacturer transforming essential medicine supply chains, and Olon Group, the global leader in developing and manufacturing active pharmaceutical ingredients (APIs) for CDMO (contract development and manufacturing organization) and generic markets, today announced an ongoing partnership to leverage Olon’s vast fermentation infrastructure to manufacture Antheia’s early products. Antheia and Olon established this partnership in 2022 to leverage Olon’s fermentation sites across Italy. Olon has since played a pivotal role as a CDMO for scaling Antheia’s biomanufacturing processes and producing its Biosynthetic KSMs (key starting materials) and APIs. Looking to 2024 and beyond, Antheia will continue to partner with Olon to unlock additional capacity to meet international demand for its first products, including thebaine. “The third-party partners we work with are a huge part of our success, so finding the right CDMO to help bring our first products to industrial scale efficiently and rapidly was a critical decision early in our commercialization journey,” said Zack McGahey, COO of Antheia. “Olon is a well-respected CDMO of high-quality pharmaceutical products and a trusted partner to us as we continue our work together to ship our first products later this year and ultimately, transform essential medicine supply chains.” Olon Biotech – a division of Olon Group - has more than 50 years of experience providing high-quality fermentation manufacturing services and is a globally licensed API manufacturer. With 5,000 cubic meters of fermentation capacity installed within its sites, Olon is one of the leading global CDMOs for biomanufacturing. Olon’s extensive global infrastructure and deep industry expertise were instrumental to Antheia’s recent commercial milestones for its first product, thebaine. “This successful partnership has yielded significant results and represents a promising future for pharma supply chains. Over the last five years, we have massively invested in our Biotech Centers, generating a significant increase in capacity and upgrading production processes for greater efficiency, and importantly, reducing the environmental impact of our production,” said Maurizio Sartorato, VP of Olon Biotech. Antheia and Olon will both be in attendance at DCAT Week in NYC from March 18-21. To meet with either team at the event, please see contact information below. Antheia Media Contact: Mission North for Antheiaantheia@missionnorth.com Antheia DCAT Contact: info@antheia.bio Olon Media Contact:Sabrina Spinasspina@olonspa.it