Wisconsin Alumni Research Foundation

Ginkgo Bioworks has been on a cell-and-gene tool collecting spree this year, and its latest acquisition is Modulus Therapeutics’ library of switch receptors and CARs.The suite of cell therapy components includes NK- and T-cell specific CAR and switch receptors, which are intended to improve the safety and efficacy of cell therapies by allowing for more precise control over activation and targeting. The custom CARs are designed to enhance a cell therapy’s proliferation and cytotoxicity to generate a more robust and durable response against target cells.The switch receptors use specific ligands to enable CAR-T or CAR-NK cell therapies to respond to environmental signals, including inhibitory ones.Modulus’ tech will be integrated into Ginkgo's cell therapy service platform, which allows partners to sample CAR domains with various functional roles and structural positions, sourced from diverse immune cell types. One such partner is Wisconsin Alumni Research Foundation, who linked up with Ginkgo last year to discover next-generation GD2 CAR-T cell therapies with improved persistence, proliferation, fitness to treat solid tumours.Tuesday’s deal with Modulus follows a series of collaborations to bulk out the synthetic biology company’s genetic medicines offerings. Earlier this year, Ginkgo gained several key technologies, including ProteoNic’s vector production platform; Form Bio’s in silico suite for construct characterisation, simulation, and design optimization; and Patch Biosciences’s AI toolkit for DNA sequence design for more effective, specific, and durable genetic medicines.

Collaboration with University of Wisconsin Professors Krishanu Saha (PI) and Christian Captini (co-PI) to discover novel and improved GD2 CAR designs to treat solid tumors and validate them in vivo MADISON, Wis. and BOSTON, April 13, 2023 /PRNewswire/ -- The Wisconsin Alumni Research Foundation (WARF), which has a mission of supporting research at the University of Wisconsin-Madison, and Ginkgo Bioworks (NYSE: DNA), which is building the leading platform for cell programming and biosecurity, today announced a partnership to leverage Ginkgo's proprietary high-throughput combinatorial CAR discovery and screening platform with the aim of discovering next generation GD2 CAR T-cell therapies with improved persistence, proliferation, fitness, and other functional properties to improve efficacy for the treatment of solid tumors. Through this partnership, Ginkgo will collaborate with the University of Wisconsin-Madison researchers Professor Krishanu Saha, Ph.D., as principal investigator (PI) and Dr. Christian Capitini, M.D. as co-PI. Professor Saha's lab focuses on developing the next-generation cell engineering techniques to advance human therapeutics, and Dr. Capitini is a pediatric oncologist who has extensive clinical experience with CAR T-cell therapies, including serving as a site PI for the clinical trial that led to the first FDA approval of a CAR T-cell therapy. The two have collaborated on the development of a GD2 CAR T-cell therapeutic candidate for the treatment of neuroblastoma, a type of cancer generally affecting young children, using a non-viral, site-specific integration method developed by Professor Saha and published in the Journal for the Immunotherapy of Cancer: Production and characterization of virus-free, CRISPR-CAR T cells capable of inducing solid tumor regression. Under this collaboration, Ginkgo will use its pooled CAR screening platform to design and characterize novel intracellular signaling domains that prevent the exhaustion of T-cells in the GD2 solid tumor context. Any novel designs will be validated in high throughput in vitro screens and in in vivo murine models. In addition, Ginkgo and WARF plan to collaborate on the development of a pooled in vivo screening platform to advance novel CAR discovery further. "Ginkgo's high throughput screening method has proven successful in enabling massively parallel testing of CAR designs, and has already led to the discovery of new intracellular domains (ICD) combinations," said Krishanu Saha, a professor at the University of Wisconsin-Madison. "By partnering with Ginkgo, we aim to unlock the potential to transform patient outcomes and reimagine the future of solid tumor cancer treatment." CAR T-cell therapies show tremendous promise for the treatment of cancer. However, their use has thus far largely been limited to targeting blood cancers because they have failed to show consistent efficacy in treating solid tumors, which represent approximately 90% of adult human cancers. Part of the challenge when applying CAR T-cell therapies to solid tumors is T-cell exhaustion, a state of dysfunction arising from excessive antigen stimulation in the immunosuppressive environment of a solid tumor. WARF and Ginkgo hope to work towards solving this challenge by utilizing Ginkgo's high-throughput combinatorial CAR discovery platform. As a platform technology company, Ginkgo can leverage its full stack of mammalian cell engineering expertise and capabilities to enable the high throughput screening of CAR T-cells to help discover and optimize future next-generation therapeutic candidates for its partners. "WARF is delighted to see this important collaboration," says Erik Iverson, WARF CEO. "We know these alliances between our university researchers and leading biotech industry partners have the potential to result in benefits that positively impact human health." "This collaboration represents a fantastic opportunity to demonstrate the potential value of pooled CAR screening approaches directly in the context of devastating diseases like early childhood cancers," said Narendra Maheshri, Head of Mammalian Engineering at Ginkgo. "It's especially exciting to work with pioneers like Professors Saha and Capitini, who have pushed R&D boundaries in the laboratory and whose approach is thoroughly grounded in the translation of their findings for clinical impact." About Ginkgo Bioworks Ginkgo Bioworks is the leading horizontal platform for cell programming, providing flexible, end-to-end services that solve challenges for organizations across diverse markets, from food and agriculture to pharmaceuticals to industrial and specialty chemicals. Ginkgo's biosecurity and public health unit, Concentric by Ginkgo, is building global infrastructure for biosecurity to empower governments, communities, and public health leaders to prevent, detect and respond to a wide variety of biological threats. For more information, visit ginkgobioworks.com and concentricbyginkgo.com, read our blog, or follow us on social media channels such as Twitter (@Ginkgo and @ConcentricByGBW), Instagram (@GinkgoBioworks and @ConcentricByGinkgo), or LinkedIn. About WARF The Wisconsin Alumni Research Foundation (WARF) helps steward the cycle of research, discovery, commercialization and investment for the University of Wisconsin-Madison and provides annual support to the university to advance research and innovation. Founded in 1925 as an independent, nonprofit foundation, WARF manages more than 2,000 patents and an investment portfolio as it funds university research, obtains patents for campus discoveries and licenses inventions to industry. For more information, visit warf.org and view WARF's Cycle of Innovation. Forward-Looking Statements of Ginkgo Bioworks This press release contains certain forward-looking statements within the meaning of the federal securities laws, including statements regarding the capabilities and potential success of the partnership and Ginkgo's cell programming platform. These forward-looking statements generally are identified by the words "believe," "can," "project," "potential," "expect," "anticipate," "estimate," "intend," "strategy," "future," "opportunity," "plan," "may," "should," "will," "would," "will be," "will continue," "will likely result," and similar expressions. Forward-looking statements are predictions, projections and other statements about future events that are based on current expectations and assumptions and, as a result, are subject to risks and uncertainties. Many factors could cause actual future events to differ materially from the forward-looking statements in this press release, including but not limited to: (i) volatility in the price of Ginkgo's securities due to a variety of factors, including changes in the competitive and highly regulated industries in which Ginkgo operates and plans to operate, variations in performance across competitors, and changes in laws and regulations affecting Ginkgo's business, (ii) the ability to implement business plans, forecasts, and other expectations, and to identify and realize additional business opportunities, (iii) the risk of downturns in demand for products using synthetic biology, (iv) the unpredictability of the duration of the COVID-19 pandemic and the demand for COVID-19 testing and the commercial viability of our COVID-19 testing business, (v) changes to the biosecurity industry, including due to advancements in technology, emerging competition and evolution in industry demands, standards and regulations, (vi) our ability to realize the expected benefits of merger and acquisition transactions, (vii) the outcome of any legal proceedings against Ginkgo, including as a result of recent acquisitions, (viii) our ability to realize the expected benefits from and the success of our Foundry platform programs, (ix) our ability to successfully develop engineered cells, bioprocesses, data packages or other deliverables, and (x) the product development or commercialization success of our customers. The foregoing list of factors is not exhaustive. You should carefully consider the foregoing factors and the other risks and uncertainties described in the "Risk Factors" section of Ginkgo's annual report on Form 10-K filed with the U.S. Securities and Exchange Commission (the "SEC") on March 13, 2023 and other documents filed by Ginkgo from time to time with the SEC. These filings identify and address other important risks and uncertainties that could cause actual events and results to differ materially from those contained in the forward-looking statements. Forward-looking statements speak only as of the date they are made. Readers are cautioned not to put undue reliance on forward-looking statements, and Ginkgo assumes no obligation and does not intend to update or revise these forward-looking statements, whether as a result of new information, future events, or otherwise. Ginkgo does not give any assurance that it will achieve its expectations. WARF CONTACT: [email protected] GINKGO BIOWORKS INVESTOR CONTACT: [email protected] GINKGO BIOWORKS MEDIA CONTACT: [email protected] SOURCE Ginkgo Bioworks

多肽（peptide）由氨基酸经肽键连接而成的一类化合物，其在连接方式上与蛋白质相同，通常将含有氨基酸数量100个以下的氨基酸序列称为多肽。多肽药物作为一种新兴药物，目前全球已获批上市的品种远少于小分子化药，但已日益成为全球新药研发的热点之一，如辉瑞、默克、罗氏、礼来、诺华、赛诺菲、拜耳等大型跨国制药企业，纷纷通过收购或并购等形式加大对多肽药物的研发投入。根据QYResearch统计：全球多肽药物市场规模在2010年约为152亿美元，到2018年已达到285亿美元，复合年均增长率为8.17%。据估计，多肽药物市场规模的增速约为全球药物市场规模整体增速的2倍，预计未来多肽药物市场将以7.9%的年均复合增长率增长，在2027年市场规模达到495亿美元水平。在全球市场区域分布方面，据Reseach Nester统计，美国是多肽药物最主要的市场，占比74%，其次是欧洲占比15%。预计亚洲地区未来将是多肽药物市场增长最快的地区，其庞大的患者群体、不断增长的临床需求以及对创新治疗的关注将推动亚太地区多肽治疗市场的增长。目前，全球多肽药物市场较为火热的疾病领域包括罕见病、肿瘤和糖尿病，其次为消化道、骨科、免疫和心脑血管类疾病。而一家致力于研究开发眼科疾病多肽疗法的美国企业：Stuart Therapeutics，在成立第三年就斩获了1100万美元的A轮融资。这家专注眼科单一赛道的多肽药企，到底是哪里吸引了投资人？开发修复性多肽序列PolyCol，针对干眼症、青光眼、干性AMD2021年3月，Stuart Therapeutics宣布完成1100万美元的A轮融资，本次融资由专注于眼科的生命科学风险投资机构：InFocus Capital Partners领投，Wisconsin Alumni Research Foundation (WARF), MiMo Capital和BioBrit跟投。此次融资的收益是用于Stuart Therapeutics的眼科治疗候选药物ST-100的II期临床试验。该项临床试验于2021年3月宣布通过FDA的审批，同年8月患者入组，并于2022年3月宣布临床试验成功。ST-100是Stuart Therapeutics目前进度最快的管线，现已实现在24小时或更短时间内完全愈合受损的角膜组织。其核心成分来自PolyColTM合成多肽平台，该平台开发出的一系列PolyCol合成多肽序列，专门设计用于修复受损的细胞外基质（ECM）螺旋胶原结构。PolyCol的结构是氨基酸的分数单链，是正常螺旋胶原蛋白中发现的序列的模仿物。它专门设计用于结合或插层到关键损伤区域，恢复细胞信号传导和胶原蛋白在健康组织中发挥的结构作用。它工作迅速，并导致组织健康的快速恢复和炎症的减少。基于该项技术现已开发出3条多肽药物管线，分别针对干眼症、青光眼和干性黄斑病变(干性AMD)。■ 干眼症干眼症（DED）是一种眼表多因素疾病。它可能是由简单地暴露于元素引起的，也可能与导致泪膜缺陷的各种生理变化有关，这通常是暂时的，但在某些情况下，损伤会变成慢性的。通常，身体以炎症细胞因子和基质金属蛋白酶（MMPs）作出反应，它们消化胶原蛋白分子的重要部分。当泪膜被破坏时，角膜表面的上皮细胞暴露并开始细胞凋亡。随着疾病的进展，角膜（包括角膜神经）的进一步损伤发生，对泪反射产生负面影响并加剧损伤。目前的治疗药物中，非处方泪膜补充剂（人工泪液）是患者的典型首选。它们暂时取代眼泪作为角膜上的表面润滑剂，并提供短暂的缓解，并且通常需要经常重新涂抹。处方类护理标准是抗炎药，但这些药物作用缓慢，仅对不到30%的患者群体有帮助。从患者和医生的角度来看，所有解决方案都有很多不足之处，存在显着未满足的需求。Stuart Therapeutics正在利用PolyCol的快速组织修复能力来直接解决导致炎症的治病组织损伤。ST-100候选药在临床实验中表明，其既可以缓解疾病相关症状，同时能够恢复神经功能，从而愈合受损角膜、结膜组织，并改善泪腺的功能。患者有望在24至48小时内缓解，而不再是现有解决方案的数周时间。■ 青光眼青光眼是一种视神经病变，其特征在于视神经的进行性变性，最终导致失明。它影响着全球大约7600万人，是世界上视力丧失的主要原因之一。其原因尚不完全清楚，目前已知能量变化、机械损伤和眼内压升高（IOP）等，可能会损害视神经及其轴突。青光眼主要是一种作用缓慢的疾病，但损伤是不可逆的，因此正确的诊断和干预至关重要。降低眼压通常需要同时使用多款药物，伴随有一定副作用，且就目前的临床研究表面，即使眼压正常，青光眼仍然可以进展。同时，患者有时需要在不同的时间表上服用多达四种不同的滴剂，依从性是一个主要问题。目前尚无已批准的治疗方法可以保护视神经免受多种作用的组合造成的损害。对于这种情况，PolyColTM平台设计出PolyCol变体，其作用是治愈对红层和下层后区域胶原蛋白的生物物理损伤，这些区域是视神经轴突离开眼睛时支撑组织的一部分，进而恢复正常的胶原细胞信号传到功能。这种修复作用是保护神经轴突，防止视觉功能丧失。该管线现已进入IND申报阶段。■ 干性AMD年龄相关性干性黄斑变性（干性AMD）是一种视网膜缓慢恶化的疾病，最终可能导致失明。这种疾病的确切病因尚不完全清楚，但干性AMD导致眼底组织的组织恶化，包括布鲁赫膜、视网膜色素上皮细胞和光感受器等，这类恶化将导致中央视野盲点。截至目前，没有批准的干性AMD处方疗法，通常采用维生素治疗，并观察进展迹象。迄今为止，针对晚期干性AMD尚未出现能够逆转该疾病造成损害的批准疗法，对一种可以改善黄斑结构和细胞环境并逆转损伤的治疗方法，存在显着未满足的需求。Stuart Therapeutics的PolyCol变体在目前的动物活体实验中表面，可以治愈视网膜中Bruch膜的损伤，为恢复视网膜色素上皮单层提供健康的底物，并恢复Bruch膜中的正常细胞信号传导功能。眼科、多肽、FDA审批数十年经验，不惧冷门赛道深耕专注于眼科多肽药物这一较为冷门的赛道，Stuart Therapeutics的信心与实力来自于其在眼科、多肽药物、FDA审批等方面拥有数十年经验的核心团队。Stuart Therapeutics的董事长兼首席医疗管兼产品开发主管Robert O. Baratta博士，在美国拥有40余年眼科医生经历，他曾在佛罗里达眼科学会、美国眼科学会和范德比尔特大学眼科研究所担任领导和顾问职位。Baratta博士在哥伦比亚大学内科和外科医学院获得医学博士学位。 董事长兼首席医疗管：Robert O. Baratta博士首席科学官David Calkins博士，是致盲性眼病、神经保护、视网膜突触组织、再生医学中视力丧失的神经生物学基础等领域的权威专家。Calkins教授同时也是范德比尔特眼科研究所的副主席兼研究主任，以及范德比尔特大学医学院的Denis M. O'Day眼科和视觉科学教授。他在密歇根大学荣誉学院获得了纯数学理学学士学位，并在宾夕法尼亚大学医学院获得了神经科学博士学位。 首席科学官David Calkins博士      研发执行副总裁Brian J. Del Buono博士在药品和生物制剂的FDA监管方面拥有近35年的跨国研发和业务开发经验。Brian拥有Juniata学院的微生物学学士学位（化学辅修）和宾夕法尼亚州立大学的微生物学/生物化学硕士和博士学位，并且是波士顿大学医学院的博士后研究员和教职员工。他的学术和企业研究重点是细胞结构和功能，特别是细胞表面和细胞外基质（ECM）之间的相互作用。研发执行副总裁Brian J. Del Buono博士除此以外，Stuart Therapeutics还获得来自麻省理工学院、哈佛大学、杜克大学、华盛顿大学医院、马萨诸塞州总医院等高校与医院在蛋白质结构、多肽合成、青光眼、白内障、黄斑病变等领域的科研支持。缺乏多肽人才的国内市场，单一赛道持续深耕是否成为出路？上个月，FDA已经批准了ST-100的III期临床试验申请，Stuart Therapeutics计划将在2023年第一季度进行其III期临床试验。未来，在继续推进现有管线的基础上，Stuart Therapeutics将继续探索眼部慢性病的创新型解决方案。身处巨大发展潜力的亚洲多肽市场，国内也有像中晟全肽、圣诺生物、智肽生物等多肽类药物开发企业，复星医药、恒瑞医药、普莱医药、先为达生物等药业也纷纷布局多肽赛道。但针对单一领域适应症进行深耕的相关企业，并不多见。在国内拥有多肽研究经验缺乏的当下，结合现有适应症临床研究基础进行多肽药物的“开垦研究”，是否是新的可行性思路？想要联系动脉网报道的企业，请点击文末左下方“阅读原文”填写表单，我们的工作人员将征求企业意见后，尽快为您服务。左右滑动查看更多近期推荐声明：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