Gordian Biotechnology, Inc.

$60 Million in Venture Capital Raised to Date from World-Class Longevity, Biotech, and Technology InvestorsUnprecedented Approach Tests Hundreds of Gene Therapies Simultaneously in Individual Animals that are Highly Representative of Human Patients, Including Horses and MonkeysScreen Results Match Preclinical and Clinical Outcomes of Two Age-Related Indications with 80% Accuracy SAN FRANCISCO, April 26, 2024 /PRNewswire/ -- Gordian Biotechnology, an in vivo drug discovery and development company, today announced its platform that enables patient predictive, in vivo screening of hundreds of gene targets for FDA-recognized diseases of aging at a scale never before possible. The company has raised $60 million to date from investors including The Longevity Fund, Arctica Ventures, Athos Service GmbH, Gigafund, Founders Fund, Fifty Years, and former Novartis CEO Thomas Ebeling. Gordian Biotechnology Gene Therapy Testing Platform Gordian Biotechnology Scientists Process Tissue From a Mosaic Screening in the Company’s South San Francisco Headquarters Gordian Biotechnology Gene Therapy Testing Platform Traditional Drug Discovery Compared to Gordian Biotechnology Gordian Biotechnology In Vitro vs. In Vivo Gene Therapy Testing Gordian Biotechnology Single Gene Therapy Screen Results Gordian's Osteoarthritis (OA) program has screened hundreds of therapies in horses that acquired OA naturally and advanced dozens of therapies into human ex vivo validation studies. The results of these ex vivo studies matched screen predictions with 80% accuracy, and several hits progressed to additional testing and optimization. Gordian presented these findings at the Osteoarthritis Research Society International (OARSI) World Congress last week. In proof of concept experiments during initial development, Gordian introduced a pooled library of 50 gene therapies into a mouse model of metabolic-associated steatohepatitis (MASH). The therapies were evaluated using the company's proprietary in vivo screening platform, which successfully recapitulated 13 out of 16 clinical outcomes for targets where clinical data exists. Today, Gordian is completing in vivo screens of thousands of novel single and multi-target therapies across four indications in highly representative animal models across multiple species. "Gordian leverages recent advancements in single-cell sequencing and gene therapy to discover and predict what drugs will be successful in a way that would have been inconceivable just five years ago," said co-founder and CEO Francisco LePort. "Our ultimate goal is to help people wake up every day, more capable than the one before." The first and only platform of its kind Screening in vivo lets Gordian run the equivalent of hundreds of preclinical experiments in a matter of months and at a small fraction of the cost of traditional preclinical studies. Thus, enormous amounts of in vivo data are obtained at the beginning of the discovery process in animal models that would otherwise be impractical to use, allowing only the most efficacious therapeutics to move into development and clinical trials. The Gordian platform consists of three proprietary components working in concert: Patient Avatars™ are animal models with biology more representative of human patients than those typically used, such as horses for OA and monkeys for MASH. Because few animals are required for screening, Gordian can use large or advanced animal models that would otherwise be impractical for extensive preclinical studies. Often these animal models acquire the disease naturally and therefore have other conditions associated with biological aging, as a human would. Mosaic Screening™ is pooled in vivo screening that tests hundreds of therapies simultaneously in a single sick animal, the Patient Avatar. The diseased tissue becomes a "mosaic," where different cells receive different barcoded therapies. The therapies are introduced at a low dose, such that each perturbed cell is separated by diseased tissue unperturbed by any treatment, minimizing interactions between treatments. Each of these cells is sequenced, revealing the effect of each therapy in the full diseased in vivo context. Pythia™ is an analysis methodology that uses artificial intelligence to interpret single-cell data from hundreds of cellular experiments and measure the effect of each therapy in vivo. By analyzing this data alongside existing human pathology data, Gordian determines which therapies are most likely to succeed in preclinical development and clinical trials. "Our most severe unmet medical needs are the result of aging. This is due to the complexities of the aging body, often involving multiple comorbidities at once, making research and development especially challenging and expensive," said Martin Borch Jensen, Gordian co-founder and chief scientific officer. "Gordian is creating a future in which age-related ailments are treated and cured as effectively as infectious diseases today." Aging is the ultimate risk factor for humans, the most expensive, yet research is under-funded. "Age-related diseases are incredibly complex, and a living animal, ideally one that is aged and acquired the disease naturally, is the only experimental system that can capture this complexity," said Laura Deming, a partner at The Longevity Fund and Gordian investor. "Our ability to understand these diseases is bottlenecked by the rate we can run tests in these living systems. Scaling that rate by over 100 fold is really exciting and is a huge leap toward curing age-related disease." In addition to MASH and OA, Gordian's current focus indications include heart failure with preserved ejection fraction and pulmonary fibrosis. The platform is capable of discovering therapies for a long list of complex diseases. The company seeks to partner with pharmaceutical companies to develop drugs as well as move therapeutics into the clinic internally. LePort and Borch Jensen studied and worked in separate scientific fields in different parts of the world before meeting in early 2018 as a result of their shared interest in longevity entrepreneurship. They founded Gordian in October of that year. Follow Gordian on LinkedIn and X and visit for more information. Photos and video available at Media Contact [email protected] About Gordian Biotechnology Founded in 2018 and headquartered in San Francisco, Gordian is an in vivo drug discovery and development company whose mission is to cure age-related diseases. Named for solving intractable problems by changing the rules, the company has developed an innovative in vivo screening platform that tests thousands of gene therapies and predicts clinical outcomes with unprecedented accuracy and efficiency. The Gordian Platform comprises three proprietary components working in concert to drive predictive ability. Mosaic Screening is the Gordian method of pooled in vivo screening, Patient Avatars are animals most representative of humans, and Pythia is an analysis methodology that combines Gordian screening data with existing human data and uses machine learning to maximize predictive power. The company is funded by world-renowned investors including The Longevity Fund, Athos Service GmbH, Gigafund, Founders Fund, and former Novartis CEO Thomas Ebeling. Gordian: Creating Time. SOURCE Gordian Biotechnology

▎药明康德内容团队编辑如果被问到是否想要长生不老，所有人可能都会不假思索地说：“当然。”但不管是东方还是西方，或者寓言故事还是现实中，追求长生不老似乎总会以悲剧收场——《哈利波特》中追求长生不死的反派代表人物伏地魔最终惨死在了自己的索命咒下；《西游记》中，多少妖精们为了吃一口传说能长生不老的唐僧肉，非死即伤。在多数普通人的眼中，长寿领域的研究也带有“魔幻”色彩。甚至在有些时候，如果一家公司宣称开发出了能使人长生不老的技术，大家的态度往往总先是怀疑。对于生物医药产业界，长寿药物的研发同样令人爱恨交加。尽管长生不老是大多数人所追求的愿望，但要摘下该领域的圣杯，却显得有些无从下手。动物研究成果斐然，如何转化成为难题衰老研究领域的首个关键发现是在1939年，研究人员们发现限制小鼠和大鼠的热量摄入就能延长其寿命。值得注意的是，饮食限制不仅延长了动物的总寿命，还抑制了年龄相关疾病的发展。科学家们在那时就提出了一个不仅仅局限于总寿命长度（lifespan）的概念——健康寿命（healthspan），用来描述个体身体健康的年数和总寿命的比例。▲长寿研究的里程碑（图片来源：参考资料[3]）要说针对该领域的研究是何时步入正轨的，可能要追溯到1990年代初期。那时，生物学家Cynthia Kenyon通过改变一种透明的微小蠕虫的单个基因，使其寿命延长了一倍。对果蝇、蠕虫和小鼠的进一步研究验证了该基因产物于胰岛素和胰岛素样生长因子细胞内信号通路（ILS）的作用并不局限于蠕虫中，这为长寿领域找到了实际的研究方向，并催生出对一系列长寿物种（例如弓头鲸和鼹鼠）细胞中潜藏的长寿密码的探索。1995年，一项基因筛查发现表观遗传“沉默“因子是一种长寿基因。五年后，研究人员发现了可以调节酵母的复制寿命的一种保守蛋白——Sir2。在随后的研究中发现，小鼠和人类能够表达7种被称为sirtuins的Sir2相关蛋白，其中4种能作为表观遗传调节因子起作用。而sirtuins也被作为一种代谢调节剂来控制对热量限制的反应，预防与年龄相关的疾病从而延长健康寿命。2004年，雷帕霉素的靶标（TOR）蛋白（在哺乳动物中，该蛋白的基因被称为MTOR）被阐明了与饮食限制之间的关系，它能够作为主要枢纽整合来自生长因子、营养利用、能量状态以及各种压力的信号，介导寿命的延长。通过降低TOR通路中各种成分的活性，在模拟饮食限制实验中的果蝇寿命得到了延长。令人感到震惊的是，携带TOR和胰岛素信号通路双基因突变的蠕虫其寿命增加了近5倍！如今，TOR和ILS已成为两种关键、平行且具有相互作用的长寿通路。图片来源：123RF而近代抗衰老研究的关键则来自于日本科学家山中伸弥博士的团队在2006年和2007年间发现的4种具有细胞重编程能力的蛋白质，这些蛋白质被称为“山中因子”。利用山中因子衍生出来的细胞重编程技术，科学家们能够使细胞“返老还童”。近十年，通过细胞重编程技术我们已能做到很多事情。许多团队都开发出了各自的方法来实现对重编程技术的精细调控，使其能够逆转细胞的年龄，但不会让它逆转得太过头而使细胞失去控制。2016年，索尔克生物研究所（Salk Institute）的Izpisúa Belmonte教授团队利用基因改造在小鼠中实现了对重编程的精准开启或关闭，使早衰小鼠在恢复年轻活力的同时不会长出肿瘤。2020年，哈佛大学衰老生物学研究中心的David Sinclair教授团队通过使用4种山中因子中的3种，使成年小鼠中已经成熟的视网膜神经细胞重新获得了在初生小鼠中才具有的修复损伤和再生能力。2022年，英国科学家则能使来自于中年人的皮肤细胞的生物钟倒回约30年，且不会使皮肤细胞因过度“逆龄”失去其应有的功能。▲利用荧光染料标识轴突，可以看到在接受了3种山中因子的小鼠中，RGC受损后可以重新长出轴突（图片来源：参考资料[6]；Credit：Yuancheng Lu）此外，还有许多研究表明，改善昼夜节律、线粒体氧化应激、促炎-抗炎平衡、蛋白质平衡以及消除衰老细胞等多种方式均能影响衰老，从而延长寿命。总结来说，对动物和人类细胞/组织的研究一再证明了逆转或延缓衰老是可行的。但令人感到遗憾的是，尽管早已有公司着手将这些成果进行转化，到目前为止，还没有在人类中得到确切证实的有效抗衰老/长寿疗法。例如Geron公司在成立当年的新闻稿中声称“绝对掌握了控制和逆转每个组织和系统衰老的技术”，其在30多年后的今天依然距离当初的承诺相去甚远。该公司目前唯一转化的只有一种治疗常见血液癌症的药物，在今年1月的结果显示其在一定程度上具有疗效。 那究竟是什么导致了衰老领域的成果转化进展如此缓慢呢？概念转变，聚焦于衰老相关疾病受认可长寿研究成果难以临床转化的其中一个原因是，严格来说，衰老并不是“一种”疾病。因此，即便开发出抗衰老的药物，也没有相应的“适应症”可供药物上市。这在一开始确实成为了整个领域都感觉棘手的难题。然而就在近几年，这种情况发生了转变。随着衰老研究的不断深入，研究人员利用可以选择性消除衰老细胞的转基因小鼠模型证实了衰老细胞是大量与年龄相关的表型和病理特征的驱动因素，包括阿尔茨海默病、帕金森病、动脉粥样硬化、心血管功能障碍、肿瘤、非酒精性脂肪性肝病、肺纤维化、骨关节炎和骨质疏松症等等。一些抗衰老生物技术公司于是调转了思路，不再执着于使单个人类个体获得超长寿命这个最初的目标，而是把目标放在这些更具体、更有针对性的疾病上。如此一来，抗衰老药物没有“适应症”供上市的难题就解决了。图片来源：123RF这种想法与一些务实的投资者不谋而合，他们也认为，抗衰老的研究有潜力解决一系列与年龄相关的疾病。全球投资平台Mubadala Capital的合伙人Ayman AlAbdallah先生就表示，他们的公司只关注那些针对特定疾病制定“可靠”计划的公司。去年，Mubadala公司领投了一项4100万美元的A轮融资，获得投资的这家名为Juvena Therapeutics的生物技术公司试图使用干细胞分泌的蛋白质来使肌肉再生，其首个试验将在一种罕见的遗传疾病——强直性肌营养不良症中开展。基于人类血液样本寻找衰老相关驱动因子并进行疗法研发的长寿生物技术公司BioAge Labs的联合创始人兼首席执行官Kristen Fortney博士表示，相比于说是抗衰老药物，想想这类药物可以应用于哪些治疗领域或许会更实际。利用这种思路，该公司已成功获得了1.27亿美元的投资，用于开发治疗肌肉、大脑和免疫相关的衰老疾病药物，并在2021年和安进达成年龄相关性疾病疗法的研发合作。通过针对衰老的三大驱动因素——细胞内关键分子（DNA、RNA、蛋白质等）改变、细胞功能障碍、组织变性来为特定疾病开发干预措施的抗衰老公司Cambrian Biopharma在2021年获得了一亿美元的C轮融资；拟开发减缓或治疗神经退行性疾病的潜在“first-in-class”小分子疗法的抗衰老新锐Muna Therapeutics也于2021年获得了7300万美元的A轮融资。技术突破多点开花，抗衰老研究领域获得进一步繁荣如果说长寿药物在适应症针对性上发生的转变是为该领域的研发打上的一剂强心针，那么近几年抗衰老/长寿领域在技术上的突破则是使其变得繁荣的重要基础。首先，上文提到的细胞重编程技术无疑是具有巨大潜力且被众人看好的。2022年年初，利用细胞重编程技术的生物技术新锐——Altos Labs获得了30亿美元的投资。根据行业媒体STAT的报道，这在当时是生物技术领域有史以来规模最大的一笔投资。该公司招揽了四位诺奖得主和全球多位相关领域的顶尖科学家共同加入，其中山中伸弥教授是该公司科学顾问委员会主席，美国国家癌症研究所的前所长Richard Klausner博士则担任了该公司的首席科学官。有这么多顶尖人物的支持，该技术的前景可见一斑。不过，Richard Klausner博士在STAT的采访中声明，Altos不是一家专注延长寿命的公司，而是一家逆转疾病的公司。▲Richard Klausner博士在2020药明康德全球论坛分享细胞疗法开发的洞见除了Altos Labs，利用该技术获得了投资人亲睐的抗衰老相关生物技术公司还包括Retro Biosciences（1.8亿美元）以及New Limit（1.05亿美元），两家公司目前尚未公布临床管线。在细胞重编程技术以外，该领域涌现出的多家中重量级生物技术公司所基于的抗衰老技术还包括利用小分子或免疫系统清除衰老细胞、自噬、恢复退化的组织等等。其中两家抗衰老公司/机构获得了数十亿美元的资金支持。一家名为Calico Labs的公司利用理解和靶向衰老的根本机制，从Alphabet和艾伯维（AbbVie）获得了超过25亿美元的投资。另一家是沙特的非营利组织Hevolution Foundation。该组织致力于使用广泛但注重基础的衰老科学来开发新药，每年将获得高达10亿美元的资金。还有一些公司的角度比较与众不同，例如专注于制造更好的年龄相关性疾病（例如非酒精性脂肪肝）的动物模型，并在这些动物中筛选基因疗法的抗衰老基因治疗初创公司Gordian Biotechnology，以及致力于控制卵巢衰老的公司Oviva Therapeutics。Oviva的首席执行官兼联合创始人Daisy Robinton希望通过该公司的产品使女性能够更好地掌控生育以及进入更年期的时间，从而极大地改变女性安排生活的方式。▲长寿领域的中重量级公司列表（图片来源：参考资料[1]，药明康德团队编译）目前，这些抗衰老/长寿初创公司正在源源不断地产出相关的研究数据，且其中不乏十分有潜力的候选疗法。例如BioAge公司在去年公布了其进展最快的肌肉减少症项目在1b期临床试验中治疗老年患者的积极结果，这些患者的肌肉产生萎缩。相比于安慰剂，患者在各项指标上产生了具有统计学意义的改善。Unity Biotechnology公司主要的管线聚焦于与年龄相关的眼科疾病。该公司也在近期宣布了其用于治疗糖尿病黄斑水肿的候选疗法达到了2期试验的关键安全性和有效性终点。BioAge公司与Unity公司的早期结果是一个开始，更多抗衰老公司的数据也将很快到来。抗衰老领域Cambrian Biopharma公司的创办者James Peyer博士说道，“在接下来的几年里，这些概念将会有越来越多的证据出现。如果我们能够兑现这一生物学的承诺，我认为这个领域将会进入一种非常非常好的生态。” 相比于长生不老，我们更需要健康的晚年长寿/抗衰老领域从数十年前的不被看好，到近几年有了长足的发展，靠的是概念上的正确转变以及技术上的突破性进展。总体来说，整个行业目前都在往更好的方向发展。在发展的同时，行业内的所有参与者都免不了回答这样一个问题——我们要的真的是长生不老吗？可能在该领域研究的一开始，研究人员就告诉过我们答案了——健康寿命。抗衰老领域的科学家、生物技术公司高管和投资人在近几年似乎达成了这样一个共识——长生不老可能并非人们最根本的需求，在延长寿命的基础上拥有更长占比的健康晚年生活可能才是人们更想要的。我们能够明显看到的是，多家抗衰老领域的公司不约而同地把“延长人类健康寿命”作为首要目标写在了其官网的首页上。Mubadala Capital投资平台合伙人Ayman AlAbdallah先生表示，虽然人类的总寿命增加了，但健康寿命增加得很少。他希望他们投资的公司能够通过探索衰老的根本原因来延长人类的健康寿命，尽管这可能还需要很长一段时间才能达成。图片来源：123RF一家初创公司的顶尖科学家表示：“我希望你的祖母在85岁时还能去徒步旅行。”加州大学伯克利分校的肌肉专家Bill Evans博士则表示：“人们直到死亡来临前都能独立生活，我想这才是目标。”未来，人人都能在七八十岁时依然健步如飞的时代或许不再是梦。让我们朝着“更长的健康寿命”这一目标共同努力吧！大家都在看药明康德为全球生物医药行业提供一体化、端到端的新药研发和生产服务，服务范围涵盖化学药研发和生产、生物学研究、临床前测试和临床试验研发、细胞及基因疗法研发、测试和生产等领域。如您有相关业务需求，欢迎点击下方图片填写具体信息。▲如您有任何业务需求，请长按扫描上方二维码，或点击文末“阅读原文/Read more”，即可访问业务对接平台，填写业务需求信息▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料：[1] No more ‘playing God’: How the longevity field is trying to recast its work as serious science. Retrieved January 31, 2023, from https://www.statnews.com/2023/01/30/scientists-ceos-founders-trying-to-make-longevity-mainstream/[2] The race for longevity: How scientists — and industry — are seeking to extend healthy lives. Retrieved January 31, 2023, from https://reports.statnews.com/products/race-for-longevity?variant=39820067405927[3] Campisi J, Kapahi P, Lithgow GJ, Melov S, Newman JC, Verdin E. From discoveries in ageing research to therapeutics for healthy ageing. Nature. 2019 Jul;571(7764):183-192. doi: 10.1038/s41586-019-1365-2. Epub 2019 Jul 10. PMID: 31292558; PMCID: PMC7205183.[4] UNITY BIOTECHNOLOGY ANNOUNCES POSITIVE 24-WEEK DATA FROM PHASE 2 BEHOLD STUDY OF UBX1325 IN PATIENTS WITH DIABETIC MACULAR EDEMA. Retrieved January 31, 2023, from https://ir.unitybiotechnology.com/news-releases/news-release-details/unity-biotechnology-announces-positive-24-week-data-phase-2[5] BioAge Announces Positive Topline Results for BGE-105 in Phase 1b Clinical Trial Evaluating Muscle Atrophy in Older Volunteers at Bed Rest. Retrieved January 31, 2023, from https://www.businesswire.com/news/home/20221205005201/en[6] Vision Revision Retrieved Dec. 3, 2020, from https://hms.harvard.edu/news/vision-revision免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

Using the latest technologies --i ncluding both single-nuclear sequencing of mice and human liver tissue and advanced 3D glass imaging of mice to characterize key scar-producing liver cells -- researchers have uncovered novel candidate drug targets for non-alcoholic fatty liver disease (NAFLD). Using the latest technologies -- including both single-nuclear sequencing of mice and human liver tissue and advanced 3D glass imaging of mice to characterize key scar-producing liver cells -- researchers have uncovered novel candidate drug targets for non-alcoholic fatty liver disease (NAFLD). The research was led by investigators at the Icahn School of Medicine at Mount Sinai. Utilizing these innovative methods, the investigators discovered a network of cell-to-cell communication driving scarring as liver disease advances. The findings, published online on January 4 in Science Translational Medicine, could lead to new treatments. Characterized by fat in the liver and often associated with type 2 diabetes, hypertension, and elevated blood lipids, NAFLD is a worldwide threat. In the United States, 30 to 40 percent of adults are estimated to be affected, with about 20 percent of these patients having a more advanced stage called non-alcoholic steatohepatitis, or NASH, which is marked by liver inflammation and may progress to advanced scarring (cirrhosis) and liver failure. NASH is also the fastest-rising cause of liver cancer worldwide. Since advanced stages of NASH are caused by the accumulation of fibrosis or scarring, attempts to block fibrosis are at the center of efforts to treat NASH, yet no drugs are currently approved for this purpose, say the investigators. As part of the experiments, the researchers performed single-nuclear sequencing in parallel studies of both mouse models of NASH and human liver tissue from nine subjects with NASH and two controls. They identified a shared number of 68 pairs of potential drug targets across the two species. Furthermore, the investigators pursued one of these pairs by testing an existing cancer drug in mice as a proof of concept. "We aimed to understand the basis of this fibrotic scarring and identify drug targets that could lead to new treatments for advanced NASH by studying hepatic stellate cells, which are the key scar-producing cells in the liver," said senior study author Scott L. Friedman, MD, Irene and Dr. Arthur M. Fishberg Professor of Medicine, Dean for Therapeutic Discovery, and Chief of Liver Diseases at Icahn Mount Sinai. "In combining this new glass liver imaging approach -- an advanced tissue clearing method that enables deep insight -- along with gene expression analysis in individual stellate cells, we have unveiled an entirely new understanding of how these cells generate scarring as NASH advances to late stages." The researchers discovered that in advanced disease, stellate cells develop a dense network, or meshwork, of interactions among themselves that facilitate these 68 unique interaction pairs not previously identified in this disease. "We confirmed the importance of one such pair of proteins, NTF3-NTRK3, using a molecule already developed to block NTRK3 in human cancers and repurposed it to establish its potential as a new drug to fight NASH fibrosis," said first author Shuang (Sammi) Wang, PhD, an instructor in the Division of Liver Diseases. "This new understanding of fibrosis development suggests that advanced fibrosis may have a unique repertoire of signals that accelerate scarring, which represent a previously unrecognized set of drug targets." The researchers hypothesize that the circuitry of how cells communicate with each other evolves as the disease progresses, so some drugs may be more effective earlier and others at more advanced stages. And the same drug may not work for all stages of disease. The investigators are currently working with Icahn Mount Sinai chemists to further optimize NTRK3 inhibitors for the treatment of liver fibrosis. Next, the investigators plan to functionally screen all candidate interactors in a cell-culture system, followed by testing in preclinical models of liver disease, as they have done for NTRK3. In addition, they hope to extend their efforts to determine if similar interactions among fibrogenic cells underlie fibrosis of other tissues including heart, lung, and kidneys. The paper is titled "An autocrine signaling circuit in hepatic stellate cells underlies advanced fibrosis in non-alcoholic steatohepatitis." Additional co-authors are: Kenneth Li (Icahn Mount Sinai); Eliana Pickholz Li (Icahn Mount Sinai); Ross Dobie (University of Edinburgh, UK); Kylie P. Matchett (University of Edinburgh, UK); Neil C. Henderson (University of Edinburgh, UK); Chris Carrico (Gordian Biotechnology, CA); Ian Driver (Gordian Biotechnology, CA); Martin Borch Jensen (Gordian Biotechnology, CA); Li Chen PharmaNest, Inc., NJ); Mathieu Petitjean (PharmaNest, Inc.,NJ); Dipankar Bhattacharya (Icahn Mount Sinai); Maria I. Fiel (Icahn Mount Sinai); Xiao Liu (University of California); Tatiana Kisseleva (University of California); Uri Alon (Weizmann Institute of Science, Israel); Miri Adler (Yale University School of Medicine, CT); Ruslan Medzhitov (Yale University School of Medicine, CT). The work was supported, in part, by funds from the National Institutes of Health grant numbers R01DK56621, R01DK128289, TR004419, P30CA196521, R01DK101737, R01DK099205, R01DK111866, R01AA028550, P50AA011999, P30 DK120515, and U01AA029019.