Drug discovery isn’t only about finding new targets. There’s still plenty of opportunity to find better ways to hit targets that are already drugged, according to Tom Miller, CEO of startup Iambic Therapeutics. Understanding how a molecule interacts with a known disease target enables drug hunters to design molecules that could be superior alternatives for patients..

药物发现不仅仅是寻找新的目标。初创公司Iambic Therapeutics首席执行官汤姆·米勒（Tom Miller）表示，仍然有很多机会找到更好的方法来达到已经吸毒的目标。了解一个分子如何与已知的疾病目标相互作用，使药物猎人能够设计出可能成为患者优越替代品的分子。。

Miller notes that a molecule’s ability to bind to a target protein while leaving related proteins unaffected improves its safety. It’s also important to understand how the distribution of a molecule across tissues in the body affect efficacy. Iambic’s drug discovery research employs artificial intelligence to make predictions about those properties and others.

Miller指出，分子与靶蛋白结合的能力，同时使相关蛋白不受影响，提高了其安全性。了解分子在体内组织中的分布如何影响疗效也很重要。Iambic的药物发现研究采用人工智能对这些特性和其他特性进行预测。

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“With a platform like this, we can not only optimize the molecule, we can [also] optimize the profile,” Miller said of Iambic’s technology.

米勒说：“有了这样的平台，我们不仅可以优化分子，还可以[优化]配置文件。”。

In the span of two years, Iambic has developed four AI-discovered molecules, the most advanced of them now on the cusp of Phase 1 testing. To support those programs and develop more of them, the La Jolla, California-based startup has raised $100 million.

在两年的时间里，Iambic开发了四种AI发现的分子，其中最先进的分子现在处于第一阶段测试的尖端。为了支持这些项目并开发更多项目，位于加利福尼亚州拉霍亚的初创企业已经筹集了1亿美元。

Some companies in the AI space take a “physics-based” approach to drug discovery, using software to run simulations that yield a better understanding of molecular dynamics—how small molecules interact with a protein of interest. Companies in this mold include Nimbus Therapeutics, Schrödinger, and Relay Therapeutics.

人工智能领域的一些公司采用“基于物理”的方法进行药物发现，使用软件进行模拟，从而更好地了解分子动力学小分子如何与感兴趣的蛋白质相互作用。该模具中的公司包括Nimbus Therapeutics，Schrödinger和Relay Therapeutics。

A different group of AI drug companies run experiments to generate data that they then interrogate to gain biological and chemical insights, an approach taken by companies such as Exscientia and Recursion Pharmaceuticals..

另一组人工智能制药公司进行实验以生成数据，然后他们进行询问以获得生物和化学见解，这是Exscientia和Recursion Pharmaceuticals等公司采取的一种方法。。

Miller said Iambic brings both worlds together, making the most of physics-based insights that are then augmented with data to make better predictions. The company’s technology enables it to identify new molecules that offer superior efficacy and safety, he said. More than finding out whether a molecule can hit a target, Iambic’s technology reveals insights into other properties, such as potency to its target, its toxicity profile, and how the molecule moves through and interacts with the body..

米勒说，Iambic将两个世界结合在一起，充分利用基于物理的见解，然后增加数据以做出更好的预测。他说，该公司的技术使其能够识别出具有卓越功效和安全性的新分子。除了找出分子是否可以击中目标之外，Iambic的技术还揭示了对其他特性的见解，例如对其靶标的效力，其毒性特征以及分子如何穿过并与身体相互作用。。

“It’s the ability to predict across numerous endpoints for a successful drug,” Miller said.

米勒说：“它能够预测一种成功药物的众多终点。”。

Iambic’s technologies can be applied to multiple indications, but the company’s first four programs, including two on pace to reach the clinic next year, are for cancer. IAM-H1 is a small molecule that blocks HER2 and variants of this cancer-driving protein. In addition to its selectivity to this target, Iambic says this molecule also has the ability to penetrate the brain—an important property for treating cancer that has spread to the central nervous system..

Iambic的技术可以应用于多种适应症，但公司的前四项计划，包括明年到诊所的两项计划，都是针对癌症的。IAM-H1是阻断HER2和这种癌症驱动蛋白变体的小分子。除了对这个目标的选择性之外，Iambic说这种分子还具有穿透大脑的能力，这是治疗已经扩散到中枢神经系统的癌症的重要特性。。

IAM-C1 is a small molecule that selectively blocks CDK2 and CDK4, two enzymes associated with tumor growth. The three FDA-approved CDK inhibitors are Pfizer’s Ibrance, Kisqali from Novartis, and the Eli Lilly drug Verzenio. All three are blockbuster products that have become standard of care breast cancer treatments.

IAM-C1是选择性阻断与肿瘤生长相关的两种酶CDK2和CDK4的小分子。三种FDA批准的CDK抑制剂是辉瑞公司的Ibrance，诺华公司的Kisqali和Eli Lilly drug Verzenio。这三者都是重磅炸弹产品，已成为乳腺癌治疗的标准。

Iambic claims its drug can selectively block its two enzyme targets while preserving enzymes closely related to those targets. Other properties of this Iambic drug include a better therapeutic window, which is the dose range in which a therapy is effective while causing minimal adverse effects. This molecule is also designed to address drug resistance in cell-cycle-driven cancers..

Iambic声称其药物可以选择性阻断其两个酶靶标，同时保留与这些靶标密切相关的酶。该Iambic药物的其他性质包括更好的治疗窗口，其是治疗有效的剂量范围，同时引起最小的副作用。该分子还被设计用于解决细胞周期驱动的癌症中的耐药性。。

With the new financing, Iambic aims to advance its two lead programs into Phase 1 testing next year. A third cancer program addressing a yet-to-be-disclosed target could follow them into the clinic. In addition to the clinical trial work, Miller said his company will continue its drug discovery research.

随着新的融资，Iambic的目标是在明年将其两项主导项目推进第一阶段测试。针对尚未披露的目标的第三项癌症计划可以将其带入诊所。除了临床试验工作外，米勒还表示他的公司将继续进行药物发现研究。

While Iambic is flexible in terms of the mechanism of action of potential drugs, Miller said Iambic’s focus is mainly small molecules rather than biologics. Expanding to indications beyond cancer could happen through partnerships..

虽然Iambic在潜在药物的作用机制方面具有灵活性，但Miller表示Iambic的重点主要是小分子而不是生物制剂。通过合作关系扩大到癌症以外的适应症可能会发生。。

Iambic already has a research collaboration with Eli Lilly, a deal struck last year that gave the pharma giant exclusive rights to the startup’s nucleic acid delivery technology. Lilly is interested in delivering therapeutic cargo to targets in the central and peripheral nervous systems. Iambic received $50 million up front, including an equity investment from Lilly.

Iambic已经与礼来公司进行了研究合作，这是去年发生的一项协议，为该公司的核酸输送技术提供了巨大的专有权。礼来公司有兴趣将治疗性货物运送到中枢和外周神经系统的目标。Iambic提前收到5000万美元，其中包括礼来公司的股权投资。

The startup could earn up to $400 million in milestones..

初创企业的里程碑价值可高达4亿美元。。

Iambic’s employee roster is split evenly between software engineers and drug development scientists. Miller said that this composition reflects the reality that AI-driven drug discovery research is interdisciplinary by nature.

Iambic的员工名单在软件工程师和药物开发科学家之间平均分配。米勒说，这篇文章反映了人工智能驱动的药物发现研究本质上是跨学科的现实。

“We really do believe that there is a duality that one has to capture to be successful at that interface,” he said. “We work hard to embrace the expertise of technology. But we also realize drug discovery and development builds on decades of hard-earned experience. And we need that reflected in the team as well.”.

他说：“我们真的相信，为了在这个界面取得成功，必须捕捉到二元性。”。“我们努力接受技术的专业知识，但我们也认识到药物发现和开发建立在数十年的辛勤经验的基础上，我们也需要反映在团队中。”。

Miller co-founded Iambic in 2019 based on research from the University of Bristol and Caltech, where he was a professor of chemistry for 14 years. Iambic’s marriage of technology with biotechnology is reflected in its investor syndicate. In 2021, the startup raised a $53 million Series A round of financing led by Coatue, a technology investment firm, and Catalio Capital Management, which focuses on biomedical technology investments.

米勒根据布里斯托尔大学和加州理工大学的研究，于2019年共同创立了Iambic，他在那里担任化学教授14年。Iambic的技术与生物技术的结合反映在其投资者集团中。2021年，该初创企业在技术投资公司Coatue和专注于生物医学技术投资的Catalio Capital Management的领导下，筹集了5300万美元的一轮融资。

That financing mainly supported development of the startup’s tech platform..

该融资主要支持初创企业技术平台的开发。。

The company built its AI technology in collaboration with Nvidia, a company whose computing technologies are integral components in the platforms of many AI drug discovery firms. In addition to investing in Iambic, Miller said Nvidia will also continue to work with the startup to develop next-generation technologies for drug development..

该公司与Nvidia合作构建了AI技术，Nvidia是一家计算技术是许多AI药物发现公司平台不可或缺的组成部分的公司。Miller表示，除了投资Iambic之外，Nvidia还将继续与初创企业合作开发下一代药物开发技术。。

Iambic was initially named Entos. With the Series B financing announced this week, it revealed the name change to Iambic. The latest financing was co-led by Ascenta Capital and Abingworth. New investors joining the round include Nvidia, Illumina Ventures, Gradiant Corporation, and independent board member Bill Rastetter.

Iambic最初被命名为Entos。随着本周宣布的B系列融资，它透露了Iambic的名称变更。最新的融资由Ascenta Capital和Abingworth共同领导。加入该轮的新投资者包括Nvidia，Illumina Ventures，Gradiant Corporation和独立董事会成员Bill Rastetter。

Earlier investors that participated in the latest financing include Nexus Ventures, Catalio Capital Management, Coatue, FreeFlow, OrbiMed, and Sequoia Capital..

此前参与最新融资的投资者包括Nexus Ventures，Catalio Capital Management，Coatue，FreeFlow，OrbiMed和Sequoia Capital。。

Photo: metamorworks, Getty Images

照片：metamorworks，Getty图片

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