On October 4, 2023 Iambic Therapeutics reported the company brings together software engineers and drug-hunting scientists, all sharing the goal of using artificial intelligence to optimize properties of small molecule drugs (Press release, Iambic Therapeutics, OCT 4, 2023, View Source [SID1234637213]). The startup will apply its Series B financing to a cancer drug pipeline that includes two candidates on track for the clinic in 2024.

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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.

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.

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

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.

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. 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.

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.

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

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.

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. 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.

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. 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.

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.

"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."

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

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.

[Story updated to remove references to Entos Pharmaceuticals, which is a different company than Entos, Inc.] Iambic was initially named Entos, Inc. 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. Earlier investors that participated in the latest financing include Nexus Ventures, Catalio Capital Management, Coatue, FreeFlow, OrbiMed, and Sequoia Capital.