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Endpoints 11 winner Iambic Therapeutics: Entering the ‘show-me’ era for AI

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  • CEO Tom Miller
  • Total raised $220 million
  • Headquarters San Diego, CA

As two biotech rookies leaving long academic careers to co-found Iambic in 2019, CEO Tom Miller and CTO Fred Manby were “incredibly self-aware” of the science and business experience they lacked, Manby said.

So they sought out advisors who could help fill in the gaps. Longtime chemist (and blogger) Derek Lowe joined their scientific advisory board, playing the role of “the reality check guy.” More recently, San Diego biotech executive Bill Rastetter became a director. In 2021, the biotech shifted focus from developing AI software for everyone from drug companies to industrial giants like Toyota and Dow, to building its own pipeline. It’s moved fast since, with its first drug already in the clinic and two more close behind, making Iambic one of AI bio’s most heads-down efforts to help produce better drugs.

Its AI models, some made with the chipmaking giant Nvidia as a research partner, simulate protein-molecule interactions, generate molecules and predict properties like stability or toxicity. The goal is to make drugs, and move fast. It’s connected its AI models to an internal software system that researchers use to design experiments that are then run in the laboratory next door.

“It’s not enough to just be excited about the current architecture,” Miller said, referencing the newest AI model designs. “People are in a show-me mode of, can these things lead to medicines that we can agree are better — on the basis of what that model provided.”

Iambic is starting to see results from that platform, all before turning five years old. Its lead program, a HER2-targeting molecule called IAM1363, entered the clinic this spring. Miller said he expects a readout, including preliminary efficacy, for that Phase 1b study in mid-2025.

HER2 is as well-validated as any target in cancer, dating back to the 1998 approval of Roche/Genentech’s Herceptin. But Iambic believes its molecule can stand apart by penetrating the brain and achieving 1,000-fold selectivity in hitting HER2 over a similar protein called EGFR. The theory is other drugs left efficacy on the table because they lack that selectivity, Miller said.

Still, the only way to know if that idea translates to helping patients is the clinic. For all the help that Iambic’s AI technology plays in making the molecule, it isn’t providing insights into what targets or properties are worth focusing on.

Iambic’s next programs take on more biological risk and design challenges. A CDK2/4 drug is “rapidly advancing” to the clinic, Miller said, targeting an IND filing in 2025. While therapies like Pfizer’s Ibrance and Eli Lilly’s Verzenio target CDK4 and CDK6, Iambic is betting on selectivity again. Avoiding CDK6 and other similar enzymes could translate to less toxicity and greater clinical benefit, the company says.

A KIF18a inhibitor also could be IND-ready in 2025, Miller added. Both could be first-in-class drugs, with Iambic’s AI technology helping achieve drug characteristics that haven’t yet been possible, he said.

“It’s not like 10% better or from 1 to 1.2,” Miller said. “It’s going from zero to one.”

Miller, an ex-Caltech professor, has embraced the CEO role, raising $220 million from a syndicate including biotech insiders like OrbiMed and Abingworth, and tech investors like Sequoia and Coatue. The biotech also has inked its first pharma deal, working with Lundbeck to discover small molecules for migraine.

With cash runway into at least 2026 and clinical data on the horizon, Iambic is poised to show if AI’s moment in biotech has finally arrived.

“The proof of the pudding is in the eating,” Miller said of his vision for the AI bio field over the next five to 10 years. “Showing in our hand, and for the field at large, that AI is leading to medicines in a statistically meaningful way that lead to more successful approvals, faster approvals, better drugs. This is the measure we will begin to gather more meaningful data on in that timescale.”

Key backers: OrbiMed, Sequoia, Coatue, Catalio, NVentures, Illumina Ventures, Abingworth, Exor, Mubadala, Qatar Investment Authority, Ascenta

Find the full list of 2024 Endpoints 11 winners here.


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