A precision medicine is only as good as its target. While targeted therapies now address many types of cancer, tumors still frequently develop mutations that help them escape a drug. One strategy to address tumor escape is combining different cancer drugs.

Biotech startup IDRx aims to use scientific knowledge of tumor biology to develop new drug combinations that cover cancer escape pathways. It’s now out of stealth backed by $122 million. The Series A financing announced Tuesday was led by Andreessen Horowitz and Casdin Capital.

Plymouth, Massachusetts-based IDRx says it takes its inspiration from the various drug combinations that have proven successful in treating diseases such as cystic fibrosis and certain viral infections. Drug combinations are already frequently used in treating cancer. But the toxic effects of multiple drugs means that these combinations are reserved for advanced cancers with limited treatment options.

IDRx aims to bring combination therapy into earlier stages of cancer treatment. The first drug in the combo will be engineered to hit the primary mutations that enable a cancer to escape. The goal is for this drug to have a wide therapeutic window, which is the dose range in which a therapy can be used without having dose-limiting toxicity. A wide therapeutic window would enable such a cancer drug to be used as an earlier treatment, the company said.

The second part of these drug combinations would consist of molecules that stop the resistance mutations that the first drug does not address. According to IDRx, this approach will shut down a cancer’s escape pathway and enable a durable response to the therapy. In the future, IDRx says its drug cocktails may include more than two drugs in order to address multiple genetic pathways of a cancer.

IDRx was founded last year by Alexis Borisy, a serial entrepreneur whose ventures include EQRx, a startup tackling high drug prices. Though IDRx plans to design its own drugs, the startup’s most advanced programs come from outside of its labs. IDRX-42 was licensed from Merck KGaA and IDRX-73 from Blueprint Medicines. Both are small molecules designed to block tyrosine kinases, each addressing different genetic drivers and resistance mutations in gastrointestinal stromal tumor (GIST), a cancer of the gut.

IDRx co-founder and CEO Ben Auspitz said in a prepared statement that GIST offers IDRx the opportunity to start with a cancer that has well-known tumor biology but also has a high unmet medical need. The startup’s founders include Nicholas Lydon, a scientist who played a key role in the development of Gleevec, a Novartis cancer drug whose approved uses include GIST.

IDRX-42 has begun a Phase 1 study and IDRX-73 is moving toward human testing. Though these drugs are being tested separately, IDRx intends for them to eventually be used together. On its website, the company says IDRX-42 could serve as a base therapy for GIST patients and adding IDRX-73 “may provide a transformative benefit.”

Blueprint Medicines disclosed the licensing of its small molecule in its report of second quarter 2022 financial results Tuesday morning. The deal gives the company a 15% equity stake in IDRx as part of the startup’s Series A financing. Blueprint could also receive up to $217.5 million in milestone payments, plus royalties from sales if the drug reaches the market.

The other disclosed investors in IDRx are Nextech Invest and Forge Life Science Partners.

Photo by Flickr user Ed Uthman via a Creative Commons license