BridgeBio's Navire preps SHP2 blocker for lung cancer trial after positive mouse study

Lungs
Navire's SHP2 inhibitor is designed to block signaling pathways that allow EGFR-mutated lung tumors to escape treatment with targeted drugs like Tagrisso. (Pixabay)

AstraZeneca’s Tagrisso is effective in treating EGFR-mutated non-small cell lung cancer (NSCLC), but patients often become resistant to the drug over time. Researchers at the University of Texas MD Anderson Cancer Center and BridgeBio’s Navire Pharma developed a drug to block key resistance mechanisms, and now they’re headed to clinical trials backed by positive results in mice.

The drug, IACS-13909, is a selective inhibitor of Src homology 2 domain-containing phosphatase (SHP2), a protein that activates certain signals in tumors, allowing them to escape EGFR inhibition and continue growing. IACS-13909 caused tumors to shrink in mouse models of Tagrisso-resistant NSCLC, both alone and in combination with AstraZeneca’s drug, the researchers reported in the journal Cancer Research.

Several factors can cause NSCLC tumors to become resistant to Tagrisso. The tumors can develop resistance mutations, or they can activate signaling pathways called mitogen-activated protein kinases (MAPK), which fuel tumor growth and survival. Those signaling pathways rely on SHP2.

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IACS-13909 suppressed NSCLC cell growth in test-tube experiments, the researchers reported. The drug also extended the lives of the mice, as compared to untreated animals.

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The promise of SHP2 inhibition in treating several types of cancer has fueled several biopharma deals in recent years. In June, AbbVie licensed an SHP2 portfolio from Jacobio Pharmaceuticals, which includes two drugs being tested in advanced solid tumors.

In 2018, Revolution Medicines raised $56 million in a series B round, which it used to advance its SHP2-targeted drug into a phase 1/2 clinical trial in multiple tumor types. And in June, Relay Therapeutics raised $460 million in an initial public offering—more than twice its original funding goal—to advance its pipeline, which includes an SHP2 inhibitor.

Now Navire is jumping into the race with IACS-13909, and it boasts a strong financial backing, too. Navire is a portfolio company of BridgeBio, which raised $299 million privately in 2019 and then hauled in $348.5 million in an IPO. BridgeBio was founded five years ago with the mission of nurturing drugs addressing “Mendelian or monogenic” diseases, which are caused by mutations in a single gene.

IACS-13909 was discovered by MD Anderson researchers and licensed to Navire. Through the research collaboration, “we continue to uncover SHP2’s critical role in activating multiple different pathways related to cancer’s onset and growth,” said Eli Wallace, chief scientific officer of oncology at BridgeBio, in a statement.

Navire will launch a clinical trial by the end of this year at MD Anderson and other U.S. sites.

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