NEW YORK – Theseus Pharmaceuticals said on Monday that it will develop THE-349 as its lead drug candidate for EGFR-mutant non-small cell lung cancer.
The Cambridge, Massachusetts-based firm plans to submit an investigational new drug application for the agent to the US Food and Drug Administration during the second half of 2023, which, if cleared, would allow Theseus to begin evaluating THE-349 in clinical trials.
According to Theseus, the new drug candidate is a fourth-generation EGFR-targeting small molecule designed to inhibit all major classes of EGFR activating and resistance mutations, including activating mutations in EGFR exons 19 and 21 and the most common EGFR resistance mutations, T790M and C797X.
In preclinical studies, the drug demonstrated it could inhibit single-, double-, and triple-mutant EGFR variants following first- or later-line treatment with AstraZeneca's Tagrisso (osimertinib). Theseus plans to present preclinical data on THE-349 at a medical conference later this month.
"Clonal heterogeneity in patients who develop resistance to osimertinib is complex, and we believe a single EGFR inhibitor capable of targeting all major mutant forms of EGFR activating and resistance mutations is the optimal way to address this urgent medical need," William Shakespeare, Theseus' president of R&D, said in a statement.
Developing what it calls "pan-variant" inhibitors is part of the firm's larger drug development strategy. In June, Theseus began a Phase I/II trial evaluating another drug candidate, THE-630, a pan-KIT inhibitor for patients with gastrointestinal stromal tumors (GIST) who are resistant to prior KIT-targeting treatments.