San Diego-based KymaThera closed a USD 80 million Series B financing led by Alta Partners to advance K-1728, its investigational oral pan-mutant selective PI3Kα inhibitor, with funding set to support development through initial clinical proof-of-concept. Venrock, Foresite Capital, new investor J. Wood Capital, and others also participated. The round brings KymaThera’s total capital raised to more than USD 100 million following a 2024 Series A co-led by Foresite and Venrock.
K-1728 is designed to inhibit disease-driving PI3Kα mutations in both the kinase and helical domains while sparing wild-type PI3Kα, with the aim of addressing the toxicity and incomplete mutation coverage associated with earlier PI3Kα inhibitors. KymaThera is developing the drug as a monotherapy and in combination regimens for hormone receptor-positive, HER2-negative (HR+/HER2−) breast cancer, and as a monotherapy for PI3Kα-driven vascular malformations.
In preclinical and investigational new drug-enabling studies, K-1728 showed activity against kinase- and helical-domain PI3Kα mutations, producing tumor regressions at low once-daily doses. KymaThera also reported a wide preclinical therapeutic window between exposures associated with deep tumor regressions and those associated with hyperglycemia, a toxicity linked to inhibition of wild-type PI3Kα.
PI3Kα mutations, largely involving the kinase and helical domains of PIK3CA, are common oncogenic alterations in HR+/HER2− breast cancer and also drive a subset of vascular malformations. A closely related clinical-stage approach is Relay Therapeutics’ zovegalisib (RLY-2608), another pan-mutant selective PI3Kα inhibitor that has advanced to Phase III development in PIK3CA-mutant HR+/HER2− advanced breast cancer and is also being evaluated in PIK3CA-driven vascular malformations.