Novartis has committed up to $3 billion—two-thirds of that upfront—toward acquiring Pikavation Therapeutics, a subsidiary of Synnovation Therapeutics that specializes in developing PI3Kα inhibitor programs designed to treat forms of cancer. Pikavation’s programs are led by SNV4818, a pan-mutant selective PI3Kα (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) inhibitor currently in early-stage clinical trials for the treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer and other solid tumors. Novartis reasons that by targeting PI3Kα, it can reduce the approximately 40% of HR+/HER2- breast cancer patients who potentially face worse disease prognosis due to the presence of PIK3CA mutations in their tumors. SNV4818 is designed to target the mutated PI3Kα enzyme found in cancer cells while sparing wild-type PI3Kα in healthy cells, unlike currently available PI3Kα inhibitors that block both mutant and wild-type PI3Kα, leading to tolerability challenges for patients. By focusing on the mutated form in tumors, Novartis said, SNV4818 aims to reduce unwanted side effects, support more consistent dosing, and make it easier to combine with hormonal therapy and other treatments earlier in care. Preclinical studies have shown strong activity against common PIK3CA mutations and clear selectivity over the normal enzyme, the company added. SNV4818 is now being evaluated in a Phase I/II open-label dose escalation and expansion study (NCT06736704) as a monotherapy and in combination with fulvestrant and palbociclib, a combination therapy that is standard of care for HR+/HER2- breast cancer. Fulvestrant was launched to market by AtsraZeneca as Faslodex® and is now sold as…
