Novartis has struck a front-loaded deal to buy Synnovation Therapeutics’ pan-mutant‑selective PI3Kα inhibitor for $2 billion, securing an asset that could defend its breast cancer franchise from challengers including Eli Lilly.
The Swiss drugmaker already sells a PI3Kα inhibitor, Piqray, that competes with Roche’s Itovebi for the breast cancer market. Both drugs hit the mutant and wild-type forms of PI3Kα. Because inhibition of wild-type PI3Kα is linked to severe high blood sugar, researchers have identified selectivity for mutant forms of the protein as a way to improve on the safety and tolerability profiles of Piqray and Itovebi.
A label expansion and clinical data for Itovebi have handed Roche an advantage in the commercial battle. And, with other new challenges now in phase 3, Novartis has bet big to reestablish itself at the leading edge of a field it created.
Novartis is paying Synnovation $2 billion upfront for Pikavation Therapeutics, a wholly owned subsidiary of the biotech with a portfolio of pan-mutant-selective PI3Kα inhibitor programs including SNV4818. The deal also includes up to $1 billion in milestones.
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Having emerged with $102 million in 2024, Synnovation started a phase 1/2 trial in patients with breast cancer and other solid tumors about one year ago. The study is testing SNV4818 as a monotherapy and in combination with AstraZeneca’s Faslodex and Pfizer’s Ibrance. Synnovation designed the trial to show whether SNV4818 is safe, well tolerated and effective while generating data to inform dose selection.
Novartis, which expects to close the deal by mid-2026, said the asset “fits naturally alongside CDK inhibitors as well as endocrine (hormonal) therapies as part of a potential combination regimen.” A phase 1b trial stopped testing Piqray with Novartis’ CDK4/6 inhibitor Kisqali and Faslodex over toxicity. At least one dose reduction was needed in 10 of the 18 patients who received the triple combination.
Mutant‑selective PI3Kα inhibitors have shown better safety and tolerability to date, leading Lilly to start a phase 3 trial of tersolisib with a CDK4/6 inhibitor and endocrine therapy in first-line breast cancer. Risen Pharma Tech is running a phase 3 trial of its PI3Kα inhibitor, which is partnered with Junshi Biosciences, in combination with a CDK4/6 inhibitor and Faslodex. Relay Therapeutics picked the second-line setting, where Piqray is approved, for the first phase 3 trial of its PI3Kα inhibitor.
SNV4818 is lagging behind other mutant‑selective PI3Kα inhibitors in the race to market. But evidence that the molecule provides broad-spectrum PI3Kα mutation coverage fueled Synnovation’s belief it has a best-in-class candidate.
