ETX-636

Novartis is paying Synnovation Therapeutics $2 billion upfront for Pikavation Therapeutics, a wholly owned subsidiary of the biotech with a portfolio of pan-mutant-selective PI3Kα inhibitor programs.\n 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.  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. 

Novartis has budgeted $2 billion upfront to buy a more selective PI3Kα inhibitor for breast cancer. The Swiss pharma already has Piqray with a similar target, but drugmakers are now entering the next-generation era as they seek an improved risk-benefit profile. The next-gen space is heating up with Relay Therapeutics set to enter Phase 3 and Eli Lilly doing a similar deal last year. The focus of the Friday purchase is a drug called SNV4818. It is being developed by Pikavation Therapeutics, which Novartis will buy from Synnovation Therapeutics. The deal is worth up to $3 billion, considering there’s up to $1 billion in milestones on the table. The asset is in a Phase 1/2 trial for patients with HR+/HER2- metastatic breast cancer and is also under consideration for other solid tumors. Piqray was approved in combination with AstraZeneca’s Faslodex for HR+/HER2- PI3Kα-mutated advanced or metastatic breast cancer back in 2019. Piqray is the first PI3Kα-selective inhibitor to secure such an FDA approval. Sales dipped 15% last year to $382 million . The drug is approaching its 2033 patent cliff. Wall Street analysts have pointed out that next-gen candidates, such as Relay Therapeutics’ RLY-2608 , appear safer and more efficacious than Piqray in the same setting when comparing across trials. Relay is far ahead in the next-gen race as it is set to enter Phase 3 development. Piqray has been associated with high rates of hypoglycemia and diarrhea because it also affects wild-type PI3Kα. By contrast, Relay’s drug is a mutant-selective inhibitor of PI3Kα, which means that it can avoid this problem. Pikvation’s SNV4818 is also a mutant-selective PI3Kα inhibitor. In a LinkedIn post shared Monday, Novartis’ chief strategy and growth officer Ronny Gal said that the “challenge in the [PI3Kα inhibitor] class is to find a more tolerable agent, one that can combine well with other classes of breast cancer drugs.” SNV4818 will join a number of other breast cancer drugs in Novartis’ portfolio, including its blockbuster medicine Kisqali, which is also approved for HR+/HER2- forms of breast cancer. In 2024, Roche’s Itovebi, which also takes the older approach like Piqray, won an FDA approval for HR+/HER2- advanced breast cancer. Other mutant-selective PI3Kα inhibitors in the clinic include Eli Lilly’s STX-478, which it obtained as part of its up to $2.5 billion buyout of Scorpion Therapeutics in January last year. Lilly is currently recruiting for a Phase 3 trial of that drug. Lilly’s other PI3Kα-targeting candidate, LOXO-783, was discontinued several years ago to focus on next-gen approaches. Elsewhere, ENSEM Therapeutics has a next-gen candidate, ETX-636, in a Phase 1/2 program. The Novartis-Pikavation deal is expected to close in the first half of the year.