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Novartis is moving to acquire Pikavation Therapeutics, a wholly-owned subsidiary of Synnovation Therapeutics, to gain control of SNV4818 and related PI3Kα inhibitor programs. The deal covers a pan-mutant selective PI3K alpha small molecule inhibitor currently in Phase I/II trials for HR+/HER2- metastatic breast cancer and other solid tumors. Synnovation is a clinical-stage company headquartered in Wilmington, Delaware, focused on small-molecule targeted therapies in oncology and immunology. Under the agreement, Novartis will pay Synnovation USD 2 billion in upfront cash and up to USD 1 billion in development, regulatory, and commercial milestone payments, for total potential consideration of up to USD 3 billion. Deal closure is expected in H1 2026, subject to antitrust review. Novartis will assume sole responsibility for all future development and commercialization of the acquired programs. SNV4818 is a small molecule designed to selectively inhibit multiple oncogenic mutations of PI3Kα while sparing the wild-type enzyme. PIK3CA mutations encoding PI3Kα are among the most common oncogenic alterations in HR+/HER2- breast cancer and occur across other solid tumor types. First-generation PI3Kα inhibitors, including Novartis’s own alpelisib (trade name: Piqray), inhibit both mutant and wild-type forms of the enzyme. This lack of mutant selectivity drives on-target toxicities including hyperglycemia, rash, and diarrhea. Pan-mutant selective inhibitors aim to widen the therapeutic window by concentrating activity on the disease-driving mutant protein. A Phase I/II trial evaluating SNV4818 as monotherapy and in combination with fulvestrant or palbociclib in patients with advanced PIK3CA-mutant solid tumors is ongoing, with enrollment of 320 participants across sites in Canada and Australia (see NCT06736704). No clinical data from this trial have been publicly reported. For Novartis, this deal represents an effort to defend and extend its position in the PI3Kα pathway. Alpelisib generated the company’s initial franchise in PIK3CA-mutant breast cancer but faces displacement by agents with improved tolerability profiles. Acquiring SNV4818 allows Novartis to develop a next-generation successor using its existing breast cancer commercial infrastructure. Synnovation retains its remaining pipeline, including SNV1521, a PARP1-selective inhibitor in Phase I, along with additional oncology and immunology programs. The PI3Kα inhibitor landscape has become competitive. Several companies are developing next-generation mutant-selective agents targeting the same biology. Tersolisib (STX-478) — Eli Lilly (acquired from Scorpion Therapeutics) — Phase III pivotal trial; allosteric, pan-mutant selective, CNS-penetrant Zovegalisib (RLY-2608) — Relay Therapeutics — Phase III; allosteric, pan-mutant and isoform-selective OKI-219 — OnKure Therapeutics — Phase I; mutation-specific (H1047R only) LY4045004 — Eli Lilly (internal) — preclinical/early clinical; pan-mutant selective Inavolisib (Itovebi) — Roche/Genentech — approved 2024; PI3Kα-selective but not mutant-selective Lilly’s tersolisib is the most advanced next-generation program and has already entered a front-line pivotal study. Relay’s zovegalisib showed consistent efficacy and tolerability in updated data presented at ASCO 2025. Lilly’s earlier mutation-specific candidate LOXO-783 was discontinued after showing limited monotherapy activity in Phase 1, which has shifted competitive consensus toward pan-mutant approaches. SNV4818 enters this field behind at least two competitors with more advanced clinical data, though Novartis’s existing commercial presence in PI3Kα-mutant breast cancer and its global development capabilities could accelerate the program’s path through later-stage trials. Your email address will not be published. Required fields are marked * Comment * Name * Email * Website

iStock, Mininyx Doodle Aside from the $2 billion upfront payment, Novartis is also putting up to $1 billion on the line in milestones for Synnovation Therapeutics’ pan-mutant-selective PI3Kα blocker. Novartis is picking up a breast cancer drug candidate from Delaware’s Synnovation Therapeutics, a move that will help it stay ahead of big pharma peers playing in the PI3Kα arena. The front-heavy deal, announced in a Friday morning news release , will involve a $2 billion upfront commitment from Novartis to acquire the Synnovation subsidiary Pikavation Therapeutics, which owns the pipeline of PI3Kα programs that Novartis wants. The pharma has also promised up to $1 billion in milestone payments. Terms for royalties were not disclosed in the press announcement. The centerpiece of Friday’s deal is Synnovation’s PI3Kα inhibitor SNV4818, an orally available drug undergoing Phase 1/2 development for breast cancer and advanced solid tumors. PI3Kα is an enzyme that, according to Shreeram Aradhye, Novartis’ president of Development, “is a well-established driver in HR+/HER2- breast cancer.” Mutations to this gene can lead to worse disease prognosis, Novartis said. SNV4818 specifically targets mutated PI3Kα in cancer cells while avoiding normal forms of the protein. This sets it apart from other drugs that target PI3Kα, which don’t distinguish between the altered and wild-type versions of the enzyme, Novartis said. SNV4818’s bias for mutated PI3Kα “has the potential to translate proven biology into improved tolerability and more durable benefit for patients through precision medicine,” Aradhye said. The Synnovation deal, which Novartis expects to close in the first half of this year, will also give the pharma Pikavation’s other PI3Kα assets, though not much detail about the programs was provided. Once under the Novartis fold, SNV4818 will complement the pharma’s existing PI3Kα portfolio, currently anchored by Piqray, approved in 2019 as part of a combo regimen with AstraZeneca’s hormone therapy Faslodex for HR+, HER2- advanced or metastatic breast cancer. The drug, however, has recently been overshadowed by newer therapies including AstraZeneca’s Truqap ( approved in 2023 ) and Roche’s Itovebi ( cleared in October 2024 ), which made $728 million and CHF 113 million (roughly $143.5 million) respectively last year. Novartis didn’t post sales figures for Piqray in 2025. In January 2025, Eli Lilly entered the already-crowded PI3Kα arena when it fronted $1 billion for Scorpion Therapeutics’ STX-478, a small-molecule blocker of the enzyme. Then drug is in a Phase 3 study for HR+/HER2- breast cancer, with a primary completion date of May 2029.