Novartis Pays $2 Billion to Replace Its Own Breast Cancer Drug

Novartis is spending up to $3 billion to acquire a breast cancer drug designed to succeed where its own earlier therapy fell short.

The Swiss pharma announced Friday it will pay $2 billion upfront and up to $1 billion in milestone payments to acquire Pikavation Therapeutics, a subsidiary of privately held Synnovation Therapeutics based in Wilmington, Delaware. The deal gives Novartis control of SNV4818, an oral PI3Kα inhibitor currently in Phase 1/2 trials for HR+/HER2- metastatic breast cancer and other solid tumors, as first reported by GEN.

The transaction is expected to close in the first half of 2026, pending regulatory review including Hart-Scott-Rodino antitrust clearance.

The tolerability problem

To understand why Novartis is writing a $2 billion check for a Phase 1 asset, you need to understand the drug it's trying to move past.

About 40% of HR+/HER2- breast cancer patients carry PIK3CA mutations — alterations to the gene encoding PI3Kα that drive worse outcomes. Novartis was early to this biology with Piqray (alpelisib), approved in 2019 as the first PI3Kα inhibitor for this population. But Piqray hits both mutant and wild-type PI3Kα indiscriminately. The result: hyperglycemia severe enough to require metformin co-administration, with hyperglycemia adverse events occurring in 33-70% of patients depending on the study cohort. Diarrhea, appetite loss, and weight loss compound the burden. Keeping patients on treatment has been a persistent challenge.

Novartis didn't even report Piqray sales figures in its 2025 annual results — a quiet concession.

Meanwhile, competitors moved in. Roche's Itovebi (inavolisib), approved by the FDA in October 2024, is a mutant-selective PI3Kα inhibitor that also functions as a degrader of the mutant protein. It made CHF 113 million (roughly $144 million) in its first partial year on the market. AstraZeneca's Truqap (capivasertib), which targets a related node in the PI3K/AKT pathway, earned $728 million in 2025. And in January 2025, Eli Lilly paid $1 billion upfront for Scorpion Therapeutics' STX-478, another mutant-selective PI3Kα inhibitor now in Phase 3 trials.

What SNV4818 promises

SNV4818 is designed to selectively target the mutated PI3Kα enzyme in cancer cells while sparing the wild-type form in healthy tissue. According to Novartis, preclinical studies show strong activity against common PIK3CA mutations — covering kinase domain (H1047R), helical domain (E545K), and other clinically relevant variants — with clear selectivity over the normal enzyme.

"SNV4818 applies new mutant-selective chemistry to more precisely target tumor biology while sparing normal cells," said Shreeram Aradhye, Novartis' president of development, in the company's press release.

The drug is being evaluated in a Phase 1/2 study (NCT06736704) as monotherapy and in combination with fulvestrant and palbociclib, with an estimated primary completion date of April 2027. The first patient was dosed in February 2025 — making this acquisition remarkably early-stage for a deal this size.

Novartis sees SNV4818 fitting alongside its CDK 4/6 inhibitor Kisqali (ribociclib), which pulled in $4.78 billion in 2025 sales and anchors its breast cancer franchise. A tolerable PI3Kα inhibitor that can combine with Kisqali and hormonal therapy earlier in the treatment sequence would be a significant commercial asset.

The people

Synnovation was founded by Wenqing Yao, who spent nearly two decades at Incyte as EVP and head of discovery chemistry before launching the company. SNV4818 is Synnovation's second program to reach the clinic, following its selective PARP1 inhibitor SNV1521. Synnovation will continue operating independently and retain its other R&D subsidiaries — this deal carves out only the PI3Kα portfolio.

"We believe Novartis's global capabilities and commitment to patients with cancer will accelerate the development of SNV4818 beyond what Synnovation could achieve alone," Yao said in a separate statement.

What to watch

Novartis shares dipped modestly on the news — about 1% on the SIX Swiss exchange and 1.5% on the NYSE — a shrug that suggests investors see this as a reasonable price for pipeline insurance rather than a transformative bet.

The real question is whether SNV4818 can differentiate itself in an increasingly crowded field. Roche's Itovebi has a head start and a dual mechanism (inhibition plus degradation). Lilly's STX-478 is already in Phase 3. Novartis is buying the earliest-stage asset of the three for a comparable price, banking on "pan-mutant" coverage across multiple PIK3CA mutation types as its edge.

With a Phase 1/2 primary completion date of April 2027, it will be years before the data justify or contradict that bet. In the meantime, Novartis has essentially paid $2 billion for admission to a race its competitors entered first.