Tersolisib

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.

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