The multi-billion deal, in which Eli Lilly will acquire Scorpion Therapeutics’ STX-478 program, is a shot in the arm for PI3K treatments, which have had a mixed history over the past few years.
There’s been no shortage of blockbuster deals as the J.P. Morgan Healthcare Conference kicked off Monday in San Francisco, and now Eli Lilly has joined the fray, setting down $1 billion up front for Scorpion Therapeutics’ PI3Kα inhibitor program in a bid to bolster its own cancer pipeline.
The deal, which includes an additional $1.5 billion upon the clearance of regulatory hurdles and sales milestones, confirms reporting from BMO Capital Markets last week suggesting that Lilly was kicking the tires around Scorpion.
Scorpion’s program, STX-478, is a novel small molecule that binds to phosphoinositide 3-kinase alpha (PI3Kα), one of the most commonly mutated genes across all cancer types, occurring in approximately 14% of all cancers. What sets the asset apart, according to Scorpion, is its semi-novel mechanism of action, where it binds to PI3K, a recurring target, but at a novel binding site. STX-478 is currently in Phase I/II trials for breast cancer and other solid tumors.
Lilly’s hope is that STX-478’s novel behavior, targeting mutations in PI3Kα at a novel site, will circumvent the safety and toxicity issues that have dogged other drugs targeting the pathway.
“The selectivity profile of STX-478 has led to a differentiated clinical profile, enabling use in combinations with standard-of-care therapies to potentially deliver meaningful impact in earlier treatment settings when there is the best opportunity to improve outcomes for patients,” Jacob Van Naarden, executive vice president and president of Lilly Oncology, said in a statement.
Scorpion president and CEO Adam Friedman also addressed the transaction in the same press release, saying, “We believe Lilly’s global capabilities and strategic commitment to patients with breast cancer will accelerate our goal of developing STX-478 to improve outcomes for the many patients with solid tumors driven by PI3Kα mutations.”
Lilly is not acquiring all of Scorpion. The Indiana-based pharma is getting the PI3K portion of the company and the name “Scorpion,” while Scorpion itself will spin out its employees and non-PI3K work into a new entity, whose name was not announced. The new company will be owned by Scorpion’s shareholders, with Lilly retaining a minority stake.
Because of its common role across cancers, PI3K is one of the most popular targets for the biopharma and oncology sector, but the class has seen mixed results. As recently as 2022, companies developing PI3K inhibitors saw large layoffs, withdrawn products with incomplete trials, and abandoned assets, in addition to an FDA advisory committee vote to shut down single-arm clinical studies of new PI3K inhibitors due to safety issues, toxicity and side effect concerns, instead recommending randomized trials.
However, in October 2024, Roche won FDA approval for its own PI3K inhibitor for breast cancer, Itovebi, alongside $2 billion plus sales projections, putting it head-to-head with Novartis’s PI3K-inhibiting breast cancer treatment Piqray, itself generating north of $500 million in annual revenue.
