SpringWorks Therapeutics launched in September 2017 with $103 million and a handful of clinical-stage Pfizer drugs. A year later, the startup has named its first CEO and is unveiling a partnership with BeiGene focusing on a targeted combination therapy for an “undruggable” cancer mutation.
The deal centers on SpringWorks’ MEK inhibitor PD-0325901 and BeiGene’s RAF dimer inhibitor, lifirafenib (BGB-283), which they will test in patients with advanced solid tumors that have RAS and RAF mutations, and other MAPK aberrations. RAS mutations turn up in about 30% of all cancers and about one-quarter of solid tumors. These tumors tend to be aggressive and treatment resistant, making RAS mutations an attractive target, but scientists have struggled to develop drugs that safely counter their effects.
“I think there is something meaningful here about this combination—some of that is driven by the fact that this is the most potent combination with a really unique inhibitor in the RAF family,” said Saqib Islam, who served as SpringWorks’ chief business officer and chief financial officer before taking the helm as CEO this week. “There is a strong scientific rationale for the combination of a MEK inhibitor with a RAF dimer inhibitor.” Inhibiting the MAPK pathway, he said, could help overcome some feedback loops that have impeded the development of these types of inhibitors for RAS-mutated solid tumors in the past.
While BeiGene will bear responsibility for carrying out the phase 1b trial, the duo will share costs and governance equally, Islam said. They plan to launch the study in the first quarter of 2019.
SpringWorks is also planning a phase 2b registration trial for PD-0325901 as a monotherapy in patients with neurofibromatosis type 1 who have plexiform neurofibromas. And it’s on the lookout for more licensing and partnership opportunities for its MEK program.
“We believe that MEK inhibitors are a promising backbone for targeted combination therapies for multiple tumor types,” Islam said. “We’re talking about BeiGene now and hope in the not too distant future, we’ll talk about the next [partnership.]”
It’s got some other business development talks around using its other assets in combination, as well as potential in-licensing of assets from Pfizer, Islam said. Other launched assets included a gamma-secretase inhibitor slated to start a registration trial in desmoid tumor next year and a pair of earlier-stage compounds including a FAAH inhibitor for neurological indications.
At launch, Pfizer CMO and SpringWorks board member Freda Lewis-Hall, M.D., explained: “Pfizer sees SpringWorks Therapeutics as a ground-breaking new model for collaboration to deliver on the promise of medical research and development, so that more people have the potential to overcome disease. We hope that our investment in SpringWorks Therapeutics will, over time, enable us to realize even more value for patients and society.
“SpringWorks Therapeutics started as an idea about a new way to get things done with—and for—patients, it’s been a tremendous team effort, and we and our partners are excited to see it become a reality.”