SpringWorks Therapeutics and GSK have entered into an expanded global, non-exclusive license and collaboration agreement to study nirogacestat (PF-03084014), an investigational oral gamma-secretase inhibitor, in combination with belantamab mafodotin-blmf (Blenrep®; GSK) and antibody-drug conjugate (ADC) targeting B-cell maturation antigen (BCMA).

Nirogacestat was first granted FDA breakthrough drug designation in September 2019 for adult patients with progressive, unresectable, recurrent, or refractory desmoid tumors or deep fibromatosis.[1]

Nirogacestat is currently in Phase 2 clinical trials for unresectable desmoid tumors. In addition, a Phase 3 clinical trial is currently in progress for nirogacestat for adults with desmoid tumors and aggressive fibromatosis. In addition, three trials are presently recruiting patients that include nirogacestat with other anticancer therapies in multiple myeloma, including the UNIVERSAL study for nirogacestat with the allogeneic CAR-T therapy ALLO-715.

Under the terms of the expanded agreement, SpringWorks will receive a US $ 75 million equity investment from GSK, with shares of common stock priced at a premium to the 30-day volume-weighted average share price on September 2, 2022.

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SpringWorks will also be eligible to receive up to US$ 550 million in additional payments based on reaching certain development and commercial milestones. SpringWorks will retain full commercial rights to nirogacestat and will be responsible for the global commercialization of nirogacestat.

“We are very pleased to expand our relationship with GSK to enable potential additional studies of Blenrep and nirogacestat,” noted Saqib Islam, Chief Executive Officer of SpringWorks.

“Our goal is to maximize the clinical impact of nirogacestat as a potentiator of BCMA targeted therapies and today’s announcement advances our opportunity to serve patients with multiple myeloma across lines of therapy,” Islam added.

“We look forward to continuing our relationship with SpringWorks for the potential expanded development of Blenrep with nirogacestat and are encouraged by the early clinical data emerging from the combination,” said Hesham A. Abdullah, M.D., M.Sc., Senior Vice President, Global Head of Oncology Development at GSK.

“Belantamab mafodotin in combination with novel therapies, such as nirogacestat, could prove to be an impactful therapeutic option for patients with multiple myeloma, as these combination regimens may further optimize the benefit-risk profile of Blenrep, especially in earlier lines of therapy.”

Expanding the agreement
SpringWorks and GSK first entered into a clinical trial collaboration and supply agreement in June 2019, later amended in October 2021, to cover the initial clinical development of nirogacestat in combination with Blenrep in patients with relapsed or refractory multiple myeloma.

The new agreement expands the original collaboration to include the potential for continued development and commercialization of the combination of nirogacestat and Blenrep in earlier lines of treatment, including newly diagnosed multiple myeloma. SpringWorks and GSK will expand their previously established governance structures to add a new Joint Steering Committee and Joint Commercialization Committee to their existing Joint Development Committee. GSK will continue funding all development costs, except for those related to the supply of nirogacestat and certain expenses related to intellectual property rights.

Highlights of prescribing information
Belantamab mafodotin (Blenrep®; GSK) [Prescribing Information]

[1] Astor L. FDA Grants Nirogacestat Breakthrough Designation for Desmoid Tumors. Oncolive.

Featured image: GSK Scietists Conducting Research. Photo courtesy: © 2019 – 2022, GSK. used with opermission.

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