SpringWorks Therapeutics announced that the company has entered into a clinical collaboration and supply agreement with Janssen Biotech to evaluate its investigational gamma-secretase inhibitor (GSI), nirogacestat, in combination with Janssen’s bispecific antibody targeting B-cell maturation antigen (BCMA) and CD3, teclistamab, in patients with relapsed or refractory multiple myeloma.

Gamma secretase inhibition prevents the cleavage and shedding of BCMA from the surface of myeloma cells. In preclinical models, nirogacestat has been shown to increase the cell surface density of BCMA and reduce levels of soluble BCMA, which may enhance the activity of BCMA-targeted therapies, including CD3 bispecific antibodies.

“We are delighted to enter into this collaboration with Janssen to study nirogacestat in combination with teclistamab. We now have three collaborations with industry-leading BCMA developers to evaluate nirogacestat in combinations across modalities, including with an antibody-drug conjugate, an allogeneic CAR-T cell therapy and now a bispecific antibody. This collaboration is an important step in continuing to advance our goal of developing nirogacestat as a best-in-class BCMA potentiator,” said Saqib Islam, CEO of SpringWorks Therapeutics.

Under the terms of the agreement, Janssen will sponsor and conduct the Phase 1 study to evaluate the safety, tolerability and preliminary efficacy of the combination, and will assume all costs associated with the study, other than expenses related to the manufacturing of nirogacestat. SpringWorks Therapeutics will also form a joint oversight committee with Janssen. Pending discussions with regulators, the study is anticipated to commence by early 2021.

In addition to its ongoing clinical collaborations with BCMA-directed therapies, SpringWorks is also currently conducting a global Phase 3, double-blind, randomised, placebo-controlled clinical trial (the DeFi Trial) to evaluate nirogacestat in adults with progressing desmoid tumours.