Regeneron and 2seventy bio have revealed the candidate spearheading their CAR-T pact. Working with the bluebird bio spinout, Regeneron has selected MUC16 as the target for the first CAR-based solid tumor program.
Bluebird and Regeneron began working together on oncology cell therapies in 2018. Regeneron got the deal started by making a $100 million investment in bluebird, positioning it to work with the biotech on candidates against six initial targets over the course of the five-year research collaboration. Bluebird has since spun off its cancer assets to create 2seventy, where work with Regeneron has continued.
2seventy provided an update on the project on Tuesday. The partners are going after MUC16, a protein found on most ovarian cancers. Regeneron is already pursuing the target with other modalities, taking anti-MUC16xCD28 bispecific REGN5668 into the clinic in 2020, but evidently sees value in a CAR-T.
The cell therapy, bbT4015, is still some way from joining REGN5668 in the clinic, with 2seventy penciling in an IND filing for 2023, and relatively little is known about the asset at this stage. The little the partners have revealed gives an early glimpse into how antibody powerhouse Regeneron is approaching CAR-Ts.
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“Preclinical data have shown robust single agent (CAR T alone) activity, including in stringent tumor rechallenge models,” 2seventy wrote in a statement. “This program represents a platform for titratable pharmacologic combination approaches to enhance CAR T cell activity with the goal of developing a best-in-class cell therapy.”
To treat ovarian cancer via MUC16, 2seventy and Regeneron will need to address challenges related to the tumor microenvironment as well as target heterogeneity and off-tumor activity. The partners' attempt to rise to the challenges centers on a Regeneron binder against a highly prevalent membrane-retained fragment of MUC16 and the use of a titratable pharmacologic agent to counter the tumor microenvironment and off-tumor activity.
The candidate is a product of a collaboration designed to pair Regeneron’s antibody technologies with the cell therapy capabilities that gave rise to Bristol Myers Squibb’s anti-BCMA CAR-T Abecma. Through the combination, the partners set out to bring the power of CAR-T cell therapies to more tumor types. The deal saw the partners split the cost of getting to the IND stage and gave Regeneron a chance to take a 50% stake in some of the targets.