AstraZeneca, Syndax ally to test PD-L1 drug and CSF1R inhibitor in solid tumor patients

AstraZeneca's new Cambridge, U.K. R&D center and global HQ - 2nd floor
AstraZeneca's new Cambridge, U.K. R&D center (AstraZeneca)

AstraZeneca and Syndax have teamed up to test immune checkpoint inhibitor Imfinzi in combination with CSF1R inhibitor SNDX-6352. Syndax is set to put the cocktail through a phase 1b solid tumor trial to equip both companies to sponsor midphase trials to demonstrate its safety and efficacy.

SNDX-6352 is the second drug advancing down Syndax’s pipeline. The compound, like lead candidate entinostat, is designed to improve outcomes in cancer patients by reducing immunosuppression. But whereas entinostat targets HDACs, SNDX-6352 works by binding to receptors found on the surface of tumor associated macrophages (TAMs).

“It is thought that TAMS mediate immunosuppressive effects in the tumor microenvironment, which may limit the benefit of some immunotherapies, including those targeting PD-L1,” Syndax CEO Briggs Morrison, M.D., said in a statement. “SNDX-6352 has been shown to reduce the activity of TAMs, which we hope will translate to improved patient outcomes.”

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Syndax is currently testing SNDX-6352 as a monotherapy in 24 solid tumor patients. But, as with lead drug entinostat, its immunosuppression-focused mechanism means its long-term future may be as an enabler of other drugs, specifically checkpoint inhibitors. Minimizing immunosuppression in the tumor microenvironment could enable checkpoint inhibitors to initiate a more forceful attack on the cancer.

That idea is at the heart of Syndax’s clinical development program. Syndax has relationships with Merck, Genentech and the Merck KGaA-Pfizer partnership to test entinostat in combination with their checkpoint inhibitors Keytruda, Tecentriq and Bavencio.

The SNDX-6352 agreement marks the first time Syndax has turned to AstraZeneca to source a checkpoint inhibitor, despite Morrison serving as the Big Pharma’s CMO before joining the biotech in 2015. The SNDX-6352 collaboration is nonexclusive.