Celgene-backed FLX picks CCR4 antagonist for clinical trials

San Francisco (Pixabay)
San Francisco, near where FLX is based

FLX Bio has picked a clinical candidate from its CCR4 antagonist program. The decision positions the Celgene-backed cancer immunotherapy biotech to move oral small molecule FLX475 into the clinic later this year.

San Francisco, CA-based FLX emerged from Bristol-Myers Squibb’s $800 million takeover of Flexus Biosciences with a pipeline of prospects the Big Pharma decided it could live without. Fundraising rounds totaling $79 million followed, giving FLX the means to move some of its early-stage assets toward the clinic.

FLX475 is set to become first to reach human testing. FLX thinks the drug can disrupt the barrier of regulatory T cells that accumulate around tumors and stop the immune system from performing its cancer killing duties.

“CCR4 represents a key pathway by which tumors recruit regulatory T cells to suppress tumor immunity. By blocking this pathway with a CCR4 antagonist, it may be possible to prevent regulatory T cell recruitment to the tumor site, reduce the number of regulatory T cells in the tumor and importantly, enable immune activation and tumor killing,” Alexander Rudensky, chairman of FLX’s scientific advisory board, said in a statement.

FLX475 is moving toward the clinic on the strength of preclinical data presented by FLX earlier this year. Those results showed FLX’s CCR4 antagonists block the migration of regulatory T cells—in the tumor but not in peripheral tissues—and aid the expansion of activated effector T cells. Adding the CCR4 antagonist to anti-PD-L1 and anti-CD137 antibodies dialed up the tumor-killing effects of these drugs. 

FLX lists the CCR4 antagonist program as the most advanced in its pipeline, despite having started life with a FLT3 and CDK4/6 inhibitor that was already in phase 1. Flexus moved that drug, FLX925, into the clinic just before being bought by Bristol-Myers. And, armed with $50 million in series B funds, FLX was set to take it in into proof-of-concept study in patients with acute myeloid leukemia.

FLX925 has since disappeared from FLX’s pipeline, although a phase 1/1b dose-escalation trial is listed as ongoing on ClinicalTrials.gov.