FLX475: A CCR4 antagonist that mounts an immune response against a broad range of "charged" and virally associated tumors
* FLX475 is still in development and not yet approved for commercial sale
FLX475 is a small molecule CCR4 antagonist designed to specifically block the migration of Treg cells into tumors without affecting Treg elsewhere in the body. We are developing FLX475 for the treatment of a broad range of “charged” tumors, which represent cancer types we believe are most likely to respond to FLX475. In cancer, the secretion of certain chemokines from tumor cells and tumor-resident immune cells is responsible for recruitment of immunosuppressive regulatory T cells (“Treg”) to tumor sites. Treg represent a dominant pathway for downregulating the immune response, and thus may limit the effectiveness of currently available therapies such as checkpoint inhibitors. Therefore, blocking the migration of Treg has the potential to restore naturally occurring antitumor immunity as well as to synergize with a variety of both conventional and immune-based therapies, such as radiation, chemotherapy, checkpoint inhibitors, immune stimulators and adoptive T cell therapy.
We believe that the inhibition of CCR4 has the potential to bring therapeutic benefit to patients across a wide spectrum of tumors in a manner similar to other immuno-oncology therapies that have been shown to be effective against multiple tumor types, while also potentially deepening or broadening clinical responses to these therapies.
We have completed a placebo-controlled, double-blinded dose-escalating Phase 1 clinical trial of FLX475 in 104 healthy volunteers. FLX475 was well tolerated in both the single-dose and multiple-dose arms of this study and demonstrated dose-dependent inhibition of CCR4 with no observed immune-related adverse events or significant clinical adverse events. We are currently enrolling a Phase 1/2 study of FLX475 as a monotherapy, and in combination with pembrolizumab, in patients with charged and virally associated tumors and expect proof-of-concept data from the Phase 2 portion of the trial in the first half of 2020.