CCR4, A Key Modulator Across the Immunological Continuum

Our proprietary drug discovery and development engine has identified the cell surface receptor CCR4 (C-C Motif Chemokine Receptor 4) as a drug target that potentially has broad applicability in oncology and allergic inflammatory diseases. Receptors such as CCR4 bind to chemoattractant molecules called chemokines that orchestrate migration and homing of cells to specific tissues throughout the body. Chemokines specific for CCR4 are secreted from tumors and from allergically-inflamed tissues, but are not highly expressed in healthy tissues. Our approach is designed to enable selective restoration of the immune response within tumor and allergically-inflamed tissues without systemically depleting immune cells and broadly suppressing the immune system, a side effect experienced with other approaches, including an existing CCR4 therapy. Each of our two unique drug candidates, FLX475 and RT193, target CCR4 in a manner we believe is well suited for cancer and allergic inflammatory disease, respectively.

FLX475: CCR4 Antagonist for Oncology

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 cells 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 and/or broadening clinical responses to these therapies.

RPT193: CCR4 Antagonist for Allergic Inflammatory Disease

RPT193 is a small molecule CCR4 antagonist that blocks the recruitment of inflammatory immune cells, known as type 2 helper cells (Th2 cells), which are clinically implicated in allergic inflammatory disorders. We ae developing RPT193 for the treatment of a broad range of allergic inflammatory diseases, the first of which is atopic dermatitis, a chronic inflammatory skin disease characterized by skin barrier disruption and immune dysregulation. We intend to initiate a seamless first-in-human trial in 2019 starting with Phase 1a single and multiple dose escalation cohorts in healthy volunteers followed by a placebo-controlled Phase 1b testing in patients with moderate to severe atopic dermatitis.