Our proprietary drug discovery and development engine has identified several immune drivers that have the ability to be “tuned up” or “tuned down” to modulate the immune system, either to suppress an overactive immune response in allergic inflammatory diseases or to initiate an immune response against cancer.
Our lead drug candidates, zelnecirnon (RPT193) and tivumecirnon (FLX475), target the important cell surface receptor CCR4 (C-C Motif Chemokine Receptor 4). 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 to CCR4 are secreted from allergically inflamed tissues and from tumors, but not from healthy tissues. Our proprietary approach is designed to prevent the recruitment of disease-promoting immune cells into inflamed tissues and tumors in order to treat allergic inflammatory diseases and cancer.

“Down regulating” the inflammatory response

In inflammatory diseases, chemokines recruit helper T type 2 (Th2) cells to inflamed tissues. Once Th2 cells enter tissues such as the skin or the airways in the lung, they secrete proteins known to drive the inflammatory response. In atopic dermatitis, there are higher levels of these inflammatory ligands compared with healthy humans and these ligands also correlate with the severity of disease.
We believe that by inhibiting CCR4, our novel oral drug candidate zelnecirnon has the potential to bring therapeutic benefit to patients across a broad spectrum of inflammatory diseases, including atopic dermatitis, asthma, chronic spontaneous urticaria, allergic rhinitis, chronic rhinosinusitis and eosinophilic esophagitis.

Unlocking antitumor immunity

In cancer, the secretion of certain chemokines from tumor cells and tumor-resident immune cells is responsible for the recruitment of immunosuppressive regulatory T cells (Treg) to tumor sites. Treg represents a dominant pathway for downregulating the immune response, and thus may limit the effectiveness of currently available therapies such as checkpoint inhibitors. 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.
Our proprietary approach is designed to enable selective reactivation of the immune response within tumors without systemically depleting T cells or broadly suppressing the immune system, a side effect experienced with existing CCR4 therapies. 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.

The key to unleashing tumor-specific T cell responses

Hematopoietic progenitor kinase 1 (HPK1) reduces the T cell response to tumor cells by blocking the T cell receptor (TCR) signaling needed to mount an effective immune response against tumor cells. We believe that blocking HPK1 activity can enhance tumor-specific T cells and bring therapeutic benefit to patients with many different tumor types, either as monotherapy or in combination with other treatment modalities, including checkpoint inhibitors.