HORMÆPharma has identified a family of small molecules that potently inhibit the proliferation of cells after de novo infection of naïve B cells by EBV. The proliferation of established EBV-immortalized LCL as well as the proliferation of EBV-associated B lymphomas are inhibited by these molecules. HORMÆPharma research identified the molecules’ target, which is a receptor present at the cell surface of B cells. Indeed, the molecules antagonize the basic constitutional activity of the cell receptor, thus revealing an unknown function for this receptor in the control of EBV infection (patents pending).
The HORMÆPharma’s lead compound HPh9.4 is an orally bioavailable small molecule, which inhibits the 3 major EBV-associated B cell events, the immortalization of naïve B cells, the proliferation of LCL and the proliferation of B lymphomas in ex vivo models.
In a model of patient-derived xenograft (PDX) of a human EBV-associated B lymphoma in the mouse NSG strain, HPh9.4 dramatically inhibits the lymphoma growth over a 3-week treatment without any obvious adverse effect.
HORMÆPharma is developing HPh9.4 toward the clinic for the treatment of three pathologies, for which EBV-infected B cells are the main driver of the disease, i.e., de novo infection of naïve B cells and LCL-like proliferation for PTLD, the persistence and pathogenic role of EBV latently infected B cells for MS, and the EBV-associated B lymphomas.