Hornet Therapeutics, a biotech company focused on developing treatments to address EBV-driven pathologies, has published data in Science, which reports IDO-1 to be a host enzyme hijacked by EBV. These data demonstrate that EBV requires IDO-1 to efficiently establish latent infection and causing downstream pathology.
Targeting an EBV host enzyme
The study specifically identified IDO-1-driven NAD biosynthesis as a metabolic pathway that EBV exploits to meet the bioenergetic demands of nascent infected B-cells.
Targeting this pathway with an IDO-1 inhibitor hinders B-cell transformation and EBV-driven pathogenesis in vitro and in animal models in vivo. This novel early intervention-approach with IDO-1 inhibition provides a therapeutic strategy to prevent EBV-associated diseases, including lymphomas.
EBV is a major driver of post-transplantation lymphoproliferative diseases (PTLDs) and responsible for a significant proportion of organ loss in solid organ transplant patients, as well as a widely suspected driver of Multiple Sclerosis (MS). The groundbraking findings reported in Science point at IDO-1 inhibition as a potential treatment mechanism for pathologies related to EBV latency.
IDO-1 inhibitors for combatting EBV latency
The use of Hornet’s proprietary, clinically-validated IDO-1 inhibitor, HTX-201, has already demonstrated significant impact on latency, tumorigenesis, tumour burden and survival in an experimental mouse model of EBV-driven PTLD.
The Company aims to first develop HTX-201 for the prevention of EBV driven PTLD, where in high-risk solid organ transplant recipients this dangerous complication develops in up to 30% of patients, and the fear of emergence of EBV-driven pathology is ever-present across all transplant populations.
By intervening early with HTX-201, Hornet is looking to simplify the management of transplant recipients in the first year post-transplant, when the risk for PTLD and graft loss is highest.
Based on the data now published in Science and with access to the clinically tested drug HTX-201, Hornet is poised to progress into phase 1/2 proof-of-concept clinical trials in solid transplant populations within the next 12-18 months.
Hornet emerges out of stealth with a strategic collaboration and licensing agreement with Kyowa Kirin, enabling Hornet Therapeutics to develop and commercialise HTX-201 (formerly known as KHK2455) in EBV-related diseases.
Professor Christoph Hess, founder and Chief Scientific Officer at Hornet Therapeutics added: “We have built a strong molecular and cellular understanding of the EBV–host interaction, and the propensity of the virus to cause malignancy and promote autoimmunity over the years. However, we unfortunately still lack an effective and specific treatment for EBV-driven diseases. Our data demonstrate that HTX-201 has the potential to hinder EBV latency in its primary host cells, the B cells. If our findings translate to clinical benefit it would be a huge step forward in this disease area.”
