On December 12, we hosted an R&D Day in New York City. Alnylam management and key opinion leaders discussed the latest progress as well as plans for the future development of our RNAi therapeutics pipeline. At this event, we announced our pipeline growth strategy for development and commercialization of RNAi therapeutics across three Strategic Therapeutic Areas (STArs): Genetic Medicines, Cardio-metabolic Disease, and Hepatic Infectious Disease.
Chronic Liver Infection
PD-L1 is a cell surface protein that is believed to play a major role in suppressing the immune system in cancer and infection.
HBV and HCV infection of hepatocytes is known to lead to increased PD-L1 expression which could subdue the immune response against the virus. Further, monoclonal antibodies targeting PD-L1 and its T-cell ligand PD-1 have shown anti-viral effects in pre-clinical and early clinical studies, but are also associated with systemic toxicities.
ALN-PDL for the Treatment of Chronic Liver Infection
In the hepatic infectious disease area, we are also developing ALN-PDL, an investigational RNAi therapeutic targeting PD-L1 in development for the treatment of chronic liver infections. ALN-PDL is aimed at knocking down liver-expressed PD-L1 to reactivate an immune response against liver viral infection without the systemic toxicities observed with monoclonal antibody therapy. In pre-clinical studies published previously by Alnylam and collaborators, an siRNA targeting PD-L1 was shown to increase the endogenous immune response and viral clearance in a mouse model of liver adenovirus infection. We plan to advance ALN-PDL as an ESC-GalNAc-siRNA conjugate.