On May 4, 2020, Vir Biotech and Alnylam Pharma announced the selection of a development candidate for VIR-2703, an investigational RNAi therapeutic targeting the SARS-CoV-2 genome. The companies planned to meet with the U.S. Food and Drug Administration (FDA) and other regulatory authorities to discuss a potential accelerated path for filing an Investigational New Drug or IND equivalent application at or around year-end 2020, less than a year since program initiation. The companies goal was to advance VIR-2703 as an inhalational formulation for the potential treatment and/or prevention of COVID-19.

In its discovery efforts, Alnylam synthesized over 350 small interfering RNAs (siRNAs) – the molecules that mediate RNAi – targeting highly conserved regions of the SARS-CoV-2 genome, which were then analyzed bioinformatically and assessed in in vitro potency assays. Multiple highly potent siRNAs were identified that demonstrated a 3-log reduction of viral replication in an in vitro SARS-CoV-2 live virus model conducted by Vir.

In dose-response assays, VIR-2703 was shown to have an effective concentration for 50% inhibition (EC50) of less than 100 picomolar and an EC95 of less than 1 nanomolar in the SARS-CoV-2 live virus model measuring inhibition of infectious virion production. Further, VIR-2703 has predicted reactivity against greater than 99.9 percent of the over 4300 SARS-CoV-2 genomes currently available in public databases that meet analysis requirements, and is also predicted to have reactivity toward the SARS-CoV genome from the 2003 SARS outbreak. With this DC selection, Vir and Alnylam will work closely together to generate the data required to enable rapid commencement of clinical studies.

In addition to the development candidate targeting the SARS-CoV-2 genome, the companies will utilize Alnylam’s recent advances in lung delivery of siRNAs, with widespread silencing of gene targets in the respiratory tract in multiple cell types, including cells in the respiratory tract that may be the targets for SARS-CoV-2 infection. In addition, the companies will employ Vir’s infectious disease expertise and established capabilities to bring forward up to three additional host factor-targeting development candidates to treat COVID-19, and potentially other coronavirus diseases.

VIR-2703 is an inhaled SARS-CoV-2-targeting siRNA that may have utility for prevention or for treatment. It leverages Alnylam Pharmaceuticals, Inc.’s latest advances in lung delivery of siRNAs and may have applicability to other coronaviruses as well. VIR-2703 is the first development candidate selected in the company’s expanded collaboration with Alnylam for up to four RNAi potential therapeutics for COVID-19.