Alnylam and Vir Biotechnology have identified an anti-SARS-CoV-2 development candidate, putting them on track to start testing the inhaled RNAi treatment for COVID-19 in humans around the end of the year.
The partners first disclosed a collaborative effort to go after COVID-19 in early March. At that time, Alnylam had synthesized 350 siRNAs targeting the SARS-CoV-2 genome, and Vir had just signed up to assess the antiviral activity of the most promising prospects to support the selection of a candidate for further development.
Alnylam and Vir now have their development candidate, known as both VIR-2703 and ALN-COV. At a concentration of 100 picomolar, the drug achieved 50% of its maximal effect in dose-response assays. Increasing the concertation by tenfold to one nanomolar boosted the effect to 95% of the maximum. The partners see scope to use VIR-2703 to treat and prevent COVID-19.
The figures are part of a snapshot shared by Alnylam and Vir to show the potency of VIR-2703. The partners also said several of the tested siRNAs demonstrated a 3-log reduction of viral replication in an in vitro SARS-CoV-2 live virus model and that the development candidate is predicted to have reactivity against 99.9% of the 4,300 publicly available SARS-CoV-2 genomes that met their analysis requirements. The siRNA is also expected to have reactivity against the 2003 SARS coronavirus.
Having identified a development candidate, Alnylam and Vir are now working to generate the data needed to start clinical development. The plan is to meet with the FDA and other regulatory agencies soon with a view to filing an IND to test the drug in humans around the end of 2020.
If Alnylam and Vir hit that target, they will have taken a drug development program from inception to human testing in less than 12 months. While other companies have, or are due to, reach the clinic ahead of Alnylam and Vir, they are either repurposing existing molecules or developing antibodies, a class of medicine that can typically move through early development faster than antivirals.
The upshot is Alnylam and Vir may come to market well after other COVID-19 treatments, but have a shot at delivering a differentiated candidate that can carve out a niche despite the competition. John Maraganore, CEO of Alnylam, called VIR-2703 “one of the most potent direct-acting antivirals targeting SARS-CoV-2 reported to date.”
Responsibility for finding out whether VIR-2703 can deliver on that potential will fall on Vir, at least initially. The deal between the two biotechs puts Vir in charge up to clinical proof of concept. At that point, Alnylam can opt in and split the cost and profits of taking the drug through the rest of development and on to the market.
VIR-2703 is one a clutch of COVID-19 projects underway at Vir and Alnylam. The partners plan to advance up to three more host factor-targeting development candidates for use in the treatment of COVID-19.