Candidates: VIR-2703 (ALN-COV) and other small interfering RNA (siRNA) treatments for up to nine infectious disease targets—including three host factors required for SARS-CoV-2 infection.

Category: RNA

Type: siRNA treatment(s) to be identified by Alnylam that target highly conserved regions of coronavirus RNAs. Alnylam has designed and synthesized over 350 siRNAs targeting all available SARS-CoV and SARS-CoV-2 genomes, which will be screened in in vitro potency assays, the companies said.

Status: Vir and Alnylam said May 4 they selected VIR-2703 (ALN-COV) as an inhalational formulation for potential treatment and/or prevention of COVID-19, and plan to meet with the FDA and other regulatory agencies to discuss a potential accelerated path for filing an IND or IND equivalent application at or around year-end 2020.

VIR-2703 was selected from more than 350 siRNAs targeting highly conserved regions of the SARS-CoV-2 genome that were synthesized by Alnylam, 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, Alnylam and Vir said, 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. VIR-2703 also showed predicted reactivity against greater than 99.9% of the over 4,300 SARS-CoV-2 genomes currently available in public databases that meet analysis requirements, the companies added, and was also predicted to have reactivity toward the SARS-CoV genome.

Alnylam and Vir agreed to use 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. The companies also agreed to use Alnylam’s 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 targets for SARS-CoV-2 infection.

In April 2, the companies expanded their 2-1/2-year-old siRNA collaboration, agreeing to develop novel siRNAs for up to nine infectious disease targets. The companies agreed to advance up to three additional host factor-targeting candidates to treat SARS-CoV-2 and potentially other coronaviruses. The companies named two of the three targets, angiotensin converting enzyme-2 (ACE2) and transmembrane protease, serine 2 (TMPRSS2), adding that the third may emerge from Vir’s ongoing functional genomics efforts to identify novel host factors pertinent to coronaviral infection and targetable by siRNA, mAbs or small molecules.

Alnylam agreed to discover potential coronavirus RNAi candidates, with Vir leading development and commercialization. Alnylam has the option to either share equally in any profits and losses associated with the development and commercialization of each coronavirus program—or instead earn development and commercialization milestones and royalties on net sales of any products resulting from the collaboration.

Another target for which a siRNA is to be developed is hepatitis B virus, the focus of the VIR-2218 (ALN-HBV02) program now in Phase I/II studies. The companies announced initial positive Phase I/II data for VIR-2218 in November 2019. The companies launched their partnership in October 2017, initially agreeing to develop up to five novel siRNAs to treat infectious diseases, starting with VIR-2218, plus RNAi products for up to four additional infectious disease targets of Vir’s choosing.

The companies expanded into coronavirus siRNAs in March.

COVID-19: 200 Candidates and Counting

To navigate through the >200 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:

FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.

DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data

KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.

TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.

GEN has also tagged the most common treatment types:


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