Relying on RNAi

Vir and Alnylam identify RNAi development candidate targeting SARS-CoV-2

Lori Lesko
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SAN FRANCISCO & CAMBRIDGE, Mass.—As hundreds of scientists work to discover a successful treatment to defeat COVID-19, Vir Biotechnology Inc. and Alnylam Pharmaceuticals Inc. believe the key lies in a development candidate for VIR-2703 (also referred to as ALN-COV), an investigational RNAi therapeutic targeting the SARS-CoV-2 genome.
 
RNAi is a powerful, natural cellular mechanism that is uniquely suited as an antiviral approach directed at coronaviruses, which have RNA genomes, according to the companies.
 
They plan 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 (IND) or IND-equivalent application at or around year-end 2020, less than a year since program initiation. The companies plan to advance VIR-2703 as an inhaled formulation for the potential treatment and/or prevention of COVID-19.
 
“I’m very proud of the quality and pace of work done by our scientists and with our collaborators at Vir to identify an RNAi therapeutic development candidate targeting the SARS-CoV-2 genome,” said John Maraganore, CEO of Alnylam. “To our knowledge, this is one of the most potent direct-acting antivirals targeting SARS-CoV-2 reported to date.
 
“As this pandemic continues to unfold, we are committed to acting with the utmost urgency to broaden and accelerate our efforts to develop investigational RNAi therapeutics against COVID-19, and potentially future coronavirus-mediated diseases.”
 
Akin Akinc, vice president and COVID program leader at Alnylam, added, “We envision that this product could have utility both as an early treatment for individuals who have been infected and in a targeted prophylactic setting (e.g., healthcare workers or family members of infected individuals). Based on the mechanism of action, which reduces viral replication, we expect that the product may prevent symptomatic disease or progression to severe disease.”
 
This family of viruses has proven to be an enemy in the past, as nearly 18 years after the SARS pandemic, there still has been no cure discovered for that virus.
 
“The SARS pandemic began in 2002 and was brought under control in July of 2003 as a result of isolation and screening of travelers suspected of having the virus,” Akinc explains. “Patients were treated similarly to how we’re treating those with COVID-19—with ventilators and antibiotics to treat pneumonia related to the illness. For some patients, antiviral medications and high doses of steroids to reduce inflammation in the lungs were used.”
 
“We are focusing our current efforts on testing VIR-2703 for COVID-19,” he continues. “However, based on the results of our initial testing, we predict there is a possibility it could be effective against other SARS genomes as well.”
 
The VIR-2703 program “began early this year in response to the emerging outbreak in China,” Akinc tells DDN. “At the time, while we and others in the field acknowledged the possibility of a serious global impact of the novel coronavirus outbreak, we did not foresee the kind of pandemic and global health crisis we are experiencing today.”
 
As China was shutting down its economy and ordering residents to quarantine at home, Alnylam began synthesizing over 350 small interfering RNAs (siRNAs), targeting highly conserved regions of the SARS-CoV-2 genome, which were then analyzed bioinformatically and assessed with in-vitro potency assays, Akinc says. These efforts ultimately led to VIR-2703.
 
In early testing, VIR-2703 has predicted reactivity against greater than 99.9 percent of the more than 4,300 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, according to Akinc. With this development candidate selection, Vir and Alnylam will work closely together to generate the data required to enable rapid commencement of clinical studies.
 
VIR-2703, as an inhaled SARS-CoV-2-targeting siRNA, may have utility for prevention or for treatment. It leverages Alnylam’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, which covers up to four RNAi potential therapeutics for COVID-19.
 
“While we are encouraged by the results we have obtained to date, we have not yet started human clinical trials, so it is too soon to tell if VIR-2703 will be effective against COVID-19 in people,” Akinc says.
 
In the context of a pandemic health emergency, “all resources and therapeutic approaches should be brought to bear,” Akinc states. “While we are optimistic about our research, we are also proud to be a part of the biopharmaceutical industry, which has come together in an unprecedented manner, to help address this global public health crisis. We are hopeful that the bright scientists working on this throughout the industry will win the battle against COVID-19.”
 
George Scangos, CEO of Vir, says with this development candidate targeting SARS-CoV-2 candidate now in hand, “we will further accelerate our efforts. Our ultimate goal would be to provide rapid worldwide access, if approved, to an effective therapeutic to combat COVID-19.”

Lori Lesko

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