With worrisome COVID-19 variants cropping up, developers including the likes of Gritstone Oncology Inc. and Vir Biotechnology Inc. continue their efforts to invent new vaccines that may get around the drawbacks of existing shots if they turn up.

Reports have differed regarding the SARS-CoV-2 variants, with New York-based Pfizer Inc. and Biontech SE, of Mainz, Germany, reporting their Comirnaty vaccine can hold its ground against B 1.1.7, first detected in the U.K., while researchers in South Africa say virus variant 501Y.V2 is capable of dodging neutralization by monoclonal antibodies as well as convalescent plasma. Moderna Therapeutics Inc., of Cambridge, Mass., provides the other vaccine, called mRNA-1273. A lab at Rockefeller University recently offered research suggesting that both products block infection by emerging variants, though manufacturers will continue to adjust their products as more evidence rolls out.

Meanwhile, Emeryville, Calif.-based Gritstone has gained the spotlight by way of its deal with Genevant Sciences GmbH, of Basel, Switzerland, whereby the former gained a nonexclusive license to Genevant’s lipid nanoparticle technology to develop and commercialize self-amplifying RNA vaccines against SARS-CoV-2. A phase I trial sponsored by the U.S. NIH is expected to start in the first quarter of this year. Gritstone is advancing Coral, a COVID-19 program to develop a second-generation vaccine with support from the NIH and the Bill & Melinda Gates Foundation and a license agreement with La Jolla Institute for Immunology.

Wainwright analyst Sean Lee noted in a report that, “unlike currently available first-generation vaccines, which only target the COVID spike protein, Coral uses the company’s Edge platform to identify a wide range of new potential target epitopes, which could make the vaccine effective against the virus even if it continues to mutate.” The vaccine deploys a chimpanzee adenovirus primer plus a self-replicating RNA booster, an approach that “combines the technologies used in the current Astrazeneca plc vaccine (chimpanzee adenovirus-based), and Moderna and Pfizer vaccines (both RNA-based) for even greater effect.” The current Coral candidate can target 15 different, highly conserved epitopes, Gritstone said.

London-based Astrazeneca’s AZD-1222 was co-invented by the University of Oxford and its spin-out company, Vaccitech, and uses a replication-deficient chimpanzee viral vector based on a weakened version of a common cold virus that causes infections in chimpanzees and contains the genetic material of the SARS-CoV-2 virus spike protein. After vaccination, the surface spike protein is produced, priming the immune system to attack the SARS-CoV-2 virus if it later infects the body. The product gained emergency use authorization (EUA) from the U.K. Medicines and Healthcare products Regulatory Agency late last year. It’s been renamed COVID-19 Vaccine Astrazeneca.

‘Hyper-variable’ vs. flu

Back to Gritstone’s Coral, which failed to thrill Baird analyst Madhu Kumar. “We don't deign to act as if this COVID-19 vaccine is going anywhere,” he sniffed in a Jan. 20 report. “We are unimpressed by Gritstone’s preclinical data, since the clinical bar for efficacy [with the Pfizer and Moderna vaccines] is already very high, leaving little ground for Coral to improve upon.” Existing COVID-19 vaccine makers “could readily adapt to new vaccine-resistant variants,” he said. “Even if our epitope analysis is wrong and vaccine-resistant variants of COVID-19 emerge, we still do not believe Coral will have any competitive edge in this space.”

Vir, of San Francisco, and London-based Glaxosmithkline plc (GSK) made known an agreement with the U.K.-based initiative called Agile to evaluate VIR-7832 in patients with mild to moderate COVID-19 in a phase Ib/IIa trial. VIR-7832 is a neutralizing COVID-19 antibody that preclinical data suggest has two distinguishing properties: an enhanced ability to clear infected cells and the potential to enhance virus-specific T-cell function, which could help treat and/or prevent COVID-19 infection, the companies said.

Also in the works by Vir is VIR-7831, “on track to emerge as best-in-class SARS-CoV-2 antiviral treatment, in our view,” Wainwright’s Patrick Trucchio said in a report. “We identify at least three variants that appear to elude several first-generation monoclonal antibody antiviral treatments, including Eli Lilly and Co.’s bamlanivimab and Regeneron Pharmaceuticals Inc.'s casirivimab and imdevimab, which received EUAs from the FDA in November.” However, “given the T-cell function in VIR-7832, we believe it could demonstrate superior efficacy to VIR-7831 and eventually overtake that compound” as Vir and GSK's lead player in COVID-19. Baird’s Kumar, though, wasn’t impressed by Vir, either, given the lead taken by already available products.

Inevitably, COVID-19 variants became a major topic in the key opinion leader call hosted Jan. 20 by Canaccord Genuity. George Rutherford, professor of epidemiology and biostatistics at the University of California San Francisco Medical School, made comparisons to the seasonal flu and to the 1918 flu pandemic, which killed at least 50 million people worldwide and about 675,000 in the U.S., according to the CDC. “The SARS-CoV-2 coronavirus has a much higher attack rate, 60%-70%, meaning that more than 60% of people who are at risk would become ill due to coronavirus exposure, whereas the attack rate of the seasonal flu and the 1918 flu is/was 5%-20% and 30%, respectively,” Canaccord’s Edward Nash wrote in a Jan. 20 report. The COVID-19 surge in November came just after discovery of the variants. “Rutherford explained that in addition to the higher R0 [or reproductive number, which designates the average number of people who will contract a contagious disease from one person who has it] of the coronavirus, which is hyper-variable compared to influenza, it may be possible that the mutations are related to an increase in cases in some areas at some time point which he referred to as a ‘positive-pressure effect.’ One example he gave was the emergence of the German strain [of COVID-19] in March 2020, after the original China strain. Since this mutant strain has a stronger transmission rate and is more infectious, it soon became the dominant strain in most of Europe and later the dominant strain in the U.S,” Nash wrote.