A made-in-Alberta COVID-19 vaccine is taking a major step forward on the path to Health Canada approval with the start of a Phase 1 clinical trial.
Entos Pharmaceuticals, an Edmonton company led by CEO and University of Alberta researcher John Lewis, has shipped a vaccine for testing to the Canadian Centre for Vaccinology in Halifax. The clinical trial will test the safety of the DNA-based vaccine in 72 participants, split between young adults and older Canadians, with the aim of moving into a larger Phase 2 trial testing efficacy of the vaccine by late spring.
“Getting the first batch out is a huge milestone,” said Lewis. “The team is exhausted. They’ve been working non-stop since March 2020. It’s a big sigh of relief now that we’ve got that batch out and we’ll be looking on with a lot of optimism toward the clinical trial results.”
The vaccine is one of two being developed by Entos. Unlike conventional vaccines, it is DNA-based, meaning that instead of injecting a weakened form of the virus into the body, it uses engineered DNA to stimulate an immune response against the SARS-CoV-2 virus.
Many of the COVID-19 vaccines already approved globally use messenger RNA (mRNA), a similar but slightly different approach to DNA-based vaccines, and have shown great efficacy against the original strain of the SARS-CoV-2 virus. They have significant drawbacks, though.
“RNA is an unstable molecule, and those vaccines require minus 80 degree Celsius storage. That is a real challenge to scale the manufacturing and then distribute the vaccines to anywhere but urban areas,” said Lewis. “And we’ve seen those challenges, certainly with the worldwide rollout of these vaccines. People are over the moon about their effectiveness, but then are finding it a huge challenge to actually get the doses in people’s arms.”
Lewis noted that the Entos vaccine can be kept in the fridge for over a year and at room temperature for over a month.
“We need to get 16 billion doses worldwide to beat this pandemic, and we believe DNA is the perfect way to approach that,” he said.
According to Lewis, the vaccine has shown a strong neutralizing antibody response in pre-clinical testing and is expected to provide protection against the original strain of SARS-CoV-2 and its main variants currently circulating worldwide. It is also expected the vaccine will provide protection after a single dose—although that will need to be confirmed through the study.
Vaccine candidate made in Alberta
While Entos’ vaccine was conceived of through homegrown ingenuity, its physical production has been pushed forward through months of work at the U of A’s Alberta Cell Therapy Manufacturing (ACTM) facility.
ACTM opened in 2016, funded by both the federal and provincial governments, as a facility to help get innovative cell-based therapies from the lab to patients. It began working with Entos in the summer of 2020 in preparation for a clinical trial. In January, after months of laying the groundwork, it produced the batch of vaccine over a two-week period to the exacting standards required by Health Canada, and sent it on to a facility in Ottawa for fill finish—the process of putting the vaccine into vials. From there it was shipped to the site of the clinical trial in Halifax.
“You hear the government getting raked over the coals because Canada doesn’t have vaccine production capability,” said Greg Korbutt, scientific director of ACTM. “Well, we do. It’s small, but look, we made a Canadian COVID vaccine here at the U of A.”
“We’re not a commercial manufacturer, but you need a place like us so that it’s ready to go commercial,” added Gayle Piat, ACTM operations manager.
The team at ACTM is now working to incorporate fill finish capability at the facility, hoping to add much-needed capacity for the service in Canada and speeding up the process for other needs that arise in the years ahead. Though ACTM was not constructed with COVID-19 in mind, the pandemic, said Piat, has proven the need for such facilities in Canada and the foresight involved in its creation.
Building biopharmaceutical capacity in Canada
Since the summer of 2020, Entos has received $9.2 million in total funding to develop its vaccine, $5 million from the National Research Council of Canada Industrial Research Assistance Program and $4.2 million from the Canadian Institutes of Health Research. The funding has been enough to bring the vaccine to its Phase 1 clinical trial, but much more will be needed to keep it on the path toward final approval. To get it into people’s arms, the total cost could run into several hundred million dollars.
“On a shoestring budget, we’re going to be able to get our first candidate through the end of Phase 1. Then we’re hoping that the federal and/or provincial governments can step in and continue the development of our first candidate,” said Lewis. “They’ve indicated they’ll also fund Phase 2 activities for some Canadian companies, so we’re talking with them now about what the bar is for acquiring that funding.”
The company is also hoping that, after it shows the safety and efficacy of its first vaccine candidate, it will be able to secure additional funding to push its second vaccine candidate forward as well. It is the company’s pan-coronavirus vaccine, designed to provide greater protection against mutations to the virus.
“We know the U.K. variant and the South African variant seem to have evaded some of the protection of some of the vaccines that are out there, particularly the AstraZeneca-Oxford vaccine. So our second candidate contains all the variant sequences,” explained Lewis.
The value of multiple vaccines
While several vaccines have already been approved for use in humans, the team at Entos maintains there remains a need for others to reach the finish line. Along with the concern about the ability of biopharmaceutical manufacturers to significantly scale up RNA-based vaccines, adenovirus-based candidates that are more easily scalable have shown less than satisfactory efficacy—between 50 and 75 per cent—against the variants.
Despite recent assurances from the federal government that vaccinations will ramp up significantly in coming months, Lewis also said it could be well into 2022 before Canada could conceivably vaccinate its entire population.
“Canada and much of the world is depending upon these platforms to vaccinate their populations. I absolutely don’t think we’re out of this,” said Lewis. “I think everybody should get an RNA vaccine if they want one, but we simply cannot scale and deliver RNA vaccines to the world in a timely fashion. So I think we definitely need other options.”
To get there, though, said Lewis, firm and timely commitments will be needed in short order for both the Entos vaccine and other made-in-Canada solutions to reach the finish line.
“It’s actually not too late for Canada to make the needed investments in its vaccine development and manufacturing. If we invest early and decisively into solutions, we can get those solutions in a timely fashion.”