Does the world need more COVID-19 vaccines? These companies think there's still room for improvement

The ultimate COVID-19 vaccine will be able to tackle all emerging coronavirus strains, easy to store and quick to manufacture. And yes, there's still time for the stragglers who were beaten to the punch by Pfizer, BioNTech and Moderna—at least according to the companies still trying to get in line. 

Not to mention, just 60% of the world has been vaccinated, according to the University of Oxford’s Our World in Data database. The rates are higher in richer regions like the U.S. and EU, while the need is great in less developed nations.

But the window to contribute to the vaccine fight is closing. A new report from Morningstar sees demand for boosters remaining heavy in 2022 but dissipating over 2023. If a company isn't already filing for authorization, they'd better get on it.  

Jean-Francois Toussaint, Ph.D., head of research and development for Sanofi Pasteur, said 20 billion doses of existing vaccines are expected to be available this year. So where does that leave remaining companies, like Toussaint’s, that have shots in the pipeline?  

Three key opportunities remain for vaccine makers: differentiation, global distribution, and pan-variant shots.  

RBC Capital Markets analysts predict that strain-specific boosters are going to be important going forward, but the key is how quickly they can be whipped up in pharmaceutical companies’ labs. Pfizer has promised they can turn around strain-specific boosters in three months. But even if that's the case, RBC and others aren't sure how relevant the new shots will be to the current omicron wave.  

“Either you have to play whack-a-mole and keep chasing the virus" with updated versions of the current mRNA vaccines, or you go after parts of the virus that "have not changed over many iterations," Allen added.

That's what Gritstone is trying to do, which Allen calls "future-proofing.” This will be key to establishing a strong presence in the vaccine market as we enter the third year of the pandemic, Allen said. First-generation shots go after the spike protein, but targeting that highly mutable portion of the virus means waning efficacy with each new variant. Gritstone's shot aims to attack the spike but also the unchanging parts of SARS-CoV-2 by inducing the body’s T cell response, which helps pad the response against infection. 

COVID-19 is still in the pandemic stage. But once it enters endemic territory, that “doesn’t mean it stops killing people,” Allen said. Companies like Gritstone should look at a pan-coronavirus approach, considering this is the third coronavirus epidemic or pandemic in 20 years, including SARS-CoV in 2003 and MERS-CoV in 2012. 

More variants are likely to emerge after omicron, but RBC said natural infection, coupled with widespread vaccination should make the next waves settle into more predictable seasonal patterns much like the flu. But that’s only if infection with omicron builds immunity to whatever strain emerges next, and the science is still unclear on that one, according to an RBC note.  

“Of course, what we worry about is that we’ll end up with a transmissible and more dangerous virus circulating. Given recent history, nobody can tell you that’s not going to happen. You have to be concerned about that,” Allen warned.  

Protection for all 

Allen says scalability is going to be crucial to next-generation vaccines. Many pockets of the world have yet to receive any shots. “As we all know, global protection actually protects us all,” he said. In parts of the world that are already highly inoculated, biopharmas looking to enter the vaccine market will have to test their jabs as boosters, he said.  

Many are already doing that, like Sanofi/GSK, Valneva and Arcturus, which have all pivoted to testing their shots after primary vaccination with one of the authorized or approved shots. Gritstone’s vaccine is in testing as a booster for people 60 years or older in the U.K. who received two doses of the AstraZeneca jab. Additional studies will test the vaccine in people who are immunocompromised and those with HIV.  

“Let’s be clear, if you’re doing any vaccine trial now in North America or Western Europe, you need the boosting study. Everybody who wants to have a vaccine, has had one, and therefore we’re boosting behind existing products," Allen said.

Morningstar sees the booster market finally becoming competitive in 2022, after Pfizer/BioNTech and Moderna have dominated in the U.S. Other markets, including China, have been tapped by inactivated virus vaccines from Sinovac and Sinopharm and AstraZeneca’s adenoviral vector vaccine, according to Morningstar. 

Research out of Israel, where a fourth-dose booster is in testing, suggests a limited impact on infections compared to a three-dose schedule. This means strain-specific boosters for future variants are needed. And, most importantly, those boosters should be pan-variant, according to RBC. 

Despite regulators' openness to emergency authorizations for vaccines, the road to getting a new shot authorized or conditionally approved in majority-vaccinated regions like the U.S. and EU remains difficult. This is evidenced by Novavax’s struggles with its protein-based jab.

Novavax originally wanted to ask the FDA for authorization by May 2021, and many delays later, the Maryland biotech now anticipates a U.S. request this month after getting green lights in Australia, South Korea and India in the past four weeks.  

Elsewhere, Medicago asked Canadian regulators to approve its plant-based jab last month. Valneva expects potential regulatory approvals this quarter for its inactivated vaccine.   

The World Health Organization is conducting plenty of research on a number of vaccine candidates, which offers an opportunity for companies still trying to get in the game. The organization reports 140 vaccines in clinical development and 194 in pre-clinical development as of Jan. 18.  

The final attribute, differentiation, could also be important. The mRNA shots have clearly cornered the larger markets. While distribution around the world has improved since the early days of the pandemic when storage was a concern, there's still room for more stable vaccines using more traditional technologies.  

Companies with mRNA shots in the pipeline could see some uptake if they're able to improve on delivery. Sanofi, which is eyeing mRNA technology for future vaccines, such as influenza and RSV, wants to improve on tolerability in the next generation as well. The existing mRNA vaccines are known to cause many recipients to feel sick the day after. This is fine in the context of a global pandemic, according to Toussaint, but next-generation mRNA shots need to improve on those side effects.

Capricor Therapeutics is making a next-gen mRNA vaccine that is delivered using an exosome, an extracellular vesicle, rather than lipid nanoparticles with the aim of averting weight loss and heart inflammation concerns, said Linda Marbán, Ph.D., CEO and president, in an interview. The jab is meant to induce B-cell and T-cell responses by going after both the mutating spike protein and the nucleocapsid protein, which is mutated in omicron but not other variants, the CEO said. The biotech anticipates asking the FDA about initiating a booster shot clinical trial in the next quarter or two, she said.

Intranasal, oral or patch administration could make for a quicker and cheaper vaccine that would appeal to people who are scared of needles, according to Gavi, the international vaccine alliance that counts the WHO, Bill & Melinda Gates Foundation and others as partners.

AstraZeneca is testing a nasal version of its authorized vaccine in humans. A VC-crowdfunded biotech that emerged in 2020 called MigVax is working on a COVID-19 vaccine pill, according to Gavi, although no clinical trials for the company are listed on the FDA's database. 

Another idea is to boost existing vaccines with an adjuvant, which gives the immune system an extra kick to fire up protection against a virus. GSK offered up its proprietary adjuvant technology early in the pandemic for use in vaccines under development.

The company said at the time that adjuvants can allow for more doses to be produced using fewer ingredients, which can help with manufacturing. But Gavi notes that adjuvants could also protect against waning immunity that has been seen with existing COVID-19 vaccines, but more research needs to be conducted. 

The adjuvant is being used in GSK's collaborations with Sanofi, Medicago and SK Bioscience. Valneva's shot also uses an adjuvant. 

Morningstar predicts that protein-based vaccines from Sanofi-GlaxoSmithKline and Novavax could find space in the market, as could an upcoming shot out of the Walter Reed Army Institute of Research called the spike ferritin nanoparticle vaccine. That prospect is entering phase 2/3 testing this year. Japan-based Shionogi is in a phase 3 trial for its recombinant protein-based vaccine, S-268019. 

“We don't believe there is much room for additional mRNA vaccines. Why? Because the ones that are out there are doing a fairly good job,” said Toussaint during Fierce JPM Week.  

Source