Universal Flu Vaccine: Can Biotech Companies Deliver?
We love animals here at Nanalyze. We once considered doling out a few hundred dollars for the 30-second opportunity to hold a panda in China, but then figured the money would be better spent on visiting cannabis clubs in Europe. But you know what animal we won’t touch? A squirrel. Why? Those little buggers carry the plague, as in the bubonic plague, as in the Black Death, as in the “Bring Out Your Dead” Monty Python skit. The plague killed up to 200 million people in the 14th century. Only one pandemic in world history has come close to that level of devastation—the 1918-19 influenza outbreak known as the Spanish flu. It killed as many as 50 million people, and a century later we’re no closer to a universal flu vaccine as we face the worst flu season in nearly a decade.
The U.S. Centers for Disease Control (CDC) and Prevention estimates about 50,000 Americans will die from the flu this year, similar to what happened in 2014-15. Most of the country (see map above) has been hit hard by influenza. This year’s vaccine was only about 39 percent effective (at last estimate), meaning that it decreased the number of cases by 39 percent. That’s pretty lousy considering that a big pharma company like Sanfoi raked in about $1.68 billion for its top-selling influenza vaccine in 2016.
The flu is a contagious respiratory illness caused by influenza viruses that infect the nose, throat, and sometimes the lungs, according to the textbook definition from the CDC. Influenza viruses come in four flavors: A, B, C and D. It’s the influenza A and B viruses that prompt many of us to get a painful jab in the arm each year and hope for the best. The influenza A virus, which is generally responsible for the most severe cases, gets even more complex in its genealogy with a number of different subsets and strains.
It takes months to create seasonal flu vaccines while the viruses are incubated in eggs. And it’s a guessing game, as experts identify which strains may be in play for the upcoming flu season. The problem is that they often guess wrong or the virus strains evolve, making the vaccine less effective. Plus, the vaccine only targets three or four of the most likely strains. That’s why scientists, a few startups and even publicly traded drugmakers are working on a universal flu vaccine.
Of Mice and Men
For example, researchers from Georgia State published a study this month in the journal Nature Communications that showed promise for developing a universal flu vaccine for influenza A strains. To understand a bit about what they did, you have to picture the flu virus, which under a microscope looks like a round pincushion with flat-headed pins sticking out. Seasonal flu vaccines target the heads of the pins—surface proteins called haemagglutinin (HA) and neuraminidase (NA)—to goad the body’s immune system to kick out antibodies that fight the disease. But the virus is constantly evolving, along with those surface proteins, which is why we need to hatch a new vaccine each year.
The scientists at Georgia State developed a drug that attacks the stalk of the protein, which doesn’t really change. Mice vaccinated with double-layered protein nanoparticles targeting the stalk of the HA protein produced long-lasting immunity against various influenza A virus strains, according to the scientists.
As investors (and possible candidates for the apocalyptic pandemic), we’re more interested in companies doing clinical trials involving our fellow primates that are producing results inching toward commercialization.
Attacking Flu at Its Core
That brings us to Vaccitech, a 2016 spin-off from Oxford University that raised £20 million ($27 million) from Google and Sequoia Capital, among others, in a Series A this month. That brings total funding to £30 million ($42 million). While the company is developing a portfolio of vaccines that include everything from prostate cancer to HPV, its universal flu vaccine took center stage when the news broke about its most recent funding given the current pandemic.
Like the researchers at Georgia Tech, Vaccitech’s vaccine, MVA-NP+M1, bypasses the surface proteins but instead goes after the unchanging core proteins inside the pincushion, which more readily lends itself to a universal flu vaccine. Instead of stimulating antibodies, the Vaccitech vaccine boosts influenza-specific T-cells that kill the virus before it spreads through the body.
The vaccine is in a Phase 2b clinical trial with more than 800 people aged 65 and older enrolled in the first year of a two-year project. The study will eventually involve about 2,000 people and is scheduled to be completed by October 2019. An earlier clinical study confirmed that the vaccine is safe to use on humans.
Fighting Virus with Virus
Vaccitech isn’t the only startup with a universal flu vaccine in clinical trial. Founded in 2007, FluGen out of Madison, Wisconsin, has raised $37.8 million. It took in more than $20 million last year between a $14.4 million Department of Defense grant, $5.5 million in debt financing and a $2 million Series A. Spun out of the University of Wisconsin-Madison, FluGen takes a different approach to developing a universal vaccine. The company has genetically altered a virus that can reproduce only once in the human body but won’t make you sick. The idea is that if you “get the flu” from the vaccine, then the odds of getting sick the next year are reduced dramatically, as the faux live virus elicits a strong immune response in the human body.
A 2016 safety test of the vaccine, called RedeeFlu, didn’t raise any red flags and showed that it was hitting the right parts of the immune system, according to FluGen. A clinical trial this year will include about 100 people, half of whom will get the vaccine while the rest receive a placebo. And then all of them, isolated for 11 days in a facility in Belgium, will get a dose of a live flu virus to see what happens. (If the zombie apocalypse starts in Belgium, you heard it here first.) FluGen hopes to have results by the end of the year before moving on to larger clinical trials. Target date for FDA is approval is 2025.
In the course of our research we came across a young startup out of Austria called Vacthera that is developing a universal flu vaccine, as well as cancer immunotherapies. While there were few details about the company’s technology that could be understood by someone without a PhD in virology, the basic gist seems to be that Vacthera is developing a universal vaccine, UniFluVec, similarly to FluGen by genetically modifying a virus. In this case, they remove a particular immune-suppressing protein (NS1) that helps elicit a powerful immune response in the body. The company thinks its product could infer immunity up to five years with a nasal spray.
That sounds awfully similar to an approach taken by Vivaldi Bioscience, a startup based in Fort Collins, Colorado, that was founded in 2006. It has taken in $27 million in funding, though the last time was way back in 2010. The company has conducted four clinical trials of its deltaFLU LAIVs vaccine, which involves a live genetically modified virus where the NS1 protein has been deleted, preventing the virus from replicating, and causing an immune system response that calls in antibody-producing B cells and T cell troops to battle.
Investing in a Universal Flu Vaccine
Biotech startups aren’t the only companies looking to market a universal flu vaccine. We briefly mentioned Inovio Biosciences (NASDAQ:INO) as one of a number of public companies developing cancer immunotherapies back in 2015. The company is also working on a universal flu vaccine, and just published a study in the journal Vaccine that showed its latest vaccine candidate provided broad protection against all major deadly strains of H1 influenza viruses from the last 100 years including the dreaded Spanish flu. The vaccine is predicated on the company’s ASPIRE (Antigen SPecific Immune REsponses) platform that delivers synthetic DNA into cells where it is translated into proteins that activate the immune system.
A more pure play on a universal flu vaccine comes from BiondVax (NASDAQ:BVXV), an Israeli company that recently (and voluntarily) delisted itself from the Tel Aviv Stock Exchange to focus reportedly on the American market. BiondVax is taking a totally different approach to developing a universal flu vaccine, focusing on a peptide-based vaccine called M-001. You can read more about the nuts and bolts of the proposed therapy on their website. The company has completed a half-dozen clinical trials involving about 700 people. Shares are up +95% since their listing in September of 2016:
It’s preparing to begin a phase three study with 7,700 participants over two years in Eastern Europe. If there’s reader interest, we’ll delve more deeply into the company’s financials and technology in a future article.
Just keep in mind that any drug development, particularly the quest for a universal flu vaccine, is fraught with risk. We also came across a 15-year-old New Jersey company called VacInnate that had taken in about $130 million in funding to develop vaccines for flu, malaria and dengue fever, among others. It blinked out of existence in 2017, another victim of the deadly pandemic called failure.
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