While the general population was focused on mask wearing and social distancing to combat Covid-19, the scientific community leapt into action and went into the lab. It was clear that no single entity would find a solution alone, and that the world would need more than one vaccine to fight the pandemic. Around the world, dozens of vaccine collaborations cropped up to bring together researchers from a variety of sectors—including academia, government, and industry—to put science to work.
Simultaneously, the US government moved quickly to purchase hundreds of millions of doses of future Covid-19 vaccines as part of Operation Warp Speed. Less than a year later, two vaccines have already been approved for emergency use in the US with more expected in 2021. But with 60 more vaccines still in clinical trials, the quest continues.
One of those making progress combines the core competencies of the two largest vaccine makers, GlaxoSmithKline (GSK) and Sanofi. They are developing a vaccine candidate based on the recombinant protein technology used by Sanofi to produce an influenza vaccine, and GSK’s established pandemic adjuvant technology. A partnership between these normally fierce competitors in the $50-billion vaccine market may appear counterintuitive, but this pairing is developing a vaccine that has shown encouraging results in adults aged 18 to 49 years, and it will be entering new clinical trials in February, going head-to-head in a comparative test with an approved vaccine. Results are expected in the second half of 2021. Now more than ever is the time to work together to meet the moment.
The Road to Clinical Testing
It might seem like coronavirus had broken down barriers and prompted companies to cross lines they might not have considered in the past, but it wasn’t the first time GSK reached “across the aisle.” GSK has long operated under the belief that in order to innovate, partnerships—with outsiders, Nobel Laureates, and even competitors—are the best way to advance science and save lives. And that unexpected philosophy is having an impact on the fight against coronavirus.
When the pandemic hit, GSK was ready to exercise the kind of flexibility that enabled it to ink the Sanofi partnership in a space of a few weeks—a Herculean task in the world of multinational pharmaceutical companies “Our goal is to work with the best and the brightest in areas we want to explore deeply,” says Dr. Hal Barron, the company’s Chief Scientific Officer and President of Research and Development. “As it relates to Covid-19, we were looking for collaborators that would advance our strategy in a way we couldn’t do on our own.”
That view is echoed by Barron’s counterpart at Sanofi, John Reed. Reflecting on how imminently logical it was for Sanofi and GSK to come together because of the scale needed, he said, “By working together, GSK and Sanofi are intending to produce one billion doses of the antigen and the adjuvant from the next year onward.”
John Lepore, Head of Research at GSK, agrees that an “always on” approach to collaboration allows the company to always be close to where innovation is occurring, especially in new fields that enable the development of new vaccines or treatments. “It’s a big world in which a lot of people are doing interesting things. It would be remiss of us to only look inwards,” he says.
Can a vaccine adjuvant help in the quest to scale a COVID solution?
It was clear right away that vaccines would play a crucial role in solving the pandemic, and researchers all over the world leapt into motion. At GSK, it was decided that the best way to help was to provide its strongest technology, their unique adjuvant, a combination of ingredients (like a protein, a lipid, or even a piece of DNA) that is added to boost a vaccine’s effectiveness.
It works like this: Vaccines contain a piece of a target virus in the form of a molecule called an antigen. When it enters your body, your immune system sees the antigen as an outside invader and mounts an immune response to attack it. This trains your body to successfully fight that foreign agent so when you come into contact—for real—with the viral molecule, your body is ready to protect itself. When an adjuvant is added to that antigen, the immune system is much more likely to see the viral molecule as foreign and it increases the likelihood and effectiveness of an immune response.
With a virus that’s impacting the entire world, vaccine manufacturers now have to produce hundreds of millions of doses of that antigen molecule. It’s a scale that would likely be impossible without an adjuvant precisely because it’s so effective in boosting immune response. When an adjuvant like GSK’s is present, the amount of antigen needed is reduced as much as tenfold. In other words, with an adjuvant in the mix, up to ten times more patients could be vaccinated.
“We’ve known for years we’re probably the leaders in this technology. We have some of the most effective adjuvants and an ability to monitor which ones are needed,” says Barron. GSK believes that through collaboration with competitors, the biggest impact they can have on the process is making sure their adjuvant technology is accessible to as many vaccine developers as possible. “It could be the difference between solving a pandemic and not solving it,” he says.
To stack the deck in humanity’s favor, in addition to Sanofi, GSK is contributing its adjuvant to several collaborations with companies and research institutions around the globe, three of which are now in clinical trials. That way GSK increase their number of “shots on goal” for a COVID-19 vaccine as these collaborations use different technologies to create antigens, and GSK believe more than one vaccine will be needed to fight COVID-19.
Back-up Plan: Antibodies, CRISPR, and a Whole Lot of Data
But GSK is looking beyond vaccines when it comes to coronavirus treatments. The company wants to prepare for several real-world possibilities. One obvious one is that despite the ‘race’, vaccines might take some time to become available to everyone around the globe. The other reality is that vaccines’ profiles will differ and might not be appropriate for all individuals.
They’re tackling a series of alternative ways to fight Covid-19 through a partnership with Vir Biotechnology, an immunology company renowned for developing drugs that target infectious respiratory diseases. The team-up was in early stages before the pandemic—GSK has a large respiratory franchise with medicines for asthma and COPD. The expectation was that it would get going in six months to a year. But once the coronavirus pandemic was underway, they pivoted to focus the joint research on Covid-19 and were able to fast track a deal in just 18 days.
The research GSK and Vir is doing leverages an overall understanding that the human body can be used as a data platform (a focus GSK has been pursuing during its 2-year partnership to develop medicines with genetic testing and analysis company 23andMe). For one part of this project, they’ve focused on developing a synthetic antibody, which is a machine-made version of a protein that the body’s immune system builds as a unique weapon to fight each new virus it encounters.
While current treatments involve injecting severely ill patients with antibody-containing blood plasma derived from multiple coronavirus survivors, GSK and Vir wondered if it would be more beneficial to analyze all of the available antibodies produced by humans, identify the one that was most effective at fighting the virus, then manufacture a synthetic version, and develop it as a therapy.
Barron says they asked themselves: “What if we bypassed the body’s approach and just made them ourselves? We don’t have to rely on the immune system.” Not only could this most-effective antibody be given to patients infected with Covid-19, it could also be used as a preventative and administered to high-risk patients before they even become infected.
Says Lepore, “There’s very likely to be a period of time where vaccination can’t control the virus in the entire population. The antibody is passive immunization. You’re immediately providing the antibody to the patient instead of the body making it.”
GSK and Vir started a Phase 3 study with the antibody in October 2020 and in December joined a NIH sponsored study for late-stage, hospitalized Covid patients. Barron noted the distinction of GSK and Vir’s treatment option. “It has a high barrier to resistance and has the potential to neutralize the virus and kill infected cells. This could allow this treatment to be effective for patients in hospital settings, where other antibodies have so far not shown an impact.”
"The timeline for starting the collaboration and executing on the clinical study was unreal, and COVID drove that” says Lepore. “We are two companies with scientific overlap in our thinking and mutual respect for each other having a continuous conversation about how we advance the science together.”
Using functional genomics to understand how genes behave
Another aspect of the Vir partnership is a technology that’s right on the cutting edge of genetics. Utilizing functional genomics, a field of science in which researchers study the purpose of individual genes in the body, the team hopes to see exactly how different genes impact coronavirus inside a cell. With the help of CRISPR, a technology that edits DNA, they will trigger gene mutations and watch how altering different parts of a cell makes it less susceptible to Covid-19.
From there, they will develop drugs that target those genes and help our cells better fend off infection. “It’s an unbiased way of identifying new biology,” says Lepore. In many ways, it’s the opposite of how drug discovery usually works. Normally, scientists develop drugs to fit within known treatment pathways, but in cases like the coronavirus where the treatment pathways are unknown, the genes will dictate the direction of research.
The Body as a Database
The use of CRISPR to discover where to focus in order to find new drugs is not limited to Coronavirus. In fact, none of this cutting-edge work is new to GSK. It’s all made possible because they already had in place a scientific strategy that goes beyond interorganizational collaboration. The broader vision, that the human body is the best place to find solutions to medical problems—to use the body as a database for making new discoveries—was already well underway. Covid-19 just turned out to be an ideal place to apply their existing strategy.
For example, in 2019 (well ahead of the pandemic) GSK started a dedicated lab in San Francisco working with CRISPR’s pioneer, Nobel Prize-winning biochemist Jennifer Doudna and her colleague Jonathan Weissman, focused on applying the technology to improve the productivity of drug discovery. “Imagine you can do experiments in human cells that allow you to understand the interactions of genes and how they contribute to the disease. That’s what we want to do using CRISPR technology.” And in turn it will help automate and improve the efficiency of research efforts. “Essentially, we want to be able to enable the brain to do the innovation and we let the robots do the mundane parts. And together I think that’s going to create an incredible resource for our entire community,” says Doudna.
Using the cell-altering tool alongside insights gained from the Vir partnership currently underway, GSK can apply the fruits of these partnerships to power cures beyond Covid-19, finding treatments for illnesses from cancer to cardiovascular disease to neurological disorders.
On a wider scale, GSK struck a deal two years ago with DNA testing company 23andMe to work together to leverage human genetics to find new medicines. (The rationale for this was established in seminal scientific papers by GSK scientists showing that genetically validated drug targets are at least twice as likely to succeed in becoming medicines.) 23andMe’s customers submit a sample of their DNA to the company and then answer an extremely in-depth questionnaire that covers the gamut from whether or not their hair is curly to what diseases they have. Then the company uses high powered analytical tools to search the database for similarities in patients who show, for example, that if they have a certain genetic variation they are more likely to have a specific disease. It is the statistical summaries from these studies, not the individual customer data, that is shared between 23andMe and GSK.
With 12 million customers—80% of whom have given consent to use their anonymized data for research— 23andMe has one of the largest crowdsourced databases of genetic and health survey information in the world. “We’re working together to identify novel associations between genes and diseases that can be converted to drug discovery programs with a much higher probability of success,” says Lepore.
Scientists from both companies then look at that genetic variation to determine if it is, in fact, that cause of the disease and use that information to develop treatments that target the gene. In this way, again, the human body is a database that allows GSK researchers to follow the science and let the body lead the way. (GSK also has collaborations with two country-level genetic databases, UKBiobank and FinnGenn, further enriching the ability to use genetic data from humans to inform drug discovery targets.)
Lepore says that approximately 70% of GSK’s targets in research are genetically validated, and since GSK joined forces with 23andMe, the companies have identified and begun work on around 30 novel research targets, the majority of which are joint projects.
Beyond Covid-19
Though no one could have predicted the pandemic, the institutional systems at work within GSK ultimately meant that stepping outside their walls didn’t have to mean treading outside their comfort zone to find solutions to this world-wide problem. The system of following the science, using the body as a database, and working with the best people for the job (even if they’re competitors) was already part of their day-to-day operations.
But that’s not to say there were no lessons learned fighting coronavirus. GSK saw that all of these problems could be solved even more quickly than they ever realized. And the new collaborations built in the last six months have the potential to live on long after the push against COVID-19. Barron says the pandemic prompted the heads of Research and Development at many major pharma companies to begin meeting three times a week to brainstorm and share data, plans, and learnings in real time. “The whole industry got together to see what’s possible,” he says. “I’m convinced it will continue post-pandemic.”
This story was produced by WIRED Brand Lab for GlaxoSmithKline
