In mid-January, as cases of a mysterious illness climbed in China and began to appear in other parts of the world, Alex Zhavoronkov realized that this outbreak was becoming a major public health problem. As founder and chief executive officer of Insilico Medicine, a biotech startup based in Hong Kong—where measures to reduce the disease’s spread were already beginning to be put in place—he began to wonder what his company could do to help.
Insilico had never tackled viral diseases before; the company’s focus was on noninfectious conditions such as cancer, immunological diseases, and fibrosis. But Zhavoronkov realized that Insilico’s approach, which applies artificial intelligence (AI) for rapid novel drug discovery, could help identify potential therapeutics to fight the virus we now know as SARS-CoV-2.
Everyone, whether requested by the company priorities or just their own values, was willing to work endlessly around the clock.—Mikael Dolsten, Pfizer
Later that month, Zhavoronkov pitched the idea to his investors and colleagues. Some were concerned that pivoting to address the novel coronavirus might be a waste of resources. “They said, ‘Look, if you do this, we can’t spend too many resources, because it’s going to go away. It’s going to be like SARS,’” Zhavoronkov recalls. During the SARS epidemic of 2002–2003, a decade before he founded Insilico, there was a surge of interest in developing treatments and vaccines—but once the virus was contained, research interest and funding streams quickly dried up. Still, enough of the people he spoke with in January were convinced that this outbreak would be more serious, and they were willing to do something to help, even if it meant recouping costs later or not at all. (See sidebar, “Ensuring Global Access,” below)
Quickly, the team got to work on repurposing their “generative chemistry platform,” which uses machine learning algorithms to design potential therapeutic molecules. Initially, the researchers focused on identifying inhibitors for a key SARS-CoV-2 protease based on the crystal structure of the enzyme. They’re now working with collaborators to synthesize these small molecules and test them against the virus in the lab.
What started out as an outbreak in China has now spread to almost every nation in the world, infected millions of people, and killed hundreds of thousands. To deal with the global threat, numerous pharmaceutical and biotech companies have adapted their pipelines to COVID-19 over the last few months. There are now close to 400 compounds being evaluated as treatments or vaccines in various preclinical studies or clinical trials and more than 700 diagnostic tests either commercially available or in development. The need for rapid solutions has brought companies together, and has pushed researchers to work at breakneck speeds—often while dealing with complications brought about by lockdowns and social distancing measures.
Companies set up pandemic pipelines
As the novel coronavirus spread around the globe, scientists at many pharmaceutical and biotech companies started to think about how to lend their expertise—either by identifying potential solutions within existing storehouses of compounds and technologies, or by applying research platforms and expertise to identify new ones. “I think everybody probably felt the urgent need to contribute,” says Dan Skovronsky, the chief scientific officer of the global pharmaceutical firm Eli Lilly. “The question that many pharmaceutical companies had, including us, was: Where are our skills, capabilities, and knowledge, and how do we best apply them?”
For companies already focusing on virus-related diagnostics, treatments, and vaccines, the switch to COVID-19 was a natural one. Pfizer, for example, had been working on vaccines for various viral and bacterial infections long before COVID-19 emerged. In March, Pfizer announced a collaboration with the German company BioNTech to develop a vaccine. Within a few months, they’d launched clinical trials of their vaccine candidates in Germany and the US.
John Kelly, the CEO of Atomo Diagnostics, an Australian startup company that developed a rapid blood test for HIV, says that his team decided to make the shift after getting several queries from diagnostics companies about whether their platform could support a test for COVID-19. The main challenge, Kelly says, was the sheer quantity of tests that they were asking for. “The numbers that these companies were talking about were significantly beyond our existing volumes.”
We’re all asking ourselves: How do we continue to work this way, to bring this same sense of urgency and collaboration to other diseases?—Dan Skovronsky, Eli Lilly
For other companies, the shift to COVID-19 has meant delving into a new research area. Prior to the pandemic, for example, UK-based startup biotech Owlstone’s pipeline didn’t contain any virus-focused products. The company’s diagnostic tools, which are designed to identify specific chemical compounds in people’s breath, had been geared toward cancer detection and tracking the progression of conditions such as fatty liver disease. The pandemic got the team wondering whether SARS-CoV-2, which is transmitted through respiratory droplets, could be detected with their technology. “We very quickly put together a team with a range of different academic clinical partners, along with others interested in breath research,” says Billy Boyle, Owlstone’s CEO. Within a matter of weeks, they had designed a clinical trial to test the technique and obtained the necessary approval from the UK’s Health Research Authority. That study is currently underway.
Big pharmaceutical companies have also pivoted from their usual work. Before COVID-19 hit, therapeutics for infectious diseases had not been a focus for Lilly, says Skovronsky. But he and his colleagues realized there were certain areas—the development of therapeutic antibodies, for example—where their expertise could be applied to the pandemic.
In March, Lilly joined with AbCellera, a biotech based in Vancouver, Canada. AbCellera already had a platform designed to rapidly develop medicines during pandemics, which it had established with a grant from the US Defense Advanced Research Projects Agency (DARPA). Scientists at AbCellera had obtained a blood sample from a recovered COVID-19 patient, and after running the sample through its platform—which rapidly screened for potential therapeutic antibodies using a combination of techniques, including high-throughput imaging, genomics, and AI—had identified more than 500 potential therapeutic molecules. The two companies launched a Phase 1 clinical trial of one of those antibodies in June.
“[AbCellera] told us that they had this blood and were embarking on this project and said, ‘Is this something that you guys are interested in?’” Skovronsky says. “It took us about as long as it took to read the email to make the decision.” Within about a week, the two companies had signed a deal, with the goal of starting clinical trials of a new therapeutic within four months.
People and resources adapt to new projects
The launch of new COVID-19 projects has required companies to quickly mobilize staff and resources. As a result, people involved in those projects have been working longer-than-usual hours. “The pace that we’ve had to work to fight COVID-19 is different than our normal course of work,” Skovronsky says. “I have many teams that meet every day, seven days a week.”
Mikael Dolsten, the chief scientific officer of Pfizer global R&D, says the same has been true at his company. “This was the one occasion where I felt everyone, whether requested by the company priorities or just their own values, was willing to work endlessly around the clock,” Dolsten says. “I think everyone is inspired by the call to action to have a vaccine or treatment as fast as possible.”
Many of the staff working on COVID-19 projects have been reshuffled from some of the hundreds of clinical trials that drug companies have been forced to put on hold due to the pandemic. In March, Lilly announced that the start of most new studies would be delayed and that new enrollment in ongoing studies would be halted. According to Skovronsky, many of the staff who would have been working on these trials were redeployed to work on the COVID-19 research instead.
Other companies are shuffling staff around in a similar way. Owlstone’s Boyle says his company’s stalled trials freed some employees and resources to focus on COVID-19. “We’re trying to make sure that we can still deliver on those core programs,” he adds. “But [we’re] redeploying the resources into the specific areas of the COVID problem in the near term.”
All of this has to happen alongside measures put in place to contain the virus’s spread—culling the number of staff in the lab, for example, and sending home people who could do their job virtually. “Most of our laboratories are operating at the reduced scale because of the need for social distancing,” says Dolsten. “[In the labs], we have prioritized people at work on COVID-19 and certain lifesaving new medicines that are very close to coming to the clinic.”
Companies have had to be flexible in other ways as well. Insilico usually synthesizes its compounds in Wuhan, China, for example, so when the lockdown started in that city, that part of their work was put on hold. “We just started synthesis in March,” Zhavoronkov says, adding that, as the epicenter of the pandemic has shifted, they’ve been able to restart work in Wuhan. “I think a lot of people who were using biotech services from China, when China went into lockdown, they started shifting to Europe and the US. Now it’s the other way around.”
Companies seek collaborations to accelerate research
The pandemic has brought together people from many sectors—academia, industry, and government. “One of the wonderful things that’s happened during COVID-19 is that people are working together more so than I’ve ever seen,” says Gary Wilcox, the CEO of Cocrystal Pharma, a company working with scientists at Kansas State University to develop novel antiviral compounds to treat COVID-19. “Scientists don’t always join together in one great big group for the benefit of mankind. But here, there’s been a remarkable sharing of information.”
Some of these collaborations have been formalized as larger consortia made up of multiple companies, and in some cases also funding bodies and governmental agencies. “There’s been a really interesting pivot towards embracing open innovation and a willingness to team up with partners outside of the life science ecosystem,” says Angela Radcliffe, the research and development lead for life sciences at the consulting firm Capgemini.
It is very tempting to profit from this, but I think for at least the very first steps, it is important to keep things open.—Alex Zhavoronkov, Insilico Medicine
In March, several large pharmaceutical companies, including Eli Lilly, Novartis, Gilead, and AstraZeneca, formed a group called COVID R&D to share resources and expertise to try to accelerate the development of effective therapies and vaccines for COVID-19. That same month, the Bill & Melinda Gates Foundation, the Wellcome Trust, and Mastercard launched the COVID-19 Therapeutics Accelerator to bring researchers in industry and academia together to identify potential treatments. In April, the National Institutes of Health announced the launch of Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV), a partnership between federal researchers and 16 pharmaceutical companies to standardize the testing of therapeutics in both the lab and in clinical trials.
“There are still some companies out there who prefer to work in a more insular fashion, and that’s fine. But most of us are working together,” Skovronsky says. “I think there’s more to come, because if we have a successful drug or drug antibody, we’re going to have to work together in manufacturing it.”
Whether the accelerated rate of drug and diagnostics development or the heightened level of cooperation among different players in the business will last beyond the pandemic remains to be seen. Company leaders are thinking about how to apply the lessons being learned now to expedite the development of therapeutics for other conditions as well. “We’re all asking ourselves: How do we continue to work this way, to bring this same sense of urgency and collaboration to bear against all the other diseases—Alzheimer’s disease and cancer and autoimmune diseases and diabetes—that we work on?” Skovronsky says. “Because those patients need it also.”
Ensuring Global Access
As pharmaceutical and biotech companies rush to bring COVID-19 tests and therapeutics to the market, they have also faced increasing pressure from advocacy groups, humanitarian organizations, and investors to ensure that their products will be broadly available. Some advocates have urged governments to override patents and asked companies to commit their intellectual property to the public domain.
A handful of companies have announced plans to promote access to their products. For example, the pharmaceutical company Johnson & Johnson has promised that its effort to develop a COVID-19 vaccine with hundreds of millions of dollars from the US government’s Biomedical Advanced Research and Development Authority (BARDA) will be a nonprofit endeavor—and that if and when a product is available, the company will work with health authorities to ensure global access. Meanwhile, the pharmaceutical company Gilead Sciences, in addition to committing to donating 1.5 million doses of its experimental antiviral therapy remdesivir to the US government, signed deals with generic pharmaceutical manufacturers in India and Pakistan to distribute the drug to 127 countries that “face significant obstacles to healthcare access.”
Some companies are being more open with their intellectual property, too, at least at the early stages of research and development. Through initiatives such as the COVID-19 Therapeutics Accelerator, pharmaceutical companies including Eli Lilly have agreed to share proprietary libraries of molecular compounds for others to screen for potential COVID-19 therapeutics. These collections are shared “without worrying about [intellectual property] protection,” says Dan Skovronsky, the chief scientific officer of Eli Lilly. Insilco Medicine, although not a member of the Accelerator, has also released the molecular structures identified through its platform without patent protection, says the company’s founder and CEO, Alex Zhavoronkov. “Of course, it is very tempting to profit from this, but I think for at least the very first steps, it is important to keep things open,” he says. “Later, once we see that something works, we might be able to recover something.”
Still, many companies, including Gilead, are retaining patents on COVID-19-related products. “We want to do the right thing from a humanitarian standpoint,” says Cocrystal Pharma’s CEO Gary Wilcox. “But we also have to recognize our shareholders, and our shareholders expect us to have a return on their investment. That’s where patents come in.” In February, Cocrystal obtained an exclusive license to develop coronavirus drug candidates identified and patented by researchers at Kansas State University. Patenting is “just a part of good science,” says Pfizer Chief Scientific Officer Mikael Dolsten. “Without patents, this is not a sustainable ecosystem. Nobody would be able to afford to invest.”