The Beginning
Although it may now feel like an entirely distant past, just three short months ago on January 22, Netflix released Pandemic: How to Prevent an Outbreak.
Over a year prior, our company Distributed Bio was tapped for this docuseries because of our work on broad-spectrum vaccine technologies for influenza (spearheaded by team lead Sarah Ives) that was eventually awarded a Gates Grand Challenge Award for “Ending the Pandemic Threat.” That Wednesday in January, the company watched the first three episodes together in a rented theater, the screening marked by Jake’s joking that no one would see the series due to the sheer number of titles of Netflix.
But in a turn of events that can only be termed a spooky coincidence, a novel coronavirus was spreading exponentially and the world was on its way to a pandemic. On January 23, the central government of China ordered a lockdown in Wuhan and other localities of the Hubei province, effectively quarantining 57 million people. Over the next few weeks, SARS-CoV-2 became seemingly the only thing the world could talk about — and Pandemic became one of the most popular titles on Netflix.
Life at Distributed Bio began to move at a breakneck pace right after the quarantine order in China. On January 27, Jake flew to Washington, D.C. with his wife Erin and baby daughter Seraphine to attend the American Society for Microbiology Biothreats conference and meet with DARPA (the Defense Advanced Research Projects Agency, an agency within the Department of Defense) and BARDA (the Biomedical Advanced Research and Development Authority, an office of the Department of Health and Human Services).
Dr. Anthony Fauci, Director of the National Institute of Allergy and Infectious Disease and now-member of the White House Coronavirus Task Force, was also in attendance. He remarked that the virus was likely no longer containable.
He was not shaking hands.
The BARDA meeting ended up being canceled, while the DARPA meeting still stood for the following day but just to discuss the novel coronavirus. Jake retreated from the conference and returned with a plan to engineer new medicines for the virus. When Jake, Dr. David Gangemi (Director of Virology), and Stephanie Wisner (a new team member working with Centivax, the spinout therapeutics company from Distributed Bio) eventually met with DARPA, the agency expressed interest — but they had already given funding away. Regardless, Jake decided to proceed, contacting Shahrad Daraeikia and Jack Wang at Distributed Bio to spearhead the effort to rapidly generate a neutralizing monoclonal antibody against the viral coat protein by evolving a panel of known neutralizing antibodies against SARS, a cousin of SARS-CoV-2. (Antibodies are proteins that serve as the soldiers of the body’s immune system that fight various pathogens in a highly specific, lock-and-key-esque relationship.)
The following week, he and Sarah flew to the Gates Foundation in Seattle, Washington to meet other awardees of the “End the Pandemic Threat” Grand Challenge award. Over the next five weeks, Shahrad and Jack ran the COVID-19 program as a side project; the disease continued to progress alarmingly — in Wuhan, then Europe, and then Seattle and New York.
On March 11, the World Health Organization declared COVID-19 a pandemic.
Moments of Truth
By March 16, six counties around the San Francisco Bay Area were given a stay-at-home order, bringing Northern California (and, eventually, the entire state) to a screeching halt. A COVID-19 case had been reported at Audentes, a company that shares the building with Distributed Bio, so both its sites had to be scrubbed. Our employees were growing increasingly concerned, as many were starting to learn of second or third-degree exposure to known cases. The COVID-19 project was progressing to demand more time and more people, just as the ability to wield more of either was quickly diminishing. Over the course of the day, Jake talked to employees about discussing their willingness and level of comfort to come in on a voluntary basis to work on the COVID-19 with their families.
That night, he went home feeling defeated, not knowing whether or not the effort was dead in the water. However, that question was answered just the next morning: Jake woke up to an army, the whole team engaged and ready to be the David to the Goliath of COVID-19.
This rallying cry took the fight to the next level. We designed an ultra-accelerated strategy to engineer and identify the optimal antibodies for therapeutics candidates, the entire company working on just this one project given health constraints — a remarkable experience for the team. We began working in shifts, days and nights and weekdays and weekends, braving engineering hiccups and supply chain interruptions in addition to the pandemic itself.
On March 30th, that resilience and streamlined efficiency paid off. We had official confirmation that we had succeeded and generated hundreds of hits with high-quality antibodies against the virus (with multiple extremely high-affinity, picomolar binders). Over the past month, we have filtered through these candidate molecules, identified our leads, and sent them across the world for other groups to run neutralization and in-vivo studies or utilize for diagnostic tests.
The Road Ahead
However, the fight is far from over. Our mission is to engineer medicines that matter at a price the world can afford. The specific goal with COVID-19 is two-fold: one, produce a medicine that would end the pandemic this fall by providing treatments in hospitals for those who are already sick — something a vaccine cannot do — and offering short-term immunity as a prophylactic for the healthcare workers and others at the front lines, and two, to produce a broad-spectrum antibody so we never have to worry about an outbreak from the coronavirus family ever again. But while it is scientifically demanding to engineer medicines that matter at such an accelerated pace, it is also a major financial challenge.
Distributed Bio has never taken venture capital money and is entirely self-funded, but the expenses of scaling up manufacturing and clinical trials run in the many hundreds of millions of dollars. We are actively working on expediting the process and acquiring funding from a variety of sources that don’t require us to compromise on our mission, but we are running into bureaucracies on a variety of avenues that are a challenge in a difficult time of crisis. At the same time, in part due to the release of Pandemic, we have attracted media attention from a variety of high-profile outlets ranging from The New York Times and MIT Technology Review to CNBC, MSNBC, and Fox, and we have built a strong grassroots support network that has become an invaluable part of this journey.
Although we’re just out of the discovery phase of the drug development process, a few exceedingly clear ideas have emerged over our work of the last few weeks that will certainly continue to unfold over the coming months.
First, our computationally guided immunoengineering platforms meant that a team of 30 people — and really 3 people for the first 6 weeks — completed engineering as fast as pharmaceutical companies with over $100 million of government financial support to engineering effective antibodies the fastest. If this shows nothing else, it demonstrates the emerging power of new technologies and, in the words of anthropologist Margaret Mead, to “[n]ever doubt that a small group of thoughtful, committed citizens can change the world; indeed, it’s the only thing that ever has.”
Second, it highlights how crucial it is that our goals are not myopic. As with a universal influenza vaccine and universal antivenom, we have set out to treat not only the current crisis, but also to target the SARS-CoV-3, SARS-CoV-4, and any future coronavirus threat that will ever attempt to plague humanity again by generating broad-spectrum anti-coronavirus antibodies. While extreme social distancing as a non-pharmaceutical intervention has proven vital to reduce death rates and keep healthcare systems above water, its socioeconomic impacts have been devastating. National and international shutdowns cannot be the answer for every pandemic or sub-wave of a pandemic. As a scientific community, we need to look to the future and ensure that we are solving the forever war against all versions of coronavirus, and as a global community, we need to fund those solutions in order to be prepared and able to act quickly.
Finally, our unique position compared to large venture-backed organizations of being an underdog, but one with extensive media exposure and global grassroots support, creates for us a better chance of an extra-financial objective of creating a permanently more healthy society. Science to create medicines is invaluable, but the people who receive the medicines should be the “why” behind the entire scientific system. The flexibility afforded by our financial structure as well as the strategic collaboration it necessitates enables us to address some of the fundamental limitations of pharma and traditional funding that do not reward medicines that shrink their own markets, price out patients from lifesaving medicines, and fail to reach major segments of the global population.
The COVID-19 pandemic is just the beginning. If we approach the next few months the right way and mobilize the international community, the crisis of this pandemic can be all but over by fall through the right combination of testing, contacting tracing, and just one successful clinically proven antibody therapeutic. And if we continue charging ahead, it will also be just the beginning of the fight for a pathogen-free humanity — engineering broad-spectrum medicines for the world to ensure that the next possible pandemic and every single one after that will never be anything more than a mild outbreak.
Stay healthy, and stay safe.
