COVID-19: When RA Capital’s “secret” maps go public
by RApport
September 16, 2022
At RA Capital, we love our TechAtlas team and the super detailed Landscape Maps they create to help us understand what can otherwise be an overwhelming amount of information. These maps explain the comparative strengths and weaknesses of as many as hundreds of competitive and complementary technologies, drugs, devices, and diagnostics in various stages of development for a particular disease or condition. Think of them like medical treasure maps that lead to the most promising technologies and companies in any given disease area. You can probably understand why we can’t afford to do all that work and just publish the maps freely for the whole world to study.
Then COVID came along.
But we’re getting ahead of ourselves. What you need to know before we tell you about mapping COVID is that each map normally takes months to create, and most are in a state of revision at a pace that’s typically proportional to the rate at which the disease’s treatment and development landscape changes. The greater the unmet need and incentives offered for success, the more programs, the more developments (successes and failures), the more often TechAtlas needs to update the maps. The antibiotics map doesn't get a lot of attention because there’s just not that much going on. Cancer has a dedicated TechAtlas team that’s always in overdrive, with maps in a constant state of flux. The HCV map has been outright retired because there’s no clear need for better medicines (though we do need better diagnostics), whereas the HIV map might get a look every five years because it’s very well managed by existing drugs, and the bar for something truly transformative is so high (i.e., a true cure) that there’s just not much to track. Some maps cover a single disease such as pancreatic cancer, whereas other maps make sense of types of drugs, such as immuno-oncology agents, that are relevant to many different cancers, which can make them more dynamic.
These maps are mostly for internal use (though we’ll readily pull them up on our screen to share with visitors, and we’ve donated some to patient groups), but we make some out-of-date versions, such as those for Parkinson’s and Immuno-Oncology, available in full resolution on our website as demonstrations of what we mean when we say “maps.” (Our graphics team also put together their own map of dog breeds, letting members of the public be more rational about a very important decision… unless your child just yells “I want that one! Please please please!”)
So then COVID came along, with preliminary signals of worry in January and February turning into a clear realization by March 2020 that we were facing a true global pandemic. One that would require a technological response unlike anything we had ever seen in response to any other healthcare issue.
Of course we decided to map it, but we knew we had to map faster than ever before and decided that we would share what we learned publicly (here), in the same spirit that motivated medical journals to make their COVID content open-source and led companies to share data in unprecedented ways.
First we spun up a team; although COVID was just one disease (unlike cancer), the number of programs, the rate of new developments, and the need to update frequently required more person-hours than any other disease we had ever mapped. We would also need to respond to emerging controversies quickly (variants, masking, myocarditis, testing false-positives, and various home remedies) and explain our insights in more detail to a less informed audience than our maps are normally intended for, all of which would take more time.
We ended up creating three separate maps, one each for diagnostics, therapeutics, and vaccines, and updated each over a dozen times – sometimes as frequently as once every two weeks. What we learned about the maps’ utility to others surprised us and shaped our thinking about the direction we may take mapping in the future. RApport checked in with a few key members of the TechAtlas COVID team to “map out” their experience.
How did the team come together?
Alyssa Larson, Associate Director: TechAtlas and the RA Capital investment team are like Bonnie and Clyde; where one goes, the other follows. As RA’s investment strategy expanded (from public companies to crossover opportunities to earlier-stage private investment to new company creation), so did the scope of TA’s work: From building our foundational frameworks and knowhow to understanding and contextualizing innovation via our maps, we help the investment team gain or maintain conviction in our investments.
This has not always been easy. Maintaining and expanding on 135 maps across ~100 indications/capabilities whilst trying to keep up with the explosion of new companies and technologies that has entered the biotech sphere in the last decade is no small feat! The rapid expansion of RA’s investment strategy and AUM has meant that Associates constantly need to juggle and reprioritize projects to allocate bandwidth to the most impactful opportunities, but it also provides opportunities for collaboration.
TA’s also become a training ground for future members of our investment team and testing site for data analysis techniques. We continue to develop on all fronts; even the maps that have been with us since the beginning are being revamped and digitized.
Could you follow a standard mapping playbook, or did things change for the COVID map?
Shan Shan Wang, Associate Director: Of course things changed. For starters, just like everyone else we were suddenly working from home. And just like everyone else we struggled to adapt to video calls and find work/life balance for a while, but ultimately that didn’t hinder us much. Collaborative documents and spreadsheets have been a part of our processes for years, but without the ability to get together in a room they became even more important.
On top of that, the initial focus in addressing the pandemic was in diagnostics and vaccines. These are two spaces that we had not invested in extensively before, which is the main purpose of most of our maps. (Check out this piece for more on why we’d rarely invested in vaccines before.) But we’re all about “embracing the unfamiliar.” When they join RA, every TechAtlas associate is given a space outside of their expertise to be their first project. Some people working on the COVID map – myself included – had little-to-no experience in virology previously (it helped that our boss, Peter Kolchinsky, is a virologist). But our ability to quickly analyze a space – even one we’re not familiar with – is crucial when time-sensitive deals materialize, and many of the same skills came in handy in the first weeks of the pandemic.
How did you decide to structure the maps?
Alyssa: We started from a blank page and there were many ways to potentially make sense of the chaos of new programs we were seeing, but we had to pick a framework that the public would relate to. So we thought about what we would want to know as people with children or older loved ones at greatest risk. As we made our maps, some of us saw people we cared about get sick and go through hell. What were the solutions we would want for them? It was a personal way of looking at the problem. We’d think about what it would be like if someone we loved started coughing or had a headache, then search for answers to each question that then came to mind. What kind of test would you ideally want? How can you prevent the spread of the virus in my own home or during trips outside of the home for essentials? What kind of treatments would you want to stay out of the hospital, or in the hospital to stay off a respirator, or just not to die? And once there were vaccines, what kind of vaccine would you accept to blunt the pandemic and what kind would we want for the long run once the virus went endemic?
When did you know COVID would be endemic? Didn’t people think that it might be eradicated?
Nate Davis, Analyst: Right from the beginning we assumed it couldn’t be eradicated and analyzed the technology landscape accordingly. It was something we pressure tested along the way, but we were pretty confident that this kind of virus wouldn’t be that easy to get rid of. We knew it would have to eventually be managed, like how we manage flu and other viruses, and the question was simply “how?”
Why three maps? Why not just one?
Shan Shan: At first it was actually two. We had a diagnostics map and thought we could fit therapeutics and vaccines on the same map. But the number of programs we had to track just exploded, and at a certain point, that map reached a limit – we simply couldn’t fit any more on the page.
Our incredible graphics team, who had already been iterating on this map that required a lot of custom imagery at an unprecedented rate, helped us separate our research into three different documents. Even then, those maps kept filling up and we had to apply some filters for what was credible enough to include and what we could keep off the map, such as vaccines that had a very low chance of making it.
What kind of information did you put on the maps knowing that the public would be able to see it?
Nate: We made sure to include an explainer on how to read one of our maps as well as an FAQ. Otherwise, we didn’t have any special data that the rest of the world didn’t, but there was tons of information coming out every day. Early data sets from small clinical or even preclinical models would be published quickly, without peer review – which takes forever – and we would pounce.
We judged diagnostics by how sensitive they were, but also looked at their false positive rates knowing that a false scare would trigger unnecessary quarantine and social isolation.
We looked at the efficacy of drugs, but also their convenience and safety since we knew many people would need to take them. We looked at what would keep people out of hospitals but also what could help discharge them sooner from hospitals, which we could see were being flooded.
RA TV: Behind the Scenes at TechAtlas
Hear first hand what it’s like working at TechAtlas from two of our Associates.
And for vaccines, we looked at antibody titer levels and the types of assays each company used to try to compare among data sets and tried to see if these vaccines would only blunt disease severity or might be sterilizing, keeping the virus from spreading. We also focused on their side-effects; we thought the vaccines were likely to be safe (though myocarditis turned out to be quite a wrinkle for younger men) but that some would be better tolerated than others and that this would impact people’s willingness to take them annually.
There was so much to learn that impacted how we would be living our lives, whether we would need to keep masking, testing, isolating, etc. We also explored what kinds of COVID vaccines would be combinable with flu vaccines figuring that this would be the preferred approach eventually. One needle shot beats two, especially when you have a child screaming her head off at CVS at the prospect of a shot. That was on our minds as we searched for information, processed it, and distilled our insights on the maps for everyone else to absorb.
Was the constant news cycle around COVID a distraction?
Jonathan Pritz, Analyst: You’d think it would be a distraction, but it was more of an asset. “We learn collaboratively,” all the time internally, but the cooperation we saw around the biotech community early in the pandemic was incredible. Everyone was learning from each other, tackling the same problems, and sharing their progress publicly. While we were making our maps, others were aggregating the same data in other useful ways, much of which directly influenced our process. It was amazing to see how much we could get done like that.
And the news cycle helped make the work feel important, which anyone would find motivating, especially in those moments when the constant updates to the map felt like a slog. It’s not every day that we can talk about what we’re working on in TechAtlas with our friends and families and they actually find it interesting.
You must have learned a lot from talking to companies. Did that inform your maps?
Jonathan: Certainly – talking to companies was a great way to compare notes, which was really important given the rapid pace of progress. Many wanted to see where they were on the map and were excited to see that they had “made it.” Sometimes we debated how we classified them, which is all part of the process.
It was particularly exciting to be able to share things with companies that they weren’t aware of and to see them adjust their strategies. That was always the point of putting the maps out there – we didn’t want to just observe, we wanted to make a difference.
What’s an example of something you impacted?
Shan Shan: We think we probably accelerated some companies’ thinking around creating combination covid/flu vaccines. Those are still in the early stages, but there was a time when many people, including at vaccine companies, said that they would never be useful or necessary because COVID would go away or that vaccines would be so long lasting that you would only have to vaccinate people infrequently, unlike annual flu shots. We were pretty confident that COVID vaccines would be necessary annually and that seems to be where everyone is now headed. Some vaccine companies also assumed that the mRNA companies would win COVID entirely, but we encouraged them to stick with their COVID programs because mRNA would continue to have tolerability problems. So even if they came to market years late, they would still be able to supplant mRNA vaccines.
Who else did you talk to besides companies?
Nate: Everyone we could find. We spoke with doctors, nurses, regulatory experts, drug manufacturers, insurance folks, people at the FDA, some working on Operation Warp Speed and the UK response, researchers at big pharmas, members of Congress and their staff, and everyone else we could rationalize listening to. We’re pretty plugged in normally, but COVID shrank the world further, and it felt like everyone was debating every new development with everyone else in real-time.
Did any major decision makers look at your maps?
Jonathan: We know interested people from across our industry including major pharmas, small biotech, FDA, CDC, and more got the maps. How closely they studied them, we don’t know. The maps can be overwhelming to many people without a guided tour. But there were definitely some people out there working on various COVID programs that got into the weeds and let us know they loved the maps.
To expand our reach, we also did regular monthly RA TV webinars that anyone could register for to give tours of the maps and discuss implications of new developments. We saw that we were reaching medical professionals, investors, government workers, teachers, and all sorts of other people. And it was humbling. We saw people with limited knowledge in biology really making an effort to understand because of the widespread impact of the pandemic.
Did Dr. Fauci see your maps?
Jonathan: That would have been pretty cool but we have no idea. We never had a chance to speak with him.
Did RA make any investments related to the pandemic that were on the map?
Alyssa: Yes, and that’s what made it kind of tricky to share the maps in real time. The work we do to map all the different disease and technology landscapes is really meant to inform our investment decisions. So making these maps was also how we reached conclusions about what to invest in. Essentially, the public was seeing a big part of our rationale for investing in various companies in real time. However, valuation is an important part of every investment decision, as is management competency. Neither of which the maps speak to, so the maps aren’t everything an investor would care about, but they are useful. And so we had to get our Compliance team comfortable with the idea of putting so much of what is investment-oriented diligence out into the world in real-time.
But one of our core values at RA is “We do not let convention stand in the way of what is right,” even if that convention is one of our own. Turned out, our compliance team is also human and worried about COVID like everyone else. They saw the merit of us making this contribution to the global effort to stop the pandemic. Of course they made sure that the maps had all the proper disclaimers and caveats that they aren’t to be used for investment advice.
Do you think anyone used them for their investment decisions?
Shan Shan: We understand that we’re a well-known investment fund and people are interested in what we think about biotech stocks. So it’s possible that some people read the maps and made investment decisions based on them. But the thing is that our maps don’t give nearly enough information for someone to just follow them and pick stocks.
For example, we funded Novavax early on believing that their vaccine would be better than mRNA in terms of efficacy and safety, and would be only slightly behind Moderna and Pfizer. But it’s been nearly two years since the mRNA vaccines launch and Novavax still isn’t approved as a booster in the US and we are still awaiting data to see if they are comparable to mRNA in efficacy (though it is a much more tolerable vaccine). And at that time, Novavax stock had gone way up and way back down. So while the map points to what we believe has the potential to be the best solution, the word “potential” means that it’s not a sure thing. So the maps are more of a hypothesis that needs adjusting as new data come in.
What were the unique challenges of a map that was more public facing than anything TechAtlas made before (possible exception of the dog map)?
Peter Kolchinsky, Managing Partner: We discovered the massive divide between the kind of communication we're used to when we speak with companies and what the public watching our RA TV webinars would absorb. We discovered the power of analogies. For instance, an antigen is like a picture of a criminal and the adjuvant is like a burning torch shining a light on the picture so your immune system sees what you want it to see. But too much adjuvant and it will rev up your whole immune system to the point of inducing a fever and other unpleasant side-effects. It turned out that analogies didn't just help us relate to the public, they also helped to bridge the divide between the scientists on our team and those involved in other aspects of running our firm and investing.
COVID drove us apart into our respective homes, but it brought us closer in other ways. Teaching the public made us better at communicating internally, and everyone was interested in COVID in ways they might not be when it comes to prostate cancer or lymphoma since most people are healthy and so most diseases are abstract to them, at least for now. But COVID had a leveling effect. It brought the finance folks, the software developers, TechAtlas scientists, and others together to solve a healthcare problem that was very real to all of us. Our "TARA" sessions (TechAtlas, RA Capital, a holdover from the days when TA and the investment team didn't mingle as much as we do now) became more colorful and filled with analogies when before some of us might have just gotten away with jargon and missed that some of our colleagues' eyes were glazing over.
Thanks again to the TechAtlas COVID team. If you’d like to learn more about TechAtlas, check out our Q&A with TA leadership.
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