Friday, May 29, 2020

Out of the Crisis #6,

Like many people, one of the things I've become aware of since the pandemic began is the lack of coordination and organization for people who are looking for ways to help. Out of the Crisis #6 is my conversation with someone who not only saw that deficit but did something about it--literally almost overnight.

Radu Spineau is a serial entrepreneur. He's also one of the people building, a clearinghouse for matching volunteers with all kinds of COVID relief and COVID-related projects. I personally have used it to recruit hundreds of people since the pandemic began. To date the site has more than 700 projects listed and 14,200 volunteers looking for ways to help.

It's no surprise that matching volunteers with opportunities isn't something that Radu had experience with. One of the defining features of the work people have stepped up to do in the last few months is just how much of it involves skills they actually don't have. Radu, who is an optimist at heart, has seen how little that matters when people want to do good. To his way of thinking, this "is a great opportunity for a lot of people to do something that they could actually be very good at and learn a lot of things, because you learn the most things in complete chaos." And that includes him.

You can listen to our conversation on Apple podcasts, Google podcasts, or wherever you like to download.


A complete transcript of my conversation with Radu is also below.

Highlights from the show

  • Radu on his background and what he was doing before (2:53)
  • Radu on being a builder and his experiences with YCombinator (4:04)
  • Radu's quarantine life and his parents quarantine life in Romania. (5:45)
  • When he realized the pandemic was significant. (7:06)
  • Where Radu's optimism comes from (8:56)
  • Launching 8:58 
  • The origin story 11:30
  • Using Discord to get set up (13:30) 
  • 1,000 people signed up to volunteer in the first few days (14:02)
  • On launching in a few days and then iterating (15:36)
  • On the high caliber of volunteers (17:10)
  • The MVP. (18:06)
  • The tech that powers the site. (19:22)
  • What helpwithcovid does and how it matches volunteers with COVID-19-related projects. (20:09)
  • How Radu knew the site had hit product-market fit (22:07)
  • Radu talks about the three times he's hit product-market fit with startups (23:09)
  • Radu on making the first cinemagraph-making app in the app store. (24:44) 
  • The numbers on helpwithcovid's projects, volunteers, and matches. (26:34)
  • The specialization and high quality of volunteers and projects. (27:06)
  • Helpwithcovid's DNA. (27:55)
  • Projects that currently need help. (29:15)
  • Skills in demand, including design, software engineers, and people to vet volunteers and projects. (32:23)
  • The wide range of people stepping up to do whatever is needed. (33:58)
  • Opportunities for doing/learning something new in chaotic moments. (37:31)
  • Starting up (38:20)
  • The digital divide in education and learning about new problems that need to be solved. (39:54)
  • The strangeness of being told to wait for help to come, then realizing you are the help. (42:28)
  • The importance of saying "I just want to help" without worrying about being qualified. (44:07)
  • Radu's biggest surprises. (47:45)
  • On letting go of ego in relief efforts. (50:30)
  • Thoughts on forming a new economy post-pandemic. (52:06)
  • On the need for entrepreneurs moving forward. (52:47)
  • Keeping health care workers front of mind. (53:44)
  • Projects to make the post-crisis world better (55:37)
  • How do we get out of the crisis? (58:53)
  • Thanks for volunteers (1:02:11)


Show-related resources

Transcript of Out of the Crisis #6,

Eric Ries: My name is Eric Ries. This is Out of the Crisis. One of the themes that has come up for me again and again is the importance of coordinating an organization. Now more than ever, we have to step up as a community, as citizens, and as people to support each other. In the early days of the pandemic, there was a severe lack of this coordination and organization. Even at the micro level, people with skills and resources to help really didn't know how to communicate and organize in a consistent way, and I think this fed our collective feeling of helplessness, and it wasn't long after that at least I started to feel like a member of a community of people, all working on the same problem.

So, how did that come about? How did it happen? Who brought us together? One of the organizations is called It helps match volunteers with projects that need volunteers, and they've placed thousands and thousands of volunteers. I personally have used it to recruit hundreds. It's been incredibly helpful in the projects that I'm working on, and we'll include links in the show notes. This is one of a million stories of ordinary people stepping up and making a difference. While many of us were feeling despair, Radu Spineanu saw an opportunity to help.

He was in dialogue with two pretty important Silicon Valley power players who suggested that there needed to be a way to match volunteers with projects, and he had a fully-functioning site to do that up and running two days later. Two days after that, it had placed its first 1,000 volunteers. In some ways, Radu's story is typical of Silicon Valley. He was an immigrant from Romania, a software engineer, came to the Bay Area, did Y Combinator, started a company, sold it, made connections, and became part of this ecosystem.

So, when the crisis hit, he was already primed to approach it as a founder, as a maker, as a builder, but that doesn't explain the whole story, because many of us could have done what Radu Spineanu did, and yet he's the one that actually did it, and that's another thing I think is so important about a crisis. None of us really know what we'll be like when we're called to service in an emergency. You can never really guess or imagine. You just have to do it, and it is on each of us to ask ourselves, "What can I make? What can I build? How can I help right now?" Here's the story of

Radu Spineanu: Hi. My name is Radu Spineanu. I work on Help With COVID, which is a clearinghouse that matches volunteers with projects that are working on the current crisis.

Eric Ries: What were you doing before Help With COVID?

Radu Spineanu: Before Help With COVID, I had started a startup. I'm a YC alum. That went through YC, and we sold that company about a year-and-a-half ago, and then I left The Acquirer in late January, and then I've been just not doing anything. I've moved back to the Bay Area.

Eric Ries: Back to the Bay Area from where?

Radu Spineanu: From LA.

Eric Ries: You're originally from Romania, right?

Radu Spineanu: Yes, a long, long time ago, about 10, 15 years ago. Yeah.

Eric Ries: How did you come to be in the Bay Area?

Radu Spineanu: I actually started a company in Romania. I started the biggest affiliate network in Romania, and I realized that, one, I really like building companies, and two, that if you want to make a difference, you just have to be here, have to be in the Bay Area because you have access to the most amazing people in the world that are not only incredibly smart, but have this big-picture vision and optimism of what you can build, and also, you have some amazing groups of people that are just willing to find two random Romanians from Romania and give them millions of dollars to start a company, which I think it's pretty unique.

Eric Ries: You talk about yourself as a builder. What does that mean to you? I mean, I'm the same way, but why do you like building things so much?

Radu Spineanu: I feel like it's just the feeling of making something out of nothing, that you see a problem, and you get a picture in your head of how to solve it, and you just turn it into reality, and that's, one, a magical feeling, but then once you see people actually use it, and sort of like the magic product-market fit, which is amazing, if you've had product-market fit, you feel it immediately, and that's the second magical feeling, and it's quite addictive.

Eric Ries: What was it like going through YCombinator? You were there in the previous era when Paul Grant was still leading it. Is that right?

Radu Spineanu: Yes. We were the last PG batch, and YC just changes your life completely. Before YC, you are just a random person, and you can email people, and it's always harder. It's like people are not answering your emails. They're like, "Oh, cool. Is this person serious? Is this person going to survive in the Bay Area for the long term?" because so many people just come and leave, and once you go through YC, you're not a random, and maybe it's not a nice way of saying it, but you're not a random person anymore. You're like-

Eric Ries: Yeah. It's like a modern-day credentialing system.

Radu Spineanu: Exactly, and you're still the same person before and after, but basically, it opens so many doors, and I know for sure that Y Combinator changed my life completely.

Eric Ries: These are dark times. How are you doing? How are you holding up? How's your family? What's your quarantine setup like?

Radu Spineanu: My quarantine setup is I moved back to the Bay Area, and I'm in a tiny one-bedroom apartment right now.

Eric Ries: Oh, man.

Radu Spineanu: I'm pretty good. I always worry about other people, especially with a lot of the stuff that's happening, and my parents are actually all back in Romania. I've forgotten my family's back in Romania. My dad is older. He's 80. He has all the underlying conditions, and I'm definitely worried, but I'm happy because I was on Twitter early on. I kind of was able to email them and call them. I tell them, "Stay indoors. Don't get out of the house." You know?

Eric Ries: Mm-hmm (affirmative).

Radu Spineanu: So, I think they're going to be okay.

Eric Ries: Do you have a sense of how the pandemic response is going in Romania?

Radu Spineanu: I mean, they went full-on where they basically are not allowed to get out of the house unless you download an app where you tell the police why you want to get out of the house.

Eric Ries: Oh, my.

Radu Spineanu: If you are over 65, you're only allowed out of the house one hour per day. That's it. It's super extreme. It's hyper-extreme, and kudos to them. They did it very early, but that's good because the medical system in Romania is just a complete mess.

Eric Ries: Was there a moment for you when you realized the pandemic is real?

Radu Spineanu: I feel that yes. I think the moment for me when it was very real is I was on Twitter, and I was kind of ignoring it because there were a lot of things happening and my life in January, but I remember I had a friend visiting from Asia, and I really, really love that person, but I was worried that, okay, this person is literally coming from China right now, and am I worried about meeting him? Did he take all the necessary precautions and stuff like that? It sort of created this instinctual feeling of, oh, maybe this is not okay. Maybe this is going to get out. I know that, maybe, again, it's not something that's very nice to say, but I feel like that's when I started actually thinking about it for the first time in a more serious way. How about you?

Eric Ries: It wasn't a moment for me. I had this growing sinking feeling that something bad was happening over the course of, really, January, February, into March, and I kept taking emergency preparedness steps that felt extreme on Monday, and then by Wednesday, I wished I'd done more, and by Friday I felt like I was hopelessly behind. So, it's like this process of trying to catch up with reality, try to understand it, try to figure it out, and not be consumed with regret and despair, especially as I realized that there were going to be severe national differences in how people responded. There was kind of a moment when we had that optimism that there would be a global coming together, a science-driven, consensus-driven political response all over the globe, and when that didn't happen, then I really had some dark days.

Radu Spineanu: That makes a lot of sense. I'm still optimistic about everything. I've gone back and forth, but now I'm back to being optimistic.

Eric Ries: Well, what do you think that optimism is born out of?

Radu Spineanu: I think that optimism is born out of... For instance, just Help With COVID, when we launched it, we literally built it in two days, and we put it up, and we had no idea if anybody's going to use it. But initially, it was started because Dustin Moskovitz and Sam Altman were getting so many emails about people wanting to help and projects looking for help. So, Sam added me to it because I previously did stuff with Sam, like YC's Request for Startups, and he knew I was sort of in this phase in the middle of things, and people stepped up immediately. We got an immediate response.

In the first day, the response was absolutely amazing, and talking about that feeling of product-market fit, it's like you could tell that there was a need where projects were already starting up, and people wanted to help. From the very beginning, I was actually super optimistic because on this side, on the Help With COVID stuff, I saw so many people offering to help. That's how it started. Now, there's a lot of things happening in the background, and even the news from yesterday with Gilead, and I was talking to some people today and just... I think it's going to be okay.

Eric Ries: So, I remember very distinctly when Help With COVID launched. I was right in the middle of starting up my first of what has been several pop-up organizations to deal with the crisis, and must have heard about it from Sam Altman, and I went on there, and I had posted my first project, I think. I don't know. There weren't very many projects posted yet, so I was relatively early, and I was just stunned with how many amazing volunteers started pouring in just that first day. It was both the quantity of it was overwhelming, but the quality of people who were really interested in helping out was really amazing. So, first of all, thank you for building it. It's been an incredibly useful resource for me and the projects that I've been affiliated with. Tell us about kind of how the idea came to you. Tell us about how you built it, and tell us what those early couple days of grappling with product-market fit was like.

Radu Spineanu: Definitely. So, it wasn't my idea. It was this email exchange between Sam and Dustin, and I remember-

Eric Ries: You're talking about Dustin Moskovitz, the Asana co-founder, Facebook co-founder.

Radu Spineanu: Exactly, Dustin Moskovitz and Sam-

Eric Ries: Yeah, and Sam Altman, who our listeners will remember from a previous episode, former president of Y Combinator.

Radu Spineanu: Exactly. So, I remember it was a Sunday, and it was like 4:00 p.m., and I was grocery shopping, and I was with my girlfriend, and I was picking out oranges, and I got this email from Sam. It was like, "Hey, I think this is a cool idea. Are you in, or are you interested in building this?" I immediately replied yes, and then I tried to convince my girlfriend to cut grocery shopping short so I could go home and build it, which didn't work very well, but I got home in an hour, and basically, I was talking to Sam and asking what's his vision for this, and he gave me some things that were important to him, and then just basically, I built the first version by... We launched Tuesday morning. So, it went incredibly fast. The whole idea was like, okay, this is a crisis. We need to move fast.

In the beginning, if you remember, you didn't know how long this was going to last. It was this feeling of maybe it was too much optimism. They were like, "Oh, maybe just two to three weeks, and it's going to be okay." So, we launched it by Tuesday. We did it on Tuesday. Immediately, started getting a lot of projects, and the first thing we did is we... I realized that, hey, because Help With COVID was on the website, and we were eating our own dog food, I realized we had a problem. 100 people applied, and we were like, to be volunteers, "I have no idea how to manage all these people, and it's too many people." So, immediately started a Discord, and I started a Discord... I picked Discord over Slack just because I had used Slack. The company I was at was a full-on Slack company, and I got burned out with Slack, and I wanted... Discord seemed like a fun thing to try out, and-

Eric Ries: Yeah, it's mostly used for gaming and kind of mass coordination more than kind of official work projects.

Radu Spineanu: Exactly. So, we created a Discord, which actually, I think, ended up being perfect.

Eric Ries: Yeah, it's a really good fit for this use case.

Radu Spineanu: Exactly, and 1,000 people signed up immediately in the first three to four days. So, going to that, right now, because Help With COVID is run by a core team of volunteers who are actually amazing, and basically, they self-selected themselves. It's like people who are on Discord and who are involved in the project now just pay attention to who's the most involved and who wants to help the most, and you just give them more responsibility.

Eric Ries: It's an amazing thing to watch. We'll put a link to the Discord in the show notes for those who want to come see how this organization is done. It's pretty amazing. But I want to go back to those first two days. So, you got the idea from Sam and Dustin, and boy, what a Silicon Valley story. Not that long ago, you were an immigrant coming to the U.S. for the first time. Now these billionaires are emailing you ideas to work on. So, Sunday night, you have the idea. You launched it Tuesday.

So, that has been a recurring theme of these conversations, is how fast in a crisis you need to get these minimum viable products out the door. So, there must have been a moment when somebody said to you, "Maybe we should take another day or two, make it a little bit more perfect." I just think about how much worse the world would be now if you'd taken a whole week to build that first version, and those 1,000 people who wound up signing up on Thursday, they would've had to go do something else. So, talk about the pressure you felt to go fast. Just mechanically, how did you get it done in two days?

Radu Spineanu: Well, I'm a startup founder, and my problem is I launch things... I've done this the whole time, where I launch things before they are ready, even with my previous startup. There were a bunch of features which were not ready yet, and we just fix them as people are using them. There was no pressure because Sam trusted me because we worked together previously, and my first email to Sam, and when Sam and Dustin were asking me, "What's important?" It's like, "What do you think is important?" I said that we have to launch it by Tuesday, and I actually wanted to launch it Monday night, so I failed. Actually, I launched on Tuesday.

Eric Ries: Let this be a lesson to a lot of startup founders out there.

Radu Spineanu: Yeah. But it was quite easy to build. It's not a complicated technical project. It's just, you have to get the first experience so it's not clunky, so we can focus on people seeing the projects, seeing that people volunteer, seeing other amazing people have applied and they want to help, and right now, the first version, obviously, I was very disappointed with, but luckily, now there's a bunch of amazing people that are working to make it better. But I do remember one of the first... It was, I think, Tuesday or Wednesday when I was looking through the volunteer list, and I saw Dave Morin volunteer publicly

Eric Ries: Wow. That's the founder of Path, for those that don't know him.

Radu Spineanu: Yes, and I'm a big fan of Dave Morin. At some point a long time ago, he emailed us at Two Tap and said, "I love what you guys are doing," but I've never had a conversation with him. But he applied to this thing as well, and I was like, oh, that's so amazing. I cannot believe Dave Morin applied.

Eric Ries: I mean, I even have had moments like that when I look at the people who have applied through Help With COVID. It's been pretty shocking, like I said, the caliber of folks who are able and willing to help. I remember what impressed me about the site, even though it was launched quickly, it was really polished. I thought you did a great job of... Some people think minimum viable product means have 100 features and have them be half good, so it's kind of like a bunch of crap. It didn't do very much, but what it did, it did very well. It was very responsive.

The website was super snappy, and I remember the signup process was really fast, no extraneous fields, no extra nonsense, no check boxes and user license agreement. It was just very fast to go from signing up to posting a project, and the responsiveness of the site actually felt really good. So, it was a great MVP not just because it was done quickly, but because you were really selective about what features to include and what could be skipped, and I was really impressed. It gave me a lot of confidence to use it, and maybe want to post more projects there.

Radu Spineanu: Thank you. I mean, that means a lot. We just basically... What we did is we focused on... We didn't care about the underlying technology. We just cared about what is easiest to get out the door and to move as fast as possible because it's not... Like you said, it is polished, but it doesn't have to have the beautiful animation from the first...

Eric Ries: Yeah. Yeah, exactly. It's polished, but not fancy, if that... That's maybe a way of talking about it.

Radu Spineanu: Exactly.

Eric Ries: It has that kind of like almost a Craigslist vibe to it where it's lo-fi, but it works very well.

Radu Spineanu: That's intentional.

Eric Ries: Yeah. Well, tell us what the tech stack is under the hood, just for those that want to know.

Radu Spineanu: Of course. So, it's very simple. It's actually just Rails and a CSS framework called Tailwind UI, and what's great about it is I don't have to... Everybody knows Rails. People have done Rails. Sorry. I don't mean to say everybody knows Rails. When I say that, it's like, Rails is very easy to get into, and Tailwind UI is just an amazing... It's an amazing UI interface to get started. So, I could purely focus on just the core features and not worry about a bunch of design stuff or Rail stuff. Yep. That's the whole stack.

Eric Ries: So, tell us what Help With COVID is. What does it actually do?

Radu Spineanu: Help With COVID is a clearinghouse that matches volunteers that want to help with the current crisis and projects that are making an impact.

Eric Ries: How does it work?

Radu Spineanu: If you have an idea to start projects, or even if you're an established project and are looking for specific help, you would go to You create a project inside our interface where you add a bunch of very helpful information, like what the project does, who's working on it, how far along are you, what specific help are you looking for, and then volunteers that have applied to help out basically volunteer to help you. You will get an email, you will get a Discord channel, and then it's up to you to be able to create, to take these volunteers and integrate them into your own project and give them guidance on how to help you.

We also have this volunteer directory where you can find very specific help. So, for instance, if you're looking for help with, let's say, Flutter, for instance, we had the World Health Organization building, they're not on the website, but Harper has been helping them, and he basically was looking for Flutter developers, so we were just basically... We told him to go and search the volunteer database, and he found... I think we even gave him a bunch of numbers of people. So, yeah, that's the second component. So, to recap, you post a project, you get volunteers that want to help you. If you're looking for specific help, you can also search the volunteer database.

Eric Ries: So, it's kind of like a two-sided marketplace, almost, volunteers searching for projects, projects searching for volunteers.

Radu Spineanu: Exactly.

Eric Ries: You said you felt like it had product-market fit. How do you know?

Radu Spineanu: The first day, the second day, first, the growth. The most important thing when you look at any project, you look at the growth, and the metrics change over time. The first metrics were number of projects created. The second metrics is number of volunteers, and then, obviously, it's volunteers applying to projects. All those numbers have been growing. But I feel like, leaving aside numbers, oftentimes you see product market fit when you look at the content that's being created, the people, the interactions between people, and it's very hard... I mean, how do you explain product- market fit in a way to people that have never seen product market fit? It's really hard to explain.

Eric Ries: I know. It's such a funny thing. It's something you absolutely know it when you see it, and yet that's not very helpful if you've never seen it.

Radu Spineanu: Yeah.

Eric Ries: So, what does it feel like? Walk us through what it's like.

Radu Spineanu: Oh, my god. It's the most addictive feeling in the world, for me, at least. When you see people literally build something, and because all of us have built stuff that nobody used, and it's part of the learning process, and it hurts a lot, and you keep on trying to... Like Sisyphus that pushed the boulder up the mountain, and you release this amazing feature, and still, nobody comes back, so you got to push it. When you have product market fit, it's just like a wind that pushes you forward where people just come, and they love it. I remember a long, long time ago I made this... So, I had three moments where I created product market fit.

The first one was the company in Romania, where this was an affiliate network, and we launched it, and it was such a big need in the market that after we signed the first one, so the first three stores... The affiliate network was like an ad network for e-commerce. The first three stores signed up, and it took us a month-and-a-half to sign up, and then we got like 20 signups in the next week or something like that, and people were loving that. I was like, this is the most amazing thing. The second time was I had failed... The first time I applied to YC, I got rejected. My initial co-founder then left, and I was going through some really dark times during Christmas. So, it was, I remember, December. I was in Eastern Europe. It was really cold. I created... Do you know cinemagraphs?

Eric Ries: Yeah. I remember that.

Radu Spineanu: So, I created the first cinemagraph-making app in the App Store, and I created this... A cinemagraph is a static photo in which something moves. So, I was really sad, and on Hacker News I saw cinemagraphs, and I got to say, I was like, this behavior of you create a video, you select the static frame, and you just poke a hole in the frame and you play the video underneath, and then you turn that into a gif or gif, not to get political, sorry, it was so weird because I just...I got like 40 users. I had just failed before. It was between... I don't remember when. I think it was between Christmas and New Year's.

I get a phone call, and it was Apple, and it was this guy at Apple, and he was like, "Hey. Here, we..." This was like 10 years ago. "We really love what you are making." I'm like, "Sorry, what?" I was like, "What?" "We do love what you are making, and we were wondering if you can add a flag feature inside of the app, because we want to feature it." I was like, "Yes, sir. I'll build it right now." It was basically like... I built it for like 40, so they featured it, and I think it got like 100,000 downloads in the week when they featured it. The process to create animated gifs was so hard, so intensive, so I actually had to learn AWS and everything was burning at the same time. So, that was an amazing feeling too. I think, weirdly, our YC company, we were at that thing were we never actually got proper market fit, which is sad, but this third time, right now it's like Help With COVID.

Eric Ries: Tell us some of your metrics. You want to share some vanity metrics, just show off for a second?

Radu Spineanu: Yes.

Eric Ries: You've totally earned it.

Radu Spineanu: Thank you. So, what we're most proud of is the number of projects. We are right now at 600 projects and 11,000 volunteers, and these projects did not exist... Help With COVID did not exist a month ago. So, 600 projects, 11,000 volunteers, and 10,000 people applied to volunteer with a project, so 10,000 matches.

Eric Ries: It's like an army of volunteers.

Radu Spineanu: Yeah. What is interesting is Help With COVID's niche, it's very specialized people. So, there is some amazing projects up there. For instance, on Reddit and so many others, so Facebook groups, a lot of people have offered to help, and everybody's helping with so many things. For instance, a very legit project is going and helping and delivering things to people who can't go out. A lot of these people are in things organized in Facebook groups, and that's actually amazing. On Help With COVID, if you look through the people that have applied here, they're really specialized, like technical people and/or startup people or product people, amazing designers, and a lot of Silicon Valley people.

This is one thing that I've learned right now, in the past year, especially the company that acquired us, is how much of the product that you create is going to be the DNA of the founders, meaning... So, this company where they acquired us had amazing product people and amazing ops people, based on the DNA, but some areas were not as strong because there was nobody to basically go to the founders from other areas and say, "Oh, this is bullshit," because everybody was afraid of the boss. So, because everybody was afraid of the boss or the founders, then there was this hesitance to actually say what's happening.

So, here with Help With COVID, the DNA is, for the most part, people that are building technology companies are people that have been heart sciences. It's, I don't want to say all in the Bay Area, because it's not only the Bay Area, but it is highly influenced with the Bay Area ecosystem, with Sam, Dustin, and you, and so many amazing people that have applied. So, the DNA of Help With COVID is highly ambitious, specialized people that want to make a difference and have the confidence to know that they can make a difference, if that makes sense.

Eric Ries: So, if someone wants to volunteer for a project, what are some projects that could use help right now?

Radu Spineanu: One project that I felt was interesting was Volunteer Safe. It's a project that helps with all the Facebook groups and Reddit groups that are, for very local Facebook and Reddit groups who are making a local impact, for instance, elderly grocery delivery or medicine delivery, and the problem is when sign up to help out in all of these groups, and someone does the matching, you actually have no idea if those people are okay, if those people are trustworthy. So, what they do is they want to do background checks based on Google Sheets, as low-tech as possible. You connect a Google Sheet to your platform, they do background checks, and they say, "Okay, this guy can actually go and deliver food to an elderly's home, and they won't rob them." Obviously, again, I'm not saying people do that. I'm saying if there's one person out of a million that does this, it's still a bad experience, horrible experience.

Another project is Apollo, and Apollo, what it does is they route physicians to where they are most needed. So, some projects are under capacity, and some hospitals are under capacity, and some hospitals are just overrun with problems. What they do is they're trying to build this technology where they route physicians based on where they can make the most impact, and they're trying to build this... It's not actually just a job board, which doesn't do anything, but it's also not the agency that takes 15% of your salary. It's just this thing in the middle that uses just technology and perhaps machine learning to find the best fit for physicians.

Other projects were the classic project, N95, which are trying to solve the mask problem, and they're not the only one. Operation Masks is another one as well. I know you are trying to do an impact on that as well. It's still a pretty serious problem that hasn't been solved yet. So, any of those projects require a lot of help because it's a lot of... A lot of them is just calling suppliers, vetting partners. That kind of requires a lot of technology.

Then there's obviously the medical projects. The medical projects that are being posted on Help With COVID are kind of harder to judge because, one, we have an amazing scientific advisor called Dr. Ambika Bumb, who had a panel which just works for the state department, and is just absolutely smart. But we might not be the right fit because what a lot of those medical products, that's why they need especially health sciences, because they need a lot of funding. They need labs. They need guidance to go through the FDA process. We try to help them, but we might not be the right fit for them.

Eric Ries: What kind of volunteer skills are more in demand, what you've seen so far?

Radu Spineanu: What we've seen is... So, there's, first of all, design. It feels like everybody needs some kind of design help. It's been a lot of requests for design help, software engineering, because just of the nature of what we've been building. You'd be surprised how much there's been a request for just people talking on the phone, meaning that can be volunteer vetting, that can be partner vetting, that could be just answering the phone for someone who wants to talk to someone, just people who are able to talk on the phone. There's a huge demand. I would put these under call center, volunteer vetting, partner vetting, stuff like that.

Eric Ries: I've been amazed working with these projects how many opportunities they are for ordinary people who are just willing to do whatever it takes to get stuff done. They don't necessarily have a specialized skillset, like engineering or design, how much value they can add to projects, all of whom need help with project management, answering the phones, crafting emails, dealing with social media, and I've been encouraging the people I know who are kind of on the sidelines to get involved, and one of the barriers I see is people have this idea that, well, I don't have a special skill, or I'm not a special person. Who would really need me? Can you talk a little bit about just the range of kinds of people that you've seen be effective across these projects?

Radu Spineanu: That's a very good question. So, on our end, like you said, it's people that want to step up, and it's simple as that. Anybody who wants to step up right now is going to make a large impact. To give you an example with our core team, the first core team member we had was this amazing person, she just joined us on... She joined me on this part in the beginning, and she's a designer during her full-time day job, but then she started doing these amazing, basically, operations of managing the Discord, grouping projects, giving me feedback and advice, doing the website. I felt like she was more like a COO than... So, the day job is design, though. She comes in, and she actually helps me just run the project and bring order into the chaos. It was just amazing.

Then you have people like Kinj, and Kinj's job is to go through all the projects, especially take care of the most projects that seem to be taking off, and he joins all the Discord of all the projects, and he just talked to everybody. He's an engineer as well. So, then during the day he's an engineer, but he's doing something completely different where he is just basically the person... It's like he's more of a... Imagine an account manager or the customer success person, where they make sure everybody has everything they need, and it's critical, and that's something that... This idea of hand-holding is at some point, especially right now, where the peak enthusiasm has been reached, and now it's a lot about going through the grind of matching the right projects, the right volunteers, and this is incredibly important, where someone has to have a big picture of everything that's happening.

So, one of the good reasons of actually joining a startup is you can make such a larger impact, meaning you have the option of being a salesperson at a big, large enterprise company, or you can take the risk to join a completely unproven startup, but perhaps you can be the head of sales or you can be the first salesperson. What happens is oftentimes you have to choose. There is this thing between risk and responsibility, but if you're willing to take more risk, you will get a lot more responsibility. Some people just don't want that, and that's perfectly okay. Some people want to put work-life balance, and they're very focused on safety, and that's perfectly okay. I want to make that clear.

But then there are some people who are just like, "One, I just want to make a large impact right now," but other people are just, "Okay, I don't care about... I mean, I care about having imposter syndrome, but I'm still going to go for it anyways, and I'm going to do my best. Most of those people can actually succeed. This idea of that we cannot do anything, it's just in our heads. I'm pretty sure Tinay joined just because she was looking to help, but then it turns out she's a designer, but actually, she's a great operations person. I am pretty sure she can run a company without any kind of problems.

So, this is a great opportunity for a lot of people to do something that they could actually be very good at and learn a lot of things, because you learn the most things in complete chaos. If you have a project that's taking off, even if it's not taking off, this idea of getting out of your comfort zone and taking on responsibility will teach you so much. So, the big picture is if you want to help, there's so many projects out there that are looking for help, and just go and help them, and if you are going to go inside of those projects, it's probably going to be a complete mess. All the projects right now are a complete mess, and that's okay.

Eric Ries: I mean, none of us are qualified to be doing what we're doing. I think that's kind of the nature of the crisis. You know?

Radu Spineanu: Yeah. How are your things internally?

Eric Ries: Yeah. I mean, it's always chaos, and there are different levels of maturity. Your point about product market fit, when we did, that started... That was just me and a founder, an education founder who I really admire, and we were trying to get other companies, other education companies kind of onboard to do it together with us so that there wouldn't be like 5,000 different competing education resources for parents who were struggling. It was very similar to what you described. It took us about... I think we did a weekend, so three or four days between having the idea for the first time and having it live. We had maybe 10 or 12 company partners for the first version of it, and we did a... We had a Twilio hotline. We'll put a link to Twilio Flex, which is this awesome technology that makes it really easy to build your own call center, in the show description.

So, we had that going. We had volunteers who could kind of answer the phone if parents called in and needed help. We had homeschooling families who were experienced with having to school at home kind of standing by to help families who never had done that before. The first few weeks especially were very, very chaotic. Now I think there's like 190 volunteers, so it's quite a production now, and they've had several spinoff sites, and there's a huge fund raiser going to launch Monday. I don't think I'm revealing anything that's not supposed to be public yet, but there will be a big fund raiser on Monday to buy technology for parents who don't have it.

Eric Ries: So, there's a huge digital divide, inequality story in education. I mean, there always has been in this country, but especially with this crisis, you have tons of schools that have moved to online education, and something like 20% of families don't have a computer at home, and they're being told by the school district, "Well, just go to the library," and the libraries are closed. So, it's kind of totally incoherent. So, we'll be raising funds to get laptops to families. What's interesting about that strategy of having the hotline, having these partners is... I really recommend this to other projects too.

By having a place that people can call, even if your website doesn't have the answer that they need, it's kind of what you did with Discord. It creates an opportunity for you to discover new problems that you didn't even know were going to be part of it. So, when people started calling in, we were not at all thinking about IT support as a need for parents in the early days of the project. We were very focused on educational resources. But there's a lot of parents who couldn't figure out how to use Zoom. I remember we had one parent who called in, and were like, "I'm trying to use Zoom. I called Zoom, but they haven't called me back."

Radu Spineanu: Wow.

Eric Ries: Yeah. Oh, boy. Zoom's a little busy right now. I don't think they're going to be able to get back to you. You're going to need to step it up now. So, we had people do IT support, and through that we discovered parents who couldn't find computers, and I was right naïve. I thought, oh, there'll be tons of nonprofits, I'm sure, leaping into the gap to get laptops for people, and we talked to tons of educational foundations who that's what they work on, and they'd be like, "Yep, we're on it. We have a program. We're raising money." We're like, "I know, but I have this one family in Gainesville, Florida right now who needs a laptop. Can you help us get them a laptop?"

That's been another interesting disconnect in this crisis. Many of the official foundations and institutions that are supposed to be solving these problems, they are simultaneously saying that they're on it and they're taking care of it, and then just going so slow that they're not actually helping. I've been a little bit shocked. Obviously, this is even more prevalent on the PPE side, but I've been told in every project I've been involved in, I've been told by multiple experts to stand down and wait for the calvary to come, wait for the official thing to be ready. Normally, that's what I would do. I hate duplication. I'm absolutely not in favor of amateurs doing work that should be done by experts. But in the crisis, it has seemed like certain areas, there's just these gaps where our institutions are not able, for whatever reason, to act quickly enough, and that has required ordinary people to step into those gaps, and it's been a little bit strange.

Radu Spineanu: It definitely has been incredibly strange, and I'm sure on the mask side, from what I've read, it's the strangest of all the things.

Eric Ries: It has been a very surreal experience, but if people are listening, I think by the time this episode comes out, we'll have new stuff up at, and we'll put a link in the show description. Hopefully, we'll give people some hope that help is on the way, but it's been quite the experience trying to find help. The thing I want to ask you about, and the thing I found so striking is we're all horrified by the news, the idea of nurses using ponchos instead of proper gowns to protect themselves, or having to treat COVID patients without masks, kids without laptops. We have people who can't get groceries, and on, and on, and on.

So, when we hear about those problems, and obviously the virus itself, when we hear about those problems we have this tendency to say, "Well, I'm not a scientist, so what can I do about it? I can't work on a vaccine," or, "I don't know anything about a supply chain. I can't help with that." We think of all the reasons why we can't help, and yet Help With COVID has been this really interesting example where people with software skills that seem at first blush very removed from the problems we were facing were able to come in and act as a force multiplier. So, talk about what you've seen here, how it's felt for you, the kind of unexpected connections between the skills people have and the needs we as a society have, and how that matchmaking can make a big difference.

Radu Spineanu: Definitely. The most important thing is, like you said, it doesn't matter if during the day you are a doctor, or during the day you're a lawyer. What happens is when you join a lot of these projects, they probably are just a ragtag group of people that are trying to make a difference. Oftentimes, it starts with either an idea or a team, and they're trying to turn this into reality. Not everybody's stepping up, but the people who do step up and who are willing to get out of their comfort zone and just go and apply and say, "I can help with this," and sometimes you just have to say, "I just want to help." This is just an example. Oftentimes, people have different skills that can be applied in different areas. So, if you are listening to this and you're wondering, well, I'm just a gamer. What do I... This is just an example, right?

Eric Ries: Mm-hmm (affirmative).

Radu Spineanu: I'm just a gamer. I don't know what to do. It's like, I don't know. If you're a gamer and you play video games, you actually might be very good at organizing. You play online video games.

Eric Ries: My kingdom for someone who could organize a 40-person World of Warcraft raid right now.

Radu Spineanu: Exactly. Here's the thing. There's a lot of projects that have visionary people. There are a lot of people that have amazing software engineers, maybe they're just very bad at organizing. So, you can make an impact, and it actually could be very fun because if you're a gamer, you figure out gaming, the difference between Overwatch or Valiant, or whatever the new game is, pretty much, it's the same. But if you want to learn the supplier mask business, that's actually a super interesting game as well, and you can treat it as a game. So, just can make connections in kind of ways.

Eric Ries: I'll put in one plug. If there's anyone listening right now who is convinced that their skills will not translate, if you can answer a phone and talk to a human being in a nice way, and you have no other skills but that, we will 100% put you to work at PPE Coalition. You don't have to call China. You don't have to talk to suppliers. All you have to do is get people's information who call in to the hotline, write down what they tell you, and then we have an entire database of responses that experts will help you put together to send them. So, you don't have to be the expert. You don't have to know anything at all. If you can talk on the phone and don't have severe social anxiety disorder, then you're 100% qualified, and we desperately need people who can answer the phone, so please look us up, PPE Coalition, on, and click the I want to volunteer button, and we'll get you plugged in.

Of course, I'm just plugging my own project because I know it well, but there must be hundreds of examples of things like that where if you know how to tweet, you could be somebody's social media manager, and don't tell me you're not qualified because you don't know that. I was talking to somebody the other day who said, "I can't help with that project because I need to partner with someone who knows strategic communications," and I'm like, "You mean writing an email?" and he's like, "No, strategic communications." I said, "You mean writing an email?" and he's like, "Oh, I guess I mean writing an email."

The world has changed all of a sudden, and there is no time for the kind of corporate BS and delays and politics we used to put up with. Now is the time we got to take matters into our own hands. I coached him through how to write the email himself, and it wasn't as good as if he'd gotten an expert in strategic communications to help him with it, but on the other hand, it got done that day, and it mattered that day. So, it was a success because a better email a week later would've been too late, and that's the situation we find ourselves in.

Radu Spineanu: That's awesome.

Eric Ries: What's surprised you the most? What were you expecting maybe that didn't happen?

Radu Spineanu: Everything. Okay. So, my first surprise, my first feeling is when it actually went into quarantine. So, I'll take you through all my surprises. The first thing is when it actually went to quarantine. Actually seeing the U.S. go into quarantine was something that I didn't think I was going to see in my lifetime.

Eric Ries: Yeah.

Radu Spineanu: So, that was my first surprise. My second surprise was... I know that this was... I should've seen this. This was very silly of me, but I didn't think it was going to last longer than three weeks. I had this feeling right when we went into quarantine where we're going to find this drug, we're going to just start manufacturing like crazy, and we'll be out. So, here we are six weeks later. My third surprise was... I mean, obviously, I have to say it's definitely the financial markets, everything that's happening in the financial markets right now. I'm completely confused about everything.

The fourth surprise is this idea of some approaches that are being pushed right now that probably are not going to work, stuff like contact tracing, which I'm very bearish on, and people pushing drugs that might not work or have serious side effects. So, all this idea of people pushing solutions just to feel better, which might not work, instead of actually thinking about approaches that might work. On the positive side, on the good surprises, it's like everything around Help With COVID is a surprise. I don't believe neither myself, neither Sam, neither Dustin thought that we were going to have 10,000 volunteers and 600 projects. I mean, I'm pretty sure none of us thought that.

I know this is going to be repetitive, but just all the volunteers and everybody applying to help and stepping up, but also the project owners and the fact that everybody's willing to help is just absolutely amazing. When we did the carbon Request for Startups for YC, that's when I had the first feeling of you can actually get people to, especially smart people, to help on the real problem as long as you don't involve your ego. I feel like that's the most important thing, is whenever people try to do good, whenever people try to do anything, they involve their ego, and the secret of doing projects that are around serious crises, whether it's humanitarian or climate change, COVID, whatever it is, you really have to let your ego go, meaning Help With COVID is not my project.

Help With COVID came out of a discussion between Sam and Dustin, and now it's run by the core team of volunteers. They are doing most of the work. When we did the climate change, you had four to five people, six, seven people who just spent a lot of time thinking about the problem and [inaudible 00:50:56] ideas and people writing design, and they deserve all the credit. So, I feel that I'm very optimistic on the world, and we're definitely going to get out of here stronger.

On the short term, let's be honest, it looks a bit bleak, and we might have to stay indoors for a lot longer than we think we will, but we're going to get out of it. We're going to get out of it, and the only thing we have to make sure is that we... Right now, the focus is technology and science, but I feel that what we're going to find out in the next couple of months is that we're going to have to stay indoors for a lot longer, and that's going to affect the economy in very, very hard ways. I think YC, what they did right now, it's like what they're focusing on is all these people who are tragically unemployed, will not have the same job again. So, kind of some stuff I'm thinking about, but this is very early on.

I haven't done anything yet. It's very early on. It's like, how do you actually... If this really does last longer, I don't know. It's like, how do you actually employ... How do you help these people who are unemployed find jobs or find opportunity? They cannot all be Instacart drivers or Uber drivers. There's just not enough demand for that people. So, how can you create a new economy around people working from home? Just stuff like that, I feel that I'm optimistic, but we're going to have to solve a lot of problems very soon.

Eric Ries: I hope a lot of those people, we will give them the support they need to become entrepreneurs themselves.

Radu Spineanu: Yes.

Eric Ries: That's going to clearly have to be part of the solution.

Radu Spineanu: I agree, 100%. You think about stuff like Lambda School. Lambda School, I know there's good PR and bad PR, but Lambda School might be the future of education. Right now, you have a lot of universities who are asking for money and switching to online, and people are realizing now, why am I paying so much money for wasting so much time? Then you have Lambda School, which was from the first online, and I'm actually a huge fan. So, we want more Lambda Schools, maybe, maybe other stuff like more online education. I think with the whole training and education, we're just going to enter a whole new chapter where this might be a new huge industry.

Eric Ries: Who do you think are the real heroes of this crisis?

Radu Spineanu: The doctors, for sure. There's no doubt, right? I mean, the people, the area that die the most are the doctors. If you look at any statistics in any country, I feel like if you look at the biggest, the most vulnerable areas are not doctors, the medical, the health people, and if you look at them, first of all, they're going in knowing that they're putting their life at risk. They are getting paid nothing. Maybe some of them are being fired. When they go home, their neighbors look at them like, oh, is this person infected or is it not infected? We're not giving them the equipment they need. They're understaffed, and they're seeing people die left and right. It's insane.

It's very easy for us to be disconnected from that because, oh, we're at home, but I feel like if you're a news organization or stuff, you should actually show people what these doctors, what these health... Not doctors. Doctors, nurses, everybody, what they're going through, because it's just like war. If war is this thing that's just, oh, we're just fighting down the population, and we're doing good and whatever, dismisses the horrors that are happening there. Right now, I feel like we're all desensitized. We're like, oh, the number of death grouped by whatever, whatever, but if there was an actual news where people would actually see what these people are going through, you would change public perception, and I feel like they should be a lot more respected.

Eric Ries: What steps do you think we could take now that will make the post-crisis world better?

Radu Spineanu: It depends. My question is... The problem is I have... It's very hard to say what's going to happen. So, you have the drug. I'm not going to try to pronounce it, the Gilead drug. There's a lot of controversy if it works or not. I was just on a call with someone before that works in New York, and they were like, "Well, we basically did an analysis, and we're highly optimistic about it. All the studies that have failed failed because they were giving it too late, and if you give this pill in the first three to four days, it's always going to work. If you give it-"

Eric Ries: We're talking about chloroquine, right?

Radu Spineanu: No, no, the Remdesivir.

Eric Ries: Oh, Remdesivir. Yeah, yeah.

Radu Spineanu: So, apparently, what works is... The problem with it, you have to take it in the first three to four days. If you take it after, it's not going to work because it just limits the spread in the beginning. The reason what's happening, everybody's so optimistic, is because apparently it does work if it's in the first three to four days. If that happens, there's a circumstance in which people are going to feel more comfortable getting out of the house, but the problem is, the best-case scenario, they can make like 10 million, 20 million pills this year. It's a very complicated process. So, we'll still be indoors for a very, very long time, according to some analysis.

For the medical equipment, I believe Ryan Petersen from Flexport has an amazing blog post, and when we were researching for 1 Billion Masks, we arrived at the same conclusion he is. The supply problem has been resolved for the most part. Feel free to correct me. The problem is leadership, where there is this mistrust between the factories and the people who are buying them, and we need someone to actually put up the hundred-million dollars, buy masks, ship them to the U.S., and then sell them at cost. Otherwise, nothing's going to get done, and usually this always should be in some sort of way the government, but that's not happening.

So, on the PPE side, what we need is leadership, and it's someone... This can be a private person. This could be Bloomberg, Eric Smith, other, where they need someone to go and say, "We need these funds, and I'm going to run this, and I'm going to be the face of it, and I'm going to take a risk." On the other side, on the side of what the person listening can do, is think about how... If there is this situation which we're going to have to stay indoors for another six to 18 months, but even if that doesn't happen, considering a lot of people who are fired or let go are not going to be employed again, it's like, how can we build a world where they're going to be able to work, and how is this economy going to change, how is the world going to change so that we can actually have these people learn a skill that is productive and that can earn them money, and build a new digital economy, so to say?

Eric Ries: Where do you think we go from here? How do we get out of the crisis?

Radu Spineanu: Okay. So, my feeling is one of these drugs are going to turn out it actually works. Well, there's going to be one of the best-case scenarios where there's going to be a slight opening up the economy. We're not going to go to bars or concerts or to work any time soon, but people are going to be able to get out of the house, go grocery shopping using masks and stuff like that. We're going to have a pretty unreal experience for the next six to 18 months, and then we'll have a vaccine, and we'll go back to normal. But I feel that I'm very optimistic, especially about the news around the new drugs, and I think that we're going to hear a lot more good news, hopefully soon, about that.

Afterward, it's just about making sure that... A lot of the stuff is out of our hands, especially with the government and stuff, but I don't know. So, thinking about this, I'm optimistic. By this summer or this fall, we'll have enough medicine for the frontline workers and for more of the people that are most at risk, and we will have a new economy that is derived based on digital and technology. There's so many problems that need to be solved, and to be honest, I think that a lot of very rich, influential people will step up, and unfortunately, will provide the help that governments are not able to provide, because obviously, I would love the governments to provide that help, but I don't feel like it's going to happen. What do you think is going to happen?

Eric Ries: No one can predict the future, and I think we are being tested like never before, and if people come together and say, "This is not the world we want to live in. We want to acknowledge the mistakes that we've made in the past, and we want to build a new normal together," I think we have the raw materials that we need. We have the science aptitude if we're willing to listen to the scientists, if we're willing to support basic research and make the long-term investments that are needed. We have the remains of the institutions our grandparents built for us in another time of crisis, and if we do the work, we can recover them and make them future-proof for the 21st century.

As you say, we have this digital technology that we could build a new, more equitable, broadly-shared prosperity economy on top of. So, are we going to do it? I think that's really the question. I got to say, of everything that has helped keep me going during this time, the spirit of the volunteers and the kind of civic engagement of just ordinary people who have thrown themselves into this problem, and especially through Help With COVID and with your help, has been really powerful. So, I wanted to say thank you for making that possible, for helping out, and for being a source of inspiration in these dark times.

Radu Spineanu: It means a lot. Thank you, but all the credits go to all the volunteers in all the projects, and to people like you, and to the listeners, you can make a difference too. Just go on the website, and it doesn't have to be with Help With COVID. It can be any website. Just go find something you're passionate about, and try to help out.

Eric Ries: This has been Out of the Crisis. I'm Eric Ries. Out of the Crisis is produced by Ben Ehrlich, edited by Jacob Tender. Music composed and performed by Colby Martin. Hosting is by Breaker. For more information on COVID-19 and ways you can help, visit If you have feedback or you're working on a project related to the pandemic, please reach out to me on Twitter. I'm @ericries. Let's solve this together.

Wednesday, May 27, 2020

Out of the Crisis #5, ANA Therapeutics: a possible COVID-19 treatment and prophylactic

Out of the Crisis #5 is a conversation with three people who pivoted their biotech company to help fight the coronavirus. Akash Bakshi, Nadja Mannowetz, and Andrew Bartynski are the co-founders of University of California, Berkeley-based YourChoice Therapeutics. When they realized the drug they were working with for an entirely different reason had potential to be repurposed as a COVID-19 treatment, they "dropped everything and got to work."

YourChoice was studying niclosamide, "a drug that had been thoroughly relegated to the dust bin of history" in spite of its safety and efficacy, for use as a spermicidal contraceptive. They had just filed with the Food and Drug Administration in early March when, in a play for humor during a meeting, someone pondered aloud whether niclosamide might be an effective treatment for COVID-19. That became their new mission.

It didn't take much searching to find out that the drug had been tested against SARS-CoV-1 (known to non-scientists as SARS, the 2003 pandemic) and had proved effective against the replication of that virus. The virus that causes COVID-19 is SARS-CoV-2 so the team believed they had not just good reason but a moral obligation to start investigating whether niclosamide would also would also treat and possibly even prevent COVID-19. ANA Therapeutics was founded. It was only a few more weeks before they found data that showed not only that the drug prevents SARS-CoV-2 from replicating, but that "it does so more effectively (at a lower concentration) than any of the drugs currently being tested in the clinic." From that moment, especially since they were the only biotech company with access to clinical-grade niclomaside, they were determined to get the drug into a phase III trial.

Along the way, from investors to suppliers to manufacturers, ANA Therapeutics had the unique experience of being a startup to which "no one said no, and everyone said yes." This has allowed the company to move forward quickly alongside the many other biotech efforts looking for a vaccine. The whole industry, including the FDA, is moving at never-before-seen speeds in order to, as Akash told me, "take multiple shots on goal."

You can listen to our conversation on Apple podcasts, Google podcasts, or wherever you like to download.


I've also included a full transcript below.

Show-related resources


Highlights from the show

  • Akash Bashi on his background. (2:16)
  • Nadja Mannowetz on her background. (2:38)
  • Andrew Bartynski on his background (3:12)
  • Their pre-COVID work: a non-hormonal contraceptive for men and women. (4:13)
  • The moment they realized their project might have applications for COVID. (6:27)
  • Their original vision for their company, YourChoice Therapeutics, and using niclosamide for contraception. (8:05)
  • Discussion about niclosamide and safety. (10:58)
  • Akash tells the ANA origin story. (13:12)
  • Andrew on waves of treatment for COVID and the potential and value of repurposing existing drugs. (15:46)
  • All three on why a startup is doing this work instead of a big company, including issues of speed and decision-making. (17:43)
  • The moment they decided to pivot and build a new company. (21:16)
  • Moving drug compounds from Europe to the US after the flight embargo and what the data showed. (22:57)
  • What happened after the pivot, and getting the drug into the clinic. (25:42)
  • How the new speed of biotech has changed their experience. (27:50)
  • The potential of niclosamide for treatment and as a prophylactic for at-risk populations, like those with co-morbidities and front line workers, and later for everyone as we begin to travel and reopen the economy. (29:26)
  • Discussion of how vaccines and treatments work together to mitigate disease. (35:24)
  • Andrew on what comes after social distancing. (39:27)
  • The timing of trials for niclosamide and how soon it could be available. (38:43)
  • What are the drug trials like? (39:06)
  • Differences between potential drug treatments that haven't panned out and niclosamide. (40:35)
  • The importance of well-controlled clinical data in trials before recommending usage. (43:26)
  • Differences between coronaviruses and other viruses. (44:41)
  • On how pursuing research into other viruses and pandemics like SARS and MERS could have helped us now. (45:47)
  • Lessons we can learn from this about what to invest in for next time. (48:19)
  • On how structural changes focused on short-term thinking, goals and outcomes, along with lack of planning for low-probability events, have affected us. (49:28)
  • Getting funding for their work wasn't difficult and it came from investors who think long-term. (51:36)
  • Scientific background on niclosamide, what we know about how it works to stop viral replication. (52:48)
  • The next necessary wave of research. (54:37) 
  • What it felt like to pivot away from their vision. (55:19)
  • Where they found special support and encouragement. (56:29)
  • Where the company is going from here. (57:00)
  • Discussion of health care workers as heroes, their risks (57:25)
  • Akash's aunt's surgery during COVID-19. (59:02)
  • Advice to companies thinking about pivoting to COVID-19 relief efforts. (1:01:05)
  • Ways for non-health care professionals to help. (1:02:19)
  • What they think the new normal looks like, and where we go nect. (1:04:29)

Transcript for Out of the Crisis #5, ANA Therapeutics

Eric Ries: This is Out of the Crisis. I am Eric Ries. I've always been a believer in science. And I'm incredibly grateful to live in an era where the scientific method is so widely deployed. And yet, we all know that as a society, we still struggle to give the respect and support to the researchers who are laying the foundation of future progress.

In Silicon Valley, it's not just the companies that have had to pivot and change direction, so have investors, VCs, the entire ecosystem of the startup community of biotech as an industry, has had to make a very dramatic change to work on pandemic relief, disease prevention, laying the foundation for future prosperity. And although I've only had a bit part in that transformation, it's been really amazing to see it happen and unfold in real time.

I sat down to interview three scientists who were working on a drug that has the possibility to get us out of this crisis in months, not years. I first met this company as the crisis was breaking, and was given the opportunity to invest. But their story is so much more interesting to me not just as an investment, but as a lesson for what it's like when the world completely changes your plans and you just have to go with it. It's also a source of inspiration and comfort to me.

People are talking about a vaccine that could be ready in 18 months or 24 months, but that feels a long way off. It's really important that we realize that there are therapies like this one that will work. We don't know exactly which one will make it to the clinical trials, we don't know which one will have the greatest effect, we don't know if we'll ever be able to develop one that can be used prophylactically to prevent the disease, but I have a lot of confidence that one of them will. Combined with contact tracing and widespread testing, a therapy like this could allow us to reopen the economy and go back outside. And that will feel pretty amazing.

Here is the story of ANA Therapeutics.

Akash Bakshi:  Hi, my name is Akash. My background is in biochemistry and cell Biology as well as molecular biology. And while I didn't spend a great deal of time in research, I somehow pivoted into IP licensing, which led me to meet Nadja and we founded YourChoice Therapeutics together, and that's what led to the genesis of ANA Therapeutics.

Nadja Mannowetz: My name is Nadja. I am the chief scientific officer of ANA Therapeutics. I got a Ph.D in biology, it was focused on medical microbiology to study Legionella pneumophila, a bacterium that causes atypical pneumonia. I then switched into studying sperm cell physiology, which led to the formation of YourChoice Therapeutics with Akash. And from there, we pivoted into ANA Therapeutics.

Andrew Bartynski: Hi, I'm Andrew Bartynski. I have a Ph.D in chemical engineering. During grad school, I was working on solar cells and fell in love with startups. So, once I graduated, I started working on a company in the Bay Area developing transparent solar cells, then I found myself moving over into the medical device space for a couple of years. And then, I met Nadja and Akash and heard what they were working on with regards to contraception. I couldn't get it out of my head, and I've been working with them ever since.

And then, when COVID happened, we felt an obligation to see if our technology had any application there and went with it once we saw there was promise.

Eric Ries: It seems clear to me that the only true long-term way out of this crisis is through science and the development of new treatments and ultimately a vaccine. And so, I'm really honored to have all of you take some time out from doing that work to share the story with our listeners. Tell us about what you were working on before the crisis started.

Akash Bakshi: So, the real truth is that before the crisis started, the three of us were working on developing a non-hormonal contraceptive, not only for women, but also for men. And very honestly, we had just submitted with the FDA to ensure that we both agreed on what steps were needed before we could kick off a clinical trial. We were waiting for a response back from the agency. At the same time, we received an NIH grant to fund all of the studies that we thought were required before going into the clinic.

And so, here we were starting a company that was just soon to enter into the clinic, maybe in three to six months, and then more and more about COVID-19 started hitting the news. And I'll let Andrew take it from there as to what happened.

Andrew Bartyniski: Yeah. So, we were having our weekly meeting on Mondays where we go through the task board and think about what to do next. And it was serendipitous, where we had this breath where we jokingly were like, "Okay, we have nothing to do, right? We just finished one of our major milestones, we just got this grant." And basically, this was when COVID really started becoming center of mind for the new cycle and everything else.

Eric Ries: Give us the timeline a little bit. When did you start the company and how long have you been working on it? And then, when was this exactly, if you recall, when you got the grant?

Andrew Bartynski: Yeah. So, we got this grant on March 5th or 6th and the submission to the FDA was maybe two days before that, like March 3rd. And so, this meeting, I think, was happening on maybe the 9th or 10th of March. There was a breath of fresh air where we just finished this big push for YourChoice. And then, we jokingly said, "Hey, what if the compound that we're working with, niclosamide, actually also works for COVID?" Because a running joke in our group is that niclosamide works for everything. Because if you look in the literature, it's shown great promise in a number of different indications.

And so, when we said that jokingly, Nadja diligently started going through the literature research, and in five minutes pulled up a paper saying, "Well, here's a paper that shows that during the SARS outbreak in 2004, niclosamide was actually a very potent inhibitor of viral replication." And so, that planted the seed of like, "Maybe there's something there."

Akash Bakshi: And actually, I'd build on it just a bit because we knew about the antiviral properties of niclosamide even earlier. Well, I think it tells a better story of how we came about niclosamide. Perhaps my story is I wanted to kill off the niclosamide program as a contraceptive as quickly as possible because I, at the time, did not believe that a pharma company would ever be interested in acquiring a company that was doing a 505(b)(2) play.

But what was really interesting in the development is that Nadja actually showed how effective niclosamide was as a contraceptive. But the icing on the cake was that there had been publications that showed that niclosamide inhibited HIV replication and HSV-2, which is the virus that's responsible for genital herpes. So, I mean, if you think about a contraceptive that can go about inhibiting STDs or STIs, you'd think that that is somewhat of a gold standard, right? And so, that was really interesting.

And that builds into the point that Andrew was making that it seemed that niclosamide was this just wonder drug. So, was there any proof that it worked on SARS-CoV-2?

Eric Ries: So, before we get into the science of that, because I want to come back to that point, for a lot of our listeners, they're not familiar with therapeutic startups and this world. So, if you could walk us through the founding of the company, you were talking about the different FDA pathways and what the exits might look like and what you were considering there. So, what was the original vision for the company and then how did you settle on niclosamide as a product to pursue?

Nadja Mannowetz: YourChoice Therapeutics is a spinout of a lab at the University of California, Berkeley. The main goal of this company is to develop non-hormonal contraceptives that can be used by women and men. And our core technology focuses on disabling sperm cells from getting close to the egg, and ultimately fertilize an egg.

One way you can think about it is, what if you don't allow sperm cells to produce energy? Because that would ultimately mean sperm cells would not go anywhere. And yeah, contraception achieved. Check. Been there done that.

There is a class of molecules that have been shown in other experiments with other cell types that once these cells are exposed to those substances, they cannot properly produce energy. And this is also true for sperm cells. So, niclosamide is known to prevent cells from producing enough energy and this is also true for sperm cells. If you disable sperm cells of producing energy, they become immotile, and immotiles themselves will never reach the egg.

And yeah, for us, this is really wonderful because niclosamide, it's not a hormone and it also has a long history of safety in humans because it's a drug that has been on the market for five to six decades.

Andrew Bartynski: Yeah, niclosamide was originally discovered in the 1950s by Bayer. And since then, originally was commercialized in Europe, and then in the U.S. in the 1980s as a tapeworm medication originally. And so, because there's not really a tapeworm problem in the U.S., I don't think it ever really came to prominence here.

Eric Ries: So, this is an established drug with a long history and track record of being safe for use in humans?

Andrew Bartynski: Right. Yeah, I think we found a paper from the WHO that was looking at any complication or adverse event reports over the course of 30 years. There were only 70 reported incidents. So, if you take a drug like Tylenol or aspirin, there's probably more side effect reports from that drug than this drug.

Nadja Mannowetz: And these side effects, they are not severe. We are talking about abdominal pain, diarrhea, nausea, vomiting. I think, yeah, these aren't pleasant side effects, but they are definitely more acceptable than suicidal thoughts, heart attack, or anything like that.

Eric Ries: How did you first become aware of niclosamide?

Nadja Mannowetz: That was based on literature research, looking for molecules that disable mitochondria from producing energy. So, you could say mitochondria are the batteries of a cell, so the energy-producing compartments. So, if you Google mitochondria and uncoupling, then you'll find several molecules and niclosamide always shows up.

And yeah, I mean, being a scientist, then you'd start asking, "Oh, what is niclosamide? What is compound X?" And if you would just Google niclosamide, you would find endless papers of, it has been shown at least in in-vitro experiments, to have anti-cancer properties, to have antiviral properties. And then, you'd think, "Oh, this is not only an effective compound, this is also a safe compound." And then, you would conclude it's a very, very promising compound.

Eric Ries: So, Akash, maybe you can tell us the company-founding story. Because I think when most people imagine a therapeutics company, they have this idea that people work for many years in a lab working on a novel compound, then it has to go through extensive trials for years and decades to be proven that it's safe, but they have an image in their mind of what drug discovery looks like. But this is a little bit of a different story because we're talking about an existing compound with known properties. How did you have the idea to try to build a company around an existing compound but on new application?

Akash Bakshi: It's a great question. This really was a team effort because I don't think that we could have done it if all three of us were not entirely on board. There was that day that a huge weight had been lifted off of our shoulder where we had filed with the FDA to try and understand what their thoughts were on the use of niclosamide as a vaginal gel. We received the grant from the NIH, we said, "Okay, well, whatever the studies are that you need to go into the clinic, you just move forward." And then, there was the day that the three of us were just chatting internally about, "Well, does this even work against SARS-CoV-2?"

And on that Wednesday, we had to send an investor update to the investors of YourChoice Therapeutics, in which we gave the update that the Pre-IND was submitted to the FDA. We also just got this grant from the NIH. We also are about to order a compound from our supplier so that we have niclosamide to run our clinical trial as a vaginal gel, "By the way, we think that this shows a lot of promise for COVID-19. And we think that we should run a Phase 3 clinical trial on this drug and we just need to order 15 kilograms," and that'll roughly cost about $500,000. "Let us know if you're interested."

And later that night, one of the investors of YourChoice Therapeutics responded and said, "We're in." All of a sudden, we were like, "Well, here we go. What do we do next?" And so, we ultimately decided to put all of the COVID work into a separate company. And that's how things started.

Andrew Bartynski: Well, I think what was interesting also and another point that Eric was getting at is, traditionally, biotech is preceded by 5 to 10 years of Ph.D work. In this case, it was preceded by five decades of published literature. And so, I think that the type of company that ANA is is very non-traditional.

So, if you think about responses to a pandemic from a therapeutic standpoint, there are going to be three waves of treatment, right? There's going to be the immediate first wave of therapies, which are the only thing that's feasible on that timeline is the repurposing of an existing drug. Because in order to do the necessary efficacy and safety testing for a new compound would take way too long for it to be relevant. And so, in order for us to make a difference in the next, I don't know, 12 to 18 months realistically, the most promising way to do that is through a repurposing of an existing drug with a known safety profile and unknown toxicity profile.

After that, you'll start to see new chemical entities come on board because then they've had enough time to actually be evaluated for their safety and efficacy. And then about the same time as that, you'll have vaccines come around, because the development timelines there also are non-trivial.

And so, our thinking, I think, in making this company was if there is a drug that has a long history of safe use that's been around for a while, that shows any hint of efficacy against SARS-CoV-2, you are obligated to pursue it because you'll be the fastest compound that could actually treat patients. And so, the goal here, which I think we take very seriously, is to try and find something that can contain the spread of this disease as quickly as possible. From a therapeutic standpoint, you have to go for a repurposed drug first.

Eric Ries: I think some people listening will be surprised to hear that repurposing an existing drug that that's being done by a startup and not by a big pharmaceutical company. Do you think that everyone who's got a drug, they would be testing every drug possible against COVID given the scale of the pandemic? Why is a startup in charge of this?

Andrew Bartynski: Great question. That's a great, great question.

Eric Ries: But Andrew, it sounds like maybe you have a better response than I'm thinking of.

Andrew Bartynski: Yeah, so my reason why a startup is well-positioned to do a repurposing play whereas a large pharmaceutical company is not, it comes down to the same reasons why startups aren't good at other things, is their speed and decision-making ability. So, small teams with high levels of trust can make great progress very rapidly, whereas in large organizations, it does take a long time to steer the ship in a direction.

And so, I think that large pharma companies will certainly be screening all of the molecules that they have on hand, but the decision time for them to choose a lead produce significant quantity to get into the clinic and run the trial may not be as quick. I think Gilead has definitely done a great job with Remdesivir and getting that into the clinic as quickly as possible to be evaluated. But I think that it is difficult for large companies to typically move that fast.

Nadja Mannowetz: I am also not sure how interested big, big, big pharma companies are in marketing a drug that is generic already.

Akash Bakshi: Yeah. So, I think that there's also a risk associated with, will the drug work or will it not work, if you had to think about repurposing a drug that you already have, which plays some role in your portfolio, which is why I think... I mean, I don't know. Actually, I don't even believe what I'm saying because everyone that is a manufacturer of hydroxychloroquine is increasing manufacturing capacity to see how that might work as a treatment against COVID-19. So, I don't know how much risk plays into it.

I don't know if pricing plays a role either in the fact that maybe if a drug is available for 30 cents, is it really of interest to make that available to everyone as a potential treatment for COVID-19? I'm not sure if that's being used as a part of people's calculation. But I do think it is... I would build on Andrew's point where it's hard to make that decision to say this is the drug within our portfolio that we're going to move forward as a COVID-19 treatment because the data that's available about niclosamide is very sparse.

It's all published from 50 to 30 years ago, and every paper that has ever come out again about niclosamide references these same papers. And so, it's very circular in the amount of information that's available. And it wasn't until we started doing additional modeling, until we started really interrogating questions that we started realizing that niclosamide is a great drug. But if you are looking to kill off an idea quickly, niclosamide would have been a great molecule to kill just because what's published about bioavailability or solubility is not particularly great.

Eric Ries: So, let's go to the moment when you had the realization... It sounds like this, originally, you floated this COVID treatment almost as a joke. That was a running joke in your team. But you emailed your investors, you got a sense that there was some interest there. What was the moment when you decided to completely pivot into full-time COVID as a product and effectively build a new company, replacing the work that you were doing before?

Andrew Bartynski: Yeah, so I think this is a moment where Akash refers to be a little bit as a bulldozer. And so, when I have an idea in my mind that I am pretty convinced about, I'll sometimes just go do things. And so, this is one of those moments where it was, I think it was 10:30 or 11:00 at night, where I just started following up to the investor update that Akash sent, and tried to put a finger on people to say, "This needs to happen." And so, I think that was when the company became nascent. That was what it was first like, "Okay, this could be a thing."

And then, I think the second moment where we were like, "Holy crap, maybe we're right," was when we first got in-vitro data back specifically showing that niclosamide is effective at inhibiting SARS-CoV-2 replication at 150 nanomolar concentrations, like 25 times more effective than what's been shown for chloroquine and 70 times more effective than remdesivir. It's like that was the moment where we were like, "Holy crap, we went out on a limb here and it seems as though we might be right."

Eric Ries: Where'd you get that data from? And who first brought to your attention?

Akash Bakshi: So, the first thing that we did... So, we raised capital. I mean, to be very honest, we set up an entity and then got money in. And the first thing that we did, as I mentioned, is we ordered compound from our supplier who happens to be in Europe. And literally, the day that we placed the order was the day that Donald Trump said that all flights from Europe to the United States would be halted on Friday.

Eric Ries: I remember that.

Akash Bakshi: And actually, even in that talk that he gave, he even said something about cargo, which scared the hell out of the three of us because here we are and we need to get drug from Europe to the United States, and we've just learned that we have two days to figure out how to ship all of this over. So, that is one major part of our brains of just logistics had never been something that we ever had, as a team, appreciation for until we had to, in a very tight timeframe, move drug from Europe to the United States when fights were being canceled.

But the second thing that we did is we sponsored research in the lab of Dr. Pei-Yong Shi and had him specifically look at the ability of niclosamide to inhibit SARS-CoV-2. So, that was the next step.

And when that data came back at 150 nanomolar, meaning for a company that was working on non-hormonal contraceptives, this is like hormonal level accuracy or precision that you're able to fight off SARS-CoV-2. That was just like a Oh-my-God moment. I mean, there are other words that we were probably using, but it was just like, "Wow, this is crazy" of how right we were. We knew that niclosamide was going to work, but it was going to work as well was still a surprise.

Eric Ries: So, how can it be that... I mean, at this point, chloroquine has become a national word that entered into the public awareness as a potential treatment. You're saying that this treatment could be dramatically more effective. Why doesn't anybody know about it yet?

Akash Bakshi: I wonder to what extent supply chain plays a role, because niclosamide is not available for off-label use or in the United States, at least, or in most Western countries, your doctor can't write you a prescription for niclosamide because no one is selling niclosamide in the United States. And so, I wonder to what extent that plays a role.

Eric Ries: Let me see if I've got this right. Last year, you thought you were going to be working on a startup related to a non-hormonal contraceptive around niclosamide, a drug that's been studied for decades and is shown to be safe and has this amazing antiviral properties.

You're just about to start clinical trials, you've raised money, you've built the company, you've got your NIH grant, and then this crisis hits. You have this idea that maybe the compound could be useful against COVID. You commissioned research that shows that it's a lot more effective even than you thought. And since the drug is already known to be safe, you realize that you're sitting on a potential treatment for the pandemic. What happened next?

Akash Bakshi: We turned all of the resources that we had developed over the last year into quickly getting niclosamide into the clinic for COVID-19. So, we were in this unique position where just a few weeks earlier, we had filed with the FDA for niclosamide as a vaginal gel. The same group that had helped us with that filing, we asked to immediately start working on the filing of niclosamide as an antiviral for COVID-19.

The supplier who had provided us GMP material drug, we then got to increase the amount of drug that we needed so that we could move that back into the United States so that we could start making pills. The group that was making the gel for us, we then said, "Hey, could you hold off on making the gel? Can you make pills with the drug that we have on-hand?" And what was crazy is no one said no, and everyone said yes.

Andrew Bartynski: Yeah, I would say that that has been the most incredible experience throughout all of this, is that in startups, you're used to hearing no nine times and yes once, and here you're truly hearing yes nine times and no once. And that's really cool.

Eric Ries: When I was talking to Sam Altman, he said that one of the most amazing things he's seen is that it's almost like the entire biotech industry has turned on a dime, and every single company has gone all-in on COVID response. And as a result, the clock cycle of the whole industry has changed. All of a sudden, things are happening faster than anyone dreamed possible before. It sounds like you're having that experience. You're like living in real time.

Akash Bakshi: That's really true. I would say that the response from the FDA is a funny story. We had filed with the FDA for the vaginal gel, March 2nd, and we ended up getting a response back April 6th, which is a very normal time frame by which to get a response. We filed with the FDA on March 23rd for COVID-19 and I think two days after we got the response for the vaginal gel, we heard back from the agency about our achievement for COVID-19. So, even the FDA is thinking at a super fast speed.

Eric Ries: When was the last time you heard about an order of magnitude speed up in government responsiveness? That's a really positive story.

Akash Bakshi: I mean, these are all things that just help us continue to move faster as we try and get something into the clinic, so that hopefully there is a treatment for individuals who are COVID-19 positive or even a prophylactic treatment for those that are at risk.

Eric Ries: Yeah. So, talk a little bit about the potential here, because I understand that you're limited in the claims that you can make so I'm not asking you to predict the future. But let's say, hypothetically, that when you do the trial, this drug is validated to have the effects that you believe against COVID. And imagine that it works the way that you imagine right now. How soon could this be helping treat people and what could the treatment mean for people who are affected?

Akash Bakshi: Yeah, it's a tough question to answer and much of it is based on the results. But yeah, just to build on, if the results are outstanding and it's very clear that we're helping people and not having a negative impact, there's no reason why we wouldn't see being able to make this available by the end of the year.

Eric Ries: You said it could potentially be used prophylactically. Explain what that means.

Akash Bakshi: I mean, that's another area that is really of interest to us is, if you use an antiviral, either just after you think that you might have been infected or if you use this just because you're at risk, what we're learning is that low doses of these antivirals can actually play a really important role in preventing a virus from really having its full course.

And so, one thing that we think about, given the safety of niclosamide over long periods of time, is that this actually seems like a great drug for individuals who are in the healthcare space, who are likely working with COVID positive patients as a post-exposure prophylactic because they're just at risk of getting COVID-19 from those that are around them, and that we think could help with 13 million healthcare workers in the United States.

But then, we also think about the other patients who are maybe over 60 or have other comorbidities like asthma, that are problematic and who can afford to get COVID-19 and that we also see as a potential, just given the safety profile of niclosamide that it could be something that they take to potentially de-risk or prevent them from getting COVID-19 in the first place.

Eric Ries: So, you're saying that for nurses like... I mean, certainly our national shame in this country has been the fact that we have frontline health care workers treating COVID-19 patients without protective equipment, who hasn't seen the images and gotten the Facebook messages about nurses desperate to find rain ponchos and God knows what else. It's been awful.

So, you're saying that those folks who are at most at risk, this is a drug that they could potentially take on a daily basis just to prevent them from getting the disease or getting the worst symptoms of the disease? What would be the effect if you took it prophylactically and it worked?

Andrew Bartynski
: Yeah. I mean, I think the best example of this would be something like PrEP for HIV, right? And so, in at risk populations, if they have sufficient antiviral drug concentration in their blood, it's possible to prevent infection from occurring. And so, that would be the goal here. Obviously, you have to run the clinical trial in a well-controlled fashion to prove that's the case.

But our hope is that once we're able to prove that this is an effective antiviral in COVID positive patients, the logical next step for us and the real broader societal need will be for prophylaxis for those who are at high risk of exposure or at high risk of significant complications if they do become infected.

Akash Bakshi: And I actually think, just building on what you're saying, Andrew, I think that a drug that works prophylactically would play a really important role in opening up the economy again. Because, I think, I wonder to what extent COVID-19 is, like how 9/11 changed travel for everyone for the rest of their lives, I wonder if this just changes how we interact or how we go about the rest of our lives.

And so, again, I wonder if travel will be the same. I wonder if how social distancing will play a role for us long-term because it's not as though COVID-19 is going anywhere. And until there's a prophylactic treatment, how do we engage in a way to prevent ourselves from getting COVID-19? Or if you have it, how do you know... Just because of the latent time that it takes to actually show itself, how do you know who's safe? And so, that's why I see this playing an important role.

Eric Ries: A lot of people that I've talked to have their hopes pinned on a vaccine. So, even people who are looking at the worst-case scenario, a very common refrain I hear is, "Look, 18 months or 24 months from now, at a worst-case scenario, there will be a vaccine. This problem will go away and things will return to normal." And of course, we all pray that that's true, but I keep having this thought as a lay person in the back of my head, I say, "Well, that sounds good, but if the virus doesn't mutate. Maybe we build the perfect vaccine for this strain, but a new strain emerges, and there's a second peak, God forbid." My understanding was that the second strain in the 1918 pandemic, that was really deadly.

And so, even in a world where there might be a vaccine coming, it seems really prudent to me or maybe even essential that we have other forms of attack of treatment, of prevention. So, talk a little bit about the difference between antiviral drugs and vaccines, and whether you see both playing an important role or is it just over different timeframes? How do those two concepts fit together?

Andrew Bartynski: Yeah. I think there's actually a great analogy here between antivirals and antibiotics. And yeah, resistance is obviously a concern. And the way that they mitigate that in antibiotics, right, is you have broad spectrum and highly targeted versions of these compounds. And so, I think a similar strategy for antivirals makes a lot of sense, right?

If you only have a single attack vector that you're going against a virus for, it's possible that it can mutate around that vector. But if you're taking multiple approaches to either inhibit replication, prevent entry of the virus into cells, or to just target the virus particles themselves, I think that gives you that robustness to evolutionary pressures.

Akash Bakshi: And I would say that I think we're all hoping for the vaccine to come out as well, right? I mean, what Andrew is pointing, an antiviral is something that you're also dependent on individuals to be compliant around. So, are you taking your pill every day? Do you take it at the right time so that we can make sure that the PK levels in your bladder sit at the right level? A vaccine is hopefully once, or I mean, some vaccines take three times to administer but at least a vaccine would help a lot in this area.

The other thought about that is, do we have... We need multiple shots on goal, so there needs to be a shorter-term response. Because even right now, let's say, without a treatment that was available, are there enough face masks for Americans to use when we go out or if you were to take public transportation? I don't think that that's available right now. And so, again, I think of this as, all of it, a jigsaw puzzle where there's not one answer but there are a lot of pieces that come together to help fight COVID-19.

Andrew Bartynski: But I also, I don't want to be just doom and gloom as though there's no hope. Right? As we've seen, social distancing does work, so that's great. That's step one. We have something that works. That's the necessary first step. And then, everything that we do from here on out will be an improvement on what was there previously, right? We know social distancing works. So, when we see flare ups happen again, we can always default back to that state.

The question is, what comes next in terms of allowing us to increase social interaction? And the way that we do that is through better basically medical countermeasures, right? So, it's through therapeutics, through vaccines that we're really able to go beyond where we are today and return to some degree of normalcy.

But I don't think the focus should be that there's no option now. I think the focus should be, we have something that works now and you can see that already taking effect in places where social distancing has been aggressively implemented.

Akash Bakshi: That's right.

Andrew Bartynski: The real question here now is to return to normalcy, what's the quickest path and what's the safest path? I think that's what we're trying to focus on.

Eric Ries: So, how soon could this happen? How soon do you think you could have some of the trials go well and you could have this drug in the hands, for example, of nurses to use prophylactically?

Andrew Bartynski
: So, our most aggressive timelines put that somewhere in the six-month timeframe. But again, that's always dependent on the outcome of clinical trials and the supply of drug that we're able to manufacture.

Eric Ries: What are the trials like for something like this?

Andrew Bartynski: That's a great question. And I think that's been one of the main difficulties that's been exposed in the COVID pandemic. So, the mainstay of evidence-based medicine is the randomized control trial, right? This is where you have your placebo group, you have your drug group, you randomly assign patients to them, you can do a very orderly follow-up where they come in, and you know all of the parameters that you're doing, you know your patients have only done what you've told them to do. And that kind of got thrown out of the window in the beginning of February.

And so, doing these trials is actually extremely challenging. And that's because we're in situations where there's no PPE, we're in situations where a variety of different medications are being used at the same time because we're looking for any way to ameliorate the symptoms of patients.

And so, what we're trying to do and our goal, is to really run a well-controlled trial, so that you can make scientifically-based conclusions about the efficacy of niclosamide. And so, what's been done so far with some of the other studies that have come out is that they've either been extrapolated from really small sample sizes or they haven't necessarily been very well-controlled, which is understandable because it's a very difficult time to do those studies. But it also becomes difficult to say what's working when you don't have good data.

Eric Ries: When I heard that the more recent data about chloroquine has been that some of the early benefits maybe were overstated or maybe were a sample size, wrong extrapolation. So, talk a little bit about why some of the existing potential treatments haven't panned out as well as you hope and how those are different from the compound that you're working on.

Akash Bakshi: So, one of the biggest differences between hydroxychloroquine and niclosamide, at least, from where we're standing is, again, safety profile is something that plays a really important role. And often what we're seeing in these hydroxychloroquine studies is a big ratcheting of a typical dose.

If, let's say, you're going to India during malaria season, your physician will likely give you one tablet that you take once a week. And that's just been my experience when I went to India with my mom as a kid. But now, what we're doing or what we're seeing individuals do is one pill a day. You ratchet up a drug that has known side effects. But by comparison, niclosamide, just because the IC50, or the concentration that's required to inhibit the virus's growth, is so much lower, you actually see that you don't need to really necessarily change the dosing from what has historically been done.

So, that allows us to just think about safety in a different paradigm, or at least hope that the drug continues and remains to be very safe in patients who are COVID-19 positive.

Eric Ries: I've heard in the vaccine world that there's some talk about accelerating the trials, accelerating the pace of getting this data by recruiting volunteers given how many people have been involuntarily exposed anyway. Is something like that possible here if there were volunteers who are willing to take the compound and have their data recorded? Is there something like that that could accelerate the timeline?

Akash Bakshi: Yeah, I wonder. I mean, I think the first trial that we're trying to run is in COVID-19 positive patients. And so, I think that necessarily those patients who are COVID-19 positive are likely looking for treatment anyways, but absolutely when we move to a prophylactic space, I think the first line of defenders that we would think of are health care workers who are an ICU user regularly engaging with COVID-19 positive patients.

Eric Ries: If somebody had been exposed to COVID right now and they were able to get their hands on this drug, would they be able to take it for this purpose?

Andrew Bartynski: I would not advocate that until clinical trials have been completed.

Akash Bakshi: I fullheartedly agree.

Andrew Bartynski: Yeah, I would strongly advise against what we saw happened with chloroquine, where somebody took something that they thought would be helpful and ended up overdosing and passing away. I think that is the worst-case scenario of what happens in medicine, and I think it's exaggerated in the current climate where people are scared.

So, again, our emphasis here is on well-controlled clinical data to support widespread use. And until that data is there, I think it's important for everyone to think, "Does this actually work?" And so, I think a lot of the treatments that are out there today, I think people need to think a lot more critically about whether those drugs are working.

Akash Bakshi: I figured you would say that, but I want to give you a chance.

Andrew Bartynski: I think it's important. That's something that you really have to hammer.

Nadja Mannowetz: And to build on what Andrew just said, I think we have to just make sure to understand how COVID-19 patients react to niclosamide.

Eric Ries: So, if you're listening to this now, do not start taking off-label drugs without having the appropriate data come in.

Andrew Bartynski: Yeah, everybody should refer to their physician, and I hope that their physician refers to their best judgment.

Eric Ries: What is it about coronavirus that is different or difficult compared to other viruses that we've battled through history?

Andrew Bartynski
: Well, they do seem to keep propping up, don't they, right? So first, we had SARS, then we had MERS, and now we have COVID-19. So, I think one thing that's problematic about them is their virulence or their capacity to spread and their mortality. Right? And so, I think that's the thing that makes this different than a standard flu that comes through, I guess.

And then, another thing that's been problematic, so they have propped up time and again, but they haven't stuck around long enough for us to be able to complete the development necessary to find a treatment. And so, COVID-19 and SARS-CoV-2 I think is the first coronavirus, to my knowledge, that was persistent enough and virulent enough for us to have the capacity to develop therapeutics or vaccines against.

Eric Ries: One of the things that really struck me about the story of COVID-19 is how many times people have referenced things that we learned during SARS or one of the previous epidemics that could have been applied here but it wasn't because we just didn't seem like it was worthwhile. Given the effectiveness of this drug was known against SARS, couldn't these trials have been done? Could we have been better prepared to bring drugs like this to market faster? Couldn't we have a fast trial pathway or infrastructure we could have developed that would make us more able to respond now?

Akash Bakshi: I think that's right, had SARS and MERS perhaps been pursued more or had there been more work that went into looking for treatment then, we could really build on that now. But instead we're picking up from where researchers left off in SARS and MERS and are trying to quickly move forward with something that works against COVID-19, and really took out all of the thoughts that they had then.

Andrew Bartynski: I think this is endemic in the infectious-disease space where the perceived necessity of a treatment is directly correlated with a number of cases at the moment, which is just like a bad metric, right? The real metric should be funding should go into something or something should be developed until there is a treatment. And then, once there is a treatment, yeah, then maybe you don't need to pay as much attention to it.

But I think that, again, this is hindsight being 2020. It's easy for us to say we should have done more at the time. But I think, again, resources are competitive and time is scarce. And so, once people see a disease decrease in its caseload or prominence, it gets relegated.

Eric Ries: Such a classic short-term thinking. One of the themes that's come up in a lot of these conversations is that this is not the moment for recriminations and blame, but I do think it's important for us to learn from the mistakes that we made in the past. So, I'm really a believer that we will get through this crisis, that there will be a recovery. It's going to get darker before it gets better, but we'll get to that other side.

What are the lessons you want people to learn from what you've seen so far? What are the investments we should be making to make ourselves more able to respond and react, make our society more resilient for next time?

Akash Bakshi: At a high level, I would think more investment in the life sciences just more broadly. I mean, I think infectious disease... So, the three of us did not originally intend or did not originally start our first company thinking of infectious disease at all. We just happened to be in a position where we could quickly move and enter into the space and do good.

I think infectious disease likely has not been nearly as much funding as it really needs. And I think more funding for the basic sciences or continued working on spaces is obviously important, I think. And we hear about that all the time, where we hear more and more bacteria are becoming antibiotic-resistant and what are we doing to create more drugs for that.

Eric Ries: The next time you hear someone saying, "What is basic research for? What is it ever done for us?" maybe they'll remember this moment.

Akash Bakshi: Oh, yeah, hopefully.

Eric Ries: It's such an easy thing to cut funding for because it has no practical benefit whatsoever, until it becomes a civilization-ending catastrophe. Then you would say, "Why did we fund this research all along?"

Andrew Bartynski: Yeah. I mean, I think there are two very structural changes that have happened in maybe the past 50 years in the world. And some of it is just the focus on short-termism. And the windows of thought have seemed to continuously get compressed in time, where we don't really have 5-year plans, 10-year plans, 20-year plans anymore. We're just constantly very focused on of short-term goals and outcomes.

And then, coupled with that, there's just the lack of planning for, I guess what are called, low probability events, right? I think this is just like a humanity or a very human problem, where if we see something that has a 1% chance of happening, in our minds, we very easily make that 1 to 0. And we do have to realize that 1% chances and 1% outcomes do happen, and we should prepare for them even if that ends up being something that we don't see the realization of, maybe it's our children that do or something like that. And so, you have to really think about the full spectrum of risks that can occur and not just the ones that we think would occur in the short term.

Eric Ries: I hope this is also something people will keep in mind next time they start criticizing tech startups for being useless. Because thank goodness, that you are working on this tiny, little obscure problem in your own little company. It probably didn't seem like it was necessarily the most world-changing thing at the time you were doing it. Certainly, I can imagine the skepticism you must have gotten from other people having done a lot of startups myself. And now, you could be in a position where we're all going to be incredibly grateful that you did it.

I would have thought that one of the difficulties in raising money for this pivot, I mean, just to put myself in the seat of an investor would be people saying, "Wait a minute, if a vaccine is coming, isn't the economic opportunity here limited to pursue this drug as a COVID treatment?" So, how did you overcome that kind of business skepticism, if you encountered any, as you were trying to get the startup and the pivot funded?

Akash Bakshi: So, I think somewhat luckily, it's not something that we've heard a lot because I think, folks think of it maybe in two ways that, A, if you develop a treatment for COVID, I think that there's definitely financial returns that are possible, if not, reputational gains that will result from doing this work. But the other is, again, thinking about the long term while we're waiting for a vaccine. So, if no other treatment is developed, there is a lot more pain that folks will feel as a result of just the economy not opening up fully. That's another consideration to think about.

And then, the last is also the fact that as we think about a treatment, sure, you can go after those that have been infected, but the prophylactic is a bit of a longer play, and one that would span the entire period up until everyone has been vaccinated, which still will be years after the vaccine is ultimately developed and shown to be effective and safe.

Eric Ries: Nadja, do want to just give us a science background just about niclosamide and how it works and maybe just a little bit about your research? I just want to make sure that people who are interested in the science behind this have a chance to understand how it works and what we're doing.

Nadja Mannowetz: Yeah. So, the mechanism in which niclosamide prevents replication of this virus is still not fully understood. But based on a previous study, we think that it works by the following mechanism. So, think of a cell that is infected with the virus, it then turns on a mechanism that is called autophagy, which means parts of the cell that are infected will be destroyed and recycled in a very orderly manner. So, in that scientific group showed that niclosamide turns on that process of autophagy, meaning the parts of the cell or the cell as a whole that is infected will be destroyed and recycled. Hence, virus replication will be inhibited.

As I said, we are not entirely sure if this is also the case for the current virus, but it is a very good starting point to do further research.

Eric Ries: What do you think the next wave of fundamental research that's needed here is?

Nadja Mannowetz: Yes, so, further research that is needed is to really understand what role niclosamide plays in the whole process. Does it prevent the virus from entering a host cell? Does it prevent the virus from inserting into the host cell's genome? Does it prevent the burst of the cells so that the virus can spread? So, these are all parts that we, as researchers, need to look into.

Eric Ries: Akash, maybe you can talk a little bit about what does it feel like to take your whole company and put it on hold to build something new, not really knowing if you'll ever get back to the original vision or plan that you had?

Akash Bakshi: I don't think I have yet ever thought that we're never going to return back to the original vision just because I think it's so important. But I will say, it's frightening because you're... I mean, the three of us have all taken a leap of faith in doing something that we think is the right thing to do. But despite being a bit fearful is the fact that I think we've been well-received, and we've received just a lot of encouragement along the way from people who I think are way smarter than us. I mean, when we say that we've not received a lot of nos, it's just because everyone has been so encouraging.

Eric Ries: Anyone who you found especially supportive or any stories you can tell us about people that really stepped up to encourage you to take this risk?

Akash Bakshi: I would say the YC network has been super helpful, I think our partner, Jared, biopartner, Uri, PB, Sam Altman. I mean, that community is what allowed us to take a breath of fresh air to really consider, to feel more financially stable and fund much of the work that we had to do to get to this point and really allow us to go full steam ahead.

Nadja Mannowetz: Yeah.

Eric Ries: What are the next steps for the company? Where do you go from here?

Akash Bakshi: So, the next step is a clinical trial, and we have some guidance from the FDA as to what they're looking for. And so, it's a matter of raising the capital that's needed so that we can begin enrolling patients and run the trial to see how niclosamide works in COVID positive patients.

Eric Ries: Who do you see as the heroes of this crisis?

Nadja Mannowetz: Healthcare workers.

Akash Bakshi: That's the real truth.

Nadja Mannowetz: Yeah.

Akash Bakshi: We're just trying to help but they're doing God's work. And it seems so thankless and they're really putting their lives at risk.

Eric Ries: Yeah, it's a profound thing. And I hope one of the things that will come out of this crisis is a renewed appreciation for things that we take for granted, like their incredible endurance and the sacrifices that they make on a daily basis.

Akash Bakshi: Without PPE. I mean, sometimes I don't want to throw out the garbage without wearing gloves. And to think that you're really exposing yourself at risk to really just help other people, they're the real heroes.

Eric Ries: I saw on social media an image someone had posted of a nurse who had a sign that said, "We're not heroes, we're being martyred and voluntarily against our will," something like that. And I just felt sick.

Akash Bakshi: Want me to be very honest? I think I got shivers thinking about it. But just honestly, I have a few cousins who are physicians, and when my aunts and uncles and I, we chat during the social distancing, I'm always asking how are they. I just think these healthcare workers, they're putting themselves at risk, but they also are putting their families at risk and the toll that COVID-19 is having on other patients is truly felt by everyone because I'm sure we all know healthcare workers and we're all worried about how they're feeling.

Akash Bakshi
: Nadja knows this or Andrew knows this that during the shelter-in-place, my aunt, she had a mastectomy for breast cancer.

Eric Ries: Oh, I'm sorry.

Akash Bakshi: And the fear then quickly became... I mean, at some point there was the fear of like, "Oh my God, is she going to have her surgery at all?" Then when it was clear that she was going to have the surgery, then the question became like, "Is she going to be at risk of getting COVID-19 for having gone into the hospital?"

And so, I just think that though the work that... I mean, the truth is that all the healthcare workers that have been doing all this work, they're putting themselves at risk, but they're doing it at the benefit to allow cancer patients to continue surviving, or allowing folks who might just hit their heads. I mean, I don't think that this is right and I think that it's really stressful that we don't have...

This is where I personally feel like there are levels of the things that we need, and PPE is the bare minimum of what we need to begin offering not only healthcare workers, but just the public at large to feel and be safer. And I think it was stressful that the CDC didn't come out with the guidance or the suggestion that we should wear masks in public until just very recently.

Eric Ries: Yeah. And there's actually been a private sector group called #Masks4All, we'll put a link in the show description, that has been leading the way on getting the public educated about the need for masks and to make sure we don't use medical masks in public. And that the governor's need to pass executive orders and a whole bunch of stuff that has to happen to help prevent transmission as the economy reopens. And we see this again and again and again in this crisis, private sector leaders, startups, investors, people you'd never imagine stepping up to lead because that's what's needed.

If someone is listening to us right now, and they have a startup and they think there's a possibility that they could pivot and go into COVID relief efforts and move away from their original vision or they're feeling some fear about that, some anxiety about that, what advice would you give them?

Akash Bakshi: I think you have to do it. Andrew is really good at talking about moral obligation, and I wholeheartedly agree with him. I think of it in a different way. If we had not pivoted, I wonder to what extent... If we were still only working on YourChoice Therapeutics, I think that I would be stressed and feel guilty for not having done something.

And the flip side of that is also that as a result of working unimaginable hours that... I joke that if we had not done this, maybe we would have just been relaxing and just watching TV. But this has really given us something to focus our attention and not feel like we're helpless. And it makes us feel like we're playing an important part of the COVID-19 recovery plan.

Eric Ries: For people who are not doctors or nurses or healthcare professionals, how can they help?

Akash Bakshi: I have an aunt who is not a physician. There are still families in the Bay Area who are unable to have meals because they're unemployed now. And so, my aunt plays a role at the Samaritan House in San Mateo County. And so, I think it's challenging because yeah, she has to social distance. But I think, you don't need to be a medical, you don't need to be a life scientist or a biologist or a tech to help someone because I think this is something that affects everyone in so many different ways.

Nadja Mannowetz: Yeah, I also heard about that program, I just forgot the name of it, where you can have a daily phone chat with an elderly person at a... Are these homes called elderly care facilities?

First, I thought, "Oh, that sounds interesting," and then I realized, "But I just don't have time."

Eric Ries: Yes. So, think of it this way. Well, I'm not using the lab trying to cure this disease, the rest of us can pick up the slack of the thing she doesn't have time to do. We'll look up that program and put a link in the show notes.

And listen, this is not a time to feel shy about that. We all have to help in the ways that we can, and I think there's so many important things that need to be done right now. I mean, I was just talking to a group called Frontline Foods, and they have figured out a way for people to donate money so that restaurants that are about to go out of business can provide free meals to frontline health workers. And we're seeing that over and over and over again, people creating these pop-up organizations that can do so much by way of helping. So, not everyone can be in the lab building the cure, but all of us have a part to play.

Akash Bakshi: That's right.

Nadja Mannowetz
: Mm-hmm (affirmative).

Eric Ries
: So, do it for Nadja. That's all I'm saying. What do you think will be the long-term impact of the crisis? What does the new normal look like?

Nadja Mannowetz: So, if I just share how I personally try to answer this, I actually don't know how it's going to feel to take public transportation at some point again, to be around other people. It is, I think, I don't know. When do you start trusting the world again? For me, I personally don't have an answer to that.

Akash Bakshi: I can build on that. And I'd say like, when is it safe to go to a bar or a social gathering again, right? Maybe a bar is a horrible example. But I just think when will it be normal again to just meet up with friends in a social setting, at a restaurant or at a place where you're closely packed in with other people? I think that's interesting. Maybe that's coming from the fact that I'm single in COVID-19, I just wonder what that's going to be like. But the other part of me is I love Indian classical music, and I think when am I going to go to a concert where you're sitting so close to the next person and not feel that I need to social distance?

Eric Ries: Where do you think we go from here? How do we get out of the crisis?

Akash Bakshi: I mean, the number one is that we need PPE. I also think the next step is a safe and effective treatment. Yeah, I think that's the only way. And then, the prophylactic as well. But how all of those things will come in and who will ultimately have the product that works, I think only time will tell.

Eric Ries: This has been Out of the Crisis. I'm Eric Ries. Out of the Crisis is produced by Ben Ehrlich and edited by Jacob Tender, music composed and performed by Cody Martin, hosting by Breaker. For more information on COVID-19 and ways you can help, visit If you're working on a project related to the pandemic, please reach out to me on Twitter, I'm @ericries. Let's solve this together.