“No Rain, No Flowers: Funding Start-ups” Lessons From Davos

"No Rain, No Flowers: Funding Start-ups" panel at WEF 2024

At the World Economic Forum’s 2024 Annual Meeting, Managing Partner Navin Chaddha spoke on the “No Rain, No Flowers: Funding Start-ups” panel. Watch the panel recording or read the full transcript below.

Sara Kehaulani Goo: Hi, good morning and thank you so much for joining us this morning for our conversation. We’re calling it “No Rain, No Showers: Funding Start-ups” here at the World Economic Forum. I want to welcome our guests who are here in person, and I also would love to welcome our guests who are joining us online. If you want to join the conversation, please use the hashtag WEF24. I’ll be your moderator today. My name is Sara Kehaulani Goo. I’m the editor in chief of Axios, a Washington, DC-based news organization, and thrilled to join you here to have this important conversation. And the topic here is we’re going to over the next 40 minutes discuss a global picture of funding for startups. And here we have some great panelists who bring different perspectives, not only from their different geographies but also their different aspects of the business.

And why does it matter? That’s what we say at Axios. The why it matters is that global funding and entrepreneurship is an important engine, of course, of economic growth, of jobs, a driver of the economy. And yet as many of the panelists will probably talk about soon, access to capital remains very tight. And just last year it was down 42%, global venture capital in 2023 year over year. So we’re here to talk about that, but also to look forward to 2024. As many of you know, there’s a lot of excitement also about AI and funding and investment in that space in particular. So without further ado, I’d love to get started and introduce you to our esteemed panel. First I’ll start with Navin Chaddha. He’s the managing director of Mayfield Fund based in the United States. Rishi Khosla is co-founder and CEO of OakNorth of UK. Ahmed Karsli is co-founder, chair of Papara from Turkey. And Jacqueline Poh, she’s managing director of the Economic Development Board of Singapore. So welcome to all of you. I’m so glad that you’re here.

Navin Chaddha: Pleasure.

Sara Kehaulani Goo: Okay, so we’ll start with you Mr. Navin. I read just a few months ago that you are a contrarian, venture capitalist and that you’re writing more checks than ever while others are pulling back. And you did raise a lot of money in 2023. So I’d love to hear a little bit more about your philosophy and this contrarian approach to investing.

Navin Chaddha: Absolutely. So first, for context for people, the firm I manage, Mayfield, we have been in business for 50 plus years. So we have seen many upcycles, many down cycles and have been very lucky to be part of a lot of iconic companies, 120 IPOs, 225 acquisitions. And what we have learned is when markets get troubled and when they are tough, that’s a great time to start an early stage company. And the aim is when you’re investing at the peak of markets, assets are inflated. And when markets dip, you can get in early, you can get in cheap and help build companies. And so our approach is when 2020, 2021 was happening, markets were peaking, money was pouring into venture capital. We slowed down based on our patent recognition over the last 50 years and we said this is the time to sell rather than to buy.

So we created a lot of distributions because paper gains IRR, TVPI is only so helpful. LPs want money back. Our job is to take small boxes of money, make them bigger and send them back. So I think our feeling is the moment the market’s got sanity and they’re tough, just lean in. So we have been growing year-on-year, are investing by 50% and it’s okay. And I think there’s a lot of talk about, and our focus is the United States, that funding levels have gone from 350 billion in 2021 to 240 to 170. But just as a reminder for people 2018 and 2019 was 140 billion and 2012 was 40 billion in the United States in venture capital.

So we should stop complaining, right? 170 billion is still 4X of what it was a decade back. And you can take any amount of inflation, put it cumulative, you still don’t get to more than 4X. So we are still up two to two and a half X. There was a lot of indigestion in private markets. It’s getting cleared up and it’s survival of the fittest. So we are extremely excited to be funding early stage companies, that’s what we do, and help them become industry leaders of tomorrow.

Sara Kehaulani Goo: And oh yes, go ahead.

Rishi Khosla: Can I just pick that up? So I’ll give a slightly adjacent viewpoint. So OakNorth’s a business, which is a digital commercial bank that focuses on really funding scale ups. And to take your point, Navin, if I look at 23 for us, you look at sort of the fall of SVB and then lastly, sort of First Republic and Signature. All of those banks really played into the entrepreneurial class, right, in terms of supporting the entrepreneurial class. And for us, again, it was one of those moments where we stepped up.

Navin Chaddha: Yep.

Rishi Khosla: Right. So last year, 23, we would’ve lent an additional $2 billion in terms of gross lending. We are a UK-based business, but we decided to enter the US because of,-

Navin Chaddha: Makes sense.

Rishi Khosla: Somewhat of the void which was left. And if I look back at our history, we started the business since September 2015. When the Brexit referendum vote happened in 2016, we were still a very small business, but we tripled the size of the business in six months, right, because everyone else retreated. Covid, right, at the beginning of Covid, everyone else retreated, we stepped forward. So I think there’s a lot to be said in that when there’s general exuberance, whether it’s in the equity or debt markets, it’s sort of the time to be slightly more cautious because everyone’s getting a bit heady. But at times like this is exactly when, if you lean in, our view is you end up building a better business and you support great businesses because the entrepreneurs which are actually doing something in this type of environment tend to be the stronger entrepreneurs who actually have the wherewithal to actually grind through.

Sara Kehaulani Goo: And can you go a little deeper on that? I’d love to get your perspective about where do you feel we are now? There’s a lot of buzz and excitement about investing in AI companies. Everybody’s putting AI attached to their business, whether that’s real or not because it does have a lot of buzz. Do you feel like we’ve hit bottom when you think about the market, down market, are we still there? Are you investing more this year?

Navin Chaddha: Yeah.

Sara Kehaulani Goo: Basically.

Navin Chaddha: We are going to be investing more this year and I think markets go through ups and downs. Humanity is optimistic. There’s always a next new bubble which gets created. The next new tulips get found. And I think this wave of AI is actually as big as the PC era, and it’s a fundamental transformation of how humans are going to interact with machines and how AI is going to be able to do cognitive tasks to amplify humans. And whenever that happens, right, like there’ll be a lot of excitement, a lot of buzz, and as a result, fewer companies, more capital chasing again, the valuations will go up. So what we have learned is we cannot, as a venture capital firm, look, as an early stage firm, we were investing in AI for five to 10 years back. And then with GenAI, it happened last September with ChatGPT.

But as a VC, what we have learned is you have to look for the next wave and catch it and be ready when it’s going to peak. But when it passes you, that’s no point if you have so far to go. So you have to have a long-term perspective. We already have like 25 plus investments over the last five to seven years and these will grow and we’ll be careful on which companies we invest in in the AI hype, but the stage we invest in primarily at the inception stage, very difficult to invest. It’s people with paper and pencil ideas and prices are still good. And our job is to find the diamond in the rough. And that’s what we love doing. And it’s a craft, right? There’s no numbers, there’s no market, there’s nothing. Sometimes there’s no teams and then you help build them and the follow on money just gets poured.

So it’s the same story. It’s the same story in which you move from one wave to the next, but this is real. Real companies are going to get created. And you guys do a great job of covering some of these things. You look at the market caps of the magnificent seven, like the way NVIDIA has grown, the way Microsoft is growing, Google, Amazon, Facebook, it’s just amazing. And today the value has been accreted with the hype towards these big companies, but there’s a lot of open problems.

Sara Kehaulani Goo: Yeah.

Navin Chaddha: So I’m very, very bullish, but very mindful of how VCs invest because everything is not going to be worth 10, 20, 30 billion. And also a word of caution to entrepreneurs, whether you take debt, whether you take venture money, it’s all borrowed money. Let’s build real companies and not just focus on just growth, growth, growth. Look at, hey, when can I be self-sustaining? So I think hopefully all of us have learned from what we have seen over the last 20, 30 years and apply those principles. Otherwise, our job is not as a venture firm. We’re not a media company to accumulate logos and buy beachfront properties. Our job is to create financial returns.

So it’s a healthy balance, right? At the end, investors, institutional investors, look at venture capital firms and say, okay, public market bonds do this, public markets do this, buyout does this, real estate does this, private equity does this. I’m giving money to the most illiquid asset class. And you’re supposed to make, as a top tier firm, 500 to 700 pips more per year than some of those other assets which are less risky. So at the end, it looks great. You’re creating startups, building brands, you’re a money manager, right, like at the end to be able to raise money. When you take money from people, you have to multiply it and give it back. And that’s where, right, people who have been in business for a long, long time just realize it’s not about this hype, it’s about making money.

Sara Kehaulani Goo: Ms. Poh, I’d love to bring you into this conversation because I read that your agency has been focusing on AI as a focus for supporting the growth of startups. So what is your perspective? We just heard the private sector perspective, the venture capital perspective.

Jacqueline Poh: I think there are many perspectives on AI, but one of the worst reasons to set up an AI company, or to invest in an AI company, or set up a fund, or aim to raise a fund is to tag AI behind everything in the hope that that’s the only reason why someone will invest in you. So I would be a bit cautious about the hype. Singapore’s put up a national AI strategy, a second version. We’ve put up our first version a couple of years ago here in Davos in fact. It combines governance as well as a big focus on use cases as well as what we’re doing for compute and the development of our own LLM, which is called SEA-LION, the Southeast Asian large language model. Southeast Asia is a hugely vibrant area and location for venture capital.

Singapore alone has 400 VC firms and funds, including some of the PEs as well and some of the biggest ones in the world. We have 1,100 AI startups. And even then I say, show me the business model. I think that we are at the stage in terms of generative AI, where it is unclear where the commercialization opportunities will lie. Just because NVIDIA is making money from GPUs does not mean that an applications company is going to make money on regs. So it’s very important for us, for any investor in any company to figure out first of all where the value is actually residing for AI. But I think that it’s hugely promising. I think the potential is there and I think that it’s given life to an otherwise possibly fairly more abundant sort of VC market in a time of rising interest rates.

Sara Kehaulani Goo: Right.

Jacqueline Poh: But the fundamentals will always remain and the smart money will follow the smart money. My own sense about the overall market is that similar to what my colleagues here have mentioned, it may be time to come in. This is a time where even though interest rates are likely to remain maybe a little higher than anyone would want for a bit longer, they are showing signs of moderating and valuations have definitely come down first in the United States and then in Europe, and then they decided to come down in Asia. And some things are looking a lot more reasonable, particularly growth stage companies being a lot more reasonable. So various ways of funding including acquisitions by existing companies. It is not a bad time if you are an existing company and you want to help that startup exit through an acquisition as well.

Sara Kehaulani Goo: And let me just mention something a little bit provocative here since you talked about AI, and this is really a question really about the distribution of investment globally. Yesterday at an Axios house event, we had Alex Karp, the CEO of Palantir, join us for a conversation. He said, this was the headline, that he criticized. I guess it was, I don’t know if it was a criticism or just an observation from him, but he said that “The European startups scene is anemic on AI and that Americans have a huge advantage in terms of their investment and the innovation they’re seeing there.” I’m not just saying that because I’m American. I would love to hear your perspective to respond to that. And is he right? Do you feel like there’s enough investment either from the private sector, barriers to entry lowered by governments or regulation to help that more even distribution?

Rishi Khosla: In terms of specifically Europe? So I think clearly if you look at where the large innovation has come from, right, so you look at OpenAI, you look at Meta’s model, you look at sort of Google’s model, Google DeepMind. DeepMind is actually based in London. Right. So fundamentally Bard is created in London. So whether the innovation, whether there’s the innovation talent, right, in Europe, I believe absolutely there is. Whether those are European companies which are actually taking those and sort of commercializing, clearly not. Right. They’re American companies. And I think that’s just a wider topic. Right. That’s just like, it’s not AI specific.

Sara Kehaulani Goo: Right.

Rishi Khosla: Right. It is a question of, again, the size of the ambition. It’s a question of the availability and depth of capital. It’s availability. I mean, I was at a previous session this morning and the Moderna CEO sort of shared the fact that they had spent $5 billion before they made their first dollar of revenue. Right. And that was in response to Oxford University talking about the fact that they’ve got a part of funding for startups, right, which lets be clear, is probably a small nine figure number. Forget about a 10 digit number. So the size of capital which is available for that for, I mean you look at how much OpenAI has raised, right, clearly from Microsoft and from others. So all of those things I think drive that fact. Now where are the users and where’s the application and therefore the outcomes from AI going to be felt? I think I’d say we’re very high on the hype cycle at the moment, right, but we’re very low on the actual outcomes delivered.

Sara Kehaulani Goo: Right.

Rishi Khosla: Right. And like with most of these things, I mean, I’m not old enough to remember the PC era cycle, but I’m old enough to remember the internet era and I remember sitting there in ‘97, ‘98. Right. And the whole world was going to change in the next 12 or 24 months and it didn’t, but it did in the next five or 10 years. Right. And I think with GenAI we’ll be exactly there. Right. And it may go quicker, it’ll probably go quicker. And I think that European companies will adapt and be users of and innovate with the technology, but they may not be the entities which are commercializing the technology but creating it.

Sara Kehaulani Goo: Right. But Mr. Khosla, you’ve also, I’ve heard your critique of there not being enough investment in certain types of companies, particularly in the UK. So I guess from where you sit, what more needs to be done?

Rishi Khosla: Well, I’m a massive, how can I put it? We’re massively passionate and vocal about the fact that the UK, and I’d extend this to most of Europe, we don’t have the right environment to actually enable entrepreneurs to scale businesses. Right. We have a great environment to help them start businesses, but the funding markets, the availability, or talent, right, in terms of just people who’ve had experience scaling. Right. You see it in the valley. Right. You want someone who can go and spin up a new product line within an existing business, right, and take it from sort of zero to one and then get someone else to take it from one up. It’s like you’ll have a list of people that have done it before, right? In Europe it’s like you’re scratching your head because it’s like the motion hasn’t been driven, right? Because there haven’t been that many businesses which have sort of gone from startup to true scale.

And so you’ve got that aspect. You’ve got the size of the ambition point, right, where if many European entrepreneurs, you get to the point where you create a business for, which is worth tens of millions, hundreds of millions. Right. And they’re willing to sort of say, you know what? That’s good.

Sara Kehaulani Goo: Yeah.

Rishi Khosla: I’m sort of going to step off this and let someone else take it forward. Whereas clearly at least the Valley mindset, et cetera, is that’s getting started. Right. That would not be a failure, but it wouldn’t be like a home run. Right. So I think that there’s the cultural aspect, there’s the availability of talent and then also the availability of funding and public markets. I mean clearly our public markets across Europe just are not, there’s no depth for growth companies and therefore they’re no growth investors.

Ahmed F. Karslı: I feel quite lucky by the way, when I hear about funding cycles, funding problems. Because as a bootstrap company, you actually don’t care. You have a chance to sort of focus on what you build, right?

Rishi Khosla: Right.

Ahmed F. Karslı: Which is one of the biggest advantages. And when it comes to tough times, as you mentioned, for a company operating in an emerging market like Turkey, tough times are just another Friday.

Rishi Khosla: That’s also true.

Ahmed F. Karslı: Just think about what we have been through in the last one year. Last year, only in the last 12 months in Turkey, we had elections; we had many political problems in surrounding neighboring countries. We had massive inflation, even if it’s getting better right now. And we had a massive earthquake where we lost more than 50,000 people. But still that helps a lot as well because you always have this advantage of building some resilience even if it is unintentionally. Just to give you a great example, we grew by four times in revenues only in the last 12 months while having those problems. So sometimes I feel like I’m quite surprised, but I here just said a year ago, close to a year ago, we made an acquisition in Spain and the investors of the company we acquired were actually complaining about inflation. And it was 6%. We were dealing with 65% inflation in Turkey. So sometimes as actually, like you guys said, those tough times might be a good teacher as well.

Navin Chaddha: Yeah, I would say you’re a black swan. That’s what venture capital and success is driven by and we need more and more of that. Right. So here is my take to be complementary to what was said. With a perspective of the United States, right, like first of all, technology innovation is happening everywhere. Right. It’s happening in Asia-Pac, it’s happening in the United States, and this is at research university level, it’s happening in Europe. So what’s different, even in the United States? If you look at 70, 80, this is in information technology, of the value gets created on the West Coast. And why is that the case? So here is what our analysis is: First, the mindset is a little bit different, I would say then ambition. Ambition is there. Is it okay to take risks? And it’s okay to fail.

Sara Kehaulani Goo: Yeah.

Navin Chaddha: So once you have that stuff right, like the sky’s the limit. Right. So you start with that. Second, and it applies to both, people who are starting companies and people who are funding them. Right. But this is what happens. If you are in a hotbed of established companies now you can poach employees from there and at the end people are building companies. It’s not the other way around. And then this business of taking companies from idea and turning them to iconic is all about mentorship. So this is where maybe VCs can add value, maybe they can’t, but there’s enough entrepreneurs and executives who are willing to give back as board members, angel investors.

So I think this is a network effect, this is a community. And what ends up happening is, it’s nothing to do with talent, it’s nothing to do with innovation. Basically scale just creates more scale and that’s what just ends up happening. And I would encourage in some of the other regions for there to be a change in mindset. It’s okay to take risk, it’s okay to fail because as Einstein said, “If you don’t fail, you’ll never succeed.” So to come up with a big success, it’s okay. Failure isn’t only an opportunity to do it right the next time.

Ahmed F. Karslı: I would like to add something on it, Navin. On Monday I had a chance here to listen to Sam Altman. You were there as well.

Navin Chaddha: Yep.

Ahmed F. Karslı: And before this panel I wanted to ask ChatGPT what advice can be given to bootstrap startups or bootstrap co-founders. And Sam Altman said on that day is that every advice is actually given and every information is there. So when I asked ChatGPT about what advice can I give to bootstrap startup founders, there were like 10 different pieces of advice there. And they all were actually more than, what can I say? But on the other side, I totally agree with you that I found out that actually the only thing missing there is the personal experiences. And I found out that currently when I want to give advice or take advice, AI plus personal experiences of entrepreneurs around me, of mentors around me is actually enough to get real advice because that is the only thing missing, which is not online.

Rishi Khosla: But even if you pick up those comments, there was a very clear view that actually his best sort of insight comes from discussions with people like his mentors.

Navin Chaddha: Correct.

Rishi Khosla: Right. And again, we’re massive believers in that, and I personally as well, and I would sort of say I’ve had people mentor me all the way through my career and different people and also for different sort of issues, questions, opportunities, et cetera. But I think that is such an important part of, again, the ecosystem.

Ahmed F. Karslı: We need to have more communities actually.

Jacqueline Poh: I have a slightly different opinion about what you’ve mentioned, which is to take risk and the existence of your company in an ecosystem that scales easily. There are many, many problems in the world, and there are many entrepreneurial ecosystems which are not built on a market that is very cohesive. So for example, Europe isn’t necessarily all one market in some senses. Latin America might not be, Southeast Asia might not be. America is a little bit more homogenous. And if you find yourself in Silicon Valley, you get a product and you get a sense that there’s a community around that, there’s capital, there’s talent, and there’s a sense of scaling muscle that works in a certain way. I think if you go to different parts of the world, and this is relevant in a world that is increasingly maybe a bit less globalized, a little bit more regionalized, that kind of scaling muscle has to change as well. So in addition to the skills that you’ve mentioned, I think that kind of adaptability is going to be something that is relevant.

Navin Chaddha: So what I would say is having invested in India and China since the mid 2000s, I completely agree with you and my advice to entrepreneurs is focus, and this is a little bit different, focus first on your home ground because there’s faster iteration cycles. Perfect the product, perfect the GTM, and it’s hard for an international company to come in and understand the local stuff. And at the end, the problems you’re solving there are very, very different. Right. I grew up in India in the late ‘80s, came to the US in early ‘90s, and there was like years before you could get a landline telephone. And necessity is the motherhood of all invention. The landlines never happened. It all went to basically cellular.

So that’s where the entrepreneurs have to innovate rather than saying, Hey, I’ll come from India to the US. First nail the problems. They’re there. The folks sitting in the US can’t even sell at those price points. They don’t even know the distribution channels. So you need something more than technology in today’s market. And if your product teams are closer to where the customers are, you win. Right. You win. And there are many, many examples, not only in tech, in CPGs, in financial services, in healthcare, the local companies in some of these markets have done phenomenally well because, so my feeling is it’s a little bit different than US, Israel, but some of these emerging economies are big. They’re big. So go solve the problems there and raise less capital. If the markets are 110th, it’s okay. You can still deliver a lot of value.

So I think that’s what I’ve learned, that get it right with something which is near to you where you have domain expertise and insight rather than somebody sitting in Silicon Valley. Right. That’s where I’ve seen the local companies we have been involved with, which are innovating and especially some of these low income markets at the bottom of the pyramid. Right. Those kinds of income levels just don’t even exist in the US. So I think that’s where my learning has been. Change the problem, focus on your unique advantage, whether it’s what you can charge, whether, how do you distribute it, like what do you do? Right. And the markets are very, very different in these countries.

Sara Kehaulani Goo: Mr. Karsli, I’m curious about your perspective. We didn’t get a chance to talk a little bit about your company. I wonder if you could share a little bit about your experience and whether the comments here and about culture, about regional versus local investment in communities make a difference. Was that the case for you?

Ahmed F. Karslı: I totally agree with everyone. Just to give you an example, the panel’s name is “No Rain, No Flowers.” But I think overwatering is also a problem, right? And I think one of the reasons why many startups didn’t focus on their own local markets, as you mentioned, was actually over raining. Because I have seen that many companies had a huge potential in their own markets, but they were actually pushed to grow as fast as possible. So they had to operate in multiple markets where they tend to lose their focus from their main market. And as a bootstrap company, another advantage is that you become really creative because you don’t have enough funding resources, which means that you have to do everything to be profitability, and you get really creative about when you’re building a product, designing the product, building a fee structure, et cetera. And that actually helps you a lot to do something in your own local market as well. That is a big advantage.

On the other side, culturally, we talked about AI. This year’s main topic is AI here. We all are talking about AI, but when it comes to AI, I really struggled in the first five years of Papara because it’s a regulated business. It was quite difficult to deal with regulators, especially when you’re a new and young startup founder.

So I noticed that we were trying to build something for some time, but the regulator might be a road blocker as well. And I’m really happy that we are talking about AI here for the last five days. It is great to see that many policymakers are happy to discuss AI. But on the other side, I’m a bit skeptical as well because I have seen many policymakers here in Davos. Actually, we’re talking firstly about the potential effect of AI on unemployment. And I can easily imagine right now that in five or 10 years, some political leaders will be campaigning against AI and they will be on the rally and campaigning like, we are not going to let robots steal your jobs. And probably there will be people there who are shouting like human first, human first.

So to prevent that, actually we need to have more connection with the regulators. And to do that, I recently, OECD did something great, OECD, maybe you have seen that, published a report on sandbox use cases of AI. We need more sandboxes like that to actually, like to have this connection between regulators, policymakers and startups. Because in the last five years we had this huge issue with policies about crypto, but crypto was only an interest for financial policymakers. AI will be interesting for any kind of policymaker including health, transport, whatever it is, which means that you have to have more connections. And it is also like the startup founders’ or startups’ responsibility to educate policymakers as well. So we need to think vice versa. I think maybe in the next five years, if you are working on AI, if it’s an AI startup, we should really start thinking about hiring a public police officer, maybe even before hiring an HR officer. So otherwise that roadblocks actually may prevent technology a lot.

Sara Kehaulani Goo: Wow.

Rishi Khosla: Can I pick up on a couple of those points? So I think on the bootstrapping point, the first business that my co-founder and I created was purely bootstrapped. We used $60,000 to build it into a 3000 person company. And the discipline that teaches you, like you say in terms of just business model, in terms of making sure you’re always doing the right thing in a way, is just dramatically different to, like you say, overwatering the business. Right. And the overwatering, I mean, we know very clearly from the last five, six, seven years that the, I mean, as some people have termed it, there was a fiscal easing rate, a monetary easing off the whole private capital market obviously caused by one very large fund and a number of other funds, which sort of went in proliferated after that. And that created a lot of, in a way funding of and spending of sort of money, which wasn’t necessarily anchored in a true business model. Right.

And clearly for that exuberance to being taken out of the market, our view is that’s good, it’s healthy. Right. I’ve been speaking to a couple of other sort of founders of businesses which are arguably larger than us, but similar stage in terms of maturity. And their view as well is that you sort of got the annoying ankle biting competition who didn’t have a model, but were just spending a lot of money to try to go and acquire customers, et cetera, that sort of paired away and therefore there’s more money to put in products, there’s more money to actually put in the right things which deliver a better experience for the customer. So that’s the first thing. And then on the other point, on the regulator, your point about having a policy officer, et cetera.

So again, like you we’re a fully regulated bank in the UK and from day one, again, we over invested in actually that regulatory relationship. Right. So we actually had someone to manage our relationship from that world almost from the get go. Right. And actually doing that and understanding where the regulation’s concerns are, the way that we think about it now is that 99% of regulation is aligned with creating the right long-term business. Right.

So if you work backwards, not from the rule book, but you work back from the spirit and the principle of which a regulator’s thinking through, how do you do the best for your customer? Is that a good thing for a business or not? I’d argue yes. Right. When it comes to financial services, how do you make sure you have the right liquidity, you have the right capital, are those good things for longevity of a financial business? You think so.

Sara Kehaulani Goo: Right.

Rishi Khosla: Right. So therefore, if you almost align yourselves with actually what’s the regulator’s mindset about what is the right long-term outcomes for communities, and you just think to yourself, how does that align with actually what would make a long-term success for your business? There is so much alignment there, and that’s the way we’ve always thought about it. And in a way, I say to our teams that sometimes when we interact with a regulator and they give us feedback, we should view it as good consulting advice. Right. And actually it makes our business stronger.

Sara Kehaulani Goo: Yeah.

Rishi Khosla: Right. So it’s just a different way again, to sort of think about these things.

Jacqueline Poh: I think that regulation is one of those interesting things. I’m very fascinated by your title, “No Rain, No Flowers,” because I thought about it a bit more and I’m like, here’s the assumption that all you need for flowers is rain. You don’t. You actually need sunshine, you need oxygen, you need carbon dioxide, you need a fertile soil, you need a whole range of things for companies to flourish and to be productive and to be profitable, make money, to be honest. And so it’s the whole environment, and regulation is one of these big pieces. Actually, you need a whole bunch of things and, because Singapore’s been trying to build this startup ecosystem for decades now. So each one of these little pieces, it comes into play. So not just the capital piece, which we’ve been speaking about, but the regulatory piece, the talent piece, the enabling environment piece, and the demand piece.

So these are the key pieces that you need, which is the soil. The regulation works really well when there is a less disruptive new technology. The minute there’s a new disruptive technology, regulators don’t really know what to do. They don’t know what to make of it. And when you have something like generative AI or precision medicine or quantum, I’ve been a regulator and you get stuck. You do get stuck.

Rishi Khosla: Because it’s not siloed.

Jacqueline Poh: It’s not siloed and all regulations are built for the last war, the last problem. So I do support the idea of sandboxes. And I think in any good enabling environment for entrepreneurship, you have to be very, very conscious about identifying the disruptive technology. In our case, it was alternative proteins. In our case, it was FinTech, it was Web3, now it’s AI. And create a little bit of a sandbox around that so that your entrepreneurs actually have room to play.

We are very cautious about over regulating. We’re particularly cautious about over regulating AI because that might kill use cases that have yet to be born and we don’t want them to be stillborn or we’re stillborn somewhere else where the regulation is more fruitful. But you need other things for this ecosystem. You need talent. You need to be able to bring in the best engineers, if that’s the case. You need to grow them indigenously, if that’s the case. You need a kind of funding environment that allows debt, that allows family offices, that allows angel investors to step in.

You need the kind of demand that is very fruitful for your company. So like in a B2C market, it’s a big consumer market. In a B2B market, it means that you do need all the companies present that can help you scale your company. And in this regard, the rain may not be venture capital, it may be venture procurement. And if you find that company that’s willing to buy from you something new and innovative on a venture procurement basis, that’s even more productive. So I’m just suggesting that the rain is not all you need.

Sara Kehaulani Goo: Yeah.

Navin Chaddha: Yeah. So I think, let me give you the history perspective on what happened in the United States because it’s getting repeated in other regions. So if you go back to 1960s, 1970s, I wasn’t also born at that time, but having Mayfield been around there, great companies like Intel, there was no venture capital industry. Arthur Rock essentially was in New York. He used to go to high net worth individuals, sell the business pitches and got the business going. Mayfield’s first fund, $2 million in 1969, and probably like 10 iconic companies came out of that. A lot of it was syndicated with other people and the best companies, Microsoft to a point, you mentioned Oracle, Apple. VCs didn’t give them money initially. It was too speculative like the AI wave is. They didn’t understand what it is. They got money from friends and family.

Even if you go to this date, Google, Yahoo existed, Excite existed. Every Silicon Valley firm passed on their seed and inception round, and then the first one or 2 million came from angels and they all became billionaires. When Google became the largest search engine, VCs came into it. They hadn’t figured out monetization. So I have seen this movie with all the iconic companies till the internet happened and after that, even Facebook didn’t raise money till it had gone to all the campuses when one of our peers invested in them. So my feeling is bootstrapping, getting customer validation, getting the customer to pay and establishing product market fit without any venture money. I would encourage every entrepreneur to go do that, right? And a lot of our companies, I would say 50 companies, which had IPO, didn’t get money at the first time. Twitter didn’t get money, right? Genentech, when the idea was there, like people look at it and say, you’ll discover biotech.

Sara Kehaulani Goo: Yeah.

Navin Chaddha: So I think whenever the idea is the crazy, it doesn’t get money, right, like basically whether it was Airbnb, all these companies, when you are the next, next thing. So I won’t get discouraged. Right. The bootstrapping point you have met and friends and family is a great way because everybody cannot, as a VC, predict where the future is. You just can’t.

Sara Kehaulani Goo: Right.

Navin Chaddha: Right. The other thing on the regulator stuff, I would say, it’s a healthy balance. So since the topics here have been genAI, my only request to policy makers and regulators is there’s a lot of fear around GenAi. Will it take jobs? What happens to trust, safety, privacy, security? Can we all get together as public and private and agree on the guardrails and norms and then let’s just go implement that, right? So if we can do that, please tell us all the fears and we’ll operate within it. Because many regulated industries, financial services, healthcare, we’re already doing it, right? Entrepreneurs are smart. You put constraints, figure out a solution. So I think time has come to lean forward and collaborate with private companies, financial investors, any kind, public policymakers and say, come on, let’s sit down. What are you afraid of?

Sara Kehaulani Goo: Yeah.

Navin Chaddha: Let’s find the solution.

Sara Kehaulani Goo: And maybe that could be our conversation for next year because I don’t think this issue is going to go away. Thank you so much. We have to leave it here. This has been an incredible conversation. I just want to thank all my panelists for the perspective you bring from the region you’re representing. It’s been fascinating. I’ve learned a ton. I hope you have too. And thank you to our panelists. Please join me in thanking them.

Built to Last – Where Will the Next Big Companies Be Created? | SynBioBeta 2023

 

Raj Judge:

Well, hello, everyone. Great to be here. Looks like it’s a great turnout this year, and we’re excited this morning to talk a little bit about built to last companies, and where the next big companies will be created in synthetic bio. And of course with me is Ursheet Parikh, partner at Mayfield, and we’re going to jump right in. 

Ursheet, let’s talk first about the current environment. We’ve got valuations that have plummeted. We’ve got capital access problems. The IPO market is shut down. A lot of negativity, a lot of doom and gloom, if you will, in the synthetic bio market, as well as in the technology market as a whole, and we’re not sure where the economy is going. So I wanted to get your thoughts just generally on what you think about the market and where things are going to head over the next couple of years. Are we going to be in a doldrum for the next five years, or are we going to be coming out of this in another six months, or are we going to be stagnating? What’s going to happen?

Ursheet Parikh:

So first, good morning, everyone. I’m really excited to be here, and I’ve never been more excited about our space. I know, with all the various things that Raj alluded to, it can feel challenging, but I think we are set up for the absolute Cambrian explosion of innovation that is coming from startups. The one thing I would say is that we are set for synthetic biology to fundamentally go mainstream and transform all of our lives in the next five, seven years.

What are the things about the current environment that make me feel so excited? So if you remember the first SynBioBeta ’09, it’s right in the depths of what felt like a tough environment, and so it’s probably easier to draw similarities to that. But what has changed are the fundamental demand drivers for our industry. They are coming because consumers want better products, and making them with the old Industrial Revolution technologies isn’t sustainable – and it also doesn’t necessarily create the best products either. And so, you have consumers who want amazing products, and biology as a technology has emerged as the core platform that can drive that. So all the advances we have in digitizing biology, engineering biology are where the cost drivers are going.

The second thing that has happened is, to see an industry like this emerge into the mainstream, you need policies. And I think, in the last several years, we’ve seen an amazing alignment of policies. Some of it got driven by the need to bring back the supply chain. Some of it got driven by things like the Inflation Reduction Act that even brought the biggest greenhouse gas emitters in the oil and gas companies to start wanting to do things with synthetic biology.

But then there’s also the big trends that have emerged like AI. And what AI is doing is, if we were to go back and sort of manufacture with biology here in the US, it was not going to be the way bioreactors were done 10, 15, 20 years ago. It’s going to be done much more with an AI-powered system at every step of the workflow. This could be in high-throughput screening to find new strains. This could be in automation. This could be in generating new products.

So I’m just so excited about this domain. And to get over to the other side, I think all of you in the room will clearly be innovating, but you’ll also have to be very methodical, very thoughtful about how you really make every dollar count because of where the interest rates are. The cost to rebuild the world with biology has gone up dramatically, and capital is going to be scarce. And so, we have to just be able to demonstrate that we can provide returns that are going to beat pretty much any other asset class.

Raj Judge:

So I love the optimism, definitely contrarian to the current mood in the economy, so that’s wonderful to hear. But we’re in a tumultuous time. We’ve got China relations. We’ve got the Russian War that we’re dealing with. We’ve got all sorts of different issues. We’ve got India growing as another potential location and market. So lots of different contractions and expansions occurring, and I know that spells opportunity for some, and it spells challenges for others. But the whole geopolitical climate and the whole geopolitical situation globally provides us with a lot of different complexities that we’ve never really had to face before. Tell me what you think about that a little bit, Ursheet. I’d love to hear.

Ursheet Parikh:

Yeah, so I think, to me, I’m looking at everything that is happening at the geopolitical level, and it’s fundamentally creating new demand drivers for things to happen in the US. I touched upon briefly on how you want to be able to go ahead and manufacture close to home. This SynBioBeta is also feeling and sounding different because we have a lot more conversation about healthcare and applications of synthetic biology in healthcare.

But the top trend that I’m seeing right now when I’m talking to a lot of people in big pharma is, how can we leverage the Inflation Reduction Act to actually start manufacturing antibodies and other biologics in the US? And if somebody’s going to go ahead and do that, they’re not just going to go and do it with the older technologies. People want to see, how do I use a different manufacturing stack? How do I use different workflows? How do I set it up to be targeted or customized better on that end?

We have been involved in a company that’s actually converting methane into fertilizer on the spot at farms, and it’s the kind of company that is clearly seeing great demand from anyone that is doing organic farming because organic fertilizers are expensive. This is using methanotrophs, but this is also seeing just a huge level of demand from the major oil and gas companies. And then, you end up having the elevation of synthetic biology as a core biosecurity initiative. And if you look and talk to our classified agencies, or you look at the government strategy, AI, quantum computing and synthetic biology are seen as these strategic technologies and platforms for the future.

So by all of these issues, the energy independence and the worries that came because of the Ukraine thing, this has fundamentally created demand for self-sufficiency and a green economy. And who else is going to make it? It’s all of you guys in this room. It’s the synthetic biology ecosystem that’s going to go ahead and make it. So I’m excited for it.

Raj Judge:

That’s interesting. Very, very helpful insights. But let me take a little more controversial probe into that question that we’re talking about on geopolitical situations and the Inflation Reduction Act that you talked about. Some say that the biggest benefactors of the Inflation Reduction Act are the largest greenhouse gas emitters as well, and they’re getting the benefit of the green dollars. So how does one look at that from an emerging company standpoint or a new company standpoint? How do you take advantage of that? Because it seems like the big guys are really getting a lot of that advantage, and politically we want to obviously support the larger companies as well on the global stage, but we also need to make sure that innovation is still occurring and younger companies are allowed to grow with those dollars.

Ursheet Parikh:

This is a very real problem. And so, if I can give an example to illustrate the point that Raj is asking us about is, if you look at the Inflation Reduction Act, the top recipients actually so far of the funding from the government have actually been in Texas and Georgia. And a disproportionately high number of them are actually the major oil and gas because in the Inflation Reduction Act, there is a huge incentive to move to a hydrogen-based economy.

A lot of what we do in synthetic biology with the green stuff really marries well with the decarbonization that’s enabled by electrification, and so there’s companies here which are working on doing things with hydrogen, using microorganisms that can go out and work things with them like the example that I just gave. But at the same time, what you now have is the large oil and gas companies being able to claim that they are able to go ahead and make hydrogen out of natural gas, and the resulting CO2, they’re just going to go pump into the ground, and hopefully it’ll stay away, and oh, by the way, they know how to pump CO2 into the ground because they’ve been doing that with fracking.

So you can see how some of these best intentions can suddenly make the fossil fuel-based economy even harder to beat. And when you are working with the government as a larger company, you just have more resources, all right? You have people who can do government affairs, you can talk about working through policy, things like that. This is where I’ll give a call-out to John. I think John Cumbers, who’s been the convener here, has done quite well in educating and bringing a lot of our community together in having these conversations. But I also do think that, as a community, we also need to get more politically active. We need to engage in conversations with policymakers, lawmakers, and then take and share the best practices that we have so that we don’t find that it’s the old economy companies that in effect end up leveraging and benefiting from all these demand dollars, but with greenwashing.

So this is a problem, and I don’t think we have a magic formula for it other than, all of us have to get engaged, involved, and work through it with each of our local jurisdictions, politicians, and senators, while sharing best practices on how, when we do the projects. If you’re doing a new bio-manufacturing thing, how do you go ahead and leverage the best of these incentives?

Raj Judge:

Yep. That’s definitely the case, and I think that we’ll have to spend a lot more time on this trying to understand where the complexities can be taken advantage of, if you will, for emerging companies and new technologies. Because we don’t want this to turn into part two of the solar energy movement 10 years ago, where there were a lot of government dollars, but ultimately they didn’t really benefit the innovation cycle that people wanted it to benefit. So more to be seen on that.

The other thing that comes out of the geopolitical state that we’re in is that, over the past 20 years, we’ve really enjoyed a free economy where R&D could get done, particularly for companies that are innovating in different geographies, whether it was teams in China working with teams in the US, or teams in Europe working with teams in the US, or for that matter in Russia and India and all of that. And now, what we’re seeing is this very nationalistic approach, even by the US, which is something that we haven’t seen before, at least in the last 20 years in technology.

And so, we’re having problems with companies developing AI-based synthetic bio or AI-based technologies and exporting that between borders. So we’ve got a company, for example, that wants to set up an R&D team in China as well as in California, and they’re having problems doing that because of the government restrictions around the export of AI algorithms and the like. So what do you see that, and how do you see that impacting the way companies are going to grow and how they’re going to continue to take advantage of talent that’s global?

Ursheet Parikh:

Yeah, I think for large companies, be it large conglomerates, large pharma companies, large companies in the industrial space, I think they have the infrastructure and the ability to actually do development in multiple geographies. I think for emerging companies, it’s going to become increasingly harder and more expensive, if you are operating at the intersection of synthetic biology and machine learning or AI, to be in multiple countries or multiple continents without running afoul of many of these rules.

So the thing that I’m most excited about and what helps drive the synthetic biology economy down the cost curve to be at par with the broader mainstream legacy technology is the ability to have AI in all of its various forms. From the old form of reinforcement learning to the newer forms of generative models, it is basically going to help us really run a lot of experiments in parallel, look at the data, synthesize, optimize. It takes what we do in innovation with biology from the old school world of biotech, which was often set upon accidents or divine inspiration, to an engineering optimization-based model.

But as I said, this is happening. If you talk about the national priority technologies, like quantum computing and synthetic biology, they are far from being real. And I think those cross-border considerations will become factors. And by the way, we’ve been involved in companies that have actually been transformed and have been made possible because of AI. One of the companies that we engaged in early on was Mammoth Biosciences, and they have become one of the most prolific innovators in the CRISPR system space. And there’s actually a session from one of their founders later this afternoon that I’ll be moderating. What fundamentally made it possible was their ability to really master high-throughput screening with a high level of automation and then using machine learning to be able to go ahead and identify candidates, and then marry that with the web biology to go do that.

Now, that world of AI was much more about, how do I use AI to screen, look for stuff, but somebody still had to then figure out, what is going to be my next set of things? What do we do, right? Now, you take that with generative AI and large language models, and you can start even taking the other side of the equation and amplifying the speed on that, and that whole loop then becomes very significantly exhilarating.

So one of my favorite books is from the nineties, from the founder of Intel, Andy Grove, and it was called Only the Paranoid Survive. And the essence of what he says is that, every decade or every five, seven years, something happens which is such a 10x force that shapes the world. And you may think it’s not relevant to you, but it comes very quickly, and it will touch every job, every business, every industry. And I would say that, for our industry and just generally for the economy, I think generative AI is actually going to be one of those forces.

It doesn’t matter what your business is, whether you have nothing to do with AI, whether you’re just doing manufacturing of reagents or whether you’re providing services. I would definitely encourage taking a step back and tuning in to see what is happening in that world and then dreaming on how it could potentially impact your business because 12, 24 months from now, I personally would be shocked if your jobs have not been touched in some way, shape, or form. And I actually think they will have been touched for the better because inherently it’s the kind of technology which is really far from replacing people, but it is actually going to be great for augmenting people to do their jobs better.

So if there was one takeaway to take from this session, it’s probably that, as alien as it has felt and far away and esoteric and behind the scenes, there is a high probability that it can actually be used to transform and accelerate your business and make it much more capital efficient. 

Raj Judge:

So there you go. Paranoid survival is what I picked up off of that. I think Winston Churchill even talked about that at one point. Let’s talk a little bit about the dovetail between how digitization software and AI are impacting synthetic bio and funding because we haven’t talked about funding, and funding is a difficult environment. It’s a difficult thing to do, and traditionally software companies get to revenue faster. They have less capital intensity. But at the same time, software is starting to get a little bit more commoditized. The barriers to entry have gone down, and now we’re seeing this opportunity with AI, particularly in synthetic bio to create something more driven by software, but at the same time with lots of barriers to entry. So let’s talk a little bit about the funding environment there. What can companies do, particularly synthetic bio companies, to become more attractive, to become mainstream, if you will, for venture funding?

Ursheet Parikh:

So if you look at the Cleantech 1.0 era which Raj alluded to, and the big returns over there accumulated in the public markets to investors. This included companies like Tesla and Phase, and overall, the private investors did not necessarily end up doing as well. Now, a lot of the public investors who got so excited about those gains have been burned really badly in the SPAC boom, where you had a lot of companies, whether they were cleantech or built by bio, go public but then underperform on stock returns. So coming out of this, what investors want to fund is companies that they can evaluate and measure and operate and measure their operations on. And this often for public companies starts with when you are in revenues and when you start showing operating leverage and earnings profits and things like that.

So this is where I would definitely encourage any private company today to fundamentally think about how they’re spending their dollars, and how they execute to demonstrate their differentiation to get better pricing. If you build amazing products that truly meet customers’ needs, you will get better pricing. You will have better margins that can then help you leap ahead.

And this is a shout-out to my colleague, Arvind Gupta, who normally is on stage with me but had a conflict today – he talks about how essentially, when you’re building a synthetic biology company, you really think down of how you’re going down the cost curve. And in the earlier years, where you are pretty high up on the cost curve, you have to find niche markets and applications where you are going to get paid a premium. And people can remember Tesla today as this mainstream company that’s selling a car which is at a lower price than the average American car. Average American cars sell at like $42,000. Tesla has a $40,000 car, but it IPOed on the Roadster. It was able to go at the first billion, and it was a premium product. It was a niche product.

So I would say thinking about amazing products, thinking about the unit economics of the products, getting to revenue quickly, and giving investors very tangible operating metrics by which they can measure the progress of your business. And this applies at seed, A, B, C, D, IPO, and even for public companies. Otherwise, it becomes just easier for investors to stick with the big large companies in an era where it feels a little dangerous to be investing.

Raj Judge:

So we’re out of time. I’m going to give you one last question. I want a quick, rapid-fire answer from it just because I think a lot of us want to hear. What areas do you see in synthetic bio as the prime areas to be looking at in terms of potential growth and investment and the like? And so, I’d love to hear what you think. Is it food? Is it materials, hydrogen, carbon sequestration, CRISPR, we’ve talked about that engineered bio? 

Ursheet Parikh:

All of those and hydrogen, but most specifically, I will highlight things which are set up to be capital-efficient biomanufacturing. And I think fundamentally AI-powered everything in synthetic biology, it will absolutely transform how everything happens. A person can run experiments or can marshal AI to do a thousand things for them simultaneously, right? I think that’s what every scientist and every engineer, every manager needs to think about.

Raj Judge:

Wow. Fantastic. Well, thank you, everyone. Thank you, Ursheet. And I hope you folks had a great time today and learned a little bit of what Ursheet thinks about the market. It’s definitely contrarian to what I saw and what I thought, and only the paranoid will survive. So thank you very much.

Ursheet Parikh:

Thanks, Raj.

Scientist Entrepreneurs — The Hard Truths of Scaling Breakout Engineering Biology Companies


Raj Judge:

Well, hello everyone. Good afternoon. I hope everyone’s had a cup of coffee and you’re all wide awake and bright eyed and bushy tailed and ready for our event here. So thanks for joining us. I think we might be one of the last events of the afternoon, so we’ll try to wake you up and keep you enthralled with some controversial discussion, and hopefully some interesting points that come out of it. Let me start by just jumping right in, because we’re limited on time and I want to cover a lot of material today. Ursheet, tell us a little bit about building a company and when you have to decide when you’re going to build it for an acquisition versus an IPO.

Ursheet Parikh:

Well, I think no success is accidental. And so if you’re doing a built to last company, it’s pretty much decided from the foundation in the first year or two. It’s the culture, the values, whether you have the stakeholders that are in it for the long haul, whether you have the focus on getting products to market. And so, yeah, it’s hard to kind of figure out a built to last company if you didn’t plan for it in the first couple of years, and got the right co-founders, investors etc to be with you on that journey.

Raj Judge:

So Ford motors. Built to last, not built to sell? Trevor, tell us a little bit about your thoughts on research. You know, you founded Mammoth Biosciences, of course, and that was built on cutting edge research. So tell us a little bit about how companies can use research to leapfrog the competition and stay ahead of it.

Trevor Martin:

Yeah, no, I think it’s actually an interesting tension in companies where you’re founded on this innovative research, and then a huge amount of your value is taking that research and actually translating it towards patients, or products, or whatever it is. And I think that one of the things we’ve done at Mammoth is really embraced that tension. And one of the things we’ve decided is similar to this idea of built to last vs or built to sell. If you’re doing built to sell, race towards product and sell products, right.

But if you’re really doing built to last, you need to keep that innovation. And one way of doing that is going back to universities and licensing. And that’s really important. But a key part of it is, do you really keep investing in that research even as you continue going towards the product? And you kind of both stay at the cutting edge of research and the cutting edge of getting close to patients. And that can require additional capital. And it means you really are building to last because those aren’t things an acquirer will necessarily want you to do. And that’s something that we’ve embraced. But it’s a very conscious choice, for sure.

Raj Judge:

Yeah. And I mean, taking off of that point, Arvind, companies ultimately got to build product and they got to deliver product. At the end of the day, it’s great to get funded and it’s great to hire a lot of people and it’s great to have some great science. But you’ve got to build a product and you’ve got to deliver it. And so how do you keep a company’s mission to market instead of mission to science?

Arvind Gupta:

Yeah, I think it comes back to founders that want to create change in the world. And to create change, you actually have to change people’s lives. And that’s through giving them something that does that, or the product. Furthermore, there’s a business model that needs to be figured out that can best bring that value back to the company from that exchange. It comes from the founders, really, and what they want to build. And kind of like what Ursheet was saying, are you built to last or are you built to sell? And built to sell is, oh, we’ll do as much as we can and see if we could flip this company, versus I actually want to change people’s lives.

Raj Judge:

And Ursheet, you’ve invested in a lot of companies and built a lot of companies in your day, including your own. How do you feel about the mission to market versus mission to science tension?

Ursheet Parikh:

So I think it comes back to the mission of the founders. Because nine times out of ten, when your company gets acquired, it doesn’t realize its mission. So if you’re really true to the mission – which is why you started the company – do you really want to go ahead and make that impact? Then you want to control your destiny. And a lot of that is then having products and a business model that allows you to go ahead and realize that. So to me, it almost comes down to, even if you want to further science and you want to have the infinite resources to advance science, the most sustainable way of doing that is to actually go ahead and create a sustainable company. And so I look at a lot of global challenges, and it’s primarily entrepreneurs who are going to go ahead and fix them.

You know, it’s like, you look at what are the most valuable companies in the world, or like, at Tesla, you look at sort of the planet health category of problems. And even a small dent on it creates currently the richest person in the world. And I’ve come full circle, because I used to think about a lot of these problems as maybe it’s for nonprofits and foundations and the legacy work. And after serving on a few non-profit boards, I came to realize that government and non-profits are not going to solve these problems. It’s going to be many of you in the room, and folks in this ecosystem, who will support and make things happen in this journey. So I’m just very, very excited when I look at the entrepreneurial energy, the innovation, and just the relentless zeal to make that impact. 

Raj Judge:

Yeah, that’s great. And Trevor, I’d love to get your thoughts too. I mean, companies are built with certain attributes that lead to specific outcomes, ultimately. Both long and short term. And we’ve talked a lot about long term and built to last. And we’ve talked a little bit about what it takes to do that. But it really comes back to what are those attributes that you ultimately embed in the company yourself to have that specific outcome?

Trevor Martin:

Yeah, I mean, I think a lot of it comes down to the original vision for the company. And that means you’re going to attract people that want that. And it goes back to this idea of build to last versus build to sell. And I say that not to denigrate one or the other – companies are appropriate for both in all honesty. It really is just a question of what you are trying to achieve. And I think when it comes to platform companies, for example, that’s where I think it’s like an abdication of your responsibility to build to sell. Because there’s so much potential. And I think when companies are acquired, often that potential isn’t realized. 

So if you really think you have a platform that could tackle a thousand things, there’s a couple of things you have to do. You have to build it so that you really are focused on the patient, right? Because if you just do research forever, you’re not going to actually create value for the people it could help. But you also need to make sure that you’re building it with this idea that it is a long journey, and it’s a riskier journey than just going down a single product. You’re going to spend a lot of money building out the platform and doing things that are going to pay off 10 years from now, but won’t pay off tomorrow. It’s a conscious choice and you really have to actually sit down with your co-founders and with the early team and say, this is how we’re going to do this. And we’re all really excited to do it or not. And then you’ll start to hire people like that. And you’ll start to work with partners that think about that. And you’ll attract investors that think like that. And I think it all just comes from those initial early decisions that really do snowball throughout the company.

Raj Judge:

Yeah, that’s absolutely an important part of building a great company over a longer term period of time. I think a lot of people get lost in the sort of short run outcomes that they’re seeking. The benefit of selling a company for a certain amount or building a company to sell. And they get lost between that and really building a company that, regardless of whether or not they sell it, will have a long term future ahead of it. And so you don’t want to reach a cliff if you will, is what you’re really kind of getting at. 

I want to delve in a little bit into the platform comment that you were getting into. And Ursheet, maybe we can start with you. And I’d love to come back to you, Arvind and Trevor. There’s an inherent tension in companies when they start between building a platform or building a product. And that inherent tension causes a lot of issues in how you fund the company, how you hire the company, how you go to market, how you build a sales team. All of those things are somewhat intertwined with this fundamental or strategic decision that occurs very early in the company. Yet you don’t know at the early stage, whether or not the company is going to be a platform or not, and whether it should be a platform. And so, I’d love to get your thoughts, Ursheet, on that as you’ve built a lot of companies. And so tell us what you think.

Ursheet Parikh:

So I’ve had the privilege of working with a lot of amazing entrepreneurs, as well as learning from a lot of amazing entrepreneurs who we had not backed, who just build those companies independently. And what kind of comes back is at the end, people buy products. So the core of this turns out to be that you may have a platform, but you know, at the end of the day, the platform in and of itself is not useful. It’s the output of the platform, which is the products. And so not having a set of products in mind that you’re building to bring to market makes for a very difficult-to-build platform because then the platform becomes more and more generic over time. 

And so innately, it starts with, you want to do 10 things. You can do 10 things in 10 years by doing them one at a time, one a year kind of thing. And so it starts with picking a few key focal points that give you the design parameters for products and the market. And that then helps bring focus on the platform development side of the house. Then as you build more products, the platform naturally expands along the way. And so at the end of the day, the companies are going to deliver value with the products that those platforms enabled. And investors will value that. And they buy into the platform primarily because it’s sustained value over the long haul. It’s not just one egg, that kind of thing.

And so the key tension is that this can’t get retrofitted into a plan. If you have investors who are coming in with a three to five year exit horizon, it’s really hard to go in and then have them sort of think about why they should do something for 7, 8, 10 years. And in deep science, deep technology, it does take, it’s… The best business of all time is the software business, where you can basically move electrons on your PC, move them out across the internet, and money in with other electrons comes into your bank account. But here, we are moving atoms. And any business where it’s moving atoms is just going to have inherently a greater degree of friction. 

Raj Judge:

I’m checking the electrons in my bank account right now. Arvind, what do you think about this platform versus product tension and how you get there? I think, is it the rule that Ursheet’s talking about? Or is it sort of the nature of the beast in the way that it ultimately unfolds? Is that the way you approach every company? Or do you let it unfold that way and you ultimately find that’s the way that it ultimately gets there, but doesn’t really start there.

Arvind Gupta:

So I’ve always said platforms aren’t products, products are products. It’s pretty simple. But I think it helps to elucidate the question of what do you actually sell? You sell products. That’s what a business does. The platform produces that in a way that either lowers the marginal cost consistently or increases the marginal likelihood of success in some way. And so the go to market for a platform company is to demonstrate those two things through product. And how you get there is dependent on the industry and all that kind of stuff. But that’s the fundamental outline.

Raj Judge:

That’s well said. Trevor, you had to deal with this at Mammoth. How did you make the decision? And what were the circumstances under which you made the decision? And exactly when in the company’s history did you make the decision?

Trevor Martin:

Yeah. So I agree with everything that was said, and that you prove the platform with the product. I think something people get really hung up on early on – and this is just my opinion, feel free to disagree – is people really think they have to have the perfect product for the platform from day one. They’re like, oh my God, I’m so scared to tell people what the product is until it’s perfect. And they do all this work and they’re scared to show people oh, it’s this or this other thing. I’ll tell you, our first product on our platform was going to be detecting fish fraud. That was not what we ended up doing. But the whole point is, you go through the exercise and you go through the thought process. And maybe you’re wrong, maybe you’re right.

And you can even be a little bit wrong at the beginning. Because many of the things you’re going to do early on in the company are for the platform anyway. It’s like you’re focused on a product, but you’re so early that you’re really building the platform with a product in mind. It’s later that you have to be really considerate, right? As you continue to go down the product path, it becomes less about the platform and more about that specific thing. But you have time early on. And it’s really more about building that mentality of, what is the product, and how is what I’m doing investing in the platform and the product at the same time? And making considered choices of when it’s not, usually at a later stage in the company when you are more confident. Then, oh, okay, this is actually something that I want to build and that people will want.

Raj Judge:

Right.

Trevor Martin:

But I think it’s more just adopting that mentality and being less concerned about being so right about the product that is a pre-seed company with a platform.

Ursheet Parikh:

I think that’s kind of very well said. And if there’s one attribute I’d really highlight, and I’ve come to sort of respect and appreciate, it’s the strategic thinking in terms of you don’t necessarily build the perfect product, right? Like when you have cutting edge technology, you have to realize the limitations of it and the readiness for it. And then there’s typically a customer or market segment for it.

And so as you kind of go down the development path of the technology, earlier versions of it may have smaller segments that will still value it. And you do want to go ahead and keep yourself honest by testing it out. Not necessarily always going into those businesses, but having a sense of what it takes. And at times, a lot of those sort of revenue things actually do validate the platform, and the partnerships, and the ecosystem. And so I’ve always been amazed at how you’ve sort of been able to kind of go ahead and keep that focus as you’ve gone from pre-seed to where you are now.

Trevor Martin:

Yeah.

Raj Judge:

Okay. That’s great. So now you know it. Platform versus product, and how they work. Let’s talk about some more exciting stuff. Let’s talk funding. We’ve got some investors on board, we’ve got a CEO who’s gone through some rounds of funding. That’s the stuff. Now we know about unicorns, we know about decacorns, and there’s a lot of funding going on. It’s been a frenzied environment over the past few years and not sure if there’s even a standard for funding these days.

We’ve had companies with revenue, companies without revenue, companies with product, companies without product, companies with IP, with some IP, questionable IP, but getting funded. And getting funded at all sorts of different valuations with all sorts of different metrics. And all sorts of different applications of what they think as investors and CEOs are the right metrics. And so having said that, Arvind, you talk a lot about the coffin corner, which is an aerodynamics concept, and I’m very much a supporter of the idea and the thought. And I think I agree that companies can find themselves in the coffin corner. Can you tell everybody about the coffin corner and what that is, and how companies can end up there?

Arvind Gupta:

Sure. So the coffin corner is a term that denotes the speed at which an airplane stalls and has its wings ripped off, and goes too fast and has its swing ripped off. And that coffin corner is when those two speeds are the same. And so I use it all the time, in terms of startups that are coming and raising money, and they’ve raised enough money where they’ve gotten traction and speed. But they’re out stripping what they’ve de-risked, and so they’re getting into thin air where if things don’t go perfectly in the round, they’re not going to be able to raise the next one. And you’re going to go from a very high valuation to zero very quickly. And that is something that is also dependent on the environment. 

And it’s not just on the execution side and this is what makes it dangerous. The funding environment can change, and that all of a sudden throws all your math out of whack. And so I think that’s where I always talk about raising rounds with cushion, buffer, and really looking at de-risking events that prove your TAM. Because we talk about platforms. Why do platforms matter? Because they increase TAM, total addressable market. And so if you’re thinking about how to go about structuring your next round, think about what is the most basic thing that needs to be de-risked that actually increases the surface area of what you could de-risk. That’s really, there’s a lot more to the coffin corner. That’s the one minute version.

Raj Judge:

Absolutely. And we’ve seen a lot of well funded companies kind of blow up like that.

Arvind Gupta:

We’re going to see more unfortunately. And I hope, I hope not. And it’s always sad for me to see. But I think what happens in a low interest rate environment is the money has to go somewhere, and then it creates these issues. And so, the best thing founders can do is know that there can be too much capital.

Raj Judge:

So prudent fundraising, as opposed to extravagant fundraising, is-

Arvind Gupta:

Having a plan and knowing what it does. So that way, when you get to the other side that you’ve, de-risked something that allows the next investor to understand what they’re investing in.

Raj Judge:

That’s great. I’ve got just another minute and a half left. So I’m going to switch over to a couple rapid fire questions. So here’s the rules. You only get one sentence to respond to this. And so hopefully you guys will come up with a great sentence that shoots the tagline. Let’s start with you, Trevor. How do you trust a VC?

Trevor Martin:

It’s a conscious choice. And it’s a choice you make. And that’s just your gut feeling honestly.

Raj Judge:

Great. And, Ursheet, I’m going to ask you the same question. How do you trust another VC?

Ursheet Parikh:

You know, aligned to the mission of the founder, and economic interests are aligned.

Raj Judge:

And Arvind, how do you trust a founder?

Arvind Gupta:

How do I trust a founder? I get to know them and understand what drives them to do what they do. Because doing a startup, especially in our field, is so incredibly difficult.

Raj Judge:

More than one sentence. I got to cut you off.

Arvind Gupta:

Oh, shoot. Sorry.

Raj Judge:

I’m so sorry.

Arvind Gupta:

No, no, no. I didn’t hear that part. One sentence. Dammit.

Raj Judge:

So sorry. The rules are the rules. I’ve got to play by the rules.

Arvind Gupta:

Fair enough. Fair enough. I wasn’t listening.

Raj Judge:

Ursheet, what does it really mean to be a founder with a mission?

Ursheet Parikh:

You know, it’s the life, the company life, it all kind of blends into one, and then the mission becomes a platform that you bring people along with you on that end.

Raj Judge:

Okay. That was one sentence. That was a Herman Melville sentence. But it was a good sentence. Trevor, what does it mean to be a founder with a mission?

Trevor Martin:

I think it really means that you wake up every day excited to work on that, and to recruit other people, importantly, to work on that as well. Because if it’s just you, you’re only going to get so far. 

Raj Judge:

Excellent. And then now the last question for all three of you. One word, not one sentence, is all you get. Over the next three years, what’s the new upcoming sector that everybody is going to invest in? Let’s start with you, Trevor. No bias.

Arvind Gupta:

No pressure.

Trevor Martin:

I think urban, and I will say human and planet health.

Raj Judge:

Arvind.

Arvind Gupta:

Yeah. Biology and reversing climate change and curing disease. Yeah. That’s more than one word.

Raj Judge:

We have a rebel here amongst us. Well, thank you very much everyone. And I hope we made it fun for you guys. And we kind of gave you some of the insights into what our esteemed panel brings to the table here with their experience and their backgrounds. And so thank you and really appreciate your attention late in the afternoon.

Arvind Gupta:

Thank you. Thank you all for having us.

From Inception to Iconic: All Raise x Mayfield

It is never a straight line from inception to achieving breakout status for companies.

Entrepreneurs navigate many stages of getting the world to share their vision – inspiring employees with their mission, getting investors to write the check, propelling customers to buy the product and most importantly, growing as a CEO.

In this session, entrepreneur whisperer and investor Rajeev Batra (Marketo, Servicemax, Outreach) chats with three founders that Mayfield has invested in – Sandi Lin, CEO of Seattle-based customer training leader Skilljar, Christina Ross, CEO of New York-based modern FP&A software provider Cube and Janice Chen, Co-founder & CTO of Bay Area-based CRISPR platform Mammoth Biosciences – to share their learnings and highlights from their journey.

Transcript

Rajeev:
Thanks everyone for coming and attending. I don’t do these that often, and it’s a pleasure when I get to, especially with guests like Christina Ross, Sandi Lin, and Janice Chen, three female founders… Actually, I should stop using the word female founders because I believe they’re just founders, and I have a certain philosophy about these things. And, Sandi and I often talk about this when I tell her that I truly approach the world being blind to color, gender, race, et-cetera. And, life circumstances, because I’ve, myself, wanted to be treated that way, but I also recognize that that’s not how the world works always. And so, it is all of our responsibilities to promote and work hard at creating equality at every single level and do what we can do.

So, I take that responsibility very seriously, and I hope it’s a lifetime of work that I can continue to dedicate myself to. And so, I’ve had the pleasure to work with Sandi and Christina, and other CEOs in the portfolio who are not men, not of traditional backgrounds. As a matter of fact, I’ve also worked for two venture capitalists who are not men. I’ve worked for a number of venture capitalists who are males, but I’ve also had the pleasure of working for Virginia, who was a great mentor and Heidi Roizen as well. She’s one of the key people who was responsible for having me come out to Silicon Valley and had me put on this path of pursuing venture capital. So, I’d like to thank everyone for being here and giving me this platform to have a fun conversation with Sandi, Christina, and Janice.

I’ll just kick off with quick introductions. I’m one of the partners at Mayfield, I help lead the enterprise software practice and I focus and specialize on application software, SaaS. And that’s what I’ve been doing, supporting entrepreneurs in that area for 14 years here at Mayfield, and I did venture capital at a couple other places before this. I have been in the enterprise software industry for a while, both as an entrepreneur and as an executive. So, with that, I’d like to introduce the panel. We have Christina Ross, the Co-founder and CEO of Cube Software, and Christina, maybe you can just give a… Maybe, I’ll just do a quick round table, and then you guys can talk more about yourselves and introduce yourself. So, we have Christina Ross, the Co-founder and CEO of Cube Software based out of New York. Sandi Lin, the Co-founder and CEO of Skilljar based out of Seattle. And, we have Janice Chen, the Co-founder and CTO of Mammoth Biosciences. And Janice, you are in San Francisco, or Berkeley, or where are you based these days?

Janice:
San Francisco, these days – the company is in Brisbane, which is just north of south San Francisco.

Rajeev:
Great, so why don’t you go ahead and introduce yourself and a bit about why you’re here and what do you hope to share with the audience today?

Janice:
Sure, thank you so much, Rajeev, for the introduction, and thank you to All Raise for giving me the opportunity to be on this panel with these amazing founders. It’s truly a privilege to be able to talk about our journeys. And so, my name is Janice Chen, I’m the co-founder and CTO of Mammoth. I actually consider myself a scientist founder, so coming in from the life sciences biotech industry. A little bit about my background – I did my PhD in Jennifer Doudna’s lab at UC Berkeley. And, you may know her from her recent Nobel prize on the discovery of CRISPR as a gene editing tool. So, I know part of our goal here is to tell you a little bit about our stories and how we got to where we were to hopefully inspire others who are considering this path.

But for me, I never really considered starting a company. Part of considering my career options was really just talking to people, attending panels like these, and learning about what PhDs did and the next step in that career, both in academia and industry. And, I think a lot of what motivated me was having someone like Jennifer be a really strong mentor and really pushing me to think big. For me, the breakthrough moment was sort of near the end of my PhD when we discovered that CRISPR could not just edit DNA, but also detect DNA. And then, being able to show that the technology could detect cancer-causing HPV in patient samples was really what unlocked me and my co-founders to realize, okay, we have something really powerful here to be able to transform it into a company.

So, sort of after that moment, it was sort of an obsession for all of us to think about how can we actually build these CRISPR technologies to address unmet needs in healthcare and really building the technologies beyond just the academic lab. Coming out of grad school, there really wasn’t much to lose, and we just decided to take the leap of faith. So myself and my co-founders Lucas, Jennifer, and Trevor decided to come together and start the company. At Mammoth, we are developing this Nobel prize-winning CRISPR technology as a programmable search engine for the genome. And today, we are discovering and developing these novel CRISPR proteins to diagnose and cure diseases. And in the future, a platform will enable industries beyond healthcare, such as agriculture, bio-security research, and more. So with that, I’ll hand it over to Rajeev to introduce the next speaker.

Rajeev:
Janice, thank you so much. That’s a really inspiring, and I’m sure we’ll learn more about how you guys are as a team, sort of taking the journey, have taken the journey forward to truly building a groundbreaking platform company. Sandi, why don’t we go next with you?

Sandi:
Sure. I’m Sandi Lin, the CEO and Co-founder of Skilljar. We build customer education software for companies to deliver product training, and specifically we’re best at end users, customers and partners or people outside the four walls of your HR and employee system. I am an engineer by training, civil engineering actually, with a focus on transportation, and supply chain, and large-scale systems. Worked for that for a few years after undergrad then went to business school. I did not identify as somebody that would ever go to business school, so I’m happy to share that experience as well. And then, after finishing my MBA, I joined Amazon as a Product Manager in 2009. So, I have some pretty large company experience as well. I kind of always wanted to be an entrepreneur, my dad was an entrepreneur, I always had that little voice inside of me that said, can you do it? Can you do it?

But honestly, I was terrified about the career risk, the financial risk, the throwing myself off the cliff to all these things I wouldn’t know, and be responsible for. And, it actually has been terrifying, so I’m happy to talk about that as well. Skilljar now, we’re about 170 people, we’ve raised over $50 million in venture capital, 400+ customers. So, it’s been quite a journey and we pivoted a few times early on, but our mission is to create the win-win-win: where anyone can get the skills they need to succeed in a changing economy; where customers can get the full value of the products and services they’re trying to use; and where companies can also drive business outcomes through learning.

Rajeev:
That’s great, Sandi, thank you for that. And, you are changing the world in many, many ways, by enabling people to really be equipped in this new digital economy. I call it the new digital economy, but because today’s software is only, still 2% tech, still only sort of 2%, 3% of the GDP. And, equipping the next generation workforce, with the ability to use the products and services to do their job better is a pretty incredible thing to do. And while doing that, you’re also enabling incredible business success. And, it is pretty remarkable, all the wonderful things you’ve been able to do in the last few years. And, I think you’ve only gotten started. So Christina, you’re up next, you have a wonderful story as well. And both of you, Christina and Sandi share something in common that you both were Techstars entrepreneurs. And, I know there was some questions around advice on sort of getting into accelerators, incubators, et-cetera. And so, maybe you guys can share that too as well when you talk about this. So Christina, with that, please.

Christina:
So, my name’s Christina Ross, I’m Co-founder and CEO of a company called Cube. We’re a real time FP&A platform for modern finance teams and businesses to make faster, smarter decisions. And, I’ll start by saying that I know not everyone thinks of finance as the type of company, or finance centric company, as being mission-driven, but we very much are. Our mission is to elevate the role of finance in an organization. When you think around the corporate table, who often has the seat that’s thought of as the back office, and that’s typically the finance persona. It’s ready for a rebranding, it is still thought in many ways, if you know the movie Office Space, stapler in the basement. But, the reality is the future of finance is incredibly strategic. And, it’s the difference between companies that do not do well or fail, and the companies that really excel.

We’re also moving finance from being a cost function to being a growth function. I’m a former CFO, I very much have been a startup groupie in many ways, for most of my career. After being at big companies like GE and a consultant with Deloitte, I found this little company, no one had heard of called Rent the Runway. There were maybe 30 people at the time, and I joined as their first head of finance. And, I repeated that journey a couple of times through different startups. And, one thing I learned in that journey was how important the finance role is to survival in companies, in stages like these and how misunderstood they were. And, one of the reasons why they were misunderstood is they weren’t empowered to do the work that they were there to do because they spend all their time manually aggregating data on all these different spreadsheets.

So, I’m sure some of you are dealing with that now or have seen it. And, what we built at Cube is a financial planning and analysis platform to not only take away all the manual pain, but empower these finance users to make faster smarter decisions and be heroes within their own organizations. So, I’m super excited to join the panel today because I felt like when I was first fundraising, there was this unwritten playbook that I didn’t have access to. And, if someone had opened up that playbook for me, it would have saved a lot of challenges. There’s so much growth and so much journey ahead still, but hopefully we can share some of those pages with you all today.

Rajeev:
That’s great, Christina, and I think it’s important to underscore again that it’s hard to get inspired by boring software – what’s software? What can it possibly do? But if companies can make better decisions about where to allocate their resources, both financial, human, and other resources, they can drive better outcomes, right? Innovate, create better products and services that actually make an impact and change the world. So that’s the connection between that and really bringing things to life. And of course, Janice, your company is at the forefront of transforming so many things. And, it speaks very closely to me and some of the causes I’m involved with given I have a special needs child.

A lot of the research that is being done around finding a cure for his condition and the condition of many children like him has benefited from CRISPR technology to create, for example, mice models and other things. And, it may even have efficacy and the eventual therapies that they might come across. So, I think there’s a few questions that came from people, and then there are some questions I think we have discussed together as a group and in our conversations. In terms of some of the opportunities and challenges you face as entrepreneurs in raising capital, hiring people, building companies, creating winning cultures. Maybe, we start with a topic around fundraising. I think that’s, that’s probably a pretty key and important one, all of you have sort of touched upon it.

I have two questions I really want to dig into – one is fundraising, there’s a few questions here. I’ll just rattle them off, and then let’s sort of make more of a dialogue around this. How do we fundraise when we don’t have product market fit? If the MVP is primitive, is their a chance to get funding? Do VCs invest at the early stages, pre-seed seed, et-cetera? And so, if you are in beta and pre traction, what are the most important data points to share when applying for grants and accelerators? Is it market size, potential revenue? Are there tools and services you recommend that can help guide a new founder estimate that stuff?

So, the point is, it feels like there’s questions around what stage do I need to be in order to engage in a fundraising process and what are some places to start? Do I go to VCs? Do I go to Angels? Do I go to friends and family? Do I go to incubators? Why don’t we start with you, Sandi.

Sandi:
All right, cut me off if I’m going too long because I have opinions. So, I think first of all, for kind of less demographically advantaged founders, this is actually a more important issue because often we don’t have the same access to generational wealth or high net worth individuals. My parents were immigrants that came to this country with nothing. So the, oh, you can self-fund yourself financially or hire a team that can self-fund themselves financially often becomes a more acute issue, I think for less represented founders more than others. And then, also I can say for me personally, I very much upfront decided I was not willing to go into credit card debt and/or sleep on people’s couches, or all the sort of war stories you hear about fundraising.

And that was a decision that I made for myself early on. So, I think one of the secret playbooks or pages that Christina mentioned is that all of the dialogue for early stage fundraising, prototypes and traction, a lot of that is just a way for the investor and the entrepreneur to get to know each other, because there are angels through VCs that will fund on a PowerPoint and there are angels and VCs that will not fund through a PowerPoint. And, the same fund, or person, or partner will say one thing and do another in any given situation, so it’s all situational. And so, a lot of the dialogue around these very fundamental business questions is more around kind of getting to know you, get to know you as a person, get to understand how you think about the space.

So for me, and I started this company in 2013, so the environment was very, very different, and I was also terrified by the fundraising process and asking for money. So, the idea of applying to an accelerator made a lot more sense for me because I kind of understood that process, right? I’ve applied to schools, I’ve applied to jobs, I kind of knew how to get through that. And then, it doesn’t hurt to apply, and if you get in that gets you along another milestone to the journey. So, I think the accelerators were much more prominent in the early stage fundraising ecosystem back in 2013 than they are now. But I’m very glad that I did so in hindsight, because I think it helped get… There’s a big difference between having zero money and having $100,000, or what it was at the time, because it’s a huge difference in terms of just being able to pay your annual bills, out of something that’s not your own pocket.

Rajeev:
And that, was Techstars Seattle, correct?

Sandi:
Correct.

Rajeev:
Great, okay. And Janice, how about you, how did the fundraising process start for you, or how did you even think about it?

Janice:
Yeah, so first of all, for us, fundraising has been a team effort. I’m not the CEO, so I didn’t lead the fundraising effort. Our CEO, Trevor Martin, is the one that led that effort, but it really was a team effort between the founders, and sort of the core employees at Mammoth. And certainly in the early stage, like Sandi said, I mean, everything’s so vulnerable, right? It’s kind of a chicken or the egg problem, I think is what a lot of the questions I think we’re getting at. You don’t have the capital, so how do you get to showing your prototype works, but you also need to show your prototype works to get the capital, right? So, there is kind of this dilemma, certainly in the early stages. I think, I can speak really only to my experience in the biotech industry.

And, this is my first startup and really my first real time job. So, I come from a unique, I guess, background where I came to this with completely fresh eyes, which has been great, but also has also been really challenging. For our industry, biotech is extremely capital intensive, it’s really hard to bootstrap. You need lab space. A lot of what’s great about coming from academia is that you do… At least in my case, we were able to do a lot of that proof of concept work as part of our research as PhD students. So, a lot of the early prototypes, if you will, were done as an academic graduate student, and we’re able to out license that technology or in license that technology to Mammoth from UC Berkeley. We had, again, a lot of great networks being in the Bay Area, being in Jennifer’s lab, connecting with Trevor, ultimately connecting with Mayfield and getting a lot of momentum around, okay, getting alignment on what is the mission of the company? How can we continue to build this platform and kind of leveraging, again, the resources as well.

Particularly, with incubators, I think for biotech companies, that’s really critical to get the lab space and show initial proof points early on. And ultimately kind of lay out a plan that you can execute on. I think, the other piece for fundraising is, for us, it was really important to make sure that we were in a position of strength when we were to go out fundraising, just to make sure that we could really leverage kind of the value creation that we had been developing at the company. But certainly, in the early days it’s hard and there’s a lot of uncertainty, but it is just being super thoughtful about who you’re talking to and making sure that the investors that you’re interested in are really aligned with you, the founder, and the company, and the mission.

Rajeev:
That’s great, and Christina?

Christina:
All right, I have a few thoughts, so let me just cover some of them. First, is I’ll start with a warning, which is, you’ll get a lot of, “why don’t you just” advice, which is what I got during the finance journey of, oh my buddy, so-and-so started a company, and he raised like $15 million before he had anything. It’s okay if that doesn’t happen to you, because you’ll hear the stories of the one-offs, you’ll hear the stories of the 1% of deals that make it worth talking about. So, fundraising is hard despite the fact that you’ll hear lots of stories about how easy it was for some people, it’s hard. Two, my fundraising strategy was to play Moneyball because the beginning is the absolute hardest, in my opinion. And then, it gets a little easier, and a little easier, and a little easier.

And if you know Moneyball, the idea is to get on base. And so each step of the way is you’re making progress in your journey, in your startup, it’s to get on base, it’s to get the next win. And, getting my first dollar of funding was moving a boulder up a mountain. So, I really resonated with Sandi’s point of, zero money and $100,000 is such a big difference. And at later, stages of fundraising, $100,000 is nothing. At early stages of fundraising, $20,000 would have made all the difference in the world. So, just make that incremental progress to get on base because that’ll allow you to go further and further. I think, the other really important thing is your fundraising, that it took me a while to figure out, is it’s all about fit.

So now, that I’m a lot more involved in things like sales and marketing, everything I relate to a funnel or a funnel exercise of what comes in at the top of the funnel and at the bottom. And, when you’re fundraising, you’re thinking about your investor funnel, they’re looking you just as much as you’re looking for them. So, one thing that changed my mindset on things was actually being in a dinner where it was mostly investors and a couple of founders, and the way they were talking about founders, how do we get in these good deals? And I was like, wait a minute, they’re all fighting over us, I thought we were fighting over them. So, get your mindset in, they’re looking for you, you’re not just looking for them.

And then, when you think of that funnel, it’s all about the right fit. If someone rubs you the wrong way, you don’t have to work with them. If, someone doesn’t understand your space, then that’s their loss. I spent so much time trying to get people to understand what our company was and how it worked, they weren’t going to be the believers because they didn’t understand it. And so, what I should’ve done is moved along earlier rather than trying to get them to see my side. So remember, it’s ultimately a fit exercise, I’m sure there’s lots of other nuggets, but those are a few things for me.

Sandi:
I was going to add also, there is a deal out there for you, especially now with AngelList and all kinds of virtual ways. You no longer have to just pitch local people in their area. So, I completely agree with Christina, I think for my first round, I pitched over a hundred potential funders, and I had actually set myself a quota where even before I was fundraising, I said, every week I’m going to meet with one new person that could be an investor in my company. And, I held myself to it, because it was very uncomfortable for me. So, there is a deal out there for you, and it’s like work.

Rajeev:
That’s some great advice. I think, a couple key things I heard here, there’s some questions around what stage should I be fundraising? At what point should I go out and start fundraising? And, I think fundraising in a way, it is a state of mind because you need capital, some sort of capital to develop your product or service and get it out there. And so, there’s an old adage that says, entrepreneurs or founders should always be fundraising. And, I don’t mean that in the sense of, you have your business to run and your product to build, but there’s this concept of you do need capital, so you always have to kind of be attuned for the fact that you are open to capital or capital conversations, especially in the early days. Because let’s face it, it’s hard, right?

So, you kind of have to have almost this subconscious background process running in your mind that this is something you have to do. Because it is not one of these things that you’re going to do all this stuff, and then you’re going to go fundraise sort of in a serial fashion, right? Yes, at some point that’s what it becomes. But, I think it is a bit of a state of mind, because in the early days, it’s the people who believe in you, they really have to believe in you and they have to believe in what you are trying to do. And, they have to be comfortable with the fact that whatever it is that you’re going to do will also change, and evolve, and morph. And so, it’s a little bit of both of those things.

And, it is a bit of a, sort of this somewhat amorphous exercise, but it’s a state of being, state of mind. And like Christina said, hey, you’re at a dinner, there’s like eight, nine people and their investors. If, you have that sort of background process running in your mind, you’re like, wait a second, these are potential investors. Now, one of them might be interested in what I’m doing or none of them might be, but they like what I’m doing, or who I am, and what I represent. They might say, listen, it’s not for me, but I know somebody else who’s really looking for something like this. So, I think that’s an important part, and the other thing I would say that I’ve observed is, there are a lot of people out there who want to support entrepreneurs. Especially, in today’s day and age, I think, A, they want to do that, B people have a lot of money.

If people haven’t noticed, the Fed’s been printing money at a prodigious pace. And so, there is that opportunity, one just has to also believe it’s possible, right? I think, yes, it’s hard, and the statistics are not very encouraging always, but I think first of all, one has to believe that it’s possible. And, that’s an important component. One question I have for all of you: at what point, and this is connected to fundraising in a way. Was there a specific point in time at which you said, I’m going to go start this, I’m going to be an entrepreneur – there’s a shift that happens in your mind.

And, was there a shift that caused you to say, this has to happen, I’m going to succeed at this and you crossed a threshold? Because, I think that’s an important part to making a commitment to becoming an entrepreneur, and then sort of raising capital then becomes part of it, right? It’s this moment that you cross this threshold. I’d love to hear that from the group here. And, did that conviction help in sort of saying, I have to find capital now, and now I’m going to go execute on some strategy?

Christina:
I can answer that. I knew I always wanted to be an entrepreneur because I became this entrepreneur groupie where I was doing startups, but I wasn’t the one in charge, so something was always inside. The way I made it happen though, that was the hardest part. So, the mind shift for me was how do I now move my life around this thing that I really want to do? How do I take what’s in here and make it part of my environment? My story was I had a full-time job as a CFO, I was making good money. I had two and a half year old twins at home, I was in my mid thirties, this isn’t really the time you start a company and take no income in. But for me, if I didn’t do that at that moment in my life, there’s no way I would have done it 10 years later.

That’s the story that I told myself to make the change. And, I had a conversation with my husband, there’s actually a very specific story where we were going to buy a house. And, we said, well, if we buy this house, we have to get a car, maybe two. And, we have to maybe have someone to watch the kids during the day. Anyway, I’ll make a long story short, we realized we would be tied down financially and I would never be able to do this. And so, we made a decision that in order to be the entrepreneur that I felt up here, I was going to have to change my life. And so, like Sandi said, I didn’t want to sleep on someone else’s couch. But for us, that meant some other sacrifices. And, I gave myself a time limit of a year, of, if I’m not making the right amount of progress in a year, I’ll revisit this.

And then, it was off to the races. So, I spent a good six months of time before I quit my job, really understanding what it meant to be an entrepreneur, reading every single book. Not about how awesome certain people are, but literally how hard it is. Because, if you prepare yourself for how hard it is, I don’t want to say it’s not hard, but it doesn’t surprise you. So again, I’ll use the example again, that I had twins and everyone told me it’s the hardest thing that ever happens to you having two babies the same age. And, when I did it, it wasn’t that bad because I was prepared for it to be the worst thing that ever happened in my entire life. And of course it was wonderful, but same thing with being an entrepreneur, everyone’s like, it is the hardest job in the entire universe. But, once you get yourself there mentally and get your environment there, then there’s no stopping you.

Rajeev:
And Christina , and how your first check come about? There’s a lot of conversation here, I’m seeing a lot of comments on, what was your first check that gave you that confidence and that allowed you to… And, did things accelerate after that? And, how many people did you raise capital from in your sort of early, early phase? And, was that before Techstars, after Techstars? And, you were in Techstars New York, right? And so, when did that first capital show up, and where did Techstars fit in? And, maybe we talk about a little bit about how you seed happened, and how you series A happened, so people get a little bit of a full picture here?

Christina:
Yeah, I had a lot of, “why don’t you just” advice in the beginning. And everyone’s like the market’s so frothy, everyone’s so wealthy, just have 10 people write you a $50,000 check, you’re all done. I’m like, okay, who are these people who are going to be writing a $50,000 check? I didn’t have the network of wealthy people, I knew a couple. I have like a rich cousin and I got a check from him, but this was a friends and family round. And, you can only pull together so much in a friends and family. But, I wasn’t getting the $250,000, $500,000 that I would need to hire people who were really going to commit to building this product with me. So, I actually started cold calling or cold emailing, I looked out on LinkedIn for people who were associated with my somewhat niche-y industry, and pitch them, literally just live pitch them.

And, I got some initial interest, but I also didn’t know how to close at the time, how to close an investor. And so, I had a lot of people sort of waiting for the round to come together before they commit their checks. And, it really took one final yes, so by the time I got the yes from Techstars, if you’re in the program, every other check… Once people heard this one signal from the market, my round literally closed immediately. So, I went from maybe having 150K to 600K in two days, covered. And then, once I had that, I was oversubscribed for my round, before I knew it, I was picking which investors I wanted or not in my pre-seed. And, we ended up having to cut it off at 1.25M.

So, it was a waiting game for the signaling. I see in the comments here, “What does good at closing look like?” So, I saw this in some of the other questions before, I was new to asking for money, and the first problem with what I just said is, I’m asking for money. I’m not asking anyone for money, I have a really amazing business that, if you’re lucky, you have the opportunity to invest in. That’s a mind shift change. So number one, I had to get out of the, I’m asking you for money for my business, and instead it’s, I have a really cool opportunity, I might have some space, maybe I can let you in. And, one piece of coaching that Techstars gave us was the language you’re using. It’s maybe I can squeeze you into the round, how much do you have? We have a certain amount to allocate.

So again, you’re thinking of it like a constraint and resources is part of it. And then, when it comes to closing, people might have some objections. So, it’s like closing a sale, too. You might ask them, they were like, oh, this is interesting, I could be interested in investing. And then, I used to leave it there and be like cool, I’ll call you later. Instead, now I asked them, well, what would it take for you to get to say 25, 50K? And, they might say, well, I really want to see another small fund in the round. Okay so, assuming there’s another small fund in the round you’re in. So get their specific objections. And then, when you get that fund and you call them, then you come back, so that’s the soft close. And then, when you want them to write the check, say, I needed in 24 hours, give them a time limit, and the round is closing.

So, you get them from whatever objective they have to saying, assuming that objective is met, we have a deal basically, and then get them to the other side. Because, everyone wants to sort of commit, but never go all the way. And then finally, the seed and series A are longer stories. And we want to give them more time to Sandi, and Janice to cover.

Rajeev:
Christina, that’s wonderful, and I can testify to Christina’s approach because she worked this magic off of the fundraising, painting an amazing vision for the company that she was building, her background, why she is committed to it, and the product that we’re building. So much so that Mayfield preempted the series A. We preempted the Series A by probably, I don’t know, 12 to 18 months, is that fair?

Christina:
Yeah.

Rajeev:
And so, she did do this Jedi mind trick on us as well, and we’re glad that it worked out. Sorry for the Star Wars reference, but Christina’s starting to do sports references and Christina’s not a sportsperson, so I’m really excited to see that. And I think, one thing that Christina, you’re describing here and Sandi you’ve described this as well, is that fundraising is a sales process. It is a sales skill, and I believe that every person in the world is in a way a salesperson. You have to embrace selling a little bit, and especially as an entrepreneur, you’re always selling, right? You have to attract capital, you have to attract customers, you have to attract employees. And oftentimes, I find entrepreneurs, especially product entrepreneurs – and I apologize if I sound a little judgy here – but there’s a little bit of aversion to, I’m not a salesperson, I’m a purist, I’m creating a product and this is going to change the world.

But, deep down we’re all salespeople, and selling done right is a good thing, because selling is about solving somebody else’s problem. And, it’s a very empathetic act because it implies that you listen, you pay attention and that person is trying to solve a problem and you have a solution for them. And, in the case of Christina, the way Christina has described this is they want to invest in you. They want to invest in an innovative company, they want to invest in entrepreneurship and entrepreneurs. And yes, they want to make a return, but this is really risky stuff. So, they are seeking a company and a founder to invest in. And so, if you tap into that, sort of think about it from that standpoint.

I think it is about understanding their needs and seeing whether what you have to offer them fits that. And so, thinking about it as sales and developing your inner salesperson, I think is something that I would encourage people to really think about and embrace. And, if it’s a place where you need help, get some skills around that, or even role-playing and working with your friends, et-cetera, it’s okay to do that.

Sandi:
Especially if we’re talking about angels, a lot of time, their goal isn’t necessarily to make money from an investment, it’s around what they can say to their friends about what they did lately, who else is in the company – I co-invested with so-and-so. And so, this is where they kind of hoard to the close, especially early stage investors are a little bit driven by fear of missing out and what else is going on. And so, to me, a lead, our quote unquote lead was not the biggest check at all, but it was somebody I knew had a lot of cache with the other, in my case, Seattle investors. And so, nobody has to know how much somebody else is putting in. Yes, it’s going to come out on the closing docs eventually, but your lead can be somebody put in $5,000, $10,000 in, but you say so-and-so is leading the round.

If, they have the right brand reputation, that will get other people to move too, especially when they want to co-invest with so-and-so, right? And then, I’m not familiar enough with the actual transaction vehicles anymore, but I think there’s SAFE and other types of convertible things where… I mean, part of Techstars coaching is also set your first goal really well, so you’re always 50% full. So, if keep your first, we’re raising 200,000, from friends and family. Even I was able to cobble down, I think a 100K of commitments from my own savings, and like Christina, I had also given myself a year. I had saved to make this possible, I had every moderately non-poor person I knew was asked to participate. Of which, you’ll be able to hustle up, with enough effort, some degree of funding, and then you’re 50% closed. And then, all of a sudden, the next day you’re oversubscribed. So, you’re expanding the round and that’s a bit of the psychology.

Rajeev:
Yeah, that’s great. And look, there’s a balance, look fundraising is difficult, especially in the early days. But, with difficult things also comes appreciation for the resources that you acquire. And then, how you think about spending them. I do wish that fundraising were a bit easier for entrepreneurs, especially for, entrepreneurs of diverse backgrounds and women. It needs to be easier, but there is something to be said about fundraising. The barriers to fundraising actually do create an appreciation for the capital you have and how you’re going to go spend it. And, because overcapitalization does create a lot of problems as well. And so, I do believe that when founders do have a tougher time raising capital, they build different types of companies. I’m not suggesting that fundraising should be made difficult, but I always think about silver linings – anything that’s hard usually produces, right? Like diamonds are created by putting a lot of pressure on things.

Let’s shift a little bit from early stage fundraising to a little bit about sort of the company building side of things. You have capital now, I guess one last thing on capital would be, is in the beginning, all capital is the same, it’s green, dollars are green and you just need the money. How do you think about the quality of the investors that you bring on board, whether they helped create a domino effect, or people who are helpful and provided you advice? And, how has that sort of affected your thinking as you built your company? Because, you need capital, but then you need things beyond capital. How do you think about investors and quality of investors as a component of fundraising and building your business?

Sandi:
I think, I might’ve gotten some advice from Rajeev once, that do no harm is a good place to expect from your investors, in the full range of things, right? Because for the most part, your choice of an investor, as long as they do no harm is not going to make or break your business. And, if you’re expecting them to transform your vision or whatever, you’re probably expecting too much. And, many investors can actually be destructive in terms of taking your time resource, kind of meddling with what should be management decisions. So, I think the first bar is do no harm. And then incrementally, I mean, it’s also true that there’s very few… And, what I appreciate, Rajeev and Mayfield is, that they can go the distance from early stage through IPO, but also realistically many investors have a sweet spot of, maybe they’re helpful in the early stage, but they’re not going to be so helpful in scaling the business later.

So at least for me, finding people that I could really kind of trust at the core value level. And, I don’t think it’s, for me at least, both my series A and series B leads had tried to invest multiple times, several years prior to actually allowing them to do so. And so, by the time that the timing was right, I always knew they were in it for the right reasons, that they were true believers in both me and the company. And I think for me, that felt really important. And, here’s where reputations with institutionals – both the partner and the firm – do matter. Because, there’s also cases, and you know what happened already to Skilljar, where sometimes a partner moves on for whatever reasons. And so, what is the firm’s reputation in those circumstances too, of standing by the company and standing by the entrepreneur?

Rajeev:
Yeah, we met Sandi when there were eight people in the company and I tried to preempt an investment in the company, I think, twice. And then, she finally relented and said, “Okay, fine, let’s do this.” So, thank you for that, Sandi.

Sandi:
Well, see, I had such a low view of investors, I didn’t trust any of them. Very bruised from pitching 100s, and especially being in Seattle, which is not an early stage capital rich environment. I think, the good advice is always run a process. And so for me, preempting was hard because I really believed I had to run a process. And then, for a series A, I said, I’m going to have undeniable tractions, so I’ll never have to go through this pain and suffering again. So that being said, I think when I spoke to Christina, I was like, “Take Rajeev’s money, because you can actually trust him.”

Rajeev:
So, let’s talk a little bit about once you have capital, how do you really think about deploying that capital? What are the things that are important to you? How do you sort of think about what’s next? So, you have capital, so what do you do? I mean, what are some of the biggest challenges that you face in starting to build your company?

Janice:
Yeah, I think that’s the most exciting part now that you have the runway, right? You have to think really critically about how you’re going to deploy the resources. I think, probably first and foremost, it’s really focusing on the product and the opportunity. It’s about building evidence for the vision, making sure you can really execute on the value proposition that you’ve defined for the company. I think, that it takes a lot of discipline, I think, as well to define sort of what the roadmap looks like for the company. I think, really being clear on what your value inflection points are. Again, I think it’s really critical to be in a position of strength when you are going to go into that next fundraising round, because as Rajeev pointed out, and Sandi and Christina, I mean, not all money is the same.

It’s really important that you have the leverage to talk to quality investors who will be able to… You have the ability to select your investors, I think that’s not necessarily the case for everyone, but if you are in a position of strength, you absolutely have the ability to say no to people that you don’t feel like are aligned with your vision. And, you don’t have to take the first check that comes through. So, I think being really disciplined on how you’re using that money, bringing in the best people. I think that’s probably number one for us, when we started out, we had the money, we said, look, who would be the best person in the world to help us execute. And that, was kind of where we focus because you can’t deliver on your mission if you don’t have the right people in your company.

Sandi:
Plus one on team, because the day you close your round is now the day you’re raising your next round, in a sense. And, to scale, you need people especially super early, and it is a war for talent out there. And, you need to give that person, the 18 to 24 months to scale the business… For them to assemble their team and scale, and I think there’s a question in the chat earlier about Techstars. Techstars specifically looks for team, right? Because, you’ve got to be able to convince those first… Well, for Techstars, at least one other co-founder to go in with you, at least at the time they didn’t take solo founders. And then, anything capital raise, and I’d love to hear Rajeev’s perspective, but on the investor’s mind is, how are they going to attract the team to take them to the next level as priority one.

I imagine in Janice’s business and some e-commerce businesses, you do have to like pay for stuff. Pay for lab of space, or pay for raw materials, but at least in software, my business and Christina’s business, a lot of it is about hiring people to build things or sell things. And so, being able get that core group together quickly and your selection of those people’s incredibly important.

Christina:
This is one of my favorite topics in the entire world, which is how to spend money and where to put it. It’s part of our mission, so I’m so glad I get to at least partially answer this question, but you have to think of capital or money as your fuel, and you either want to put more fuel into your business or pull back depending on how the business is performing. So, one common mistake I see at the very, very early stages, when people get their first pre-seed capital is actually not spending it fast enough because they want to make it last long enough. You just need to know that when you put that fuel in, what do you expect to get out, and are you seeing those results to determine whether or not to double down. For example, you put money into your business, you hire a sales person or another engineer, and suddenly you’re producing 10X more.

Then, put as much money as you can, as quickly as possible to get to that end state to raise more money. So, you sort of have to start with where is your next stage, which might be your next fundraise, or it might be a certain set of deliverables or milestones, and budget your capital to get you there. But, feel free to spend what you need to take you there, but also know when is the right time to pull back if you’re not seeing the results to give you enough time to meet those end results.

Rajeev:
That’s great, and in all of this ultimately, right, I know we were talking a lot about fundraising, and ultimately all of you are trying to build great products and services, create customers with the hope that eventually you don’t have to raise any more capital. And, that your businesses are getting financed through customers. And so, like everybody said, once you have the capital, kind of really thinking about what other key priorities the business becomes incredibly important. And from my perspective, financial capital, when you raise capital, it’s about turning it into human capital. And, that’s the number one determinant. And, I think while we have incredible opportunity now with remote and distributed work, it also presents a lot of critical challenges.

It is a really competitive market, so thinking really about key hires and being able to move pretty quickly, and making decisions pretty rapidly about things that are working and things that are not working. And, I do believe for most entrepreneurs, they probably spend too little time thinking about hiring. And unfortunately, hiring is a full-time job and you’re a full-time CEO, do you kind of have two jobs. But, that’s I think a pretty, pretty important piece. I think, we just have a couple more minutes left, maybe we’d do a rapid fire type situation here. One piece of advice for everybody in the audience today, maybe Janice, why don’t you go first?

Janice:
Sure, there’s so much really good advice I’ve received since starting. And, I think the one that’s kind of resonated with me most is just make sure that you’re really building your guiding principles and values for yourself, and for your company, and keep asking the why. I think, for me, and I’m sure for everyone else on this panel, that journey is really turbulent and unpredictable. And so, you’re going to experience a huge bandwidth of emotions, right? And, I think if you can understand your why, understand the purpose of what you’re doing, what the company is doing, it’ll keep you grounded and it’ll keep giving you the power to move forward. So that, would be my advice.

Rajeev:
Well said, Christina?

Christina:
Venture capital, if you’re assuming you’re taking venture capital, is a 10X, a 100X business, you’re going big. So, get into the mindset that whatever you’re doing when you’re pitching is big, big, big, your big, your idea is big, what you’re trying to do is big, And, get your head around that as opposed to, well, we can grow two, three X, and have an exit. No, we’re thinking big, so just get your mind around that. And that, was also game changing for me.

Rajeev:
Sandi?

Sandi:
I would say, in a different kind of track, take care of yourself, it’s your company and your ability to sell investors. Candidates will only reflect your own sort of mental and physical wellbeing. And, I know it feels hard, but you are not your company, it feels like your company, it feels like your identity, it feels like every rejection is rejection of you. And so, to keep perspective, take walks, try to eat healthfully, get enough sleep. These things are really important for you to be on your A game, because if you’re not in your A game, it’s hard for your company to be on it’s A game too.

Rajeev:
That’s great, thank you for that, I think that’s pretty spot on and amazing advice from all three of you. And, thank you for letting me be part of your dreams, and living vicariously through all of you. And, I really appreciate all the entrepreneurs here who are trying to change the world and really make an incredible impact. And, for me, I’m always just… I wake up just not even believing that I get to do this for a living every day, to work for each and every one of you. So, thank you so much.

Sandi:
Thank you for having us.

Janice:
Thank you Rajeev, and All Raise.

Rewiring the Brain to Improve the Quality of Life | Mayfield x TechCrunch Disrupt

TRIPP is a digital psychedelic platform that fully immerses you into alternate realities to improve your mental and emotional well-being. Nēsos’ purpose-built earbuds retrain neural pathways to control inflammation, creating the new category of e-mmunotherapeutics. Mindstrong is transforming mental health through innovations in virtual care, data measurement, and data science. The brain is in a state of constant evolution, responding to new electrical signals from the senses and nerves. Hear from these neuroscientists, physicians, and entrepreneurs about how to build brain-based businesses that improve the quality of life.

Transcript

Ursheet Parikh:

What we are going to talk about next is really more mind-bending than my favorite movie Inception. I’ve always been fascinated with the brain, but at the same time just frustrated by how slow new treatments for our physical and mental health that involve the brain have been in coming to market. It’s not uncommon for new treatments to take 10 years only to find that they don’t work and cost several hundred million dollars. We think that part of it is because the brain is just a very unique organ. It’s different between animals and humans, so a lot of the traditional sort of drug development pathways don’t work. It’s also designed to keep drugs out of the brain, but at the same time, it’s very, very pliable and constantly forms new connections based on what we see, what we think, what we hear consciously as well as subconsciously.

And so we thought that it’s time there was a new way, so we started thinking about rewiring the brain. And at Mayfield, we believe in partnering with pioneers. None of them are bolder than the ones who are going to be on this panel, who are rewiring the brain to make our lives better. It sounds like science fiction, but this is all very real. And we’ll look to our panelists to convince us what they’re doing is real here and now. And so with that, it’s with delight and pleasure that I get to introduce this amazing panel of serial entrepreneurs. One is a former gaming executive, one is a neuroscientist, one is a physician, and they’re all building breakthrough businesses that involve working with the human brain.

First off, we have Nanea Reeves. She is the founder and CEO of TRIPP. She’s also a former gaming exec and she’s building a digital psychedelic platform that exposes us to alternate realities for improving mental and emotional wellbeing. We also have Konstantinos Alataris. Konstantinos is an entrepreneur that has actually built one of the biggest successes in the human computer interface world. He did a company called Nevro, which is a spinal cord stimulator to alleviate pain. It’s a $5 billion company, and he’s on doing his next company Nēsos. Nēsos is purpose-built earbuds that actually connect your brain to activate it and get it to control your immune system. It’s a new class of therapeutics called e-muunotherapeutics and we are excited to hear about what he has to say and where they’re going.

And then finally, we have Paul Dagum. Paul’s the former CEO and founder of Mindstrong Health, which is transforming mental health with virtual care data measurement and data science. And he’s onto his next company called Applied Cognition, and that’s addressing disease conditions in neurodegeneration, like Alzheimer’s. So Nanea, Paul, Konstantinos welcome. Glad to have you all with me today. Paul, let’s start with you. What is your vision for Applied Cognition?

Paul Dagum:

Thank you for having me on your panel, Ursheet. Today we have 47 million Americans who have preclinical Alzheimer’s disease. Those numbers are growing, and many of them will progress to cognitive impairment or dementia. Our mission is to develop the first FDA approved digital therapeutic for Alzheimer’s disease.

Ursheet Parikh:

And how is this going to get delivered?

Paul Dagum:

How far have we gone in our vision? We’ve assembled an amazing team of micro technology engineers, material scientists, product and industrial designers, mechanical engineers, software engineers, clinical scientists and Alzheimer’s neurologists. They each come from iconic institutions, have achieved tremendous individual distinction in their respective fields, and they share our passion for our mission. Where we’re at in terms of development, we are using and leveraging advances in microtechnology, in material science and AI to develop sensors that can measure the neuropathology of Alzheimer’s disease in an unobtrusive and continuous way.

Ursheet Parikh:

That’s pretty amazing. As you were talking about sort of the type of team members that you have, it’s amazing that so many different disciplines are coming together to take on what has become the big… While we are in COVID and there’s one pandemic, they’re dealing with the long term epidemic around mental health. So delighted to see you out on this journey. Nanea, what is your mission and inspiration for TRIPP?

Nanea Reeves:

Well, I think the thing we’re most excited about at TRIPP is really believing in the future of computing moving from the hand to the head and being the next gen wellness application for that transition. We’re very much committed as a team to create heart-centered experiences that help people transform the way that they feel, but we work very closely with academia and medical in the neuroscience community to make sure that we’re measuring and validating all of our design choices. And it’s a very cool experience, it sits somewhere in between mindfulness, producing the effects of mindfulness and psychedelics, and we deliver through VR and AR currently.

Ursheet Parikh:

Yeah. I’ve seen that it’s featured as one of the top applications on Oculus.

Nanea Reeves:

Yeah.

Ursheet Parikh:

What are the other platforms besides Oculus?

Nanea Reeves:

We’re also on PlayStation VR. So that gives us the largest audience in XR wellness to date. And we very recently launched on the Nreal glasses, our first wave of augmented reality experiences. So we think of it less vertically about VR versus AR, really there’s a convergence into one device that we’ll see over time. It’s really, for us, about how do we innovate around reality layering and do that all within this wrapper of creating beneficial experiences. And it’s kind of a narrative violation to use tech for making you feel better, but we really find that that mission is really exciting, not only to the end user but also to attract really great talent who want to use their skills to make a difference in the world.

Ursheet Parikh:

Yeah. I know, a lot of the smartest people of my generation have spent their life creating digital addicts, selling digital dope.

Nanea Reeves:

Yep. Yep.

Ursheet Parikh:

So I’m sure a lot of my friends are excited about the prospect.

Nanea Reeves:

Yeah. And you think about using AI in ways that we have in the past to manipulate you to feel so badly about yourself that you’ll buy something to fix you. Can we kind of reframe that in ways that make you feel good?

Ursheet Parikh:

Great. Konstantinos, you’ve had an amazing history even before starting Nēsos, but what inspired you to start Nēsos and what does Nēsos do? 

Konstantinos Alataris:

So for us, a starting point, frankly, was the role of inflammation – understanding more research around chronic underlying inflammation as one of the root causes in many diseases, from mental health, neuropsychiatric, neurological and autoimmune disorders. The other part of this equation was the fact that there is a lot more research and understanding. First of all, understanding that the brain and the immune system are in communication and interaction, constant interaction, with something that kind of recent in the last 20-30 years, we kind of understand more. And there is masonry through which the brain, not only senses, but can control inflammation levels mainly through the autonomic side of the brain.

So that, for us, those two elements and previous work that we’ve done that allows us to start interfacing with the autonomic part of the nervous system give us the idea that maybe now we can target this pathway that controls inflammation through engineered neural signaling. So that’s kind of what we’re trying to do and right now the best way to prove it is going to the clinic. So we have three programs in the clinic that span neuropsychiatric to autoimmune diseases.

Ursheet Parikh:

Konstantinos, that’s great. I’d love to get into exploring – how do we know this stuff is real? But can you just elaborate a little bit more on how the product works? Do I kind of inject myself, do I get operated on to put something in my head? What made it possible for you to sort of go from that category of products that you did 10 years ago to this new category of products?

Konstantinos Alataris:

Yeah, a little bit, the anatomical solution was that there is a branch of the vagus nerve, which is a big part of the autonomic nervous system, that actually is external, outside of your ear. So we have an access point. So for us, the access point is on the outer ear and the way we’re accessing or delivering the therapy, which is engineered nerve signals, is through an earbud. So that’s what makes it a kind of a form that people are familiar with and easy to use. So these are earbuds that you need to place in your ear for a few minutes a day. And through that, we’re trying to intervene into that masonry and retrain it to control it as it used to, because we know in the disease progression, it stops controlling it as well as it used to.

Ursheet Parikh:

Just mind blowing, right? No pun intended that you actually put a new kind of airpod and you don’t listen to any music through it, but it kind of goes and tells your brain to activate the immune system to fight disease. This does sound like science fiction. So how do we know this thing is working? Why should people believe this stuff is real?

Konstantinos Alataris:

Well the clinical data, which is from one study, we’ve published in the Lancet, the rheumatology edition, and there are more publications coming up. There is quite a lot of research from many academic institutions and researchers that have published the data that have shown the connection, not only the ability of that pathway to relate information to the brain about inflammatory levels, but also the other way from the brain to send instructions to the spline in order to modulate pro inflammatory cytokines. So that pathway has been very well enumerated, right now we’re trying to see how well we can restore that pathway. And there are other approaches with more invasive tools. For us, given that we have this access point, we plan to fully explore that among different indications. So that’s how we came here.

Ursheet Parikh:

That’s great. Yeah. I’ve seen your paper that was published in Lancet, which is unlike a lot of the other journals like Nature and Science. All the doctors I know do read Lancet and the fact that the success of your first trial was covered in that and now you’re running randomized control trials. So the net of what I’m taking is that you’re going to say, “We’re going to let the data do the talking.” And it won’t be on just surveys, it’ll actually be on diseases, like rheumatoid arthritis, where you actually have objective endpoints that you can see in x-ray to show that it kind of works out on that end.

Konstantinos Alataris:

For us, just because of the diseases that we’re trying to treat, there’s very well defined endpoints. So the data has to talk and develop the credibility around this therapeutic approach. I think that’s the best rather than pointing to preclinical work, which is relevant at the beginning. Now we’re in the clinic, as you said, we are doing randomized placebo control studies.

Ursheet Parikh:

Yeah, so Nanea, Konstantinos is actually going with a pure therapeutic label and so he’s going to go do the trials and then prove it and then kind of get the claims. You have dipped in the market available to consumers as we speak. How are you demonstrating the effects and the benefits of TRIPP?

Nanea Reeves:

Well, we don’t currently make any claims on efficacy, especially with the consumer product. We think there’s a lot that can be done to support people in the subclinical dimension with our wellness offering. But what we have found is that the body of data being produced by our service, we collect survey data in app with every session. And now because we have a significant audience producing over two and a half million sessions, that data actually has become very meaningful to researchers, et cetera. It’s enough data to train AI as well. So in addition, though, we have throughout the years, and it does move at a much slower pace than my startup motor, we’ve stood up some clinical trials. We have received funding from the national institutes of health, specifically, NIDA, for use in addiction recovery. We are now approved to move into phase two on that research.

We have some exciting RCTs up and running with the New York Office of Mental Health and other entities analyzing our product and the effect on their population. So eventually we could start to target more focused interventions for different in indications, but right now we see that the data itself that our services producing has really helped just harden our engagement in a way that a lot of the other clinically focused XR companies aren’t able to do at the scale that we have. We have excellent retention. And when you look at even the attrition rate in clinical trials and XR wellness, especially in mental health apps, we’re blowing doors off that data currently with our largest monthly cohort using TRIPP four months or longer. And so for any kind of intervention, if you don’t have adherence and especially in a digital therapeutic, I think it is going to be a commercial failure after years of development.

Ursheet Parikh:

Yeah. I think you touched upon two very key points. One is you want to have these products and that these products have to engage. But the second is that these are sort of connected products and you get a closed loop view and the data actually helps make the treatments better over time.

Nanea Reeves:

Correct.

Ursheet Parikh:

And so that kind of accelerates the pace at which new products can kind of be created. Paul, what would you like to tell the audience who say this is sounding like science fiction? How do you sort of convince them?

Paul Dagum:

Yeah, I think what I would say to the audience is, I think we all are aware of, there’s a tremendous amount of research in Alzheimer’s and we’re really tapping into amazing work being done by scientists and clinicians around the planet. One of the things that we’ve learned recently in the last few years is the interplay between neurophysiology, cerebral vasculature and neurovascular that you’re coupling and the importance of that house and the neuropathology of Alzheimer’s. So what we’re doing is we’re tapping into that mechanism and we’re instrumenting it and hoping to be able to measure target engagement of our therapeutic interventions. I think a lot, like what we heard from Konstantinos, our journey is a regulatory pathway so we have to be very scientific and evidence based. And the bar is the FDA at the end of the day for us. So that’s what I would share with the audience.

Ursheet Parikh:

Yeah. It’s great that while these things can kind of be made to work in a certain way that you guys are putting this level of sort of rigor in development, because for a whole new class of acclaim that is so groundbreaking, that level of rigor is going to be key to adoption. I think we’re going to be out of time soon. And so I want to move to a lightning round. All of you are immensely successful, I believe no success is accidental. And so, what would be the one learning that you have from your journey so far that you’d like to tell our audience, right? Nanea, do you want to go first?

Nanea Reeves:

Sure. I think really coming from a sense of purpose will help you really stay narrowly focused on surviving as a startup, especially in the face of opposition. It really keeps me going to know that I really do feel mission driven and I think anything is hard to do, especially from the ground up. So if you don’t have that connection, it’s going to make it infinitely much more difficult to succeed.

Ursheet Parikh:

Yeah, no, that’s that’s well said. Paul.

Paul Dagum:

Yeah. I would share that from my experience going from science to product takes a lot longer than you think. And so I would encourage young entrepreneurs to find patient investors.

Ursheet Parikh:

Thanks. Konstantinos.

Nanea Reeves:

Like Ursheet.

Konstantinos Alataris:

Well, for me, it’s always coming from a culture that talks about the journey, but the journey is about the people that you go with. I do believe that the people that come with you, the team, has even importance as far as making the right steps to discover what’s in front of you. So although I went alone, you shouldn’t go alone and the people that are with you determine your success. That’s my lesson.

Ursheet Parikh:

Well, that’s very well said. At Mayfield we’ve had this strong people-first philosophy and it goes back to our founder, Tommy Davis, who started Mayfield in 1969. He famously said, “People make products. Products don’t make people.” And so I think mission, purpose, patience, people, are all hard learned lessons, but as relevant as they’ve always been. I could go on for hours with you guys, right, I mean, there’s just so much that I think you guys have to offer and so much fun we could have talking about more stuff. But I think we are out of time and thank you, Nanea, Paul, Konstantinos for making this happen and thank you TechCrunch for hosting us.

Saving Lives with Precision Biology | Mayfield x TechCrunch Disrupt

Illumina is the world leader in next-generation sequencing. Adaptive Bio is the leader in immune-driven medicine. Mission Bio pioneered single cell multi-omics for genotype and phenotype. And Endpoint is developing precision therapies for inflammatory illness, sepsis, ARDS and more. Hear from these 4 leaders who are leveraging biology breakthroughs to save lives on a wide range of topics including translating innovation from bench to bedside, aligning incentives with the ecosystem, getting to reimbursement, exploring SPACs and beyond.

Transcript

Ursheet Parikh:

The session that we had with Ugur Sahin was about BioNTech’s journey and how they became the platform company that has saved millions of lives for us this year. As you can see, BioNTech represents a new way of innovation, where advances in engineering, biology, and information technology come together to help us transform healthcare. We are now seeing the emergence of a whole new class of companies. Several of them will be created by our panelists in the room today.

It is my honor to introduce our panelists. First off, we have Chad Robins. Chad is co-founder and CEO of Adaptive Bio. They are powering the age of immune medicine. Chad has led Adaptive from concept to category leadership and a $5 billion market cap to build this enduring company.

With him, we also have Mostafa Ronaghi. Mostafa is the co-founder of GRAIL. GRAIL is one of the leading companies for early cancer detection. It was recently acquired by Illumina for $8 billion, and Mostafa has also been the CTO of Illumina, which is a leader in genomic sequencing. He’s also the CEO of SPAC.

We also have two rising stars: First, Yan Zhang, the CEO of Mission Bio. Mission Bio unlocks single cell biology to help discover, develop, and deliver new treatments for cancer cell and gene therapies.

Finally, we also have Diego Rey. Diego is a serial entrepreneur. He was also the first bio investing partner for Y Combinator, and he’s now the co-founder of Endpoint Health. Endpoint is a precision therapeutics company that is focused on immune-driven illnesses, where one of their top indications is actually critical inflammatory disorders like sepsis. That is the number one killer of people in hospitals. A lot of COVID-19 deaths have been because of sepsis, and they are soon to be starting several phase three trials.

All of our panelists have been using the engineering marriage of biology and technology, and are going to be saving so many lives. It’s truly an honor and pleasure to have all of you with me here today. Let me start with Chad. Chad, can you share with us what Adaptive does, and how that is saving lives?

Chad Robins:

Sure. Thanks Ursheet for having me on the panel today. Adaptive is an immune medicine platform. What our real goal is, is to learn how the adaptive immune system naturally sees disease so that we can diagnose disease by reading or decoding how the immune system naturally would diagnose disease, and at the same time, we can harness the power of the immune system for drug discovery.

Your immune system does two things: it detects, and it treats. So essentially, what we’ve done at Adaptive is we’ve created a series of technologies to be able to decode, down to the DNA level, your immune receptors. We can not only decode them and sequence them, we can then match them to the diseases that they see and bind to, and ultimately go in and target and kill.

We’ve developed a series of products from research, that no matter what you’re doing in the immune system, now you have a much more powerful set of tools to be able to do the research, to clinical diagnostics, to be able to diagnose disease, to drug discovery, to harness the power of the new medicine to treat disease.

We’ve got a couple of marquee partnerships that are helping us along the way. One is with Microsoft to be able to essentially create this extremely large map of how our bodies see disease. This is your T-cell to antigen map or T-cell receptor to antigen map, and that’s for early detection of disease. We also partner with Genentech in drug discovery. We’re attacking cancer in an entirely new way in cell therapy by essentially creating a personalized therapy for each patient based on what your immune system sees in your individualized cancer.

Ursheet Parikh:

Chad, that’s pretty awesome, and it’s great to see Microsoft and Genentech as strategic partners talking about the marriage of tech and bio.

Mostafa, congratulations again on the acquisition of GRAIL. It was a long journey. Well, can you tell our audience, what are the fundamental innovations in liquid biopsy that GRAIL pioneered, and how that is going to transform healthcare?

Mostafa Ronaghi:

Thank you Ursheet for having me at this panel among other friends. It is a pleasure to be here. The way we looked at blood was basically a switch in the body, and whatever happens in the body, it would end up in the blood, and you would see the traces of DNA. In the late 2000s, we started seeing a few publications showing that fetal DNA can be detected in the blood, and that grabbed our attention to look for basically traces of tumors in the blood system.

So, we started the research activities that ended up being four companies, actually, from Illumina. The first one was Guardant. The second one was AccuraGen, and then AccuraGenDX, and the last one was GRAIL.

In GRAIL, we took a fundamentally different approach. We had to increase the sensitivity by at least another hundred-fold to have the ability to detect cancer in earlier stages. We believe that cancer is a curable disease, and the best cure for cancer is actually surgery, but you have to detect it early.

So we started actually a multi-pronged approach, a technical approach, to tackle the sensitivity issue. Of course, cheaper sequencing helped a lot in that regard, and we expanded the panel, and we started looking at RNA, DNA, and mutilation, and then we decided mutilation is going to give us the sensitivity and specificity related to the tissue. So, we basically created a good tool set of technologies and technical tricks around mutilation to offer the GRAIL test, and I’m happy to see that the test was launched a couple of months ago, and we’re already actually saving lives.

Ursheet Parikh:

That’s great. So, can we expect to just go see our doctors once a year and along with our cholesterol and diabetes screening, also start getting cancer screening?

Mostafa Ronaghi:

Yes, I do believe that, actually. This kind of liquid biopsy test is going to be the standard annual checkup kind of test. In the long run, I do believe that liquid biopsy is going to be used for other diseases, and this is going to be the first line of screening tests that you would do, replacing medical imaging in the next couple of decades. It’s not going to happen in this decade, probably, as we are going to need medical imaging to compliment this data, but eventually we are going to actually replace medical imaging as a first line of screening for all kinds of diseases.

Ursheet Parikh:

Yeah, that we truly believe, and we have a company at Mayfield called Mirvie that was actually doing liquid biopsy to predict and prevent pregnancy complications, so really buy that.

Moving over to you, Yan, there’s been a war on cancer for 50 years, right? How come we’ve not cured it? How is Mission Bio helping find cures for cancer and other genetic diseases?

Yan Zhang:

Thank you so much, Ursheet, first of all, for having me at the panel amongst some of these most prestigious and brilliant colleagues here. We have been at war against cancer for 50 years. We have not been standing still. So frankly, a huge amount of technical advancement, including for example, next generation sequencing pioneered by Illumina in the past decade has built a strong foundation for us to actually much, much better understand the genomics and the underlying mechanisms and diseases, as well as the therapeutic advancement, such as what Chad had already elucidated.

I think we’re at the junction, because all of the new technologies are coming together in addition to genomics, in addition to cell biology, in addition to all of the IT and big data. We are at the cross section where we actually now have the ability and have the knowledge to go one step further, so that’s where Mission Bio comes in.

Our technology is microfluidics, where we can enable a deeper understanding of biology and of diseases and therapeutics at a single cell level. We can’t be here without all of the other advancements that have already happened in the past 50 years. We’re really lucky to be at the intersection.

So how we think about cancer is we really need to get to the root of the disease. The root of the disease is genetics. It is the protein that it produces and the pathways. It is at a single cell level. We actually, frankly, have not won the war against cancer. A big part of that is because of drug resistance. There was a small body of the cells, which we actually today, the therapeutics don’t treat, but those are the ones that continue to evolve and respond, as well as there are many other factors that really come back stronger, possibly because of a co-occurrence of many mutations and really adaptive to the therapies.

To really understand at the single cell level and understand the fundamental genetics against them, we’ll be able to help society and the community to design better drugs, design better therapies, as well as be more effective in clinical trials. So we’re really glad to play a very big role, and we believe that will potentially move treating from just prolonging life for months or years to actually curing cancer.

So that’s a big ambition, but we’re not stopping there. Using the tapestry platform at the single cell multiomics, we actually also play a very big role to be the analytical platform for cell gene therapy. As Chad mentioned, cell gene therapy is really the new frontier of treatment of not just cancer, but many genetic diseases. These rare diseases cumulatively account for hundreds of millions of people who suffer, and many of them don’t have cures, and in the past we tried to cure symptoms, but with the new gene and cell therapy, we can actually cure the disease itself by making changes to our human genome.

But it is the frontier. The frontier is going to require the whole ecosystem to help support those new therapeutic ideas to be a reality to be successful. So by deploying single cell multiomics, we can help the industry to better understand the therapeutics, to characterize and quantify the therapeutics in terms of the safety, efficacy, to actually accelerate the development and quantification, and help deliver them back to the patients. So we are extremely excited to participate and to lend our hand to this entire ecosystem so we can, as a society, win the war.

Ursheet Parikh:

Yan, that’s well summarized. I think someone I respect just mentioned that they look at you as an ETF for the whole sector, because you are powering and enabling so many… An exchange-traded fund for the whole sector, because you’re empowering and enabling so many of these next gen therapies. Diego, I got to put you on the spot. I get to work with you. Mayfield’s been partnering with amazing entrepreneurs from inception, be it founders of Genentech, Amgen, Millennium Pharmaceuticals. But when I met you for the first time, I really paused, and just to be sure I’d heard right, because you said you wanted to reinvent pharma. Endpoint is well on its way to building a new class of pharma company, so tell us how.

Diego Rey:

Sure. Thanks, Ursheet. Great to be here. Yeah, didn’t mean to really pick on any particular company, but in the past, pharma companies were built on what I would call a molecule-first approach, and it’s because this is what really worked. Taking a molecule and then turning it into a drug is a huge feat, so it made sense to start with a drug, and then to see what illnesses can the drug actually go and help. One of the issues, though, is that this approach can lead to a one size fits all therapy that doesn’t always work for everybody.

Today, the world is very different. Now we have new enabling technologies and infrastructure that we’ve been discussing here, thanks to companies like Illumina, and these things really enable us to harness a huge amount of biological data that we couldn’t before. So, instead of starting with a molecule, we can now start with a, very much like Chad said, start with individual patients and data from these individual patients, even within the same illness, and then figure out how to help each of these patients based on their unique needs.

Endpoint is a therapeutics company with what we call a precision-first approach that is really only made possible today. So, instead of starting with a molecule, what we do is we start with patient biology to develop and later commercialize new medicines based on patient subtypes that we can go in and identify. At the end of the day, we believe that this will enable enormous improvement in patient outcomes.

As an example that you highlighted earlier, in critical care, where we’re starting, this is an area where there’s more deaths than there are in all cancers combined, and at the same time, it’s an area where there are very few, if any, effective therapies. So this is an area with this approach that we think will bring to market some of the first life-saving therapies for these patients.

So, to answer your question, I think what we realized is that a fully integrated therapeutics company with a precision-first approach is not only now possible, but it’s really, really badly needed, and so we’re building it, and that’s Endpoint Health.

Ursheet Parikh:

So in many ways, what you’re saying is you’re really focusing on truly understanding the disease and subtyping the disease, and then finding what would be the best treatments for it. Well, we really wish you a lot of success because we do want to see these treatments come to market. Earlier this year I spent about 10 days in an ICU for a close family member, and that was very sobering.

Chad, moving on to more fun stuff, how are you looking at the convergence of biology and technology, and how do you see that transforming healthcare, and what is the next frontier for it?

Chad Robins:

Yeah, sure. I thought, because this is traditionally a tech conference, I would give an analogy that I think is applicable to the audience, although I do have to say that probably one of the largest opportunities in tech is this convergence and this application of technology and machine learning to biology.

But if you think about it, and because we have Mostafa here, we’ll take a little bit, think about this as 1.0, 2.0, 3.0. If you think about the hardware, 1.0 being the IBM, if you will, over time got faster, cheaper, smaller, easier to use. The same thing happened with sequencing, right? You had these large sequencers that took up pretty big areas that got smaller, faster, cheaper, easier to use, and now if you think about that, that is really 1.0. 2.0 is, what are the applications of these machines in the parlance of tech. Microsoft came along and made it so that the everyday person could use these machines. So 2.0 to me is how do you use this instrumentation for diagnosis and/or drug discovery? I think my 3.0 is really now layering on machine learning on top of that, which is not just machinery. It’s the power of cloud computing and machine learning that now can take the information that’s generated from these machines and the applications on top of these machines to then make a patient decision.

Another thing that Mostafa said is the concept of early intervention leading to better patient outcomes. So now, and I will also say that what Diego and Jason are doing at Endpoint Health is really sifting through this information combined with biological information to determine how these drugs are going to work on patients on an individualized basis based on their biology.

Specific to Adaptive, and you asked what’s next in the new frontier, I’m going to highlight our work with Microsoft, explain how that works, which is essentially… Let me first give you some biological stats. The human genome is fixed, right? You’ve got about 30,000, other than some pointless mutations, you have 30,000 genes in the human body. Your immunome, or your adaptive immune system genes, each person has about a trillion of them in the body, about a hundred million unique. In the population, there’s about 10 to the 16th or 10 to the 18th, like trillions of choices.

Why I’m saying this is because our body’s job is to be able to recognize anything, any potential invader, anything foreign that it could potentially see, find it, and then go kill it. So what we’re doing with Microsoft essentially is building this massive map between your T-cell receptors or your immune receptors that recognize disease and antigens. Antigens are signals of a disease. So, what happens is every disease has editors that are specific for that disease, and it’s a little flare, think of it. It goes up on the outside of the cell, your T-cell recognizes it, it springs into action and kills it.

So the idea in, let’s use Microsoft Excel since we were on the tech analogy, we’re essentially building this massive VLOOKUP table, disease by disease, between your T-cells and your antigens. We’re able to feed that through chemistry, some proprietary assets or technologies that we have, where we can physically start creating these connections. But that only starts it going. What happens is then Microsoft on top of that, we have all this machine learning to impute and come up with more connections that essentially build out that map.

Now the idea, and you asked about, hey, when can you go into a doctor’s office and get a screen for cancer? The idea here is that we’ll start with one disease at a time. We did this for COVID, and T-Detect. There’s a franchise called T-Detect. We did T-Detect COVID, we’re now doing it for Lyme disease. We’re also in process for irritable bowel, basically a differential diagnosis between Crohn’s, IBS, celiac. So if you walk in with the same set of symptoms, we can rule in, as opposed to a rule out test, where you go from specialist to specialist, doctor to doctor over a two-year patient odyssey, now we can definitively diagnose based on your immune receptors, based on your body, what it’s seeing, referencing this map. We were never going to get every receptor, so again, that’s where this machine learning power comes in and says, we can be 99.99% confidence that if you have a receptor, that it binds to a certain antigen, and that’s specific for the disease, so you can reverse diagnose disease from the receptor itself.

So that’s what we’re doing, and eventually going from one disease to differentiated panels or differential diagnosis to essentially an immune checkup, where you go into your doctor’s office, and we’ve mapped hundreds, if not thousands of diseases, including our approach to cancer, which is instead of looking at the cancer itself, we’re looking at the immune response to the cancer that clonally expands, and it might be complementary to some of the liquid biopsy approaches that GRAIL and others are doing. So, that’s really the next frontier for us is diagnosing disease essentially from reaping your immune system.

Ursheet Parikh:

That’s amazing. We are going to get truly a fundamental understanding of the human state and the state when things go off track, so that’s great. Mostafa, what are the big entrepreneurial and investment opportunities you see?

Mostafa Ronaghi:

I’m actually very excited about the rise of cell therapy. That’s an area that has shown a lot of recent progress, and we see that there’s actually is working on a lot of different approaches that have been implemented, so I’m very hopeful that cell therapy is going to be the next generation therapeutics, at least against immunological disorders like cancer and other diseases and so on. Chronic diseases.

The technologies that enabling actually the cell to PR, the single cell technologies and the spatial biology approaches, and I think that’s a trend that’s going to continue. We really need to have the same cost trajectory as we had for sequencing to reduce the costs, to tackle this issue, to provide much more comprehensive information to understand the cells much better. The tool sets like synthetic biology tools are very exciting now actually being implemented in cell therapy, and it’s giving you actually the specificity and the sensitivity for the therapy.

Ursheet Parikh:

Yeah. Yeah, I think that the ability to truly engineer the cells and the genome and how that creates therapeutic effect along with an ecosystem that allows for mass production on these things. I think these are so fundamental, so seminal, and clearly a big area of investment for us at Mayfield.

Diego, I wanted to get to you next. You’ve been an entrepreneur and an investor at YC. How do you see company building in engineering biology different from just a tech or a software company?

Diego Rey:

Sure, yeah. Actually, maybe to start with a similarity, based on something that Chad mentioned, he put it I think really well that I think that because of all these advancements in technology and infrastructure that we’re seeing, we’ve been discussing here on the panel, I think the barrier to entry to building companies in engineering biology has really lowered. So now, we can really build applications, just like Chad said, in an analogous way maybe that the tech industry went from, for example, building chip foundries to building apps.

So I think this has really opened the door to a lot of first-time founders, and this is now increasing diversity in our field, which is really a great thing. At the same time, I think unlike tech, engineering biology still takes a lot more time. Sometimes it could cost more, and it also takes more diligence from an investor as well, so those would be some key differences.

Another observation though is actually one from a former colleague of mine, Jared Friedman, a partner at YC, and what he pointed out was that life sciences founders, from his point of view, of all the companies YC is seeing, they now have over 400 life sciences companies. He’s noticed that life sciences founders are more hesitant to start a company, even though in many cases what they’ve developed is more mature than what most tech founders have when they’re starting their company. So, I’d say that we really need more life sciences founders to go and start their companies.

Ursheet Parikh:

Yeah. I mean, I recognize that while there’s a lot of similarities, one thing is that the business of moving atoms has always been harder than the business of electrons, right? Software has been amazing because you can sit on your laptop and just move electrons and magic happens, and so it becomes easier to iterate, pivot, all of those things like that, and it does require a different mindset and view.

But you’re right that what has been amazing is that 20 years or 10 years ago, starting one of the life sciences companies required $10 to $20 million, and now we have a very, very large number of amazing companies that we started out with the first couple of $200,000 to $300,000 with a whole ecosystem here in the Bay Area. So, that’s great.

Yan, we are clearly very impressed with you and your leadership at Mission Bio. Given all the opportunities you had, what made you pick Mission Bio as the company to lead?

Yan Zhang:

Yeah, great question. I’m still learning to be an entrepreneur, I feel like. I spent about 20 years with the larger companies, but it’s such an exciting space to be. But I think how we can be successful, is the intersection we talked about the building applications. That’s Mission Bio’s philosophy. We’re not launching just a platform, we’re really launching the applications. But in order to be successful in identifying those applications, killer apps, and actually be useful, and translate that to market acceptance, we have to collaborate and partner very closely with our customers. In this case, academic cancer center KOLs, or the pharma companies, other entrepreneurs, to make sure our tools and our applications can meet their needs.

So that’s what’s really attractive to me is that to be able to come with a commercial mindset and really collaborate with a lot of creative minds who are driven by technology, but bring those creative minds together, while really solving a practical problem with the partnership. I think that’s an amazing thing. In our small company, we have statisticians, bioinformaticians, engineers, and biologists, right? All of us, and then we come together to solve one single problem. I think that’s amazing. That’s what I think we can do together to achieve the unthinkable from the past.

Ursheet Parikh:

Got it. So it’s like you pretty much found Mission Bio to have this platform that then allowed you to build applications around different disease areas.

Yan Zhang:

That’s right.

Ursheet Parikh:

And really make it easier for various drug developers to develop that.

Yan Zhang:

Yeah.

Ursheet Parikh:

That’s great. Chad, you did a bio platform company in a decade when most bio platform companies failed, right? Is there one or two things that you can talk of as how you succeeded while most of your peers didn’t make it?

Chad Robins:

Well, truth be told, we had a vision that the immune system absolutely was a platform. Platform was a dirty word when we got started, but my brother and I had no experience in biotech, so we really had no other opportunities for funding. So we said, hey, we’re going to go with our vision, and before we raised a hundred million dollars five years later, we bootstrapped it with friends and family money.

Essentially, we’re trying to land a rocket booster on a platform in the middle of the ocean on a pretty frequent basis, and in order to do that, we have got to get people to believe that the impossible is possible. We’re trying to cure cancer. One of the things that we’re doing with Genentech is essentially, Mostafa talked a lot about cell therapy, but that is what we’re trying to do. Vein to vein, we’re trying to essentially see how your immune system sees your individualized cancer, take that out, reprogram it, put it back in, 30 days, and have an individual therapy.

So to do that, people have to believe, and that means you have to create an environment, you’ve got to create a set of values and culture that really allows it. People make companies, right?

Ursheet Parikh:

Yep.

Chad Robins:

We’ve got great technology and IT, but it’s the people who make companies. I call myself a CCO or the chief cultural officer, and probably the most important job that I do is to hire and retain the best talent and create a culture that makes people believe that we can do the impossible.

Ursheet Parikh:

That is so well said and it’s something we believe in so deeply. I think we’re almost out of time, and so I was going to leave with the last question for Mostafa, on what would you pick as one silver lining coming onto the other side of COVID?

Mostafa Ronaghi:

I think the opportunity in biology has expanded vastly, and I’m happy to see a lot of entrepreneurs from other spaces actually coming into the biology space, like Chad. It’s amazing to have those mindsets. The funding environment is actually very healthy, and this is going to continue for the next few years. Love to see foundational technologies and also foundational therapies, therapy platforms that will emerge in the next decade.

Ursheet Parikh:

That is awesome. Thank you so much, Chad, Mostafa, Yan, Diego. Delight to have this conversation with you. 

Taking Care of the Next Generation | Mayfield x TechCrunch Disrupt

KiwiCo empowers kids to explore, create and learn with hands-on kits. Mirvie provides a personalized window into pregnancy for early detection and intervention. Grove is committed to a plastic-free future with its line of eco-friendly beauty, home and lifestyle products. Hear from these 3 exceptional entrepreneurs about their mission to create a better world for our generation and the next ones, building movements and communities, and the milestones in getting to escape velocity.

 

Transcript

Kamini Ramani:

Welcome, everyone. I’m Kamini Ramani, CMO of Mayfield, and I’m thrilled to chat with three amazing entrepreneurs who are taking care of the next generation by making our world safer and healthier for families and kids. To start at the very beginning of life, we have Maneesh Jain, a serial entrepreneur of many breakout healthcare companies, including as founding CEO of Cirina, which was acquired by GRAIL, which is now part of Illumina. Maneesh leads Mirvie, which is redefining pregnancy health with an early detection RNA test. Welcome, Maneesh.

Maneesh Jain:

Thanks, Kamini. Pleasure to be here.

Kamini Ramani:

Next, we have Sandra Oh Lin, an engineer and the former head of eBay’s fashion business, who leads KiwiCo, which has delivered over 25 million creativity kits to everyone starting from newborns to the kids at heart. Welcome, Sandra.

Sandra Oh Lin:

Thank you, Kamini. It’s great to be here.

Kamini Ramani:

And finally, we have Stu Landesberg, a former TPG private equity executive turned founder of Grove Collaborative, a digital-first eco-friendly CPG brand and marketplace. Welcome, Stu.

Stu Landesberg:

Glad to be here.

Kamini Ramani:

So to start with, can each of you take us back to your founding moment, which propelled you to start your company? We’ll start with Sandra, whose company KiwiCo is about a decade old, followed by Stu, and then finally with Maneesh. Sandra.

Sandra Oh Lin:

Absolutely. So KiwiCo was born partially out of personal need. My two youngest children were getting to that age where I wanted them to get hands-on. I thought it was a great outlet for them to exercise their creativity, see themselves as makers and creators. And so, I started to pull these projects together. And as an engineer by training and as kind of a maker and creator growing up, this was something that was really important to me so that hopefully they would see themselves as producers and not just as passive consumers. And as I started to pull these together, lo and behold, I was not the only busy well-intentioned parent that wanted these types of enriching activities for their kids. And so that’s how KiwiCo was born. And we still continue to pursue that vision and mission, not just for my kids now, but for millions of kids around the world.

Kamini Ramani:

Thank you. Stu.

Stu Landesberg:

So love that story. Grove was also born from a personal passion for the category. Grove seeks to redefine the home and personal care categories – hand soap, dish soap, laundry detergent, paper towels, shampoo – categories that have for a long time been a harmful force in human and environmental health in many ways. The founding moment for Grove really came after a lifetime of being focused on sustainability. In my prior life I came head-on with the reality that although the majority of consumers prefer conscientious products, in broad distribution in most retail outlets, the vast majority of shelf space and the vast majority of purchase still goes to conventional brands. And so I started Grove really to change the category and change the products that people are buying to ones that we can all feel really good about in terms of the impact that the products have not only on us as people, but also on the planet around us.

Kamini Ramani:

Sounds great. Maneesh.

Maneesh Jain:

Thanks. That’s much needed for sure. Our story goes to the beginning of life. And so, the problem we’re trying to address is really the unexpected complications that develop in pregnancy. I think the statistics here are just staggering. One in five women experiences complications like a preterm birth or preeclampsia, gestational diabetes in the course of pregnancy. And it’s about five times the rate of cancer incidents.

So for my co-founder Steve Quake and I, it was not just a statistic. It was also personal. We experienced unexpected complications through our own journeys to becoming parents, respectively. And our founding moment came really in the summer of 2018. So Steve had spent about 10 years at Stanford with an international collaboration using RNA technology to predict complications like preterm birth months in advance. And I had just come off developing the first early detection test for cancer at Cirina and GRAIL. And so we knew this was possible and we really felt compelled by having a potential solution to address this big need, which can help families right at the beginning.

Kamini Ramani:

You know, all really important stuff. Thank you. Thank you for your vision and your dedication. And we are proud to be partners with you on this journey. Maneesh, the life-saving stuff you’ve built has got to be just so needed in the world and so easy to deliver, but it’s incredibly hard to get it to market. Why? And what are you doing about making it easier?

Maneesh Jain:

Yeah, great questions. I think, particularly as we look at women’s health and pregnancy health, we know that it really hasn’t had a lot of innovation for decades. And I think there are a few reasons. One is that historically it’s been an area that’s underinvested, and certainly, Mayfield and other firms are helping to change that. So we definitely appreciate that. The second piece is that technology was really not available to tackle the complexity of biology for some of these conditions. And that’s changing as well with our RNA technology. And finally, frankly, a lot of the talent has chased cancer diagnostics and cancer therapeutics.

And so it’s time to move some of that to women’s health, and we are hoping to make that difference as well at Mirvie. I think finally, I’ll just add that I think aside from those more systemic factors, just the process to get these products to market, to get innovation to market, is rate limited by clinical trials. And as we all know, it can take very long. It can be very expensive. And that really is a barrier sometimes to innovation getting to market, particularly in this age of the pandemic where that has been exacerbated. So one of the areas that we really had to innovate around was to do more Direct-to-Patient trials. So we could really accelerate that path to market, and we are being fairly successful there. So potentially, that’s a new paradigm to accelerate innovation to market.

Kamini Ramani:

Thank you, Maneesh. And I’m glad to see that you’ve been able to thrive even during the pandemic in terms of achieving your goals. And I know that interestingly enough the pandemic, Sandra, has been a force that’s actually lifted your business in the era of Zoom school and kids like Stu’s daughter interrupting his Zoom calls routinely and parents being more involved in their kids’ lives. How have the needs of modern families changed, and how has that actually accelerated KiwiCo’s adoption?

Sandra Oh Lin:

Yes, we’ve all been there, Stu. So I can definitely empathize with those moments. Yeah. I mean, I would point to a couple of things that we’ve seen in terms of the dynamic shifting and families really evolving. So one is for sure I think parents have become much closer to their children and not just in terms of perhaps being physically stuck with one another at some point at the beginning of the pandemic, but really beyond that. So if you think about having a real front-row seat into your child’s education, that is something that definitely happened across the US and around the world. And so you see the combination of virtual schooling or schooling from home, learning from home, as well as schooling in school. Those two are coming together, and there’s a real partnership between those activities. So the learning that’s happening at home, as well as the learning that’s happening at school.

And I think that what we’re seeing is, as kids head back to in-person school, we are continuing to see that partnership remain relatively strong as parents lean into their kids’ educations. The other thing that I would point to is I think generationally, you end up reflecting and saying, “Are we teeing up this world in a way that’s better for the next generation?” And I think given where we are right now and in the situations that we’re in, I think parents are really asking themselves this question. Is the world better for this next generation, with the divisions that we see, with a raging pandemic, with climate change, et cetera? And so, what we are trying to do as parents then is think of ways in which we can actually equip our kids to become those creative problem solvers. To become those active citizens, to become those people, hopefully in the future, who can envision this better world and actually make that happen. So that’s another thing that we’re seeing these days too.

Kamini Ramani:

That’s amazing. And you know what? You don’t need to talk to Stu about climate change. He lives it. I’m so sorry about Hurricane Ida and the Tahoe wildfires. It’s a scary place to be in the world. And so, Stu, what I wanted to ask you was, you’re upending an industry in CPG, which has classically been known as a bad player when it comes to plastics and other things. So how are they reacting to this climate change acceleration and environmental disaster zone that we’re going into?

Stu Landesberg:

It’s really interesting. I feel like we…many of us grew up in a time where the brewing environmental crises were optional to pay attention to, right. It feels only like in the last few years that it has become so in our faces that climate change is going to change all of our lives. And I think when we look out at our industry, consumer products have been a huge contributor to many of the environmental crises that exist today. To take probably the single largest issue there just as an example. We, as a society, create one trillion pounds of plastic, with a T, every year, one trillion pounds, of which almost half is single used plastic packaging that’s used for less than six months. And the industry that contributes sort of in the biggest weight of that, I bet you can guess, is the consumer products industry.

So this is an industry that absolutely needs to change. But it’s also an industry that’s invested, truly, hundreds of billions of dollars in building brands and physical infrastructure around legacy products that have negative footprints. I mean, if you imagine, for example, your laundry room as a kid. Think of what color the laundry bottle is there. It’s the same color you imagine in the laundry aisle, right. That is an iconic piece of plastic that generates billions of dollars of free cash flow every year and has billions of dollars of infrastructure behind it.

The challenge for these companies, and I think one of the reasons that our industry is so slow to act, is the entrenched sort of infrastructure dollars are so material that it requires a company like Grove who has no attachment to the legacy system to come in and say, “We’re going to create an entirely different supply chain. We’re going to use plant-based ingredients. We’re going to use infinitely recyclable packaging and try to move entirely away from plastic.” And we can do that because we don’t have the attachment to the sort of legacy base of embedded assets. And I think when you look out at the industry as a whole, you see this incredible contradiction where people genuinely, I think, recognize the crises to which their industries have contributed and genuinely want to create change.

I think Sandra said it well about leaving the world better for our children. People who work in the industry aren’t evil. We all get it. But I think it’s really hard for large organizations to move at the speed that the problems require. And so that, I think, is the opportunity for Grove and where we try to be able to differentiate is really by moving more quickly and more aggressively on urgent problems that defy the existing paradigm.

Kamini Ramani:

Hey, we’re at TechCrunch Disrupt. It’s all about disrupting, right. So all for that. Now it’s great to have a vision. You’re amazing entrepreneurs. Zeitgeist is lifting your businesses, but you need money. And the three of you have followed very different strategies. It’s almost like the Goldilocks story where Sandra only has raised 10 million in the lifetime of KiwiCo. Stu, you raised upwards of 450 million, and Maneesh has raised 30 million so far for Mirvie, but he’s obviously a very experienced fundraiser from his prior companies. How did you get investors to believe in the promise of your company? And how did you build a zone of trust with them? I would say, at this point, any one of you who wants to jump in to answer can. There’s no particular order. But maybe we start with Maneesh.

Maneesh Jain:

Sure. I think just to build on what Sandra and Stu said, the time for disruption is right. And I think one thing the pandemic has done is it has given us all time to really think through that and not just go on with life as it is. So I think it really comes down first and foremost to a shared vision in terms of attracting the right investors. And I think the phrase, “It’s a marathon, not a sprint,” is definitely front and center. If you want to make life better for the next generation, it’s not going to happen in one year, right. We need to think a little bit longer term. And if it’s a worthy goal, it’s going to take time. So I think alignment around that is a pretty fundamental thing that is important at the beginning.

For us, the other thing was coming from the cancer world, which is, there’s lots of capital and lots of companies. Coming to women’s health and pregnancy health, it’s really been underinvested. So part of the journey is really explaining to investors that underinvested historically also means that there’s a very large untapped opportunity here. So in our case, there’s about 50 billion spent every year for unexpected complications in the medical system, and that could be reduced drastically.

So I think just making that connection between historically underinvested equals high untapped potential is a connection we try to make. I think the last thing I’ll add is just in terms of keeping up with the trust because I think that trust is pretty important between investors and entrepreneurs. It’s really, do what you say, right. We all have big visions and things we want to accomplish. But what is the first, second, third step? And it’s really delivering on those smaller goals along the way, I think, that just helps foster trust and attracts more investors. We’re excited for what’s ahead.

Kamini Ramani:

Thank you, Maneesh. Sandra and then Stu, quickly on journey to investors and continuing to stay in the zone of trust. And then leave me a minute for my lightning round. 

Sandra Oh Lin:

Yeah, absolutely. I mean, I agree with a lot that Maneesh actually said. And I think that foundation of trust is absolutely imperative. If I think about our investors and our board members, I think it’s a matter of, as he mentioned, kind of alignment or around ambition and vision. But it’s also gaining their trust upfront around decision-making and doing what’s right for all stakeholders. And so, in my opinion, I think that means being very upfront, being very forthcoming with opportunities, as well as with challenges so that they believe that you’re going to be very considerate in terms of your decision-making and your planning. And they trust you to do your job basically is what it comes down to. And we’ve been really in a very fortunate position where we’ve been profitable and cash flow positive now for over five years and running. And so, it definitely has been a marathon and not a sprint. So, absolutely agree with that sentiment.

Kamini Ramani:

Stu.

Stu Landesberg:

Yeah, I would just… I mean, the thing I would add is I think financing is, you often, or at least I often see the headlines and it all feels inevitable. We’ve had a number of financings, as you mentioned. Our series A took us four years to raise, and I pitched 175 investors, 100% of whom said no. And eventually, I was able to get somebody to scrap and claw a little bit in. And 175 no’s and half a yes, still is a successful financing. And so, ultimately, I think of fundraising a little bit as, it’s a necessary thing to get the resources to go create the vision. And also something that’s just a process just like anything else in the business and just like any other sort of business process and partnership to about preparation, perseverance and ultimately the people on the other side, right. Are you bringing in someone who’s going to be a productive force for the company over the long term, because it’s certainly been my experience that we are better because I have great investors as partners.

Kamini Ramani:

Absolutely. And thank you for sharing that vulnerability. It wasn’t easy in the early days. And I think the entrepreneurs in this audience need to hear that because we at Mayfield say we partner with founders from inception to iconic, and Stu, you’re definitely getting to iconic status, whether you like it or not, but the inception stage was tough. So we have two minutes to go, lightning round. It’s the year 2030. You’re still leading your companies. In a word or a phrase, how would you measure your impact? Sandra.

Sandra Oh Lin:

Generation of innovators and change-makers.

Maneesh Jain:

If I had to pick a phrase, I’d say pregnancy health uncomplicated.

Stu Landesberg:

No plastic.

Kamini Ramani:

Love it. And since we have a little bit of time, if any of you want to share taking care of the next generation, what’s one cool thing that your kids are doing during the pandemic? Anybody.

Stu Landesberg:

Well, my kids like to join my Zoom calls, as you already sort of shared with the audience. Princess fairy Francis Margaret Landesberg appreciates the shout-out. No, but I think, at least for me, I think my children have taken a materially bigger interest in all of the things around the house because we’re around somewhere often… so much more often. And so, I think that it’s amazing to have them be a more active participant in all of the elements of life, including my Zoom calls.

Kamini Ramani:

And Sandra’s kids are doing KiwiCo kits. We know that.

Sandra Oh Lin:

They’re doing KiwiCo kits. I mean, they did… It was fun. They put together Zoom kind of recipe trading and cooking with their friends and that type of thing. I mean, one thing that I would say was really great about that time, and this is kind of seeing the silver lining in it is that I felt like I was able to see them in a different light. I got to see them with different angles that I wouldn’t necessarily have had visibility into. And I think they saw the same for me as not only a mom but as an entrepreneur and as a leader because they would pop in like Stu during Zoom calls and that type of thing. And I think that was something that was actually quite special that they were able to see me as a multidimensional person. And I am able to see them as multidimensional people too.

Kamini Ramani:

That’s great. Maneesh, Anything to add?

Maneesh Jain:

Well, I’ll just say, closer connection to teenagers is a good thing, maybe too close from their perspective.

Kamini Ramani:

Thank you. Thank you so much. Taking care of the next generation, and we are honored to have you here. And hopefully, our audience has enjoyed this chat. So onward and upward.

The New Human and Planetary Health Pioneers | Mayfield x TechCrunch Disrupt

Mammoth Biosciences, co-founded by Nobel Laureate Jennifer Doudna, is the industry’s first CRISPR platform company. It has already delivered a breakthrough Covid test and has inked partnerships for novel CRISPR diagnostics, therapeutics and biomanufacturing with leading healthcare companies. NotCo is combining artificial intelligence and deep science to re-invent the food industry, starting with a milk alternative product with many more to come. Hear about the founder journey from these breakout companies and tips for scaling your business.

Transcript

Arvind Gupta:

Today, it’s my true pleasure to introduce two of the fastest rising stars in human and planetary health, Matias Muchnick, CEO of NotCo, and Trevor Martin, CEO of Mammoth Biosciences. Mammoth Biosciences, co-founded by Nobel Laureate Jennifer Doudna, is the industry’s first CRISPR platform company. It has already delivered a breakthrough COVID test and is in partnerships for novel CRISPR products with leading healthcare companies. NotCo is combining artificial intelligence and deep science to reinvent the food industry starting with a milk alternative product with many more to come. Both have recently achieved unicorn status by reinventing their respective industries.

I also have the pleasure of personally knowing both gentlemen for years – Matias through IndieBio and Trevor through Mayfield. I’m excited to hear their thoughts in scaling the next generation bioplatforms for human and planetary health and sharing that with you. So, let’s go ahead and get started with Matias. How is NotCo reinventing our food system?

Matias Muchnick:

Well, Arvind, I think from the get-go, we had this vision of taking the animal out of the equation with food. And consuming food really as it is, right? It’s not only something that keeps us alive, but really something that we enjoy the most. And we’ve sacrificed already too much in this world to actually sacrifice the taste of food. Now, the way we’re creating the food that we love to eat is inefficient, unsustainable, the overuse of resources; water, land, energy, CO2 emissions, you name it. The animal industry has become the major environmental detriments known to humankind. Deforestation, water scarcity, ocean depletion, loss of species, and I can go on. So one of the biggest problematic things that we saw is that we don’t understand food. And the food system has been operating under an obsolete technology for the last 80 years.

So using AI, using science, using technology, how can we create the products that we love, but coming from sustainable sources, such as plant-based ingredients? Now, plant-based ingredients were absolutely unknown. So, there are more than 300,000 species of plants in the world that we have no idea what they can do. And we’re human, so we’re biased, right? We have no idea if the combination of pineapple and cabbage can create the taste of milk. And it does, right? So that’s how we’re utilizing AI to debunk, to hack the system of plants, to really bring all of those tastes and textures that we like in food, and that nutrition, but in very, very sustainable ways. That’s how we’re doing that. In Latin America, we started, and then deploying in the US and Asia and probably more and more regions in the world.

Arvind Gupta:

Amazing. Thanks for that. And Trevor, how is Mammoth reinventing our healthcare system today?

Trevor Martin:

Yeah, at Mammoth, what we’re really excited about is, in short, delivering on the promise of CRISPR. And in particular, what we’ve done at Mammoth is that we’ve built up the world’s largest toolbox of novel CRISPR systems. And if you’ve heard about CRISPR, then you might’ve heard about Cas9 or Cas12a. And these kinds of legacy systems are really doing amazing things. And there’s really exciting work that’s being done. And I think there’s really great therapies that will be created with them, but there are limitations to what they can do. And at Mammoth we’re really all about pushing CRISPR beyond its boundaries and really enabling new types of products with these new proteins. And that’s the foundation of Mammoth, is that kind of CRISPR toolbox of proteins like Cas14 and CasPhi, and others. And then on top of that, we build products and diagnostics and therapeutics. Both internally at Mammoth and with partners. And in diagnostics, what we’re really focused on is really democratizing access to high quality molecular information.

And I think unfortunately, during the pandemic, we’ve seen that it’s actually pretty difficult to get high quality molecular information anytime and anywhere. And you almost face this choice of, do you want a result that’s extremely accurate and molecular, like say a PCR? Or do you want a result that’s very accessible and maybe easier to use like a lateral flow or an antigen or antibody test? But you can’t have your cake and eat it too. And I think what we’re excited about at Mammoth is that you really can design something that has that high molecular accuracy with that more accessible profile, being more similar to a pregnancy test. And I think we’ve seen our diagnostics work accelerated during the pandemic. We’ve gotten lots of great partnerships with organizations like GSK and the NIH who we’re really honored to work with to advance these technologies.

So, that’s one of the things that excites us on the diagnostic side. And on the therapeutic side, what we think is really enabled there, is in particular, permanent genetic cures and in vivo editing. So, in vivo editing means rather than taking cells out of the body and then changing them, and then putting them back in, which is how many of the therapies are done today, what if you actually could edit the cells in the body without having to remove them? And that really opens up a lot of doors about different diseases that could be treated and tackled. And there, we’ve really innovated around what we call these ultra small CRISPR systems. So you can think of it as a little, tiny, compact car versus a huge freight truck in terms of what you’re trying to deliver on a ship or something.

And along with many other kind of interesting innovations from these proteins. And on the diagnostic side, it’s just a totally new way of thinking about CRISPR, where you’re actually using on this property called collateral cleavage to actually amplify and read out a signal. These are both just things people didn’t think were possible or things that CRISPR could do, could be that compact, could do that kind of collateral cleavage. And I think that’s only the beginning of what’s possible is what’s really exciting. And Mammoth is going to continue to innovate in diagnostics and therapeutics, and really is at the forefront of building out this toolbox of what’s possible with the next generation of CRISPR.

Arvind Gupta:

Yeah. Thanks. And it’s amazing what both of you guys have created at this point, right? Both of you have companies that have massive technological platforms that are driving innovation very deeply in your respective industries. But it wasn’t always that way, right? I mean, I’m an inception stage investor and it’s remarkable how different the beginnings are from where things end up going. So, for the audience, I think it’s always nice to hear about these beginnings. So, Matias, we can start with you. Tell me, was there a founding moment? What was it like in the very beginnings of NotCo? Did you think this would happen? I mean, how did you think this would happen?

Matias Muchnick:

I probably would be lying if I said yes. I didn’t think this was going to happen. Now, the vision was less. Now, probably someone told me what getting here was going to take, I would’ve not done it, right? Because it takes so much time, it takes so much effort, so many sacrifices and the chances of failing in the middle are so, so high. And so, how was NotCo? Literally, and I’m not going to see at the beginning, it’s only two years ago. We were valued at $1.5 billion, but let’s not forget what it was two years ago. I was calling the guy who was delivering cases in the supermarket, if the cases were right or wrong. And so, that only happened two years ago. So, the unicorn status, or wherever we are right now, Trevor and I, doesn’t imply that we’re not operating this company, we’re analyzing the strategy where we need to go, right?

But at the beginning it’s a vision. It’s a team aiming to execute what the vision is. And building, in the building blocks of what do you really need to do in order to become a billion dollar company? And sometimes you fail miserably on those building blocks, because they weren’t the building blocks that you needed to do and construct in order to get where we are, right? So, at the beginning, it’s very purpose driven. It’s very visionary, but if I need to give any advice, it is that vision and that romantic speech has to be mandatory, converted into execution by an A-team. And the team makes, and people make companies. Not anything else. You can have the best product in the world, if you don’t have a great execution, then the company is not going to fly at all. So, I think those three things, what NotCo has done to become the company that produces products faster, better, more accurate, and less costly than anyone in this space. Nothing more than that.

Arvind Gupta:

Wow. That’s, that’s amazing. And I was very privileged to see some of those beginnings. And Trevor, tell me about how Mammoth came together and how, how it happened for you.

Trevor Martin:

Yeah. Mammoth is a rare Stanford-Berkeley team-up.

Arvind Gupta:

Yeah, Rare.

Trevor Martin:

Being graduate students, maybe, by a little bit, lessened the rivalry. But yeah, no, I think to one of the points Matias mentioned, it really all comes down to sharing that same vision of what’s possible. Whether you think you can achieve it, or how crazy it is, maybe the crazier the better, but I think that’s really what draws you together, and then what binds you for the journey. Because yeah, there’s going to be ups, of course, but then there’s going to be big downs. And, I also agree with Matias as well that, markers on valuation, like unicorn stuff are exciting and should be celebrated, but they’re really just markers of other more important value that’s being created. And it’s also just the beginning, right? I think when you have these kind of, really crazy visions about the impact you can have, that’s still early days, frankly, for what these companies can accomplish.

And I think that what’s really cool is that you don’t want to lose sight of what you’ve accomplished, but also that’s just building a stronger and stronger foundation for really tackling these really audacious goals that maybe you didn’t even think you could get to at the beginning of it. And for us, what really bound us together was this idea of delivering on the promise of CRISPR and really saying, “Can we leverage something that’s really fundamental science? And as quickly as possible, bring that through to actually diagnostics and therapeutics that can benefit patients?” And that’s a very audacious goal in itself and a huge journey. And I think you have to be a little bit crazy to think you can do that, especially with brand new technologies that are coming right out of the lab. But I think that’s what’s exciting about startups and what makes Silicon Valley, Silicon Valley.

And now I think that mentality is becoming more global, which is awesome, is that idea of just why not you and why not now, right? And yeah, it’s going to be really hard and there are going to be many, many failures, right? It doesn’t guarantee success, but really having that opportunity, I think is one of the most exciting things.

Arvind Gupta:

Right. Yeah, well I’m glad that the people can hear that you guys even, both of you building these large companies that are just getting larger and tackling bigger problems, started somewhere. It’s hard to remember that sometimes. 

And so, I always say that that platforms aren’t products, and people buy products, right? But founders go and talk to investors about, “We have a platform. It can do all of these things.” It’s always interesting, this tension between this whole platform idea versus, “Hey, we’re going to have this product and a singular focus.” We’ll start again with you Matias, how did you create focus for NotCo and choosing NotMilk, or some of the products that you have? What I first tasted, the NotMayo? How’d you choose those products versus the literally infinite other products you could have made?

Matias Muchnick:

Yeah. It’s always a matrix of decisions. There are different dimensions of complexities in the decision-making of what’s the next product to actually launch. Now the important thing is to really say no to 75% of what you’re thinking you’re going to launch. And really achieving the 25%, because that’s literally the 80/20 rule of startups, right? We had the idea, and you tasted it. There are probably products in the market that we’ve prototyped in the past that never reached the market. And they didn’t reach the market because we said, “Okay guys, what’s the mission of NotCo really in this world, right?” It’s to move the needle of sustainability. It’s to move the needle of the CO2 emissions. How are we going to do that? Is this going to be throughout a cheese? A yogurt? A Nutella? It’s going to be with milk, Right?

Where’s the biggest opportunity, as well, in the market, right? Who are the first movers? So there’s many dimensions, but what is the complexity of scaling this product, right? Who are the players? Why are we better? What’s the value proposition? Is it clear or no? What’s the market feed of products? So there’s many, many layers of complexity as you might sound, but there’s an underlying gut feeling that drives a lot of what the entrepreneurship spirit is. If you’re analyzing absolutely all the data, let me tell you, you’re not the first one to do that. You know? People have been drawn by the data and understood that data before you did. But, that’s what entrepreneurship really is, that gut feeling of there’s something there that no one else, even the data, is not telling you, right? So you need that spirit as well. So it’s a very good combination between rationality and the gut feeling, or the intuition of an entrepreneur.

Arvind Gupta:

That’s amazing, that you don’t hear that very often, this idea of, “oh, there’s all this data out there,” but really, if you don’t trust your gut, that data can lead you astray. And Trevor, with Mammoth, it’s an incredible platform of technology. How are you navigating the future and choosing what to do, and what not to do?

Trevor Martin:

Yeah, I think saying no is the hardest thing. And that’s also the most important thing when you have a platform, because, there’s the common adage that startups are more likely to die of indigestion than starvation. And I think, there’s definitely some qualifiers on that, around, I think it is good at the right stage of the company to really open up and explore. But I think you need to know when is the time to then constrain the exploration and really focus down on a product, because the product does make the platform, at the end of the day. And I think that intuition going to that gut idea. I don’t know if data will ever necessarily get you there. You definitely want to have as much data as possible. And you don’t want to just blindly make these decisions, but, yeah, you can definitely fall into analysis paralysis.

And at the end of the day, is that intuition around when is the time to go from exploration to focus? And maybe back to exploration in other areas, and just a constant cycle of trying to determine that. And I think that’s one of the most important skills that any platform company, really, is being able to strike that balance.

Arvind Gupta:

Yeah. Got it. And so, both of you guys have recently achieved unicorn status, which is something that all founders are looking forward to. And, as a milestone, as a marker, right? It’s not the end, it’s not the goal, but it’s a marker in the journey of entrepreneurship, and in the maturation of a company. So I’ll ask the same question to both of you guys, right? What keeps you going when you hit this milestone? And is there a vision that you’re trying to get to, or is that vision always changing and moving? Kind of like the horizon, right? As you chase, it just keeps staying in the distance. How do you manage this? And what keeps you going through all this? Matias, you go first.

Matias Muchnick:

Yeah. I mean, it’s a great question to which, unfortunately, I don’t have a great answer to. I think there’s a combination of things that keeps me going. I founded this company to move the needle. If we’re not in a report of sustainability saying, “Hey guys, you know what, in the world, the CO2 emissions have been reduced because you have NotCo,” we’re not ready. We haven’t complied with the mission. So what keeps us going is the purpose of why we created this company. It’s the mission why we created this company. More importantly than professional or economic development of myself or the management team or the founders, that’s not the case. It’s very mission-driven. It’s very purposed. And, every time we’re going and climbing this mountain, we see another mountain and another mountain and another mountain. And you need to enjoy the ride, and being on the top of the mountain, it’s pretty unbelievable to look around and say, “Holy hell, what did we do to get here?” It’s amazing. So, yeah.

Arvind Gupta:

Oh, that’s great. Trevor, what about you?

Trevor Martin:

Yeah, no, I think if you enjoy what you do, it is like the horizon. You’ll always fall into that, it’s not a trap, but it’s like, you’ll always have, as soon as you achieve something, that’s old news. And now, there’s something else like, “Ah, if I just get that done, then I’ll feel like we’ve had more of an impact.” But yeah, I think for us, it really is down to the potential of CRISPR. And there’s so many thousands and thousands of diseases that could be diagnosed and cured, and we could spend the rest of ten lives working on that. And I think that’s why we also do things not just internally, but work with partners to try and scale our ability to have that type of impact. And in general, if we can just keep having cures and keep having diagnostics, I don’t think anyone on the team will ever get tired of that, basically.

Especially if we can always be innovating on the backend and just constantly pushing the envelope of what’s possible. And I think in terms of what keeps us going, I know for me personally, it’s the team that you work with, right. I mean, that’s probably true for anything, whether it’s personal life or professional life, as long as you work with people that you respect and you think are really awesome and invigorate you, you could probably do literally anything for decades. So I think that’s a really key part of any startup growth, as well as building that team that you just want to go in the trenches with no matter what.

Arvind Gupta:

Yeah. It’s kind of interesting, you guys both said it at different times, but I think the secret to the success that both of you have in completely different industries are common, right? Incredible team, and an incredible vision of the change you want to create in the world. That’s been clear from this conversation, from my perspective. There’s no wavering on what it is that both of you are setting out to do and being surrounded by people that you love and are capable of making it happen. Well, I think we’re out of time here, unfortunately. I can keep going with you guys forever, but thank you so much for making the time to join me and talk to the audience at TechCrunch. And I hope everyone learned as much from it as I did and had as good a time as me. Thank you guys again.

Bioplatforms for Saving the Planet | Mayfield x TechCrunch Disrupt

Twist’s synthetic DNA is re-inventing the fields of medicine, agriculture, industrial chemicals, and data storage. Ginkgo has developed custom strains of organisms to make fragrances, fertilizers, lab-grown meat, hunt for natural antibiotics, and engineer probiotics. Hear about the founder journeys of these two iconic entrepreneurs from inception through IPO and beyond, and how they are changing our world for the better.

Transcript

Arvind Gupta:

It is my pleasure to introduce two powerhouses of the current synthetic biology revolution, Emily Leproust, CEO of Twist Bioscience, and Jason Kelly, CEO of Ginkgo Bioworks. Twist’s synthetic DNA is reinventing the fields of medicine, agriculture, industrial chemicals, and data storage. Ginkgo has developed custom strains of organisms to make fragrances, fertilizers, alternative proteins, hunt for natural antibiotics and engineer probiotics. Both companies are leaders in the current biology revolution. I’m super excited to hear their unique perspectives from the cutting edge of our future. Emily, this is the transistor moment for biology as a technology. If we’re to continue that computer metaphor for biology, how do you see writing DNA as being able to write the software for life?

Emily Leproust:

Thanks Arvind, thanks for having me and you’re right, that it is the transistor moment – what happened with Fairchild and with the companies in Silicon Valley when they decided to manufacture transistors and miniaturized them. That really unleashed all the amazing things we’ve seen with computers and at Twist that’s what we’re doing. We’re taking the known chemistry for writing DNA, miniaturizing it and we can write DNA better than before. And basically every piece of DNA we make is kind of like a line of code. And so our customers buy a bunch of lines of code and then they have to…

Jason Kelly:

Have to pay by the bin.

Emily Leproust:

Yeah, yeah. To compile them. And so, we send them to Ginkgo and many others and unfortunately for the field, bio is still difficult. And so that means that our customers need a lot of lines of code to combine them and find the one that works for them. And so what will happen is as there are more lines of code compiled, there’ll be a bigger knowledge base. And people will be able to advance biology much faster at the same time as we keep shrinking the DNA and keep blowing the curve, increasing the throughput.

Arvind Gupta:

Fascinating. And so really you’re seeing DNA writing as being, not just putting together base pairs, but actually the compilation layer for the entire language of life.

Emily Leproust:

Yeah, exactly. And I am a very bad coder. I was a bad coder, now I’m a terrible coder. But when I used to code every time I would write a line I would have to compile right away to make sure that the code worked. I’m a chemist by training. So I have some excuses, but yeah, exactly. That computation takes time. Our customers use the design, build, test, learn engineering principle. And so our customers design the line of code. We build it and then they go test it and, and they learn from it.

Arvind Gupta:

Got it. And so you mentioned that you and Ginkgo are working together. So Jason, how is Ginkgo using the software of life to make organisms do useful things for humanity and further to that are organisms actually the programming language of life?

Jason Kelly:

Yeah. So, well, I think I’ll start just to mention, Emily kind of mentions off the cuff that they print DNA, but let’s just pause for a minute of how insane that is. Right. So just for, for folks who might not know this field, right? This literally means going in a computer you’re typing, ATC, GGG up into the kind of thousands of letters of code, you’re hitting print. And then off goes in order to Twist and they literally build the piece of DNA that you want. Right. And then our version of sort of installing code in a cell means that you’re going to open the genome of a cell. So think of like a bacterial cell would have a three million letter piece of DNA that tells that thing how to swim and grow and eat. And you’re going to install maybe 10,000 new letters of code in there.

Right? And you’re going to do that by opening the genome, kind of cut and pasting it in. If you’ve heard of things like CRISPR, that’s the kind of technology that allows that cutting and pasting, you put that new DNA in and then the cell reads it and executes it. Right. And so really that sort of programming metaphor, it’s pretty strong here, right? DNA is literally digital code and Emily has the world’s biggest compiler and you pay by the bit. Okay. Right. That’s what’s going on. And what Ginkgo does is we operate as essentially cell programmers, right? So we’re making use of Emily’s compiler, we’re Twist’s biggest customer ordering that DNA. Right? And then when we get it shipped to us, we install it in the genome, grow the cell up, and then basically run a debugger, right.

I’m sitting in front of a 200,000 square foot debugger, which is basically a bunch of robotics and all automation that opens the cell up, looks at what happened based on the changes you just made to the DNA. Is it making the right proteins, the right small molecules, what’s going on? Because as you know, as a software developer, you’re not going to get it right the first time, you’re going to want to see the output of that debugger. You’re going to want to make some changes to the code, hit compile again, get another order from Emily, put it in and see if it worked and go through that. Ultimately, hundreds of thousands of versions of that code until you get the one that does what a customer wants. And so that’s Ginkgo’s business. We essentially operate as an outsource programming shop. We have our own debugger. We order from Emily’s compiler, we build you a cell, and then you, our customer go off and bring that, that cell app to market. And we take a royalty kind of like an app store economy, basically.

Arvind Gupta:

Wow. And so really, this metaphor’s working out quite well, all the way to the consumer end that you’re talking about Jason.

Jason Kelly:

Yeah. I mean, to give you some examples, we have customers in the animal-free meat space, right. Who are engineering and you know this well Arvind.

Arvind Gupta:

Yes, I’m familiar.

Jason Kelly:

IndieBio really launched this whole area. But, what people are looking for is an animal-free product that still tastes good. And the way you do it is you basically engineer cells to produce animal proteins by taking the code, like a company, like Impossible Foods would take the code for hemoglobin. Right? Which is the protein that makes blood red. They put that ATCGG in a computer, hit print, get the DNA from Emily, install it into a brewer’s yeast, brew it up and instead of beer coming out, Hemoglobin comes out, you add that to a burger and suddenly it smells right and tastes right and cooks right. It’s an Impossible Whopper. That’s a consumer product with synthetic biology on the backside. There’re many things like that that we’re working with. We work in the agricultural space on microbes that produce fertilizers. The applications for this are quite broad.

Arvind Gupta:

Yeah. And I think you’re getting to the actual underlying power of biology as a technology. Right. I mean, how many industries did you name just rattling off your customers?

Jason Kelly:

Well here’s, what’s interesting. Again, people that understand computers get this, right? If you were like, what industries will computers impact? And, the answer is, well, every industry that uses information, right? Because fundamentally a computer is a programmable device that moves bits around, it moves information around. So what did it disrupt? Media, telecom, finance, advertising, anything that involved pushing bits, right. What didn’t computers disrupt, hamburgers. Because hamburgers aren’t made out of bits, right. Hamburgers are made out of atoms. And biology, programmable, I swear to God, it runs on digital code. It’s crazy. Okay. You put new code in, it does new things, but it doesn’t move bits. It moves atoms. And so if you think about the industries that bio and engineered cells are going to disrupt, it’s all the physical goods industries, and yes, that’s going to range from pharmaceuticals to building materials, to agriculture, to medicines, right down the list. Anything with an atom.

Arvind Gupta:

Fantastic way of putting it. Jason, thank you. And for me personally, I’m so excited because I think we could be using this technology to fight climate change and improve human health and all of the above, and really advance that quite quickly. And so Emily, you’re talking about DNA printing, right. And actually making these, but I know that Twist is doing so much more than just that or what else can we do with printing DNA, other than putting base pairs together?

Emily Leproust:

Yeah. So in addition to enabling customers like Ginkgo to do the great thing that Jason just outlined, there’s a few other areas where you can leverage DNA. One of them is in advancing diagnostics to the next level. So if you take the example of cancer, for instance, most cancers are found at phase three or phase four because you feel you have a mass and then they can always be seen in an optical scan, a C scan or an x-ray. And it’s often too late because despite hundreds of thousands dollars maybe even millions of dollars to treat, survival rates are actually pretty low. But you can use the power of DNA to take a blood sample and then use our DNA to extract the cancer genes, and just read that. And so what that means is, and it’s called liquid biopsy and it is delivering the fact that cancer cells are always shedding DNA.

So even though you have just a few cells, here’s a phase one phase two, there is part of that DNA in the blood cell. It’s almost like a shadow of the cancer cell. And then if you can, using Twist we can extract that those cancer mutations and sequence them. And you can get a diagnosis at phase one of phase or phase two, it’s a lot cheaper to treat and the survival rates are much higher. So that new field of liquid biopsy is absolutely enabled by the DNA that we make. Another exciting field, which is very different, is around data storage. So we are frankly, on a path where we are actually running out of sand, running out of silicon. If you plug the amount of data being created and you do the math just in the not so distant future, actually there won’t be enough silicon to store all the data that’s being produced.

There’s a better way to store data than on silicon, that’s using DNA. Our DNA is our hard drive, but you can find men with DNA that’s a million years old and you can see with it. And so DNA has the potential to be basically a per manage storage media. It’s also super dense. So you could put hundreds of Google data centers in a sugar cube, which obviously takes a lot less energy than those millions of square feet data centers. And so the density and the permanence means that we are pushing the technology to enable DNA to be the media of choice for archiving. So it’s not going to be hot data storage where the data is in and out all the time. But if you’re going to read the data once a year or less, DNA is going to be perfect.

That data layer is actually 60% of the market. So those are kind of two exciting new applications of DNA. There are more. We’re mostly working with pharma partners to discover drugs against how to drug target. So we are becoming the drug discoverer of last resort. If you’ve tried to find a drug against a target, you can’t, you come to us and we’ll do it for you. It won’t be cheap. It’ll be a premium offering. You’ll have to pay royalties. But so far, we’re betting a thousand for heart targets. 

Arvind Gupta:

That’s so cool, what you guys are doing and storing DNA, storing information in DNA. I think, all of the things you talked about, right? Like this, you said earlier, right. That you have a bigger compiler. Right. So finding drug targets for therapeutics speaks to that database. Right. So the more information you have, the more power you have in biology – is that fair to say?

Emily Leproust:

Yeah. And especially in drug discovery, it’s really a numbers game. People talk of one in a billion, right. You have to try a billion antibodies to find the one. And so if you have the machine that rises to the billion, well, you have a better shot at finding that one antibody. So there’s still a need for traditional ways. The traditional ways where you take a target, like COVID, for instance, and you immunize a rat or a mouse or a rabbit or shark or llama, and then you extract the antibodies produced by the animal. But it doesn’t work for many targets where there is ology between human and the animals. So that’s where we come in and we can really move the needles for those diseases.

Arvind Gupta:

Thank you for that service as well. So, Jason, if we’re going to extend this idea that we’re starting to see emerge here, that there’s a tech stack, for biology. That’s very similar to the tech stack for IT. How do you see the industry expanding? You’re touching all of these different industries through your offering, where do you see this tech stack going and how does it push the boundaries of what’s possible?

Jason Kelly:

I’ll make one quick comment on the data storage thing. I think it’s so cool. DNA is basically the product of who knows how many millions of years of evolution, upstream of DNA to choose that as a medium, to transmit information across generations. You’re going to pass on your genetics to your offspring. DNA is basically what God invented to do that. Right? It makes sense that it’s so information dense. It makes sense that it uses basically no power to store that information. It’s like the evolutionary end to data storage and it’s really cool. So it’s really exciting to connect the dots between that and sort of our electronic data needs.

So I think it’s a super cool area. It’s orthogonal to, well, everything we’re talking about on the cell programming side, right? Like the cell programming side is boy, we need everything for programming cells. We’re so bad at it right now. We’re basically writing assembly code, jamming in bits. We have no higher order to answer your question on the tech stack. There’s no basic. We’re writing assembly. But there’s no reason that stuff can’t get built. There was a day in computing where we wrote assembly. And so that’s kind of what I feel like we’re in today, we’re sort of in the mainframe era of computing, right? Like it’s, you’re still at the metal, you got to be an electrical engineer to be a computer programmer.

That’s sort of the era. And what we’re trying to do with Ginkgo is increasingly extract more and more of that away from the end customer of the platform. In other words, take for example, a company that got built on our platforms, a company called Motif. So it’s in that same animal-free meat space. They want to do egg proteins, milk proteins. They just raised a 226 million dollar round a few months ago. This is a company that didn’t exist three years ago. What they did on day one was they said, all right, we’re not going to build a lab. We’re not going to get a bunch of laboratory equipment, hire a bunch of scientists. We’re going to outsource the cell engineering to Ginkgo’s platform. And they got to make use of all my infrastructure on the first day and really catch up in that area. They didn’t have to be bio technologists.

You know, the folks who run Motif, they’re experts from the food industry. And so I think that’s one of the changes we’re hopeful to make happen as the tech stack matures, is if you’re an entrepreneur and you know some particular area, it could be fashion. It could be building materials, whatever, and biotech could be disruptive in that area. You could use Ginkgo, get the biotech disruption without having to be a PhD scientist. And that allows for a new kind of breed of entrepreneur in the synthetic biology space. I’m really excited to try to make that happen. Cause I think there’s a lot more ideas for what to do with biotechnology and people that can bring those to market than there are PhDs like me in bioengineering. Right. So that’s one of the goals.

Arvind Gupta:

Yeah. No, that’s absolutely right. And it’s really amazing. I know that you guys just signed a partnership with Huue as well, doing sustainable and nontoxic indigo dies. And so yeah.

Jason Kelly:

Genes for jeans.

Arvind Gupta:

That’s right. Watching Ginkgo enable all of these companies I think is just utterly massive.

Jason Kelly:

Again, Huue is going to get access to a few hundred million dollars of infrastructure here and it’s a 15, 20 person company, right? Like that’s the idea, again, this will make total sense to people, in sort of the TechCrunch crowd. Like it’s the same story as AWS, right? Amazon invests billions of dollars in data centers, so you don’t have to. That’s the general model here. It’s not that complicated for the tech crowd – actually, for biotech people, it’s a bit more of a new model. But for the tech and software people, it’s pretty obvious.

Arvind Gupta:

And so Emily, I think Twist is known for its incredible ability to expand and grow. And I think you’re behind so much of that. What’s the driving principle behind your agility and vision? What makes this happen?

Emily Leproust:

Like you said, we are addicted to revenue growth. That’s what we want to deliver. That’s what our investors expect. It’s three things. One thing is innovation. For instance, for data storage, we are increasing the number of features on the silicon ship by a million times, right. We go from a million pieces of DNA to a trillion. We’re skipping the billion. So massive innovation and go for the really hard problems and just crush it. The second is, frankly, very violent commercial execution, right? You just, we have to go take market share. And so we just are very aggressive commercially. And then the third thing is the people. If you start a company, you have A level people, if you’re not careful and you let the A people hire B people, the B people hire C people, and then they C people hire losers and then you’re a big company. So where we’re super careful to only hire A people and enable our employees to do the great things we need.

Arvind Gupta:

Amazing and yeah, clearly, right? You could see immediately why you two are not only super successful leading the way, but also two of my favorite people in the world. So I really appreciate you guys just taking 20 minutes out of your extremely busy days to speak with us and educate us on where the future is going. So thank you guys so much.

MedTech Insights with Salvatore Viscomi MD & Ursheet Parikh