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

5 Essential Moments in Building a Company

Collision: Building the Zone of Trust

Transcript

Alex:
Hello everybody. My name is Alex. I’m very, very glad to be here today because we are not doing what I usually do, which is sit down with a couple of people from the worlds of startups and talk about numbers and money and all of that. Instead, today we’re going to talk about relationships and in particular, the relationship between board members and founders and how they evolve over time. But thankfully you won’t just be hearing from me. We do have two excellent people with us today, Tracy, Navin thanks for being here. How are you doing?

Navin:
Very well. It’s a pleasure to be here.

Alex:
No, I’m really looking forward to this. I think that this is not a topic we talk about enough out loud. I know that founders talking amongst each other, so do venture capitalists, but I think that the actual relationship building between long-term partners is actually under discussed. Maybe the only thing in the world of startups it’s actually under discussed this year, but I want to go back in time to start to set a little context for everyone who is maybe less aware of the Poshmark story, then the three of us are. So Tracy starting with you. Can you tell everyone how you ended up moving to California and then joining the Poshmark founding team?

Tracy:
Yes. I grew up in a New York area. I was very interested in fashion and that was my world. And I came out to the Bay Area to really partner with a really strong technology and business team. And so came to San Francisco and networked around. And this is where the origin story and Navin comes in, really early as I did not know that the Bay Area did not have a whole bunch of fashion folks. There are none. And so as I met, I ended up meeting my co-founder and we still work together today, Manish, and it was via Navin and his firm that really put those two pieces together.

Alex:
Yeah. And that’s why this is so interesting to me because often founding teams meet their investors. But in this case, Navin your crew had an active role in that. So tell us just a little bit about how that all kind of came together.

Navin:
Absolutely. So Manish and I go back to 2003, 2004, and as he was leaving his last company, he and I started spending time together and looking at what to do next. And one of the areas he was very excited about is building a social fashion marketplace, which would be built on the iPhone, on the mobile thing. But one of the things he recognized is, he’s one co-founder short, where he needs a woman who relates to women fashion, which would be the focus of the company. And that’s where we met Tracy through the network in 2010, introduced them. They spent probably five, six months together, and then they came and pitched us in January of 2011. And that’s what led to the series in financing of the first money of Poshmark, the series in financing in January of 2011.

Alex:
So this is where I want to pick up on a more specific question. I’m curious. What about their pitch was attractive to you? I know that you knew the people, but was it the thesis, the economics, what really drew you in to cut that first Series A check?

Navin:
Yeah. So Mayfield is a people first firm. We believe in people first, market second. We believe people make products, products don’t make people. So it’s all about the people. Then we looked at the problem they’re solving and it was really a pain killer, where you help buyers and sellers of fashion to come together through mobile. The third thing we look at is, they were shifting from search based e-commerce to discovery-based e-commerce based on social and the market for fashion is a trillion dollars. So if you scratch the surface and get to 1% of the market, you’re $10 billion in GMV. So that’s what led to us getting excited about funding the Series A at Poshmark, but it started with people and ended with people.

Alex:
So Tracy, now I want to know a little bit about the early relationship building between you and Navin. I know a lot of startups have monthly board meetings when they’re very, very young, some do quarterly, some are a little bit less frequent. How did you guys go about in those early days, getting the level of trust you’d want to have with your earliest investors?

Tracy:
Sure. I’m going to answer that but first. I just want to take a small detour and add to what Navin just said. We can look back 10 years with rose colored glasses. And the truth of the matter is the world was very different when we were pitching Poshmark at that Series A to Navin and his firm. And I want to give Navin a lot of credit because it wasn’t just the market and what we’re going after and all the things that make business sense. What we were pitching was quite, quite innovative. And I think that if you just looked at the idea itself, it might’ve been really hard to wrap your head around committing and investing to what Poshmark is today. And I do think the people first nature of Navin and Mayfield really helped us come together because he could see the passion and the partnership and the team and really behind not just the great idea, but how we really felt like we were positioned to solve it. So I just wanted to put that in there. And now remind me your question again, please.

Alex:
Essentially building the early relationship. Once you were an operating company board meetings, how were you guys trying to get close essentially in relationship sense? Because things are hardest when your company is the youngest.

Tracy:
Yeah. I think one thing a lot of founders miss with their investors and board members is that they are part of your team too. And that, especially in the early days when you don’t have a lot of people to lean on, and a lot of people who deeply understand what you’re trying to build, your investors and your board members are there with you. If you take them with you on your journey and it’s up to you to form that relationship. So in the early days of Poshmark, Navin was another team member, he was someone that we bounced ideas off of. He gave us support when we needed it, intellectual, financial, emotional, all of the type of support that founders need in the early days. So I wouldn’t say it was just about board meetings. Those are kind of the official ways to connect. For us, team is everything and culture is everything. And that’s how we approached our early relationship with Navin and Mayfield.

Navin:
If I could add, right. I have a firm belief when founders are working with founding investors, is the role of the investors to invest in relationships, not transactions. You need to spend a lot of time with the founders in aligning your mental models and assuring them you will be their safety net and you will be loyal to a fault, but at the same time, you’ll practice radical candor. There you’re going to care deeply but challenge directly, and that healthy balance where they know they’re looking out for you. And it’s not only the board meetings where you spend time with them. It’s all the offline time you spend with them, ends up building a healthy relationship and ends up building the foundation off a built to last company.

Alex:
Yeah. But it feels like you guys had a lot of time, and one thing I think we’ve seen in the more recent venture capital world and startup world in the last 12, 24 months has been an acceleration of everything. Even just due diligence has gone from months to weeks to days to now I’ve heard from some investors, hours. So it seems to me, there’s this demand by the market to get to trust so much sooner. Navin, can you get to a comfortable level of trust with a founder pre-investment these days given how fast things are going? Or is that not as important to you?

Navin:
No, it’s extremely critical and there’ll be a lot of investments we won’t be able to do because we don’t know the founders or we are not able to spend quality time with them. Our belief is getting aligned on the mission, the values, and the culture is critical. And if somebody is only interested in our money, it’s not a good fit for us. So we are a firm, which is people first, we believe in investing in relationships and not transactions. And we have to invest time before we invest money. So we’re not in any rush, right. Business building and venture is a marathon, it’s not a sprint.

Alex:
Tracy. I want to ask you about this from the other direction, because Poshmark went through a number of rounds before it went public. And so you had to add, I presume a good handful of people to the board as you went along, did you put the same amount of time into kind of getting to trust with each board member as you did with Navin in the early days?

Tracy:
Well, there’s never, time is a finite resource. So I would say Navin got a head start with many years with us, but I would say that the approach is the same. We think that culture is one of the strongest pillars of the Poshmark brand, whether it’s external to the company or internal to the company. And as I said before, we really think that our board and our investors are part of the team that can help us get to this crazy lofty vision that we have. And so as we added more members to the team, it’s part of building culture. So if you say that the founders and Navin were at the beginning, right. But we had a dream that was much bigger than just us. And so, as you add people, it’s like, well, what can this person add? And what can that person add? And how as a collective team, do we get stronger and stronger as we go? And so that was the approach. In addition to fundraising that we took, as we built out the board.

Alex:
I want to double-click on that really quick, because I’m just thinking about how many startup CEOs telling me that they were juggling multiple term sheets when they’re raising their next round. So it seems like if you’re a founder, money isn’t the problem instead of kind of probably finding cultural fit slash trust within an investor is probably more important than ever given that there’s so many different fundraising options, Tracy.

Tracy:
Well, listen, if you’re lucky enough to have options, then I would opt for culture. Cash is king, and you have to keep your company alive, right?

Alex:
Yeah.

Tracy:
And if you’re building a solid business and you’re building it methodically, then you should hopefully have some options. So I would try to go for all of it, but you do have to make trade offs.

Alex:
Okay. Navin I want to move this back to you for a second, because I’ve heard about somethings that investors are doing during the pandemic because it’s shaken up the ability to get coffee and so forth with people. And I’ve heard about venture capitalists, playing video games with founders to establish a deeper relationship. Virtual HQ’s are a big thing. So are those the outliers that I’m hearing about when it comes to kind of founders and board members getting closer or are those things relatively common when it comes to really trying to get to trust for early stage company?

Navin:
I think it’s a hybrid. Some people and some venture firms are getting complete comfort doing this virtually. And then there are firms like us, which are using a virtual model where you start building a relationship and start having conversation with founders, or then you figure out how you can over them on a socially distant hike, how you can get them to your home. How can you get to the bottom of who they are, what their dreams are, what their passion is and figure out, you’re a services firm at the end of the day, how are you going to help them achieve their dreams and mission? So I think it’s a hybrid model, but every firm is different, right. One has to be comfortable with what their business model is. You need to believe in your model, your north star and follow that. And to me, since business building is a marathon. It’s not a sprint, spending that time upfront is so critical, so critical. And I tell the founders, don’t just get gamed by what the VC’s saying, go check them references on them, whether virtually or, and you can go on LinkedIn, you can go on PitchBook and see who they are. Really understand because entrepreneurs are going to have choices, really understand who’s going to be with you when things don’t go well.

Alex:
Right. Or who’s going to take credit for it all if things do go well, which is another particular issue we don’t have time for today. Tracy, I want to go back to you and talk about board diversity. One thing that I keep hearing a lot about is bringing on increasingly diverse voices to cap tables. And I’m curious amongst your founder friends, how much does that come into play when it comes to selecting net new board members for companies as they scale?

Tracy:
Well, it’s what you intention. So for us, that’s very important, particularly because what we have built and what we continue to build is something new and it hasn’t been done before. And so we do really benefit from various voices and perspectives. And so bringing on board, Jenny Ming, who is a retail veteran to help us think through scaling Poshmark, beyond where we are today, bring onboard Serena Williams, who is a powerhouse entrepreneur, fashion label producer. And also just how to build brands and to connect with audiences is a perspective we had, but she brings so much more there. And so since we’ve added some different voices to the table, the conversations have come to life and have changed. And so I’ve seen firsthand, not just in building diverse teams, but also like I said, your board is part of your team. So having that perspective has been very helpful for us in the later years.

Alex:
Yeah. So Navin, I want to take this back to you for a second, because you were talking earlier about going on distance hikes with people, having them over your house, kind of presuming a lot of locational proximity, that you’re going to be nearby. A lot of VCs also talk about pattern matching and trying to figure out kind of what might work based on past results. And I wonder if those things don’t in a sense accidentally discriminate against more diverse founders who may not be in the Bay Area, for example, or who may not have the exact same kind of like pattern matched background. So how do you go about building trust with founders who may not fit the kind of usual rubric that you see or that you’re kind of most comfortable with to kind of get out there and invest in more diverse people?

Navin:
Yeah. And I think in today’s world, right. Like there is easy ways to check founders. You’re only one or two degrees of separation away from them based on common connections. But then we have a strong conviction of embracing the unconventional, the different and the unusual. And we believe it’s often the founders who don’t come out of central casting that have the grit necessary to succeed against seemingly insurmountable odds. And at the same time, we have another belief that great people evolve. Almost no one comes into the job, but all the skills and experience they need, this is where our role as a coach, as a VC can help them grow as long as they are continuous learners. So the amount of time you spend, it may not be physical, you can reference check them, but have candid conversations and say, what drives you? What are you looking for? What does success look like for you? Have you made tough decisions? How do you value teamwork? So I think it’s more of a psychology test and it may feel we have an x-ray on founders where we look at who they are rather than looking at their metrics and really studying them and making sure these are the people we want to invest our time and money in and help them grow and achieve their dreams.

Alex:
Navin I want to stick with you for one more. We’re a little bit short on time. So I’m going to squeeze in a couple of quick ones here. I was actually playing video games with a Midwest based seed stage VC last night. And we were talking about when to leave boards and I wanted to bring this to you because he said that he doesn’t really stay on boards past Series A, that’s not really his domain of expertise and so forth. So how do you as a founder or maybe as a different board member, remove board members over time as maybe the company evolves past their expertise without breaking the trust that you had as a group and they were active on the board itself?

Navin:
Yeah. So I think let’s look at the Poshmark situation, right. I have such a close relationship with the founders. I’m going till the end. IPO is just a financing event. I’m there for as long as they need me, today we are the largest shareholder, a year from now we may not be. Where the services from our job is to help them, but there’ll be other where more independent board members can fulfill the need. Then we can post the ideal. Then you transition, but we are loyal to a fault. We are committed for the long run, but it’s all dependent on the founders because if they need something that may feel that I can’t offer you step back. But if he can offer that you continue on the journey. So it’s a collaborative decision rather than just saying I did the Series A, I need to stay on it.

Alex:
Got it. Tracy does that square with your experience as a founder? Does that make sense?

Tracy:
It does and all your questions tied together. It’s, if you can build your board to want to have you win as the number one goal, then all of this just comes, right. And everything else, it might be ups and downs, but these decisions are easy when you have the same goals in mind, when you get into a lot of trouble. And a lot of the horror stories that I hear is when those goals are not aligned and that was never a mindset to begin with. It was more about, I need cash, let me have a cash infusion. They looked at their board members as transactional people and not as a person, what does this person want to see from me, et cetera.

Alex:
Yeah. So we have time just for one more, Tracy, I’m going to leave us with you. So thinking about more red flags, just for all the founders out there who are listening in right now to us, what would you say are a couple of things to watch out for that are potential negatives and maybe even some positives amongst board members, as they go out there to raise more capital and pick their board member team.

Tracy:
So I think there’s a simple thing that a lot of people don’t do as you are raising money, as you are looking to add to your board, do you want to spend a Saturday afternoon with this person? Do you like them? Can you trust them? We have really good instincts. We can decide that you’re talking about short investing or due diligence timeframes. We know within five, 10 minutes, whether we think we can trust someone. And so we have this skill, use that skill and apply it during this circumstance. And I think it’ll serve you quite well.

Alex:
Okay. Well, Navin, Tracy, sorry. We have to wrap it up there and throw it back to Toronto. I had a bunch more, but sadly that’s all the time we have. Thank you much.

Navin:
It’s a pleasure being here.

Tracy:
Thank you.