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Good morning, everyone. Welcome. Thanks for being here. It’s great to be back in person. I think last year, this was happening all on Zoom, and at least I became a Zoom zombie after a couple of years of that.
Anyway, I’m excited to talk to two of my favorite entrepreneurs about their journeys and their lessons learned. I’m really inspired by what they have done and what they’re going to do. These are going to be life-transforming companies. And so, without further ado, let’s get going. Janice, could you share what’s your mission?
Sure. Thank you so much, Ursheet, for having me here and for the organizers for making this possible. It’s great to see you all here on a Thursday morning.
My name is Janice. I’m the co-founder and Chief Technology Officer at Mammoth Biosciences. We are a biotech company based here in the San Francisco Bay Area, and we’re developing the Nobel prize-winning CRISPR technology to reshape disease detection and treatment. Our mission is to improve lives by reading and writing the code of life with this really transformative technology that’s already changing the way that we do research and ultimately the way we treat patients and actually do medicine.
We think a lot at Mammoth about not just one enzyme, one disease, one indication, but we really think broadly about how we can apply this technology as a platform. Again, our bread and butter at Mammoth is discovering and developing these novel CRISPR proteins that we can then use to develop next generation diagnostics and therapeutics, and ultimately enable the continuum of healthcare. So not just thinking about treatment, but also detection and making sure we value all of that equally as patients move through their healthcare journey.
For us, it’s been a privilege to have worked with Janice and her team since inception. The way I like to describe it to a more tech audience is that, before Mammoth, if somebody had to develop with CRISPR, it was like building an application for a mainframe. You’d end up having to build your chips and your servers and your operating system. With Mammoth, it’s like you have Intel or Microsoft of bioengineering. They provide a platform, they build some of their own applications, but then the ecosystem is going to work with them. The mission, I think, as Janice said is to just save lives as quickly as possible.
And then, Diego, what is your mission this time around? Diego is a serial entrepreneur, before starting Endpoint he was the first bio partner at Y Combinator. He’ll be able to chime in with questions as well for me and others. Go ahead, Diego.
Sure. Yeah. Thanks, Ursheet. Thanks everybody for being here. My name is Diego Rey, Chief Scientific Officer and co-founder at Endpoint Health. At Endpoint, our mission is to dramatically improve outcomes in disease areas that have huge unmet needs. The way we’re doing this is by starting a new biopharmaceutical company from scratch with a data-first approach as opposed to starting with a molecule first.
Roche acquired my last company, GeneWeave, and while at Roche, my co-founders and I came up with this thought of, “What if we started a company like Roche today from scratch? What would we do differently?” The conclusion was that we’d start with data as opposed to starting with a molecule, given all the enabling technologies that are out there.
As a consequence in taking this approach, we’re revisiting diseases that don’t have good therapeutic options with a very high mortality, things like sepsis and acute respiratory distress syndrome that killed most of the COVID patients unfortunately, and even before the pandemic were the highest mortality rates in hospitals. We’re also revisiting chronic inflammatory diseases in rheumatology and gastroenterology, where existing therapeutics don’t have the best response rates and aren’t serving all patients.
By revisiting these diseases and taking a data-first approach, we can see subgroups of patients within those diseases that are biologically distinct and defined. And then we use that information to then figure out what molecule would best serve that specific subgroup of a patient. That’s the approach we’re taking at Endpoint.
Yeah, I’m actually thrilled. One of the things that Endpoint is addressing is the diseases that kill more people than all cancers combined. What I’m super amazed with is that Endpoint will have gone from inception to getting the first products in phase two clinical trials within four years.
This moves us to what I really want to get right into, the meat of it. Both of you ended up doing things that were not obvious from a business model perspective. It’s hard enough doing a deep science company, but both of you had this strong sense of purpose and mission to help patients as quickly as possible. You ended up, in the process, doing things that were unconventional, that a lot of VCs and most of the industry didn’t get, but now three, four years in, have turned out to be great decisions. I’d love for both of you to share what it is that you did at inception that was just so against the grain but is driving your success?
Sure. I can start. Mammoth isn’t the first CRISPR company, right? There have been a lot of successful CRISPR companies before us, but those really focused on one enzyme, in particular the Cas9 enzyme, and using that for gene editing medicines.
At Mammoth, we realized by really understanding CRISPR and being part of that field for so long, that CRISPR is so much more than one enzyme. It’s really a tremendous diversity of proteins that all have unique capabilities that can really transform all aspects of medicine, not just gene editing.
When we started the company, we recognized already that there was this concept of discovery to application that we had really been unlocking in graduate school, and I think the diagnostics application, for example, was a beautiful representation of what happens when you uncover an enzyme and really understand how it works and unlock a new application.
Today people talk about CRISPR diagnostics, it’s a very common term, but actually three, four years ago, no one knew what it was. It essentially didn’t really exist as a term, but we’ve been leading the charge and pioneering that field. But again, that’s just one particular example. Now as we continue to mine this entire universe of CRISPR, we’ve identified enzymes with new capabilities that are really leapfrogging the existing Cas enzymes to really think about how we can use it for permanent genetic cures.
So again, being able to go from this treasure trove and this evergreen pipeline of new systems to being able to unlock new applications and unlock a lot of just opportunities for improving patient care has been something that a lot of the traditional CRISPR companies didn’t really have the opportunity to do because they were really just focused on one protein system.
I think that initial goal for Mammoth and that opportunity and that capability that we have at the company was something that we knew was something very valuable, not just for Mammoth, but really the ecosystem at large. Ursheet talked about the Intel model. We truly want to be driving the ecosystem for CRISPR. It’s going to change the way we do medicine in this century and beyond, and for Mammoth to be leading that effort is something that is a huge responsibility and opportunity for us.
I think, Janice, there’s just so much in what you just said. If I had to pick a few of my favorite points on that, one was this point of, a lot of inventors think of their invention as “my precious”, and then try and keep it to themselves… And that’s very common in life sciences, right? This whole point about we are going to go do it for an ecosystem, then not just do one thing, do a broad platform, but still do one thing well at a time, and then not being shy to let the obvious answers lead you to sometimes what look like non-obvious conclusions. You can do diagnostics and therapeutics in one company and they don’t have to be separate companies. Diego?
Yeah, sure. I guess maybe one of the things you highlighted is how we’re doing something different or in a different way that maybe some of the challenges that came about because of taking that approach from an investor point of view and so on. I guess a key one for us was that by taking this precision-first approach as we call it, we don’t start with a molecule, we start with the data, then let that guide us to the molecule. That means that we don’t have a molecule, right?
Early on for a lot of investors, especially biotech investors, that was the key question. It’s like, “Well, where’s your molecule?” That did introduce a big challenge for us when we were getting started. If you don’t have a molecule, what are you? Are you a data company? Are you a diagnostics company? That was something that we had to navigate carefully. Fast forward, we get to the point where we actually identify the right molecule, bring it in, all that makes sense in retrospect from the outside point of view, but getting started, it was a bit of a challenge.
That’s well said. Taking this to a more personal note, in the end it doesn’t matter how great the science is – people build companies and people buy products, right? At a personal level, what have been the key pivot points in your journey to where you are now? Janice?
Yeah. Mammoth is my first company, and it’s the first company of my co-founders Trevor Martin and Lucas Harrington. So it’s a tremendous opportunity and very exciting for us because we can really think about how we want to build the company from first principles, but also take risks and think outside the box. We’re not tied to the way things used to be done. We can really think in a unique way and build off of each other’s capabilities to really challenge each other and rethink how we want to build the next great biotech company.
Obviously, the first big step was from us moving from being Ph.D. students, graduating from Berkeley and Stanford – we represent a unique and rare union of Berkeley and Stanford students. And then moving on to starting Mammoth has been a very exciting time for all of us. I think none of us at the time could imagine what Mammoth could be, but obviously as we slowly grew, the company partnered with world class investors, partnered with really just talented employees and other advisors. It’s been our lifeblood project to take things from again, being inventors on the core technology to really enabling a new category of CRISPR.
But it’s been four years and there’s been tremendous inflection points for the company as we, again, started with our core discovery platform, really proven out the diagnostics application, closed key contracts with government agencies and industry groups to accelerate the development of a first CRISPR-based COVID test, and then closing partnerships with major biopharma to really accelerate the development of CRISPR in the clinic, and then now continuing to build world-class business.
I mean, it’s been a huge amount of teamwork and really just mission-driven individuals to pull together. Now we’re about 150 employees, and we just closed our Series D about six months ago. We’re really in a high-growth mode and are continuing to think about how we can be that next generation CRISPR platform company.
Congratulations on the Series D which was north of a billion where the biotech market had been in correction for a while. That was great validation for all the work. Diego, what have been the key turning points for you? I’d like to hear about those going back all the way from your grad school days when you started your first company in the depths of the last recession to now.
Maybe I’ll take it even one step further back. I studied electrical engineering originally at UC Santa Barbara. That was my undergrad. The first big jump was going from engineering into the life sciences. After UCSB, I went to Cornell to do a PhD in biomedical engineering, I did a minor in biophysics and applied engineering physics. And then while at Cornell, we started GeneWEAVE Biosciences. Each step of the way was a key learning and a key training ground, I would say. And so during the PhD, my fifth year, I left the PhD program to start GeneWEAVE. I came back later and finished the degree and got the degree afterwards.
But we started GeneWEAVE, and our first check was in 2010. We were trying to get off the ground in 2007, 2008, 2009 before that. It was a different world back then in terms of how everything was going, how the markets were going. And so the next obvious key training ground is GeneWEAVE and the whole GeneWEAVE experience.
We went from seed to Series A to Series B company in a five-year period, and then we were acquired by Roche in 2015. Roche was a phenomenal training ground as well. So I spent two and a half years there before stepping off, and then between Roche and Endpoint, I joined YC as their first life sciences visiting partner.
Again, another phenomenal training ground because we were a diagnostics company. We were developing tests for detecting and identifying bacteria and guiding antibiotic therapy and hospitalized patients, so focused completely on just building that product and building that company. And then fast forward to YC and all of a sudden I had the responsibility of being involved with and helping out all the life sciences companies, whether therapeutics, diagnostics, tools, devices, health IT, etc. Actually, I learned a lot in the process, and then on to the new training grounds at Endpoint.
That’s great. As you go on this personal journey, one thing I’ve come to admire about you is how you have an amazing team of co-founders with you. I’d love to hear the story of how you picked your co-founders. What’s your advice, and then how do you find the roles? It’d be great to hear your perspective. It’s hard to start a company, but it’s even harder if you’re the only founder.
Yeah. Like I said, there’s four co-founders. One of them is my former PI, Jennifer Doudna, at Berkeley, and my other co-founder Lucas Harrington and I were grad students in Jennifer’s lab at the same time. We had started working in the lab and really being at the forefront of the CRISPR field back in 2014. This was actually just a couple years after the seminal Cas-9 gene editing paper, and that’s what received the Nobel prize a couple years ago or last year. That’s really just been a huge catalyst for me personally because I’ve been able to become a deep expert in how we can use CRISPR and understand the fundamental mechanisms for making them a very powerful tool and technology.
Lucas and I had known each other through grad school, we were very close partners, great friends, we critique each other all the time. We’ve become basically siblings over the last several years, and so it was very natural for us to think to say, “Okay, well, this is all the opportunity here in the field. How can we actually accelerate that even further and take that into a company.”
At the time we didn’t know Trevor Martin who is our other co-founder and the CEO of Mammoth. Ursheet and many others actually introduced us because they saw that Trevor and Lucas and Jennifer and I all had a similar vision to transform CRISPR into these new applications. And so it was actually a series of speed dates, quite literally over a couple weeks and then we said, “You know what, let’s just take the leap of faith. Let’s build something together. We’re stronger as one versus trying to be fragmented.” So it was a huge risk because, like I said, Lucas and I knew each other very well. We had only known Trevor for a couple of weeks and months, but we knew that this was going to be a partnership that we’re willing to take the risk for because it was such an important problem that we wanted to solve. And then of course, with Jennifer’s support we began really thinking about how we can bring great people together.
That’s really been, I think, the key to where we are today. Like Ursheet said, this is my first company, but it’s hard to imagine doing it without co-founders. There’s just been so many ups and downs throughout the journey and to have people that you can commiserate with and inspire each other and push each other. I think that’s also made a huge difference.
I think that as far as our roles, I mean, it was natural for us to fall into our respective roles. Trevor is our CEO. He’s really been driving forward a lot of the business development and moving forward, the new opportunities that we have with our technology. I’m the Chief Technology Officer. I really oversee the day-to-day development of the diagnostics business, and then Lucas is our Chief Scientific Officer. He’s really focused on the discovery applications, as well as enabling new therapeutic applications with the technology.
That was very natural for us to fall into our roles. We’ve been able to really support each other in that way. We have really clear swim lanes as well. That’s super helpful with co-founders. It’s very easy to say, “Okay, you do that. You do that.” There’s no conflict around roles. I think that’s super critical if you’re thinking about finding the right co-founder relationship.
But then we all come together to think about strategy for the company. It really is a team effort. It’s not one person driving the strategy. It’s the three of us, and now with the extended team we come together to really think about how we want to build this company. But like I said, I think finding the right co-founder relationship is really critical to the success and scaling of the company.
Yeah. As I have seen Mammoth develop over the years, even your founder relationships, it’s very much like the Golden State warriors where everyone’s a star and the team really works well together, and there’s a lot of respect for each other and the culture and the process. As you said, you have two co-founders whom you had known for five plus years, and then one that you aligned with over a few weeks.
As we talk and see all of that, this is also a testament to how important founder leadership skills are in terms of how you develop trust and build relationships. That’s all very well done. Diego?
Yeah. Actually, Jason, Leo and I are co-founders at Endpoint Health. We were co-founders at GeneWEAVE as well. After Roche, we got the band back together, so to speak, and started another company. The way we met originally was, Leo and I were lab mates at Cornell. Leo studied microbiology. I was studying biomedical engineering. We’re in the same lab. We both had the same fundamental interest, which was what happens between a lab bench and a product in someone’s hands. How does that happen? What you’re working on can become useful to somebody in the form of a commercial product. We started hanging out at the business school.
We ended up taking a course. It was entrepreneurship for engineers and scientists. It’s one business class that we took for credit in grad school. We had to make a business plan around a concept idea for a company for that class. That became the beginnings of GeneWEAVE.
In that process, we realized we’re learning on the job obviously when it comes to the business and industry side. We didn’t have any of that experience ourselves prior to that. We were full time students leading up to grad school. And so we ended up getting introduced. We went to business school professors, and we said, “Hey, do you know any entrepreneurial business students that you might introduce us to that are crazy enough to want to join a couple of guys coming up with neat ideas that might become a company one day?”
We ended up getting introduced to a few different folks. The key first thing about picking the founder was that it was just this immediate chemistry when we met Jason. It almost was obvious. It was like following the low friction path. We each don’t know what we’re actually going to do in the company yet. We’re barely getting to know each other, and so it’s more honestly a gut feel of how you feel with that person, you work well together, etc. That’s how we got started and got together.
As you start defining the roles, I think the key thing is that it takes a lot of self-awareness. It’s a combination of what needs to be done, what are you good at, and what do you want to do, and finding the balance between those three things. Where do you want to go? How do you want to build your career? We settled into our roles in that I’m the Chief Scientific Officer, as Chief Technology Officer at GeneWEAVE, same role though at Endpoint Health. Jason is our CEO, and Leo is our Chief Operating Officer.
The other piece, I think, as we started growing is that early on, you wear multiple hats, right? For example, Jason was our CEO, but really he was also our head of product in defining what we were building. For me, it was CSO and head of research. Leo was COO and operations has a lot of sub-components. As the company grows, we ended up bringing in folks that were more focused on product.
I think as things evolve, it’s the balance of those three key things and just doing what the company needs and, honestly, what you’re good at and what you like doing.
I think I can emphasize your point on self-awareness when it comes to finding co-founders. I remember my second company I had with a co-founder that was introduced to me by someone. We had this first meeting, which went on for hours and it was pretty clear that it had to be, but it does require a certain leap that does feel right in the gut.
Compared to the 2008, 2009 timeframe, there’s never been a better time to be an entrepreneur. While we may have some correction happening in the late stage markets or the public markets, in the early stage we have more money available to entrepreneurs and founders than ever before.
What is your advice, Diego? As you make a company, especially if it is going to be a mission-oriented or a deep technology company, what should you look for in your early investors? Do you do a party round? Do you pick focused partnerships, and how do you pick your investors? Why do they matter or do they matter?
Sure, yeah. At Endpoint, we were in a privileged position to actually have more of a pick of our investors than the first time around. Depending on what opportunities you have around the table, there may be less options. The more recent events were really where we had that opportunity. Full disclosure, Mayfield is our seed investor and lead investor. The reason that we went with Mayfield was that we wanted to build a company that was going to be founder-led, and it was going to be a longstanding company. We didn’t want to flip it. We didn’t want to sell it anytime soon. We didn’t have an exit strategy essentially.
At the same time there may be opportunities that help you fulfill the mission of the company that might turn into an exit for an investor, whether that’s an acquisition or an IPO, but as founders we wanted to be in it for the long haul. And so we were looking for investors who shared that belief and would back that.
It was clear when we met Ursheet and the folks at Mayfield that’s what they wanted to do. The way I looked at it was that way back in the day, Mayfield invested in Genentech, Amgen, Intuitive Surgical, Millennium Pharmaceuticals, more recently in tech companies, and now the next Genentech is the goal, or even multiple Genentechs.
We were lucky to find Ursheet who shared that belief and it was clear that he was being sincere about it. He held true to it throughout. Mayfield has participated in every one of our financing rounds since then, and has been a phenomenal supporter. That was a key thing, the shared vision of where the company was going to go and thinking many, many steps ahead. I think that was the key thing.
Yeah. I mean, certainly the same for us. Mayfield led our Series A, and of course we’ve been partners with Ursheet since the early days. Like I said, he was actually part of helping cultivate the founding team and getting Mammoth on the right track to where we are today. It’s been a tremendous opportunity, and I think it’s a testament to Ursheet’s commitment to founder-led companies. I think that’s been a shift in the model, especially in biotech, where there’s the old school way of, “Okay, let’s really just put in an experienced management team.”
That model is changing, and I think we’re seeing that really pay off in a lot of ways. Like Diego said, we are thinking about the long game. We’re not talking about building a company and then flipping it. We’re really thinking, “How will this be the next Genentech? Let’s go far. It’s a marathon.” I think finding investors who are really aligned with that and are in it for the long run is actually really, really key because you need to have the alignment and the values and the mission. We’ve been really fortunate too in this environment to be able to have the opportunity to be selective. That’s obviously not the case for a lot of people and throughout different times in the environment. But I think we’ve really been thinking about how do we find the highest quality investors to help continue to build Mammoth to where we want to be.
I know we started late, but we do have a buffer to go on a few minutes. If you have questions, you can put them on Slido or raise your hands, and we can get to those anytime.
We have a bunch of questions actually. They’ve been very active sending them in. Let’s start with, what are the important contributions from Mayfield that you’ve had other than funding?
Like I said, I think it’s hard to imagine Mammoth without Mayfield’s involvement, honestly. I mean, from the early days just helping… They really understood what we were trying to do. Again, we’re not trying to be a traditional diagnostics company or a traditional therapeutics company. A lot of people didn’t get that. They were like, “Wait, you’re trying to do both. What does this mean, and now you’ve got this discovery?”
Mayfield just got it. I think being able to have a thought partner to say, “Okay, how do we continue to evolve this business, this strategy.” And then of course build in other world class team members and advisors, I think, has been critical. Your early employees in the company are super important as are your early investors, right? They really help set the stage, set the tone. I think having Mayfield part of that journey has been really critical to our success.
Exactly. Very much the same thing on our side. I guess the one thing I would add is really helping us to think big, right? Mayfield has built very large companies in the past. They’ve seen it before. Having that foresight and comparables is really helpful to see how those lessons learned might be applicable to what we’re doing at these early stages if we want to get there. That’s been a big help as well.
I’ll try and expand on a couple of specific points. First is we live by a core set of beliefs that you can find on our website. One of them is that no success is accidental. And so if you have recipes and lessons, they can translate, but they have to be adapted, and that is where the second part comes in.
If I look at my job, it’s more like that of a coach. Entrepreneurs are athletes and elite athletes. When an elite athlete is able to connect with the right elite coach, then you can go on to win the championship. There’s a lot of deep trust that goes into forming that relationship, and the coach’s job is to adapt their style to the entrepreneurs, the situation, the game.
It’s not just any one thing. Yes, there’s things you can do like make introductions and help with hiring and process, but it’s really the ongoing relationship. I think for us, this people-first mindset does come with a position of deep caring and love.
Okay. I’ve got another one. What was your journey in finding product market fit, coming from academia and into a market with pre-existing competitors? What signals do you look for and where did you find those signals?
Like I said, our first focus of the company in terms of applications was diagnostics, and of course very well understood problems where diagnostic testing has its gaps, and that’s been amplified throughout the pandemic. When we first started we saw this is a new way to do molecular detection with the new technology and one that has a ton of longevity because you’re able to continue to evolve the core engine to achieve what you would like in terms of you’re optimally diagnostic, right? The right sensitivity, specificity, accuracy, low infrastructure, going into decentralized environments.
All of these different elements were captured by what CRISPR had to offer. For us, it was very clear that there was a really good fit with what the technology was today and then having a line of sight for what it can be in the future. That was on one specific application. And then, like I said, as we continued to push on our discovery pipeline and saw we’ve got these additional enzymes with capabilities that allow for really efficient delivery into tissues and organs to change the way that other enzymes have not been able to do with respect to in vivo gene editing, precision medicine and permanent cures.
That was obviously a clear value unlocking and really enabled new ways of doing genetic medicine. It’s interesting because we go from a discovery first approach to application, but it also goes the other way around where we say, okay, here’s the unmet need in healthcare – how does that actually link up with what our technology can enable?
It’s a two-way street, but I think being able to have powerhouses on the technology side and discovery and development, but then also key people who are understanding what the market needs, what is the unmet medical need, and bringing that together allows you to find a really great product market fit.
A quick lesson learned from the GeneWEAVE days where we got started and where we were building a diagnostic as well. In this case, it was one for MRSA, methicillin-resistant staph aureus and looking for drug-resistant bacteria. We thought initially, what’s being reimbursed in the clinic is detecting the gene that’s responsible for the drug resistance. We started building a test that was gene specific, and along the way we realized that actually what clinicians really wanted to know was, “How do I treat this patient regardless of how he got there?”
And so we found a much simpler way to get there with a phenotypic approach, which actually looked at, “Is the bug susceptible or not to the drug?” rather than looking for the actual gene. That ended up opening up a whole world of other applications. The key lesson there was looking more towards the endpoint, which actually ended up being the lesson for starting Endpoint Health and why we named the company Endpoint Health was that, what are you really trying to solve? Really try to define that first and then go back and figure out what’s the right technical solution to get there rather than jumping into the technology first.
We got time for a quick one. What words of encouragement or advice would you give students wanting to leave academia for their next opportunity?
Just do it. The earlier, the better. This phenomenal opportunity is out there. You could always go back and finish the degree like I did, if it comes to that. I encourage more folks to do it. You don’t leave academia and stop learning. You’re going to learn at the company as well, especially if you build it.
Yeah, completely agree. Just take the risk. Take the leap of faith.
This is for me a pretty near and dear topic. I’ve had various careers where I’ve kind of meandered out, and I’ve come to one conviction that the only way to make an impact at a global scale and change the lives of billions of people is by making companies happen. Entrepreneurship.
You may have the best science, the best research, the best ideas, but they don’t translate into impact in government. They don’t translate into impact in jobs, right? A great time to do a company is when in your gut you feel you just have to do it because it probably will be the hardest thing that you do, but it’ll probably be the most fun thing that you’ll do.
It’s actually not necessarily the easiest or the fastest way to make lots of money. It’s definitely the best way to become a billionaire. But if you are looking for the first 5, 10, 20, 50 million, you just have to find a rocket ship of a company and then get a seat on it. At that stage, don’t worry about what seat on the rocket ship, right? Just get there, and whenever you are in a hyper growth environment, you get to learn.
But once you get a sense that you want to go do it, absolutely commit yourself. And the company doesn’t grow faster than its founders. I feel thrilled to be in a position to have these conversations every day with so many of you and then champion folks like the teams at Endpoint and Mammoth. They’re duking it out for who’s going to be Amgen, who’s going to be Genentech.
But with that, thank you so much. Great to be back in the ‘living with COVID’ world. Thanks once again.
Thank you. What a great way to finish. Thanks for the insightful session. Thanks Mayfield. Thanks Janice. Thanks Diego. Thanks Ursheet. I’m sure they’ll be around and answer questions if you catch them. Thanks everybody for coming.