Neil Patel

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In the world of scientific innovation and entrepreneurship, few names shine as brightly as David Schaffer’s. With a track record of launching and nurturing successful companies in the biomedical field, David’s journey is not just a story of academic achievement.

David talks about building eight companies within a short time frame of just over a decade, one of which he took public. His latest venture, Axent Biosciences, has raised $100K in funding from SkyDeck Berkeley.

In this episode, you will learn:

  • David Schaffer’s journey underscores the seamless transition from academia to entrepreneurship, blending research rigor with real-world impact.
  • Through initiatives like Bakar Labs, David has cultivated a fertile ground for scientific startups, fostering collaboration and driving tangible solutions in biotechnology.
  • David’s portfolio of eight companies reflects a commitment to diverse applications of biomedical research, from gene therapy pioneers to groundbreaking genome editing ventures.
  • The choice between staying private or pursuing acquisition hinges on each company’s unique trajectory and strategic partnerships, showcasing David’s keen understanding of the entrepreneurial landscape.
  • David’s companies are at the forefront of biomedical advancement, pioneering breakthroughs in targeted gene delivery, regenerative therapies, and beyond.
  • Networking and learning from others are paramount, as David advises aspiring entrepreneurs to surround themselves with those who challenge and inspire, fueling a relentless pursuit of innovation.
  • With a legacy rooted in excellence and a vision for a better tomorrow, David’s impact on the world of scientific innovation is profound, shaping the future of biotechnology for generations to come.

 

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About David Schaffer:

David Schaffer is a Professor of Chemical and Biomolecular Engineering, Bioengineering, and Molecular and Cell Biology at the Helen Wills Neuroscience Institute at U.C. Berkeley.

David has served as the Director of the Berkeley Stem Cell Center since 2011. In addition, he is a co-founder and, since 2013, has served as Chief Scientific Advisor and a member of the board of directors of 4D Molecular Therapeutics. He has also co-founded five other companies.

David has served on the board of directors of the NASDAQ-listed company uniQure NV since January 2014. He received a B.S. in Chemical Engineering from Stanford University in 1993 and his Ph.D. in Chemical Engineering from the Massachusetts Institute of Technology in 1998.

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Connect with David Schaffer:

Read the Full Transcription of the Interview:

Alejandro Cremades: All righty hello everyone and welcome to the deal maker show. So our guest today I got to tell you he’s quite the rock star I mean he’s done a day multiple times you know we’re talking about 8 times and 8 times in a very small timeframe. You know we’re talking about like maybe like a little bit over a Decade. Ah. 1 of them. Actually you know he took public. You know right now is trading at about one point two billion plus ah market cup ah about the incredible journey. You know we’re gonna be talking about how you know he went you know about clinical trials with one of his companies. The first one also thinking about. Acquisition versus staying private. Also the incubator you know program that he is pushing. You know which has saying had remarkable success with the company is collectively raising over 300000000 and then also a new company that is launching so. Again, building scaling financing and exiting all the above that we like to hear so without farther ado let’s welcome our guest today Davidchafer welcome to the show.

David Schaffer: Thank you so much Alejandro thrilled to be here.

Alejandro Cremades: So originally born in Latin America you know out of you know a meetup you know that your parents had in grad school so give us a walk through memory lane. How was life growing up for you.

David Schaffer: Sure I actually don’t remember unfortunately being in latin America I lived there all of six months before my parents decided to move back up to the Us. But yeah, my my father was an academic. My mother did drug development for her career worked in a ah couple of different pharmaceutical companies. But you know, grew up. Pretty much like any other kid. Um all the way through high school and then went to to college. Ah at at Stanford University which you know ironically is is Berkeley’s rival these days so ah, um, but after finishing up at Stanford moved to mit for graduate school salk institute for a postdoc. And came up to Uc Berkeley in 9099 to start up my academic career and have been here ever since. Ah for 25 years so most definitely my home.

Alejandro Cremades: So what got you into engineering out of all things why engineering.

David Schaffer: It was ah you know motivated in part by my parents. My father was a very very basic biologist with an academia a professor so extremely basic, not application oriented and my mother was on the kind of the opposite end of the spectrum. She was ah an Md a physician who did drug development and ran everything from phase one to phase four clinical trials in our role at at Nevartis and then at Sanofi I wanted to be somewhere in between I wanted to be more applied than my father was I like making things. But I also you know, enjoyed this idea of ah being able to pursue things of interest to me, you know academic freedom so that ah made me an engineer and in academia. So I I figured out pretty early on that That’s what I wanted to do for my career and thankfully it worked out.

Alejandro Cremades: So out of all things you know like you said you know academia. So I mean Academia you know it’s a really interesting route that you decided to pursue especially you know, given the fact that you’re also a serl entrepreneur. So how do you think you know that balance you know between the two you know have ah shipping up for you.

David Schaffer: 1 of the reasons I really like academia is that it’s design your own career ah in some cases people decide to really focus on the research programs. They’re building within their labs which I’ve done for you know much of my career. People can decide to focus on teaching they can decide to become a chair a dean a provost a chancellor which I’d never you know that was not my my interest ah people can play a role in translating their technologies from their academic labs into industry and at different times of my career I’ve had different interests in that spectrum. But really, ah you know, roughly for the first half of my career I was really focused on building up my academic program and and our research and working on solving what I found to be some interesting problems and the second half of my career so far I’ve been focused on taking the the results of that work and translating it ah from the. Public sector into the private sector and getting it into companies that can then advance it to human clinical development but academic freedom affords you the ability to do all of the above. So I very much enjoyed it.

Alejandro Cremades: So so.

Alejandro Cremades: No kidding now. Obviously for you, you ended up kind of like establishing your own incubator you know or or or I would say like system to really just like span out. You know, companies out of it. So. How did this come about because I mean out of out of this.. Obviously you know like your biggest success today you know came out which is for the molecular seraptics which you ended up taking public but how did the whole concept and structure for this. You know, come together.

David Schaffer: It was ah you know as I mentioned I developed a really strong interest in getting our technology from an academic lab into a company and that was motivated you know and by and large by my my experiences with you know learning from how my mother worked that companies are the entities that take basic research. And advance them into clinical development and eventually into products that can be scaled to really help society. So I always knew I wanted to play a role in forming companies and started doing that you know as you mentioned about a decade ago ten eleven years ago or so and learned through each one of those of those companies that I’ve co-founded i. A lot a huge amount. Um, we did some things right? You know I made some mistakes and you know once you learn ah a few mistakes you know fortunately, none of them are fatal all of 8 of my companies. Ah while the 2 have been acquired, no longer exist the other six do. But you know I felt that yeah I wanted to. You know in addition to doing research be an educator because that’s the the heart of academia education and research and so I had the opportunity starting around three years ago or so to take the leadership role of an organization. Ah a multi-usec campus organization called q b three. Which is focused on scientific innovation and and entrepreneurship. Ah Q b three you know back in around 2006 formed the very first incubator in the University Of California system at Ucsf ah, 2008 formed the very first University Affiliated Venture Capital Fund anywhere in the country.

David Schaffer: So the organization has had a longstanding history of being innovative at that interface between Academia and companies. So I became the overall director around three years ago ah we um, opened up. What’s now the largest university owned and operated by a technology incubator in the country. Ah, called baker labs which is ah a partnership between Q B Three University California Berkeley and a ah terrifically generous donor foundation and baker labs is ninety Five Thousand Square feet we’re home to 31 companies as you mentioned those companies have collectively raised. Ah, three hundred and ninety million dollars have created 350 jobs in the state of California and you know fortunately for me as well. I’ve been a terrific home to 2 of my own companies as we fund spun them out of the university and then enable them to grow and in 1 case move on and and outgrow the incubator.

Alejandro Cremades: So obviously you know in total you’ve launched a 8 companies you know and you even have your own you know umbrella you know where you would you just like spin out ah companies yourself. So what? what ended up being that framework you know from the way that you think about. An idea to the way that you think about bringing it to life to the way that you for perhaps you know like plug in the right team and then finance it and and let it grow and and fly.

David Schaffer: Sure it always started of course with the idea and I wasn’t necessarily looking for ideas to build companies around you know during the first ten fifteen years in my career I was looking for big problems. You know things that I yeah my engineering. You know side of my brain ah felt was a big problem that really deserved a solution deserved a technology to solve the problem So I started working on problems in Gene and cell therapy began to publish on each of them, patent them, etc and at at some point. A solution to a problem reached a critical mass where it could be the basis of a company you know, even though I didn’t really and intend to start spinning companies out of my lab I was just interested in solving problems. But if you put together a you know a compelling technological solution to an important biomedical problem. Ah, that has publications and patents around it that becomes a great package for for starting a company so started doing that around 2012 or so and you know, kind of caught the bug. It’s something that I found to be fascinating each one of those companies is is very different from each other and had a different kind of. Organic growth ah path but you know roughly we’ve started companies when we hit that critical mass of of having you know Ip and and technology that addresses an important biomedical need then? um I’ve I’ve typically started it by.

David Schaffer: You know, onboarding or or bringing on board a graduate student or postdoc who was involved in creating the technology. These folks are really smart I’ve known them for you know 4 or five or six years meaning I have a lot of trust and a lot of confidence in them and there are folks who will move mountains to to make the technology work. You know they. If they originally played a role in inventing it? Um, but I’ve also typically paired them together with more experienced leadership. Um, as time has gone on ah to to mentor and enable those people to grow and then of course the you know the ah traditional process of pitching vcs raising funds. Um. In many cases. We’ve actually also done it done it non-dilluively through bd partnerships with larger companies and you know that’s ah each one of those companies is has ah launched with in some cases a huge amount of my time invested in other cases I’m a more of a consultant and board member. But I like to continue to stay involved with each one of them and and you know have the joy of watching them grow.

Alejandro Cremades: That’s amazing. So then let’s talk about the first one and your first baby and and an amazing success which was for the molecular therapeltic. So obviously you know you guys got started with this and that was back in 2012 so what? What was really the concept. You know what what? What ended up becoming the company and really the the business.

David Schaffer: Sure it was ah technically for you was my second company. My first company I started in 2012 I wasn’t as actively involved in that it was ah myself and another professor and he ended up playing a ah bigger role within that company. Ah, four d was based on technology that I started inventing in my lab back in 9099 and my doing that work was really taking on 3 leaps of faith that all did end up working out. The first is that gene therapy was going to work and was going to be an important therapeutic modality.

David Schaffer: And gene therapy of course is the idea that you can use Dna as a medicine that if somebody has a broken gene such such as cystic fibrosis or Hemophilia you could deliver the correct version of that of that gene and as a result potentially treat the disease. That’s an oversimplification and there are other ways that gene therapy can be used but you know to ah to a to a good extent. It’s about delivering correct copies of broken genes. Um, so in addition. It’s really hard to deliver Dna. You know most of the time the body thinks that Dna is a bad thing. You know we associate it with viruses and and bacteria foreign dna but you can use viruses and um take away their ability to replicate. And trick them into delivering a piece of medicinal dna rather than their own Dna and there was one particular virus I’ve been working with for almost thirty years called adnoassocid virus and my second leap of faith was that was going to be the one that was going to be a a virus that the field was Goingnna was going to succeed in using. And the third was that natural versions of this virus weren’t going to be good enough and we we felt that we needed to engineer much more efficient targeted versions of this virus. It’s ah it’s a respiratory virus. Not a very good one and when you start showing it cells outside of the lung show it a neuron or ah, a heart cell or a muscle cell.

David Schaffer: Virus says what is this you know evolution has not prepared me throughout tens of millions of years to be able to infect and deliver dnas to the cells successfully so we invented a technology that enabled us to reprogram these viruses and make them much better at carrying that Dna to a variety of cells and tissues throughout the body. Yeah, basically adapted a ah protein engineering approach called directed evolution that was emerging in the field at the time and actually went on to win the nobel prize in 2018 and we were the first to use that with aav and with gene therapy.

Alejandro Cremades: So.

David Schaffer: Ah, so that’s fast forward to 2013 um the technology was ripe gene therapy was starting to work and the capital markets were in good shape so that was ah that was the time to to spin out that that technology into 4 d.

Alejandro Cremades: So let’s talk about then for the 2 I mean the the way that you guys were able to take it all the way to ipo I mean what was that like I mean sounds like a wild you know journey.

David Schaffer: In 2013? Um gene therapy was starting to work a man as you well know 2008 was a huge disruption to the world into the capital markets and a lot of capital was sitting on the sidelines for a few years and then right around 2012 or 2013 the capital market started recovering people were looking for things to invest in and biotech became a ah big one and there were 3 real major areas where where investors started coming into biotech was in cancer immunotherapy.

David Schaffer: Genome editing and gene therapy so gene therapy which was really a backwater of medicine for for a couple of decades. All of a sudden came to the fore and there was a huge amount of interest in it. So um, at that time people were coming to me because we have been publishing for 10 years about this. New technology to be able to engineer versions of this virus a at will and optimize them for delivery in the eye or in the lung or in the brain or to muscle so we had this this strong track record and people were coming to me. Ah, which was again kind of ah a change from what I was used to ah so. They were both investors as well as as larger companies that were trying to launch their own gene therapy programs and needed to delivery vehicles. So we spun our company out four d I co-founded it with a a berkeley alum by the name of David Kern who’s currently the Ceo. So David and I spun out four d along with a. Ah, graduate student from my lab. Melissa Cotterman is her name. She’s been terrifically successful and we decided to finance the company not through the traditional Vc route initially but through business development partnerships because there were companies coming to me asking for you know, can we get access to your to your. Novel viruses. So we we made a couple of deals. Um use that capital initially to grow the company and then started doing. You know we did a series a and series b series c um, we had a couple of offers for acquisition during that time as well. But I felt.

David Schaffer: Really that you know at that stage gene therapy was relatively new within industry and there weren’t a lot of large partner companies that really know how to do it so you know part of the reason or part of the rationale for being acquired by a larger company is to achieve synergies that they know things that you. You don’t and they have capabilities that you don’t and we we kind of felt that since gene therapy was so new within industry that we you know potentially could become the big company that was doing that kind of work and so we decided to stay private throughout. Um and then in Twenty Twenty December of 2020 ah, ultimately, you know took the plunge and and decided to go public so it was myself the Ceo and the chairman of the board who did the ah all the ttw meetings in the ipo roadshow I probably wouldn’t have you know because the ah the old way of doing ipos of course was through trains. You know, planes trains and automobiles. Ah, packing a week or more with tons of meetings with investors and hopping on the plane and and you know nonstop this was of course in the middle of covid so people had the luxury of being able to do Ipos from the comfort of their own bedrooms which is exactly what I did back then. And so I had you know 75 investor meetings over the course of a couple of months and it ended up being a pretty successful ipo. Ah 21 x subscribed Goldman Sachs is our lead bank b of a the second bank and you know the the important part of going public. Of course is that.

David Schaffer: The company then had the capital to be able to do what we were all enthusiastic about which is get the technology further into clinical development where we can start helping patients.

Alejandro Cremades: So I guess you know in this case I mean incredible right? You know like being able to build a company that you know is worth more than one point two billion. No I think that this was just like part of you know, continuing to push also more companies I mean in total eight you know that you’ve done. Ah, the second one you know we chain which also you know went through our liquidity event you know was basically rewrite now in rewrite. You know it was. It was pretty much like 3 years in when you guys decided to go through an eman a transaction I guess you know the the question here you know is what were you guys doing there and. Why did you decide to get the company acquire versus staying private and private and growing. It.

David Schaffer: Yeah, it was ah every company of course is its own unique thing and ah the right? you know quote unquote right? Decision is different for for each one. So I’ll I’ll give you a little bit of background about rewrite. So it was a genome editing company. Was really the brainchild of a brilliant graduate student of mine named Shaette Halperin ah where he and I and another investigator published a paper in in nature back in 2018 and the company was based on that technology and it was a way to very efficiently do genome editing. And change a stretch of Dna inside of a cell ah and overcome a couple of hurdles ah to to really improve the efficiency of that process and so you yeah, the field as a whole is is pretty familiar with this word crispr now right? So crispr was a technology that was originally um, ah. Published in 2012 by Jennifer Doudna who’s a professor as well. University of California at Berkeley where I work and so Jennifer and I have our colleagues. We’ve published together and and shaqued you know, published this this ah terrific paper that ended up being the basis for for rewrite. Um, which was spun out of Berkeley with Chica as the Ceo. Ah so we were developing this genome editing technology and were in a discussion about a partnership a bd deal and as sometimes happens that bd deal ended up morphing into an m and a discussion.

David Schaffer: And this was with ah with intellia intelia is a is a larger public genome editing company and it it made sense for rewrite to talk to and tell you about m and a in that we had a ah the core of ah what I thought was fantastic technology for genome editing. But there are a couple of other pieces you need in order to to grow independently as a company we needed delivery because we had a genetic cargo to be able to fix a broken gene. We hadn’t worked on the delivery for it. Ah, and there’s this other. Delivery technology lipid nanoparticles which intalia had working very well especially for for 1 target organ the liver and in addition, you know at 4 d we built the clinical infrastructure. You know the regulatory gmp manufacturing and and clinops capability. That was going to be a big build that we had ahead of us at rewrite and tallia already had that because they they were already in the clinic. Um, at the time so they were interested though in early stage technologies to be able to improve their genome editing capability. So this ended up being really strong complementarity. Ah, between between their large company and our at that time you know 2 to 3 year spinout company and we’re able to come to to terms that everybody was happy with and so it really made sense to get acquired in that case and I’m thrilled that as intelia has mentioned in a couple of public communications.

David Schaffer: They’ve continued to diligently advance the technology forward and I’m looking forward to the day where they take it into the clinic.

Alejandro Cremades: And this is just one of a you know, many that you’ve done because I mean another one that you also started and and that ended up being getting acquired that was say ignite a immunotherapies and that was acquired by Pfizer so I guess what were you guys doing there. At ignite and and I mean now here we’re talking about the Pfizer and by the way for the people that are listening. You know just to close the gap on on rewrite you know it was acquired for 45000000 up front and then 155000000 in milestones but now moving to ignite you know. What were you guys doing there and and obviously Pfizer you know a massive company I mean how is perhaps different. You know the m and a process with a company like that.

David Schaffer: Yeah, that one is very different in the sense that Pfizer made the initial investment and there was you know the possibility that they would and ultimately be the acquirer of the company. Ah so you know we had ah you know it was fully an option to keep the company independent and continue to grow. Ah, but we were almost hoping that that Pfizer might become a long-term partner or potentially an acquirer. It was a cancer therapy company and cancer therapeutics take you know takes large amounts of time. Lots of clinical expertise and enormous amounts of capital. Ah, to be able to advance into the clinic and ultimately to get a regulatory approval. So in that case, you know having a a partner with tons of expertise and deep pockets like Pfizer was really an asset to to ignite immunotherapies. So the the technology behind the company is that I mentioned to you that we had been working with avgenetherapy and that became the basis for four d and we invented this new way of engineering viruses. Ah maybe I’ll I’ll take a second or 2 to talk about the technology. Ah so we all know from covid right? that viruses evolve in nature. And we had to keep taking you know vaccines say 1 step ahead of viral evolution. Usually that’s ah, that’s a bad process. You know enables viruses to continuously adapt. So can they can escape our immune systems etc we began to turn that on its head and actually use viral evolution as a good thing.

David Schaffer: So specifically, you know we’re using these viruses as delivery vehicles to carry dna medicine inside of a cell but they haven’t been prepared by evolution to be able to infect some really important cell types like a v I mentioned is a respiratory virus. You know it’s it’s not really great at infecting the brain or or the heart or the retina. So what we began to do is evolve aav but in the laboratory and artificially so we created a billion different versions of a with changes within ah the the structural proteins of the virus that mediate the delivery and then we perform a highthroughput selection. So that we can identify the 1 variant that excels at the brain or at the heart or at the liver etc and then this variant this new engineered variant often ends up being 10 or one hundred or a thousandfold better than the natural version of the virus at getting into that tissue and that then becomes our clinical candidate. We would advance into into a phase one trial so we did that for 4 d using this harmless virus called aab most of us have been infected with it. Never even noticed it because it’s it’s harmless. It’s very quiet doesn’t cause human disease. So with it igniterminunotherapies. We wanted to do the same thing. And engineer a virus but in this case, it was a very different virus. It was vaccinia and vaccinia is a virus that replicates and typically kills a cell. So why would you want to do that. Well if you could engineer a version of Vaccinia that replicated and selectively killed a cell inside of a tumor.

David Schaffer: This could be ah, an immunotherapy the basis of a therapeutic for ah for cancer. So we implemented for the first time the idea of evolving vaccinia or creating new versions of Vaccinia that would excel at being able to replicate within a tumor that became the basis of ah the. Lead technology and ah Pfizer acquired that so they could further develop it for for clinical application.

Alejandro Cremades: So then so then for this I mean obviously incredible Exit tool Now it sounds like you know you have a bunch of companies. You know that you’re operating in parallel ah you know spanning from C to like series a B and it sounds like you’re also. In the process of rolling out something New. So what? But can you tell us about this new company that they they’re probably going to be hearing about soon. But.

David Schaffer: Sure. Ah, so we have I have 5 companies right now that like you mentioned the the youngest is a pre-seed company and the the most senior is ah is a series b company series b was led by by morningside ah a company right now that we’re. Raising for is ah is a stem cell company. So the majority of companies that I’ve worked on have been gene delivery companies and this is ah a cell therapy company.

David Schaffer: And the idea or the difference between those 2 is that in the case of gene therapy you’re typically delivering a piece of Dna to be able to improve or rescue the function of a cell if it’s a situation where a disease is killed off a lot of a tissue killed off a lot of cells. then gene delivery isn’t going to do it. You actually need to rebuild the tissue. You need to deliver cells ah to repopulate and rebuild the tissue. So a stem cell is an incredibly valuable source of cells because a stem cell can divide in an immature state for a long time. And then he can coax it into differentiating or specializing into a particular cell type and then he can implant that cell into the body into a place where the tissue has been depleted due to a disease. So as an example by the time that somebody ends up with Parkinson’s disease they’ve typically lost somewhere around fifty to eighty percent of the cells within that region of the brain called the striatum so we need to rebuild that tissue and so we’ve been differentiating stem cells into the type of neuron that’s lost in parkinson’s disease and then you can implant. Cells into the brain and be able to repair the brain from the effects of parkinson’s so we’ve been working on a couple of disease targets like that such as ah, um, Parkinson’s disease epilepsy as well as type one diabetes and growing.

David Schaffer: Company building the team around this technology and at the same time pursuing both you know equity financing as well as ah, potentially Bd relationships to enable the company to further grow.

Alejandro Cremades: So obviously you know incredible um you know journey incredible experience that you’ve had over the past twelve years you know building scaling financing exiting companies. If I was to put you into a time machine and I bring you back in time and bring you back in time to that point where maybe in 2012 you were thinking about you know, starting the journey of being a founder and let’s say you have the opportunity of having a chat with that younger David and you’re able to give that younger David one piece of advice. Before launching a company. What will that be and why given what you know now.

David Schaffer: Yeah I’ll say first off that younger David was pretty clueless at the time about starting companies in that you know was a very very different world from what I was used to ah probably the advice I would give is you know it’s the same advice I would give to young professor David back in 9099 which is to spend more time talking with people and meeting with people and networking with people in that. Ah you know well I’m a fan of Warren Buffett and Warren Buffett has this saying that he likes to surround himself with people who are better than he is and then he naturally drifts in their direction. So I probably didn’t spend. As much time as I should talking to smart successful people out there and learning from them learning what their secrets are I you know, granted that as a ah professor in Berkeley I didn’t have access to the kind of network that I have now. Um, but I I would have been more proactive in reaching out and talking with people and and getting on their calendar and taking them out for coffee or a beer and learning from them because I think that you know as I mentioned ah none of my mistakes have been fatal. You know all 8 companies that I started ah are still well. The 2 that are acquired. Don’t exist but the other six do. But I think I could have saved myself or spared myself the fate of making a couple of key mistakes if I’d I’ve learned from other people and that’s really you know to come full circle what I’ve been trying to do with our incubator.

David Schaffer: Ah, it’s to spare my colleagues the fate of making some of the same mistakes that I did.

Alejandro Cremades: So David for the people that are listening that will love to reach out and say hi. What is the best way for them to do so.

David Schaffer: Sure I’m I’m easy to find on the internet. You know David Shaaffer Berkeley ah email address is schafferat berkeley.edu I am I respond to emails nonstop and love talking to new people and learning from them and. Hopefully sharing or thing or 2 that I may have learned that they that you know could benefit their future so more than happy to talk. Especially if you have a newco and would love to become part of a thriving ecosystem that we’ve been building here in our incubator called baker labs.

Alejandro Cremades: Amazing. Well hey David thank you so much for being on the deal maker show today. It has been an absolute honor to have you with us. Thanks.

David Schaffer: It’s been an honor to be here. You thank you so much. Alejandra.

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