Inside The Race To Reboot Human Cells - EP 60 Nabiha Saklayen

Once you're at— you've locked into this iPSC state, you have the potential to become any cell type in the body, like hundreds of different cell types. And over the past like 10, 15 years, these amazing scientists, you know, I have a Google alert, so I get all the iPSC papers that come out in real time. It's like exploding. Yeah. People are making cartilage, people are making cornea, people are making every type of neuron, spinal stuff, spinal stuff, retina, heart.

Welcome to the Core Memory Podcast. This is Ashlee Vance. Thank you as always for listening. We're going to be talking about one of my favorite subjects today. It's a biotech subject. It's, um, one of the most fascinating, interesting fields of science and tech in biology to me, which is, which is kind of like taking ourselves back to their stem cell-ish state, rejuvenating them, and then rejuvenating us, hopefully. And our guest is Nabiha Saklayem. She is the co-founder and CEO of Celino, which is based in Massachusetts, I assume Cambridge.

Yes, Cambridge, Kendall Square.

Kendall Square. That was a good bet. Good bet. Thank you so much for coming on the show.

Thank you for having me. I just loved hearing that you love this topic as much as I do. I do.

I, it's, I think we probably talk— we're going to be talking about things called IPSCs, and we do this probably more than any podcast, I think. But I am just convinced this is, this is like one of my favorite things to cover. So, so people need to learn about this stuff. And I try to keep the acronyms low, but you will need to know IPSCs, which is induced pluripotent stem cells. And we got all kinds of videos and stories about this stuff if you need to catch up. But yeah, so like a couple of my guests, I don't know in which order these podcasts will air, but people will be hearing that the JPMorgan conference was taking place in San Francisco this week and we were bombarded by biotech people. And so that's what brings you to town.

That's right. Yes. I've been coming to JPMorgan for many years and it was an exciting JPM conference this time.

What was, what was the buzziest stuff?

I think a lot of optimism. Last year was pretty dark and not very optimistic because biotech funding drying up. Yes, biotech funding crushed. You know, it's an interesting moment in time. What's happening on the AI front is undeniable. So a lot of venture capital, all venture capital went towards it. And now we're going to start to see some of those outcomes. I'm, you know, I'm reading all about all the potential IPOs this year. That's going to be very exciting.

Yeah.

But biotech was severely hurt by the withdrawal of capital because the timelines are longer, clinical trials are longer. And I think all the VCs sort of looked at their portfolios, the ones that invest both in tech and bio, and said, well, my returns on bio aren't looking so hot. Yeah. So Maybe we should pause on that. But January, I think coming in, you know, Lilly and NVIDIA announced this big collaboration. There's just a lot more enthusiasm about human health.

Yeah.

Because the way I see it, now that we're on our path towards AGI, and we can talk about when that's exactly gonna happen, but—

Do you know? If you know, you tell us.

I really don't, but I'm excited for it and I'm sort of preparing for what's next. Yeah. And that's going to be how do we have agency over our own health in a very personalized way. So it was very positive. People were happy, people were optimistic. So it's a good way to start the year.

Okay, well, that's good. Yeah, these things always go in waves. It's kind of funny. I mean, I mean, for me as an outsider to watch the ups and downs and it's— I always get a— I get a totally skewed perspective because I spent my entire life talking to startups and from my frame of view, it's like, oh, there's all, you know, it seems like things are going well. I keep running into more and more interesting biotech companies, but then I hear from everyone that it's, it's, it's hard out there. So yeah. What do you think? What is the best place? Like, should we, should we describe iPSCs to people first or should we start with Celino and what you guys do? I just want to get people a little bit of a grounding of where we're at.

Let's start with iPSCs.

Okay. Okay.

And you mentioned in your intro that it's It's an acronym that comes up a lot, and I've gone back and forth on this with my co-founder, like, okay, how do we address this? iPSCs, what is it? And I think our strategy is to lean into it. So iPSCs, induced pluripotent stem cells, amazing cell type. The core discovery around how to make these cells was from Dr. Shinya Yamanaka. He won the Nobel Prize.

Quite, quite quickly too.

Yes. Yes, he did. Because it's just incredible. This whole promise of being able to generate everybody's own stem cells was exciting. And what Shinya and his team, what they were able to accomplish is take an adult cell who's a skin cell and at current biological age, you know, I'm 36, so that would be my biological age. And then figure out 4 factors that—

Proteins.

Exactly. The Yamanaka factors now. OSKM, that when you introduce them to your adult cells, they reset the epigenetic age. And that's really exciting because you're getting to age zero.

Yeah.

And it's sort of the early stages of our life when we were being formed during embryogenesis.

Yeah. So he was taking skin cells off of a rat or a mouse. And like you said, I mean, this is like a probably a middle-aged rat. Mouse and it has all that gunk and things that kind of come with cells aging and hits them with these 4 proteins and it goes back to the stem cell state. Obviously, we for many years, stem cells controversial because you have to harvest them and things like that. And so this is kind of lab-made stem cells from your own body.

And I love that. And that distinction is really important. What's interesting about iPSCs, they don't exist naturally in our bodies. They're quite intense and chaotic and like can turn into every cell type in the body. Very powerful. So it is important to make them outside the body and maintain them, maintain quality, make sure they're safe. And that's different than any other stem cells we might have in our body. Like we do have stem cells in our body. They are at our current biological age. They do have the job of giving us support and reinforcements, making new mature cells. So that's all good. But as we're aging, those stem cells in our body are also aging. So anything— when you hear about stem cell clinics, etc., there are processes where they'll take these mesenchymal stem cells, take them out of the body, purify them, reintroduce them into a joint or a spine. And yeah, you do hear these stories of patients benefiting once in a while. But when you look at the large clinical trials that have run with those adult-stage stem cells, there's not enough convincing clinical outcome data.

Yeah.

And iPSCs completely changed that.

Yeah. And when— brief detour. Yes. In my journey with Brian Johnson, I've seen him get these, these adult stem cell injections, I think in the Bahamas, if I remember right. Yeah. So that, that's kind of a thing. But with these iPSCs, okay, so Yamanaka has this amazing discovery. Another scientist named Alex Ocampo, who's a great human being, he kind of starts to advance the field toward, you know, Yamanaka showed you could take it back to this, this blank slate. Ocampo began showing there might be longevity things to be had here if we, if we work with these cells there. This blank slate is, is amazing, but also tricky in some ways because you don't really want your cells to necessarily be a blank slate. You really want like a young liver cell or you want a young neuron or heart cell and And so we've spent this, this last decade plus looking at ways of, okay, we know how to reverse it, but now how do we kind of give it an identity and how do we not have that process spin out of control? Sometimes if this thing runs away, it becomes cancerous, it forms a tumor. And then we have this problem of we do this stuff outside of the body, like you're saying, it was like, how do you get it into the body and have it be controlled and go to the right place and do the right thing? And that's sort of been the mission, right, of the last decade of of quite a few companies. Is that fair?

I'm so impressed how much you know about this. Oh my gosh. Yes, it is spot on. Yes. So I mean, you know, once you're at, you've locked into this iPSC state, you have the potential to become any cell type in the body, like hundreds of different cell types. And over the past like 10, 15 years, these amazing scientists, you know, I have a Google alert, so I get all the iPSC papers that come out in real time. It's like exploding.

Yeah.

People are making cartilage, people are making cornea, people are making every type of neuron.

Spinal stuff.

Spinal stuff, retina, heart, you name it, every part of the body.

Yeah.

And it's really exciting because now we have robust biology, small molecule protocols or transcription factor-based where you can program your iPSC state to get to your specialized cell state. I think that's like a word I've been thinking about a lot. It's specialized.

Yeah.

And then you want to make sure it's safe. That's— that final cell type is important because you want to check it. You want to make sure there are no iPSCs in that population. And there's a bunch of tests and quality control metrics that are important for— from a regulatory standpoint.

So you want— if you're making liver cells, you want to make sure that you don't still have some of the more stem cell-like ones because that— I guess those might be the ones that you don't know which direction they're going to go. And it could be potentially.

That's exactly right. I do think this is what's interesting. There are about 10, 15 clinical trials running all over the world for Parkinson's where you're making the iPSCs and then you're programming forward to a dopaminergic neuron. But each program is— the cells that are being transplanted are at a different stage of specialization. Some are more progenitor, some are more mature, some are mixed. So we're already getting into the nuance of like, what is the right stage of cell maturity? Because if it's too mature and you're transplanting those cells into the brain, they might not engraft and be able to do their job. So, but hey, it's happening. It's exciting. So the biology is super, super robust. And now we can start thinking about scale and the manufacturability, all of the things that are important for access. But the initial data, I do want to double-click on Parkinson's. Yeah, well, astonishing.

So, okay, let me— I want to talk about Celino, because all these things that you outlined, um, you guys are helping kind of like the industry along into to being able to manufacture these things better, smarter, faster. And so I want to, I want to talk about all that. You brought up Parkinson's because I did want to ask you right before we jump in on this next avenue is, yeah, I wanted to give people a state of play. You mentioned all these startups. I see it too, um, where It's kind of funny because Yamanaka comes up with this discovery. It goes— it's like everyone immediately gets this Nobel Prize, I think 4 or 6 years after the discovery. So really fast. So people see this is a massive thing. But then there's, there's like a little bit of a lull about people like really acting on it. And then, and then now there's a ton of startups. It's very hard for me to tell because I'll see things. Parkinson's. We have spinal cells that we've made. Has anyone actually made a therapy yet that people are getting, or is all of this stuff like just heading into clinical trials?

Yeah, I mean, wow, what a great time to have this conversation. So Shinya Yamanaka, discovery happened 2006, Nobel Prize 2012. Yeah.

Okay.

And right now we're entering 2026 and the first conditional marketing approvals for an iPSC-derived therapy are about to happen in Japan.

Okay.

For Parkinson's.

For Parkinson's.

And heart disease.

And you mentioned it, so it's a neuro— you're getting a—

Neurotransplant.

One type of neuron.

That's correct.

Okay. That is replacing damaged—

Dopaminergic neurons.

Okay.

These are the neurons in our brain that secrete dopamine, and Parkinson's patients lose these cells.

Okay.

So if you give them new cells, you're able to reverse the symptoms of Parkinson's.

And that's Japan this year?

Yeah.

Like a clinical trial, or that's—

Yeah, Japan has a very interesting framework and then we can definitely talk about what's happening in the US. Also amazing. Actually, the whole world is moving fast on Parkinson's, so it's great. But Japan has a very unique structure where when you show safety in your phase 1, which this program has, came out of Jun Takahashi's work and now is being run by, led by, commercialized by Sumitomo. Once you've shown safety, then you can get a, you can go to their regulatory body for a conditional marketing approval. So It's available for commercial use, which is very exciting, but it also is acting as the pivotal trial.

Okay.

So safe, good to go. The initial data looked really promising. I mean, one thing I want to mention, all of our degenerative diseases where our cells are dying, they're being lost. Every person is different. So I do think like it's hard to say, okay, does this work or not? Everybody might need a different dose, different number of cells, different timing. But I do think in the next 5 years we're going to see a lot of data coming out. So that's very exciting. In the US, there's an amazing program for pluripotent Parkinson's replacement out of BlueRock Therapeutics. It's a subsidiary of Bayer Pharma. Okay. That was very exciting too, because they showed some incredible reversal of Parkinson's symptoms in their phase 1, and now it's getting ready for a pivotal trial. Over 100 patients that are going to be part of this. But energy and momentum is high. And you mentioned sort of how do you get these cells into the brain? What happens? The innovation on that front has been remarkable. Like those, those bottlenecks. And when, when I think about why it's taken this much time for us to start talking about, wow, things are happening, pivotal approvals, because all of those building blocks had to be brought together.

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It's an injection, multiple injections, actually. So it's really interesting inside the brain.

Into the brain?

Yes. Yes.

And okay, I'm trying to think if you— how do you get through the skull? Do they have to—

They do drill a little hole and then they inject it and everybody has a different type of syringe. A different sort of system where they're using imaging, usually MRI-based insertions, but some are trying to move into OCT. So there's a ton of innovation also happening on how to scale the surgery, what type of hospital delivery systems are necessary to be able to do this at point of care. We have a fantastic collaboration with Mass General Hospital. It's great. They're down the street from us, so it makes it easy to sort of You know, we're building the platform right in Kendall Square and they're across the river in Boston. It's been amazing because they have so far made all of their cells by hand.

Okay.

Personalized. Start with patient cells, turn them into iPSCs manually, then make the dopaminergic neurons. And they had the N-of-1 study. They complete— they published that in 2020. It was very revolutionary because it was entirely personalized. Then the patient wouldn't have to undergo immunosuppression. So now we're coming in and we're taking their very complex manufacturing process. The iPSC generation is very, very tedious. Yeah. And we're automating it. And it's exciting because we want to show that there's flexibility in where these cells are made. And if you build tech stacks that can be deployed even at the point of care, then there's a lot of flexibility in how we could replicate this type of model for delivery where surgery, manufacturing, patient care all happening at the same time. And then how do you scale that across the country?

Okay.

So yeah, so there's just so much happening right now, you know, and I also feel a very collaborative spirit across all the countries. Japanese, the Americans, the Chinese are working on this too. European companies are working on it because in the next 5 years there will be multiple commercial options available for patients with Parkinson's. And patients can choose, do they want something off the shelf because it's time sensitive and they're okay with immunosuppression, or they want something very personalized, then it's going to take a different manufacturing approach.

And what, like, what have we seen with these patients, the Parkinson's patients, when the new cells go in, do they just replace the damaged older cells or is everything kind of together?

Yes.

And then how dramatic without giving people false hope or anything like that, 'cause it's, we're still in this trial phase. But yeah, like, is this total, you talked about it for a second, total reversal or is it just kind of helping you out a little bit in your condition?

Yeah, great question. For Parkinson's, it's interesting. The neurons seem to be gone. And so it's less of a replacing those damaged cells. They've gone and there are different, scientific reasons for that. We still don't fully know. We know some, we're going to find out more. But it is introducing new cells that can secrete dopamine and help with what's going on in the brain and allow us to allow these patients to regain better functionality in their bodies. So the data has been quite widespread, and I think you're right to ask that question like, okay, what's real, what's not? There seems to be a sweet spot on like the number of cells that are being put in. Where are they being put in? How many are alive when they're gonna be put in? They're not all answered, but there are several patients that have seen significant improvements in their tremors, for example, which I think is very exciting. Yeah. That's like very, that's a big pain point for Parkinson's patients. So you, they get more mobility, more independence. And the BlueRock trial I find very compelling because now they've already been tracking their patients several years out. So it's the longest duration studies that we have in, in recent years. It's up to 2 or 3 years now, which is exciting. So you see those benefits sustained, but it is in a specific cohort of patients that receive the highest dose.

Okay.

So I think with the pivotal, there's going to be more information on how this is going to work for a range of different patients. I'm very optimistic, though. I do think— I mean, you know, the FDA wouldn't give them a green light if things weren't looking very promising to do that. I think, you know, I think that's powerful about how advanced modalities are regulated in the United States. Like, it's a very high bar. So very excited, rooting for this team to push that through.

Okay. Okay. And now I want to I mean, we're hitting on a couple of bits and pieces here, but kind of what you guys work on, I'll take a stab. You can fix it. This is just from what I read going across.

Sounds great.

The internet. But, you know, if you're going to make iPSCs, obviously you have this choice of what cells you want to take. We talked about skin cells. It's relatively easy to get those. It looks like— okay, so broadly, you got to pick what kind of cells you're going to make and then you have to put some process around this to actually make the IPSCs, and we already talked about you want those to be good on the other side and, and to have some control over this. And then obviously this is still relatively early days of this tech in some ways. So you have, you know, just got lots of people have to make their own IPSCs and, and, you know, it's an industry being born. And so there's not, there's not kind of this, this ground truth or somebody supplying this kind of stuff in a lot of cases. So it's, expensive, time-consuming, and you want it done well. And so it looked like you guys take blood samples and so those are the cells that you're getting to make the iPSCs. And then you are a brilliant engineer by the looks of it, by background. I'm sure we can get into this, but what I saw you guys talking about was kind of along the lines of trying to mass manufacture these things for other companies. And then having— you have this laser system that's kind of like zapping out irregularities or I guess iPSCs that are still in as you're trying to create these other cells. And that seemed like one of the biggest breakthroughs that you had was this process of making these in a consistent way. Am I— is this— and so you want to be a supplier of iPSCs, is that—

We want to be a supplier of iPSCs to the whole world.

Okay.

Yes, totally. And It's really cool to know that my PhD work is useful.

That's the origin. So you went to Emory and then you went to Harvard for master's and PhD. Yeah, that's right. And not in biotech.

Oh no, definitely not. I was not a fan of biology in high school and I went to high school in Sri Lanka and my biology teachers were so upset that I didn't do biology the last 3 years. It was too much memorization for me. And I loved physics. So physics, math, and thought I would do aerospace. And my— I think my mom convinced me, like, why don't you do physics? You could always go do aerospace after. It seems broader. And yeah, so pursued that and got to Emory. I'm an immigrant to this country and like very happy to be here because the pace of innovation that happens is Unbelievable.

Yeah.

So my undergrad was very just, you know, setting the foundations, like learning how to do research in a lab. An amazing advisor, Eric Weeks. We were doing, we were studying squishy physics and it was interesting. I learned a ton, but I couldn't figure out how this would translate and like, what do I do in my PhD? And at that point I was very focused on I wanna be a physicist. That's the lens through which I wanted to see the world. Very universal first principles. So when I got to, when I got to applying to graduate schools, I didn't quite know exactly where I wanted to go. And for my generation, you know, physics is an old discipline. So it's like, okay, particle physics, string theory, biophysics, and quantum were the four options. Yeah. And bio seemed interesting at that time. It was kind of like there was, there were things happening that were, and we were starting to put more structured systems in place for biology. So I got to Harvard full of imposter syndrome, but started poking around all the biophysics groups and, you know, learned about the connectome, learned about what's happening in soft robotics, and then ended up picking a semiconductor ultrafast optics group that was dabbling in biology. There was some biology happening, but not really. But what I loved about it, it was new skill sets that I'd never encountered. So I was doing a lot of simulations and then doing a lot of fab in the cleanroom, e-beam lithography, photolithography, and then moved into using those nanostructures to apply lasers to them and then study those properties. And the whole secret sauce is being able to make very precise bubbles with a pulse laser on top of a nano-patterned surface.

Yeah, I wanted to ask you about this. Okay, so you mentioned, I mean, this is your PhD work.

Yeah, this is—

becomes the foundation for this company. We talked about this laser process a bit, but I mean, okay, so this is going to be the secret sauce is that these techniques you developed for your PhD happen to be really great for this process of, of zap, of controlling this iPSC creation and zapping out using a laser and these bubbles to zap out unwanted cells.

That's exactly right. That was all very serendipitous. So the last year of my PhD, I wanted to spend some time with biologists. I thought it would be a nice chapter for my thesis that I did work with some biologists, and there's some amazing biologists all over campus. So I emailed a bunch of them expecting that nobody would respond, but I got some amazing responses. Like George Church responded, Derek Rossi, and I was like, and they kept saying, this is really cool. This is single-cell precision. We don't have that in biology right now. Everything is passaging-based and pipetting-based. Nothing's changed since the 1900s. You can do this with single cell. That's cool. But I did have a life-changing visit to the Harvard Stem Cell Institute as part of that quest.

Okay.

I go there and meet Laurent. She's— she's the lead scientist there, and she's one of the best iPSC scientists in the world at making iPSCs by hand. So she was showing me how they do it. They watch your iPSCs emerge over many weeks and days with their eyes, decide what's good and bad with their very—

In a dish?

Yeah, in a dish, in a— in a lab and you do the same process inside cleanrooms. That's the manual way to do it, but it's multiple months of nurturing them and then using your best judgment to decide what's good or bad. And then at the end you do your tests, all your genetic testing and whatever else you need to do, and then you see if that worked or not. And the yield is, is hard.

I heard about this. The yields are terrible.

It's very— and reprogramming is like low efficiency as it is. So she showed me all this and she was like, yeah, these, these cell types are powerful. We can make them from adult cells and they can become anything. It just sounded like magic to me.

Yeah.

But she convinced me. She was like, you need to apply your tech to iPSCs.

Got it.

And she was very convinced. Um, that helped a lot in terms of my co-founder and I, we were like, okay, she's the expert. She's very convinced that we should try it.

She's in the office. What, what was her name again?

Laurent. Oh, my, my co-founder? Marina. Marina. Yeah.

And, okay. And, and she's a—

Applied physicist.

Okay. We met at Harvard.

Okay. And kind of got sucked into the startup world.

Okay.

And then the first experiments that we were doing with iPSCs, again, we were able to very precisely manage cells with laser bubbles. And can we talk—

what's a laser bubble?

Yeah.

So I watched the video on the website and I could see this laser zapping bits of the cell out.

Yes.

And I was reading about the bubbles, but I didn't understand the bubbles.

Yeah. So actually, when you, when you take an ultrafast laser and you focus it super tightly, maybe 100 nanometers in liquid, you will generate bubbles, cavitation bubbles. That doesn't scale very well because the focusing is hard in like a 3-dimensional or 2-dimensional space. So that was where my field was. And then myself and then like my generation of scientists that were like this, maybe 10 of us in the world that were doing this, like, okay, what if we, instead of trying to focus the laser directly onto cells, what if you had a surface that you could grow the cells on and the surface becomes where you focus the light and you generate bubbles there? So that's what— that's the core tech at Celino. We make these surfaces that can absorb some of the laser light and then generate a very localized bubble. And it's nice because it's physical. So then the bubble can remove cells very in a focused way.

Is the nature of the surface top secret?

It— yeah, it kind of is. But, you know, we have like— we have— we have like, I think, 10 issued patents. So there's definitely like stuff out there.

Figure it out a little bit.

Yeah, we definitely like It's interesting. It's really interesting to bring those semiconductor principles all the way in through, okay, now we have the most, you know, high-throughput imaging, very easy with the surface, being able to generate lots of bubbles in a targeted manner, having this closed-loop framework of AI being able to detect cells and then remove them with the bubble. And we use it for two different things. This is our optical bioprocess. Actually, it's really cool. We received just last year the Advanced Manufacturing Technology designation from the FDA. For this manufacturing process as it applies to iPSCs. Okay. And it's cool because you can do very high-quality cell management with some humans in the loop, but it's running autonomously.

Hello, geniuses. Let me tell you about E1 Ventures. They are a venture capital firm in Silicon Valley, a longtime supporter of this podcast, and a longtime supporter of big, fantastic, world-changing ideas. If you have such an idea, hit up E1 Ventures or send me a note and I'll put you in touch with E1 Ventures. It's, it's quite a, quite a deal for listening to this podcast. Thank you again, as always, to E1 Ventures for their support. Have you had to build your own machine? Yes. Okay. So you've, you've built We build a lot of machines, kind of substrate or whatever this is.

Yes, it's a film. Nano film.

A film. Yeah. Okay. So I'm picturing— I mean, so there's some kind of surface with this film. You've got all this optical gear, these cameras watching what's going on overhead. And then, and then what this machine is, is, is, is it mixing all the things you need to make the iPSCs? It's just— is this all— what does this look like? Is it a room or is it a, you know, like lab bench sized type thing?

Great question. It is right now kind of a lab bench size. We have a few different formats.

Okay.

So the first work cells we built were larger, they were for high-throughput experimentation to get the process set up. And we were using well plates to run the optical bioprocess and see, could we grow and manage iPSCs in the same container for a long period of time? That's not normal in biology. Biology always moves cells around. So once we proved that, then we were like, okay, now we want it to be closed because the next expenses are clean rooms and we want it to be sterile and clinical-grade production. So now the optical bioprocess is has entered a closed cassette. So that's our Nebula system and it's being built for clinical-grade manufacturing. It's pretty exciting. It's not that big. It's like a slightly large refrigerator size. If you think about it.

It's like if I bought an Illumina sequencer. That's exactly. It's like—

It's about that size.

Fridge size. That's right. So just like a gene sequencer is helping you do all this process or what is it like 10x Genomics is doing like some single-cell sequencing for you and you have this in your office, you guys would have this like IPSC maker.

Exactly. So we have these IPSC makers, we call it Nebula, and yeah, and we just want to have many of them make lots of IPSCs. And it, you know, capacity-wise, we're playing around with it right now. The Nebulas that we have running have capacity for about 60 parallel cassettes each.

Okay.

And but we can— we want to plug and play and have that. It's exciting because, you know, have us building these machines, it's It's a little bit like because this industry is so new, we were building so many foundations. So the way I think about it, like the optical lithography steppers were very important in ASML. They do a great job of them. They build these machines and TSMC runs the fab. Where we're ending up is we're also going to be running the fab because there's nobody else that is running fabs yet. But it's, it's, it's Yeah, it's, it's pretty awesome. My team has had some incredible breakthroughs. I do wanna comment on this, like everything we do is so multidisciplinary. Like most of our team are engineers from all different flavors and backgrounds. We have fluidics engineers from oil and gas, we have like folks from self-driving cars, and we have bioengineers, we have stem cell scientists, you have a bunch of physicists building optical systems. So it's tackling this complex manufacturing process from every angle we could possibly think of.

So I presume there's some sort of computer vision AI tied to all these cameras looking at what's happening with the cell and picking where to zap and all that.

That's right. That, that started for us in, I would say, like 2019. And that's when we, right after we got our seed investment from Vinod Khosla. And it was a good time because a lot of these label-free imaging algorithms were already developed from Allen Institute and Google, and we just them for iPSCs.

And you guys are about 6 years old as a company.

We're even older.

Okay.

Because we incorporated in 2017 and then the first 3 years it was very tiny team. We were all doing everything. We're just trying to see if any of this made sense. So yeah, 2017. So it's going to be 9 years.

All right. I should know the answer to this because otherwise I'm giving you too good of an opportunity to say there is no competition. But are there other startups trying to mass produce iPSCs?

There are other groups trying to automate the bits and pieces. There are companies building instruments for the clone picking, others that are trying to expand to large volumes. You know, what we, what we're focused on is starting from adult cells and each for each person being able to get to a very high quality bankable batch of iPSCs. And that's like high precision needs just a lot of focus. I would say what's different about my team is just We are so multidisciplinary. It's rare to come by teams that are this multidisciplinary.

Yeah.

That's been really exciting and we kind of lean into more of that. Yeah. And you know, the other thing I'll say is I'm very collaborative. So I'm like, hey, you're building tissue foundries. Awesome. Let's do it together. Actually, we just announced a collaboration with Polyphrog.

I saw that. We broke the story on Polyphrog.

Yes. I love that team. And actually like—

So, and they're making organoids. They're trying to grow organoids.

They're making tissue. So we're gonna make the personalized stem cells and they're going to make tissues. I think it's very, you know, but if people look at it from the outside, we get a lot of questions. You're using the same language, you're talking about the same things, but we have to fit those pieces together. We need more of that in bio because a lot of times the bio strategy is own everything in-house, do it end to end. But the next wave of technology innovation is going to be so different that everybody has to start specializing and then putting those pieces together.

Yeah, it reminds me so much of the rocket industry in some ways. I mean, it's so funny because everyone for a while wanted to make a rocket startup and then you want to make your own engine because the engine's like the part where you like flex. And, and well, first of all, people want to make their own engine. It's like it's, it's just this desire. If you're in the rocket business, it's a bit silly. And then, and then it's a little bit of the way how you're different from the other guys because the rest is just like a tin can on top of this this engine. But I saw it time and time again. I mean, it's ridiculous. You have 30 companies all spending hundreds of millions of dollars each. Every single— almost all of them fail because the engine's really hard to build. It would be better in a lot of ways if just somebody had the perfected engine that they were selling and then everybody could focus on the other stuff. And, you know, I just— I guess I see this equivalent in biotech a lot where everybody's having to make all these basic bits and pieces But what they really want to be doing is the science at the end.

That's right.

But you're spending all your money and time.

So we're very focused on that iPSC piece. There will be some like 2D differentiations that we're going to bring into the platform that are the more robust the biology, the more excited we're to bring it onto the platform and start scaling it. Yeah, but it's, it's a good time. I think there's like a new wave of friendships forming.

Yeah, I saw on your website, I mean, it looked like you maybe can't comment on this because of the language on the website, but, you know, I saw you guys kind of list trials that other people are doing. And so my assumption was you're working on these projects. But if I remember right, there was one around retinal cells. There were a couple around Parkinson's, and then there was one around heart tissue, I think. So, so these are, these are— we mentioned one of these already, but these are kind of like the front runners of spaces that people are exploring with possibly with your technology.

That's right. Yes. And some we've announced and some we're going to announce. The ones we've shared, we've shared our collaboration on Parkinson's with Mass General. We love that one as being a really nice framework for regulatory in the United States and being able to copy paste that to any future programs. Then we have a peripheral artery disease collaboration with a clinical stage company that's South Korea-US based. It's all autologous, by the way, personalized, which is something we actually focus on.

Oh, actually, let's talk about that for a second.

Yeah, yeah, yeah.

Please.

Yeah.

Because I do see you guys emphasize that. I mean, and you talked about before, like if you, if you get an organ, obviously you're always worried that the immune system's going to reject it. When I was reading, you guys were emphasizing like, hey, we're taking the blood straight from you and we're making your iPSCs. And I guess in my head I always pictured that You're rebooting to a stage where— and I'm not a biologist— I was like, oh, you probably plucked out anything that matters for that particular individual. But like, so is it the case here that you actually want your own iPSCs if you can get them because your body's going to be happier about that?

That is very correct.

Okay.

It's interesting. I think that was the original vision around iPSCs, like everybody getting their own high-quality blank slate stem cells that you can turn into anything you want., but it's been hard to make them consistently across human beings. Actually, even within an individual's iPS lines, there's always variability. So you actually have to pick like very carefully which one's a good one. So yeah, we, my co-founder and I, we talked about this a lot when we decided to go hard at this. And we really felt that creating a way to make a high-quality iPSC reserve that could be used for therapies, could become a source for future applications was very compelling to us because I do feel that regenerative health is the category I'm thinking about a lot. Like, how do we build that? We want to have iPSCs ready to go, and then everybody will need a custom stack of applications, whether it's cellular twins or it's actually replacements of cells, tissues, and organs, or whatever it might be. It has to be based on our own biology. We're very different. And one of the challenges with using donor-derived replacements is immunosuppression, which doesn't always work depending on patients. So some of the first, a lot of the first programs are actually off the shelf with immunosuppression. So that's part of the challenge that I think will have to be addressed. But now it's exciting because everybody is thinking, okay, let's, you know, we're building confidence. These off-the-shelf versions are starting to show clinical promise. Let's go even further. Because if it is a patient's own cells, the body will identify those cells as, as their own, as, you know, you are me, I am you. That's great. We're matched and the immune system won't attack them. So the expected outcome is you'll have clinical benefits that last longer. It's better and longer.

All right. I'm going to Debbie Downer on us for one second. I mean, you know, we've, we've talked about all the joyous potential of all this. I think there's a couple of things I wanted to go over. I mean, one is you've already talked about the yields, which I know. So you're working on. But this is— this has just been a major limiting factor in this whole field, not only making the iPSCs, but then having enough of them do what they're supposed to do. Is this like solved in the sense of if we can make enough, that helps with the secondary problem because you have more good things doing their job? Or is this still like an unknown that even if we can make enough of the perfect iPSCs, that that it'll actually do its thing?

Yeah, great question. We focus really hard on making that first— picking that first high-quality clone and making sure it's the best clone that you can possibly—

What makes a good clone? Like you were saying that, like, people even just with their eyes could tell it was a bad— I can see why.

Shape, circularity, density, how they're growing over time. Growth rate is important. And then of course, like you look at karyotype, you look at sequencing data. Sterility, all sorts of— there's like a list of 10.

You just want a really pretty, healthy cell.

Exactly. And then also make sure that when you look at kind of the genetic level, that they're good and they're good and they're stable and you don't have any big errors. So there's two components to it. So we take all of that data. There's the visual piece, there's the in-process characterization, and then there's the end QC where the FDA has very high expectations that you've got to pass these QC and then you can use those IPSCs to become your therapeutic cell. And then you also test your therapeutic cells with like a bunch of testing too. So it's actually well established. It is a high bar, but everybody is rising to the occasion to meet that. So once you have a good iPSC, I do feel great about all the technology companies that are working on expanding to like lots of cells. So, and, you know, they're very proliferative, so you can freeze them, you can thaw them, you can expand them. So that's nice. Been a ton of progress on that. And then turning them into your desired cell and tissue is more complicated. But we see great protocols in the neuro space. We see good heart cells coming out. Liver is hard. Liver is a hard cell type. Beta cells, islets, pancreas are hard. So those are going to take more, you know, progress. I'll say this, you know, in terms of numbers, I'm really focused on scale and like COGS. I just have to be, otherwise it's not going to be scalable.

Yeah.

So we are on a— we're right now on track. So when we started the company, a manual iPSC generation process in a high-grade cleanroom for a therapeutic grade, anywhere between 1 to 3 million. That's what you would be quoted for. Just making iPSCs.

But like for one person's therapy? One person.

Just one person's therapy. And we have, we have this, we're trying to bend this cost curve and we have a target of getting it to about $25,000 by 2030.

Okay.

So we're, we're on that, we're on that slope.

Treadmill's a lot.

Yeah, it ends up being that way when you've been doing it long enough. Yeah. But we picked that as like a target cost because that's when like if IPSCs are $25,000 and your differentiation is gonna be costs $10,000, $20,000, end to end, you're at a pretty reasonable place. So then there's flexibility on pricing. And right now, I do think these are, these are being seen as truly reversing curative treatment. So there's a lot of discussion on how should they be priced because, you know, they could anyway.

So the pharma company's worst nightmare, you get cured.

So we have been pushing ourselves and we're on track And, you know, we are backed now, but we have a government contract with ARPA-H. Yeah. So that's actually the thing we're tracking together.

Yeah.

Like, how do we go down that slope?

Okay.

It's very exciting.

Okay. And here's my other Debbie Downer question in a way. I mean, and it's funny because there's tons of IPSE startups. We listed off a whole bunch of stuff, all this interesting research. You've got NewLimit, which is a company backed by Bryan Armstrong and other VCs. So lots of money behind NewLimit. Retro's done some of this. It's backed by Sam Altman. I think they're raising funding from others. Altos Labs, very famously, Jeff Bezos, I think Yuri Milner are said to be the big investors there. They were hoovering up all kinds of iPSC whizzes and they've been secretive, but I think— assume they're working on something there. So there's money in this. Sometimes I cover so much longevity tech, you know, and then I just— it's funny because like then some of the people I trust best in that field are really kind of down on iPSCs and they just think they're very limited and that it's just not— it's going to be too hard. There's this whole teratoma issue with them running, you know, running amok in this process. And, and we've seen people try to come with therapies. Look, it's early days in the field, so I, I don't get too judgmental, but it's like people have had trouble making it work like they, they thought they would. And then, then people seem to think— I don't know, sometimes it's like it makes all the sense in the world to me that if you're if your liver— well, obviously if you have— you've lost sight in your eye because of this retinal degeneration, fix that. But I think the broader claim for some of my longevity friends is like, this is not a system-wide repair. You're kind of doing these one-off— it's not— it's not reversing longevity in the way they want, which is— which is like whole body and really going back. So anyway, so there's a little— I feel skepticism. I feel like there's been so much excitement because you see the potential of this and then people are skeptical of like, is this actually ever going to work?

Totally.

It's a very long-winded question.

I feel you. I feel you. And I've been spending time with, with, with a lot of folks even this week talking about what's the future and, you know, people who really want to live forever, you know, so they're very deeply like they care about what's happening. Yeah, I, I've seen in the past couple of years there's like two pathways that are emerging related to Yamanaka factors. One is what's happening outside the body, and that's going to serve tissue replacements, new cells, new organs, new tissues that will be injected back into the body. And then the other part is like partial reprogramming. What's going to happen in vivo? New Limit is a great example. They're a great team of how do we figure out what could we do in our body to rejuvenate? And for me, I think both will be necessary. I think they'll both be necessary because there's fundamentally, I, there's a, there's a biological mismatch that I'm feeling right now where, you know, our bodies, you know, evolution, the way evolution built human bodies, mostly focused on stay healthy, reproduce, raise your kids, and then your body doesn't need to be prime time.

Done what you're supposed to do.

Yeah. You know, I hate to put it that way, but that's, that was the thinking or, you know, not thinking. I guess that's just how it evolved.

And it happens pretty early, you know.

But the, the reality is we've already— we're past that 40-year lifespan. Like, we're already— people are living to 60s, 70s, 80s, 100, 100 years. Um, but yeah, our bodies are made for something different.

You're just kind of training to be 18, you know.

Exactly. And, uh, just our body's not ready for this 80-year, 100-year, 120-year lifespan. Um, now I've been thinking about this a lot, and I, I I think it'll come down to the specific organs. So liver, very regenerative. So it's just replacing itself. You can rejuvenate it. And I think that's a great approach. The gut, very regenerative. The brain and heart, I think, is where the buck's gonna stop.

Yeah, neurons don't really regenerate.

They don't. And most heart cells don't either. So they do have an expiration date. And there's some— I was reading some theoretical papers written by physicists about looking at kind of the lifespan of these organs and like, yeah, we, we basically tap out with the brain and heart. So that's gonna be interesting because they're not dividing. So you're accumulating somatic mutations, you're gonna have an expiration date. So I'm, if I had to speculate, those are the two organs that would have to be replaced.

Yeah.

I just don't know how we would, but you know, I, I believe in Meaning iPSCs might not work there? I think they would work.

You think that those would be the most—

Well, those are ones where making cells, tissue replacements, or the entire organ outside the body and having to replace it because partial reprogramming—

I see. I'm sorry. So yeah, you're doing the whole organ, right?

I think so. Yeah, but that's my theory right now. But the other organs I think are very open to rejuvenation, like skin and everything else. Yeah.

Yeah.

Okay. And okay, so, so some of the sensory too, like retina. And hearing also could be in that category. But we'll see. You know, I don't, I don't, I want both because it'll depend on the application. I just don't think there's gonna be a one-size-fits-all solution. There's not gonna be a magical solution that fixes it in the near term.

Yeah.

But maybe in 200 years there could be something.

Yeah.

That's amazing.

That's okay. This is all fascinating. All right. You mentioned earlier that you went to high school, I think, in Sri Lanka, but you told me before that you grew up in— you were born in Germany?

Yeah, it hopped all over the world. No, actually, I was born in Saudi Arabia.

Okay.

My parents are from Bangladesh.

Okay.

My dad was working in the Foreign Service. Went there till I was about 5, then a year in Bangladesh, then Germany for like until I was 13, another year in Bangladesh, then Sri Lanka for high school.

All because your father was doing this, the Foreign Service?

Yes.

Yeah.

Yeah.

And then when you came to the US, you came on your own?

Yeah, I came on my own. Yeah, I was— yeah, my mom was like— my mom has this— she's incredible. She's the reason I am who I am. My number one champion. But I remember in high school, I was very— I'm an only child and very attached to her. So I was like, oh, like, I don't know where— how far should I go? Like, And I went to a British school, so the UK made a lot of sense. It was easier to go there. And she looked at me, she's like, you're gonna go wherever in the world you need to go to get the best education. So yes, I remember my first trip to the US was senior in high school. I got on a flight, came to Emory for my scholar's interview, and that was it. Yeah.

And then, okay, and then where do your parents live now?

My mom is in— she's in Cambridge now. She just moved there. And my dad's in Bangladesh. Okay.

Yeah. Okay.

So, yeah.

And you guys, so you've been at this, you said, I think since 2017.

Yeah.

And I mean, it's hard, right? I mean, you're doing hard tech, you're doing deep tech. You already talked about some of the— you've probably already experienced a few ups and downs in the biotech investing. Yeah. So this feels like it's been a journey for— it must be hard, right? I mean, to kind of keep people excited over it.

It's freaking hard.

Yeah.

It is freaking hard and rewarding and hard and hard and hard. It's a lot of like hitting your, banging your head against the wall to like make something work. And the way I talk to my team is like, I always want to see them pushing themselves to fail because you want to be at the cusp of like design experiments where it's really hard and you're not like, if you got it right in the first try, it most probably wasn't ambitious enough. And they hate that because there's, you know, they wanna design something they feel that'll work. But I'm like, listen, just push yourself and it should work the 5th time.

Yeah.

And that happened this year where they got something to work on the 5th time. I was like, that's, that's the right level of ambition. And yeah, um, in terms of the stuff is hard, um, I do think I have an unusually high level of resilience, which is something I think a lot of investors look for and people look for in founders. Having traveled so much as a kid. Like, I'm very adaptable. Yeah, I'm very able to move between different cultures and languages. So that's great. But high school was kind of an intense time for me because we moved there in 2004. That was the year the big tsunami happened.

Yeah.

And Sri Lanka went from being in a ceasefire in the civil war to like going full-blown out civil war. So it's like a 14— I think I was 15 at the time— year old. It's very jarring.

Yeah.

To have to go to school, live a normal life, but there's security checkpoints everywhere. It's an intense— it was an intense war. It's a suicide bombing-based war. So yeah, we, we had this mantra of making every day count with my mom. She's like, let's make every day count. And, you know, when you're in the Foreign Service, you don't really— you usually don't get to leave. You stay. And that was the time where academics— I found some, you know, I got interested in physics and just focused. I needed a focal point because everything was so chaotic and saw some deaths, like my favorite school librarian. She died in one of the attacks. My chemistry teacher was severely wounded. Like, he's the reason I ended up doing so well in chemistry globally at that time. So focused on academics. Turns out it, you know, if I focused, I could, I was very scholarly. So I got great grades and won all these academic things. And that became sort of my motivation to just push myself and see what else I could do and grow and just be curious, pursue my curiosities. But yeah, that, those teenage years were hugely transformative. Because I don't, I don't take anything for granted. And I'm always trying to make the most of the opportunity I have. I'm so privileged. I'm so privileged. Like, my, my parents come from a, are from a country of like 170 million people and, you know, like different opportunities for women. And I get to do all of these things. So that's been a big driving force. And, you know, startups are like surfing or being like very choppy waters. There are highs and lows. And I'm always like trying to be the most optimistic but also grow. Like, there's a lot of self-reflection. What can I do better? Where can I grow? And I think that's the reason I get to do this for this long.

Yeah. And when you were talking about doing well in chemistry and it just in general, I mean, were you— you were doing like contests in Sri Lanka and things like that, or were you doing like international sci— I don't know.

Yeah, great question. A little bit of both, I guess. So So the school was a British school, so we did all the exams.

All the A-levels.

A-levels, exactly. So I had, you know, I was top 10 in the world for chemistry. I had a perfect score for math. And I did, this is a fun fact, I did win the Commonwealth essay competition.

Okay.

Which was really interesting.

Like not a science paper or something?

No. Yeah, it was, yeah, I thought I would be a writer actually.

Yeah, I was gonna say, you must be all right if you win that.

Yes.

And it's like a short story or?

Yes, it was like an essay, a couple of pages about I think it was about a girl that like a young woman who works in for a nonprofit and she goes to this rural village in Bangladesh and like experiences health disparities. That's a theme right there. Yeah. Yeah. So yeah, that was that. And debate. I did a lot of Model United Nations and theater. There was a lot of ways I could have gone with probably. Yeah, I guess so. My mom is very like, listen, You got to be well-rounded.

Yeah.

You know, you want to be a scientist, but you have to, you have to care about music and literature. And I appreciate that. Yeah, that's good.

You're writing, you're getting into physics, and then now you're running a biotech company. I guess it is a physics company.

Yes, it is a physics company. Yes. Yes.

Okay. And all right, that is all. That is all fascinating. How did you find— how did you find coming to the US?

Um, it was great.

Um, I went— I played— so I used to play collegiate tennis and I went to Pomona College and we played a big tournament at Emory. Emory looks like a very nice campus.

Very nice. And, um, it was my first time being that far away from home. Um, I was very fortunate. I was a Woodruff Scholar and it just took that financial pressure off my family. Um, and they, they did a great job of taking care of me and just creating all these opportunities for me. Very warm hug. Actually, I'm going back in 2 weeks to do the— for the charter dinner, the keynote, which is like amazing. It's a huge honor at Emory. Yeah. So I'm excited to go and talk to kids, talk to the current students about my journey. And Emory is very good at biomedical sciences and entrepreneurship. I didn't do either one of those when I was there, so that'll be fun. Yeah.

That does sound cool. Is Coca-Cola like a massive—

It's huge. Yeah, actually, they're the Coca-Cola Foundation. It's the Woodruff Foundation that paid for my scholarship.

I remember seeing all these Coca-Cola signs.

You know, if you look at Emory's quad from like a satellite view, it looks like a Coke bottle.

Okay.

It's pretty amazing.

Did one of the— somebody from the company go there just because it's local?

And I think Woodruff, Robert Woodruff, he was just very passionate. I don't remember. I should know this if he went there, but he was very passionate about supporting Emory. Okay.

Yeah. And as far as choosing where to do the startup, I mean, you're at Harvard and so Cambridge is a natural choice. I have to confess, and obviously there are many biotech companies in that neck of the woods, I tend to find them to be a little less aggressive and slower moving than the ones out here. And, you know, I guess there's a debate where you're going to put this thing, but it would just just made all the sense for the obvious reasons to do it in Cambridge.

Um, I think that's a very— that's a powerful observation. I mean, I do think the whole— like, everything about Boston is about institutions and regulations. Yeah, there's a process. I, um, I— we ended up staying in Boston. It's quite accidental, um, but because we were backed by Engine Ventures, and they had this amazing lab space. It was actually— I was looking for a lab space where we could do lasers and chemistry and biology, and that didn't exist in Boston at the time, but they were setting that up with the Engine. So they're like, come on over, and they were— we'll also invest. This sounds great. Here's your first $1.5 million, like, leave academia. And we started building a really strong team across like hardware and bio and a little bit of AI. I say the Boston talent on the hardware side is really, really strong. So that was exciting. That was one of the reasons we stayed grounded. But very quickly I found myself out here on the West Coast. So most of my other investors are out here and that's helpful to make sure we're thinking in the right— at the right level of ambition and pace. But I will say I'm happy it worked out this way. Because we have ended up building a very thorough technology stack.

Yeah.

And it sort of, you feel the, the pressure of Kendall Square. Like everyone's like, hey, how's the FDA gonna feel about this? Like, what, what about this? What about that? These are questions that come up every week. So it, it wired our brains to pursue those goals with a lot of dedication and focus.

Yeah.

And so, yeah, but I, I do think there's some big Conversations happening right now because when we moved to Kendall Square, it's like 3% vacancy and now it's 25%.

And they're putting new buildings. I was just there. There's like new buildings going up and everything.

Yeah, I think, I think we overbuilt. Yeah, that's part of it. But there's also movement of more of the traditional biological assets to China. A lot of manufacturing moving there, a lot of early stage preclinical work moving there.

Right. Right.

So it's a different, it's a different focal point. So I think it's a good opportunity now for, there's a lot of talk on Twitter about this recently, like how to do more deep tech biotech merging in Boston. Yeah. Because we have some great talent out of MIT and Harvard. A lot of the talent is leaving Boston, like right when they graduate, which is, that's something to keep an eye on.

Yeah. Yeah. And I guess, I mean, San Francisco's always long had a big biotech presence. I guess Genentech probably kind of kicked off a lot of this in some ways. And then the universities. But, and then San Diego used to, is still a biotech player, a major one. But I hear about them less and less. I mean, there is this SF-Boston rivalry, at least for me these days. And it's, I feel like San Francisco kind of bulked up in some ways on some of this.

It is true that the venture dollars for more biotech, I think, is higher in San Francisco now than it is Boston for sure. Also. So, but that's okay. I mean, I think we have to step up our game. Yeah, I do see us now that we're going to start supporting more trials, kind of expanding the business. I do think our R&D sort of building machines headquarter will be in Kendall Square. It's a great place for us with the talent pipeline that we have set up coming out of MIT, Harvard, and the local companies. But AI, I think, can be in a lot of different places. Yeah, because the talent is everywhere right now.

I'm going to ask what might be a stupid and long-winded question, but I think about this a lot. I remember I think it was kind of like in the end of my high school years, we, we, Craig Venter and other folks, you know, did a whole genome. And from this, you know, obviously a big race to kind of get the first genome done. And then, you know, immediately it was like, oh, we're going to cure all disease quite quickly now that we have this. That turned out to be much more difficult. And then as I became a reporter and got locked in Silicon Valley in the early 2000s, there's so much excitement around synthetic biology. This— it's like based— playing off this genome, we're going to— we're going to transform biology into engineering. It's all getting— computized and this is going to be great. It will be manipulating things every which way we want. And, and, you know, things take time and, and we do do some of that, right? I mean, I mean, in, in many, many senses like this has happened. I feel like we keep running into this issue, which is that then the human body turns out to be so complex that all our best laid plans get undermined a bit. So, so this, this, this idea of biology, this will be the century where where biology becomes like computation, like engineering. And so there's always something that excites me, is happening in bits and pieces, feel like it's not happening on the level we kind of thought. Like if you, if you, oh God, this is a very hard question. I mean, so much money and attention being put on AI, which plays into some of this stuff, but then I always get most excited of like, well, maybe actually this is the century where it really is biology. The bigger story. Um, yeah, I don't know. I mean, I don't even know what my question is. I think you get the gist of just, are we going to learn how to engineer all this stuff, or is the human body— you know, we'll be able to do some interesting things, but this is just too complicated.

Ah, great question. My goodness. I have been waiting for a virtual model of the cell like my entire adult life, which people are working on. They're working on, and it's interesting. Yeah, we'll have one cellular model But then how do we extend that to the 37 trillion cells in our body? And that's an even more complex model. Oh gosh. Yeah. You know, it's my journey of getting very excited about physics and the universe and stars and how did we get here? What happened? That was my childhood fascination. And then there's within my PhD, kind of towards the end, I was like, wow, like our bodies are so complicated. We don't understand much.

Yeah.

And we can't systemize it. We don't have equations that we can write about it. Yeah. So it's really interesting. I mean, to me what comes to mind is how do we think about, you know, human intelligence and our ability to process what's happening at the universe level, but also at the inner body level. Can we really truly understand how we work? The optimist in me, I think, says in the next century we're going to make some big moves. Absolutely. The quality of data will be important. How we understand what's going on will be important. It's really hard to measure things in biology, like at the molecular level, at the cellular, at the machinery level, and how everything is talking to each other. But I do think we'll make progress there. Will we know everything? I'm not sure. I'm not sure. And that's okay. And I want to be grounded in the facts. But hey, like, if you told me when I started my company, we're going to see spinal cord injury patients learning how to walk, with new cells.

Yeah.

Blind patients starting to see and read and be, be allowed to drive with new cells. I wouldn't have believed it. So there is rapid progress happening and it's an exciting time to have more technologists enter the space from different disciplines. Yeah. I think what I struggle with a little bit sometimes is trying to— hoping that biology will end up being more simple than it is. It's just not. Yeah, I think it's very complicated.

It's like a little A very long question. I guess that's the heart, some of it. Yeah. I'm going to let you go in just a second because we got to get you back to Cambridge here. And but the— I cover a lot of— you just brought up the spinal cells and I got excited for a second. So I cover— I've covered Onward quite a bit. They make an implant, a spinal implant, which is electrodes on the spine to help people who are paralyzed walk again. But, you know, it's a bit it, it's like amazing. But then there's limitations on how much these people can walk and how all this works. You've seen like, is this piece— so there's been what, there's research or there's been trials on people getting these spinal stem cells?

Great question. There's an incredible researcher, Okano, in Japan, and he was the first to lead an iPSC-derived cell replacement. It's a trial. It was a trial, a small trial. And there, there was one patient that saw huge benefits and is learning how to walk, and then others that saw some level of benefit. So that was very exciting. I think that trial is going to expand now and they're doing more. And then we have a partner, Matrix Self. They're making a personalized version of that. And what we've done is we've sent them IPSCs, they've different from multiple, multiple donor lines and then they've differentiated them to make neural tissue that's firing. That trial is going to come up. So it's a, it's yeah, it's, there's, there's some clinical evidence now that this is possible.

Wow. Okay.

So I'm happy to send you the name of the program and yeah, actually Sensei Okano was at JPMorgan and he did a little, he's great. He's great. He's— we met him over the years and he's very, very scientific. He has taken so much data and very practical. And I think that's why there wasn't like a ton of hype around it because he's like, listen, this happened one time, we got to do it more now. Also, there's some interesting learnings around when to intervene with the patient. So getting in at the right time as soon as the injury has happened.

You want it? Yes.

So I'll send you that. It's pretty incredible. So there is a patient in Japan that's learning how to walk.

Super cool.

Okay.

So if I want a Nebula system today, do I buy it from you or do I just kind of like tell you what I want and you guys send me the IPSCs?

That's right. We'll send you the IPSCs.

And is that the model going forward?

That's the model going forward.

You guys are always going to run the machine?

Yes. Yes. They're going to run the foundry and do the manufacturing.

And you mentioned, I mean, we're right here in the early days of 2026. You said it's going going to be a big year. We just outlined a whole bunch of things that are coming from these, these various trials. I mean, that— and that's kind of the push for you guys, is, is, um, I don't know, I was just going to highlight anything big that you guys had coming for the year. It sounds like this is the push. You've been working on this machine, machine's working, people need their iPSCs, and, and you're going to make them. That— is that the thrust?

I think that's the biggest push. And we've been thinking a lot about how to continue building on— we think about it very much build foundations, strong foundations. So So invented the tech stack for manufacturing, figuring out on the regulatory side, there's more that's going to come on the regulatory side. There's a ton of AI alignment that my co-founder is working on across all the regulatory agencies globally, like how to use AI to do manufacturing like this. There's going to be more openings on different ways to access therapies through different regulatory jurisdictions because I think it's an interesting time. There's a lot of conversation on how the US clinical trial structure should evolve because China has a different structure. Australia has a different structure. Japan has a different structure there that have different ways you can develop and test these. And the US has a, has a, has a longer process. So that's really interesting. Stay tuned for that. And I think for us, it's thinking about what's next. You know, like I'm pretty energized with the momentum and like thinking very creatively, how could it be possible to start giving everybody access to their own iPSCs? Yeah. So I'm working on that. It's a lot of brainstorming. So yeah, that's going to be fun.

I feel like I might be just about to end this on a sour note, but I just thought of something else you were saying earlier when we were talking about like, oh, well, the pharma companies want to see stuff like this happen. I felt like you got— I saw a look on your face that was less, less happy than others. And then I didn't know if this is something you wanted talk about openly or not, but yeah, I mean, you could see a world where, yeah, I mean, this is, if you're like one and done, this might not be great for the business model of current.

You know, that's a really interesting point. I think my, the look more on my face was capturing the whole like range of pharma responses.

Okay.

And you see like some pharma that are diving in deep into it. Bayer is one of them. They're one of my investors. They're like going all the way. They have a huge pipeline. They're thinking about scale. And then the other ones, it's been like hot and cold over the years because they have good— they have questions that are very practical. How is this going to scale? What's the reimbursement going to look like? I do feel that with this clinical data coming up and everybody building infrastructure aggressively like us and many others, uh, this conversation will come up again because the medicines are transformative. Yeah. There's no denying it. And when you have clinical data, but it could be that the access models are different.

Yeah.

Like, you know, I'm curious to see how, what role pharma's gonna play in how these medicines are delivered because a lot of times it's like academics inventing the therapy, running a trial at a hospital, and there's some manufacturing partner like us, there's a surgical partner. Like where is pharma going to plug in? Like how do they want to work with this? And pharma is not set up to be this personalized. Yeah. You know, that's just not their model. So I do think these are interesting questions and I see them as opportunities to figure out how do we get this out there to the world.

And you talked about like today for a therapy for one adult, it would be on the order of millions of dollars, $2, $3, $4 million. You want to by 2030 get this to like $25,000. $5,000 for, for the iPSCs for that particular therapy. Is there a reason that number then would be kind of capped around, around that figure, or does it just keep going down?

I do think we're going to make tons of advancement. I mean, then, you know, you start— you have to optimize further on the boring stuff like reagents and media and shipping and clean rooms and— well, actually clean rooms are covered in our model, but But yeah, I mean, you look at sequencing and that's seen like tremendous—

That's all I was curious about.

Yeah, totally.

If it sort of hits that same curve where you go from multi-billion—

I would love for it to get to the thousands. Yeah. Oh my gosh. Yes. That's— but you know, one step at a time. So my team is very practical. Yeah. So I gave them a number that felt more practical.

Well, and if it— so if it was like $25,000, yeah, it's just somebody has to figure out who's paying for that because I mean, I guess that's kind of the raw cost and then somebody's gotta make some money on top of that.

Okay.

And then that's a lot for an individual. I mean, it's like if it's like lifesaving, you're going to want to do it. But if you have to pay $100,000, $75,000.

That's right.

And then what does the insurance company get out of that? Because, yeah, you're kind of doing this.

It's not— there is talks right now thinking through the Parkinson's reimbursement path and like the anchor that I've heard is more in the half a million as a price point. And because you can expect many years, maybe 5, 5, maybe even 10 years of benefit for the patient, that insurance companies, payers would be interested in that.

Okay.

TBD.

Yeah.

But, you know, I think there's been some progress with Casgevy on that and the CAR-T therapy. So I'm optimistic.

Yeah.

Yeah.

Okay.

Yeah.

Well, I'm sorry to bog everyone down with the money minutiae on this exciting technology, but it's important.

Hey, listen, these are, these are the questions we have to ask and work on. And actually they don't bog me down because I, I feel like things are moving in the right direction.

Yeah. Yeah.

And we just have to keep pushing harder. I just hope that like we have good data coming out. No, like safety issues in some of these trials. There's a cool study by Melissa Carpenter, who's one of my advisors, and she like looked at every pluripotent and stem cell therapy trial in the world and it's like about over 1,000 patients that have been dosed. No major adverse events. We just got to keep on that track.

Pushing.

Keep pushing and keep building. And it's hard because everybody's doing the manufacturing their own way. The trial is different, but overall, yeah, the data is compounding.

Okay. Okay, good. Well, I had so many people that told me to have you on the show and, and you lived up to their billing. You're You're brilliant, obviously, and, and really fun to talk to. I felt, I feel like we accomplished something here, which is in some of our episodes we've talked about IPSCs like on and off, or it was part of something else. And I feel like we got a, we got a good base and understanding of where all this is heading. So thank you so much for coming in and trekking out to our studio here at Playground in Palo Alto. And thank you for your time.

Thank you, Ashlee. This was so much fun. And, I, I love how you, how you look at technology and trends. So this was— I have some good takeaways and nuggets about how we might think about this next 10 years for the IPSC world. So this was awesome.

Okay, maybe we accomplished something out here in the world. All right. All right. Thank you so much and safe travels back. Thank you. Core Memory Podcast is hosted by me, Ashlee Vance, and/or Kylie Robison, or both of us together. It is produced by me and David Nicholson. Our theme song is by James Mercer and John Sortland, and the show is edited always by the John Sortland. Thank you so much to Brex and E1 Ventures for all your support, and thank you most of all to everybody for listening or watching. We love you. Please leave us a like, a review, a subscribe, all those tremendous things. Thank you, and we'll see you again.