Episode 48: Jonathan Thon - Founder & CEO at STRM.BIO

Embark on a fascinating exploration of biotech entrepreneurship, guided by an expert who's been in the trenches: Jonathan Thon, CEO and founder of STRM.BIO. We'll give you an insider's view of his journey from academia to the cutting edge of biotech, unveiling his trailblazing work on platelet production and the transformative potential of extracellular vesicles in gene therapy.

First In Human is a biotech-focused podcast that interviews industry leaders and investors to learn about their journey to in-human clinical trials. Presented by Vial, a tech-enabled CRO, hosted by Simon Burns, CEO & Co-Founder. Episodes launch weekly on Tuesdays. To view the full transcript of this episode, click here.

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Chapters

• 0:06 From Academia to Entrepreneurship
• 8:43 Leveraging Extracellular Vesicles for Gene Therapy
• 16:32 The Future of Biotech and Entrepreneurship

Transcript

Speaker 1: 0:06

You are listening to First In Human, where we interview industry leaders and investors to learn about their journey to inhuman clinical trials presented by Vile, a tech-enabled CRO hosted by Simon Burns, ceo and co-founder. Featuring special guest host Rich McCormick, evp of Clinical Strategy and Head of Oncology. In this episode we connect Jonathan Thon, ceo and founder of StormBio. Stay tuned to learn more about Thon's journey from academia to entrepreneurship, breakthroughs in platelet production and innovative use of extracellular vesicles in gene therapy at StormBio.

Speaker 2: 0:45

Hi, I'm Rich McCormick, Executive Vice President of Clinical Strategy here at Vile. Today I have the pleasure of welcoming CEO and founder of StormBio, Jonathan Thon, to our first inhuman podcast. Hi, Jonathan, Would you mind telling us a little bit about yourself?

Speaker 3: 1:00

Happy to. I'm Jonathan. I'm the CEO founder of StormBio. As you've said, I was an academic scientist before becoming an entrepreneur. I was a professor at Harvard Medical School for a number of years, banded my first biotech company out of my academic lab and joined that company as its CEO and Chief Scientific Officer. I ran that company for almost a decade. About three years ago stepped away from that company and found Storm, which is my second biotech company.

Speaker 2: 1:28

Can you tell us a little more about your journey from being a professor and lecturer at Harvard Medical School to becoming an accomplished biotech entrepreneur, as you mentioned in your intro? It would be interesting to hear about your transition from CEO and CSO at Platelet Biosciences.

Speaker 3: 1:44

The story really begins with my PhD work at UBC. I'm Canadian. University of British Columbia is a Canadian university that I did my graduate school studies at. During grad school I was working with Dana Devine, who's the Chief Medical Officer for Canadian Blood Services. Dana was studying what was called the platelet storage lesion, or this characteristic of blood platelets to go bad after a very short period in time in storage really three days.

Speaker 3: 2:10

Platelets critically important. They're the band-aids of the bloodstream. I was tasked with trying to understand how to extend the lifespan of a platelet unit beyond three, four days. We did a lot of tremendous work in that lab, but it became pretty obvious to me that the solution wasn't to extend lifespan by a day or two. The solution here was to disconnect the product from the donor and make human platelets. It was with that idea that I actually came to Harvard, initially as a postdoc developed a microfluidic device to make platelets. This was one of the first cell therapies that were being created at the time. During the course of that work it was promoted to a professor at the university.

Speaker 3: 2:50

The work advanced to a point in my academic lab where the next steps were ones that required a little bit more infrastructure and more of a commercial focus. So scale up, release a product, regulatory process, things that the university or the academic lab really wasn't set up to do or do most effectively. Now, I didn't go into my academic career thinking I was going to become a CEO. Quite the opposite. I had never taken a business course up until that point.

Speaker 3: 3:19

It was also pretty obvious to me that at this point, the technology we're building a cell therapy was way too early to out license to any company. Quite frankly, the conversations I was having with investors at the time were ones around whether this was a medical device or a drug, small molecule, and I was telling them it was neither one of those things. I was being told that if it was neither one of those things, it wasn't a thing. I was like no, it is a thing, it's just not one of those things Really large companies, pharma companies, want to position to in license this technology. Staying at Harvard and continuing this would have meant the rest of my academic career so probably the next 30, 40 years of my career to do what felt to me we could do over three to five years. In order to do that, I had to create a company of my own Platelet ended up being an experiment in creating a vehicle to translate some of these ideas, discoveries, into the market. Then everything else that followed was a very steep learning curve.

Speaker 2: 4:20

That's interesting. Your work has involved translating scientific advances into preclinical and clinical stage programs. Can you share an example of a particularly challenging scientific breakthrough that you worked on and how it eventually made its way into practical applications?

Speaker 3: 4:40

Thank you. Well, triggering platelet production was that the university. In my academic lab, we had discovered a way of exposing this parent cell to stresses that would trigger new platelets for being produced. This was a microfluidic system that we were building it on, so it was roughly the shape of a business card. The channels beneath that business card were a lot smaller still and it was initially a two-dimensional device that I had to convert into a three-dimensional device to increase the surface area, to increase the scale. When we converted to a three-dimensional device, we also had to tackle challenges of even distribution of cells and flow across the surface area per channel. And then, as we started parallelizing channels, the same thing across multiple channels. So we took up as much real estate as possible. With an app business card size space. We began stacking business cards, so to speak, and then had to deal with manifolding inputs and collapsing output challenges so that we could flow through a single tube into a larger device, collect the product and pull that all back into a single output flow.

Speaker 3: 5:48

In the process of doing that, discovered that media is probably the single most expensive component of any cell culture process and we were wasting a lot of it through single perfusion of media through our device, and so we had to develop technologies and strategies to recirculate media and, as the devices got larger, recognized that it was too much work for one scientist, two scientists, PhD level scientists to be running over the span of one to two days and, quite frankly, that was not a scalable solution.

Speaker 3: 6:17

So had to automate the process. Had to miniaturize the footprint as well so that we could fit more devices into a smaller surface area. Had to adapt the manufacturing so that we could move from what were initially machined devices, which were easy to iterate on but expensive per device, to microinjection molded systems that were a lot more expensive up front but became pennies on the dollar when you're manufacturing thousands of these devices that go and then refining the operating conditions to optimize efficiency and yield. So, as I'm responding to your question and recognizing that in retrospect we probably did a lot of work, but all of those things were important in scaling up what was a promising initial technology but turning it into a practical application.

Speaker 2: 7:03

That's great. So a notable achievement, as you mentioned, is the production of functional human platelets from stem cells. So you talk a lot about the discovery. How do you envision this breakthrough impacting the medical field in?

Speaker 3: 7:15

the future. Platelets are necessary anytime anyone goes under the knife requiring large quantities of blood if they're in surgery, chemotherapy, receiving cancer treatment, childbirth accidents, war there are tremendous implications to platelet availability. The challenge here is that if you're in a civilian environment, you've got huge shortages in long weekends, civic holidays, particularly warm or cold days where donors don't go out to donate blood because the entire system is dependent on volunteer donors. What we discovered, as well as we were building a company, is that if you're thinking about more international military systems, the movement of blood products and specifically the movement of platelets, telegraphs, military engagements and countries watch for this right it telegraphs where something is going to happen. That's meaningful because there's not enough storage time in that product to bank it in advance of an incursion or a defensive position. So this is a tremendously important product that had tremendous implications both in civilian and military applications, and the initial idea or the initial foundation of that company of platelet was based around producing these plates, making them available so that they could solve those challenges, one of the interesting things that I was also able to inject into the company.

Speaker 3: 8:43

I think it's very rare, especially for an early technology like this one, that anyone gets an opportunity to introduce a second idea into a company. But I was fortunate enough to get a second idea into the company before I left and turned leadership over to who followed me at platelet while I went on to Townstorm. And the second idea was one around cancer or oncological applications. So cancer cells will actually coat themselves in platelets to hide from the immune system and they use that coating of platelets to help them metastasize inside the body. And so the idea went if we could load platelets with anti-cancer drugs, we could also leverage that innate biology and that direct contact of platelets with cancer cells to help deliver anti-cancer agents and also prevent metastasis and kill cancer cells before they actually took holes.

Speaker 2: 9:34

So at Storm Bio, you're leveraging extracellular vesicles or EVs to deliver gene therapy. Could you explain how this approach differs brown traditional gene therapy methods and what advantages it offers?

Speaker 3: 9:47

Definitely, For starters, the vesicles that we're making. They're cell-derived vesicles. The vesicles that we're making are targeted and they bypass the liver in vivo. Now this is a big fucking deal, and I say that seriously because when we talk about the state of the arts, you know viruses, liponantoparticles, and we talk about targeted. What we mean to say is that 90, 95% of the product ends up in the liver and maybe 2% end up in the target of interest. But we have got here at Storm is a delivery platform that bypasses the liver in its entirety and that has huge implications in safety and dose.

Speaker 3: 10:27

Now, if that's the primary differentiator, the second differentiator here is that these vesicles are quite a bit larger. There is largest to largest viruses. What that means practically for us is that they've got a large carrying capacity. We can fit bigger cargo in. We have successfully put in DNA, RNA, rmps and CRISPR-Cas9 complexes. We've been able to multiplex multiple different modalities of asset into the same vesicles. This is important because Editors like prime dual-flap editors. They're getting larger and they're not fitting into conventional delivery platforms. As the field starts moving away from just single base permutation defects into more complex genetic diseases, we're going to need to multiplex different kinds of cargo into the same classical to go after those more complex diseases, and in order to do that you need to be able to package them into the delivery platform. And the third sort of interesting component to this as well which we found is that in addition to controlling how many vesicles we inject per animal, per person, which is the conventional definition of dose, we can also modulate how many copies of cargo we put per vesicle, which is a really interesting independent lever that can help modulate dosing. And you can imagine scenarios where if you're delivering an editor, you may not want a lot of copies of that editor per vesicle, but you may want a lot of vesicles to blanket canvas a number of cells, whereas if you're delivering a DNA or a messenger RNA for well-typed protein expression, you may want a tremendous amount of cargo per vesicle so that you increase as much as possible the amount of protein that's being expressed on delivery. So that's a really interesting lever that we can play with.

Speaker 3: 12:08

And then the third point here is that these vesicles are innately and yet privileged, which means that practically we can repeat dose with them. Our field has for the longest time talked about one-and-done therapies for gene therapy, but one-and-done practically is tail wagging dog. You know we're talking about one-and-done therapies because we can't come in with a second dose or a third dose. But if we could and we can this really opens up the landscape in terms of the diseases that you can go after which is pretty much everything else and the approaches you can take to go after those diseases. Now there is one more point I want to make here, and I think this is tremendously exciting. It really requires an understanding of how the gene therapy market has developed to date.

Speaker 3: 12:53

But I think one of the most exciting pieces about the platform we're building is the breakthrough in the simplicity, the versatility and the scalability of the manufacturing platform itself and the implications that has on COGS, and I'm hopeful that we can talk a little bit more about that in some of the next questions. Because what we can do with our manufacturing platform is produce unloaded vesicles as a single off-the-shelf banked product, and because the loading of our vesicles happens exogenously, we can have a single common bank for multiple drug products. What that means is that you can use the same product from one clinical application to another and keep the same drug master file, and that, I think, is really, really exciting. I mean it means that preclinical clinical data from one study can be repurposed for a different disease. It means that you only need to update the clinical protocol as you move from one clinical study to a different clinical study, and it means that you're able to keep the cost of development really low.

Speaker 3: 13:58

And what I was mentioning about understanding of the nuance in the field is that investors, as they think about cell and gene therapy, they're primarily concerned with this idea that cell and gene therapy companies require approaches that cost huge amounts of money, huge amounts of investments in preclinical clinical development, and that's been a key issue for our space.

Speaker 3: 14:24

What we've got here is a platform that has the potential to limit the validation of cell and gene therapies to talks and efficiency of cargo, independent from the delivery platform itself, and that has the capacity of massively reducing the cost of development for partners. I'm going to end this with just one more point, and I'm going to quote Peter Marks, who's the director of the Center for Biologics Evaluation Research at the FDA. He gave a presentation at the meeting at the MESA this last year, and at that meeting he said that if we could get this paradigm to work rather than having a manufacturer go back and do all of the preclinical toxicology and give us all the manufacturing information each time they submit something. They would just cross reference, and this would allow us to focus on innovation that's going to benefit people. He said we'd start by allowing an individual company to leverage the information from one application to another and then, if that's working well, we can consider expanding that concept further, and I think that's really at the heart of what we're trying to build this storm.

Speaker 2: 15:25

Yeah, that's really exciting. I really appreciate that level of insight. So you mentioned being at a conference recently and I know that you do a fair amount of speaking. Both you know conferences and meetings worldwide, so maybe could you share a piece of advice that you would emphasize when speaking with an aspiring scientist or entrepreneur. You know that's in the biotech industry Do it?

Speaker 3: 15:49

Maybe three things I can share. The first is do it. There are all the reasons in the world that everyone will highlight regularly for why something shouldn't exist or couldn't work, but if you can see a path whereby it can, you should do it. You know, for all the reasons everyone keeps pointing out that these breakthroughs can't or shouldn't exist. They're obviously not going to exist without you. And because no one else can see it but you can, you need to pave that path forward and make it possible for others to follow suit. You know, if you're wrong, you tried, you gave it a great shot and the idea was tested. If you're right, you know you've changed everything and that's worth doing. I think that's the first. That's probably. If there's a single take home, it's that you know.

Speaker 3: 16:32

The second I would say is that communication is key. That people can't see what you see is inherent, but that's not on them, that's on you. You know it's your job to make it possible for them to see it so that they can understand it and they can support. And communication isn't something anyone's naturally or what's. You know, some of us are a little bit better than others, but for the most part it's a practice skill and one that you should practice so you can get better at it.

Speaker 3: 16:57

And the third and this is going to sound a little bit tongue in cheek, but you need to understand and get comfortable with a company's natural arc, and I tell this to young entrepreneurs a lot that this does require checking your ego. Now, a mentor once said to me that there are three stages in one's career the first stage, where no one believes that what you are proposing is possible. There's the second stage, where people believe it's possible but no one believes that you're going to be the one that does it. And then there's the third stage, where people take for granted the advancement is obvious and no one remembers that you've had anything to do with it, and that's OK. You need to recognize that that's what success looks like, and you shouldn't do this for your ego, but to bring a new discovery to light. That's great advice.

Speaker 2: 17:44

So how about maybe providing some insight into the current landscape of innovative therapies and technologies, and just where do you see the field going over the next five years?

Speaker 3: 17:54

The current landscape of biotech, I think, is inextricably tied to markets and financing and you know, what can be sometimes a little bit frustrating for all of us is that we keep ping-ponging between these alternate streams. On one hand, progress will be limited by a dearth in investments, and that's particularly felt when that investment is not going into less popular fields or markets that have fallen out of favor. That's seasonal Right. On the other side of it you know this, over capitalization of select companies or specific industries or approaches is also not the answer. You know, stem use, creativity, innovation represses competition and the challenge here is that in biotech and in life sciences, industries are dependent on financial markets that are moving on a monthly, daily, hourly pace, whereas biological innovations to proof of concept, to clinical success, to commercial return on investment, happen on five to ten year time frames.

Speaker 3: 18:57

Five to ten years is a long time with significant ups and downs.

Speaker 3: 19:01

You know it requires committed investors with long time horizons and significant risk tolerances.

Speaker 3: 19:07

And, at the risk of likely miscrowding Warren Buffett here, someone's sitting in the shade today because someone planted a tree a long time ago.

Speaker 3: 19:17

Right, the clinical and commercial successes we're seeing today in gene therapy are being built on investments that are being built on investment that were made more than a decade ago, and every one of those are stored companies with moments they felt they wouldn't survive or overcome Across years, years where industries fell out of favor and have only become popular again because of the staying power of these companies that then finally hit a practical, meaningful milestone and shift investor interest back into them. And so you know. You ask me where the clinical, commercial biotech success over the next five, ten years will be. Now, it's going to be in these companies that were created over this last decade, likely with a deep emphasis in cell therapy and gene therapy, in cell and gene delivery, and they will return to favor when the market stabilize and those same companies that are able to last through this more difficult period start hitting on some of their meaningful clinical and commercial proof of concepts.

Speaker 2: 20:14

So that's great insight. So you are rooted in academia, but also a successful business leader. So how do you balance the pursuit of scientific knowledge and entrepreneurial success?

Speaker 3: 20:27

I think there's a place for most, and I think that neither can exist without the other. There's a lot of supporting industries in between. I found it easier actually to teach scientists business than to teach business people science, and one thing that I feel can't be emphasized enough is that biotech companies will live and die by their science, and so, for biotech companies specifically, I see a tremendous amount of value in having scientists and the CEO and executive suites. What I have taken from my experiences is that we need smart, ambitious young scientists, and both academia and industry and across all of those spaces in between, to drive that innovation, and it's in them that we should be investing, not the seasoned executives with multiple license under the belts. Let them be mentors and have these new ideas injecting and driving innovation in space.

Speaker 2: 21:21

Well, that's great. So, jonathan, it's been a pleasure meeting with you today and thank you for being a great guest on Biles Firsting Human podcast. The team here at Bile wishes you and your team at Storm Bile nothing but future success. I appreciate it, thank you.

Speaker 1: 21:43

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