Inside Brown University’s Bold Bet on Regenerative Medicine

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David: At Brown University, they’re working to use something called the extracellular matrix to help the body promote tissue healing and regeneration. It could be a game changer for heart disease and a host of other ailments. Today, we meet XM Therapeutics and the ecosystem at Brown Technology Innovations that’s working to make this amazing technology a reality for patients.

Welcome to the Angel Nest University Innovation Network, where we profile the most exciting and important technologies from the world’s leading universities. I’m David Hemenway. I’m a five-time founder and now an active angel investor.

And my mission here is to introduce the innovators and the businesses that are leading the way to the future. Melissa Simon, Director of Business Development at Brown Technology Innovations, and Karen Bullock, Director of Brown Biomedical Innovations, work together to provide early funding and guidance so that these amazing ideas that start in the research lab can make it to commercialization. They join us today along with Dr. Jeffrey Morgan, Professor of Pathology and Laboratory Medicine at Brown, and Frank Amund, the entrepreneur who BTI recruited to scale XM Therapeutics.

Thanks, everyone, for being here today.

Guests: Thank you. Great to be here, David.

David: Thanks. So Dr. Jeff Morgan, congratulations on creating such an amazing platform. You said it’s not a single solution, but even potentially a whole new class of therapeutics.

Dr. Morgan: And what strikes me about this is so fascinating is that you’re helping the body heal itself potentially, right? Yeah, that’s correct, David. And before I dive in, this is a testimony to the Brown ecosystem, the efforts of Karen, Melissa, finding Frank, and making those connections. So I think it’s an ecosystem your listeners should really take a close look at because there’s a lot of great ideas coming out of Brown.

As I said to you in an earlier discussion, yeah, I think this is a new category, a new class of therapeutic. And I’ll get into that in a moment. But I just want to tell you about our most recent data which was published in the American Journal of Physiology.

My lab at Brown made the particles, and then we handed them off to Dr. Frank Selke over at Rhode Island Hospital. Dr. Selke is chief of cardiothoracic surgery and also a co-founder of XM. And what Dr. Selke’s team did was they tested our particles in a model of heart attack, a myocardial infarction in a mouse model.

And so that data, very exciting proof of principle data, shows that when we injected our particles into the heart of a cohort of mice versus controls, our treated mice showed a significant reduction in the scar that normally occurs after myocardial infarction after a heart attack, an increase in vascularity, and an increase in fractional shortening, which is a metric of the heart’s ability to beat. So we published that data in a peer-reviewed journal and very excited about that. And I think, as I said, it demonstrates proof of principle and a new category, as we alluded to.

Namely, if you think of it, you know, you have small molecules, you have growth factors, you have monoclonal antibodies, all distinct categories of therapeutics. You now have gene therapy viral vectors on the scene. But at XM, we’re working on extracellular matrix particles.

These are large particles, about 200 microns in diameter. We make them by growing human stem cells as spheroids. And then we decellularize those living spheroids.

And what’s left behind is a particle of extracellular matrix, human extracellular matrix. And what we showed, in addition to the physiological metrics, we also showed in that paper that when we inject these particles, they stay localized in the heart, which is really exciting. So I think as a new therapeutic, we’re just at the beginning of this cultured human ECM.

We have capabilities of modifying it, different cell types, et cetera. So I think it’s a wide open, white space for a new class of therapeutic.

David: Frank Amund, you’ve been an investor in medical technologies as well as a CEO with prior exits.

Tell us, if you would, what you see as the potential for XM Therapeutics and how you came to join Dr. Morgan and Brown Technology Innovations.

Frank: Yeah, thanks very much. So, you know, in short, the huge potential for XM Therapeutics lies in our unique approach to target an area of medicine that has been underappreciated, as you pointed out, the extracellular matrix or ECM for organ failure and tissue repair in chronic diseases such as heart, kidney, and liver failure.

Specifically in chronic diseases, which affect particularly the aging population, the ECM really drives the overproduction of collagens beyond what is needed for a healing response. And this leads to a buildup of scar tissue, which is known as fibrosis, as well as inflammation, tissue stiffening, hypoxia and lack of oxygen, and ultimately organ failure. Now, numerous studies have confirmed that it’s possible to stop this process in animals by modifying the malfunctioning extracellular matrix.

However, a practical clinical approach to be used in humans has not been developed yet until we came along. Our approach consists of producing healthy extracellular matrix particles in the laboratory, which are then injected practically through a catheter or a syringe into the diseased tissue. There, they engraft, and they actually modify the local extracellular matrix to provide a regular healing response and reduce that scarring process or eliminate that scarring process, eliminate the inflammation, and eventually regularize or normalize the healing response in the tissue.

David: So you’re actually using the body’s own mechanisms to heal.

Frank: That is correct, and we do that without cells. We actually look at the extracellular matrix to do that. We believe that this is a much more effective way, and this is a very practical approach. So in terms of investment and potential, this has an application just about any part of the body because the healing response that I’ve just described is universal, but we have a very practical way of doing this.

This does not rely on complex gene or cell therapies. This is literally making these particles in the laboratory. They’re non-immunogenic. They can be stored. They can be injected simply, and the process can be scaled up significantly. So it’s a very practical biologic product for a very, very important disease category, which are these chronic disorders.

David: Sounds like it could be an enormous market for XM.

Frank: Indeed.

David: Karen and Melissa, your work here seems really transformative, the way that you create a path and help companies innovate in the market. In the case of XM, I’m curious, what is it that made you decide to get involved?

Karen: Hi, sure. This is Karen, and maybe I could start by talking a little bit about the program that I run at Brown called Brown Biomedical Innovations. The program supports faculty who are working to translate biomedical discoveries from their research into technologies that can ultimately be developed into solutions for patients like therapeutics, diagnostics, or medical devices.

Often when academic researchers make a discovery or an invention that they think may have the potential to be commercialized, they find there’s a gap, sometimes with finding funding to continue to develop the technology and also finding commercially relevant development expertise.

So our program, with that, we aim to bridge that gap by supporting the critical early technology development work with funding and other resources. Then we collaborate closely with the Technology Innovations Office to find the best commercialization path, whether that’s out licensing to an industry partner or formation of a startup company.

A few years ago, Jeff Morgan submitted a proposal to the program, and Jeff is an expert in engineering three-dimensional microtissues from cultured human cells, and they have all kinds of potential applications in research and therapeutic approaches.

The project that Jeff proposed was to explore using his existing microtissue technology to produce extracellular matrix, or ECM. And this material could then be used therapeutically for tissue healing and regeneration, first in the heart, as Frank had already mentioned. There are others in the field exploring therapeutic uses for ECM, but we could immediately see that there were several major advantages to this approach and that this approach would have over existing technologies and development.

So those existing technologies primarily rely on purifying extracellular matrix from animal sources. So with Jeff’s expertise and the potential uses of this technology, we were really excited to fund and support this project. And with our support, Jeff was able to adapt his technology and develop the process for making and testing the ECM.

And then we worked with Melissa in the technology development office to file the patents on the technology and also prepare to form a startup company, which included finding someone to run it.

So I’ll hand it off to Melissa to talk more about that.

David: Yeah, I wanna pick up on that point because I think it’s really important that at Brown, you are actually open to bringing folks in from the outside.

Melissa: That’s right. Absolutely. I mean, we recognize that successful university startups often require an external experienced entrepreneur.

Faculty inventors rarely wanna leave their positions within the university. And postdocs or grad students may be more inclined to join or even lead a startup, but the company would greatly benefit from the mentorship and guidance that someone with prior startup experience would be able to provide. So we’re always looking for experienced entrepreneurs who we can bring into our network and match with inventors to take technologies forward.

So I actually met Frank through a partnering platform at a virtual MedTech conference in 2021. And at the time, I actually wasn’t specifically looking for someone to match with Jeff and with this technology. But once I read Frank’s profile, I knew he had the right background for this particular project.

Thankfully he took the initial intro meeting with me. Then I introduced him to Jeff and really the rest is history. And coincidentally, Frank had just received an offer for the company he was previously leading so timing really worked out well for him to come in, complete that acquisition and then transition over to co-founding XM.

Frank: I would amplify Melissa’s remarks and say your listeners need to realize that not all the good ideas are North of Providence or South of Providence. There’s a lot of smart people, professors, students at Brown University right there in Providence, Rhode Island.

And I think it’s been overlooked and I think it’s worth a look by your listening crowd because I think they’ll be very surprised at the innovation taking place.

David: So Jeff, when you became a professor at Brown University, did you ever think that you’d turn into a medical entrepreneur?

Dr. Morgan: David, well, yeah, actually I had an experience, my first experience in this space as a postdoctoral fellow at MIT and the Whitehead Institute and had one of the early patents in gene therapy and actually was a co-founder of a company called Somatics Therapy Corporation which was eventually acquired. So I caught the bug there.

I came back into academia and have always had a keen interest in translational type of work. And so it’s exciting to work with Frank Allman on a new class of therapeutic and looking forward to the future. I do wanna stress one attribute I think is important maybe for your listeners.

When they hear stem cells, they may think, oh, this is a living tissue, living cell product. Well, quite the opposite. We grow these living spheroids, human stem cells, and then we carefully decellularize them with a detergent.

So now these particles are extracellular matrix particles, but they’re not alive. They’re something we can store, can be taken off the shelf and used widely, injected to various locations in the body for different indications as Frank said.

David: You clearly lean towards being an entrepreneur and it sounds like the ecosystem now that’s developed at Brown really suits you and some of the other professors very well.

Dr. Morgan: Yeah, absolutely. I think we’re seeing a big uptick in terms of this with Melissa and Karen’s leadership and then the excitement. There’s a lot of excitement that goes to developing a therapy and seeing it get into the marketplace. There’s nothing more exciting than that, I think.

David: I’ll ask Karen and Melissa, what kinds of projects are the most fundable from your perspective for people who are listening who may be thinking about diving in?

Melissa: Sure, maybe I can start. So we’re looking at projects like Jeff’s all the time and we look at things in the biomedical space such as therapeutics, diagnostics, medical devices, even some life science tools.

And I would say clearly the projects that are the most interesting to us are the ones where there’s a clear unmet need and the product can clearly address the unmet need. And so sometimes that’s something that academic researchers need to really think very carefully about. What is the need that they’re trying to address and even do some deep research into figuring out whether that need actually really exists in the eyes of the customer.

And so if there’s a clear unmet need and a feasible path to potentially develop an exciting new technology, those are the things that we’re the most interested in.

David: Frank, it seems like you’ve made a lot of progress already. What does the next year or so look like for XM?

Frank: Yeah, we’re continuing down the pathway of validating the technology. And that means two things primarily in terms of further proof of concept animal testing. We are moving for the first time away from a cardiac indication into a geriatric wound healing model. In the heart, we are now treating large animals, which is the natural progression towards a human clinical trial.

And then very importantly on the manufacturing side, moving from the academic sort of environment into a fully scalable and automated GMP facility. So all of this is going on in parallel and we continue to turn cards, as we like to call it, towards that clinical aim.

David: Frank Amund, Karen Bullock, Brown Biomedical Innovations, Melissa Simon, Brown Technology Innovations, and Jeffrey Morgan, the professor at Brown University who started all of this.

Thank you all very much for joining us today. Thank you. Thank you.

Guests: Thank you, David. Thank you.

David: You can learn more and reach today’s guests at our website, theangelnest.com, where you can also reach me if you have a comment or a question or an interesting topic that we should talk about.

A reminder that we don’t make or recommend investments at The Angel Nest. This program is for informational purposes only. We produce The Angel Nest with help from Rob Higley. Today, it’s Kathleen Conte at the controls of CDM Studios here at the famous Art Deco Film Center building just west of Times Square in New York. I’m David Hemenway. Thanks for listening. So long until next time.