Podcast Transcript

David Brühlmann [00:00:42]:
Translating a regenerative scaffold from concept to the clinic raises questions every biotech scientist will recognize. How do you manufacture a biomaterial consistently, define its critical quality attributes, and navigate a regulatory world where medical devices and biologics rarely overlap?

In this second part, Eva-Maria Balet takes us deeper into the process development, clinical realities, and founder lessons behind Regenosca and TissueSpan. There’s plenty here that applies well beyond MedTech. Let’s get back into it. Here is the first part of our conversation. 

On this podcast, we talk a lot about biologics and cell and gene therapies. With those, we discuss critical quality attributes, batch-to-batch consistency, and so on. I’m curious now, since we’re talking about a medical device, how does that work in your world?

Eva-Maria Balet [00:02:49]:
I think that’s a very good point. I’m glad you mentioned it. TissueSpan is a medical device, so we’re not creating living tissue in the lab. Instead, we’re creating a mechanical support whose primary function is structural and mechanical—to enable the body’s natural healing process. From a regulatory and quality perspective, this actually gives us a strong advantage because we can define and control clear quality attributes. The key attributes for us are sterility, implant dimensions, and mechanical stability—parameters that are well understood and can be robustly controlled during manufacturing as well as through final product testing.

To ensure batch-to-batch consistency, we rely on a combination of validated manufacturing processes, in-process controls, and final product testing, all aligned with regulatory expectations.

Because the mechanism of action is based on defined structural properties rather than biological viability, we can demonstrate a high level of reproducibility and reliability. So, to summarize, while biology ultimately drives the healing process, the product itself is engineered in a way that allows for precise control and consistent quality from a regulatory standpoint.

David Brühlmann [00:03:57]:
Let’s shift gears a bit, Eva, and talk about the progress you’ve made so far, where you are today, and how your clinical studies are going. Tell us a bit about where you are right now in the development process.

Eva-Maria Balet [00:04:11]:
We’re very proud because we’ve now treated our first patients. We developed the technology in the laboratories of EPFL, and we carried out extensive preclinical testing in various animal models. Across those models, we observed excellent tissue regeneration, including the regrowth of muscle cells, epithelium, vascular structures, and nerve structures. Based on these excellent preclinical results, we received approval to conduct a first-in-human (FIH) study.

We’ve now successfully treated five patients. For us, these early human data are extremely valuable because first-in-human studies tell you things that no in vitro experiment or animal model can fully predict.

First of all, demonstrating human safety is essential. You can generate a great deal of preclinical data, but ultimately, real confidence comes from clinical experience. Many diseases are also difficult to replicate accurately in animal models. Often, you’re working with otherwise healthy animals, which don’t fully reflect the complexity of the diseased human environment.

This first-in-human study provided insights into both safety and efficacy. One of the most important aspects, however, is understanding how the product fits into real surgical practice. Can surgeons use it easily? Does it integrate seamlessly into existing procedures? Does it require additional training?

For TissueSpan, the results were very encouraging. We found that it integrates naturally into the surgical workflow without requiring major changes. We also demonstrated a strong safety profile, with no implant-related adverse events. Importantly, we observed very positive patient outcomes and high patient satisfaction. That really validates how the product performs in the real world.

David Brühlmann [00:05:44]:
What indication are you currently focusing on in these clinical studies?

Eva-Maria Balet [00:05:50]:
Our first indication is in uroginecology. More specifically, we’re focusing on urethral stricture disease, which is the narrowing of the urinary tract. It’s an attractive initial indication because the current gold standard often requires harvesting the patient’s own tissue, for example from the inner cheek (buccal mucosa). That creates a clear unmet clinical need and offers a significant opportunity to improve patient care.

There are alternative treatments for urethral stricture disease, but recurrence or failure rates can be up to 80%, depending on the treatment approach and the complexity of the stricture. So there’s a real need for better solutions. What’s also very encouraging is that, based on our first-in-human data, we’ve already been approached by surgeons in other specialties.

For example, in prostate cancer surgery there’s interest in using TissueSpan to support tissue repair and help prevent urinary leakage, and preparations for a first-in-human study are underway. Leakage prevention is also a major challenge in other surgical fields, such as colorectal surgery, which opens additional opportunities. More broadly, our vision is to make TissueSpan a versatile tool for surgeons, supporting soft tissue repair wherever it’s needed. So while we’re starting with one focused indication, we see strong potential to expand into multiple surgical specialties and patient populations over time. Our ambition is for TissueSpan to become part of the standard surgical toolkit for soft tissue repair.

David Brühlmann [00:07:07]:
That’s excellent. Are there any limits where you think your current technology won’t work, or are these tissue repair mechanisms fairly universal throughout the body?

Eva-Maria Balet [00:07:18]:
We’re really focused on soft tissue repair. For example, I don’t see this technology being used for bone regeneration or for replacing an entire hip joint. Our focus is on tissues such as muscle, vascular tissue, and the gastrointestinal tract. When you look at these tissues from a histological perspective, there are many similarities. For example, the urethra and the esophagus both have an epithelial lining that protects the underlying tissue from external substances such as urine or food.

Beneath that epithelial layer, there’s smooth muscle that enables the organ to function properly. Those shared structural characteristics are one reason we believe our platform has the potential to be applied across multiple soft tissue indications.

David Brühlmann [00:07:57]:
Coming back to the preclinical studies, you mentioned animal models and their limitations. I’m curious, when you refer to animal models, is that in combination with in vitro laboratory models? How do you typically balance those approaches in your field?

Eva-Maria Balet [00:08:18]:
At the beginning, we used what we call in vitro models. That means working in the laboratory with isolated cells. Our first objective was to demonstrate that cells could grow on our implant, that the material was not cytotoxic, and that cells could infiltrate the scaffold. All of that work was performed on the laboratory bench using isolated cells. However, isolated cells are not a complete living system. The next step was to move into animal models. There, you work with a living organism and perform the surgical procedure. Because urethral stricture disease was already our target indication, we selected a urethral reconstruction model. In this model, a segment of the urethra is surgically removed and replaced with the implant, which is then sutured into place.

This is also the first opportunity to demonstrate that the implant can be handled and sutured appropriately in a living system. At different time points, tissue samples are collected to follow cell ingrowth, tissue regeneration, and implant remodeling. Using immunohistochemistry, we can stain for different tissue types.

In our case, it was particularly important to demonstrate rapid formation of the urothelium, the inner lining of the urethra, because that layer creates a watertight barrier and prevents urine from penetrating into the surrounding tissue. It was also important to demonstrate the regeneration of smooth muscle. At the beginning, you only see small stained regions representing individual muscle cells.

Over time, those develop into organized smooth muscle bundles, allowing you to observe the regeneration of functional muscle tissue. You can also identify newly formed blood vessels, demonstrating vascularization, which is essential because newly regenerated tissue requires its own blood supply to survive. So our development followed the classic progression: first in vitro studies using isolated cells, followed by animal models to demonstrate both the biological repair mechanism and the practical feasibility of implanting and handling the scaffold in a living system.

David Brühlmann [00:10:19]:
You’ve already made significant progress with your technology and your company. As we all know, being an entrepreneur isn’t always easy. There are plenty of ups and downs. What has been the hardest moment so far in your company’s history, and what did it teach you?

Eva-Maria Balet [00:10:36]:
I think one of the hardest moments for us was around our first first-in-human (FIH) trial. We had just received approval and were ready to start. Then, two weeks later, COVID hit and everything shut down. There was no manufacturing, no surgeries, and instead of starting in 2020, we only treated our first patients in 2022. That was a very frustrating period because you realize that, even with the best planning and preparation, there are things completely outside your control.

What we really learned from that experience was the importance of adaptability. Instead of standing still, we focused on what was possible: continuing development, optimizing our processes, strengthening other parts of the company, and preparing ourselves even better for when things restarted. It taught me that progress doesn’t always happen in the way you expect, but it’s important to keep moving forward, even if the steps are different from what you originally planned.

David Brühlmann [00:11:28]:
Yes. I had one director who always told us, “Once you’ve made a plan, it’s already out of date.“

Eva-Maria Balet [00:11:36]:
Exactly. You can already start preparing Plan B and Plan C.

David Brühlmann [00:11:41]:
That’s true. But it doesn’t replace planning, does it? Another important part of being an entrepreneur—and something you’ve also made great progress on—is fundraising. You closed a pre-seed funding round in 2024. We all know that during 2024, 2025, and even today, raising capital has been quite challenging.

What was most challenging about that process? And what advice can you share with Smart Biotech Scientist listeners about communicating your science effectively so that you can secure funding?

Eva-Maria Balet [00:12:15]:
When we raised our pre-seed round, one of the biggest challenges was translating a strong scientific and clinical vision into something investors could clearly understand and believe in. Up to that point, much of our focus had been on solving a clinical problem and developing the technology. But suddenly the discussion shifts. It’s no longer just about the science—it’s about the business.

Investors want to understand who your customer is, how you’ll bring the product to market, what your cost structure looks like, and where the real value lies. So we had to broaden our thinking. Which indication should we enter first? How do we build the market? What should our go-to-market strategy look like? And what’s the long-term vision, including potential exit opportunities? What I learned is that biotech and MedTech investing is about connecting three elements: strong science, a clear clinical need, and a credible business model. You also need to communicate that in a simple and compelling way. It’s really about storytelling and capturing investors’ attention within the first 30 seconds. In the end, it’s not about simplifying the science; it’s about making the value of your innovation understandable from both a scientific and a business perspective.

David Brühlmann [00:13:24]:
I’d like to dive a little deeper into the business perspective. You’re currently pursuing—or rather, you’ve recently completed—an Executive MBA, where you’ve been developing new business and leadership skills. What are the most valuable skills you’ve built? And are there any you would recommend founders develop as early as possible?

Eva-Maria Balet [00:13:42]:
I completed the Executive MBA, and it was a very valuable experience. I finished it in September last year, and I completed it while running the company, which made it especially rewarding. What made it particularly valuable was that I could immediately apply everything I learned to my own company in real time—from accounting and investor relations to communication and strategy.

In many ways, I feel like I grew together with the company, constantly learning along the way. The MBA gave me a structured framework and the tools to navigate areas that aren’t typically part of a scientific background, especially finance and the language of business. Another important benefit was the opportunity to exchange ideas with executives from many different industries, which really broadened my perspective and challenged my thinking. Looking back, one thing I would have started earlier is building my financial and business vocabulary. As soon as you step into a leadership role, especially as CEO, being able to connect the science with the business side becomes absolutely essential.

David Brühlmann [00:14:45]:
As we’re wrapping up, Eva, what question should I have asked you?

Eva-Maria Balet [00:14:53]:
That’s a very good question. I think you’ve covered a lot of ground. We’ve talked about our product, the science, the clinical studies, fundraising, and many other topics. So, honestly, it’s difficult to think of another question.

David Brühlmann [00:15:10]:
No worries. With everything we’ve discussed today, what’s the single most important takeaway you’d like listeners to remember?

Eva-Maria Balet [00:15:19]:
I think one key takeaway is that translating science into real-world impact requires much more than great ideas. It depends on collaboration, mindset, and the people you surround yourself with. Even this conversation is a nice example of that. It happened through networking—through one of our collaborators, who introduced us. In many ways, that’s also how we’ve built Regenosca: by bringing together people with different expertise and perspectives. For me, whether it’s innovation, entrepreneurship, or opportunities like this, real progress happens through meaningful connections and collaboration.

David Brühlmann [00:15:55]:
Fantastic. Eva, where can people connect with you and learn more about your clinical studies and the latest developments?

Eva-Maria Balet [00:16:03]:
The easiest way to reach me is through LinkedIn. I’m always happy to connect, especially with people interested in biotech innovation and entrepreneurship. If you’d like to learn more about our work, you can also visit the Regenosca website or follow the company’s LinkedIn page.

David Brühlmann [00:16:17]:
Fantastic. Eva, thank you so much for joining the show today and for sharing this exciting science. Smart Biotech Scientists, you’ll find all the relevant links in the show notes. Eva, thank you once again for being with us today.

Eva-Maria Balet [00:16:31]:
Thank you very much for the good conversation.

David Brühlmann [00:16:34]:
Building something new means solving problems that no in vitro model or animal study can predict, while surrounding yourself with the right people before you begin. Eva-Maria’s candor about the hardest moments, the language of investment, and where this technology is heading is a reminder that mastery is built one challenge at a time. If you enjoyed this episode, please leave a review on Apple Podcasts or your favorite podcast platform. It helps other scientists like you discover the show. Thank you for tuning in, and we’ll see you next time.

Disclaimer: This transcript was generated with the assistance of artificial intelligence. While efforts have been made to ensure accuracy, it may contain errors, omissions, or misinterpretations. The text has been lightly edited and optimized for readability and flow. Please do not rely on it as a verbatim record.