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Speaker: From the campus of Harvard Medical School, this is ThinkResearch, a podcast devoted to the stories behind clinical research. I'm Oby, your host. ThinkResearch is brought to you by Harvard Catalyst, Harvard University's Clinical and Translational Science Center. And by NCATS, the National Center for Advancing Translational Sciences.

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Brain implants have the power to connect the brain to machines, helping treat various neurological conditions. But, like microchips, brain implants are typically stiff and rigid, unlike the brain material which is soft. The rigidity of the implants can cause scarring and even infection. CEO and co-founder Dr. Paul Le Floch talks with us today about the creation of Axoft and the new world of soft brain implants.

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Hi, Dr. Le Floch. Welcome to the show. You are currently the co-founder and CEO of Axoft, a neurotechnology company developing soft brain implants to treat neurological disorders. Can you walk us through your career path?

Paul Le Floch: Yes, of course. As you said, Paul Le Floch, a very typical French name. I grew up in the suburb of Paris in France. I did a master in Paris in executive engineering and I had an undergrad in-- actually-- in marine science, so I wanted to stay close to science. So in parallel I did another master that was more in applied sciences, applied physics, applied chemistry. And I've always been in between the engineering and the science side.

After that, I wanted to travel. And I ended up starting my PhD in materials sciences and mechanical engineering at the Harvard School of Engineering and Applied Sciences. And, yeah, from one thing leading to another, I started to work on bioelectronics, which is the field where we try to integrate electronics and biological systems together.

So they-- so, for instance, electronics can get information from biological systems. And within this field more toward brain implants technologies at various scales, either in tissue cultures or in animals. And that's how it started.

Speaker: Thank you. Can you talk to us a little bit more about your company and the need that inspired you and your team to create the brain implant.

Paul Le Floch: The company is actually founded by myself, by my PhD advisor, Jia Liu at Harvard, and Tianyang Ye, who was a postdoc at Harvard. Tianyang and I had this understanding that electronics cause a lot of damage into the brain because electronics materials have never been designed to be implanted into biological tissues. Electronics metals have been designed to make chips.

So we realized that there was a strong pull to develop new materials that interact better with biological systems and that's when Jia joined Harvard, and I was in the middle of my PhD, and I started to join his lab, and be his first grad student, and work on that. So from there, when we already had the concept of Axoft, but it was just applied to the research.

At the end of my PhD the project was getting very good results and we wanted to keep scaling it up and move toward more like pre-clinical settings and test the capabilities of the system to actually help-- potentially help patients because the problems that were driving us, that were problems from neuroscience, are actually similar to the problems that clinicians encounter regarding the capabilities of medical implants.

Speaker: What are some of the advantages and the challenges to using soft technology in this particular way and this particular avenue?

Paul Le Floch: Obviously, soft is good for the tissues in the body that are soft because two things that are alike usually get along together well. So when you make the implant very soft, it integrates well with the brain tissues. But the difficulty is that soft materials, like rubber, have never been developed for industrial, scalable process for nanofabrication. They are also less interesting in terms of electrical characteristics, like physical and engineering properties.

So we had to figure out how we can screen through the whole spectrum of soft materials and find the ones that will actually be good enough for this application. It's more difficult because we are trying to design a technology at-- from raw material instead of what's available in terms of process, so that makes the whole development pipeline longer and harder. But hopefully the outcome is more interesting because we have more flexibility and control over the technology.

Speaker: What can we expect for the future of your company? What's the future for Axoft.

Paul Le Floch: So the goal of Axoft is to increase the bandwidth of communication between the body, between the brain and the nervous system, and electronics, and the modern technology. We hope that will become the company that finally allow us to unlock the potential of the brain to communicate with-- as many neurons or as many electrical signals in the body as possible.

This will lead to a transformation of the treatments for the patients. We can imagine easily a future where patients with paraylisis that have a brain that can be totally healthy can actually recover a sense of independence, can work by using their thoughts to control objects, such as the computer, the phone, or robots. But it also applies to even diagnostic device, long-term diagnostic of neurological disorders-- such as refractory epilepsy, where the treatment of some patients is simply limited by the capabilities of the technology.

Speaker: That's amazing. As a CEO you need skills that might not come naturally or maybe are different from the skills you use on a daily basis with the engineering and the sciences. But what skills have helped you in your business success?

Paul Le Floch: That's a very good question and I think I have a good example. So the skill I'm going to talk about is definitely communication and some sense of leadership.

When I was in France, in my first master, I was president of an association of students to organize the events for the whole school and that really pushed me to work on skills that I didn't have. So it can-- just presenting things, managing conflicts, motivating people. And I can feel myself in the same spirit when I was doing this association back in France when I'm sometime running the company as CEO.

Speaker: Thank you for sharing that with us. So you attended one of our courses specializing in medical device development, Transforming Care with Emerging Novel Devices, or TRANSCEND. Could you talk a bit about your experience and some of your takeaways?

Paul Le Floch: Yeah, so class at TRANSCEND was-- I don't know if I can say that-- transcending. Yeah, because there were a lot of super qualified, super experienced people coming and that gave me a strong base of people to interact with and also some clues about what are the next steps. To me-- I don't come from the background of medical devices and health care.

I was opening to hear the perspective from experts and people who've been working in this field for so long and tell us, oh, you actually need to think about that because between your experience as a scientist and having an impact on the life of people from the clinical perspective but also from the business perspective how you build the business. There is a difference. And the class gave me takeaways to avoid some of the pitfalls that the researcher can fall in when they try to start a venture.

Speaker: So I want to step back for a moment and ask you a question about the technology for your company. One of the examples you said was someone maybe in the future someone who has paralysis maybe able to work a robot, or a computer, or a phone by using their thoughts. Can you draw the connection between--

Paul Le Floch: Yeah.

Speaker: Thank you.

Paul Le Floch: Essentially, to do that, we need an implant that can record or stimulate neurons electrically. The reason it's not working very well right now is because the tissue tends to reject the implants and you have these strong scar tissues that form around your implants or sometimes the implant is moving within the brain. And that limits our ability to have an implant that lasts for many years and have an implant that you can scale up to measure more neurons or stimulate more neurons at the same time. So most implants don't last for very long because of that.

So what we do is we figured out which materials that are almost as soft as the brain tissues we can use to make the implants-- the part that goes inside the brain. And that's solve those two problems that I just mentioned to-- about the temporal and the number of neurons, scalability. And this implant is connected to a chip that can be placed at the level of your skull.

So this one is outside of the brain, but it's still connected to the device. And this does all the electrical functions that allow to transmit the signal to the outside world or signal from the outside world to the brain. So this is one part of the system.

And if you think in particular of the example of paralysis, you have two other pieces in this system that needs to be developed and that we'll work on in the future. One is the software that analyzes the data that you get from the brain and that sends a command to this third part that is the effector. So the effector is what you described. It's the computer, the robots, or whatever that is human-made and electrically controlled. Or not even human-made, you could use your brain to stimulate your hand. Who knows?

Speaker: Thank you. That is super helpful. So I'm going to bring this back forward a little bit. And you talked about the future or what you hope is the future of your company and then about TRANSCEND and the skills you learn there. How do you see some of the business-focused skills you acquired benefiting the work of your company and moving your company forward.

Paul Le Floch: So there is one thing about the size of the markets-- how do you evaluate the size of the market with different types of approach, but top down. And being realistic about the assumptions that you make, the notion of talking to customers and users to refine this, I think it gives a clear direction to the company.

And the second thing that-- it's related to business, but it's more about product development that leads to the business-- is the steps of product development and regulatory pathway for medical devices that we don't obviously know as a researcher and it offered a very nice framework to think about where we are in terms of development and what are the natural next steps.

Speaker: Well, thank you so much for joining us today for this conversation. We look forward to hearing more about Axoft and what's next.

Paul Le Floch: Awesome, thank you so much, Oby.

Speaker: Thank you for listening. If you enjoyed this episode, please rate us on iTunes and help us spread the word about the amazing research taking place across the Harvard community and beyond. We are always looking to connect and collaborate with the research community and would like to hear from you. Please feel free to email us at onlineeducation.catalyst.harvard.edu to inquire about being a guest on the podcast.

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