The Future Of Medicine & Helping People Walk Again with Asaf Toker, CEO at Matricelf

(Joel Beasley at 00:00:03) Hello, my friends. Today we're talking to Asaf, CEO at Matricelf, and we discuss how their bio garage will one day allow paraplegic people to walk again, how being a physician and entrepreneur are really the same thing, and why it's critical to be a team member when you're the boss. All of this right here, right now on the Modern CTO podcast. Here we go.

(Intro/Outro Narrator at 00:00:35) This is the Modern CTO podcast.

(Joel Beasley at 00:00:44) You guys are working on regenerative tissue engineering. I saw the word bio garage, which was kind of mind-blowing. Can you tell me a little bit about what is regenerative tissue engineering?

(Asaf at 00:00:57) Sure. First of all, good evening.

(Joel Beasley at 00:00:59) Good evening.

(Asaf at 00:01:00) Yeah. For us, it's 10 p.m. here in Israel. So it's good morning for you, but good evening for us. Basically, you know that there are millions of patients all over the world that are suffering from what we call a tissue-related disease in which there is a tissue damage that leads to a disease that is usually a very expensive disease, a chronic disease, which has a huge economic, social, and medical burden. Those diseases, like, for example, diabetes, Parkinson's, heart failure, kidney failure, liver failure—any tissue that you give me, I'll give you the disease. So in those diseases, the best solution, the holy grail, is tissue engineering. You go to the garage, and you mentioned the bio garage. When you have a problem with your car and you go to the garage, for example, you have a problem with your brakes, they change your brakes.

(Asaf at 00:02:01) And what is unique about regenerative medicine is that instead of basically trying to find good medications for the symptoms, we are basically curing the disease because we are changing the damaged tissue with a new and functioning tissue.

(Joel Beasley at 00:02:20) Okay. Interesting. So I thought it was mainly focused on paralysis, but that's just one type of tissue-related disease?

(Asaf at 00:02:30) Exactly. We are basically developing a platform in which we can basically create any tissue that we want. The first indication that we are targeting to the market is spinal cord injury, but we can do it very similarly to Parkinson's disease or age-related macular degeneration or basically any other tissue-related disease.

(Joel Beasley at 00:02:57) So are tissues today able to be transplanted from one person to another?

(Asaf at 00:03:03) Yes. You know, for example, somebody who needs a heart, a new heart, usually they take a heart from a cadaver and transfer. Yeah, yeah. So it is possible. The main problem, and this is what we are trying to solve, is that when you just—a short notice about tissue engineering—when you build a tissue, you basically need two main ingredients. You need cells on one end, and you need a matrix or a scaffold on which the cells basically build the tissue. And most of the companies that are dealing with tissue engineering, including tissues from cadavers, are based on either cells from a different patient or a scaffold that is usually a synthetic scaffold.

(Asaf at 00:03:56) And our human body is a very sophisticated machine. It understands very fast that there is a foreign cell or a foreign matrix in the body. It triggers the immune response and eventually leads to tissue rejection. And what is unique about Matricelf is that we are building completely autologous implants in which both the cells and the matrix are coming from the patient themselves. So we have no immune response to our implants.

(Joel Beasley at 00:04:29) That's crazy. So when you're talking about using cells and the matrix from the patient, it makes sense to me that you're able to scrape cells from a patient and culture those. But can you give me an example of what the matrix is? Because in my mind, I'm thinking that's a bone or a tendon or something that really should stay inside the patient.

(Asaf at 00:04:52) Sure. What we do is we use a specific organ that is called omentum. This is an intra-abdominal tissue. It's a unique fatty tissue that basically covers the abdominal organs. And we use this tissue to create the matrix as a thermo-responsive hydrogel in which we take induced pluripotent stem cells and differentiate the cells within the matrix to become basically whatever tissue that we want.

(Asaf at 00:05:26) And what we noticed is that the matrix changes its properties as the differentiation process develops. So, for example, if you are creating a neural tissue, the matrix changes its properties to become a neural support matrix as the differentiation progresses. If we are differentiating it to become a cardiac tissue, as the cardiomyocytes differentiate, the extracellular matrix changes its properties to become a cardiac support matrix. So we have a very unique matrix to support the cells creating a tissue.

(Joel Beasley at 00:06:07) So you're saying that when you take this tissue from the abdomen and you mold it into how it would fit to be cardiac tissue, it actually changes its properties?

(Asaf at 00:06:18) Exactly.

(Joel Beasley at 00:06:19) What causes that?

(Asaf at 00:06:21) So we know that the cells, they secrete various factors. And as they secrete more and more factors, it affects the surrounding matrix. So the matrix changes to support the cells to help them become the specific tissue.

(Joel Beasley at 00:06:40) Okay. That's amazing. You mentioned making neural tissue too. So can this tech be used to treat neurodegenerative diseases as well?

(Asaf at 00:06:50) So it depends on the disease because some neural diseases are genetic. And if we take the cells from the patient himself, then the cells already have those genetic defects, and therefore, the disease will reoccur. So there are some technologies that we can modify the genes, but it is very, very complex. So it really depends on the disease. We target diseases in which there are no genetic abnormalities. It's only an issue of a tissue failure, and we simply build the new tissue.

(Joel Beasley at 00:07:30) Okay. Very cool. So how did you get into this? What were you doing before your company, Matricelf? Is that how you say it?

(Asaf at 00:07:37) Yeah. Matricelf. It's a shortcut of three words: matrix, cells, and self. Because we use the matrix and the cells from the self, from the patient himself.

(Joel Beasley at 00:07:50) Very cool.

(Asaf at 00:07:52) My background is, I'm a physician. I'm a pediatrician, and I worked in several HMOs in Israel in senior positions. Over the last few years, I was involved in entrepreneurship and was running a few startups as the CEO. Three and a half years ago, I was approached by the team in Matricelf, by the founders, who asked me to join as the CEO.

(Joel Beasley at 00:08:17) That's super cool. So where's the tech at now?

(Asaf at 00:08:21) We did a pre-IND meeting with the FDA to basically understand the regulatory roadmap for us. Basically, what we are currently doing is following this roadmap towards first human clinical trial in 2025. So we have some additional efficacy trials in rats, then a safety trial in rats as well, and the next phase will be first human clinical trials.

(Joel Beasley at 00:08:51) That's super cool. So how's it going with the rats? How's the efficacy been so far?

(Asaf at 00:08:56) So we did, so far, efficacy trial in mice, and we showed very nice recovery of those mice both in an acute and a chronic setting. And it was published last January in Advanced Sciences. Currently, we are building the chronic model on a rat, which we just completed a few weeks ago. And we are now moving to the pilot study for the chronic model in rat for a contusion injury in the spine.

(Joel Beasley at 00:09:28) Crazy. So you got a paralyzed rat that you're trying to help walk again?

(Asaf at 00:09:33) Yeah. Exactly. Exactly.

(Joel Beasley at 00:09:35) Man, so from a technological perspective, not necessarily a regulatory perspective, how far away do you think we are from being able to cure paralysis in people with this tech?

(Asaf at 00:09:49) Yeah. So, you know, it's the million dollar question. Many companies tried different ways to cure paralysis, and unfortunately, they all failed. We hope that since we're using a complete autologous implant and there is no immune response to our implants, then the nerve connections will be able to be efficient enough to make people walk again, feel again, and function again. And this will be a game changer.

(Asaf at 00:10:22) The first human clinical trial is planned for early 2025. And we believe that if in such a trial, a patient will be able to take his iPhone and text a message by himself or drink a cup of coffee by himself or walk again. This will be a game changer.

(Joel Beasley at 00:10:44) Yeah.

(Asaf at 00:10:44) And this is what we're aiming for. Fortunately enough, we have, apart from the amazing technology, we have an amazing team of scientists. And I think that one of the most important things is the motivation because we get emails and phone calls on a daily basis from patients all over the globe that currently we are their only hope. This gives us a lot of motivation to try and find a cure to this devastating medical condition.

(Joel Beasley at 00:11:18) I bet. That's really powerful. So what's it going to look like to go to the doctor and receive this treatment from a patient perspective?

(Asaf at 00:11:27) So it's not that simple. It takes us four months to build the tissue. Once a patient will be, unfortunately, involved in, for example, a car accident or a ski injury, physicians, the neurosurgeons will know that they will never be able to walk again or to function again. We will take a biopsy from the patient's omentum, this intra-abdominal fatty tissue. We also take a blood sample from the patient to collect the cells, and then the process itself takes approximately four months.

(Asaf at 00:12:05) And after four months, once we have the tissue ready, we will do a spine surgery in which we basically clear out the scar tissue at the injury site and implant, basically filling the gap of the injury with our implants.

(Joel Beasley at 00:12:24) That's insane. That sounds so futuristic.

(Asaf at 00:12:28) Yeah. And again, if you come to our labs, we already produce those implants. And you can see the neurons actually go out of the implant to try to connect with the neighboring implant. And in mice, we saw that they actually reconnect the area before and after the injury site. Basically, the mice regain their walking abilities.

(Joel Beasley at 00:12:56) So for the neurological diseases, you mentioned it doesn't work on ones that are genetic. So dementia, that probably isn't an option, but a stroke. Is that something that helps with?

(Asaf at 00:13:09) Parkinson's disease. There are several diseases that are good candidates for a second indication, which we are currently debating within the company which one it should be. And we hope that during 2023, we will start in parallel to the spinal cord injury program to develop another indication as well.

(Joel Beasley at 00:13:35) So as CEO, what does your job look like at the company? What are you doing for Matricelf?

(Asaf at 00:13:40) So the CEO basically supervises everything. So you need to know a little bit finance. You need to know a little bit legal. You need to know about the science. You need to build a business plan. You need to talk with investors. You need to talk with partners, basically represent the company in every major milestone that we have. You know, it's a very interesting job. Fortunately, I have, as I said earlier, I have an amazing team. It's one big family and really joyful work. And the mission is so huge that we hope that we will deliver those amazing implants to patients.

(Joel Beasley at 00:14:29) Yeah. So I'm curious about the business side of it. How does funding work for a company that's so research-based right now?

(Asaf at 00:14:39) So it's very expensive to develop those implants.

(Joel Beasley at 00:14:43) Yeah.

(Asaf at 00:14:44) We raised funding privately. Last year, we IPO'd at the Tel Aviv Stock Exchange. So we are a publicly traded company. So we raised most of our money from the public, currently planning to expand. And as you asked me the previous question, what are the roles of the CEO? So one of the main roles of the CEO is basically get money to the capital to support the research activity.

(Joel Beasley at 00:15:16) That's super cool. Have you gotten interest from any of those billionaires that are focused on living forever, like Peter Thiel?

(Asaf at 00:15:24) No. We think it's a little bit too early to approach them. I'm sure that as we progress and deliver good clinical data, I think it will be in their interest to approach us and see what we do because you need to be in our lab five minutes to understand the magic. It's true magic to see those functioning three-dimensional neural tissues basically connect with each other.

(Joel Beasley at 00:15:53) Do you have videos of this online where people can check it out?

(Asaf at 00:15:57) Yeah. We have a website. We have presence in social media. In our website, there is a presentation. There is a movie. And people who want to learn a little bit more, they can either read the articles that are in their website, or they can contact us. We answer everyone who contacts us.

(Joel Beasley at 00:16:17) So our podcast really thrives in the cross section of technology and leadership. A lot of people listen for advice on how to be better leaders for their teams within their companies, and those are skills that really span every industry. And so I'm curious. I know you moved from doctor to some entrepreneurial ventures to now. What's been one of the biggest lessons you've learned entering more business leadership roles?

(Asaf at 00:16:46) I think that being a physician, being an entrepreneur, or being a CEO is the same. The main idea is to be a human being, to be a good human being, to help your employees, the people that are approaching you, and to be nice. You know, I saw a few months ago, a CEO that fired most of his team by Zoom.

(Joel Beasley at 00:17:13) Oh, Robinhood?

(Asaf at 00:17:15) Yeah. And again, if you want your team to follow you, they need to understand that you will be there for them always. Once they understand it, they will do anything to help you deliver the common goals of the company. So the first tip I can give to somebody who wants to become a CEO is to work on his personality skills, on how to communicate with people, how to talk with them, and how to be a good person for their employees. Just for example, we have every day, and I mean every day, we have a company lunch in which we sit all together. It's a—I mean, we're not 100 employees. We're only 12. But we sit together in the lunchroom, and we talk about our families, about our trips, about things that are not related to work. And we do it all together as a big family. So we know that once we have such an intimacy within the group, then the group becomes a special unit that will do everything in order to bring good results for the company.

(Joel Beasley at 00:18:38) That's really cool. I recently interviewed the CEO of a company called Apadana Solar Technologies, and they're larger now. I don't remember their headcount, but maybe in the hundreds. But when they were smaller, also, lunch was a big thing for their company, and he would actually make lunch for his employees every day. And as the company has grown, he's continued to do that. And so now he runs a cafeteria where he, as the CEO, is in there making lunch for every person that wants it every day. And I thought that was really cool and a great way to lead by example with empathy.

(Asaf at 00:19:18) Yeah. You know, being a good person is good not only for the company. It's good for everyone. But for example, as a CEO, if somebody is sick, I always call them the next day to see if everything is okay, if they need anything from the company. If somebody comes back from a vacation, you always call and say, how was the vacation? And we talk about the vacation. So it's running a company, but basically making the people that are working with you—and again, it's working with you. They're not working for me. They work with me in order to bring good news for our investors and for the patients. And when you do it and you have a great team, it brings you one step closer to achieve your goals.

(Joel Beasley at 00:20:13) I love that distinction you make, working with you instead of for you. That's something that at our company, for some context, I was an individual contributor podcast producer for a long time, and then suddenly we started making all these podcasts for other companies. And now I lead a small team, and I still am not and never have been comfortable thinking of it like employees and boss. I always say coworker because I think that's weird to impose that kind of social hierarchy on top of the managerial hierarchy that's already there.

(Asaf at 00:20:51) And I'm sure that they know that you are the boss, but you are part of the team. I mean, you can be the boss without being a part of the team, but then your team is not really working with you.

(Joel Beasley at 00:21:07) Right.

(Asaf at 00:21:08) But if you are a part of the team and you are leading the team, then the team will go with you to achieve those goals.

(Joel Beasley at 00:21:18) Absolutely. Well, Asaf, I got one more kind of leadership question for you, and then we can give you the soapbox to shout out whatever you want to shout out for Matricelf. But what's one thing you wish you knew before you started into your business ventures?

(Asaf at 00:21:39) Wow.

(Joel Beasley at 00:21:40) Like, if you could go back and tell young Asaf.

(Asaf at 00:21:42) Yeah. Usually, when you start a business, you are certain that it will be a walk in the park, and it's not. It's not a walk in the park. It is usually very complicated. It's the world of the unknown. There are many challenges that you never expected them to happen. But if you go straight and you are committed to what you do, you can overcome all those challenges and basically get to what you're looking, what you are seeking. And at the end, it might not work. I mean, we know that it might not work. We might implant it in patients, and it will not work because we are not mice, we are not rats, we are not monkeys, we're human beings. But as long as we are clear with our goals and we know the advantages and we know that we might fail, I think that makes us doing our work better.

(Joel Beasley at 00:22:51) Man, that's a fantastic way to wrap it up, man. Thank you so much for sharing your knowledge and advice as a leader as well as about the super cool stuff you guys are doing at Matricelf. It really does sound like a game changer, and I'm excited to follow your company. Is there anything you want our listeners to take away from the episode, any last shout out for your company?

(Asaf at 00:23:13) At the entrance to our lab, we have a nice sentence that Steve Jobs once said. People who are crazy enough to think that they will change the world are the ones who do. So we believe that we are crazy enough doing some very crazy stuff in order to change the world. So again, thank you very much for your time, and I hope that we will make people walk.

(Intro/Outro Narrator at 00:23:42) Thank you so much for listening. And if you found this episode useful, please share it with a friend or colleague who you think would get value from it. And if you have topics that you would like to hear discussed on the podcast, either add me on LinkedIn or send me an email [email protected]. Every time I get an email or LinkedIn message, it absolutely makes my day and inspires me to keep going.