Medsider: Learn from Medtech and Healthtech Founders and CEOs - Why Early Risk Retirement is the Best Investment You Can Make: Interview with Dr. Sam Mazin, co-founder and CTO of RefleXion Medical

Episode Date: April 5, 2023

In this episode of Medsider Radio, we sat down with Dr. Sam Mazin, CEO of RefleXion, a therapeutic oncology company with a novel technology that marries positron emission tomography (PET) and computed tomography (CT) with radiotherapy. Sam received a Bachelor of Applied Science in Computer Engineering from the University of Waterloo, Canada, and holds a Ph.D. in Electrical Engineering from Stanford University. He co-founded RefleXion Medical in 2009 and is the inventor of the company’s core technology, which aims to improve treatment outcomes in patients with tumors in the lung or bone resulting from primary and metastatic cancer. In this interview, Sam shares why a startup medtech company should focus on retiring risk and pitching investors as early as possible. He also talks about the most important aspects every entrepreneur should consider when designing clinical trials to meet various goals.Before we jump into the conversation, I wanted to mention a few things:If you’re into learning from proven medtech and healthtech leaders, and want to know when new content and interviews go live, head over to Medsider.com and sign up for our free newsletter. You’ll get access to gated articles, and lots of other interesting healthcare content.Second, if you want even more inside info from proven experts, think about a Medsider premium membership. We talk to experienced life science leaders about the nuts and bolts of running a business and bringing products to market.This is your place for valuable knowledge on specific topics like seed funding, prototyping, insurance reimbursement, and positioning a medtech startup for an exit.In addition to the entire back catalog of Medsider interviews over the past decade, premium members get a copy of every volume of Medsider Mentors at no additional cost. If you’re interested, go to medsider.com/subscribe to learn more.Lastly, here's a link to the full interview with Sam if you'd rather read the summary instead.

The more you can chip away at that risk, whether it's technical risk or clinical risk or market risk or regulatory risk, you know, the more you're creating value in the company. And so I think that's how I look at. That's how I've come to look at being productive. It's not the how many tasks did I, you know, achieve today quantitatively. It's what is the Pareto curve of those tasks in terms of risk, right? what task helps me retire a key risk as quickly as possible. And when I do that, that is productivity, at least in the entrepreneurial sense. Welcome to MedSider Radio, where you can learn from proven med tech and healthcare thought leaders through uncut and unedited interviews.

Now, here's your host, Scott Nelson. Hey, everyone, it's Scott. In this episode of MedSider, I sat down with Dr. Sam Mazen, who received a Bachelor of Applied Science in computer engineering from the University of Waterloo in Canada and holds a PhD in electrical engineering from Stanford University. Sam co-founded Reflection Medical in 2009 and is the inventor of the company's core technology, which aims to improve treatment outcomes in patients with tumors in the lung or bone resulting from primary and metastatic cancer. Here are for you the key things that we discussed in this conversation. First, test and tackle the highest risk concepts of your

product in the early stages. This is one of the most efficient ways to put your initial and often limited capital to use. Second, talk directly to the appropriate audience when determining the type of clinical studies to run. You should design your clinical programs around what a single consumer wants to see from your research instead of trying to meet the needs of different user groups through a single study. Third, it's never too early to start raising capital. Instead of waiting until you've perfected your product, start reaching out and pitching to potential stakeholders as soon as you can. And don't be afraid to re-approach investor groups that previously said no. Before we jump into this episode, I wanted to let you know that we recently released the second volume of Medsider mentors.

What summarizes the key learnings from the most popular Medsider interviews over the last six months or so. Look, it's tough to listen or read every single MedSider interview that comes out, even the best ones. But there are so many valuable lessons you can glean from the founders and CEOs that join our program. So that's why we decided to create Medsider mentors. It's the easiest way for you to learn from the world's best medical device and health technology entrepreneurs in one central place. If you're interested in learning more, head over to medsiderradio.com forward slash mentors. Premium members get free access to all past and future volumes. If you're not a premium member yet, you should definitely consider signing up.

In addition to every volume of Medsider mentors, you'll get full access to the entire library of interviews dating back to 2010. This includes conversations with experts like Erica Rogers, CEO of Silk Road Medical, Dr. David Albert, founder of Alive Corps, and so many others. In addition, as a premium member, you'll get to join live interviews with these incredible med tech. and health tech entrepreneurs. Learn more by visiting medsiderradio.com forward slash mentors. Again, that's medsiderradio.com forward slash mentors. Sam, I kind of, I provided an high level overview of your bio at the outset of this interview.

But let's start there. Tell us a little bit about your experience leading up to starting reflection. Or some folks call it reflection, but I think the proper way to say it is reflection. You're starting the company and kind of your, you're, you know, starting the company and kind of your current role as CTO. Sure. And nice to be here, Scott. I was trained in computer engineering at the University of Waterloo.

I'm from Canada and just fell in love with technology. This was during kind of the dot-com boom of computers and the internet and things like that. I came to Stanford for graduate school thinking I was going to focus in communications technologies. And I came across an advisor who, you know, every master student is paired with the academic advisor. And mine said, hey, you know, you really ought to consider the field of biology because I see biology and computing really coming together. And so that turned me on to a completely new world.

I was not considering medicine or biology in any form. I was looking at ones and zeros pretty much all day long. But so I started taking classes in that space, and I fell in love with this field called medical imaging. which, you know, just a way to see inside the body non-invasively. And I fell in love with this concept of essentially using math to make pictures of the body. And so, you know, that was a really attractive field for me, attractive enough that I decided to do a PhD in that area.

And it was after I completed my PhD and started a postdoc that I also came to know a little bit more about a related but completely separate field called radiation therapy or radiation oncology. There was someone who was offering a seminar in this, in kind of an adjacent department, and I decided to attend the seminar and learn a little bit more about radiation therapy. And it dawned on me that, you know, hey, here's an interesting way to treat cancer, except there's a big problem in this field of radiation therapy, which is that, you know, you're using radiation to shoot at tumors. But the problem is you can't really see where you're shooting. And so it makes some people unsettled to hear this, but it really is a big problem in the field. You know, you make pictures

of the body before you go in for a treatment, but then during the actual treatment, it's really difficult to actually know exactly what's happening. And so you go through this very complex and long process to try to make sure the beam is, you know, on target. So this idea dawned on me that, hey, you know, I knew a lot about how medical imaging worked in terms of these modalities like, you know, I'm sure you're familiar with CT and MRI and pet imaging. Specifically pet, I knew the physics of how that worked, but, you know, there's this idea that just hit me on a new way to use pet that would solve this problem in radiation therapy. And so that's what led me to eventually create reflection and start the company and file for the first patents and things like that.

I didn't know it was going to become a company. I thought it was just a neat idea. But, you know, I was pursuing an academic career and this idea then kind of took hold of me. And I couldn't let it go. And that's how I ended up ultimately starting the company. That's awesome. I love those stories when it's like, this is a really killer idea. I never kind of sort of had this intention to build out a full on company around it. But what was sort of the, that point in time when you're like, this is, this actually really has legs. You know, this should actually be a company that pursues this, you know, this idea and this,

this platform with more rigor. Well, I didn't know anything about business plans and, and, you know, entrepreneurship. I mean, my dad is an entrepreneur himself. So I guess you could say it's in my blood. But I didn't really know much about. well, could this really be a company? I took a business school program at Stanford to try to help, you know, help me do that, where they put us in a team and we formed a business plan.

And it seemed like there might be something there. But you really wasn't until I told this idea to my high school friend who was actually in business school himself at a different university that I told him about this idea. And I told them, hey, look, you know, I need some help here. I'm not sure. I think this could be something big, but I just don't know. And he eventually agreed to, you know, help me out. He started entering this into basic, basically using it for his classwork, started interviewing clinicians with me about the potential for this technology.

And that's when he started to become convinced that this could be something meaningful. So we decided to start the company together. And this was back in 2009 when we co-founded the company. But it was really, I think, the combination of my. my co-founder and I, you know, thinking about it together as well as, you know, starting to really talk to potential users, you know, so these would be radiation oncologists, the doctors who prescribe these treatments and deliver these treatments with new technologies. You know, it wasn't kind of everyone was saying yes, go, go, go. But the ones that were saying yes and enthusiastic, I think gave us a real indication that this is something at least worth continuing to explore and building on. Yeah, that's great. And the platform itself is called, how do you pronounce it? Is it syntax or scientics?

Cynx, yes. Syntics, okay. Yeah, synchx therapy. So the, yeah, and syntax technology, what that really is, it's a way to use cancer itself to tell the radiation therapy machine where to shoot directly. It's the first, what I would call autonomous radiotherapy system where instead of the traditional problems of radiation therapy where you have to form these kind of anatomic images with other modalities and try to line up things. And usually there's a person involved to interpret

the image. Here, it's the cancer acting as a beacon. It's providing a homing signal to the machine. And the machine is locked on to that target continuously in real time, accounting for things like motion, like patient breathing, which is one of the biggest challenges in radiation therapy to account for. And so it's... It's the technology that enables this autonomous form of radiotherapy. The name Cintics comes from scintillation, which the system involves pet imaging technology. Pet detectors have crystals that literally scintillate or light up when they sense the emissions coming from the cancer itself. And then the X and Cynix stands for X-rays because X-rays are the therapy.

we're using to direct radiation back to its source or reflect the radiation back where it's coming from, namely the cancer itself. So Syntics Therapy is both the seeing and the treating happening at once. Got it, got it. And we'll go back in time to learn a little bit more about the history of the company, you know, dating back to, you know, that 08, 09 timeframe. But if I'm, I want to put myself inside issues of a patient and you provided just a great overview of kind of like what you're doing. But walk me through that. Is there anything that I swallow or is it literally just like you're providing the machine, the machine does all the work and it's just kind of like a normal CT for a patient. Help me understand that a little bit. If you're a patient and hopefully you're never

a patient, but if you're a patient, you know, the way a synchance therapy would feel like is almost equivalent to getting to how you would feel if you were getting a PET scan. And what is a PET scan? A PET scan is a scan where you're administered usually intravenously with what's called a radio tracer. It's a radiopharmaceutical. It's a very small amount of drug that it's in such small quantities. The body doesn't even know it's there. But it's tagged with a radioactive label so that wherever that drug goes, it's going to send out signals. Okay. And what a PET scanner is is really just a device where you lie on this table and the device just senses all those signals and makes a map of where those signals are coming from in the body. The most common type of radio tracer

used is actually a form of sugar. It's called fluorodeoxy glucose. It's a glucose analog. And it just it highlights exactly where tissues in the body are consuming sugar or cells in the body are consuming sugar rapidly. And you might imagine tumor cells or cancer cells because they're dividing very quickly and they're growing and they usually have inefficient ways of doing that, they're consuming glucose at a much higher rate than normal tissue. And so, you know, if you were to just Google PET scan cancer, you'll see images of what PET scans look like. You know, those kind of bright spots in the image are where you're seeing glucose being used a lot more actively and those tend to be where tumors are. So, so from a patient's perspective,

if you were to get a synchytics therapy, you'd be undergoing the same process as getting a PET scan where you're injected with that form of glucose in your vein. You're kind of sitting in a lazy boy chair for about 60 minutes as the radiopharmaceutical distributes throughout your body and concentrates in those areas of cancer. And then you lie on a reflection machine and not a PET scanner.

And the machine will be using that information to target and deliver radiation to one or more cancer sites in your body. So another way to think about it is we're turning a PET scanner into a treatment device for the first time. Got it. That's cool. That's super helpful, helpful overview. And you're, and this is, you're actively commercializing this technology right now, syntax. That's right. We just received FDA clearance for Cintex therapy, you know, in early February. Got it.

And so we're commercializing it right now. Okay, very, very cool. And if, for those listening that don't get a chance to read kind of the summary recap of this interview, the website's Reflection.com, but it's spelled R-E-F-L-E-X-I-O-N. R-E-F-L-E-X-I-O-N dot com. I pronounced it reflexion before Sam politely corrected me that it's reflection, reflection. but that's how it's spelled. So definitely encourage you to check out the site if you don't get a chance to,

or if you don't get a chance to read the interview recap. It's a beautiful site. It's, it's, it's really, really well done. Thank you. Yeah. So it's very, very, very cool technology and it'll definitely be fun to see, see where the company goes from here. So on that note, let's kind of step inside the old Medsider time machine and kind of go back, you know, you know, maybe about 15 years or so and learn a little bit more about about the journey, right, that you've been on. And so when you think about kind of maybe those early years, when you're thinking, this is, this is a great idea. This could be a business. Oh, yeah, this maybe this maybe should be a full-on company.

Those first prototypes of syntax, you know, when you think about kind of the iteration and what that process looked like, you know, are there one to two things that kind of really stand out where, you know, maybe I would do things differently or, yeah, this is what we got, you know, we did really well. Talk to us a little bit about kind of that iterative sort of prototype. stage of the company. Sure, yeah, and it was a critical stage, as you might imagine for us. So Syntics therapy, because it involves using PET to detect and radiation therapy to treat at once, it involved a new way of actually building a radiation therapy device. And so, you know, what is a radiation therapy device, you know, first of all, it's really a what's called a linear accelerator, which is a device that accelerates and makes basically high energy x-ray beams, and that's the therapy that you're actually delivering to the tumor.

But it delivers those beams at multiple angles around the patient so that you can concentrate radiation dose in the tumor while spreading it out or kind of smearing it out across other healthy tissue that you don't want to irradiate. So it's a way to kind of concentrate your dose in a particular area. And typically these radiation therapy systems rotate the linear accelerator at a rate of about one revolution per minute. So it takes about 60 seconds to go around the patient,

kind of this slow C arm, big C arm that's moving around the patient to deliver the treatment. Because of the way we're using PET in a real-time way, that we need to take those emissions that are streaming out of the cancer in a sub-second way because the cancer is moving due to the breathing of the patient and other factors, we can't have a slow-moving radiation therapy machine. We need actually something that moves much faster. So instead of one revolution per minute, we needed to rotate a linear accelerator at one revolution per second.

And so that was obviously a big required increase in the speed of these high energy and complex electromechanical systems. And so, you know, that was a big technical risk for us because, you know, We went to, when we were trying to raise money for the company, we obviously went to venture capital. You know, we went, you know, the traditional doors down Sand Hill Road knocking on all the doors and hearing a lot of no because the no was, you know, it was a rational no. It was, it was, wait, you want to raise 10 million bucks to build a machine that you don't even know it'll work until you build it. And that's just like the ticket in to see whether all this might, might even work.

And so, you know, we were forced to also go to strategic companies, you know, ones in the imaging or radiation therapy space, none of whom could, you know, thought we could actually build this thing. So it was the biggest, you know, hurdle. It was a bit of a catch-22 because, you know, the only way to solve this hurdles you needed to raise money to prove you could solve it. But that was the biggest, you know, risk for us as a company. Can we even, you know, can this even be built? thankfully we actually found some intrepid investors that decided to really take a chance and and give us the it turned out to be an $11 million series A round back in 2014 to actually take a shot on goal and actually try to build this system. Probably the most important thing we did was we recruited not only a brilliant person in the pet imaging space but a brilliant engineering leader. His name is David Larkin. And he actually came from intuitive surgical, where, you know, that company has developed some

amazing systems on the surgical robotics front. But, you know, he brought a philosophy into the company that I thought was really critical for us to answer these questions early on. And this was the big learning for me. And I got to learn from, you know, a true expert like David, where, you know, he kind of told, you know, this kind of scratchwork team he put together pretty quickly of this concept. of follow your fear. Like what is it we are the most afraid of?

What is it the thing that we think will kill us? And let's work on that. You know, it's so easy to kind of put blinders on because, oh, I can at least get this task done and I know I can build, you know, the gantry for this system and I know I can do this and that. But if I'm really worried about whether a linear accelerator is going to handle, you know, the G forces at one revolution per second and or if I'm really worried about the device which is called a multi-leaf columnator, which was a completely new version of that device,

a new topology that we had to design from scratch. If those are the things that could end up killing us as a company, let's work on those first. So before we even tried to build a full prototype of this machine, we tried to answer those questions first. Can we rotate a linear accelerator at those speeds? Can we build at least a crude form of a multi-leaf collimator, at least the concept to just answer the question, can this be done? And I thought that was probably the most important set of early decisions the company made was to invest, what sounded like a lot of capital at the time, but really wasn't efficiently invest that capital to turn over those cards,

the critical cards to answer the question is it worth continuing. Yeah. I absolutely love that advice of like lean into what is going to make you most, you know, what makes you most fearful, right? What makes you sweat? It reminds me of a phrase, I think I first heard it from Seth Godin, who's kind of a mostly known for his kind of marketing chops, but he often would say, like, if you're feeling nervous about this next thing that you're working on or that you're preparing for, that's usually a good thing, right? If it makes you nervous, if it feels uncomfortable, lean into it. And your feedback around that kind of those first,

kind of getting to those first inflection points, you know, from a technology standpoint, you know, it kind of reminds me of that, right, of what really lean into it. You know, if that's what you fear most, go after it. That's a very good, you know, it also, I think on the flip side, if you're not fearing something, then yeah, maybe you're not working on the right thing, to your point, right? It is a good sign that you are, like, there's a reason why you should lean in. And if you're not feeling that fear, you know, that's probably a bad sign. Right, right.

Yeah. And just that, because it's so easy, right, especially when you're in the early, in the early stages of like doing all, like checking all the boxes, the low hanging fruit, right? Of like, and you'll end up feeling somewhat productive, but it's like you basically did all the easy stuff and haven't tackled the most fundamental, you know, things. And so, and it sounds like, you know, that's what it was, was it David? you mentioned? What was this? Yeah, David Larkin. David Larkin. Yeah, yeah. We really encouraged the head of our R.D department.

Yeah, yeah. Don't go after the low-hanging fruit, like tackle, you know, go ahead in the big stuff, right? The heavy lifting. Yeah, because at the end of the day, you're trying to retire risk. And you want to retire, you know, retiring risk translates directly to value creation. You know, your stock is worth so little at the beginning because the risk before you is so high. And so the more you can chip away at that risk, whether it's technical risk or clinical risk or market risk or regulatory risk, you know, the more you're creating value in the company. And so I think that's how I look at, that's how I've come to look at being productive. It's not the how many tasks did I, you know, achieve today quantitatively. It's what is the Pareto curve of those tasks in terms of risk, right? what task helps me retire a key risk as quickly as possible.

And when I do that, that is productivity, at least in the entrepreneurial sense. Right, right. And that's something, I mean, I can't emphasize or agree with you anymore, right? Around like, that's so key for any entrepreneur, especially if you're in the early stages of your project, even if you don't really have a formal company, is to be thinking about what gets you to the next major inflection point, right? And what are the key risks? And how can you, to your word, Sam, retire those, right? How can you check those key risks off to get to that next inflection point, right?

And then from there, identify the next key value inflection point. And what are the risks associated there? And like, viewing it very kind of methodically and sort of a phase-by-face process and, you know, trying to answer those key questions around de-risking, right? What risk can you can you either remove entirely or, you know, reduce significantly? So that's great stuff. I want to circle back around to your FDA clearance, right? You mentioned that, you know, we're recording this in late February.

It was early February that you got, you know, clearance from FDA. And I remember reading a comment from Todd Powell, your CEO, around the unprecedented hurdles, right, that it took to kind of get there. And so, and I don't, I don't, you know, want to put you in a position where you're, you know, going super deep into the, into the regulatory weeds, so to speak. But just maybe at a high level, talk to us, talk to us about, like, that process, right? because that's usually kind of a daunting effort regardless of what you're working on is just regulatory in general. But it sounds like, you know, with your, I mean, the novelty of what you've built, right, at reflection, I'm sure the hurdles were that much higher. And it seems like that, you know, for Todd to make a comment.

So, yeah, we'd love to get your thoughts on that kind of subject matter in general. Hey there, it's Scott. And thanks for listening in so far. The rest of this conversation is only available via our private podcast for MedSider premium members. If you're not a premium member yet, you should definitely consider signing up. You'll get full access to the entire library of interviews dating back to 2010. This includes conversations with experts like Renee Ryan, CEO of Cala Health, Nadine Miarid CEO of CVRX, and so many others.

As a premium member, you'll get to join live interviews with these incredible medical device and health technology entrepreneurs. In addition, you'll get a copy of every volume of Medsider mentors at no additional cost. To learn more, head over to Medsider Radio.com forward slash premium. Again, that's MedsiderRadio.com forward slash premium.