Episode 2 | Entrepreneur Spotlight – RefleXion

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Episode Guests 

Michael Weingarten, M.A.

In this role, Michael Weingarten, M.A., leads a team of nine Program Directors who manage all aspects of the NCI SBIR & STTR Programs including a portfolio of $182M in grants and contracts annually. The SBIR & STTR programs are NCI's engine of innovation for developing and commercializing novel technologies and products to prevent, diagnose, and treat cancer. Mr. Weingarten has implemented a set of key initiatives for optimizing the performance of the NCI SBIR Program at the NIH. These include the establishment of a new model at the NCI for managing the program - the SBIR Development Center.

Samuel Mazin, Ph.D.

Samuel Mazin, Ph.D., co-founded RefleXion Medical in 2009, where he is the inventor of the company’s core technology. While a postdoctoral researcher in Radiology at Stanford University, Dr. Mazin was selected by the Kauffman Foundation as one of 13 postdocs in the nation to commercialize promising innovations. His prior research at Stanford was focused on the design of a novel X-ray computed tomography (CT) system, resulting in several journal papers and a patent, as well as the Joel Drillings Award from the American Heart Association (AHA). His work on a PET-based algorithm received the prestigious Cum Laude award from the SPIE international medical imaging society. He has been invited to speak about biology-guided radiotherapy by cancer centers worldwide. Dr. Mazin received a Bachelor of Applied Science in Computer Engineering from the University of Waterloo, Canada, and he holds a Ph.D. in Electrical Engineering from Stanford University.

Episode Transcript

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MICHAEL: Hello and welcome to Innovation Lab, your go-to resource for all things biotech startups, brought by the National Cancer Institute's Small Business Innovation Research, SBIR Development Center.

Our podcast hosts interviews with successful entrepreneurs and provides resources for small businesses looking to take their cutting-edge cancer solutions from lab to market. For more, check out our website at sbir.cancer.gov. I'm Michael Weingarten, the Director of NCIS SBIR and today's host.

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In this episode, you will hear from a medical imaging company, funded by the NCI SBIR program, about the journey from post-doc to biotech startup. RefleXion Medical Founder and Chief Technology Officer Sam Mason will share how the company leveraged SBIR support on their way to receiving FDA clearance for their technology that revolutionizes radiotherapy for tackling metastatic disease.

Now, without any further ado, here's Sam Mason, Founder and Chief Technology Officer of RefleXion Medical.

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MICHAEL: I thought maybe a first good question would be if you can kind of tell us how you started your journey as an entrepreneur.

SAM: Well, I was trained in computer engineering at the University of Waterloo in Canada, that's where I did my undergraduate, and then came to Stanford for graduate work in a field called medical imaging, so that's where I fell in love with medical imaging, by just taking a class and understanding how just with, you know, basic energy systems, we can see inside the body without touching the body, so I was just fascinated by that.

It was during a post-doc in the same program that I had this idea for RefleXion. I was pursuing an academic path, but I was struck by this idea because it was it was a natural marriage of the field I was in with a field that I was just recently exposed to, and that was radiation therapy. And so that's what kind of set me off on this entrepreneurial journey.

I was not planning to be an entrepreneur, but it was an idea that I guess wouldn't let go of me and so I just had to keep pursuing it and eventually I co-founded the company with a high school buddy of mine, Akchi Nanduri [phonetic], you know him as well of course, and the rest is history.

MICHAEL: I think it would be really interesting for the audience just to learn a little bit more about the technology that you're developing now and kind of maybe a little bit more about the original idea and how you guys developed it.

SAM: This is a technology that is really meant to tackle, for the first time, stage 4 cancer with a machine. The idea germinated while I was a post-doc and I knew a lot about how medical imaging worked, how CT scans, MRI scans, PET scans worked, and particularly PET, which involves the administration of a radiopharmaceutical in the body that literally has cancer light up, so that a PET scanner can kind of see where cancer is, it's one of the best ways of actually visualizing cancer in the body.

You know, to my knowledge that had not been used at all in conjunction with radiation therapy, which is using high energy X-rays to treat cancer, at least at the time of treatment. So I thought, you know, wouldn't it be great if the machine that's being used to treat the cancer could also see it and not only see it, but see it live in real time?

So my idea was actually a way to circumvent the slow PET imaging process and instead of using a PET image, which is what how naturally people would think of a PET scan, the innovation was to use the actual emissions, the stream of signals that are literally coming out of cancer cells to the PET scanner, use those same signals, but integrate a radiation therapy machine around it that will detect those signals in real time, and then shoot back or reflect the radiation back where it's coming from, hence the name of the company.

And so that was the germ of the idea that my co-founder and I started to really pursue in earnest. You know, we didn't realize how long of a pursuit that would be and how arduous, but -- and we're still on that journey, of course, as a company, but that's how it got started.

MICHAEL: The RefleXion technology, how is it an improvement over the current state-of-the-art in terms of what it will offer for patients going forward?

SAM: RefleXion, because it uses this pad signal or what we essentially call it a biological signal to direct the radiotherapy beam, it's the first time you have this real time direct targeting mechanism that's being mediated through a radiopharmaceutical, through an actual molecule that is taken up by the cancer itself.

So the reason why that's important and significant is because current radiation therapy technologies are all based on some form of anatomic imaging, as opposed to real time biological targeting, and so that really limits their ability for a variety of reasons to treat more than just one or two tumors in the body.

And if you really want to tackle stage 4 or metastatic cancer, where patients unfortunately have more than just one or two tumors in their body, they can have 5, 6, 7, 10, sometimes more, you need a technology that is going to be able to achieve that and so that's exactly what we call biology guided radiotherapy, which we've now dubbed as Syntex [phonetic] therapy, to be able to really add an option for the stage 4 or metastatic patient beyond the current standard of care.

And in addition to that current standard of care, which is predominantly drug therapy, and really do better in that field and in that that type of patient, you know, as we all appreciate you know when someone is diagnosed with cancer, one of the first questions you might ask that loved one or friend is, you know, did you catch it early or what stage is it?

And because stage is such an indicator of not only how advanced the disease is, of course, but the types of treatments that are even available and how effective they might be, and the later the stage, the narrower the suite of treatments that are available for that patient.

So that by stage 4, typically it's only drug therapies that are available, although there are many exciting drug therapies, a lot of innovation has happened on that front, if you look at outcomes data, it's still very poor compared to the efficacy that you see in earlier stage disease where local therapy like surgery or radiation are the predominant modes of care.

So what we're trying to do is add a new option and bring radiation, external beam radiation as a modality in the stage 4 setting alongside the drug therapy to try to really give the patient the best chance at beating back their cancer.

MICHAEL: This technology will actually enable the first time that you'll be able to effectively use radiation therapy for phase 4 cancer patients in an effective way, is that correct?

SAM: That's correct. I mean, there is, you know, a real push in the clinical community to use radiation in the stage 4 setting now, in metastatic patients now. However, it's really limited to what's called the LIGO metastatic disease, so these are patients with just a few, maybe one or two tumors. And it's really difficult for these technologies to scale, to treat more than just a few tumors in the body.

So this really does open up the door to more broadly treat metastatic disease in scale to larger patient populations. And we think, we believe, you know, anywhere around any clinic around the world because, you know, one of our goals is to really be able to improve the efficacy of treatments for stage 4 cancer and you can only do that if you are in the Community setting, not just in the academic center setting, and so you know, we've also designed this machine to be in the community clinic as well.

MICHAEL: Maybe you can talk a little bit more also about the role that SBIR played in helping you develop the technology and also in growing the company as a whole.

SAM: Of course, the NCI SBIR program has been such an important part of RefleXion’s development, especially on the earlier side when it was really hard to convince investors to put money in the company. So Akshay [phonetic] and I, we were knocking on the doors of the venture capitalists on Sand Hill Road saying, “Hey, you know, we need $10 million bucks to build a machine that we won't know it'll work until we build it.”

And you can imagine the type of reception we received right off the bat. And so, you know, we had to really look for ways to find capital, but also find validation for this technology. The NCI SBIR program was one obvious way to help solve two of those two issues. You know, a start up, I think many entrepreneurs will say, initially is really about runway. You know, how much time do you have to get to that next milestone? And time is money.

It's capital that you need to survive, to keep going, not just keep the lights on, but keep moving forward and developing your technology. So our first interactions with the NCI SBIR were through contacting a program director there at the time his name is David Balin [phonetic] and we, you know, pitched to him just like we're pitching to an investor, right?

We tried to basically convince David that this is a groundbreaking technology, because one of the challenges with any type of grant mechanism is you still have to go through a process where you have to show some preliminary data to show that your technology will work, right? You're gonna get scored through a scientific review process. And it's a bit of a chicken and egg problem because we didn't have this machine to generate the preliminary data. We needed money to build the machine.

So what was great though, is that, you know, as David came to understand, you know, part of this chicken and egg we were in, you know, it was important guidance we received from him on how to go through the process and be successful in being able to get those first grants from the NCI.

But those were our first interactions back, I think in around 2010 or so, when we received our first phase 1 grant, which was important, again, not just for the capital part, which again helps with the runway, but validation, you know, investors look at it as well, look, this did go through a rigorous scientific review process. This also went through a process that the NCI SBIR has in terms of getting other entrepreneurs to review these applications.

And so there's both a commercial and a scientific basis for passing that gate and so, you know, that's certainly recognized by the investment community. So I think there are a multitude of factors that, you know, why we wanted to try to get SBIR money, you know, as soon as we could.

Predominantly, those funds and those projects were aimed at mitigating the technical risk of the project and that was really the biggest risk. You know, we had to build a machine. In the radiation therapy field, these machines rotate at about 1 revolution per minute and we had to build a machine that for the first time would rotate these high energy, you know, linear accelerators at 1 revolution per second.

And so that was a really large technical risk we had to overcome. And, you know, as it turned out, one of the things I learned along the way in terms of how investors think about risk, that's the hardest one for an investor to get their minds wrapped around. It's the hardest one to predict and assess. You know the clinical risk, well, you can assess that by what does it take to kind of develop a clinical study and how long without trial to, you know, to read out and you can look at your outcome data to mitigate that.

Market risk, you can get your head around well, what does the adoption curve look like? How are customers adopting this technology? Technical risk is a really funny beast because you don't necessarily know what you don't know, and so because of that, investors really shy away and that's why we had a really tough time raising venture capital I think in the early years.

So that's I think where the NCI SBIR program helped us the most and where I would advise other entrepreneurs, you know, if technical risk is a big challenge for you, it is a great program to try to leverage.

MICHAEL: What has been the most meaningful part of this entire journey for you?

SAM: When you actually see your own idea touch a patient in a positive way, that's the most meaningful part right there, that makes it all completely worth it and more. You know, the other, I think, really inspiring part of it is to watch, you know, such talented people that, you know, we managed to recruit into the company, make this vision become a reality and it just gives you such a hopeful feeling for what humanity can do when you have kind of a shared mission and vision of what's achievable, what's possible.

I think we take it for granted, but concepts, like this one, which seems so much like science fiction, right? Literally you put a patient on the table, the machine senses where the cancer is and treats it without even touching the patient. You know, we take it for granted that those types of technologies are developed on a continuous basis and I think it just, you know, seeing it firsthand is such an inspiration to myself for what we, you know, as humans can achieve.

So, you know, there are multiple reasons why I'm so proud to be, you know, part of this company. The RefleXion X1 machine is now installed in four sites across the US, so specifically at Stanford, City of Hope in Southern California, University of Texas Southwestern in Dallas, and UPMC in Pittsburgh. And we have been treating patients for almost 2 years now and there have been I think over 4,500 patient treatments delivered by those machines I listed.

So we're very proud of the fact that we're already having an impact in cancer care and finally using our machine to try to beat the disease. Of course we are, as you mentioned, we're also waiting for FDA clearance for the biology guided part of the machine, which we're calling syntax therapy, and that's what engages the PET scanner to be used for, you know, basically using those emissions to guide the radiotherapy beam in real time and have the cancer literally talk to the machine and be able to open up applications like metastatic disease and others for cancer treatment.

FDA guided us to a de-novo pathway, de-novo literally meaning new. In fact, they also gave us breakthrough device designation status, particularly in cancers in the lung. Because of that newness, we had to also cross a clinical bar of evidence that was traditionally higher than previous for external beam radiotherapy systems. So we conducted a clinical study last year that was successful and now we are, we believe very, very close to, knock on wood, FDA de-novo approval for syntax therapy.

So that's something we're hoping to launch early next year, if all goes well with the approval, and we get syntax therapy along with the conventional image guided therapy that will continue into patients as soon as possible.

MICHAEL: What are just some of the key lessons learned along your commercialization journey that you can share with us?

SAM: The first one is it takes longer than you think. I mean, it's funny how – I don’t know arrogant or I know the right word is, but we were pretty optimistic, let's just say, and, you know, a cold dose of reality would hit us on a monthly, quarterly, yearly basis. You know, people would tell us it's going to take longer than you think and they were right, so plan for that.

I think, you know, if your science is sound, or at least your evidence for what your building is sound, unless that changes along the way, then there's no reason why you should stop pursuing it. And I think the other key lesson is, and this is something thankfully, we had ingrained in us from the beginning because neither Akshay [phonetic] or I were in the radiation therapy field to begin with. Not only that, we weren't and aren't MDs either.

So we were already in a space very outside where we were comfortable with, both from an industry and a clinical perspective. And so we knew right away we need to hire people that are more experienced and smarter than us in these areas. The smarter, the better, try to be the dumbest person in the room. It's hard to go wrong when you do that, but recognize that, recognize where you really do need to complement your team early on and throughout the company's life and be honest with yourself about that.

So those are probably the two most important lessons I'd say I learned. An entrepreneur is literally like by definition charting unexplored territory. And so that, you know, that means that no one knows what that next bend in the path is going to look like. It's always easy to look back and you see the entire path, you see all the windings that happen, you can also connect those dots really well, but not knowing the future is something you have to become comfortable with and realize that that also is a sign you are charting an unknown territory and so don't let that dissuade you, I would say.

I like to tell people that entrepreneurship requires three important traits: vision, persistence and ignorance, and we shouldn't underestimate the importance of ignorance sometimes, because it, I think it keeps us appropriately naive and it encourages us to be optimistic.

MICHAEL: Well, listen, Sam, I want to thank you for joining us today. I think this has been a wonderful experience. It's been great working with you and with others at RefleXion over the last 12 years now and we really look forward to your continued success as the company moves forward.

SAM: We really appreciate what you guys have helped us do.

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MICHAEL: What a great story. Special thanks to Sam Mason from RefleXion for speaking with us today. As always, don't forget to check our website sbir.cancer.gov for the latest funding opportunities and commercialization resources to support your journey from lab to market.

This was Michael Weingarten from NCI SBIR. Please join us again for the next installment of NCI SBIR Innovation Lab and subscribe today wherever you listen.

If you have questions about cancer or comments about this podcast, email us at NCIinfo@nih.gov or call us at 800-422-6237. And please be sure to mention Innovation Lab in your query. We are a production of the U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute. Thanks for listening.

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