NCI-funded biotech innovators Eric Broyles, CEO and Founder of Nanocan Therapeutics, and Margaret Jackson, CEO and Foudner of BYOMass, share advice on the priority steps aspiring entrepreneurs should take when starting a small business.j TRANSCRIPT [music]   BILLY: Hello and welcome to Innovation lab, your go to resource for all things biotech startups, brought to you by the National Cancer Institute Small Business Innovation Research, or SBIR Development Center.   BILLY: Our podcast host interviews with successful entrepreneurs and provides resources for small businesses looking to take their cutting-edge cancer solutions from lab to market. I'm Billy Bozza, a program director at NCI SBIR and today's host.   [music]   In this episode, you will hear from two therapeutic companies funded by the NCI SBIR program about starting a business and how they kick started their journey going from lab to market. The first company, Nanocan will share their vision, licensing journey, and the various considerations that went into forming their cancer therapeutic startup.     Then we will hear from Biomass and how this company went about building a business team, established a corporate structure, and found resources for managing their business. Now, without any further ado, here's Eric Broyles, founder and CEO of Nanocan.   ERIC: Hello, my name is Eric Broyles, and I am the founder and CEO of Nanocan Therapeutics Corporation, which is a company that Harvard's Dana Farber Cancer Institute has spun out a patented technology that we believe will be revolutionary in cancer care.   Our company is at the preclinical stage, which means we have not done in human clinical trials yet, that is our next phase that we're going to move into over the next 6 to 9 months. We will use a proprietary nanoparticle drone delivery mechanism that actually can intratumorally deliver immunotherapy for certain solid cancers, cancer tumors. And then we have a formulation that works on brain and lung, that is a liquid formulation of this technology.   So I want to talk about why I started a company to undertake this endeavor. And one of the most important things to me is vision. What is the vision that you have? And I met a professor at Harvard Medical School who had invented this technology and just hearing his thoughts about how he developed the technology, what his hopes were for the technologies placed in the marketplace, really inspired me, and I was inspired by again his creativity, his genius, really with making this invention.   And so I really formulated my own vision for how I wanted to take -- where I wanted to take this product. And I was encouraged and inspired that that I would have an opportunity to lead and develop a commercialization of a technology that can save lives.     As an entrepreneur, you have the ability to be creative. You have the ability to make a positive impact on society, and you also have the ability to achieve financial rewards. I want to talk about the steps we took to secure the IP rights to the invention.   Initially I had to meet with Harvard University to share my vision and market approach for their intellectual property. And I'm trained as an attorney and so I understand intellectual property, but it's also very important in that step, after you share your vision and get buy in from them, you should engage good IP counsel, intellectual property counsel.   Following that, you will eventually get a term sheet for your technology, again, this assumes you have not invented the technology yourself. You'll get a term sheet. We got a term sheet and then you will get a draft license agreement. It's important for your license agreement, certain key terms, what's the scope of the license? What's the term? How long will you have the right? Is it exclusive or not? What's the geographical limitations? How much do you have to pay in royalties and are there other payments that you need? And then what are the milestones you have to achieve to maintain your rights to the IP?   Those are all key questions. Again, good IP counsel will be able to -- will know these things and be able to guide you through those topics. What are the right types of corporate structure that you should consider? Well, they're your usual suspects in which are going to be C corporations, limited liability corps, S corps. These all have their pros and cons. Most institutional investors of venture Capital fund or private equity fund, they're used to seeing a C corporation structure.   There's some investors that may want to see an LLC structure, an LLC provide you certain tax benefits. You could write off your losses, particularly during your pre-revenue stage, and you're just spending money. And then there's an S-Corp structure, you should seek good accounting advice and good legal advice to help you figure out which of these structures works best for your company.   And then you should also talk to other entrepreneurs about why they chose the structure that they did. It may depend on the industry, your timing of getting in and out of the business. Those are all important considerations that the right guidance will help you to figure out.   And then thinking about financial tools and funding sources, I would encourage you actually to be open to all types of funding source. Non-dilutive grant funding that like NIH provides or NCI is very important, it's a very good source of funding, but you should be aware that it does take a lot of time to prepare the applications. There may be a gap between when you submit the application and when you get notice of award funding. And it requires that you really pay attention to details and follow very specific instructions, and have very thoughtful responses because it's a competitive process, but it's definitely worthwhile, and I'd encourage you to consider it.   And then obviously there's raising private capital and the private capital, it could be venture capital, it could be a family office. Check your university and see if there's an angel network or check your local community to see if there's an angel investing group. There's several of these groups across the country that may be a good fit and you have what you call friends and family and you'll have to figure out which of these sources of capital works best for you.   And then there'll be key terms, again, you should get good legal counsel, they'll help you sort of work you through these issues. But you should also, again the importance of your vision is critical because you're going to get a lot of no’s and it can be discouraging to you at times, but keeping that vision in the why you decided to be an entrepreneur in front of you will help you to sort of work through those no’s and the challenges that you might encounter and will encounter.   How have I put my team together for Nanocan? So for me as the founder, the sort of two important considerations were number one, what am I doing? And then number two, who am I doing it with? I wanted to have a really a cohesive team and really pick people that I enjoyed working with. It doesn't mean we all have to be alike, in fact, you shouldn't all be alike, you need to be able to challenge each other.   But you should really share, have alignment on vision, which I think is important and share certain common values, particularly having visions about where the company is going and I was fortunate to be able to build a team that shares my vision and has -- And then look at the expertise that they bring in figuring out the gaps in your own expertise.     You should have a law firm prepare your employment agreements or consulting agreements. You'll have to figure out how you're going to compensate your team. If you have some seed funding, you may be able to pay them, but typically early stage companies, it's heavy on incentives and really light on cash compensation.   And then you also want to assemble a board of advisors who can help, you know, open doors, they have expertise, they have their networks, and that can just give you good guidance and direction, which would be very important. I have Dr. Nguyen who's actually a professor at Harvard and also, a researcher at Dana Farber and he's part-time with us but adds great value for our business.   We have another colleague who runs our clinical trial, we have another person on our team who's good at international projects, and that's important, that’s an important part of our vision, expanding our technology internationally. And then you need good financial advice and we actually have an in-house CFO with extensive experience, starting his career at Merrill Lynch and working on a number of high finance projects.   And then our advisory board, it actually includes the inventor, it includes oncologists from the top institutions in our country that were excited about our technology, and they make themselves available and you should really be respectful of their time, but really also leverage their expertise in the network. It can be very important and save you a lot of time and headache being a good steward of your relationship with your board of advisors.   So what were some of the key challenges we faced and how we overcame them? In any drug development project you're going to hit snags, so be prepared for that. Make sure you have access to the right expertise, which is why it's very important for you to have a good team and a good board of advisors. Our company had challenges securing a human grade immunotherapy for our inhuman trials, but through our network we were able to overcome that challenge.   We also had challenges finding the right CDMO partner and again leveraging our board of advisors, our team, we were able to find the right partner. I'd also encourage you to consider attending conferences like CPHI which has a broad range of players in the pharma and biotech industry who can be helpful to companies.   I thank you for your time. I wish you the best as you bring your technology to market and really appreciate this opportunity to share with you.   BILLY:   What a great journey. Up next we have Margaret Jackson, founder and CEO of Biomass.   MARGARET:    Welcome to NCI SBIR Peer Learning and Networking, first steps for starting small business. I am Dr. Margaret Jackson, founder and CEO of Biomass. We are a preclinical stage precision medicine company, focused on developing novel therapeutics for cancer anorexia-cachexia.   Biomass, as an early startup, was able to accelerate based on receiving both SBIR and federal contract phase one funding. So why did I decide to start a small business? I decided to start Biomass for three key reasons. First, passion, I'm incredibly passionate about finding a cure for cancer induced anorexia-cachexia.   I know the patient. My father passed away over 30 years ago with his debilitating disease, and yet fast forward 30 years, there is still no approved treatment. We can do so much more and we need to do it so much better. Second, expertise, I have over 20 years of drug discovery and drug development expertise in developing novel therapeutics and taking programs from early concept right through to early stage clinical trials. It's a wonderful thing when you can combine your passion and your career together to develop something truly important for patients.   And thirdly, culture. To develop a novel therapeutic, you can do it at large pharma or as a startup, both the pros and cons. At large pharma, there's fabulous resources, fabulous talent, but there's hierarchy, bureaucracy, slow decision-making. In a startup, you have a flatter structure, meaning being able to be more nimble, enable rapid decision making, build closer-knit teams, and faster execution of your programs.   At Biomass, we have developed our own culture. Scientific excellence, innovation, and people are at the core of our culture. We have a very high bar as we are developing drugs to survive and develop that first cure for cancer induced anorexia-cachexia. There is clear accountability to get things done with high integrity.   So guidance to anyone considering a startup. I would suggest don't be afraid to fail. Be afraid to not try. So how did we assemble our business team and what were some of the important considerations? As an early startup, it's really important to have the right people with the right talent at the right time to do the right job that helps you grow your business.   But as an early startup company, quite often you're cash constrained, often referred to as bootstrapping. And it's really important for you to consider how best to deploy your capital. Quite often for the business team, you do not need them in full time in the organization, but they are required at specific times for specific functions.   So the first question to ask is, do you need individuals as a full-time employee within the organization or can you use resources externally that can be more capital efficient? An example would be there isn't a need for chief finance officer for an early stage company, but it's essential to have an accountant, because you as a full-time employee can bring money into the organization, can receive the invoices, but you do need somebody externally who's able to pay those bills.   In addition, you need someone who's going to be able to do your monthly accounts and also your annual taxes, but that could be done as a monthly retainer or can be done at an hourly rate. Likewise, it's important to have business development expertise, but not required full-time. It's essential for thinking about in licensing or out licensing at certain periods of time, and also for setting up your templates for consultancy agreements, confidentiality agreements, and master service agreements.   Again, not required full time. IP is king for a company and therefore it's really essential to have an IP attorney which can be external to actually support your IP strategy, at times when needed. And finally, it's essential to have outside counsel. You don't need to have a chief legal officer internally in your organization, but you certainly do need an experienced life science outside counsel who can actually help you demystify term sheets from investors or any other additional contracts that may come from any other organization.   So the guidance at this stage of an early stage company when forming a business team is to consider resources outside your organization to support the organization, which can be done at a monthly rate or at an hourly rate.   What are the considerations for determining the right type of entity for starting your new company? There are essentially seven classes of business structures, and it can be overwhelming, but essentially the business structure you choose influences everything from day-to-day operations to taxes and how much of your personal assets are at risk.   In life sciences, limited liability companies, LLCS or corporations, C-Corp are the most common. LLCs can be a good choice for medium to high risk businesses, owners with significant personal assets they want to be protected, and owners who want to pay a lower tax rate than they would with a corporation.   Corporations offer the strongest protection to the owners from personal liability, but the cost to form a corporation is higher. Corporations also pay income tax on their profits and again when dividends are paid to shareholders on their personal tax returns. Corporations have a completely independent life separate from its shareholders, and if a shareholder leaves a company or sells his or her shares, the C-Corp can continue doing business relatively unstirred.   Corporations have an advantage when it comes to raising capital because they can raise funds through the sale of stock, which can also be a benefit and attract employees. Corporations can be a good choice for medium to high risk businesses, those who need to raise money, and businesses that plan to go public or eventually be sold. So guidance, really speak to outside counsel about what works best for your business vision.   Are there any technology specific considerations when starting a therapeutic small business? Yes, we live in a virtual world where technology is critical for communication, documentation, and archiving. It really is important to make sure that operations are in place. So for accounting, an example would be QuickBooks, which is great to be able to provide purchase orders to vendors for drug discovery, drug development work, helps you track your invoices against statements of work, helps you track expenses.     You're able to do a payroll and also provides reports such as your balance sheet and profit and loss. Payments can be also done both nationally and internationally using Bill.com. It is really important when working with external vendors or consultants or even with employees internally, that DISA and reporting is archived and easily accessible. Examples of being able to archive and share would be using Box or SharePoint.   In addition, it's important to have a dear room that's available for diligence with external investors. Examples would include dearrooms.com and also SharePoint. This means that you're able to give restricted access to individuals to confidential information that is clearly marked as confidential.   For data managed for high throughput screening data, regular screening data, biological data, chemical structures, antibodies, sequences, et cetera, it is important it's all in one central repository. And an example where this can be easily accessed, visualized, and interrogated is using software like CDD, Collaborative Drug Discovery, which also has the benefit of having access to an electronic lab notebook where your study protocols can also be uploaded.   And finally, as you're working with investors and trying to keep on top of the CAP table, it is important to make sure that you're able to access that and make sure there are no mistakes and a great software is Carta.   So the guidance for any startup company is to make sure that you have the proper operations software in place, do not store confidential important information fragmented and in people's inboxes. They need to be correctly archived and accessible and be able to visualize.   So what kind of financial tools and resources would I recommend to an early life science company? I cannot stress enough how important it is to go after non-dilutive funding. It is important for three reasons. One, it means that your research has been peer reviewed, it's scientifically validated, which is really important when talking to external investors.   Number two, it means you receive money, you get your company off the ground, you advance your research, and you create value in your company. And third, mid range you get money and not at the expense of taking equity of your company. There are multiple types of non-dilutive funding. There are the Small Business Innovation Research Awards, the National Science Foundation, Department of Defense, federal contracts, Bill and Melinda Gate Foundations, in addition to multiple grant opportunities that may be present on websites, all of areas that you're investing in.   There are multiple resources to help you apply for these grants, if this is your first time. There are books that are available online from Amazon which actually walk you through step-by-step how to apply and submit these grants. But most important to be aware of is you need to give yourself about eight weeks prior to submitting any grants to ensure that you actually have risk completed all your registrations.   You need an employer identification number. A Small Business Association registration, registration with ERA comments, SAM.gov, Grants.gov. And there are companies out there who have actually experienced writing grants and are now consultants to help the next generation apply for grants such as EGC and Free Mind.   The other opportunity to receive money is through dilute of funding. This is where you receive money from angel investors or from venture capitalists for seed funding or Series A investment. That'll be the first time you experience a term sheet which can be overwhelming, and there's a great resource called Venture Deals by Feld and Mendelson that you can purchase online, which actually take you through step by step the pros and the cons, all of each of the descriptions on the term sheet, of the economic terms, the controlling terms, the permissions, and the restrictions.   In addition, there are local networks to help you demystify term sheets. An example in Boston is the Capital Network. They also help you understand a cap table. There is also multiple incubators or accelerators that you could join that actually help you to understand how to get your first investment and how to meet investors. An example for women founders is Springboard Enterprises supporting life sciences and digital health.   And also really important to build your network of other CEOs or C-Suite executives who have lived and breathed this. So the guidance for applying for funding and the resources at your fingertips is to really build your network of individuals who have had the experience of doing this and have been successful in achieving funding.   What do I know now that I wish I had known first when setting up a small business? Well, setting up a startup company for the first time is a very steep learning curve, but a very rewarding experience. It is important to surround yourself with really great people, great talent that will help you as an individual grow, but also help the company grow.   It's very exciting to get your first non-dilutive funding and it's very exciting to get your first investor, but you should be very mindful of how the deals or the term sheets of an investor equity financing actually affects your eligibility to apply for an SBIR grant.   So if you have a single investor with over 50% of the company, you as a company are no longer eligible to apply for an SBIR grant until you have further investors who come to the table. So it's very important as part of the investor negotiations to ensure that you are still eligible to apply for non-diluted SBIR funding.   [music]   BILLY: There you have it. Special thanks to Nanocan and Biomass 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 Billy Bozza from NCIS 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 [email protected] 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.     [music]   END OF FILE                  

RefleXion Co-Founder and Chief Technology Officer Samuel Mazin, PhD, shares his journey from postdoc to startup and the NCI SBIR support that helped develop a biology-guided radiotherapy that provides treatment for metastatic cancer patients with limited options. TRANSCRIPT [music] 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. [music] 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. [music] 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. [music] 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 [email protected] 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. [music]                          

National Cancer Institute’s Small Business Innovation Research (SBIR) Development Center Director Michael Weingarten and Program Director Monique Pond introduce the Innovation Lab podcast series and provide insight into the benefits the program can provide biotech innovators with no strings attached. TRANSCRIPT: [music] MONIQUE:     Hello and welcome to Innovation Lab, your go to resource for all things biotech startups, brought to you by the National Cancer Institute’s Small Business Innovation Research, or 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. I’m Monique Pond, a program director and team leader at the NCI SBIR and today's host. [music] The Small Business Innovation Research is a congressionally mandated funding program designed to propel technological innovation across the United States. Here at the National Cancer Institute, the SBIR Development Center is the institute's engine of innovation and the hub of small business funding. Today, as we kick off our first podcast series, I would like to introduce our program and walk you through some of the topics that we plan to cover in our upcoming series. [music] For our very first episode, I've invited one of our co-hosts and the Director of the NCI SBIR Development Center, Michael Weingarten. Hello, Michael. MICHAEL:     Hi Monique, how are you? MONIQUE:     Doing well today, thanks for joining us. Appreciate your time. MICHAEL:     Yeah. Happy to be a part of this and really excited that we're launching our own podcast. MONIQUE:     Great. So Michael, you started the SBIR Development Center back in 2006. Can you tell me how that came about? MICHAEL: I was actually hired back in 2005 by the director then, Dr. John Niederhuber. And Dr. Niederhuber was really interested in taking a new look at how we could manage the SBIR program at the  NCI. He was interested in bringing a strategic focus to this program. So he came to me and he asked me to come up with a range of different ideas for how we can improve the program overall and improve the impact of this program. So we took a fresh look at the SBIR program and I came back with a set of recommendations, really that were based on looking at some of the best practices from across the government and some of the top agencies running SBIR programs, as well as just some ideas that we came up ourselves with. And probably the most important recommendation that we had was that we actually set up a center at the NCI, that we could run this program where individuals could actually spend 100% of their time just with small businesses and just managing SBIR's. For the program and for our companies to be successful, we really did need program directors working at the NCI who had industry experience as well as some prior track record and experience with the commercialization of technologies. But we need people spending 100% of their time working with companies and guiding them and advising them, and that's what we're able to do with the SBIR program now that we've set up a center. We have a team of about 22 people now and we're able to offer just a range of resources and assistance to companies who really need our help. MONIQUE:     So, Michael, tell me, what does the typical small business coming into the program look like? MICHAEL:     Well, when companies first apply for NCI SBIR funding, they're usually startups and fairly small. So I would say the typical company that approaches us first for funding maybe has two or three people when they first get started. A lot of times they’re a spin out from a university or a recent startup and they don't have a lot of experience in working with the NIH. So typically, you know, they're -- We like to spend a lot of time with companies really educating them about how the NCI SBIR program works, what our different funding opportunities are, really how NCI can really help play a role in growing their company. MONIQUE:     Great. And why should a small business be interested in applying for NCI SBIR funding? MICHAEL:     Well, SBIR funding can be a really good deal for a small business and for a number of reasons. First off, we don't take any sort of intellectual property position in the company. All the IP that's developed under a grant or a contract through an SBIR is owned by the small business. We also don't take any sort of equity position in the company. All of our funds come to the company either through a grant or through a contract. So all the stock continues to be owned by the startup itself.   MONIQUE:     So NCI is sort of playing the role of an early-stage venture capitalist, but without taking any IP or equity stake in the company. Would you say that's fair? MICHAEL:     Yeah, that's a good way to describe it. Because we're the government, we're actually able to take on more risks than probably a private investor would. So we typically will invest in these companies at an earlier stage of development than most investors would and we can help the company get the key data that they're going to need in order to be successful over the longer term because we're willing to take on a little bit more risk than a private investor would. So yeah, I kind of think of the NCI SBIR program as being kind of a seed fund for startups in the cancer space. MONIQUE:     Early-stage seed fun, I like it. All right, so after a company goes through the NCI SBIR funding program, do you find that many companies are ready to, you know, commercialize their product, launch their technology or do some also go into the venture capital world for follow on funding? MICHAEL:     That's a great question. So typically because of the large costs involved in life sciences, in terms of taking something from the lab all the way to the marketplace, at some point, most of these companies are going to need to be able to go out and raise some private capital. That private capital can come from angel investors, it could come from partnerships with a large pharmaceutical or medical device company, or it could come from raising funds for the venture capital world. But NCI SBIR funding could be a really key component to get many of these companies through preclinical development and actually into clinical trials. So we can really help a company move their technology along to make them attractive to private investors in the future. MONIQUE:     How would a cancer researcher enter and journey through the NCI SBIR program? MICHAEL:     Well, probably the best thing they could do is go up to our website initially and that’s at sbir.cancer.gov. That's a great starting point [unclear] learn more about the program. We have information on our funding opportunities there, applicant resources, our awardee resources. We also have information about any upcoming events that we're doing. Just as an example, in addition to podcasts like this one, we also put on webinars frequently throughout the year where potential applicants can listen in and learn more about different funding opportunities that we're offering. So go up on our website initially, read up a little bit about the program, and then if you're interested in funding, we also encourage you to try to set up a meeting with one of our program directors and you can e-mail us through the website just to set up a short conversation so we can learn more about your company, whether you're a good fit for the SBIR program. MONIQUE:     So, Michael, what would you say make small businesses successful in obtaining SBIR funding from the NCI? MICHAEL:     I would say a couple of things. First, start early in your planning. We have three different receipt dates throughout the fiscal year. So you do have a lot of opportunities to apply, but give yourself enough time to write a strong application. And probably the first step in that whole process should be connecting with the program director at the NCI SBIR program, that way you can talk about your idea and you can get some feedback on whether we think that's a good fit for the types of projects that we trying to fund under the program. It's also a really good opportunity for you to review your specific aims on the project, that's probably the most important aspect to your application. And one of the things that we offer every applicant is the opportunity to go over your specific aims with a program director in our program and then we'll give you some real direct feedback and some suggestions on different things that you might not be thinking about.   Once you've done that, I think that really does set you up well to write an application. If you have not applied to the NCI SBIR program before or you haven't received an SBIR from the NIH as a whole before, you could also participate in our Applicant Assistance Program. It's a really helpful program for new applicants that we offer and essentially it’s an opportunity for you to get access to a coach who can guide you through the whole application process. So if you're interested in learning a little bit more about our applicant assistance program, that's a resource that you can learn a little bit more on our website, again at sbir.cancer.gov, but that those are really kind of good starting places. MONIQUE:     Our three receipt dates for NCIS SBIR are January, April, and September. So for those listening, definitely contact a program director at least a month ahead of those times, I would say, and that way you know you'll be able to meet with somebody and have a good, you know, robust conversation about your specific aims, as well as answer any questions that a company or someone on the team might have about the application. So, Michael, what other resources does the program provide outside of funding? MICHAEL:     The way I like to think about our program at NCI is funding is obviously necessary for these small companies, but it's not sufficient for them to be successful. So we try to offer a range of other resources to our companies, all based on our meetings and conversations with companies that are in our portfolio and really understanding what kind of needs that they have. So we've actually launched a range of different resource programs that we offer and I can mention just a couple right now. When a company first enters the program, they're actually eligible to participate in a program that we call I-Core or Innovation Core. And I-Core is actually an entrepreneurial training program, the best way I like to describe it is it really teaches a small business that's new to the program how to build a business model around the technology that they're developing. We find that I-Core really helps set up our companies quite well to take the next step as they're continuing to develop their technology and then to apply for the next stage of funding, which would be phase two project under our program. We also run a program called our Investor Initiatives Program. We've been running that for about 15 years, right now and over that timeframe, we've developed relationships with most of the large investors in private capital that invest in cancer technologies, whether those be drugs, devices, diagnostics or digital health technologies. And because we're the NCI, we can help open doors for small businesses that we’re funding so that they can start conversations with investors who might be interested in funding their companies. And we have a panel of about 80 different investors that once a year will actually review our portfolio and help us identify the most promising companies that we're funding in the portfolio. And then they actually will grade and rank companies and help us identify companies, that we will then provide funding for, to go and present their company and their technology to private investors at some of the largest investor events around the country. And so our goal through our Investor Initiatives Program is to really help our companies make introductions for them to investors who could then hopefully -- we'll consider investing in them also. MONIQUE:     Thanks Michael for the description of the funding, as well as all these additional non-funding resources that sound like they can really help the company get going, who might be starting out or early on in technology development. So I appreciate you taking time to speak with us today. MICHAEL:     Happy to, thanks for the opportunity. [music] MONIQUE:     Don't forget to check out our website, SBIR.cancer.gov for the latest funding opportunities and commercialization resources to support your journey from lab to market. This was Monique Pond 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 [email protected] 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. [music]  

TRANSCRIPT [music] MONIQUE:     Is your biotech startup developing a cutting edge cancer technology? We can help bring it to market. Innovation Lab, a podcast from the National Cancer Institute’s Small Business Innovation Research Development Center, SBIR, has all the resources you need on your journey from IP to IPO including: interviews with successful entrepreneurs, SBIR program resources, funding opportunities, commercialization tips, and more. I’m Monique Pond, an NCI SBIR team leader and program director, and I’ll be one of three hosts for this podcast along with the Director of the NCI SBIR Development Center Michael Weingarten and another Program Director from this center Billy Bosa. Ready to get started? Subscribe and tune in for helpful information for taking your biotechnology from lab to patient. [music]