Startups and Commercialization of Research with Satish Nadig, MD, PhD

Erin Spain, MS [00:00:03] Welcome to Science and Translation, a podcast from NUCATS, Northwestern University Clinical and Translational Sciences Institute. I'm your host, Erin Spain. NUCATS can help facilitate bringing your research to market by fostering biomedical ingenuity and entrepreneurial activities. Through its focus on translational innovation. Today's guest is here to discuss collaborating with pharmaceutical and biotechnology companies and the importance of having institutional support when launching startups or exploring the commercialization of research. Dr. Satish Nadig is a transplant surgeon and a basic scientist who joined Northwestern in 2021 as the Edward G. Elcock Professor of Surgical Research and director of the Comprehensive Transplant Center at Northwestern University Feinberg School of Medicine. He has co-founded a biotechnology startup company and now serves as the chief medical advisor at another. He is passionate about improving organ transplantation through technology and says we're on the cusp of an era of technology and transplant. So you've been at Northwestern now for just a little over one year. It's been a very productive year. Tell us about yourself. What brought you to Northwestern and what you've been up to since your arrival?

Satish Nadig, MD, PhD [00:01:28] I was a Charleston, South Carolina, lifer, and I received a phone call one day to explore an opportunity to lead the comprehensive transplant center here at Northwestern. And it became a no brainer, honestly, to lead a top tier institution, top tier program that's really on the cusp and the leading edge of not only clinical work moving transplantation forward, but the science of moving transplantation forward specifically for what I do in my research. It was really a hub of nanotechnology and to be able to get a core group of people moving in the same direction I thought could make a huge impact on the field. So it really was a no brainer for my family and I. And we, we packed up and moved to Chicago.

Erin Spain, MS [00:02:12] You mentioned nanotechnology. Actually, Northwestern has been called NanoU before. There is just a lot of nanotechnology research happening at Northwestern. Was that something that you were excited about collaborating with folks in Evanston and Chicago?

Satish Nadig, MD, PhD [00:02:26] Oh, yeah, 100%. I'm not, by training, a bioengineer. I did my Ph.D. in regulatory T cell biology of cellular biology, transplant immunology, and it became clear to me that we really needed to partner with people that were in different fields, to have different perspectives on how we can make patients lives better in transplantation. And it's a real kind of renaissance of that. When transplantation first started, there was a lot of early researchers in the field of transplantation that were partnering with engineers in the 1920s, 1930s and 1940s to really lead up to the first transplant that ever happened in 1954. So now we're really back to that. But now with just better technology and newer technology, and I think that's allowing us to be on the cusp of that next era that you were discussing.

Erin Spain, MS [00:03:12] Let's dive a little deeper into your research and your research interests now, your focus on innovations in transplant tolerance, including cellular therapy, as we talked about nanotechnology and transplant immunology. Tell me about your research right now and how it's really evolved in recent years.

Satish Nadig, MD, PhD [00:03:28] Globally speaking, the theme of my research lab looks at treating the organ rather than the patient. So the current standard of care right now is that a patient gets an organ transplant and then has to take systemic anti-rejection medication that goes throughout their whole body to suppress their whole body's immune response to keep the organ from rejecting. But what if we could just immunosuppressed the organ and keep the patient off of all of those poisonous anti-rejection medications? I think that's really the future of transplant and in the future of how we deliver medications to patients. What's really interesting about transplants, a very unique field. The organ is out of the body for a period of time before it gets transplanted. So when it's isolated in a preservation solution, why not use that opportunity to treat the organ so that we're pre treating and preserving rather than just preserving the organ alone prior to transplantation? So what's interesting in transplantation now is that we're using the same anti-rejection medications that were developed in the 1960s, 1970s and 1980s, the same preservation solutions that were developed in the 1980s, and that largely the same techniques that were developed in the 1990s. So we're behind the times and it's time to change and we have the technology to do it. And Northwestern's on the leading edge of that technology. So one of the things that I do in my research lab is we've created a nanoparticle that packages anti-rejection medication on the inside of it, and it's targeted to particular cells in the organ itself prior to implantation. And what we found is that just 1/10 of that dose of that medication delivered in a package nanoparticle is as good as, if not better than a full dose given in the preservation solution. That doesn't really work. But we also know that you obviate the side. The facts of the anti-rejection medication when given to the person in their whole body. And so we're not in clinical stages yet. We're in pre-clinical trials right now, but that's one aspect of the lab. Another aspect is we often now the standard of care is taking organs and putting it into that cold preservation solution. So it's not just a preservation solution, but it's cold. And no one's really looking at what does that do to the metabolism of these organs in an immunologic sense. So what does it do to the immunometabolism? Now, Erin, if I asked you if you were put into a four degree cold air plane and travel across the country, I think you'd be pretty upset, you know, and organs get pretty upset, too, and they're really revved up to react against the ischemia reperfusion injury that happens when they get implanted. But if we can query these cells specifically the endothelial cells is what I work on in that preservation phase, we can make them less apt to react in the ischemia reperfusion injury as well as early rejection responses. So globally I look at how do we pre-condition these organs while they're out of the body so they can work better when they're in the body. So and patients can be off these anti-rejection medications.

Erin Spain, MS [00:06:29] You have experience turning research into a startup company. I would like you to talk about that a little bit, your entrepreneurial background and how important it is to the work that you're doing. 

Satish Nadig, MD, PhD [00:06:39] I think it's a real paradigm shift in surgery and in medicine. Now there's two different perspectives in how we can move our research forward, and they don't need to be mutually exclusive. Historically, people would either go the NIH or extramurally funded route, and that's the quintessential academic route, or people would go the industry route, but they wouldn't really merge the two. And I don't think that there's anything wrong with that, number one, but I think it's actually a necessity in order to get something from the bench truly to the bedside in a timely fashion. And both of those things can really work together. And so what we did was we realized that this nano therapeutics with the anti-rejection medication was really a platform technology. And we developed a company called ToleRaM Nanotech in 2014, was a co-founder and the first chief medical officer for that company. And we got funds that we raised from not only government funding sources, but also grant funding like STTRs and SBIRs to push that technology forward. We could only do it to a certain point, to be fair, because we were all still practicing clinicians or I was still a practicing clinician, and two of my partners were scientists, Ph.D. scientists at the time. But what we realized is that technology was really important, and there was another company that was quite interested in utilizing that technology in in a different way, but also keeping transplant at the center. And so I exited my company and joined that company. That company was called Pandora's Technologies. And what we did was we set up a pipeline and we said, we'll do the R&D in our labs and we have some of the employees of Pandora Technologies in our lab and they're at the postdoctoral scientist level. We do the recapitulate that R&D and clinical grade in a clean cell facility and we had a clean cell facility in my last institution. And there's a robust Mathews Center for cellular therapy here at Northwestern, and that's done at FDA, GMP level. And and then we recruit patients within the walls of this institution. And so there's a real pipeline of bench to bedside. Now that's the industry side. So a lot of the mechanisms of how these particular technologies work can be done in parallel and can be applied for with what would be considered more conventional grant funding. Now there's pros and cons to both. One of the biggest pros for conventional academic grant funding is you get vetted by peers in the study sections and supported by the National Institutes of Health, which gives you clout and some street cred in the scientific world. But more importantly, it's highly scrutinized at a very high level from a scientific perspective. The downside is it takes a long time. A lot of times it's not enough money to move it forward in leaps and bounds towards the patient. On the investor side, the mechanism is not really what investors care about so much, the industry cares about so much and they really want to put the funds into getting it to the patient with a much quicker timeliness. And so there are pros and cons to both, but where they converge are these particular types of grants that I mentioned, which are small business technology transfer grants like stars and SBIR, where both of those worlds can converge. So I think the future of in my field, the surgical scientist really is an amalgamation of both industry related partnerships as well as a federally funded or extramural conventional grant partnerships that can attack the problem from both an observational and a translational perspective, as well as a mechanistic and a detail oriented perspective as well.

Erin Spain, MS [00:10:14] Tell us a little bit about the culture of these. Collaborations that you have. Explain what it's like working with these groups and do you feel like maybe the culture is a little different in the Southeast where you just came from versus here in the Midwest in Chicago?

Satish Nadig, MD, PhD [00:10:29] I think the culture is pretty similar from the Southeast to the Midwest. As far as the institutions have been involved, the institutions have been very open to this idea of partnering. Now there is some reticence, and I'll be very honest with that from any academic institution to let industry in the door, because there certainly can be industry that is, the motivations are not pure and there's a potential it's not as varied as what we know is conventional grant funding and those things. But once that's vetted and you have a really strong relationship with the CEO of the company that that you're working with, I think that relationship is phenomenal. The collaboration is phenomenal because the impetus and the motivations are very different than in conventional grant funding, if you will. The motivation is how do we get this into patience now? What are the hurdles? What do we need to do to get this particular technology into patients? Now, what's really important from a academic perspective is to make sure that I am 100% sure as to the best of my ability to know that these technologies are going to be good for patients. And so that's where it's important to have a real strong finger on the pulse of what the culture of the company you're working with is and if it's quality based. And so that's what you vet in the beginning when you first start to work with the company. Is is this data real? Is this data vetted? Is this company quality based? And can I help this company move to the next level? And that's where academic institutions like my previous institution in Northwestern come into play, because we bridge what companies call the valley of Death. When they have a good technology and they need to get it to a patient, they often have to outsource the clean cell facility or the Center for Cellular Therapy. They have to get advisors that are physicians that say whether this can be translated to patients or not. They have to be able to recruit patients. They have to get clinical trials to look back and see if these what the outcomes are of these. But if you're in an academic setting and you're somebody like myself that has access to all of these resources, you can be a one stop shop and bridge the valley of death for many of these startup companies that may have to outsource all of these opportunities.

Erin Spain, MS [00:12:53] NUCATS actually offers not only cross campus collaborations, but pilot grants and other funding opportunities to help evaluate these commercial potential for research projects. Tell me about what a valuable resource this could be for investigators who are looking to do what you're doing.

Satish Nadig, MD, PhD [00:13:09] There's a lot of resources here at Northwestern, and and the resources that we can offer to these types of startup companies are access to different departments, where if, for example, the company that I work with has different pipelines, for example, a corneal pipeline with the product that they have, which is called a liquid cornea, is a closest to clinical translation. I'm not an ophthalmologist, but I work with them and I can identify ophthalmologist, which I have. Dr. Ramez Haddadin in ophthalmology, works closely with the company as well. They have a long pipeline. We have a phenomenal pulmonary and lung transplant program here. I've identified people to be partners in that way. So we have access to different departments and divisions. We also have access, as I mentioned, to clean up facility. We have access to research labs and we have access to state state of the art technologies that we can help to make sure that these technologies are working and are controlled in the proper manner and are able to be translated.

Erin Spain, MS [00:14:05] It sounds like, you know, a biotech company is an pharmaceutical companies are really going to play an important role in you reaching some of your ultimate research goals, which is basically to get people off of these poisonous anti-rejection medications. Is that true? Would you say that these partnerships are critical to making this happen?

Satish Nadig, MD, PhD [00:14:23] I think they are critical, and I think they're becoming more and more critical as time goes on where the culture of research funding is so difficult for people and so competitive. And it takes a long time. Very, very rarely does somebody apply for a grant and get it on the first try, especially with the NIH. And so by the time that you get the grant and then do the research, a lot of the technology and the science has evolved. And so I think it is very critical to really get these things into patients. And if you identify what's the definition of a homerun for a clinician scientist, it's having an idea that gets into a patient and improves their lives within your lifetime. If you do that once in your lifetime, then you are enormously successful. And I think that industry can really help you hit that homerun.

Erin Spain, MS [00:15:11] Think another way a lot of physician scientists like yourself think of successes through the people that you mentor and this. Next generation that you're able to bring along. And one of your mentees, Meredith Taylor, is a NUCAT  trainee. Can you discuss the value that you put on mentorship and how training programs at NUCATS that prioritize mentorship better prepare this next generation of scientists to succeed?

Satish Nadig, MD, PhD [00:15:36] I think it's enormously important. This idea of mentorship is so it's funny to me that it's just not inculcated in our culture at the get go because we are a product of our own mentors. I see, Father, because I. I stood on the shoulders of giants and that's it's so true for all of us that are in the positions that we are in to be able to have the privilege to mentor the next generation. And one thing I always say is that if there's something that someone's doing that they're the only person that's doing it, then it's not a program. There's just a person doing a thing. But if they're able to develop the next generation and have more people that they can mentor and teach, and that kid that can take that product or that research to higher level, then then you can take it. Then it's a real program and that ends up being people's legacy, not the actual act of doing that discovery, but more of being able to teach others to do that so that they proselytize that and take it to higher, bigger heights in the next generation. And that truly is their legacy. So mentorship for me is extremely important. And I'll tell you, it's so important that Meredith came from South Carolina here when I moved here because I was very supportive of her potential. And I think that's it's really important to be able to identify talent and then cultivate that talent for.

Erin Spain, MS [00:16:59] Folks who are listening, younger scientists who want to follow your career path. What are some pieces of advice you would give right now as far as having this entrepreneurial spirit, being involved with startup companies? What are some things they can do to get off on the right path?

Satish Nadig, MD, PhD [00:17:16] So a few things is once you know, you have a good idea and that idea has been vetted through your mentors and and other people that are in the field that they can identify that really have your best interests at heart and say it's a good idea. Then just be hungry, be hungry and seek out opportunities. We don't opportunities don't come to us. We create our own opportunities. And so don't take no for an answer. Learn how to do it. Put yourself out of out of your comfort zone. Nothing good ever came from someone staying in their comfort zone. So if it feels a little uncomfortable, that's a good thing. That means that you're growing and really be persistent and and think out of the box. I'm not a bio engineer, so seek out bioengineers, for example, or seek out people that have different perspectives than what you have and try new things. The first time anybody starts a company, they're not an expert at starting a company. But you seek advice, you stay humble, you stay hungry, and you learn from people around you. And you listen to people around you and you heed advice. And at the end of the day, you listen to your gut as well. So not all advice is good advice. Sometimes you learn from your mistakes, but learn from others mistakes as well.

Erin Spain, MS [00:18:27] It sounds like in a lot of ways you're just getting started here at Northwestern. So tell me, what's next for you? Tell me what's next for the Comprehensive Transplant Center and all of these things that you have going right now at Northwestern.

Satish Nadig, MD, PhD [00:18:41] The best thing about this job is I'm surrounded by really good people. And so for me, I have the best job in the world. I set an ambitious vision. I have really great people around me. I just get out of their way. And so it's really fantastic what we have here in the Comprehensive Transplant Center. So I think on the research side, we really want to be a hub for transplant tolerance. We have been with works of Joe Leventhal and James Matthew over the years where we have more people off immunosuppression than anywhere else in the world. We need to be a hub for nanotechnology and a real, real player in the field of transplant tolerance, where not only we're the center of it, but we have a seat at the table for things that we're not necessarily doing primarily, for example, xenotransplantation, etc. Clinically, we have to be a top five program. There's no reason we can't be. And we've done more organ transplants in the last year than we ever have in the history of Northwestern, and we've done them differently. And so doing more is fine and great and we're going to help more people. But the most important thing for us clinically is to do them differently and expanding beyond what we think of as conventional organs to transplant liver, kidney, pancreas, which is our mainstay organ transplants. But we're moving forward and partnering with our OBGYN colleagues to try to push the envelope a little bit and do uterine transplantation, for example. So lots of these things are early stages and a lot of these ideas are just getting started and some things we've already accomplished. And for example, this past year we we did the first combined lung liver transplant successfully at Northwestern and one of the few in the country which gained a lot of press. We did the first. Robotic implantation of a kidney robotic donor nephrectomy as well here at Northwestern. So we've had a lot of firsts. We partnered with our thoracic surgery colleagues and did a lung kidney transplant across a cross-match. The first one, to my knowledge, globally, that's been done across a positive cross-match with a desensitization protocol. So we're really pushing the envelope to see how we can do transplant differently, not just how we can do more.

Erin Spain, MS [00:20:44] The name of this podcast is Science in Translation. What does that idea of science and translation mean to you?

Satish Nadig, MD, PhD [00:20:51] Well, that idea just embodies what it means to be a surgical scientist. I think that one of the reasons we all go into academics is to change the way we practice medicine. And so what what the idea or the title of science in translation means to me is taking care of patient, identifying how we could do it better, going to the bench, doing the research to figure out how we can do it better, and then taking it back to the bedside and actually implementing that. And if we can do that successfully, as I mentioned before in the podcast, once in our lifetime. Hopefully more, but if we can do it once in our lifetime, then I will feel at the end of my career looking back, that that I was successful and at least having a say in changing the paradigm of how transplant was practiced.

Erin Spain, MS [00:21:39] Well, that's a great pl ace to leave us today. Thank you so much, Dr. Satish Nadig, for joining me and telling us about your projects and your background and what you're doing here at Northwestern. We really appreciate it. Thank you. 

Satish Nadig, MD, PhD [00:21:50] My pleasure. Thanks for having me.

Erin Spain, MS [00:21:52] To subscribe to Science in Translation wherever you listen to your podcasts. To find out more about NUCATS, check out our website, NUCATS dot northwestern dot edu.