Business Of Biotech

Transforming Chronic Kidney Disease With ProKidney's Bruce Culleton, M.D.

• Ben Comer • Episode 284

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On this week's episode of the Business of Biotech, Bruce Culleton, M.D., CEO at ProKidney, talks about moving from academic research to industry and the role a key mentor played in his career path. Bruce discusses his experiences as a first-time CEO at ProKidney, a late-stage autologous cell therapy biotech focused on pioneering new treatments for chronic kidney disease (CKD), the benefits of FDA's Regenerative Medicine Advanced Therapy (RMAT) designation, how delaying or avoiding kidney dialysis would be a game-changer for CKD patients, and more.  

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Ben Comer:

Welcome back to the Business of Biotech. I'm your host, Ben Comer, Chief Editor at Life Science Leader, and today I'm speaking with Bruce Culleton, MD, CEO at ProKidney, an autologous cell therapy company that aims to disrupt the treatment landscape in chronic kidney disease, an incurable condition that typically leads to kidney dialysis. ProKidney hopes to delay or even eliminate the need for dialysis among chronic kidney disease patients by preserving kidney function, and has a lead candidate, Real Parent Cell, entering phase three clinical trials. Bruce is a first-time CEO with deep industry experience, and I'm excited to speak with him about his journey to the chief executive role at ProKidney, his clinical development strategy and engagement with the FDA, and what a new treatment could mean for patients with chronic kidney disease. Thank you so much for being here, Bruce.

Bruce Culleton, M.D.:

That's my pleasure, Ben. Thanks for the invitation.

Ben Comer:

Oh, I mentioned you're an MD. Uh you worked in academia and uh as a researcher and associate professor. What interested you initially, Bruce, about nephrology as a field of study?

Bruce Culleton, M.D.:

Um, I think Ben, sometimes it comes down to um when you're choosing subspecialties for uh for a lot of medical students, it comes down to the mentor. It comes down to who you're exposed to either during your medical school or for me during my internal medicine training. And uh, and my mentor was a nephrologist at that time. Um, I trained in nephrology in in Canada. And my mentor at that time was uh an Irish nephrologist who was well known for his research in the in the sort of intersection between heart disease and kidney disease. Uh, he was a very strong personality. Dr. Patrick Parfrey was his name, is his name. And uh um Dr. Parfrey at that time was also the coach of the national Canadian rugby team. So very big, very strong, very firm in his opinions. And uh he twisted my arm to uh to move my way into nephrology.

Ben Comer:

Well, speaking of the the crop, you know, the connection between kidney and heart disease, you also did a fellowship in clinical epidemiology at Boston University on the Framingham Heart study. Um, I wonder what you could say about that experience. It's a a you know fairly famous uh study.

Bruce Culleton, M.D.:

So um Dr. Parfrey was the one who connected me with the Framingham Heart study as well. So um Pat was sitting on a data safety committee with the head of the um Framingham Heart study at that time, Dan Levy, and uh they were on a data safety committee for a large phase three kidney product. Um and the head of Framingham in some hallway conversation said, Look, we were in Framingham. And so um within 12 months I found myself moving to Framingham, Massachusetts. Um and uh that as you alluded to is a very famous study. Um that started the study started back in the 19, I think back in the 1940s. And when I was there, they were on their third generation of participants that were coming back every two to four years for exams. And just for your listeners, that study was originally established in a small town about 30 miles outside of Boston called Framingham, mainly a blue-collar town at that point in time. They recruited 5,200 uh people from the community, and the plan was to follow them every two years for infinity, if you like, uh, for as long as they were alive. And that's what they did. And then they recruited their offspring, and now they're still recruiting participants in the Framingham Heart Study, where they have been recently. Um, and Framingham was responsible for identifying cholesterol as a risk factor for heart disease. It elucidated the role of hypertension and its impact on the heart and stroke. Um, it elucidated the role of smoking, um, of thickening of the heart muscle. I could go on and on. Thousands of publications came from one this from this center. And uh, my focus when I moved there was on the intersection between kidney disease and heart disease.

Ben Comer:

Well, it's incredible that you got to be uh a part of that. Longitudinal studies um are so so important, um, especially as you know, new drugs come into the marketplace. Um, that's uh that's pretty cool. In 2007, you made the jump uh to industry. You worked at Baxter in renal therapeutics. Uh, you got a master's degree in business administration too, uh, from the Kellogg School at Northwestern during your time at Baxter. What um what circumstances led to that jump? What made you decide to leave academia for industry?

Bruce Culleton, M.D.:

Um, so it came down to it came down to actually a couple of things. So the the first was um I wanted to have a bigger difference. Um I was I was seeing patients, we had, you know, worked with a great team, very successful at getting grants um and uh and recruiting researchers into our team. But I saw patients also on almost on a daily basis. And I was seeing just individual patients and having impact on individual patients, but I really wanted to have a bigger difference. Um, and that led me to think about how I might do that. At the same time, the medical lead for um the uh for Baxter Healthcare within the renal division is uh was a woman called Sarah Pritchard. And again, this comes down to just meeting people, getting to know them, and establishing connections. And Sarah and I met at a meeting um five years before that, um, introduced by Dr. Parfrey. And uh Sarah invited me to come down and speak to their team, understand what they were doing. I was very happy with what I was doing in Calgary, but they made me an offer to move to Chicago and join Baxter. And I de-risked that move by talking to the Department of Medicine and said, look, if I don't like this, can I come back? And he said, Absolutely. Um, but I loved it. Um my wife and I moved to the Chicago area. Uh, we both really enjoyed it. I loved um uh really making connections that I never did in academia. So the connections were with marketing, were with strategic finance, with engineering, with people that typically within academia you're not exposed to. And those those sort of newer perspectives were uh were just eye-opening. And I also got to see how the company thought about business, about how you think about bringing a product to market, how you could create a sustainable business. And and and immediately I became interested in the business side of things. Even though I was there as a medical director for one of their dialysis programs, immediately I became interested in not just the business side of kidney failure, but also the global business side. So you know, diabetic kidney disease, as an example, is diabetic kidney disease in the US and Canada and the UK and elsewhere and elsewhere and elsewhere. But how that care is delivered differs in every country. And that's that was also fascinating. So I loved it. They supported my MBA at Kellogg. Um, and then that just sort of made my interest in different parts of business even even even more so after that.

Ben Comer:

Yeah. So you were exposed to these uh not just kind of uh internal and local or or organizational business issues, but also you know, the the global business arena. And you said that Baxter help pay for the for the master's degree. Uh is that right?

Bruce Culleton, M.D.:

Yeah, they paid for it. Yeah, they had a great program. And I know a lot of companies do this, but you know, it really has a meaningful impact on on someone's career when they do that.

Ben Comer:

Yeah, absolutely. Um you left Baxter, uh, you went to Becton Dickinson, uh, and and then to CVS, staying in the the kind of kidney area. Um, what what did you learn through those experiences? Um, and and then what circumstances led to your joining uh ProKidney in 2023?

Bruce Culleton, M.D.:

So my my BD, my Becton Dickinson experience was pretty short, um Ben. So I was there for about for about 18 months. I was uh I was leading uh two things. One was their medication and procedural solutions medical affairs business, and I also was leading a clinical development uh program that they had, and they had over 100 trials in development. And so that was that was actually um very fascinating for me to be part of that. But then an offer came from CVS, which was too good to pass over, um, and that's why I left. And so the offer that came from CVS was from um from Dr. Alan Lotvin, who um had a senior role at CVS. And Alan reached out to me and said, Look, we're thinking about creating a kidney business within CVS. Would you be interested? And so I joined as their chief medical officer. I think I was the second or third employee, and we established a new business called CVS Kidney Care. And and our goal at that time was really to disrupt how kidney disease was identified, um, how the services were rolled out to kidney patients, and also how dialysis was performed. And it was around that same time where um the Advancing American Kidney Health Initiative, I think that was the name of it, that was a bipartisan uh that was an executive order, sorry, in President Trump's first term, which really highlighted some of the unmet needs in the care of kidney disease patients. Um it also established some new value-based care pathways. And so we were focused on several things. We were focused on home dialysis. We actually completed a clinical trial for a new home dialysis device. We uh we were partnering with satellite health care in several dialysis clinics. Um, we also joined the value-based care program and had value-based care uh activities primarily in the Chicago area. And and we did some fascinating things around digital interventions. Um, and uh even even tested some digital interventions to help identify patients with chronic kidney disease and sort of nudge them to get better care um within their local community. Um yeah, a fascinating experience at that time, around the time when the value-based care thing was taking off in the kidney space as well.

Ben Comer:

Yeah, that's uh that's really interesting. Um were the digital devices actually diagnosing uh chronic kidney disease or or or what would you say about that?

Bruce Culleton, M.D.:

So there they were they were digital interventions, so they weren't necessarily digital devices. So I'll give you an example. It could be as simple as we would um we would identify within um a health insurance database someone that has chronic kidney disease and didn't see a nephrologist within the prior three or six months, someone with advanced chronic kidney disease. So we were able to use that database and then to um provide an intervention, whether it was at the at the pharmacy or whether it was simply through a communication to their home through their through their uh um health insurance. So it was it was those types of nudges, I think, that tended to um move uh patients to see to to direct to see care. Um and all that was done within um a health insurance environment like CVS and Aetnahat at that point in time. And we actually saw changes in behavior based upon some of those interventions.

Ben Comer:

Um I want to come back to how you landed at ProKidney, but um you brought up uh dialysis and at-home dialysis. Um it's not a fun process for patients. Uh, you know, I I believe still most patients are going to a a dialysis um center like uh Fresnius or Davita, or I guess they're a single entity now at this point, but it's a very big business. What do you have a sense of what percentage of patients with chronic kidney disease are actually doing dialysis at home versus having to go to a clinic?

Bruce Culleton, M.D.:

Yeah, it's um it depends upon what country you look at, Ben. But in the US, um it's been a year or so since I looked at the figure, but I would say it's something like 87% of all patients are treated in center.

Ben Comer:

Yeah, okay, that's what I thought. And it's a big business, like $100 billion globally or more, I believe.

Bruce Culleton, M.D.:

Um it is, it's a huge business, and it's a business that is really craving for innovation. I gave a talk at um ASN's Kidney Week in, I think it was 2019, at their plenary session, and I did it with an entrepreneur inventor called Dean Kamen. And Dean and I uh peered up for that talk. And part of, you know, when I started talking about the need for innovation in the kidney space, I I referred to my journey where I left sort of clinical and academic practice, where I spent a lot of time in the dialysis unit. And just a couple of weeks before this talk that I gave at Kidney Week, and that was separated by over 10 years. And I went to a dialysis clinic here in Boston, you know, 10 years later. And um the only difference that I saw in that dialysis clinic was flat screen TVs. It was like time stood still, nothing changed, but they had flat screen TVs and better better chairs. Yeah.

Ben Comer:

Yeah. Uh that's uh that's a pretty amazing. Um, let's let's go back to uh ProKidney and and how you ended up there. What were the circumstances that that brought you to ProKidney?

Bruce Culleton, M.D.:

Yeah. So so at CVS, CVS was we were really testing these new care models. And some of them were working and some of them were not working, but CVS didn't want to scale the models because there were also competitors in the space that had already scaled regionally and some of them even nationally. You know, examples would be Strive and Monogram, who really, you know, have advanced the value-based care programs across the country. And so rather than continue to develop ours, I mean CVS did have a lot of capital. They ended up investing in um established value-based care models. And we wound down or sold back some of the assets that we developed to CVS and to EDNA.

Ben Comer:

Yeah, and value value-based care for for those that are listening that may not know exactly what we're talking about here, the the main, the main benefit, I think, of value-based healthcare is that you're you're paying for the care based on outcomes. Is that correct? Or how how would you describe it in the con in this context?

Bruce Culleton, M.D.:

Correct. So if let's just say that you are a Medicare um member on dialysis, then um through more historical ways of payment, your dialysis company would get reimbursed from Medicare every time you had dialysis, a certain amount. Under a value-based care program, the the dialysis model. That's the fee-for-service model. That's right. Fee for service model, yeah. Under a value-based care program, then that patient would, or the provider of the care for that patient would only get reimbursed based upon the outcomes, meaning keeping patients out of hospital, meaning certain quality metrics are met. Those types of outcomes, at the end of the day, they would get reimbursed from Medicare for that type of outcome as opposed to just a fee for service.

Ben Comer:

And so the incentive structure changes. The incentive is no longer getting people into the dialysis clinic, it's actually making the patient better.

Bruce Culleton, M.D.:

Correct. Yeah, correct. And the newer programs, they were originally the original programs were set up for dialysis, and the newer programs have now expanded into the pre-dialysis space as well.

Ben Comer:

Um, so what when did you join ProKidney? What year did you join uh ProKidney? Um, did you, you know, was uh did you meet Pablo Lagaretta Lagaretta, who I believe founded the company? Um let let us know about you know the kind of those circumstances.

Bruce Culleton, M.D.:

Sure. So um so I joined in um I think it was July of 2023. We just we just wound down some of the businesses at CVS. And um a board member on ProKidney, um, Dr. Lotvin, um, who hired me at CVS, he was on the board of ProKidney. He um, you know, he twisted my arm to to look at the opportunity at ProKidney. And and I was looking at several different opportunities, some of them in the dialysis space, but Alan twisted my arm, and obviously I met with uh with Pablo, and um and I was uh somewhat skeptical. It sounded like science fiction, um, but I was also very intrigued. And it took me several months of really looking at some data, talking to colleagues across the world, um, before I said, yes, I'll join ProKidney. And and obviously I talked to Pablo as well. And and and I knew Pablo. Um, I've met him several times before that in different other settings, didn't know him that well. But he did, he was uh a founder of a co-founder of ProKidney, and his investment in ProKidney really moved the company into phase two and eventually into a phase three clinical study program. And his investment was, and he's been public about this, his investment was driven by kidney disease in his family.

Ben Comer:

Right.

Bruce Culleton, M.D.:

Um, and his co his big co-investor who remains a big investor in pro-kidneys, Carlos Slim. And Carlos Slim's investment was also driven by kidney disease in his family. So they have not just a financial interest, but also personal interest in in us being successful.

Ben Comer:

And just as a side note, Pablo Lagaretta, uh extremely successful entrepreneur who also founded and is the CEO of Royalty Pharma. Um, how familiar were you, Bruce, with autologous cell therapy uh before joining Pro Kidney? Was it a a you know a a modality that you had had worked with at all? You know, what was what you know, how much did you know? You know, did you know what you were getting into?

Bruce Culleton, M.D.:

Um I didn't know much and and I didn't know what I was getting into. Okay, quite quite. Honestly, you know, and I was and but I was uh I had my eyes wide open and and I've always been curious, always been curious. Um and so I was curious in in this setting as well. Um I didn't know cell therapy, but I knew the kidney space. Um and I knew the kidney space really well, and I knew how to lead teams, um, and I knew how to you know create a strong culture, and I knew the business of the kidney space, but I didn't know cell therapy. And um, and we had experts in-house who knew cell therapy, but it but there was a learning curve for me on on the drug product for sure.

Ben Comer:

And you didn't I don't think you joined as CEO, right? When when did you when did you know that you wanted to be the CEO of a cell therapy biotech?

Bruce Culleton, M.D.:

So I joined as um as an EVP of commercialization and clinical development. They created a role for me, and and that role was really a successor role to the CEO when they created it. Okay. Um, but uh neither, I don't think anyone expected that transition to happen as fast as it did. So I joined in July and November I was the CEO. Um, and and there were, you know, there were some challenges that I've been public about within ProKidney, one of them on the manufacturing side, um, which we've overcome. The team did an amazing job to overcome some of the challenges, but we had an auditor as part of uh Q a QP auditor from Europe that is part of uh any program where you where you're doing a clinical trial in Europe. And um, the auditor found some critical and major deficiencies in our manufacturing, um, in our manufacturing plant. And uh that combined with some other challenges um the board had with the management team led to the board asking me to um to step into that into that role in November of 2023. Um and and I've um you know I've thoroughly enjoyed it, Ben. It's been, you know, um it's been uh hard work. Um it's been a lot of it's been a lot of work. It's been you know bringing in some really talented people. It's it's around fixing some mistakes that happened in the past. And I think now we're on, you know, really good trajectory. We've had some great interactions with the FDA. We've made some uh big strategic trade-offs in how we think about our clinical development program, and we've really fixed what we're doing on the manufacturing side as well. So we're in a great spot. And I guess what I'm most proud of, um, if anyone asked me, if what I'm most proud of, is we have 250 employees. And I could say all of our employees are dedicated to our mission and our sense of purpose. And that's all around how do we give patients who have advanced chronic kidney disease more time away from dialysis? How do we give them and their family members a lot more time by delaying as long as we possibly can the need for dialysis? And you alluded to it. Dialysis is not easy. And anyone that's been on dialysis will tell you that that their life changed overnight. And uh that's where we want to have an impact.

Ben Comer:

You know, I I should have asked you about this earlier when we were talking about dialysis, but uh for for the listeners, could you just uh maybe give us an idea of what the kind of uh traditional process and administration is for dialysis, how you know how often, how long, what it what it looks like.

Bruce Culleton, M.D.:

Yeah, of course. So for I'll talk about those 87% of patients who get their dialysis in a treatment center. Um so what that means is three times per week they leave their home. They commute, either drive or commute by taxi or public transportation to dialysis center. Um, they sit in a chair for up to four hours, they have two needles put in their arm, and the blood comes out of one of their needles, goes through a machine and goes back into the other needle. The the procedure itself is frequently complicated by infections and low blood pressure. And many patients, when they leave their dialysis unit, they um they um are not feeling any better, sometimes worse than when they went in. And many of them, there's a metric that's used that's called time to recover. Many of them will say it takes me 24 or even 36 hours to recover from my dialysis treatment. And then they have to do it again.

Ben Comer:

Yeah.

Bruce Culleton, M.D.:

And there's no end in sight for some patients who you know aren't suitable for a kidney transplant. This is their life forever.

Ben Comer:

And and what happens if you don't go to dialysis if you skip it?

Bruce Culleton, M.D.:

So if you don't go to dialysis, your your fluid that is typically removed in a dialysis treatment that accumulates in your body. The electrolytes, importantly, like potassium that's removed in a dialysis treatment, that builds up in your body. The potassium itself can lead to arrhythmias and sudden death. The fluid accumulation could lead to a collection of fluid in your lungs, and you'll have trouble breathing, so much so that some patients will actually die of heart failure.

Ben Comer:

Right. Right. Um, I wanted to ask you about um the manufacturing briefly. Uh it's not, you know, autologous cell therapy manufacturing is not the same thing as uh, you know, large bioreactor monoclonal antibody manufacturing. You're you're based in Boston, Bruce. Um, can you uh give me a sense of what the manufacturing uh capability looks like at ProKidney? Are you doing your own manufacturing? Are you working with CDMO? Um I I think you have uh you have some facilities in North Carolina, is that right?

Bruce Culleton, M.D.:

Correct. So our manufacturing facilities are in Winston-Salem, North Carolina. Um we have one facility today that's supporting our phase three program, and we're building out another facility next door. Um in that manufacturing process, so just to give your listeners an example of what happens. So for us, we obtain a kidney biopsy from patients who are enrolled in our study. Um, and that small piece of tissue goes back to our manufacturing facility. That that tissue may have 50,000 to 100,000 cells. Um, over the course of the next few weeks, under the right culture media, um we uh we end up with billions of cells. And then we select out a certain type of those cells through a manufacturing process. And that type of cells that we that we end up selecting out have markers that resemble tubular and interstitial cells in the kidney, but they're the same, they're the patient cells, they're their own cells. So they the there's no concerns about rejection when those cells are injected back into the patient. We take those billions of cells and we put them into separate vials based upon a dose that's required for the patient. Um, and then that vial, that one vial, then gets shipped back to the study site and it's injected back into a patient's kidney by an interventional radiologist under CT guidance. And so that's a very specific location where we inject those cells. Um, and then what happens to those cells is we believe that those cells help the patient's innate repair and recovery mechanism. And what we've seen clinically is really a stabilization of kidney function after those cells are injected.

Ben Comer:

Okay. All right. Um, I wanted to ask you, you know, there's over 35 million Americans, I think, with chronic kidney disease, 800 million plus uh worldwide. We've talked about um dialysis, hopefully getting some patients out of dial or preventing them from going into dialysis. What what do you see as kind of the biggest opportunity uh for these patients or the biggest unmet need? Is it simply avoiding dialysis or are there other elements to chronic kidney disease that that you hope to tackle?

Bruce Culleton, M.D.:

So um just for your listeners, of those 33 million, 30 plus million patients in the US with kidney disease, most of them don't even know they have it. And so the greatest opportunity to help them would be through screening and awareness. So even patients who have high blood pressure, their their kidney function is not getting checked. And it's easy to check it. It's it's a urine test, it's a blood test. There's not even a complicated blood test. Um, a lot of patients who've got diabetes don't even know they have kidney disease, even though that's recommended as a screening tool for everyone with type 2 diabetes, for example. So the biggest impact, I think, from a society perspective would be to improve awareness and education around chronic kidney disease. So those 30 plus million patients who have kidney disease will get detected early. And we have good drugs, um, even good lifestyle measures to help those patients in very early chronic kidney disease. Most of those patients, by the way, will never end up in a dialysis unit. Oh. So today in the US, I think we have, you know, somewhere over 500 to 600,000 dialysis patients. Um, most of them that start at the top of the pyramid will never get down to knee dialysis. They have competing risk factors. And unfortunately, many many of them will die of one of those competing risks, like heart disease, for example, or some of them may just simply die of old age. Um now, for those people that do end up with more advanced chronic kidney disease, and and our estimates are there's about four million people in the US who have um lost over 70% of their kidney function. Now, that's a lot of people. And that's a lot of people who are on the path to dialysis. And every year there's somewhere between 130 to 150,000 people who start on dialysis. And those are the people that we want to prevent. We want to keep we want to prevent people from going from stage four to need dialysis. And that's really where our target population is. But again, getting back to the biggest opportunity, it's it's detecting kidney disease early, lifestyle, um, lifestyle changes, and there are new drugs that clearly make a difference in slowing down progression of kidney disease if patients are identified.

Ben Comer:

It's uh it's almost unbelievable that patients are are not tested, particularly type 2 diabetes patients are not screened for chronic kidney disease when you can actually take an action, you know, to to slow it down. What and you said that the there are recommendations to get tested. Um what what what would be needed in terms of, I guess, guidance? Maybe it's a a you know a Medicare coverage issue. I'm not sure. But um, you know, what would be from a policy perspective, what would be a good way to make sure that that people were screened more often and and could find out, you know, that they they had chronic kidney disease and could take action?

Bruce Culleton, M.D.:

So there are guidelines on this. Um there are also guidelines on on screening, and um those guidelines are paid for in certain populations, uh, like patients who have diabetes for so long, you know, they're the the provider will get reimbursed for that for that screening. But as you know, um it's not just about the reimbursement to the provider. Sometimes these visits you know have out-of-pocket costs for patients. And not every patient can afford out-of-pocket costs, um, especially if it leads to uh more and more visits. Right. And so access to care is is continues to be a real challenge. And and kidney disease is overrepresented in um in poorer communities, rural communities, some ethnic backgrounds. And so there are, I would say, societal challenges that come with making sure that everyone who's got kidney disease is is detected early and and treated the right way.

Ben Comer:

Is the percentage of um of patients that get dialysis at home increasing? Um it is I assume it's more expensive for home dialysis versus in clinic dialysis, but I don't know that to be true.

Bruce Culleton, M.D.:

So um the two questions there is home dialysis increasing? I think slowly. It's it's not, you know, it's a it's it's very challenging, but it slowly it's increasing. And there have been some policy initiatives that help increase, help improve um um number of patients who are treated with home dialysis. The the economics for the provider are also important. And under value-based care initiatives, home dialysis tends to be more profitable for a value-based care provider. So that's also a move in in definitely a move in the right direction. Um, and then there's just uh just a lot of education that needs to come with it. And, you know, some of this is patient education. You if you can imagine being told for the first time as a patient you've got kidney failure and that's a surprise for you, completely out of the blue, and you need to start dialysis. Um, you're more likely to say, I want that treatment in a clinic where I have nurses around me, than say, I want to do that at home. Even though the outcomes for you are better at home. The outcomes are really better for you at home. And the societal costs are are lower at home, all things considered. But most patients still end up in center.

Ben Comer:

What uh getting back to to pro-kidney, what is unique about autologous cell therapy uh as a modality for treating uh chronic kidney disease? You know, what do you like about that approach? It sounds you know, it it sounds like you had kind of a um a baptism by fire rising up to the CEO role very quickly, having to kind of clean up some manufacturing issues right away. You got to know all about autologous cell therapy as a modality uh um very quickly. Um what you know, what do you like about it? What you know what do you see as its kind of uh chief promise?

Bruce Culleton, M.D.:

So what I what I like about it is that even though it's a complex process to make our product, it's the patient's own cells. And every product is slightly different because it comes from the individual patient. So every product is its own batch. And if you think about personalized medicine, this is personalized medicine at its best. It's the patient's own cells that go back into the patient that are healthier and we believe sort of encourage the innate repair and recovery mechanism to work on stabilizing kidney function. So that's the piece that I really like. There's no gene edits, even though I am a big fan of gene therapy. There's no gene edits. Um, and there's there's no pretreatment for the patient. You know, in other, in other sort of cell therapies, let's say in the oncology space, you know, there's a pretreatment for the patient. They're often extremely sick. Um and and the pretreatment may make it even more difficult for them over a short period of time. We don't have any of that. It's uh it's simply patients' own cells, they're relatively stable, slowly progressing, you know, year over year, but they're not, you know, in a hospital acutely sick. Um and so there are clear differences between what people hear around CART cell therapy versus what we're trying to do in the kidney space.

Ben Comer:

Right. I mean, the uh it's a a huge advantage to not have to chronically administer immunosuppressants, which you know, autologous cell therapy is a complicated process, but that kind of in and of itself is is very significant. Um what I guess what would you say is the or what do you see as the biggest challenges that that you'll have to overcome, Bruce, to make make this successful and get it out to patients?

Bruce Culleton, M.D.:

So obviously we need to we need to finish our phase three program. Um we will we're um we're currently currently doing really well on enrollment. Um we will have a readout, um uh a top line readout for accelerated approval in May or June of 2027. So that's not too far away. Um should that be successful, um, which we all think it will be, but should that be successful, then I think some of the challenges that we will have will be primarily on the commercial side. You know, how do we scale up appropriately? How do we manage to get the capital that we need to scale up appropriately? How do we manage the demand?

Ben Comer:

Yeah. Have you so it sounds like you've started to think about launch and commercialization and and what that might look like. Um you know, you're you're already starting. I guess what are your what are your initial thoughts in terms of the scope of a launch? You know, how how big would that potentially be following approval?

Bruce Culleton, M.D.:

So the the the the process is is more complex than someone waking up every morning and taking a pill. Yes. A lot more complex. With that said, once you have your two injections, because we inject both kidneys three months apart, once you once we inject both kidneys, you're done. Primarily you're done. So you don't have to worry about taking your pill every morning or twice a day or something like that. You've actually gotten your treatment, and then we will follow you over time. But um, but you know, one of one of the one of the things we need to think about is how do we how do we ensure that we when we launch that the patient experience and the provider experience is um best in class. Yeah. Because this is there are a lot of touch points. It's not just with the nephrologist, it's also with the doctor who does the biopsy, then it's with the interventional radiologist who does the injections, and then it's back to the nephrologist for follow-up. You know, that experience for a patient really has to be seamless.

unknown:

Right.

Ben Comer:

Right. So you you kind of work to standardize that process as best you can, make it as most efficient as you can, and then simply replicate it out from there. Is that right? Yeah, that's right.

Bruce Culleton, M.D.:

And the interventional radiologist needs to be trained appropriately. The nephrologist needs to know how to have that conversation with their patient before you prescribe it. So that whole process, in my mind, is critical in the first, you know, 12 to 18 months after launch. And so the way, you know, we would be thinking about this is how do we make that a best in class process? So the patient experience is great, the provider experience is great. And and that may mean that we just don't, you know, go gangbusters like you might if you had a small molecule and you wanted uptake across the country.

Ben Comer:

Um, what about, you know, global launch? Is that some, is that, you know, will you conduct additional trials? Uh, do that kind of as a second step? Are you thinking about um potentially commercializing outside of the US? Uh, are you doing that work in parallel? How do you how do you think about that?

Bruce Culleton, M.D.:

So um we we made a big um strategic trade-off um in the summer of 24. And and in the summer of 24, we were um we had two phase three studies that we were running. And this decision was made before my time, before I joined ProKidney. One phase three study was primarily US, and the other phase three study was primarily Europe and Asia. And um, we had something called an RMAT designation at that at that point in time. And an RMAT designation typically gives the sponsor certain benefits, including an accelerated approval pathway and even a pathway where you really don't need two phase three studies. So in the summer of 24, I asked that question like, why are we doing two phase three studies? Both studies are expensive, they're diluting our resources. Um, where's our where's our um where's our market that we want to launch in? And where do we think as a company we can be most successful? And that was clearly the US. So after a discussion with the FDA, we made a decision to stop our other phase three study. Okay. And that that saved us about 150 to 170 million dollars. That really helped with our cash runway. And those are some decisions that you have to make because you're constantly trying to balance, you know, what do we really need to do, and how will our cash runway take us there? And so that was that trade-off we made back then. And now our cash runway takes us into the mid of 2027 after a readout. And that's what you really want is you want your cash to take you to a readout and a little bit longer after that readout. So that's where we are today. So we're we're very fortunate given the fact that a lot of biotechs are working with less than 12 months cash. Yeah, right. So just getting back to Europe then. So we don't have plans today, but we we you know are definitely open to working with partners who may be interested in you know, expansion in Europe or expansion in parts of Asia. Um, but our focus today is truly our focus is executing the phase three program that we're doing today well, so that we'll have a positive readout in uh in May or June of 2027.

Ben Comer:

And we're talking about uh real parent cell. Uh that's the lead program uh at ProKidney. Um I saw, I think it was uh a November kind of corporate report um or presentation. You had at that time enrolled over half of the population needed for the phase three trial. Um you've mentioned when you expect uh to get that kind of uh top line data read. Um, and you for this particular lead indication, you're pursuing patients with chronic kidney disease caused by type two uh diabetes. What what percentage of the overall CKD population does that represent? And and also is type two diabetes the the kind of primary driver of uh of CKD?

Bruce Culleton, M.D.:

So um if you look at all the patients who start dialysis in the US today, the 130 or 140,000, 60%, 60% will have type 2 diabetes. Wow, okay. Um now is that uncontrolled type 2 diabetes? No, not necessarily. I mean, some of them may have had poorly controlled type 2 diabetes over time, but I wouldn't say that I wouldn't universally say that it's all uncontrolled. But of that 60%, there are some patients who just have type 2 diabetes and another reason why they have kidney failure. And then there's another group that about 40% of the total that have kidney failure due to type 2 diabetes. And and those are the patients that we're really trying to um have a therapy for.

Ben Comer:

Do you um do you anticipate expanding the indication uh beyond patients with um chronic kidney disease caused by type 2 diabetes?

Bruce Culleton, M.D.:

Yeah, we do. I mean, we we don't have a program looking at that today, but if I could just explain to you what happens to most patients who end up in stage four chronic kidney disease, and that's really we're we're studying stage four patients with type 2 diabetes, and they've lost over 70% of their kidney function. But what happens is is in that sort of final stage before dialysis, a lot of patients have mainly fibrosis and inflammation that's driving their progression. The underlying cause of their kidney disease is already established, it's already, it's already sort of injured the kidney years and years and years of high sugars, for example, and the inflammation that come with that. In this late stage, almost in every form of kidney disease, there's a there's a big driver being fibrosis and a big driver being inflammation. We think what we're doing is having an impact on that fibrosis and inflammation. Okay. And and there's probably nothing unique about it because they have type 2 diabetes. It's really that fibrosis and inflammation. So we chose to focus on type 2 diabetes because that's the greatest unmet need. But at the same time, we hope to be able to develop programs in the future where we can almost have like an umbrella therapy for all those patients who have stage four disease as an option for those patients as well.

Ben Comer:

At what point is it too late for a real parent cell to help? I mean, for patients with kidney failure, you're, you know, you're not going to regenerate or or you know, bring that back, right? Yeah. That's true.

Bruce Culleton, M.D.:

So what the way we've designed our studies today is if your estimated glamural filtration rate, your EGFR, your measure of kidney function is less than 20, you can't get into our study. And that's probably going to be what our label would say too, is that we can treat patients down to a level of 20 mls per minute, but not less. Do I believe it works in someone with 15? Yes. Um, but the the risk, the safety risk also increases the lower your kidney function is. So your kidneys become smaller, it becomes harder to do a biopsy, it becomes harder to do an injection, and so your risk around safety events also goes up. So we try to create that right balance between choosing patients who we really think will benefit while at the same time being a little bit, you know, um conservative around the safety side because, you know, we're still an investigational product, and we wouldn't want this innovation to stop because of safety issues.

Ben Comer:

Uh you mentioned earlier that um real parent cell has uh has received FDA's regenerative medicine advanced therapy designation, RMAT. You talked about some of the key benefits there, one of which, a big one, that you only potentially have to do one phase three um trial. Uh it's an accelerated uh regulatory pathway. Um are there any other benefits conferred by that designation? And and then I'm uh after that, I want to ask you a little bit just about you know your interactions with the FDA and and sort of what that looks like. And I have listeners in mind, you know, who may be, you know, in the early stages of starting up a cell therapy company or are thinking about various regulatory pathways and designations. And so um any kind of color you can provide, you know, on what those interactions look like, um, I think would be would be useful. But aside from the the singular phase three trial, the accelerated pathway, uh is there anything else that you would mention that you know you think is important as part of that designation, that um that RMAT designation?

Bruce Culleton, M.D.:

Yeah, so so the RMAT designation certainly allowed us to have more regular interactions with the FDA, particularly around you know, developing the protocol or CMC strategy and lots of other things as well. But for me, I'd say the two biggest, the two biggest things we've already hit upon. One is one study, one phase three study, and the second is an accelerated approval pathway using a surrogate endpoint, and we're using EGFR. And and that all those two big decisions came about by having great interactions and meetings with the FDA face to face. Um interesting. And and I will say that um at least in my time at ProKidney and even my pre previous reactions with the FDA, you know, they're scientists. Um they're they're for the most part extremely rational thinkers based in science. And um sure there's a policy piece to it, um, but but usually when you have a discussion around the science and the clinical data and sort of an understanding of you know how your product might potentially work, it's been really good. I mean, they've been they've been great to work with.

Ben Comer:

When's your next meeting with the FDA?

Bruce Culleton, M.D.:

So we don't have any um we don't have any meetings coming up in the next six months or so. Um the next big clinical meeting will obviously be around our our readout when we get to our top line data. Um, and then there'll be some more manufacturing and CMC type meetings, you know, between now and then.

Ben Comer:

If you uh I guess best case scenario or uh best of all possible worlds, uh when would you like to see uh this product approved and start getting out, you know, out the door to patients?

Bruce Culleton, M.D.:

So I think best of all possible worlds, like we have a readout in let's say June of 27. We put uh we put the finishing touches on our BLA, we submit that at the end of 2027, and we get approval in 2028. Okay. Best case scenario is probably mid-2028. Give me two slides.

Ben Comer:

Not a bad timeline.

Bruce Culleton, M.D.:

No, no, it's pretty good.

Ben Comer:

Yeah, yeah, yeah. Um, we're uh we're getting to the end of our time here, Bruce. What uh what would you say are your your top priorities um uh for the rest of this year and you know, looking into the beginning of 2026?

Bruce Culleton, M.D.:

So um we're almost at the end of this year and and we've met all our goals for this year as a team. So we've done, I I think our broader team hasn't done just an amazing job this year in getting us to where we are to finish the year. Next year, our priorities are are primarily around preparing for that top line readout in 2027 and being ready for that BLA that we need to uh that we need to put together. So that's what our activities in 2026 are really driven around. Completing the study, making sure we have the data in place to do the readout, making sure we have everything else on the clinical, technical, manufacturing side ready for that BLA submission. That takes you know 12 to 18 months at a minimum to get ready for. So, really, that's really a big driver for us in next year. And I'll say the other big thing for me is um is just maintaining uh the culture of our team. Um you know, we're we're all driven by a sense of purpose. We've had patients come into our team meetings, our all-employee meetings, and we all see why we're doing this and why it's important. And and we're not gonna get anything done unless we have everyone behind us.

unknown:

Right.

Bruce Culleton, M.D.:

And so that's also a big thing for us next year.

Ben Comer:

All right. In the uh the final uh two minutes, I was um you know thinking about this interview coming into it, and this this question popped in my head. It's not related to to pro-kidney, um, but I'm I'm curious, you know, as a kidney expert, maybe you could answer this. Someone who's in, you know, the the worst stages of kidney failure, the only real option they have is transplant. Let let's say, and this is a hypothetical, I promise, but you know, let's say I I have a sibling who has severe kidney failure. It's we I find out that I could potentially give them a kidney to save their life. Um, how and there's a you know, we we don't have time to get into the whole issue of available kidneys for for you know donation and and how that happens, but um, how risky is that? You know, would it make uh from a cost-benefit kind of analysis, would would it make good sense for me to give one of my kidneys to a sibling in in that instance?

Bruce Culleton, M.D.:

So then usually those um, whether it's a living-related donor or just an altruistic donor, someone who just in the good of the good of their heart says, Look, I'm gonna give out my kidney. I don't need both. That matches, right? There are some altruistic donors, they all have to go through a pretty rigorous medical assessment. So, so the medical risk of of donating a kidney becomes minimal because you know you can't donate a kidney if you've got diabetes or you know, uncontrolled high blood pressure or other things that might complicate your post donation recovery. So they undergo a very rigorous assessment. So that's one. And then number two, having talked to many kidney donors, the um the emotional benefits that come with helping someone to to that degree to keep your loved one alive and their family. I mean, that benefit outweighs any small risks that may come on on the clinical side.

Ben Comer:

I think that's a fantastic way to end. Uh Bruce, it was really a pleasure speaking with you. Thank you so much for coming on the show.

Bruce Culleton, M.D.:

That's been my pleasure, Ben. Some sometime maybe we can connect more on transplantation. There's also some lot lots of real innovation happening in the transplantation space.

Ben Comer:

Yeah, that'd be great. Let's do that. Uh, we we've been speaking with Bruce Cullaton, MD, CEO at ProKidney. I'm Ben Comer, and you've just listened to the Business of Biotech. Find us and subscribe anywhere you listen to podcasts, and be sure to check out new weekly video casts of these conversations every Monday under the Business of Biotech tab at lifescienceleader.com. We'll see you next week, and thanks as always for listening.

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