ProKidney Corp. (PROK) Earnings Call Transcript & Summary

We're going to get going here at the -- with our next company presenter at the BofA Annual Health Care Conference. My name is Jason Gerberry. I'm one of the biopharma analysts here. And I'm pleased to be introducing ProKidney and CEO, Tim Bertram. So Tim has some slides he's going to run through. And if time permitting, we may have time for a little discussion.

That's perfect. Perfect. Thank you, Jason. Thank you all of you for coming to hear our story about ProKidney. I thank you for your interest, and hopefully, we'll have some time for questions. I'll be making forward-looking statements today. You can find the details on this and on our website if you want to follow that further. So what is ProKidney? And what is our real goal and mission? ProKidney is trying to bring a halt to one of the most expensive unmet medical needs that we currently have today, and this is kidney failure. Why is kidney failure so significant? It is a $130 billion problem that exists within the U.S. and Europe. It is very, very sizable. The problem is that it also has a major impact on the patient and on the family because the outcome usually is dialysis. And as a result of dialysis, we see additional costs that go to maintain that patient in a very low quality of life. The product that we want to bring forward, currently in a Phase III, is a cell-based product composed of 3 different cell types based upon over 15 years of research, in which we identified and evaluated the healing process of the kidney to identify these cells that would help preserve kidney function when placed back into the patient. It is an autologous homologous cell therapy. So there's no concern for rejection. There's no need for special medications either before or after the administration of these. Because it's autologous, it can be delivered repeatedly without any concern for rejection. The approach that we're taking in this Phase III is to get approval from both the FDA and the EMA because of the significant unmet need in both major jurisdictions. What we're very excited about, however, is that there is the potential, if successful, to be able to have an impact on the cost, not only the cost to the patient, but the cost to the health care system. Because of the enormous investment that occurs, any delay or putting off of the costs associated with this are substantial. So this slide shows just how substantial this problem is. What really is striking when you look at this slide is to look at the number on the far left, $80 billion spent each year simply on the prelude or the disease state of chronic kidney disease before end-stage renal disease. Once patient goes on to end-stage kidney disease, an additional $50 billion is spent. Collectively, this is a cost of about $93,000 to $100,000 per patient per year, tremendous impact. It's the single largest line item in the CMS budget. What's also quite devastating about this is if you look in 2020, by the end of this decade, we will see a change from 74 million to over 80 million people affected. So the disease state is not slowing down. If anything, it is continuing to accelerate as the concern for diabetes and hypertension continue to accelerate. What's also quite significant is that a number of new medications have been brought forward to address this problem. Billions of dollars are spent on these medications, and they're actually quite good. What you can see here is the SGLT2s, what's shown in each of these graphs here. So thousands of patients have been evaluated in these randomized controlled trials. What's very, very important about this is to look at what stage of chronic kidney disease were used to assess these different medications, the SGLT2 in each of these 3. What you can see, with 76 mL per minute, that means that the patient has lost about 25 mL per minute of function or about 25%. This is actually an early stage of chronic kidney disease, and the patient may not even be aware of the disease state. If you look at the more severely affected, where about 57% of the kidney has been lost -- function of the kidney has been lost, you can see that there is some effect. But let's look at the effect very carefully. The gray line represents the normal patient journey. And you can see -- and even when mild chronic kidney disease or more severe, you see a progressive decline. So even with mild or moderate chronic kidney disease, when administered the SGLT2, as shown in the blue line, all you do is attenuate the decline. The decline is inevitable. And it is this, with one of our most advanced therapies to treat this disease, it is this that we decided to take a look and see if we could actually bring benefit, a greater impact to these patients. As a result, and I'll share with you shortly the data, we've taken this cell-based therapy to evaluate patients that have lost 50% to 80% of their kidney function. Why is that important? At this stage, at these earlier stages of chronic kidney disease, the costs that are being incurred by the health care system are limited. As you get to the more severely affected patients, where they've lost up to 80% of their function, this is where the costs start escalating substantially, and the cost of the health care system is significant and the imminent movement of that patient on to dialysis exists. So we're very excited about bringing this forward and, hopefully, in a complementary fashion to some of the other medications, which are also coming forward to be able to benefit these patients. So what is the addressable patient market? One in 7 people are affected with chronic kidney disease. That's a very sizable amount. As I look across this group, and I see that we've got somewhere around 20, 21 people, there's probably 3 of you, whether you know it or not, have chronic kidney disease in 1 of those stages, just based upon the probable demographics, what we've got and the incidence of this and prevalence of this disease. What you can see here is that we are focusing on the later stages. And even in the later stages, there's about 4.4 million patients that are affected with the disease in this range. This is the more severe range. It is the range in the lost kidney function, which is where most of the costs are incurred. So what is this product? REACT, as we call it, which is the Renal Autologous Cell Therapy, is from the kidney of the patient that is affected. Chronic kidney disease is not a disease of the cell, particularly in diabetes, it is a disease of the tissue in the organ. So the cells have lost their ability to do what is normally their function. What we developed over 15 years of research was to be able to take a standard biopsy in which hundreds of thousands of biopsies are taken from patients routinely in the United States each year. And with that biopsy, we are able to make 5 to 10 products available to the patient in our manufacturing process. Our manufacturing process is proprietary, but we have a 98% success rate. We can make 5 to 10 products from each biopsy. So that allows us then to basically have an off-the-shelf product, an autologous product, off the shelf, with that number of injections possible for a patient, allowing then the patient to be managed in a way that is appropriate for their disease. What we do then is, after the 5 to 10 products are produced, we freeze them for distribution to the patient at the time of injection and when that therapy is to be delivered. What's very, very important for us is that the delivery process, and I'll show you in a moment why this is important, but the delivery process involves a conscious sedation injection of the cells directly back into the kidney cortex. Why is that the case? Because what that allows us to do is get the cells back from where we took them. It allows for a rapid effect then for the cells to distribute properly to the locations where there is disease. This process has actually been shown to be quite safe, and I'll review that data with you here shortly. So I just described the process of how we get it, but what is actually the active biological ingredient in the REACT product? That is shown here. So over a number of years of research, we realized that there were 3 cell types in the kidney that were responsible for normal healing and repair of the kidney, which people with normal kidney function are very capable of doing. The kidney has a tremendous ability to repair and regenerate itself. However, with chronic kidney disease, what happens is these cells, although present, are in diminished numbers. And what we've been able to do then is by identifying these 3 cell types taken from the cap mesenchyme, ureteric bud and the podocyte, which are the 3 building blocks of the kidney during embryologic development, we've been able to show that with this injection procedure, as shown here in this dog kidney, where the cortex and the labeled cells, which are shown in green, when injected back into the cortex, within 24 hours, distribute throughout the kidney. This is a very significant benefit because what we also realized is by looking at these, the question became, where do the cells go throughout the kidney? And when looking back at the labeled cells, what we could see is that the cells went to damaged glomeruli, but not all damaged -- not all glomeruli were equally damaged. Some were heavily damaged and heavily labeled. Others were only partially damaged. And so the cells, which we demonstrated later, in vitro, have the ability to be able to migrate to areas of damage and localize in those spots. And this showed then very clearly that areas of glomeruli that were damaged as well as tubules, shown here, where the cells completely replaced the damaged epithelial cells, with now the cells that we had implanted. But not all tubules showed that effect. And similarly, within the interstitium, they migrated to be able to change and modify the fibrosis and inflammation. Last year, we did additional publications, and we continue to publish on our mechanism of action. And one of the interesting findings was that these cells will spontaneously form organoids. For those of you familiar with this space, organoids have been found to be a very strong indicator of the regenerative and reparative potential of cells that are put back into tissues. What you can see here is that the cells actually spontaneously go back to form tubules and nephron-like structures in vitro. This occurs spontaneously, and it's important that they maintain that as we go forward to inject it. What's also very, very exciting is when we inject these cells into animals that had diabetic kidney disease, shown here, where they had extensive fibrosis, damaged tubules and inflammation, protein casts, when this kidney was injected with REACT, this is what we saw. There was a restoration of glomeruli, very similar to those who have been normal. And tubular casts were diminished and the tubules looked very similar to what was normal. So this was quite an exciting outcome, and this has been published and presented to show in multiple animal models. We've shown this in 4 different animal models. All animals had chronic kidney disease and then showed this level of change. So collectively, if we look at this, the mechanism of action can be shown here to basically be the cells will integrate back into the tissues. This is important because there is a regeneration and repair of the nephron structures. They've also, as a result of being an autologous homologous, we've shown that they can exist there for up to 6 months as a half-life. This is consistent with published information about these cells and shows that we have a normal cell population returning to do the job that they were originally intended to do. What's also been quite exciting is that we've been able to demonstrate that these cells release multiple cytokines, which were responsible for reduction of the fibrosis, inflammation and restoration and maintenance of the nephron. So collectively, this accounts for the preservation of kidney function that we see in the animals and, as I'll show you here shortly, in the patients. Collectively, what we've been able to do is ask the question, is this cell specific for diabetic kidney disease, which accounts for 50% of all chronic kidney disease? Or could it be applied generally? And what we've been able to show is, although we're focused largely on type 2 diabetic kidney disease, we've also been able to show substantial improvement in other forms of chronic kidney disease, including congenital anomalies of the kidney and urinary tract. We have these programs ongoing. They're in different stages. And what we will be doing is, as this year goes on, in particular, and I'll talk about that in a minute is, we'll be releasing this data to show investors what the impact of this cellular therapy is in chronic kidney disease. So if we stand back, I'm about to go through the different trials that we have. And if we stand back and ask, how do these fit together to form a package that could be commercializable? I'll share with you the 002 data. This formed the foundation, and it showed that the effects that we were seeing in animals could be replicated in human beings that had severe chronic kidney disease. What we've also done is we've asked the question, could we treat patients that are very severely affected, borderline going on to dialysis and continue to see preservation of their kidney function, thereby delaying that? And I'll share that data with you in a minute. We've also got a program that we're starting where the question comes, since I can make 5 to 10 of these and the injection or dosing is only 2 injections, the ability to give supplemental injections on demand is another study that we're looking at, and we're showing, and that's shown here. And that will be reported later this year, an update on what we're doing in terms of the progress of that trial. And then lastly, a trial that's active, an open-label trial, is called 007, which will give investors a view into the 2 Phase III trials, which are blinded, and allows you to get an early sense of what the results are of when we inject not in a single kidney, which all the Phase II trials were, but now with a sufficient safety input, the regulators have said that we could dose both kidneys and give an injection in each kidney. And that will be given and provided in the 007. So collectively, what we have, this trial is active. It's in the United States, ongoing, it's the 006. The other trial is 016, will be run rest of world, and we hope to start that later this year. Both of these have been reviewed and endorsed by the FDA and the EMA. And we hope, collectively, then this will allow for us to look at registration in the 2026 time frame. In addition to that, one of the things that we're excited about is payers. Payers are interested in the durability and in the potential for repeat dosing. And so collectively, the package is designed not only for regulatory support, but also to promote premium pricing. So let's go through some of this and share the data that we're showing -- that we're seeing. So this is the 002 trial, which, as I shared with you, was this cornerstone in our package. This is a one-to-one randomized controlled trial of 83 patients. What we did with this is we took a biopsy and the patients were assigned to 1 of 2 groups, either an active group, as we called it, in which 2 injections, 1 full dose of REACT was given to the patients after the product was manufactured, separated 6 months apart and in 1 kidney. So because of safety concerns and what we wanted to do is make sure the other kidney that was not injected would not be damaged at this time, we didn't know for sure at that time. We injected twice in the same kidney that you've been biopsied, and then we followed them for 24 months. Because we needed a concurrent and contemporaneous control, we put another group of patients for 12 months on best standard of care and followed them. And at the end of that time, if they still qualified, they were going to be crossed over and participate in the active or get the REACT injections. These patients, shown here, these were type 2 diabetic kidney disease patients that have lost between 50% and 80% of their kidney function. This is an important part because we have been using this patient demographic for the past 8 years. And so we've been staying consistent with our dosing regimen, with the product given and with the patient demographic. What I'd like to show you now is some of the results of that and show how it's very, very similar to the animal data. What you can see here in this graph, showing eGFR over the course out to 24 months, it shows each one of the injections and the follow-up time points. This particular line, very similar to what I showed you in the SGLT2 graphs, this is standard of care, and you can see the decline. They declined approximately 3.6 mL per minute per year. So there was the usual decline seen on best standard of care. In contrast, patients that were assigned to the active group, the first injection resulted in a stabilization of the function of the kidney. The second injection resulted in an increase in the function of the kidney that was seen by an increase of approximately 4.6 mL or, said differently, there was a total of about a 7 mL to 8 mL per minute difference between the treated and the best standard of care. So this was quite exciting and was substantial interest to us, and we'll continue to report this later in the year, and I'll get to that in just a minute. I also mentioned the 003 trial, and this is where we really went to look at severely affected patients, patients that have lost between 80% and 85% of their kidney function. Once you've lost 85% of your kidney function, generally, that's when your eGFR is about 15 mL per minute, and that's when you're going on to end-stage renal disease and need for dialysis. So these were patients that were very close to dialysis. What we did here, because these patients were so ill and anticipated to go on to dialysis within a few months, we ran this as a single-arm trial, but followed the same basic approach: a biopsy, 2 injections, 1 kidney and followed them out for 24 months. This time, though, the key entry criteria were quite different. They were 14 to 20. You can see in this data, what we have is the patients came in, and they had an average of 15.5. They had lost 84.5% of their kidney function on average. What was interesting about this is that 7 of the 10 patients actually had a 30% increase in their dialysis-free living time compared to what would be predicted for standard of care. That translates into about 16 months of dialysis-free living. What's very, very intriguing was that 6 of the 10 patients actually had an improved eGFR or stabilization, showing that the effects that we were seeing in the less severely affected patients were being manifested also in the more severely affected patients. Very interestingly, 4 of the patients in this trial never did go on to dialysis. Unfortunately, 2 died, 1 from COVID, 1 from myocardial infarct. But very interestingly, 2 of the patients, now 2 years out, actually, more than 2 years, because we continue to follow these patients, have not gone on to dialysis. And one of those patients actually has an increase in their kidney function as a result of the REACT injection. So it looks as if, in these very severely affected patients, we can get the same biological outcome as we did with the others. So one of the questions that comes forward for us is this, how safe? You're taking a biopsy. You're injecting these patients. Injection is a very thin needle, 25-gauge non-cutting needle that we inject into the cortex, but nonetheless, we've now had 3 interventions to the kidney, and the question has been, how safe? And what we can see here, if we look at each of the 4 different trials, if you look at 202 injections, the Phase I, Phase II study is very clear that REACT is very well tolerated. So the biopsy and the injection procedure is well tolerated across all of these different studies, even the very severely ill patients. To help digest all of this and to give you a sense of kind of a reference point, what this slide shows you is what are the common causes of SAEs or problems with biopsies, standard routine biopsies that are run today? If we look at the 6 most significant adverse events from a biopsy itself and compare it to what we've seen in all of our different Phase II clinical trials, hematomas are the most common at 11%. Our biopsies were actually only 4%, and the injection itself is very, very low at 1.5%. So the safety on the most common SAE of biopsy was looking very good. If you go through and look at each of these, you can see that we're below all of the different SAEs observed commonly with a biopsy with our procedure. What I wanted to do, as I said, give you a sense real quickly of what the -- something that we'll be talking about this year, and that is this 007 trial. We hope to give investors a perspective of what's going on in the Phase III. The Phase IIIs are blinded, and I'll talk about them in just a minute. This arm of this Phase II study, there are 50 patients, randomly assigned, 25 to this group and 25 to this group. This cohort 1 is actually a mini form of the Phase III, and we anticipate to be able to release interim data to investors to be able to see towards the end of this year. That will give an insight into what the progress is for our Phase III program, which is blinded. The second cohort is designed to give us a sense of re-dosing triggers. I had talked to you about the fact we can make 5 to 10. If a dose of REACT is 2 injections, could we then give third, fourth or fifth to continue to extend the dialysis-free living? To answer that question, we need to know when to give it properly. And that's what this particular arm of this trial will tell us, and we will report on that. That, combined with some of the other studies, will allow you to be able to see whether or not it could be possible to talk about extended dialysis-free living in these patients. So our Phase III program is 2 studies, 1 focused in the U.S. and 1 focused in the rest of the world. They're essentially the same, 600 patients in each trial, one-to-one randomized. We have a SHAM biopsy, SHAM injection arm. We have the -- excuse me, SHAM biopsy, SHAM injection arm, and we have the REACT treated arm. What's unique about this is that because our safety profile is so strong, the regulators have indicated that we can inject in both kidneys. And this is going to be quite exciting because what that should do is it gives us now access to therapeutic to the entire renal mass. We're going to be showing you that same approach in the 007 trial that I mentioned earlier, so you'll get insights into that as we go forward. So these trials, we predict the interim analysis of the first proact 1 we anticipate to occur next year. And then the following year will be proact 2 interim analysis. So overall, our registrational program is designed to not only address FDA and EMA with the agreements, but also to get input from HTAs. We continue to work with HTAs around the world to make sure that the data that we're bringing forward to them is of interest and will allow us to get premium pricing. One of the questions that we get asked quite a bit is this, will patients accept an interventional trial? This study was not sponsored by us. It was run from COGS, and it asked the question, would patients accept some side effect or an intervention that have chronic kidney disease? And what it showed was that about 93% of patients with chronic kidney disease would accept an interventional or a therapy that has some side effects. The same thing, when it was asked, what about physicians utilizing this? It was also seen that physicians feel that in the area that REACT is affecting, that this is a high unmet medical need, and so it would be used by physicians as well. So this was quite exciting for us, and it also highlighted that the Stage IIIb, which is where we are looking as our primary patient population, that these people will take anything to help slow the progress of the disease. They're all in. So we anticipate that this should translate into good product update. One of the things I suggested is that there may be significant cost savings. This illustrates if we can assume that the median health care cost is about $100,000 per year per patient, that's from CMS, with private payers, they'll pay up to $400,000 per year per patient. Since the average time a patient will remain on dialysis is approximately 5 years, if we could offset these costs with a price even in the $200,000 range, it could offset costs substantially between $0.5 million and $2 million. There's potential for significant health care reduction. One of the things we've focused on is to drive down our COGS. We have published that our COGS for Phase II are approximately $100,000 per patient to make the 10 doses. We anticipate by the time that we go commercial, between various benefits that we can obtain through supply chain, automation and bioprocess improvements, that we can see a 50% reduction in our cost of goods, being able to bring this as to one of the lowest-priced cell therapies to the market for such an unmet medical need. Our Board is really impressive. We've had the opportunity with people that have built companies from the ground up, William Doyle and John Maraganore of Alnylam. But we also have experts in the medical management of patients with chronic kidney disease in Brian Pereira and Alan Lotvin. Brian actually started the KDIGO group and has been heavily involved in the management of chronic kidney disease for many years. We also have very, very strong financial backing with Jen Fox, Jose and Pablo Legorreta. The management team has over 300 years collectively of developing medicines, and the group collectively have developed 15 medicines over their lifetime. I think one of the things that we've got to think about, for us, at least, is what will we share in terms of catalysts in the coming year? We intend this year to share different catalysts that will highlight the advances that we're making, as I've already shared with the Phase II. And we'll be announcing the outcome of the progress that we have with our Phase III trial as well this year. So there'll be a number of catalytic events as we go forward. So I think as investors ask the question, why ProKidney? What is the reason to invest in an advanced therapy? And what we can see here is that we really have a very large TAM with a very serious unmet medical need that, to date, has not been addressed. We also have some initial clinical success to indicate that there is a benefit for these patients, even when they're on the doorstep of going on to dialysis. And we believe that with the ability to be able to bring this forward in a cost-effective manner, working with investors, that we can have value creation for the investor, for the payer, for the patient and for the physician. So I thank you for your time. I'm sorry, Jason, I took up most of the time, but if there's any questions, happy to answer them.

Well, maybe 1 just for me. Your 007 trial, just thinking about bilateral dosing and the benefit that you can see. Your Phase III is a time-to-event endpoint. I assume that's based on single kidney dosing. So if the results that we see with bilateral dosing, could we potentially -- I'm just wondering the read across to your interim update and analysis and what the Phase III endpoint was sort of predicated on?

So the Phase III is dosing both kidneys once, right? The 007 is dosing both kidneys once. So the Phase III is a time-to-event trial with death from cardiovascular, renal dialysis or less than 15 mL or a 40% decline in eGFR. We will take that -- those same endpoints and express those from 007 as well as bridge back to the eGFR slope of 002. So 007 will form this ability to be able to compare for investors the 002 data, which was eGFR slope, the Phase III, which is time-to-event and get a window into what's likely to be the outcome of the Phase III. It's a small trial, but that's...

Sure, sure, sure. Okay. We're out of time, but...