Prokidney Aktie

Welcome, everyone, to the 44th Annual JPMorgan Healthcare Conference. My name is Anupam Rama. I am one of the senior biotech analysts here at JPMorgan. I'm joined by my squad, Rati Pinge, Priyanka Grover and Joyce Zhou. Our next presenting company is ProKidney. And presenting on behalf of the company, we have CEO, Bruce Culleton.

Good morning, everyone. And thank you, Anupam and JPMorgan for inviting us back to the conference again. It's a pleasure to present this morning. So at ProKidney, our goal is to transform the treatment landscape for patients living with advanced chronic kidney disease. Patients who are at high risk of kidney failure and facing a real prospect of ending up on dialysis.

We believe that our lead product, rilparencel, there's a meaningful opportunity to intervene and change the course of a patient's progression to kidney failure. So these are the customary disclosures and disclaimers.

So there are over -- today, there are over 3 million Americans with advanced chronic kidney disease. These are patients that over the next few years that are very high risk of developing kidney failure. Many of them will require dialysis. The lucky few will get kidney transplants. They all share one goal, and that's the need for more time. So more time for spending 3 days -- more time from not spending 3 days a week in the dialysis center, more time for life's moments and more time and flexibility with the people that matter the most.

So we are advancing this goal through the development of rilparencel, an autologous cell therapy that's made from patients' own kidney cells. Across multiple Phase II trials, we've seen kidney function stabilization with the use of rilparencel. Excluding our Phase III data, which is ongoing, we've treated over 150 patients and rilparencel has demonstrated a very favorable safety profile. It also doesn't require any preconditioning or immunosuppression after treatment, unlike many of the other cell therapies.

Importantly, we are now marching towards a pivotal Phase III readout in about 5 quarters from today. So in Q2 2027. Our goal is to make rilparencel available to patients who urgently need it and to provide different and better treatment options for patients with advanced chronic kidney disease.

So 2025 was a pivotal year for us. But before I touch on our accomplishments, I want to begin by recognizing the approximately 250 ProKidney employees whose hard work and dedication made last year a pivotal one for our company. Their commitment drove meaningful progress across every aspect of our business, and I'm extremely grateful for their contributions.

Key highlights from 2025. We aligned with the FDA on an accelerated approval pathway using eGFR slope as a surrogate endpoint. We presented positive Phase III data as a late-breaking clinical trial at ASN's Kidney Week. We generated significant momentum in the Phase III PROACT 1 study. That's our pivotal Phase III study and the readout that we anticipate in Q2 2027 because of this momentum around enrollment.

And finally, we initiated expansion of ProKidney's in-house manufacturing footprint in facilities in Winston-Salem, North Carolina. So 2026 is going to be a year of highly focused execution for us. We prepare for a readout in 2027 for our Phase III data. We expect importantly, to complete enrollment for the accelerated approval efficacy analysis by mid this year.

We will continue to execute on our R&D plan. That's important for us to be able to explain our mechanism of action. I'll get into that in more detail later in the presentation. We also maintain active engagement and dialogue with the FDA under our RMAT designation. And finally, as we continue to prepare for commercial launch, we build out additional manufacturing capacity in North Carolina, where we own and operate those facilities.

So just before I dive deeper into some of the data, I'd just like to quickly level set on some of the progress. So we are solely focused on the one product, rilparencel, a first-in-class autologous cell therapy and getting that cell therapy to market. We're running the ongoing Phase III study, just the one Phase III study is all we need for FDA approval in patients with advanced chronic kidney disease and type 2 diabetes. And we have generated robust clinical data to date.

We have a very experienced clinical -- a very experienced leadership team, and we have cash runway that takes us past the data readout into mid-2027.

So a little bit about how we make our product. So rilparencel is manufactured using a patient's own kidney cells. And unlike some other cell and gene therapies, rilparencel doesn't consist of any gene editing. There's no preconditioning, no pretreatment and there's no immunosuppression after a patient received rilparencel because it's their own cells.

The process starts by harvesting a small piece of kidney tissue through a pretty standard kidney biopsy. That kidney tissue is transported to our manufacturing facility. When it shows up, there are about 50,000 to 100,000 cells that are available for us to work with. We expand them through a series of passages, and we end up with well over 1 billion cells that undergo a selection process.

The product is then cryopreserved and shipped back to the clinical study site for injection into the kidney cortex. 3 months after the first injection, we inject into the other kidney in the kidney cortex. All the injections are done by CT imaging by a trained interventional radiologist.

This is just a little bit about our manufacturing facility. We've got -- we purchased 2 adjacent buildings. Our approximate square feet is 180,000. We currently support our clinical manufacturing from these facilities. We have ongoing capital investment to manufacture -- to grow out that manufacturing infrastructure and to support what's required for a BLA submission. And these facilities also have some administrative research and cGMP manufacturing operations for a cell therapy platform.

So I'd like to spend just a few minutes to sort of set the stage on the unmet need in the patient population. So this is a complex slide. This is a framework of how we think about chronic kidney disease. It was developed by many scientists quite knowledgeable in this field, and this framework is used globally to understand the classification of chronic kidney disease, but also to understand the risk associated with different categories of chronic kidney disease.

So the rows represent kidney function as measured by estimated glomerular filtration rate or eGFR. You could see on the top row, if your GFR is above 90, you have normal kidney function. And in contrast, down on the bottom row, if your GFR is less than 15, you have what's called kidney failure. Most of these patients either have a transplant or are on dialysis or some are waiting to be started on dialysis.

The columns represent kidney injury as measured by the amount of albumin that's lost in your urine. And these are different categories of UACR. And then you could see that based upon where a patient may fall in a row or a column, then the heat map tells you what risk they have for developing kidney failure.

The area that's imposed by the blue line, the blue box, this is the area that we are focused on. These are the patients that we believe have the greatest unmet need. And these are the patients that we're currently enrolling into our Phase III clinical study. So we have seen over the last 5 years, a significant advance in the treatment of patients with chronic kidney disease. In particular, there's been many landmark clinical trials that have looked at patients who have chronic kidney disease and type 2 diabetes.

Some of these landmark trials are shown on this slide. Most of the participants in these trials have Stage II or Stage III chronic kidney disease. A few have advanced CKD that you could see on the right-hand column, subjects with Stage IV CKD. Primarily, the patients that have enrolled in these studies with Stage II and Stage III CKD, that exists because that's where the biggest population of patients with CKD currently reside.

There are well over 10 million Americans, well over that with Stage II and Stage III chronic kidney disease. But in contrast, patients with Stage IV chronic kidney disease are much lower. There's probably about 1 million Americans with Stage IV CKD. About 40% to 50% of them have coexistent diabetes, and that's the group that we hope to help with rilparencel.

A little bit of a complex slide here as well. So this is from one of these landmark studies that I just showed on the prior slide. The data here is illustrative of what's seen in the other landmark studies as well. So on the left-hand side in the left panel, you'll actually see change in kidney function as measured by eGFR. The blue line represents patients who are treated with dapagliflozin, an SGLT2 inhibitor. The red line represents those patients who are treated with placebo.

And much like other products in this space, there's an acute decline in eGFR, an acute decline in kidney function within the first 3 months. And then over time, that progression slows. But what you do see because of that acute decline, and if you look at the table in the box, the table in the left-hand panel, at month 24, there's a difference of only 1 ml per minute in progression of kidney disease. So 1 ml per minute.

So what that means in a population of, say, thousands of patients that becomes statistically significant. It's also clinically meaningful when you think about a population of patients with CKD. On an individual patient, 1 ml per minute doesn't seem like too much. Now these agents also confer cardiovascular benefit. And so they're also extremely important at reducing the risk of cardiovascular endpoints in these patients as well.

Now please take a look at the right-hand panel. So this is a slightly different look at this study where the endpoint is the cumulative incidence of a decrease in kidney failure in eGFR -- sorry, a cumulative incidence of a 50% loss in kidney function as measured by eGFR and kidney failure and death.

The placebo group is shown in red. The dapagliflozin group is shown in the blue. As you could see by looking at the blue curve, many of these patients continue to have events. Despite being part of the new pillar of care for patients with chronic kidney disease, these are not cures. Patients do continue to have events. They do continue to lose kidney function and many of them still end up on dialysis. So there's several ways that you could look at this to make that a little bit more meaningful. One is something called the number needed to treat. And in this study, you need to treat 19 patients with dapagliflozin for the course of the study to prevent one of these composite events.

Another way to look at it that's not shown on this slide, but it's in their paper, is that on average, treatment with dapagliflozin for 2 years delays dialysis for 4 months. So that's still relevant for a patient, but it's not delaying dialysis for years. It's delaying dialysis for 4 months. So that's the unmet need.

Now I'd just like to spend a few minutes on our clinical study program, our Phase III study design, an update on enrollment as well as just an overview of our R&D plan. So all the studies that we've -- all the clinical studies that we performed using rilparencel are shown on this slide.

There are 2 ongoing clinical studies. One is the Phase III study. The other is a long-term follow-up study called Study 008 in patients that have been previously enrolled in one of our prior Phase II trials. So this is REGEN-006, our Phase III program, also called PROACT 1. This is a randomized sham-controlled blinded parallel 2-arm clinical study. I know there's been a lot of talk around FDA's expectations within the cell and gene therapy around clinical trials. This design meets their expectations.

So this is a robust clinical study design in a cell therapy, using a cell therapy. Patients enrolled in this study will have to have type 2 diabetes and advanced CKD. You could see the key entry criteria on the left-hand side of the slide. Randomized patients are stratified by SGLT2 use and baseline eGFR, and they're allocated to the intervention or the rilparencel group or a sham cohort, that's the control arm.

Patients and the principal investigators are blinded to the treatment allocation. As stated earlier, we have alignment with the FDA for accelerated approval using eGFR slope as the surrogate endpoint. In the same study, patients will be followed over time for the confirmatory analysis, which will be performed when 122 patients have one of the composite clinical events.

As stated earlier, we've done a really good job. The teams have done a really good job in enrolling patients this year. A special thank you goes out to all our study participants, our study sites and also to our internal clinical operations and manufacturing teams who've really been dedicated to this over the last several years, but we made significant progress this year and a special thanks to them.

So if we stopped enrollment today, which we're not going to do, but if we stopped enrollment today and just followed the currently enrolled participants, we would have 80% power for the surrogate endpoint efficacy analysis in Q2 2027. We're going to continue to enroll patients. And by mid this year, we'll have sufficiently enrolled patients for 90% power. And we are very confident based upon that enrollment, where we stand today and if you look like the pipeline of participants that are coming into the study, we're extremely confident that we will have our analysis in Q2 2027 for our top line surrogate endpoint readout.

So let me talk a little bit about our R&D. Last year, we made a commitment to invest additional funds to support a lot of R&D work to further elucidate the mechanism of action for rilparencel. So we had done as a company, a significant preclinical work in the 2011 to 2015 time period. This was deprioritized when ProKidney moved to the clinic.

Notably, this decision missed the real transformative shift, I would say, to single cell and spatial omics as a means to interrogate biological systems. So now we have 4 different related programs in progress. This includes in vitro, ex vivo, in vivo in animals and in vivo in human descendants.

We are working with some of the top scientists across major institutions in the U.S., and we anticipate release of data related to our MOA throughout 2026.

So shifting gears now a little bit to some big news that we had this year, and that was related to our Phase II REGEN-007 data and why it's important because we think it provides some window into what we'd expect with our Phase III results.

So as a reminder, we presented in 2024 results from another Phase II trial at the ERA meeting in Stockholm. This year, actually, last year, it was in November of 2025, we presented a late-breaking clinical trial at ASN Kidney Week, and I'll just get into the design of that study in the interest of time.

So importantly, patients were -- patients who were eligible had type 1 or type 2 diabetes, a GFR of 20 to 50 and a UACR between 30 and 5,000. Patients were -- in 2021, we started to enroll patients, and they were allocated randomly to 2 groups. The first group is the group of most interest to us. And the reason why that's most interesting to us is because those participants were treated in the same way as our Phase III clinical study program. They had a biopsy, then they were injected into the biopsied kidney and 3 months later, they got an injection into the other kidney. That's the same treatment schedule we have for our Phase III program.

Group 2 was more of an exploratory dosing design. In Group 2, all patients had a biopsy. They received an injection into the biopsy kidney and then there was a period of waiting. And a second treatment was only given if there was a trigger and that trigger was an increase in UACR or a decrease in eGFR. What we know is of those 25 subjects that were enrolled in Group 2, 15 of them had a second injection and the time to that second injection, the median time of that second injection was 10 months.

So a much longer time between first and second injection in Group 2 than in Group 1. Also I want to point out on this slide that there was a pre-injection period. That was the control group for both Group 1 and Group 2, and that included all historical eGFR values going back to 2 years.

The primary efficacy endpoint was the difference in annual eGFR slope in that pre-injection period versus the period following the last rilparencel injection. And the primary safety endpoint was frequency of procedural and rilparencel-related adverse events.

A few things to point out on our baseline characteristics. So the first I'll note is we were underrepresented in this study of patients who are important from a chronic kidney disease perspective, and that is black Americans and patients with Hispanic and Latino ethnicity. As you could see, we were also underrepresented by women who have chronic kidney disease. And we have recognized the challenge associated with this and have gone out of our way in our Phase III program to correct that. And I'm glad to say that we've seen some significant changes in enrollment in our Phase III program with making sure that we have better representation from patient groups that are actually overrepresented in the chronic kidney disease space.

Also note that we enrolled some patients with type 1 diabetes. That's not the case in our Phase III program, which is all type 2 diabetes. And please have a look at the eGFR as well. The average eGFR was less -- was just above 30. We've narrowed the target population in our Phase III program to patients with more advanced chronic kidney disease, and I anticipate an eGFR somewhere just north of 25 mls per minute in the Phase III program.

These are the main results of the study. In Group 1, the annual decline in eGFR slope improved by 78% after treatment with rilparencel. Pretreatment, the decline was minus 5.8. Post treatment, the decline was minus 1.27. That was statistically significant and very clinically meaningful in this patient population.

In Group 2, we didn't have a statistically significant result, but we did see an improvement in the annual decline by 50% in Group 2. And just as a reminder, that group was also treated differently than what our Phase III program is at this point in time.

Safety, no rilparencel-related serious adverse events. That's pretty consistent with what we've seen in our other studies as well. And the safety profile overall, even related to the injections is pretty consistent with what's reported, a little bit better actually than what's been reported with adverse events related to a kidney biopsy.

We include this slide to graphically represent the primary efficacy endpoint. And as you could see the slope of eGFR prior to treatment with the 95% bounds on that slope in the blue shade, you could see that slope changed considerably after patients were treated with rilparencel. This table represents serious adverse events that were observed.

We did see a few events in patients who had -- who were related to the kidney biopsy. This is well described in the literature. We had one hematoma, a patient with a hematoma that was uncomplicated in a patient who received a rilparencel injection, and there were no serious adverse events associated with rilparencel as a product.

Finally -- or sorry, so just in summary, our key findings, bilateral dosing of cryopreserved product, which mirrors our Phase III program resulted in stabilized kidney function after treatment with rilparencel and the safety profile is pretty consistent with what we've published previously.

Our focus now is on continued enrollment of PROACT 3 to complete our R&D plans for this year and to prepare for BLA submission and commercial launch after top line readout. I will say one other thing on REGEN-007 data. And we do think it's a window into our Phase III program, and we may get into this a little bit into our Q&A as well. But when we also cut the data for Group 1 and just looked at those patients who are Phase III eligible, so patients who met the Phase III criteria, we actually saw a greater difference in decline pretreatment versus after treatment.

So just quickly, a quick update on our key financials and milestones for 2027. At the end of September, we had $270 million in cash to fund our operations. This will take us into mid-2027 after our top line readout. We anticipate this year as one of our key milestones to complete enrollment for the accelerated approval cohort within PROACT 1. We expect that enrollment to be complete by mid-2026. And again, we're working towards that top line readout in Q2 2027, and we feel very confident about that.

So in conclusion, I'd like to finish by returning to what we have as our North Star. And our 250 employees come to work every day with one purpose, and that's to bring a transformative therapy to patients with advanced chronic kidney disease. And that's a therapy to extend time to provide more options and to bring hope to patients and their loved ones.

Thank you all for your attention today and your ongoing interest in our company.

Thank you, Bruce. I'll ask the first couple of questions, but there will be an opportunity for the audience to ask questions. So when I prompt, just feel free to raise your hand. Bruce, when I think about ASN last November, what do you think are some of the key points that the Street is underappreciating as it relates to rilparencel, the data you presented at ASN and the derisking that it has for PROACT 1?

So I think just on the derisking, Anupam, I think there's a few things that the Street underappreciates. So one is certainly the effect size, right? So the effect size that we saw that I just went over with our Phase II data, was substantial, we've taken a very conservative approach to that effect size in our Phase III readout.

We've assumed a -- in our power calculations, we've assumed a difference of only 1.5 mls per minute between the intervention group and the control group. What we saw in the Phase II data was a difference that was greater than 4 mls per minute. So arguably, we've taken a very conservative approach. And we've had some lengthy discussions in-house as to why we did that, why it's 90% power, why we've assumed a smaller effect size.

And honestly, it comes down to when we're ready to turn that card in May or June of 2027, we want to be sure that we don't find ourselves in sort of some port of nebulous p-value, something that's in the 0.06 or 0.08 or 0.10. So we wanted to be quite confident in the analysis at that point in time. So I think that was one.

The other thing I'll point out is consistently what we've seen in our Phase II data is we see a greater benefit in patients who have the highest risk of kidney disease and patients who have an eGFR that's less than 30. I think sometimes it's underappreciated that we changed the design of our Phase III program in early 2024 to narrow the target population from a GFR of 20 to 50, we narrowed it down from 20 to 35. And I think that also gives us more confidence moving into the Phase III readout.

And then I saw in the slide that you -- in 2026, we're going to get some fuller understanding of mechanism of action of rilparencel. What's your current understanding of the mechanism of action? And what could we learn this year?

So we certainly know a lot more about our product over the last couple of years, and we've done some -- we understand what happens when our cells come into our manufacturing facility and how that product looks different at the end of manufacturing.

And what we see in those cells that are coming out as our final product is that they have less markers of inflammation, they have less markers of oxidative stress, and they have less markers associated with fibrosis. So we know that those cells are quite different than the cells that come in from the disease kidney from the patients. We also know that the final product, the cells seem to be plastic, at least that's how it's described to us by our R&D leaders. And plastic means that if they're exposed to a different environment, they may actually have a different phenotype depending upon what that exposure is. So we've learned a lot about those cells.

Now our working hypothesis today is that we believe when the cells are injected into the kidney, they do have an anti-inflammatory effect. They do have an effect on oxidative stress. And we also believe that they take advantage of the innate sort of restorative mechanisms that are already in the kidney and they take advantage of those, and we think that's what's leading to stabilization of kidney function. But at the same time, Anupam, we -- as you saw our R&D plan, we have a pretty robust plan, and we are working with some -- not just internally where -- we have some great leadership in the R&D group, but we're also working with some top-notch people across academics in the country.

When we think about sort of that May, June data for next year, the top line of PROACT1, obviously, we're going to get eGFR slope. That's the key endpoint for AA, accelerated approval. Any other endpoints we should be focused on within that update? And then also on eGFR slope, kind of what's a win scenario?

Yes. So the key for the top line is, as you said, it's the eGFR slope. That's the key thing. We'll -- we've got some planned subgroup analysis around that as well, Anupam. But I would say the other key component of that top line readout is safety. I mean not only do we need to show the efficacy, but also we need to continue to demonstrate a very strong safety profile.

Questions from the audience? I've got one last one.

Yes, go ahead.

Very beautiful data. My question is, how many times does the biopsy sample expand in culture? And does every type of nephrons can proliferate? That's the first question.

So I'm sorry, I missed the second part.

Second question is does all type of nephronal cells expand after the culture?

Okay. That's great. Two great questions. So thank you for your question. So we've actually had some really good success at biopsies that come into our facility and biopsies that we're able to make actually cells on. We're over 95% across all our studies, and we've continued to improve on that in our Phase III program.

What we -- and then getting into the second half of your question, so the cells that come in from the kidney biopsy represent the standard kidney biopsy cell. The cells that we -- that are in the product that's finally made have primarily markers of tubular and epithelial cells, less so on the endothelial side, mainly markers of tubular and epithelial cells. And as I said earlier, they also have markers that are less inflammatory, less fibrotic as part of that final product.

Next question is, does injected cells reform the nephrons?

I don't think so. I don't think anyone has ever been able to demonstrate the formation of a full nephron. And so I don't think that, that's the case in what we're doing either. More to come in 2026, but I don't think we'll end up with that type of data to show that we're forming new nephrons.

Maybe final question for me. Your slides also talked about in 2026 becoming -- doing some commercial prep work. What does that encompass in 2026 heading into the data next year?

Well, so some of that encompasses actually getting ready for a BLA submission. And there's a long lead time to some of the items, especially related to CMC. So big focus and the internal team around ensuring that we've got everything ready for our CMC part of the submission.

And then the other thing is as you know, it takes a long time to build out future capacity around manufacturing. And so there's some early work being done around expanding our manufacturing capacity in our buildings as well.

Thank you, Bruce.

Yes. Thank you.