All right. Okay, I think we're ready to get going. Thanks, everyone, for joining us again at our Guggenheim Inaugural Healthcare Innovation Conference on day three. Appreciate all the attendance and conversations. I'm Vamil Divan, for those who don't know me, one of the biopharma analysts here at Guggenheim. Joining on the stage is Edward Malarkey from the Guggenheim side. And the next company we have in this room is ProKidney. We have Bruce Culleton, the CEO of the company, kind of going to run through the story and some of the recent highlights. But a pretty active time, I think, suffice to say, for ProKidney over the last year, year and a half. So thanks so much for joining us, Bruce. And maybe we'll just start there.
If you can give, I think, a story that's maybe a little less known to some of the investors out there, just an overview on the company, kind of how you've gotten to where you are now, and then your lead asset, rilparencel, and then we'll dive deeper from there.
Yeah. First, Vamil, well, thanks for the invite. We're happy to be here and excited to catch up over the next half hour or so. So we're a company that's based out of North Carolina. We have offices in Winston-Salem, in Raleigh, in Boston. We're about 200, just over 200 employees. Our lead asset is something they call rilparencel, and rilparencel is an autologous cell therapy. Our primary indication is directed towards patients who have advanced chronic kidney disease and diabetes, type 2 diabetes. And how we sort of get rilparencel to patients, we first do a kidney biopsy. Those cells are shipped back to our manufacturing facility in Winston-Salem. And through a series of steps, we end up with a cryopreserved product, which then goes back to the clinic and is injected back into the patient's kidneys.
We have a phase III program, which I'll get into in a few minutes. We're pre-commercial, late-stage clinical.
Okay. Perfect. And it has been a little bit of a winding path over the last year or so. So maybe you can talk through some of that because we certainly get questions from investors on just sort of how you got into here, obviously, on your phase III program and kind of now it's full speed ahead with the phase III, but just the pathway to kind of making your way to the public markets. The company's been around for a while, but making the public markets and some of the decisions you made over the last year or so to get you where you are.
Yeah. So the company actually started at least the IP behind the company started about 10 years ago or so, started at Boston Children's Hospital. Autologous cell therapy for children with bladder issues. Over a period of time, the co-founder of ProKidney, the founder of ProKidney at that point in time, ended up focusing more on the kidney and the cortical cells within the kidney to improve kidney function. We went public in 2022 as part of a de-SPAC. And around this time last year, I was asked by the board to take over as CEO. We've had a really busy year. So within days of starting as CEO, we announced some phase II data from our largest phase II program. We paused our phase III clinical trial, and we paused our manufacturing.
All that was a result of primarily some remediation efforts that we had to do within our manufacturing facility. We were really operating in many ways like a phase II manufacturing facility, and we needed to be more compliant with phase III standards. Rather than continue our phase II program, we just paused it. We corrected all our remediation challenges that we had within our facility and ended up being GMP compliant at the end of May and getting an EU certificate of compliance in the June-July time frame. We amended a protocol, our phase III protocol, based upon our phase II data to be more focused on patients who have advanced chronic kidney disease, so those who have a GFR between 20 and 35.
That's also the same population that is less studied and also the same population where there's the greatest unmet need because those patients are on a slippery slope to dialysis or a transplant. So that brought us up to, I think, around May or June, Vamil. We had more phase II data that we released in the June time period, interim data from another phase II study called 007, which I'll speak to in a second. And then more recently, we've made some changes to our clinical development program. We were awarded an RMAT from the FDA from CBER back in 2022, I believe it was, in the fall of 2022, in the spring of 2023 or fall of 2022. We started asking ourselves questions this year as new management. Why are we doing two large phase III clinical studies?
Why don't we have an accelerated approval program available to us? So at the end of the day, we stopped one of our phase III studies just to focus on PROACT 1, which is really being executed here in the United States. And we went to the FDA and had a discussion around the accelerated approval program, which I'm happy to provide some guidance on that today as well.
Yes. Let me go one more, and then I'll turn to Edward to ask a few more details on the earlier data you've shared. But in terms of this phase III, you had the update yesterday with the quarter, and it sounds like you're saying that it could be good enough, I think was the wording that you used in the release. So maybe you can just talk through as much as you can around the conversations there and what exactly would you need to show for that to be sufficient, or is it maybe needing additional data?
So we went under RMAT. We went back to the FDA in October, had a very collegial, open discussion. I mean, the review team were obviously aware of some of the data that we produced publicly around our phase II data. We went into the meeting and had two main questions. One is, is a single, randomized, well-done trial with compelling clinical data sufficient for full approval? And they said yes. So not two, one. So they said yes. And then we also asked, is the accelerated approval pathway available for us to use under RMAT? And they also said yes. And then we had a discussion on, well, what does that mean? And they actually talked about slope eGFR, which is something that we were very interested in, even going back to the initial discussions with the FDA.
And we left that meeting really with an understanding that we need to go back to them with a proposal on how we're going to use slope eGFR for conditional approval. And that's something that they're very open to. So for anyone that follows sort of the kidney literature and the regulatory viewpoint on surrogate endpoints, there's been a lot more openness on using things like UACR or slope eGFR for either full approval or conditional approval, really depending upon what your product is. And we've seen really important, significant shifts within the FDA. And we saw that at our meeting where they're actually interested in us going back to them with a slope eGFR proposal, which we will do in 2025.
Okay. All right. Edward.
Okay, Bruce. You talked a bit about the phase II data that you've generated, but maybe if you could give us some of the highlights from those trials and how that gives you confidence for the PROACT 1 study that you're running?
So we ran two large phase II clinical studies. The first one, we presented final results at a congress in Europe at the end of May. That study did show in a select population of highest risk patients, those who had stage four chronic kidney disease and high levels of albumin loss in their urine, that Rilparencel seemed to have more of an effect in those patients than patients who didn't receive Rilparencel. And that effect was over 12 months, but also some data showed that extended beyond 12 months. It was a signal of efficacy, essentially, in these high-risk patients. That study was the first big phase II program that ProKidney had executed. And there was one thing that was different than where we stand today. The Rilparencel in that program was really a fresh product, and now we use cryopreserved product.
And the way it was administered in that study, it was administered into the same biopsied kidney, not just once, but twice, into the same kidney. Now that after the company got more comfortable and the FDA got more comfortable with our safety, they granted us the ability to inject both kidneys. And that's what we did in the other phase II program with the data that we released, interim data that we released, I think it was in June. And that's called 007. In that 007 program, we biopsied one kidney, injected that same kidney, and then injected the contralateral kidney about three months later.
What's really important is within that study, there's a cohort that really mirrors the same type of therapeutic approach that we're using in our phase III program, where the endpoint is eGFR, where we're using cryopreserved product, and we're actually injecting both kidneys, three months separated first from the second injection. In that 007 program, which we think is a window into our phase III results, which we think is even more important now because we probably have an eGFR surrogate for conditional approval, in that 007 data, for patients that had 12 months follow-up after their second injection, we saw a very minor change in eGFR over the course of 12 months. I think it was minus 1.3 on average over the course of 12 months.
And when we tried to compare that group to an external synthetic control group, we saw a change over the course of 12 months in that synthetic control of about 4 mL per minute, which is what you expect to see in this population. So if that holds true for our phase III program, especially around a conditional approval around eGFR, then if that data actually holds true for that, then we feel very positive and very comfortable that that's the right approach. Now, the other thing on 007 is this was only on 13 patients who had 12 months follow-up. We expect to have data in the first half of 2025 for the full cohort that we expect to have over 12 months follow-up. That'll be somewhere north of 20 patients, probably 20-22 patients with that longer-term follow-up.
Okay. Yeah, and speaking of that sort of 1H25 update, so are there any benchmarks or how should investors be thinking about the updated eGFR data?
It's an open-label study. I haven't peeked at the data, so it's nothing here for me to sort of hide or not hide. If we see that same stabilization of kidney function that we saw in the first 13 subjects that had over 12 months of follow-up, we hope to see that again in a larger subset of patients, 20-plus patients when we release the data towards the end of the first half of 2025. Why is that minus one mL per minute change in kidney function important? It's important because that's about the change that you see in older adults just part of healthy aging. If we do see that in a population of patients with an average eGFR of around 30, where you expect a steeper decline in kidney function, then that has real meaning clinically.
Of course, so obviously, that's what we're hoping we'll see in the data.
Yeah. Well, a last question for me before I turn it back to Vamil Divan, but on the commercial opportunity, right? So there's millions of patients in the U.S. with type 2 diabetes and chronic kidney disease. And this could be a really large commercial opportunity for rilparencel cell therapy. So how should we think about what that commercial opportunity is and maybe also the scaling with the manufacturing that would come to address such a potentially large population?
So first, we're studying a population with a GFR between 20 and 35, right? So they're advanced. Those patients have advanced chronic kidney disease related to diabetes. So that's not the 30 million people with chronic kidney disease or the number that we hear around the broader population impact of chronic kidney disease. These are the sickest before they get to dialysis or need a transplant. But that market is still very big. We're still talking about 500,000 new patients almost every year and over 2 million patients that fit within that sort of GFR range who have diabetes. So the market is still big. But what we've seen in this space over the last, I think since 2021, has really been an enormous shift in what's available to treat patients with diabetic kidney disease.
And I think the first SGLT2 was approved for diabetic kidney disease use in April of 2021. Since that, we've had more data on SGLT2s, nonsteroidal MRAs, GLP-1s, all of that in a diabetic population. So if you're a patient with diabetic kidney disease, this is all great news. But there's a couple of things that we all need to recognize in that data. First is the patients who have a GFR between 20 and 30, and a lot of those trials are a small amount of patients. And two is there's a residual risk. And in all these trials, there's a residual risk, meaning that patients get treated and some patients still have events. And that residual risk is not inconsequential. That's a substantial residual risk despite the drugs proving themselves in large-scale clinical trials. So patients will still continue to progress.
We see where we are as an option for patients who've been on therapy and continue to progress into stage four chronic kidney disease and where there is a therapy as an option for them to prevent them from going on to dialysis.
A couple of questions, maybe just following up on that a little bit. One, in terms of your phase III program, with all these changes happening in the kidney space, how are you sort of managing that? Maybe you can just talk about the use of SGLT2s, use of GLP-1s, and how is it impacting everything about powering assumptions or kind of how. Maybe that'll be a first question. And then second question sort of tied to this big population of patients potentially, but with these other treatment options. I don't know if you have any market research or other data. What percentage is a realistic target of patients that might be willing to go through a procedure like this to get something like rilparencel when there are some other options now before?
Yeah. So I'll address the first question, which was around have we modified our phase III program in any way just based upon all this new data that's come out in this space. We've made some changes, so we stratify for SGLT2 inhibitor use, for example, just to make sure that we've got equal SGLT2 inhibitor use in both arms of the study. In our protocol and in all our discussions with our principal investigators, patients need to be on standard of care and what's working for them if they can tolerate it. So that standard of care obviously is RAS inhibition, SGLT2 inhibitor use, and maybe GLP-1s or maybe something else, but we're really encouraging those investigators to treat patients with standard of care because that's where we think we're going to fit on the commercial side as well.
So those are the big things, I think, where we've made changes in our phase III program. And we've narrowed the GFR range in our most recent protocol, again, based upon our phase II data, but also based upon the changing therapeutic landscape within this population as well.
Okay.
And then your second question was.
Just around the kind of, if there's any market research or other data on that?
On patients.
Percentage of these patients that may be open to.
We've done a little bit of market research in this space, but nothing to the size and robustness where I can say, well, how many, what % of patients will accept rilparencel as a treatment. Some of the research that had been done in the past were in patients who had less advanced chronic kidney disease, so clearly, that's a little bit of work that we need to do. What we're seeing in our clinical studies in our phase III program is patients are receptive depending upon how the nephrologist talks to them about it, and that's not a surprise, right, so one of our investigators has talked to patients around. I know it's three needles. It's a biopsy and then an injection in one kidney, an injection in another kidney, but if you end up on dialysis, it's three needles every week.
Really, if you position this as a way to keep people off dialysis, I think patients will be more receptive.
Okay. Helpful. There's another topic that comes up frequently, both with investors and also, I think, with doctors. I think your clinical data definitely stands out as showing there's something happening. I think some questions around exactly how rilparencel is working. And I know you had some data at ASN recently, and I think you're planning on sharing some more next year's. Maybe you can just talk about the work you've done to kind of really try and elucidate and then communicate the mechanism here.
Yeah. So I'll take you back a little bit if I could, Vamil. So early on, I think the company invested a lot of effort into preclinical work and then, before being public, went through some time where access to capital was limited. And they really prioritized doing clinical work, phase I, phase II studies, and deprioritized some of the R&D work. So one priority for me coming in last year was we need to do more work on understanding our mechanism of action, right? And part of it is that we all know that there's drugs that get approved where the MOA is not clearly defined. But we're talking about a very new therapy here and an intervention that it's more than just taking a pill every day if you have to, right?
So we prioritized doing some work on the MOA, and we also looked back at all the data that's been done in the past. Here's my take on where we are on some of this. So you get questions around what happens to the cells when they're injected. We don't believe they form new nephrons. So there are still some markers of cells that are around for six months, but we think there's a decay in the cells over the course of three to six months. What's happening? How do you explain an improvement in kidney function? The early preclinical data would say that there's less inflammation and there's less fibrosis.
And that played itself out in kidney disease models in rats where rats injected with rilparencel or selected renal cells like rilparencel actually lived longer and their kidney function improved and they had decreased improvement in other kidney function markers. But all that is probably driven by paracrine or local effects driven by changes in inflammation and changes in fibrosis. We know that that's a pathway for patients who have diabetic chronic kidney disease. That's what happens to them as they get to stage four disease. It's more inflammation, more inflammation being converted into fibrosis and scarring. We also know that's a final common pathway for a lot of different types of kidney disease. So there's a potential for us in the future to even think more of an umbrella therapy for patients who have kidney disease and not just diabetes.
For now, we need to focus on diabetes. The other thing I'll say is at ASN, we had, I think, five abstracts that really just better characterized what our product is. Some of the markers, which are less inflammatory, less fibrotic, we see a change in those markers as the cells mature during the manufacturing process. So more work to do, but I think we're making progress on our that it's a priority for us.
Okay. And maybe one last question here just around the manufacturing side because we've obviously seen that with other companies in this sort of space. So maybe you can comment on sort of where things stand right now manufacturing-wise and what would you need to do between now and potentially getting this product to the market in terms of build-out?
So we're operating a GMP-compliant phase III manufacturing facility in Winston-Salem. We've had that, as I said, audited by EU QP last year and a certificate of compliance issued this year. So we feel comfortable where we are from a compliance perspective. But in order for us to move that to a commercial manufacturing facility, we need to work with the FDA around our CMC. And we've made a lot of progress around our CMC. We've actually hired some leaders in the space with experience in autologous cell therapy and CMC work with the FDA. So part of our FDA engagements in 2025 is to get approval from them on our CMC plan.
Okay. We're almost out of time, but maybe just as a recap here, what investors should be looking out for over the next 12, 18 months from a catalyst data perspective?
Yeah. I mean, I think the news that's going to come from us is going to be our 007 data, bigger cohort, longer follow-up on some of the patients. That's going to come out in the first half of this year. We continue to do some work around.
Would that be more like at a conference or is that more just like a company disclosure or not?
I'm thinking of timing. So it's probably not going to be at a conference if I think about the timing, but we will present it at a conference sometime in 2025. So that's around 007. Continued work on our MOA, right? That's going to be an evolving story. I don't think it's going to be we wake up one morning and the light bulb goes off, but we'll continue to release data around our MOA. And then third, we expect to talk more about our accelerated approval pathway. We'll have a better understanding of what that is, when we expect to read out, and we should be able to talk about that in the first half of next year as well.
Okay. All right. Great. Thanks so much again for joining us. Congrats on the progress, and we'll be watching closely. Thank you.
Thanks, Vamil. Thank you. Thank you.