Okay. All right. I think we're ready to get started. Thanks, everyone, for joining us for the second annual Guggenheim Healthcare Innovation Conference, day three here. I'm Bimal Devan, one of the bio-pharma analysts here. Joined up here next in this room, we have the ProKidney team. We have Bruce Culleton, the CEO, James Coulston, the CFO. We're just coming off a busy week, seeing you guys last week at ASN, too. Maybe just to kick things off, Bruce, for people maybe less familiar with the story, just sort of give an overview of the ProKidney story, how you've gotten to where you are now, and then we'll talk about ASN and future steps from there.
Sure. Yeah. Happy to. And Bimal Devan, thanks for inviting us, as always. Nice to see you again. We are a company that's trying to solve a problem that's familiar to millions of Americans. A lot of Americans understand, have a relative, have a friend who's developed kidney disease and ended up on dialysis. We have a product. It's an autologous cell product that's in a phase III trial. Our goal is to give people more time, more time to stay off dialysis and more time to find an organ if they need to find an organ for kidney replacement therapy. We are really trying to preserve kidney function in those patients with really advanced chronic kidney disease. Our company is based out of North Carolina and Boston. We have about 250 employees. 250 employees, I would say, who are aligned to our purpose.
Our purpose is to keep people out of the dialysis unit.
Okay. Great. Maybe we can talk about your Rilparencel and the progress you've made to date. Just to summarize for people, you had a couple of different posters or presentations at ASN last week. What were the main takeaways from that?
Sure. I'll start with the progress that we've made to date, maybe over the last two years. Collectively, we've made an enormous amount of progress. We had some challenges early on around manufacturing. We paused our clinical study because of the manufacturing challenges. We've corrected everything. We're now in GMP compliance for a phase III clinical study. We've had some really positive interactions with the FDA. Those interactions include going to the FDA and really asking, do we need two phase III randomized controlled trials? Under our RMAT, we didn't. We actually stopped one of those phase III trials that was primarily being conducted outside of the U.S. We also went to the FDA and asked if we could move down the accelerated approval pathway using eGFR slope as an interim readout for our phase III analysis. We're completely aligned with the FDA on yes.
We have an accelerated approval planned readout in Q2 2027, so about 18 months from now, using eGFR slope. The other couple of things, big progress that we've made, we've continued to enroll extremely well. We're over 50% enrolled for our phase III readout. We've had some really good data recently at ASN, Kidney Week, where we presented data on our phase II study called 007. If you follow our story, you'll see that we were pretty excited about the data. It exceeded our expectations, certainly exceeded my expectations. We saw a 78% improvement in the decline in kidney function in patients enrolled into one of the groups in the 007 study. That group where we observed that benefit was the meaningful group for us because that treatment paradigm used in that group mirrors exactly what we're doing in the phase III program.
Can you maybe talk about that? Because there's the group one and the group two. What are the differences between the two?
Group one, patients who were randomly allocated to group one received the kidney biopsy. When the product was ready, they received an injection in the biopsied kidney. For those of you who do not know us, we actually inject the autologous cell product directly into the kidney cortex. It is done by an interventional radiologist under CT imaging guidance. The first injection is in the biopsied kidney, and the second injection is in the other kidney three months later. That is group one. These were all diabetics, some type 1, some type 2. Group two was more of an exploratory dosing regimen where patients were, when they got randomized to group two, they received a kidney biopsy. They received a first injection about three months later. Then they waited.
That wait was essentially waiting for them to get worse, as measured by a change in eGFR or a change in urine albumin. If they got worse, they received a second injection. If they met one of those triggers, they received a second injection in the other kidney. Of the 25 people randomized to that group, 15 of them received a second injection and 10 did not. Of those 15 that received the second injection, the average time from the first injection to the second injection was much longer than group two. I think the average or the median was 11 months. The dosing exposure was very different in group two. We did see a 50% benefit in group two, not as much as a 78% benefit in group one.
That 50% benefit was not statistically significant, but it certainly suggested that there was a dose-response relationship.
Yeah. Okay. So the group one, as you mentioned, is sort of the approach you're taking in phase three.
Correct.
Maybe you can talk about what you're hoping to see from the phase III trial as much as you want to share on powering assumptions or what you're thinking.
Of course. Yeah. Our phase III study, just to talk about that for a second and then what we expect to see. Our phase III study is a double-blind sham-controlled study that we're running at over 60 sites in the U.S., a couple of sites in Taiwan, a few sites in Taiwan, and a couple of sites that we're just opening up in Mexico. It's sham-controlled, and it's blinded to the patient. It's blinded to the principal investigator and the site, except for a safety physician that's at the site. That goal was originally designed with a confirmatory endpoint of a composite time-to-event that's pretty standard for the kidney space for composite hard endpoint. That composite is time to the first of a 40% loss in kidney function. It's measured by eGFR, transplant, dialysis, or renal or cardiovascular death.
That was the confirmatory endpoint as originally designed, with our estimate being somewhere over 600 patients that we need to get to those events. Since then, we've had the discussion with the FDA around accelerated approval. Our accelerated approval readout has different assumptions because it's only based upon slope or change in eGFR. Those assumptions are a 3 mL per minute per year progression in the sham group and a 1.5 mL per minute per year progression in the treated group for a 1.5 delta. We believe we've got 90% power to detect that difference. We also believe that those estimates are conservative.
We've invested so much in this company that we wanted to make sure that our assumptions going into that power calculation were on the conservative side, not just on the treatment effect, but also on the assumed progression in the sham group as well.
Okay. Maybe just the progress you've made. You talked about second quarter of 2027 having the top-line data. Just as much as you, again, want to share in terms of the interest in the trial and the enrollment and how it's progressing so far.
We've had a good year on enrollment. I will say that when we announced the top-line data for phase two, that really excited a lot of the investigators. Our enrollment has stayed pretty consistent. We're essentially enrolling to our projections for the course of the year and moving into next year. I don't expect that will change. We had a PI investigator meeting at Kidney Week. Lots of excitement. People are very interested in the study, wondering how they get their names on the eventual paper and things like that. Definitely lots of interest from our site investigators.
Okay. A couple of follow-ups on things you mentioned. You mentioned the sham control. We talked about this a little bit last week. How are you doing, given the nature of this procedure? How are you making sure that the blinding stays appropriate?
I won't get into this in any detail, but I think the FDA has recently changed their viewpoint on historical controls with some of the smaller studies in non-kidney disease or rare disease. I think you probably may have seen some of that just in the news. We are fortunate that, in some ways, we started the study with a randomized sham control group. That sham- control group, to give you some perspective on it, if a patient is randomized to the sham- arm, then they end up going, they have all the procedures are exactly the same in the way of eligibility criteria, follow-up procedures with a significant exception. That is, they actually don't get a kidney biopsy or they don't get injected with the product. They go to the CT scan suite. The interventional radiologist and the team have a script.
They have to stay in there for so long. They're gowned. They have the procedure, the area prepared around where the biopsy would normally happen. They get a small injection. They actually do get a sedative. Everything feels the same for that patient. They go into the recovery room, same length of time in the recovery room. They go home and they get post-procedure blood tests. Everything for that patient should feel like they've gotten a procedure, as well as for the coordinator, as well as for the PI. We've gone out of our way, I think, in many ways to try and make sure we maintain the blind of the study.
Okay. Another poster you presented at ASN was more tied to the mechanism of action. Maybe you can talk about what you presented and then your latest thoughts on how Rilparencel actually make an impact.
Yeah. We've presented a few abstracts over the last couple of years around mechanism of action. Much of it is tied to, over the last couple of years, really characterizing what our product is and how does that product change from the time a biopsy comes into our manufacturing facility until we have a cryopreserved product at the end. To give it a little bit of perspective, when we get the biopsy into our manufacturing site, we're working with somewhere around 50,000-100,000 cells in the biopsy. When the final product is made, it does get aliquoted, if you like, into multiple different vials. The amount of cells that we have left at the end of the manufacturing process is in the billions. We go from 50,000-100,000 to billions of cells.
Those cells at the end of manufacturing, they have a very unique phenotype. Those cells have both markers for tubular cells and epithelial cells. We have some data to show that they're more likely to progress into a tubular cell or more likely into an epithelial cell based upon what their environment that they're exposed to. Our R&D team would say that they're plastic, meaning they have some degree of plasticity in the direction that they move. The presentation at Kidney Week really just described those cells a little bit in more detail and showed that we do have markers of antifibrotic markers and anti-inflammatory markers on the cell surface, which speaks to how we think our product works.
It does have some mechanism that's related to antifibrosis and anti-inflammation, either directly or helping the kidney's innate repair mechanism, like you see in acute kidney injury in some patients who get better, helping that innate mechanism actually improve and lead to greater kidney health.
Okay. All right. Great. One thing on back to the data is that we talked about the efficacy that you saw. We didn't touch as much on safety. Maybe you can just share again what you've seen so far and then I can think about the phase three. What's an acceptable safety profile for us? There's an invasive procedure. Do you think it's acceptable?
First thing I'll say about safety is there's a lot of literature available around what's the safety of a kidney biopsy because that's one question we get is a kidney biopsy. I could say what we're doing to really mitigate any of those safety concerns. First and foremost, we have strict eligibility criteria built into the study. You can't have a bleeding disorder. You can't be recently hospitalized. You can't be on anticoagulants. Or if you are, you can still come in, but you need to be able to stop them for a certain period of time before the biopsy. In essence, we're dealing with chronically sick people, but not acutely sick people. We've removed that sort of risk. We have very experienced interventional radiologists that are doing the procedures, and they do them under imaging, CT guidance for the most part.
We're trying to mitigate that risk as much as possible. There's always going to be a risk. That risk is everything from minor pain at the biopsy site or the injection site to local bleeding to local infections to more major complications such as systemic infections to even hematomas around the injection or biopsy site. I'll have to say that what we see in our data, not just 07, but our cumulative data, is that we see no serious events related to Rilparencel itself. We do see the occasional blood in the urine and some hematoma from the injection. It's a pretty strong safety profile for what we're doing, for sure. We do see that occasionally. We see a renal biopsy safety profile that's better than what's reported in the literature.
Occasionally, you still do have some complications from the renal biopsy as well. We're never going to get rid of that. I don't see a way of how we can. This would be classified as a minimally invasive procedure, but it's still an invasive procedure.
Okay. That's good. Maybe we can shift more to the commercial side. I was just a couple of years away from that point. Huge market opportunity that you're going after. There are a lot of exciting developments in the kidney space. Maybe we can just talk about sort of your particular patient population. How are they currently managed? We hear a lot about the SGLT2s, GLP-1s. What sort of impact are they having in the sort of later stage patient population? Maybe just sort of frame the numbers in terms of what you think is the eligible population for your treatment.
Sure. I'll start, and then I'll ask James Coulston to talk about sort of the overall addressable market. Over the last four or five years, we've really seen emerging therapies in the kidney space, great for patients. Some people call this the golden era of kidney therapeutics. We even have four pillars of care as we think about diabetic kidney disease and their treatment. RAS inhibition, older, SGLT2s started to come on board for kidneys in 2021, followed by non-steroidal MRAs, followed by the GLP-1s. Talking to our KOLs, I think we all feel like this is a substantial improvement in care. KOLs that we talk to as well will say that, look, it's very difficult, especially in this advanced kidney disease population, to get adoption anywhere above 50% for SGLT2s. That adoption percent goes down for the other therapies.
I'll also say that just when we talked to the FDA, they're really interested in us maintaining standard of care. What they consider to be standard of care is RAS inhibition and SGLT2s. They seem to be less concerned about non-steroidal MRAs, I'm sorry, and a little bit less concerned about GLP-1 use. They really want the standard of care to be around RAS inhibition and SGLT2s. I'll also say that one point that we like to make when we talk about these newer therapeutics is they are great for patients. They do slow progression. They will keep people off dialysis. Patients still progress. They slow progression, but do not lead to long-term preservation of kidney function. They're also not used a lot in patients with the advanced kidney disease target population that we have in our study.
I'll throw out one stat because I know there's a lot of people that are interested in, say, GLP-1s and what impact they have on kidney disease. We often use a term called number needed to treat. That number needed to treat simply is a way to reflect how many patients you need to treat to prevent one event. In the FLO study, in the big kidney disease GLP-1 FLO study, you needed to treat 85 people to prevent one kidney replacement therapy event. They still work, but there's still a lot of progression that happens.
With regards to respectable market, according to USRDS, there are a million to a million and 1/2 stage 3B and 4 CKD patients with diabetes in the U.S. Just a 1% penetration to that market would result in 10,000-15,000 patients potentially treated by Rilparencel annually, which is significant for a cell therapy. When you think about commercial opportunity, we haven't really talked about pricing. One way to think about it is the value that Rilparencel could potentially deliver to the healthcare system. Rilparencel aims to treat patients that are most likely to progress to dialysis. Dialysis costs the healthcare system for Medicare patients up to $150,000 annually. For patients who are covered by other insurers, it can be up to twice that amount.
For every year that Rilparencel is able to stabilize kidney function and prevent a patient or delay a patient from progressing to dialysis, Rilparencel has the potential to deliver $150,000 of value to the market.
You mentioned the numbers, potentially a lot of patients. Can you talk a little bit about the manufacturing sites or where you are now, and then what do you need to sort of get to at the time of commercialization?
Sure. First of all, we have the manufacturing capacity to manufacture all the product required for a phase III clinical study. In addition to that, we have the ability to launch our product from our current manufacturing facility. We also have additional space that we can expand our capacity in the manufacturing facilities that we currently own. We plan to do so and have that available for us about a year after launch. We have the ability to expand further even beyond that. I think with that being said, if Rilparencel is as successful as we hope that it will be, we think that demand will likely outpace our capacity.
Okay.
Can I add a couple more stats?
Sure.
If you don't mind.
Yeah, we love stats.
Just on the Medicare side. James Couslston is right about the numbers. 7% of the overall Medicare budget is used to manage patients who have end-stage kidney disease. That is 1% of the overall Medicare population. 7% of their budget, 1% of the population. If you back up into the non-dialysis CKD group, now CKD, that often comes with people who have diabetes and heart disease, etc. If you just say, do you have CKD or not, 24% of Medicare recipients—sorry, 24% of the Medicare budget goes to treating CKD patients. 24%. That is because you just usually do not have CKD on its own. Like we are doing in our study, they have diabetes, they have high blood pressure, they have heart disease, and things like that. It is a common condition.
Almost 1/4 of the Medicare budget goes to treating patients, paying for patients who have got some form of kidney disease.
Okay. Interesting. Last couple of minutes here, maybe we can just talk about the company's cash position, where you are now, what's your runway, and then maybe just summarize what catalysts we should expect within that runway.
Sure. As of September 30th, we have $272 million of cash. That funds our operations to mid-2027. From a catalyst standpoint, what's important about our cash runway to mid-2027 is our key catalyst is phase III data for the accelerated approval, surrogate end-point, eGFR slope in 2Q 2027. We have cash to phase III data for accelerated approval. In addition to that, we will share some additional data next year related to mechanism of action as we progress our translational studies. We also anticipate completing enrollment for phase III for the surrogate endpoint in 2026.
Okay. All right. That's great. I think let me wrap it up there. Again, thanks so much for attending the conference. Nice progress coming out of ASN, and look forward to watching things going forward.
Thanks .
All right. Thanks.
Yeah. Thanks.
Thank you, Bob.