Hello everyone, and welcome to the H.C. Wainwright fourth annual kidney conference. My name is Lander, I'm a Senior Research Associate at the firm, and here with me is Bruce Culleton, CEO of ProKidney. Hi Bruce, thanks for joining us.
Oh, thank you Lander. It's great to be here.
Of course, yeah. Maybe Bruce, for those who may not be familiar with ProKidney, could you please provide a brief overview of the company and how you're approaching chronic kidney disease or CKD?
Yeah, absolutely. Lander, we're a pre-commercial autologous cell therapy company. We have a single asset that's being tested in patients with advanced chronic kidney disease and type 2 diabetes. We went public in 2022, and that was on the background of about 10 years of preclinical and early stage clinical research. We have offices in Boston, Raleigh, and Winston-Salem, North Carolina. The Winston-Salem location is where we do our manufacturing. In many ways, we're a different company today than what we were in 2022 when the company went public. We now have close to 250 employees, and these employees have really driven an enormous amount of progress over the last 18 months. Just quickly, some of those big highlights: we resolved all of our quality audit findings after we put a manufacturing pause in place at the end of 2023.
We restarted our Phase III clinical study about this time last year after a protocol amendment. We've had two late-breaking Phase II clinical trial presentations at scientific congresses. We've changed our regulatory strategy, allowing us to seek approval on just one singular Phase III study. Last week, it just so happens we also released top-line efficacy and safety data from another Phase II study called REGEN-007.
That's very helpful. I think it's important to contextualize a little bit CKD. What's the current therapeutic options for CKD patients and what's ProKidney's target population?
Yeah, today, maybe I'll just start by saying I think we're living in a golden era of new therapeutics in chronic kidney disease.
Yeah, right.
For patients with diabetes and CKD in particular, there are four pillars of care: renin-angiotensin system blockade with either ACE inhibitors or ARBs, SGLT2 inhibitors, non-thyroidal MRAs, as well as GLP-1 receptor agonists. These landmark clinical studies, I mean, every year there seems to be a new landmark clinical study, but those using SGLT2 inhibitors and GLP-1 agonists focus largely on patients with less severe kidney disease, primarily stage two and stage three. We find ourselves in a very unique situation where we think our product is most suitable, Rilparencel is our product's name, most suitable for patients with even more advanced kidney disease where there's less data. We're focused on primarily stage 3B and stage four chronic kidney disease.
Okay, perfect. As you mentioned, you're focused on more advanced CKD patients. Where do you see Rilparencel fitting into the current treatment landscape with SGLT2 inhibitors and GLP-1 therapies?
We hope, and honestly I expect, that as time goes on, there's going to be even better utilization of SGLT2 inhibitors as well as GLP-1 receptor agonists for patients with diabetes and chronic kidney disease. We also know that these therapeutics are not cures, and even within the control setting of randomized control trials, many of these patients lose kidney function and continue to develop kidney failure. We see Rilparencel as a real option for those patients that continue to progress, that's a real issue, and continue to need dialysis at some point in time as well. We see ourselves as that potential option to keep patients off dialysis.
Awesome. Moving into the technology itself, you already described a little bit what Rilparencel is. Could you please elaborate a little bit more on the procedure itself from tissue acquisition to the injection process?
Yeah, of course. Lander, under an interventional radiologist, under the prescription of a nephrologist, the IR typically takes a kidney biopsy. We've trained the IRs to take the biopsy primarily from the kidney cortex. It's mainly done under CT guidance, though it can also be done under ultrasound. That biopsy is then shipped to our manufacturing site in Winston-Salem. When the biopsy arrives, it has somewhere between 50,000- 100,000 cells within the biopsy. Over the course of the manufacturing process, we select out a certain type of cells, mainly tubular epithelial, and the end product ends up being 2-3 billion cells. We then dose the patient based upon the size of their kidney. A bigger kidney gets more cells, a smaller kidney gets less cells.
The typical injection, which is also done by an interventional radiologist under CT guidance, the typical dose in one kidney is somewhere between 250 million and 500 million cells. The first dose is typically given in the same kidney that was biopsied, and the second dose is given three months later in the other kidney.
Okay. Maybe going more into the mechanism of action, you at the American Society of Nephrology meeting last year, you presented data exploring Rilparencel's mechanism of action. What should we expect from the next mechanistic update in the second half of 2025, and how will this build upon prior findings?
Yeah, I will start by saying I don't think we still have work to do on our MOA, right?
Okay.
We've got older data which suggests that its impact is primarily through fibrosis, antifibrosis, anti-inflammation, but we still have some work to do using more of the more up-to-date techniques to demonstrate MOA. What we did at last year's ASN, we focused primarily on characterizing Rilparencel and the changes that occur from the biopsy until the final product. This year we've submitted abstracts that characterize Rilparencel and the secretome during cell manufacturing. We describe cytokine gene expression and metabolic reprogramming that gives us even more insights into the MOA. Just as a teaser, we have a very unique new model to test MOA that I'm hoping gets presented at ASN. We don't know yet, but if it does, I think many people will find it extremely interesting in how we're thinking about proving what the MOA is.
Awesome, that's exciting. Maybe before we jump into the pivotal trial that's ongoing, last week, as you said, you announced positive top-line results from the 007 study. Congratulations, by the way. Can you walk us through the study design, the key findings, and how these results may provide read-through into the ongoing Phase III PROACT-1 trial?
Yeah, of course, Lander. We were excited about last week's announcement too. We didn't expect the result that we received, at least the market result that we received, but we were pretty excited about the results when we first had a look at them. REGEN-007 was a multi-center U.S.-based Phase II open label study. Patients were randomized into two arms, and those two arms were, I should say that the patients were diabetic and had chronic kidney disease with a GFR between 20 and 50. The two arms that patients were randomized to, one was group one, and group one is really important for our Phase III insights into our Phase III program because group one had the same dosing schedule that we're using for our ongoing Phase III program. Patients received two scheduled injections, one in each kidney, approximately three months apart.
We think that, because of the dosing schedule, that's the most insightful data as part of the 007 readout. Group two tested an exploratory dosing regimen in which a patient received one dose, and received only a second dose based upon biological triggers such as a change in eGFR or an increase in urine albumin loss. That second dose for those patients who ended up getting a second dose was on average 10 or 11 months after the first dose. Very different than how we're executing our Phase III trial at this point in time. The pre-specified endpoint, the primary efficacy endpoint, was the difference in annual slope in eGFR in the two-year pre-injection period versus the period after the last Rilparencel injection. Patients had an approximate follow-up of 18 months after the last injection in both groups.
Quickly, we randomized 53 patients, 49 of them ended up getting treatment, and they were part of the modified intent to treat readout that we provided. In group one, again, that's the important group providing us a window into what Phase III may look like. Their annual decline in eGFR slope before treatment was 78%, and they declined annually at - 5.8 mLs per minute. The 78% refers to the difference from the pre-injection to the post-injection, and post-injection, the annual decline was - 1.3 mLs. From - 5.8 mLs to - 1.3 mLs is 78% improvement in the decline of kidney function. This difference of 4.6 mLs is what we were surprised with. It exceeded our expectations. It was statistically significant, but more importantly, clinically meaningful.
The benefit observed in some of the other landmark papers is typically between 1 ml and 2 mLs per minute per year, maybe sometimes a little bit more than 2 mLs, but we observed 4.6 mLs. Smaller population, but still this was something that we exceeded our expectations. Importantly, of that group one, 24 patients, 15 of them also met our Phase III inclusion criteria, and those patients had similar results as the entire group one, again making some suggestion perhaps of what benefit we might see in Phase III.
Okay. Go ahead, please.
Oh, just quickly, in group two, we also saw a benefit in group two. The benefit was not as great, but it certainly suggested that there was a dose response. It also confirmed to us that we're on the right track in dosing patients with two injections, one injection in each kidney.
Perfect. Besides the results, you also announced that you're planning on submitting the full 007 data set to the American Society of Nephrology meeting. What additional information should we expect during the Kidney Week in November?
All we released this week was the safety results, the primary top-line safety, which was consistent with safety events we see with the kidney biopsy, as well as the primary efficacy. For Kidney Week, everyone will see, get a better understanding of, you know, the patient characteristics at randomization, what happens to the slope over time. You expect to see a figure with confidence intervals around those pre-slopes and post-slopes. Also expect to see some subgroup analyses. You know, we've been asked, because we have type 1 diabetic patients in the study, was there a difference in type 1 versus type 2 diabetes patients? Was there a difference in patients older versus younger, more albuminuria, less albuminuria, SGLT2 use or no SGLT2 use? Lots of other sort of just a deeper dive in the data that we anticipate being able to share in November.
Perfect, that makes sense. Based on the 007 results, I'm just curious to know what your thoughts are in terms of stabilization versus improvement. Would you consider stabilization already a significant clinical benefit for these patients?
I don't think we have, I don't think we're generating new nephrons. I don't think that's how Rilparencel works. I don't think we're going to get an improvement in kidney function. Lots of variability, but I don't think we'll get a consistent improvement. What we are seeing is very close to a stabilization or preservation of kidney function. The - 1.3 mLs annualized change that we saw in the treated patients in group one is very similar to what you'd expect to see in an older adult as part of normal aging. We do think we're seeing, and this was consistent with prior reports from us as well, just a preservation or stabilization of kidney function, which is very meaningful for patients.
Okay, perfect. Maybe diving into the ongoing Phase III, the PROACT-1 trial, could you guide us through the general study design? I know that this time we have a sham control group. Remind us a little bit about the endpoints.
Of course, yeah. The key entry criteria, type 2 diabetes and chronic kidney disease, in essence, we're looking at patients who've got a GFR between 20 and 35. Eligible patients are randomized to receiving Rilparencel or a sham, and that sham includes a sham biopsy and sham injections, all done in an interventional radiology suite. The treatment, if you end up getting Rilparencel, you get a biopsy, Rilparencel three months later, and the second injection three months later. We do follow both patients over time. The study was designed for a time, it was a time-to-event study. It still is a time-to-event study. The events are at least a 40% reduction in eGFR, an eGFR less than 15 for more than 30 days, or chronic dialysis, or transplant, or death from kidney or cardiovascular causes. It's a composite endpoint.
Endpoint.
Right now it's designed to enroll over 600 patients, but again, that's driven by how fast events may happen. Obviously, the longer we follow patients, the more likely we're expected to see the desired number of events.
Okay, perfect. In terms of results, do you expect concomitant use of SGLT1 inhibitors or GLP-1 receptor agonists to enhance the therapeutic effect of Rilparencel?
Two things. We've stratified randomization by SGLT2 inhibitor use at baseline. We think that's more important than GLP-1 agonists, for example. Reasons I can get into later if we needed to, but that was the stratification that we decided to use. We also believe the mechanism of action is different. We don't see a decrease in albuminuria with Rilparencel. We don't think this has an intratumoral hemodynamic effect. We think it works differently than SGLT2s or GLP-1s, for example. For that reason, we think the effect may be additive. We don't think it's synergistic. We have no information to say it's synergistic, but it's probably additive if we demonstrate a benefit.
Okay, perfect. What’s the current enrollment status of the trial, and what’s the feedback that you’re getting from investigators at the clinical sites?
We haven't provided any guidance, broadly speaking, on our enrollment status at this point, but I anticipate we'll provide some updates towards the end of this year or maybe early in 2026, particularly as it relates to potential accelerated approval. With regards to our investigators and others that work at the sites, I'd say we've got some very, very engaged sites, some very interested investigators. We consistently hear support on the population of patients we've chosen to study because these are an understudied population, as well as the innovation that we're bringing to the space. I've gone on some tours to meet investigators. I've presented some of our MOA data, some of our Phase II data, and even the radiologists that show up tend to get very excited and interested in what we're doing.
Perfect. To the extent that you can share, of course, in terms of regulatory dialogues with the FDA, a Type B meeting is scheduled for this summer to discuss potential accelerated approval pathway for Rilparencel. What would a successful outcome of that meeting look like for you? Do you expect your current cash balance to fund operations up to the Phase III readout?
Yeah, so a successful meeting for us would be confirmation from the FDA that eGFR slope can be used as the surrogate endpoint for accelerated approval, number one. Number two, confirmation that our estimated treatment effect, our assumptions essentially, is clinically meaningful within the framework of an accelerated approval pathway. Number three, confirmation that our study population that we intend to use for accelerated approval is acceptable. This would provide us a timeline for when we'd expect accelerated approval readout. That timeline, we hope, will come before we run out of cash for operations. We think it will. Currently, we have, as of May, $328 million. That takes us into Q2 2027 to fund our operations.
Perfect. Awesome. As you look forward to our potential commercialization, where do you stand in terms of manufacturing readiness and scalable production capacity for the product?
All our manufacturing is going to be done in Winston-Salem. We've got capacity to produce product for our Phase III patients. We also have capacity for our initial commercial launch. We expect demand at launch. We also have started expanding our facilities in Winston-Salem, and we will build additional capacity almost like in a modular fashion as we expect demand to grow over time.
Okay, perfect. Currently, PROACT-1 is primarily focused on the U.S. How do you envision the potential expansion of Rilparencel into additional territories in the future?
There are lots of patients outside the U.S. that could also benefit from Rilparencel. We are not going to ignore those countries outside of the U.S., but right now, our focus is on execution and getting to market in the U.S. We are always open for opportunities that might come our way from potential partners who might be interested in looking at countries outside the U.S.
Okay, amazing. For the sake of time, Bruce, would you like to summarize the upcoming catalysts for the next 12 months or the current fast position relative to these catalysts, or clarify anything that investors should be aware of?
I think I covered most things. Obviously, we're pretty excited with our Phase II data. We will give an update on our Type B FDA meeting very, very soon. We touched upon this; Kidney Week is an important time for us, not just the MOA, but also full results. Hopefully, we'll get a late-breaking clinical trial presentation. I think we will, and we'll be able to talk more wholesome about what the data showed.
Perfect. Thanks again, Bruce. This was highly informative, and we look forward to upcoming updates.
Great. Thank you, Lander. Appreciate it.
Of course. Thanks.