Good morning, and welcome to the ProKidney Virtual KOL Event. At this time, all attendees are in a listen-only mode. A question and answer session will follow today's formal presentations. If you would like to submit a question, you may do so using the Q&A text box at the bottom of the webcast player. As a reminder, this call is being recorded, and a replay will be made available on the ProKidney website following the conclu sion of the event. I'd now like to turn the call over to Et han Holdaway, Senior Director of Corporate Development and Investor Relations at ProKidney. Please go ahead, Ethan. Thank you, operator. Good morning, everyone, and welcome to ProKidney's Virtual KOL Event and recap of the phase II RMCL-002 final data. Joining me this morning are Dr. Steven Coca, Professor of Medicine and Nephrology at the Icahn School of Medicine at Mount Sinai, Dr. Arnold Silva, Director of Clinical Research at Boise Kidney and Hypertension Institut e and CARE Research Network, and Dr. Bruce Culleton, ProKidney's Chief Executive Officer. Before we begin, I would like to remind everyone that we will be making forward-looking statements during the presentation today. I encourage you to refer to the most recent SEC filings regarding risk factors associated with these statements. I would now like to turn it over to ProKidney's CEO, Dr. Bruce Culleton. Thank you, Ethan. ProKidney is delighted to sponsor today's event. It comes at an inflection point for our company as we are now emerging, in many ways, from a six-month company reset. What better way to emerge from this reset than presenting final data from our phase II study? By having two esteemed nephrologists present their own views on the unmet medical need for many patients with chronic kidney disease, and providing an o verview of the changing therapeutic landscap e that's created more options for improved patient care. Today, it's my absolute pleasure to be here with Dr. Steven Coca and Dr. Arnold Silva. Dr. Steven Coca is a Professor of Medicine at the Icahn School of Medicine at Mount Sinai in New York, the Associate Chair for Clinical and Translational Research for the Department of Internal Medicine, and the Director of Clinical Research for the Division of Nephrology. His research focuses on the utility of blood and urine biomarkers for risk stratification of patients with acute kidney injury and chronic kidney disease. He's been part of several large NIH-funded consortia on biomarkers and kidney disease, and he has over 300 publications, received multiple awards, including the Distinguished Researcher Award from the American Society of Nephrology in 2021. Dr. Arnold Silva is Director of the Home Hemodialysis and Peritoneal Dialysis programs at Boise Kidney and Hypertension Institute. Dr. Silva has been appointed Clinical Assistant Professor of Medicine at the University of Arizona and has taught in many areas of biology, biochemistry, and physiology for California State University and University of California. He's been very active as an independent investigator in the basic sciences and clinical research throughout his career and currently acts as a principal investigator on many projects for Boise Kidney. I'd like to start by saying a few words about our company. We are a company focused on helping patients with advanced chronic kidney disease. CKD has a substantial global impact on patients, their families, and overall healthcare costs. Our goal is to preserve kidney function in patients with advanced CKD caused by diabetes, the number one cause of kidney failure globally. We believe our proprietary cell therapy offers the potential, the possibility, if you like, of keeping patients off dialysis by preserving kidney function. We have phase II data, but of course, this needs to be proven in our phase III program. to do this, we've assembled a very talented team with several new leaders added over the last few months. Shortly, you will see how this talented team and all of our employees are contributing to our near-term milestones and will contribute to our success in the future. Let's take a step back and review why we believe rilparencel is so special. As you can see, chronic kidney disease is a significant problem. While one in seven adult Americans have some degree of CKD, there are more than 3 million Americans who have Type 2 diabetes and advanced Stage III-B and Stage IV chronic kidney disease. These are patients that have few kidney treatment options and are at very high risk of progressing to kidney failure. Within this large population, I'd note that more than 135,000 CKD patients in the U.S. alone continue to progress to dialysis every year. We believe there's a substantial opportunity with our product, rilparencel, as we believe we can preserve kidney function to delay or eliminate time on dialysis. Today, we will walk through data that provides the context for the importance of rilparencel. We hope you will see the unmet medical and societal need, even in the face of a changing therapeutic landscape, where patients now have greater options for cure than ever before. But many patients continue to progress to kidney failure, and we believe rilparencel may be able to preserve kidney function and possibly provide greater benefit in high-risk CKD patients. And now I'm honored to hand over to Dr. Steven Coca for an overview of the treatment landscape for patients with diabetic CKD. Dr. Coca? Thank you, Bruce, for that introduction. It's a pleasure to speak to you today about the treatment landscape for patients with diabetic kidney disease. My name is Steven Coca. I'm a professor of medicine and a practicing nephrologist at the Icahn School of Medicine at Mount Sinai in New York City. This slide depicts the temporal progression of studies that have occurred for efficacious trials in diabetic kidney disease over the better part of the last three decades. From the 1990s and early 2000s, we had evidence from trials of ACE inhibitors and angiotensin receptor blockers, that they do slow the progression of diabetic kidney disease. But then there was a multi-year period, over a decade after th e IDNT and RENAAL studies from 2001 into the 2010s, where there were many therapies that failed to show efficacy in DKD. This included potential therapies including bardoxolone, sulodexide, anti-TGF-beta, monoclonal antibodies, and many others that just failed to show benefit. And it led to some pessimism and nihilism both in the scientific community and in treating patients in the clinics. And fortunately, as you can see to the right of this graph, in the last decade, we've had an explosion of trials, efficacious trials across multiple classes in this space. We have in blue, the SGLT2 inhibitors trials. We have in orange the GLP-1 receptor agonist trials. In pink, the trials of the non-steroidal mineralocorticoid receptor antagonist, finerenone, and also in purple endothelin antagonists. Thus, we now have multiple agents that we can layer on to risk factor management in patients with diabetic kidney disease, representing therapies that can be taken orally on a daily basis, or injectables in the case of the GLP-1 receptor agonists. We had exciting data from the FLOW trial presented last week at the ERA conference, showing that this is essentially now the fourth pillar of therapy to add on to this lifestyle management. Now, simulation studies, assuming that you could apply these four drugs on top of maximum tolerated ACE inhibitor or ARB doses for DKD, show remarkable risk reductions in lifetime risk for CKD progression, as well as all-cause mortality. These data just came out from Brendon Neuen a few weeks ago showing the simulation. But this is the best-case scenario where these patients get this multiple drug therapy over years on a daily basis, and ongoing throughout their life. And this compliance is not typically reflected in clinical practice. There's problems with side effects, adverse events, compliance with a multi-drug regimen, as well as costs of these agents over time. So we know in reality that many of these agents are started and stopped in approximately 25% to about 50% of patients do not continue with SGLT2 inhibitors, GLP-1 receptor agonists, or finerenone, about a year or more after starting these therapies. In addition, while the risk reductions achieved by SGLT2 inhibitors in some of the seminal CKD and DKD trials, including CREDENCE, DAPA-CKD, and EMPA-KIDNEY, are very impressive, with the hazard ratios of approximately 30 to—representing a 30%-40% risk reduction in development of the primary composite outcome that involved kidney progression. This slide also shows you that despite the efficacy, again, that we were so in desperate, in need of to treat these patients with, with diabetic kidney disease, the number one cause of end-stage kidney disease in the United States, there still remains a large residual risk despite these optimal therapies on top of the RAS inhibitors, and you can see that represented by this, the, the red arrow, that many patients are still progressing despite these therapies. These trials enrolled higher-risk patients with DKD, as you can see here, represented across the heat map, the KDIGO heat map, the eGFR and albuminuria matrix. Again, the FLOW trial showing that 24% risk reduction with that hazard ratio of 0.76. But one thing to note about these trials and the patients included is that they largely included patients with a GFR of 25 and above, which means patients—many patients with Stage G4 CKD or DKD were excluded from these trials, due to potential concerns, for events that typically occurs in, in these advanced groups. So we don't have data on, or robust data on the efficacy of these renal agents in this group with advanced diabetic kidney disease. While it gave a little world from simulations like this one done by Go and colleagues, if you start multidrug intervention early when GFR is still preserved, in this example, GFR 70, so that would be Stage G2, you can really delay progressive decline in kidney function and delay need for dialysis by approximately 11 years. But in reality, these patients are not referred to nephrology. A lot of attention is not paid to them. We know the real-world data suggests that only 20%-30% of these patients are actually receiving the guideline-directed therapies, including the SGLT2 and GLP-1 receptor agonist. And in reality, the reflection of clinical practice is what Go shows here in the bottom left corner. Patients who are recognized or referred at more advanced stages of kidney disease, in this case, with an eGFR of 30, and there, while interventions may help to some degree, you can see the absolute benefit derived is much smaller at these later stages by the late application of these therapies. Again, representing the need for other types of therapies to potentially extend that runway and delay the onset of end-stage kidney disease. In conclusion, as you can see, it's been a very exciting time in nephrology in this space, as there's been tremendous progress in treatment options in diabetic kidney disease over the last 5-7 years. We now have therapies that can slow the progression to end-stage kidney disease. But I think I've also shown you we cannot completely stop progression. There's still a substantial residual risk of progression despite these modern therapies, and really, there's an inability to treat all higher-risk DKD patients with these triple or quadruple-based oral or injectable therapies due to the issues I mentioned with compliance or adverse effects over time. Even in an ideal world where you could treat these patients, it does not completely abrogate the progression. There is still progression occurring. Finally, we really have minimal data on how to slow progression in advanced diabetic kidney disease, especially those in Stage G4. Thus, I think this is a compelling statement, is that there is a need for more treatment options for advanced stages of diabetic kidney disease to prevent progression to end-stage kidney disease, which is really just such an unfortunate outcome. Because even with survival, which is markedly truncated once patients start dialysis, it is a time-consuming, difficult way to live. Attached to a machine at least three days a week for in-center hemodialysis, attach the machine even more often on home dialysis, whether peritoneal dialysis or home hemodialysis, and still many cardiovascular complications and infectious complications happen to these patients while on dialysis. So it is of utmost moral and clinical importance that we, we really do everything in our powers to prevent patients from progressing to end-stage kidney disease. Thank you for your attention, and with that, I'll pass it on to Arnold. Hello, everyone. Thank you, Dr. Coca, for that excellent presentation. I am Dr. Arnold Silva. I am a nephrologist and director of clinical research at Boise Kidney and Hypertension Institute in Boise, Idaho, which is affiliated with the Cardiorenal Research Network, also known as CARE, and it's my pleasure today to speak with you about chronic kidney disease, CKD, and the current treatment landscape, and also where this is going, as far as the future. To start, I think it's important to consider that chronic kidney disease is really a tremendous burden for us in clinical medicine worldwide. It affects over 40 million Americans alone, and there's similar numbers in Europe. So just looking at the U.S. and Europe, we're approaching 100 million people that are affected by kidney disease. But disease in the kidney goes beyond that. It's linked to cardiovascular disease and metabolic disease. Our most common cause of chronic kidney disease is Type 2 diabetes, but also Type 1 diabetes, glomerular diseases that are impacted by autoimmune dysfunction, as well as hypertension, and many other systemic diseases can affect the kidney. But a staggering number, we began to see this as we did larger clinical trials in chronic kidney disease, is about 90% of our patients with chronic kidneys remain undiagnosed. And that is a challenge in and of itself, in that these patients have not been diagnosed and unaware of their disease and thus are not going to be seeking treatment and various treatment options that continue to urge clinical trials for their underlying kidney disease. Chronic kidney disease is also progressive, and as patients lose kidney function, and we look at function as their GFR, their glomerular filtration rate. As their GFR declines, that's associated with an increased cardiovascular risk, and if they continue to progress to kidney failure, also known as end-stage kidney disease or ESKD, those patients have a very high mortality. To put some numbers to that, a 40-year-old patient who has end-stage kidney disease and is on dialysis, their mortality is comparable to an 85-year-old patient in the general population. Now, we've put a lot of efforts into our patients with end-stage kidney disease to improve both the quality of their life as well as extending the quantity. But unfortunately, despite heavy investments in research over the last two decades, we've not improved survival in this population. The other issue that comes along with this is cost. Our patients with end-stage kidney disease are about 1% of the total U.S. Medicare population, but they consume about 7% of the Medicare budget. So given the high mortality as well as the high costs, the need to really look at chronic kidney disease much earlier has been what our focus has shifted to in the last five years. A number of new therapies have emerged that do give us some encouragement. Almost everywhere in the medical literature, you'll see that the SGLT2 agents, which were initially developed to treat Type 2 diabetes, along with the mineralocorticoid receptor antagonists, the MRAs. Both of these therapies have been shown to reduce proteinuria, that is, protein in the urine, and that is an independent risk factor for progression of chronic kidney disease. Both will help slow the decline in eGFR, but it's important to know that while these are encouraging things to see, patients continue to progress and will lose GFR greater than 2 ml/min/year. Roughly 2% or more, despite these therapies, is lost from their kidney function each year. In order for us to really preserve kidney function, to really arrest progression of disease, we need to reduce eGFR decline to less than 1 mL/min/year. Up to now, we haven't had any therapy, medical or otherwise, that has been capable of reaching that goal. Cell therapy, however, with REACT, does give us a lot of promise moving forward. This autologous, homologous approach that has been developed by ProKidney now has an excellent safety profile in over 100 patients. And given this is an autologous, homologous approach, patient's own tissue that we're using, we haven't seen any immune reactions or tumors from this therapy, and the overall procedural risks are also quite minimal, which has given us the green light, really, to proceed with more studies with REACT. And I find it most encouraging that phase II data in over 100 people has been shown to reduce the decline in GFR in these patients to goal, that is, to less than 1 ml per minute per year. And I think that this is very promising for our patients as we move forward. And I think that as clinicians, this can really open the door to a whole new treatment paradigm for us in chronic kidney disease. And with that, I am gonna turn this back over to Dr. Culleton to finish up this presentation. Thank you. Thank you, Dr. Silva. It's my pleasure to present the final results of our recently phase II clinical study. The data we will review phase III clinical program, and we believe it demonstrates the potential of rilparencel to further improve the treatment options available for patients with advanced CKD caused by diabetes. On this slide, we have the design of RMCL-002, phase II study, which is now complete. We previously presented interim results from this open-label study in November last year. Just last week, we also presented the final results of this study in Stockholm as part of the late-breaking clinical trial session at the European Renal Association's Annual Scientific Congress. In this study, patients with CKD caused by diabetes were randomized after kidney biopsy to one of two treatment arms, the active group or the deferred group. Active group patients received two rilparencel injections, the first as soon as rilparencel was available, and again 6 months later. Follow-up visits were scheduled every 3 months after the second rilparencel injection, until 24 months after the second injection, when the study ended for each subject. Deferred group patients received standard of care for the first 12 months after randomization. At the 12-month mark, they were eligible to receive the first of two rilparencel injections, with the second injection administered 6 months after the first. Follow-up visits occurred every 3 months for 12 months following the second injection. Notably, the biopsy and the two injections were all performed in the same kidney. This differs from our other large phase II study, which ends 007, and our phase III studies, PROACT 1 and PROACT 2, which I will explain in more detail later. As phase II trial, the study objectives were focused on the safety and efficacy of two REACT injections 6 months apart and delivered into the biopsied kidney using a percutaneous approach. Study endpoints included procedural and REACT-related adverse events, along with change in kidney function, as assessed by change in estimated glomerular filtration rate, or eGFR. The characteristics and demographics of the RMCL-002 population were well-balanced, with patients with higher risk CKD comprising a significant portion of both treatment groups. 43% of all enrolled subjects had Stage IV CKD. The average baseline eGFR was 34 and 32 ml/min, and UACR of 740 and 5.98 mg/g in the active and deferred arms, respectively. Blood pressure and glycated hemoglobin were well controlled. The safety of rilparencel remains a significant focus for us, as we understand the highest risk CKD population often has multiple comorbidities and tend to be older patients on many medications. The biopsy and rilparencel injections continue to be well tolerated, and we are pleased to report that there are no significant rilparencel-related serious adverse events. The rate of procedure-related events is consistent with published reports of events observed during kidney biopsies, which are commonly done to assess and diagnose chronic kidney disease. On the next two slides, I will be presenting some of our efficacy results and in my opinion, the most interesting data from the study. Additional slides will be available on our website. Overall, our conclusions do not differ from the conclusions we reached in November with the interim analysis. Here on the left side of this graph is the deferred group again, as they received standard of care. Then 30 of these patients received rilparencel at month 12 and again at month 18. They are followed out to 12 months after their second injection. Subjects in the deferred group who received standard of care showed a -3.3 ml/min decline in average eGFR over 12 months. After rilparencel injection, their average eGFR decline was only a -0.8 over the next 18 months. We feel confident that stabilization of eGFR after rilparencel injection in this high-risk population reflects the potential for preservation of eGFR in patients with diabetic chronic kidney disease and is one reason why we feel phase III program. on this slide, we highlight the CKD Stage IV patients with severe Class A3 albuminuria. On the left, we have 13 subjects meeting this criteria who were in the active group and 14 subjects in the deferred group or the standard of care group that met these criteria. Over 12 months, the average change from baseline in eGFR in active patients was -1.1 ml. In contrast, the average change in eGFR in the standard of care group was -6.1 ml/min. This same standard of care group is also reflected in the bottom curve of the right panel. As we've previously described, these same patients received rilparencel after 12 months of standard of care. For these same subjects, we reset their baseline eGFR at the time of rilparencel injection, and their change from this new baseline is reflected in the top curve on the right panel. Their average change from baseline after injection was essentially zero, compared to -6.1 ml/min for 12 months before the injection. As you can see, these subgroup analyses of high-risk Stage IV CKD patients, treatment with rilparencel was associated with a stabilization of kidney function, as assessed by change in eGFR over a 1-year period. We feel this data strongly supports rilparencel having its biggest impact on the highest risk CKD population, a population that's progressing to dialysis. We believe the data in hand demonstrate rilparencel's potential for the preservation of kidney function in Type 2 diabetic patients with advanced kidney disease. Rilparencel's benefit was most notable in the sickest patients, those who had Stage IV CKD with a high UACR. Consistent with previous study data, rilparencel was well-tolerated and continues to demonstrate a safety profile in line with the kidney biopsy. Because of the unmet need described by Doctors Coca and Dr. Silva, we modified phase III pivotal trials, the PROACT 1 trial, to enrich the number of patients with the highest risk of kidney failure. The amended protocol was submitted to the FDA in March. We have since received central IRB approval, and we look forward to enrolling new patients into this study very soon. We have a robust clinical trial program with rilparencel, as highlighted in this pipeline chart. I'd like to point out that interim results from our open-label REGEN-007 program will be available shortly. Patients in Cohort 1 of this study will receive rilparencel in the same phase III study program. rilparencel is injected into the biopsied kidney and then injected into the contralateral kidney 3 months later. Furthermore, in the study, rilparencel is cryopreserved, again, somewhere to our phase III program. results from this study will be helpful in providing us confidence in our phase III studies. In closing, I'd like to thank Dr. Coca and Dr. Silva for their very helpful perspectives. I hope you find them as insightful as we do. This is a very exciting time here at ProKidney. We are all looking forward to build upon this RMCL-002 data with the interim analysis from again, REGEN-007. We're also pretty excited to restart phase III enrollment in the near future. With that review, I'd now like to open up the call to your questions. Begin conducting our Q&A session. As a reminder to the audience, you may submit questions below the webcast player, and to our analysts, please raise your hand to indicate you would like to join the queue. With that, we'll take our first question from Justin Zelin at BTIG. Thanks for taking the questions, and thanks for putting this presentation together. I I really appreciate it. Maybe for our KOLs, Dr. Coca and Dr. Silva here. Obviously, with the FLOW study recently announced their results here in the New England Journal, publication, just wanted to get your thoughts on, on that data set and whether there's any overlap in the patient population here with REACT. And I have a follow-up. Hi, Justin. Thanks for the question. This is Steve Coca. Yeah, the FLOW trial, another exciting trial that I alluded to in the presentation. Again, those with severe albuminuria and going down to a enrollment GFR of 25, so there is some overlap. Two things to note from the trial, though, if... I, I, I didn't display the Kaplan-Meier curve from FLOW, but they would look just like the ones with, from the three, SGLT2 inhibitor trials that I presented, and there's still a significant residual risk of progression in the, non-treated, in the treated group, with semaglutide. Also, there was, there was a significant amount of, of stoppage of the drug. I think approximately 25% stopped by one year. So again, these are potential therapies that we can apply, but it's not gonna... Oh, and one last point is the eGFR slopes, again, attenuated with semaglutide, but still not achieving that goal of less than 1 ml per minute per year. So another arrow in the armamentarium, but still potential, again, to add more and arrest kidney disease because it does not completely abate and attenuate that progressive eGFR decline. Arnold, do you want to add anything? Thanks, Steve. I, you know, I just really concur with what you have said here, and I, I think it, it points to the importance of us needing something more than just the current medical therapeutic strategies that have been in development, and that we continue to see encouraging results from these c linical trials. Yet, even though there's an attenuation in the eGFR decline, which again, I find encouraging. It's really not enough. We, we do need something more than what we, what we currently have available and currently have seen in even the most recent clinical trials. That's very helpful. And my last question, both of you mentioned a goal of eGFR decline reduction to less than 1 ml per minute per year. Would that be a clinically significant goal for the REACT product? Or what would you deem to be clinically significant for this product? Thanks. I think that would be a great goal. As we see from the RMCL-002 data, it appears to result in a slope less than 1 ml per minut e per year. It is really the Holy Grail because the epidemiologic data of normal aging suggests that patients lose GFR at approximately 1/2 mil to 1 ml per minute per year. So anything in that realm is essentially equivalent to that loss due to normal aging. I, I agree as well. I think, when we look, at really anybody, we're all over time losing kidney function, so there is a normal aging process. And whether it's diabetic kidney disease, or kidney disease from many other different systemic diseases, I, I think getting under that, 1 ml per minute mark is really where we're strivin g to be. And we're, we're not there yet with the, with the medical therapies. Okay, thanks for the question, Justin. The next question comes from Judah Frommer. Yeah, hi. Thanks for taking the question. Maybe just first to follow up on phase III trials, PROACT 1 and 2, would the expected annual eGFR decline be similar to the rate you just disclosed, or higher-risk patients would be expected to have quicker decline? Who's that for, for Bruce or for Arnold? I guess, I guess whoever wants... I guess the high level question, maybe for the KOLs is, is just, you know, should eGFR decline be expected to be greater in the higher-risk population? Yeah, I, I can comment there. I mean, typically what we have looked at in many of these trials, are the high-risk population, and I think Dr. Coca showed in his slides. Often these patients were, with eGFR range in the 25-45 range. So that is, that is a higher risk group. Many of those patients with proteinuria, and they're often progressing at, at greater, as far as GFR loss, over, 4 ml per minute, per year, and, or certainly in that territory. So this is a population that everybody is interested in, because they are losing function, quite rapidly, both from their, current, eGFR, where they stand with moderate to advanced disease. Many of these patients have significant proteinuria, which, again, is another risk factor. So, yes, I would expect, especially when you look across multiple studies, to see the patients in this group to be progressing at a faster rate. So, Steve, if you want to come in as well. Sure. I guess is the heart of the question, does it need to get to less than 1 ml per minute per year to be a success? I think, again, that is the ultimate goal, but for success on a clinical and scientific basis, of course, slowing the progression in this high-risk group compared to the control arm, you know, in a statistically significant manner, is gonna be a success. And let's not forget that although it is invasive compared to the other treatments, it is a much potentially when it's the short-term pain, long-term gain, compared to taking multiple medications on a daily basis or the injectables in the case of the GLP-1s. You get this done, and you don't have to worry about that daily compliance. And so there's that potential for the ease of achieving this reduced risk. Again, with the invasiveness, but without the... We know how much problem patients have with multi-drug compliance, and they miss doses, they stop taking them for various reasons. They don't feel well. They think it's their medications. They hold them for undisclosed periods of time. You know, the therapy is getting there with this treatment, and that's, that's one of the reasons I've been so excited about the program from the beginning, because it's hard convincing patients to take these pills every day for something that's gonna potentially reduce your future risk. It's, it's not necessarily symptomatic at these stages yet.... And you overcome that barrier with this type of therapy. Okay. And just getting back to your comments on the FLOW trial, and obviously, GLP-1s are gonna be a topic of discussion across lots of diseases these days. But I guess for the high-risk CKD patient population, I guess how realistic is it that, you know, GLP-1s are gonna reduce the prevalent population there? Or is the idea more that maybe there are fewer high-risk CKD patients over time, because maybe patients are taking GLP-1s and they're not getting to later-stage kidney disease? Or do you think that, you know, this high-risk population could shrink, as more patients do get onto GLP-1s? You know, I know there's been these potential debates about, are we really gonna shrink this population? I mean, we still have a massive inflow of obese and diabetic patient population out there that all estimates suggest will continue to grow double, triple over the next few decades. So yes, you're getting some reduction in that pool, but I still think the in is greater than the out on what you're gonna prevent, and thus the total addressable population is still gonna be very large and robust despite GLP-1s or any of the other therapies. Thank you. Okay, thank you for the questions. The next question comes from Jonathan Miller at Evercore. Hi, guys. Thanks for taking my question. I would like to ask both the KOLs a question about eGFR as the endpoint. Obviously, it's notoriously variable from a patient-to-patient basis, even within individual patients. So when you think about the variability of the data on an individual patient basis, could you talk a little bit about how the SGLT2 trials are mitigating that error rate? And what are the, you know, best practices for running these trials with the endpoints that can be a little noisy? I can start on that one. Yes, eGFR can be noisy, especially one point in time on an individual patient. But we do have all the trials to date, including the REACT trials, you have multiple time points where you're assessing eGFR in a repeated measures fashion, so that does help hone down on an individual base slope. And the FDA-approved endpoints for the sustained 40% decline, sustained 50% decline in eGFR, all require a confirmation at 30-90 days later, so that it's not just that individual fluctuation that can result in a noisier signal. So I think even though there is some noise, it's not perfect, it is the clinical standard. You know, as opposed to employing something like a measured GFR with iothalamate, while that can be somewhat more accurate, it would not be representative of clinical practice. Makes sense. I guess the follow-up to that then is, you know, given that eGFR is the, the gold standard, how do you rank that relative to disease progression into ESRD or onto dialysis or any of those time-to-event, progression endpoints that, you know, ultimately are what cost payers a lot of money and, and what result in the, the real, decline in quality of life for patients? Well, that's why the endpoint's always the composite. It's the, it's the absolute decline in GFR or end-stage kidney disease. And the thing about defining end-stage kidney disease is you define it as the time to start renal replacement therapy. But that is highly individualized, sometimes not just on the kidney function alone, but the other factors that are present, whether it be hyperkalemia, fluid overload, those are the two actual driving issues where you potentially start dialysis at different levels of GFR. So it's actually nice to have the eGFR, even though it has that noise, is more standardized because, if patients reach, for example, a GFR less than 15 at Stage 5 CKD, sustained eGFR less than 15, it creates a common finishing line. 'Cause there may be some patients who don't start dialysis, again, for personal or individual physiologic reasons until GFR is 6, 7, 8 ml per minute. But, that's my opinion. Arnold, do you wanna add anything? Yeah, Steve, I, you know, I think when we look at these endpoints and the newer endpoints that the FDA has accepted, the eGFR slope and also the proteinuria endpoints, and despite the noise, and we see noise in both of these endpoints, they're helpful because we can look, especially with repeated measures, we can look at the trends in the patients early on, and I think it's helped us not only get information- ...sooner, but it also helps us conduct much more cost efficient or cost-effective trials, as opposed to looking at the previous hard endpoints progression in end-stage kidney disease, need for renal replacement therapy, and so forth. So I think this is, I mean, there's no one perfect endpoint, of course, but I, I think it's very helpful, and it, it helps us conduct these trials in a much more efficient manner. Thank you. Thank you. Makes sense. I guess one final one on the design of the REGEN-007, obviously, phase III trials, which have bilateral injections into one injection in each kidney, versus the data we've seen so far with two injections into one kidney. And obviously, we don't have a ton of data here yet, but just speaking speculatively, is there any reason to expect that moving to both kidneys would be dramatically better or worse? That not having two injections in one kidney would, you know, diminish the impact on an individual kidney, or by contrast, does moving to both kidneys necessarily double your impact? You know, do you have the thoughts about what that change in protocol might do to the phase III data relative to 02? Well, I can take a start on that one. We have some data with injecting both kidneys, but it's limited at this point. I think potentially we could see a bigger effect as far as eGFR preservation because we are doubling the landscape so to speak as far as renal cortical tissue by utilizing both kidneys. That's gonna be very interesting, I think, for us to see as we get more data in upcoming trials. So far from a safety perspective though we've not seen really any new concerns or additional concerns for the safety impact. So I'm encouraged moving forward with the next trials. Okay, thank you. I concur 100%. Thanks for the questions. The next question comes from Jason Gerberry at Bank of America. Oh, hey, guys. Thanks for taking my questions. I guess first, any thoughts or views maybe on the reason why patients in the deferred arm saw better stabilization of eGFR than patients in the active cohort? And then for the KOLs, just curious, you know, as you think about the d urability of benefit you achieve with these injections, how you'd frame sort of what you need to see at a minimum for the durability versus, you know, what would get you particularly excited about REACT from a durability standpoint? It's Bruce. Are you, are you... Would you like me to answer your first question? Is that directed at me? Uh, sure. Okay. You know, it's something, as you can imagine, we've looked into, like, why, why, why did we see less of an effect, if you like, in the active treated patients for the first 12 months versus those patients who crossed over on, from standard of care? And I don't think we've got—we definitely don't have a smoking gun on this. What we do see in the active patients is a slight imbalance in high levels of proteinuria in that group versus the control group. And we also just understand that the way the study was designed, a lot of the patients that were first exposed to rilparencel were those that were randomly assigned to the active group. Because those randomly assigned to the deferred group went another 12 months without getting rilparencel. The study started in 2017. That's important because the study started in 2017, and I would say that, you know, the team at that point in time, this was the big first study that they'd done. There was some learning in protocols and training, all those things that you'd probably expect to see when a study like this was rolled out. So again, no smoking gun, but certainly some speculation on why, why that would be the case. I will say that, you know, the, as you've seen, the stabilization of kidney function in the crossover group is something that that makes us optimistic for the future. You probably, you know, you're aware that we'll have 007 data coming out soon, and I think that will help us understand how all this fits together as well. Great. Thank you for the questions. The next question comes from Elliott Bosco at UBS. Hi, all. Elliott Bosco from UBS on for Ellie Merle. One question for Bruce and then one for the KOLs. For the upcoming 007 readout, could you discuss what types of endpoints you plan to share and any other color on the readout, such as expected patient numbers and follow-up? Sure. I, I can address that, for sure. So we've got, so we said back, I think in, we have a readout for 007. We were gonna—It's an open label study, so we didn't want to present any data off at least more than 10 patients who had, 12 months follow-up after their second injection. And so we're, we're sticking to that story, and we'll be presenting that, that data soon. The endpoint, it is a phase II study, and, the goal of that endpoint was, looking at change in kidney function after treatment with rilparencel, as measured by eGFR. Great, thank you. And then for the KOLs, if rilparencel were available today, how would you be thinking about using it, and what would that conversation look like with your patients? Well, I can start, and I think if it were available, and provided, you know, the patient was a potential candidate for this, I think we would certainly be looking at any patient with Stage II- B disease or worse, with chronic kidney disease, for cell therapy. And what I found so far in the clinical trials is that the patients are very receptive to this therapy. Dr. Coca had mentioned some things about compliance, and when we look at all the new medical therapies, there's always a compliance issue, the more pills you add or if you add injections. This is something when we introduce it to patients so far in the clinical trials, they're very receptive to this. Especially as we've had increasing numbers for the safety profile, which are very encouraging. I think this discussion would begin with most patients, well, certainly with stage 3B disease and higher, and offering the therapy with the potential of arresting their kidney disease, and possibly preventing dialysis, or at the very least, deferring or delaying the need for dialysis for some time. And that's what I hope the conversation is gonna be down the line here. Okay, thank you. I'll just concur, just say that, you know, this is the only clinical trial program I've been a part of that is. I think Dr. Coca is breaking up. Dr. Coca, can you hear us? Okay, we'll move on to the next question from Ashiq Mubarack at Citibank. Hi, guys, this is Ashiq Mubarack on for Yigal Nochomovitz at Citibank. Thanks for taking my question. I just wanted to get a better understanding of what eGFR trajectories were like for these patients, maybe prior to their first injection. And more, you know, maybe the more important question is, was there a meaningful shift between maybe the curve before and the curve after treatment? I'm just wondering if there may be patients with a higher rate of decline, regardless of risk status, if that would make a difference to how their treatment response might have been observed post both injections. Thanks. Yeah, I'll jump... It's Bruce. Thanks for the question. So, I actually don't have that data. I know some of that data was presented very early in the course of the study in early interim analysis. I think at the time of the de-SPAC, I think some of that was presented. It's not part of our study protocol analysis, and part of that is because the data collected pre-study was done in a less rigorous fashion with time points that weren't always well-defined. So it's a great question. I just don't have the data in our final analysis to tell you what the answer would be. Okay, got it. Thank you very much. Yep. Okay, and I think we have time for one last question from Clara Dong at Jefferies. Hi, this is Clara Dong for Kelly Shi. So maybe just one question on the REGEN-007 study. So intensification of the REGEN-007 study analysis coming up. So we're just, just trying to understand how does this readout really inform the pivotal trial, given the similarity of the bilateral injection? And the REGEN-007 trial also has two cohorts, with one receiving a second dose if a pre-defined trigger is met. So, you know, while looking at this redosing trigger, will we also get any color of this redosing trigger at the update as well? Thank you. Yeah. Hey, Clara. So the 007, why we think it's important is primarily for cohort one, and because cohort one, as you just alluded to, there are injections in both kidneys. We're also using the cryopreserved product, which is the same product we're phase III program. so we think, you know, the results that we're gonna see for 007 give us more of an indication of maybe what we'll phase III program. cohort two doesn't do that, as I think you're alluding to. I mean, cohort two has a trigger, and so after first injection, some patients may wait for some time before getting the second dose. Then their second dose, because it's actually triggered because of a change in eGFR or UACR, it obviously means that there's something like a slope that's changed, for example, with eGFR. What my goal was, as we stated back in November, is to really, you know, give the data as we know it, that applies to... That could be helpful in, in, in understanding where the phase three results might actually end up going. So that's gonna be our focus with our upcoming zero seven release. Super helpful. Thank you. You're welcome. Okay. I think I'll hand the call back to Ethan for any questions that may have come in over the webcast. Hey again, everyone. Thanks again for joining us this morning. This concludes the Q&A session. I'd like to thank Dr. Coca and Dr. Silva for joining us today and for all their insights. As a reminder, the presentation from the call and a replay will be available on the ProKidney website. So this concludes the call, and you may disconnect your line.