Thank you so much for joining us here on the 3rd Day of the 41st Annual J.P. Morgan Healthcare Conference. We're thrilled to have you here, and we're thrilled to have ProKidney. Up here, we've got the CEO of ProKidney, Tim Bertram. Tim, I'll hand it over to you. Thank you very much, Jim. Welcome, all of you. I look forward to sharing our story. Thank you for taking some time with us this afternoon on a rainy day. May not have had a lot of options, but at least you're gonna spend some time here, and we'll tell you our story. Our forward-looking statement can be found on our website if you want to read that. Just to assure you that we will be making forward-looking statements. I think the big question that exists is what is ProKidney? We only became public about six months ago. The question that occurs is what are we doing? What are we trying to solve? What is our plan to solve the problem that we think we want to address? The problem is really quite impressive. For those of you that may think that chronic kidney disease is something that's solved through dialysis, it's actually one of the leading causes of death and dialysis in the country. Importantly, 75 million people. As I look out over this audience, there's about, let's say 30 people here. Believe it or not, there's about four or five of you sitting in this room that have chronic kidney disease and do not know it. You won't know it until you approach the late stage of chronic kidney disease, which is CKD4 usually. What that means is all of a sudden you come in and you're alerted that you're gonna have to go on dialysis in a very short period of time. This situation is addressed even more significantly in the fact that you really have no other alternatives, yet $130 billion are spent each year on this disease. What is our goal? What is our mission? Why do we think we can bring? Our goal here is really to try and stop and prevent renal failure. It's a very simple mission. It's a very simple goal. One of the other things that we want to do is we want to try to reduce the cost. It's not only the burden to the patient, but to reduce the burden to the healthcare system. How do we think we're gonna do that? 18 years of research have been devoted to this project. 18 years of research have been devoted to defining this product. 18 years of research have been devoted to making sure our manufacturing process is accepted throughout the world. Our product is a cell-based therapy. Believe it or not, when the diseased kidney begins to get to failure, there are cells within the kidney that exist that are trying to heal that kidney. What we have through our proprietary method of manufacturing is developed the ability to be able to pull those cells out of the diseased tissue and create a product which actually restores the healing and the capability of that kidney to be able to return to what it was like before the disease impacted it. Our plan is simple and straightforward. We've been working on this, as I said, for 18 years. We've reviewed for 15 years our project work, the manufacturing aspects with the regulators around the world conducting the PharmT ox studies. In the past eight years, we've been doing clinical trials. These clinical trials have been reviewed by both the EMA and the FDA, and we have a plan forward as to what we wanna do with that. Ultimately, the contribution that we have here is not only to patients, but to bring society better medicine that gives not only quality of life improvement, but quantity of life back to the patients. We have a comprehensive clinical development program. We intend to put out in 2023 information about what we are actually trying to do, what we're working forward with, so that you as investors, the analysts and others that are looking to participate with us in our journey financially and also, of course, medically and regulatory, a series of publications that will outline very clearly how this product works, what its impact is, and where the events are going to occur. One of the things which some of you may be aware of is, as we released yesterday, a very exciting study for us. I'll talk more about it in a little bit, but it actually described the ability of REACT to prevent patients who are faced with death or dialysis. That is a very difficult choice to be confronted with. 20% of patients die the first year they go onto dialysis. 15% of patients, when confronted with that question, actually choose not to go onto dialysis, therefore, choosing death. This is a very serious diagnosis. We took patients on the doorstep of death, and we showed that REACT could work. I'll talk more about that. Very exciting. Small study, but very, very important because it was consistent with what we have seen over the past eight years in a very seriously diseased patient population. One of the other things that we'll be talking about, which is quite interesting for us and was designed actually for you as investors, is as we've developed a study in which we will be dosing both kidneys. Up to last year, all of our studies were done with two injections into one kidney, and that was done for safety reasons. The kidney that we biopsied, and I'll talk more about that in a minute, was the same kidney that we injected the product back into. We were only addressing about 50% of the real estate. Because of our safety profile and the high tolerability of our product, we now are able to dose both kidneys. I'll be sharing some of that as we go forward. Another very exciting thing that has occurred as we did our studies looking at patients, and I'll show this data to you in a minute. What we're seeing is, we reach a plateau over a period of time. There's a durability. The patient's disease is continuing. What we've done is propose to the FDA that we want to be able to dose multiple times, more than just two, but maybe four, maybe eight, maybe up to 10 times with a patient. That study was accepted by the FDA, and we'll be reporting on that this year. Then, of course, the big report for this year will be that we're going to launch the second arm of our phase 3 program. The first arm was launched, the first protocol was launched here in the U.S. at the start of last year. Second quarter, we anticipate starting the second of two independent trials for registration in the rest of the world. With that backdrop and that story, how does this all fit together? How can we make a comprehensive clinical package come together to support registration for a very large market and bring a label that will allow for reimbursement and for investors to get a return? What this highlights here is, it's really the cornerstone of how we develop this. The 02 trial that you see in the center, this was a tremendous study that allowed us to see how powerful REACT was. It demonstrated that our product could actually, for the first time ever, return function and increase function in patients that had chronic kidney disease. That was remarkable. It struck us so much, we asked the question, could this product actually work in patients on the doorstep of dialysis? I talked about that previously. When we took that designed the 03 study to see what would happen with that. Of course, as I just shared with you, the 015. What's significant here, as you look at the three studies along the bottom, is what it ties together is the dosing, the redosing, and the treatment range or the indication size that we've got. How do they fit together? If we're going to redose, we need to be able to define the redosing triggers, and we need to show that we can dose both kidneys. That's the 07 trial. The pieces of the foundation for the phase 3 trial are all laid out, and therefore clear for the regulators to be able to interpret the data that we bring forward. What I wanna remind everyone is that our phase 3 program involves injection. One injection in one kidney, one injection in another kidney. It's two injections for the body, but it's one injection in each kidney. Collectively, these things come together then to form the registrational package. Why ProKidney? Why do you as investors want to contemplate ProKidney? What's the value creation? Well, we've got a really tremendous board. I'll talk more about their skills, abilities, what they're bringing to the leadership of the company in a moment. You've got a management team that has developed 15 medicines previously across the management team. Over 200 years of development experience brought together. We believe that the capability is there. What's really driving? What's the passion for the company? The real passion and drive is that too many patients today, treated on the best standard of care, still go on to progress to dialysis. This is a very concerning thing because it's high cost, major patient impact. However, our initial clinical success clearly indicates we can preserve kidney function, and that is really the story that we're taking forward. You as an investor are seeing high probability for the management team, high probability for the technology, high acceptance by the regulator, and really an overall opportunity to address a very serious unmet medical need. How serious is this need? Well, singularly, chronic kidney disease accounts for the single largest Medicare expense as a single line item. What does that measure in terms of numbers? You're looking here at numbers that are already spent by a single payer. It's just CMS, it's just what our tax dollars are supporting. What's amazing is that $80 billion are spent each year on patients that are actually declining and progressing toward end-stage renal disease. Once they get onto dialysis, an additional $50 billion is spent. As I shared with you, 20% of those patients are dying in the first year. This is a very serious, costly problem, and by the end of this decade, 8 million more people will have chronic kidney disease. What are some of the new therapeutics capable of doing? What is the latest advance that we've got? What's illustrated in these three graphs is something that's quite telling. This represents the SGLT2 data that's been published. There's several thousand patients here represented in this data. If you look at the gray line, the gray line in each of these graphs shows what happens in the patient's journey. There is a steady progressive decline in their kidney function, ultimately ending in failure. What's also equally impressive is look at the blue line. The blue line is showing what today's best standard of care can do. What's also very telling in the data is if you look at the first graph, this is done in patients that have approximately 56 mL per minute of eGFR. What does that translate into? These are normal people. They don't know that they've got chronic kidney disease necessarily, unless they've got diabetes or their physician has prescribed it. What's fascinating, at that level, we're seeing about 2.2 mL per minute difference, but it's still a decline. What's equally fascinating, if you see a decrease of only 10 mL per minute, so about 10% of the kidney function, the effect size of the SGLT2 is cut in half. This is a very, very significant observation for us, and we see this is where our fit. We've been testing patients as low as 15 and as high as 50 mL. We're slotting into the very sickest of patients. Patients then in this massive population are available to us. We have really selected the worst patients. There's about 4.4 million patients that would qualify for REACT based upon the eGFR of 20-50 mL per minute and diabetic kidney disease. Diabetic kidney disease accounts for about 50% of all CKD in this country. If we then ask the question, with a market size that big, what really is the opportunity or the likelihood that patients would take this medication? Well, this is a paper that was just published a few weeks ago by a group of academics in the FDA. Interesting question that was asked here was, would you... And there's over 1,000 patients that were cited in this. Would you, with chronic kidney disease, take an intervention that had side effects? What was interesting is almost 94% of CKD patients said that they would. To refine the assessment, investigators made it more quantitative, and they said, "What if you only had a 20% chance of kidney failure? Would you still take an intervention that had side effects?" 75% of the patients indicated that with as little as 20% probability of having kidney disease leading to failure, they would take an intervention that had side effects. Interestingly, we can flip this around. What about physicians? Would the physician use a medication that had side effects? What's shown in the left-hand graph is what's referred to as the heat map by the Kidney Disease Improvement Group organization worldwide. It's an independent group. As I showed you, when you look at the... When you look at the upper left-hand part of this heat map, what you can see is this is the level of disease that is being targeted by today's best standard of care. What REACT is targeting is that lower band, those very highest risk patients. If you look down further, when physicians were asked would they prescribe such an indication, look in the lower right-hand panel. What you can see there is that there's general agreement that treatment is going to be needed for these patients. What about the question, would they pay for it? We did a survey looking at what disease modifications exist and what are the prices that would be paid. One of the things when we showed this before is people have said, "Well, these are all orphan indications." In fact, I wanna highlight for you the Alnylam medication on the far right. This is an indication for a patient population of 290,000, almost 300,000 patients, a very large patient population. What it shows is that the payers will pay easily up to a $365,000 median payment, which would be across all of these groups. What's also interesting is this was about a 20% penetration into the patients that have a prevalence with this. Disease-modifying therapies can command a high price, payers will pay it, and you can get good penetration into the disease market. What does that mean for us? What it means for us is that a patient that has CKD4, what we just released earlier this year, where there is about 1 million of these patients. If we had a 20% penetration with a 5-year ramp, we would have somewhere around 200,000 patients per year in a patient population that would readily accept an intervention that even had side effects. If we go to the 3B, what you can see is that we've decreased the penetration. We would predict in these patients that fewer would accept it. We still know that a high percentage of them would go forward. Leaving us is a TAM, an addressable market in the neighborhood of 450,000, assuming the information that I just shared with you. What does that mean for the payer? It means for the payer that we probably have the ability to achieve one of our goals, and that is, reduce the cost to the healthcare system. The healthcare system currently pays about $93,000, $100,000 per patient per year. Average lifetime on dialysis is about five years. The costs add up very, very quickly to close to over $2 million, particularly if you have private payer. What is the technology? To the point, where are we going? Our technology is a cell-based therapy. It's an autologous cell therapy. We start with a biopsy, a simple biopsy, where thousands of these are done routinely in the U.S. every single year. What we do is it's shipped to our manufacturing plant, where our proprietary methods allow us to identify the cells which are responsible for the healing of the kidney. Our manufacturing process allows us to be successful in 95% of the cases. 95% of the biopsies we receive, we can make five to 10 products. The process takes about 12 weeks, and we can administer it in a minimally invasive conscious sedation approach, outpatient. The injection itself takes about two minutes. It's delivered with a non-cutting needle, and the process is shown to be safer than a standard biopsy. What is it composed of? It's composed of 3 key cell types. The mechanism of action has been worked out in four different animal models. We identified these three cell types, and what we demonstrated, and you see in the panel in the upper right, is that when these cells are labeled and injected into the kidney cortex, they rapidly migrate in a 24-hour period throughout the kidney. Where do they go? What do they do when they go there? Shown in the lower panels is the histologic assessment, and what it shows is the labeled cells in blue. The cells will go to damaged glomeruli, damaged tubules, and areas within the intertubular, internephron space to reduce inflammation and fibrosis, and that's shown by the blue labels. This has been shown repeatedly then as a mechanism for insinuation and release of the cytokines needed to rejuvenate and repair and restore the kidney. What's illustrated here, and we published at the end of last year more information about the mechanism of action. What we showed is that the nephrogenic or the protective potential that our product has referred here to as this Selected Renal Cells actually underlie the ability of the kidney to restore and repair itself. You look on the right, this gets very revealing of how it's working. The control is shown in the upper panel, shows normal glomeruli. In the lower panel shows the tubules or the parts of the nephron. The diabetic kidney disease, what you see in blue, that shows fibrosis and areas of inflammation. We injected REACT into that architecture. You see the tubular ectasia and the protein casts in the lower. What you'll see on the far right is what the kidneys look like after the REACT had been injected. What you can see is the glomeruli have healed. There is reduced fibrosis. You don't see the blue. What you also see is the tubules are not ectatic and filled with protein. There is a restorative, regenerative potential here that we are delivering to animals that otherwise would die if they'd not received REACT. What's our mechanism? Our mechanism is one of an integrated cellular integration into a kidney where they remain for up to 6 months. This is a normal half-life for these cells. In that space, they release cytokines, and they change the fibrosis and inflammation, and they restore kidney function. What does that look like? How are we bringing this to patients now to be able to impact them? As I shared with you, we have a phase 3 program, which is actively enrolling in the U.S. trial. In the rest of the world, we will be launching that in the second quarter of this year. Our phase 3 programs, the 003 trial, which was for CKD4, we just released that trial results. That's been completed. The REGEN-015 trial is actively enrolling, what we plan to do is report throughout this year another small trial that we've run in patients that have chronic kidney disease for another cause called CAKUT or congenital anomalies of the kidney and urinary tract. I wanna share with you real quickly some of the data to show why we believe that this is going to work and have impact and translate into the clinics. This is a phase 2 trial in which we took 80 patients that had diabetic kidney disease, 20 to 50 mL. These were the late stage high-risk patients. We randomized these into one of two cohorts. Either they received their REACT, the biopsy, and the product made and were injected immediately after enrollment, or they remained on standard of care. They were used then for one year as a concurrent control on best standard of care and then crossed over and received their injections in the biopsied kidney, two injections six months apart, just like the active. What this showed, and what's very important here, is to see, compare and contrast what I showed you previously with the SGLT2, today's best medications versus this, shows the eGFR spread over time. The line at the bottom is the same as the gray line I showed before. It is the standard decline on best standard of care. This is showing a 3.5-4 mL per minute per year decline. What the upper line, the blue line shows is what happens with REACT. Same thing we see in the clinics as we saw in the animals. The first injection, we can see that the kidney function slightly increases. By the second injection, we see that it actually continues to go up. By two years after the injection, we're seeing the kidney function plateau. Very long, durable effect that's not been seen previously with other forms of medication. What we've also done, and I wanna share real quickly here with you some of the details that we had that we just published yesterday, is in these very severely affected patients that were on the doorstep of death or dialysis. It was a single-arm trial. In a single-arm trial, what we did is we had a run-in. There was no standard of care. These patients, if they were not treated, were to go on to dialysis or choose death. In this single-arm trial, what we did is we did the same things we did before, biopsy in the kidney and then two doses to the same kidney that was biopsied, followed then for out to two years. What this graph shows, particularly the one on the left, it's very, very revealing. Again, notice on these patients on the doorstep of dialysis and death, we've actually stabilized their kidney function. What's interesting, though, is that it's still very progressive. As we reported there, seven of 10 patients actually had a 30% increase in dialysis-free living. What does that mean? 16 months of life was added to these patients. What's also very exciting here is that two of 10 patients have yet to go on to dialysis two years after injection. These were patients that were told they will go on to death or dialysis within a few days to weeks, now who have had two years of life, dialysis-free living added to that. Very impactful, very relevant, and a very exciting outcome. For our registration, our registrational package is being run on two independent trials. I've talked through it. It's a one-to-one randomized controlled blinded sham injection run in the U.S. and in Europe. This is being done actively now, and we look forward to this leading to the registration. Both EMA and FDA have agreed to the design. The endpoint is a time to event trial with 40% reduction in eGFR, death or dialysis, and death can be due to cardiovascular or to renal. We look forward to sharing that with you. Ultimately, as I get toward the end, what I hope you're seeing is that the REACT registrational program is setting us up not only to make a transformational change to medicine, but also to make a very big change to the healthcare system itself with the intervention with payers where they can actually win. In addition to that, we have to manufacture what we have got, and we've got a very aggressive manufacturing process. We want to be the lowest priced cell therapy, having the biggest price or biggest impact that we can for that price. What we've currently reported is that it costs about $100,000. It's a relatively cheap cell therapy. We've got plans to reduce that by 50% by the time we go to commercial. There's a real value proposition here for the healthcare system as well as the payers. Lastly, what I'd like to do here real quickly, as with our time is highlight our board. We've got a fantastic board with extensive leadership in the area of finance through Pablo, our Chairman. The insights that are bought by Jennifer Fox and James Coulston are all very, very important on the finance side. We've also got company builders, people like Bill Doyle, John Maraganore, all have developed the same kind of transforming therapy as we have here. In addition to that, we've got people who have run companies and executed them, including Bill, Alan M. Lotvin, people that have developed medicines such as Uma Sinha and Brian Pereira. It's a very extensive and well-studied and understanding board. With that, what I'd like to do is just remind you, I do believe that this is a high value, good return for you as an investor. This is where you're going to see medicine transformed, and we're gonna have a major impact on healthcare if we achieve our goal. With that, I'd like to thank you. I'll turn it over to you. Yeah. Thank you very much. We can move to Q&A at this time. We'd like to welcome a few other members of the ProKidney team is up on the stage. Please come. Alan. Yeah. You can introduce them or you want me to? Please go ahead. Yeah. I'd like to introduce our Chairman, Pablo Legorreta. He'll be joining us. Chief Financial Officer, James Coulston, and our Head of Clinical Development Worldwide, Global Head, I'm sorry, Clinical Operations, Ashley Johns. With that. Thank you very much. For anyone who'd like to ask a question, please just raise your hand and we can have the microphone brought over. In the interim, I can kick us off with a question here about how the enrollment and the registration, the first registrational trial is going. How have you seen momentum in 2022 and over the course of 23? Yes. Our, we're continuing to progress as we have anticipated. I'm gonna ask Ash to give further insight, but we are, as we have guided, on a path towards interim results in end of 2024. Tim essentially covered it. We are on target with our projections for our interim analysis in 2024. Enrollment is going as planned. Excellent. Those results you shared about 003 and the potential to expand into that later stage population, does that impact the registrational trial at all? Is there any anticipation of including those patients? No, that's a good question. The. That was done for us to see how far we could go with this product, with this really transformative medication. What it was is to give us an idea. This is a very friable, very labile, very sensitive patient population. We've seen no product-related adverse events. If something was going to show up, it would have shown up in that patient population. There were several things that were a benefit for us. One, it gave us confidence. The same biology is being seen in a patient population that has very little kidney function left. That was exciting. It also is a very strong indicator for the regulators, for physicians, for patients, that the product itself is safe and tolerable. It was quite important to us that we ran that more as a test of the basic biology and the safety. We anticipate that it will be a line extension eventually, and that we'll be able to migrate into that, and it's a very important patient population from the payer's perspective. They see those patients. They're gonna start very soon writing $100 thousand dollar checks. They see this as a prevention as being a very valuable potential product. Absolutely. Thank you for sharing. I know that you're enrolling across the U.S., Canada, Europe. Is that right? Yeah. How's the split of trial sites, and how do you think about enrollment or are those phased at all in terms of time to enroll across those markets? Go ahead. I can jump in on that one. The first registrational study that we launched last year, REGEN-006, is primarily conducted here in the United States. There are six other countries that are participating in that study. Again, there's less sites overseas. We are again anticipating that most of the enrollment will come from here in the United States. Our second study, REGEN-016, actually has a really good mix across three regions. Latin America, North America is excluded in that study. It is in 006, Europe and Asia- Pac will also be included in 016. I think that's important to remember. 006 is truly global, all four regions. 016 is everywhere but the United States. Thank you. Very helpful. Turn to the audience for a minute, see if anyone's got questions. I know you mentioned the investments, from a manufacturing standpoint. Do you envision those post readout of phase 3 data? Are you focused right now first just on that registrational trial? Good question. James, I'm gonna turn that to you. Very good question. That's a regular debate, so welcome to the discussion on that. Can you repeat the question? Yeah, absolutely. It's more so around the timing of the investments to kinda streamline and reduce the cost on the manufacturing side. Sure. I think, you know, we have the opportunity to manufacture on our own or perhaps, you know, engage with the CDMO. It could perhaps be a hybrid approach in order to minimize the amount of cash that we have at risk, and also to maintain commercial flexibility. Okay, great. Thank you. I think, I'll do one more check on the iPad here, but, that may be all we have from the Q&A today. Oh, please. Yeah. Yeah. I guess just on the sham control arm. Can you elaborate on that since you have to do the biopsy and get the cells? With the new control arm- Yeah. what exactly goes on and... That's a good question. That was a extensive discussion, both with the EMA as well as the FDA. Our sham procedure, and I'll let Ash give some details here in a minute, but our sham procedure is just that. It is a sham. What the patient will have is a conscious sedation. They will have a nick in their skin at the time of what they would've received as the biopsy, and then they'll have another nick over the kidney of each side at the appropriate time. That we know, because our patients are very high risk for kidney failure, there'll be no biopsy taken in the sham at the phase 3. There will be the anesthesia. They will think that they've gone through the process. We will be, and this is important, we will be allowing those patients at the end of the study to be able to enroll and receive product, but they will not get, any biopsy. Ash, you wanna- Yeah. I'll expand on that just a little bit. It's important to note that in the registrational studies, the standard of care is equal in both arms. Everyone is going to have optimized standard of care. The only difference is truly receiving REACT to undergoing those procedures. Mm-hmm. In the sham arm, it is all scripted. They are going to undergo everything except actual manipulation of that kidney. They're gonna have the sedation, they're gonna hear a biopsy click of the procedure biopsy gun. They're gonna hear the investigator in the room talking. They're gonna hear the study coordinator in the room talking. They're gonna really and truly think that they've had this procedure. They'll leave with a Band-Aid on their back. Again, if they, if they go rip that off, they'll think that they still had something with that tiny skin nick. But again, it's gonna be simulated as close as possible, and we do that through scripts and intensive training of these proceduralists. No, that's helpful. Thanks so much. Maybe just a couple quick ones. The number of cells, you know, vis-a-vis like you've iterated for 18 years. Would you just summarize sort of how you got to the sort of? Right. What is the number of cells that's sort of optimal? Sure. We use an allometric scaling. The size of the kidney is used to establish how big it is. The size it is then determines the dose, just like you would in any other dosing regimen. We use 3 million cells per 100 gram with that. What you're gonna end up with is depending on what the size the kidney is, will depend on the number of cells. The number of cells within a given volume is also established. We can very quickly then calculate exactly what a dose is for that patient. Each patient is customized, if you will, or each patient's dose is set for them specifically. It is this allometric scaling procedure which we've used. One last point, 'cause this is an important one, the consistency that we have seen, this same exact scaling metric has been used in 4 different animal models and in every single clinical trial that we have conducted to date. There's high consistency for what we have seen. Tim, maybe just to add, how much patients are receiving. In our phase 2, the 80 patients got between 4 and 8 CCs, right? Right. It was about 400 million-800 million cells. Right. -roughly. Yeah. The vast majority of patients got towards the high end, right? No, they actually were toward the lower end. Okay. Yeah. Yeah. Yeah. It was between 4 and 8 CCs, depending on the size of the kidney. Yeah. Go ahead. $400 million. Yeah. In that neighborhood. Again, it's gonna vary depending on the patient's size of their kidney. Yeah? Yeah. Be happy to take any other questions at this time. Pending those, I'll turn it back over to Tim for closing remarks. Yeah. Thank you all for participating in this. We're very excited about what we're bringing forward. We realize it's something different than what many of you have seen in the past. The high safety, the high effect size, and the ability to drive down our costs, we believe is going to benefit the patient, the payer will have something, the physician, and most importantly, all of you as investors putting your risk and your capital to work with us, we really believe that we can make a difference for you. Anyway, thank you all.