Announcing the business combination of Social Capital Suvretta Holdings Corp. III and ProKidney LP. Joining us on the call are Chamath Palihapitiya, Chairman and Chief Executive Officer of Social Capital Suvretta Holdings Corp. III and Founder and Chief Executive Officer at Social Capital; Kishen Mehta, President of Social Capital Suvretta Holdings Corp. III and Portfolio Manager of the Averill strategy at Suvretta Capital Management; Pablo Legorreta, Founder of Royalty Pharma and Chairman of the ProKidney Board; and Tim Bertram, Chief Executive Officer of ProKidney. We would first like to remind everyone that this call contains forward-looking statements, including, but not limited to, Social Capital Suvretta Holdings Corp. III's and ProKidney's expectations or predictions of financial and business performance and conditions, the timing of development milestones, competitive and industry outlook, and the timing and completion of the transaction.
Forward-looking statements are inherently subject to risks, uncertainties, and assumptions, and they are not guarantees of performance. We encourage you to read the press release issued today, the accompanying presentation, and Social Capital Suvretta Holdings Corp. III's public filings with the SEC for a discussion of the risks that can affect the transaction, Social Capital Suvretta Holdings Corp. III's and ProKidney's businesses, and the outlook of the combined company. Social Capital Suvretta Holdings Corp. III and ProKidney are under no obligation and expressly disclaim any obligation to update, alter, or otherwise revise any forward-looking statements, whether as a result of new information, future events, or otherwise, except as required by law. This conference call is for informational purposes only and shall not constitute an offer to buy any securities or a solicitation of any vote in any jurisdiction pursuant to the proposed business combination or otherwise.
Nor shall there be any sale of securities in any jurisdiction in which the offer, solicitation, or sale would be unlawful prior to the registration or qualification under the securities law of any such jurisdiction. With that, I'll turn the call over to Chamath Palihapitiya.
Welcome, everybody, to the merger of DNAC and ProKidney. Thank you for taking the time to learn about this company and this transaction. Before we go into any further detail, what I would really like to do is introduce my partner in this, Pablo Legorreta. Pablo is the Founder and CEO of Royalty Pharma and is the largest shareholder and Chairman of ProKidney. Before we really talk about the company, I'd love for everybody to hear his perspectives, not only on this transaction, but also on the space and what he thinks about the long-term commercial opportunity of providing a really meaningful solution for chronic kidney disease.
Thanks, Chamath. Hello, I'm Pablo Legorreta, Founder and CEO of Royalty Pharma, as well as Chairman and shareholder of ProKidney. Given the challenging environment we're all living in, we're particularly appreciative of the time you're spending to get to know ProKidney. I will begin by briefly providing a bit of background on myself and the 25 years of experience I have gained in funding innovation in life sciences through Royalty Pharma and building biotech companies like ProKidney as a private investor. Since I founded Royalty Pharma in 1996, we have pioneered the life sciences royalty market and have been at the forefront of developing royalties as an asset class. The idea behind Royalty Pharma was simple: Innovation has been the driving force behind the profound transformation of the life sciences R&D ecosystem.
Consistent and growing medical research funding over many decades by world governments and more recently by disease-specific research foundations led to a better understanding of human biology, transformed drug discovery, and, importantly, launched the vibrant biotechnology industry. The United States government, through the National Institutes of Health, funds medical research by providing over $50 billion in grants to scientists at academic institutions and research hospitals. This consistent funding over many decades has resulted in an enormous number of discoveries and patents, as well as royalties owned by these institutions. How does Royalty Pharma fit in and, in fact, help accelerate the innovation that takes place in the R&D ecosystem? We fund innovation both directly and indirectly. Directly, when we partner with companies to co-fund late-stage clinical trials and new product launches in exchange for future royalties.
Indirectly, we acquire existing royalties from universities, research hospitals, foundations, and inventors. As a business, Royalty Pharma captures and offers investors the best attributes of biopharma without exposure to the common industry challenges. We collect royalties on many of the most attractive biopharma products, which are marketed by the top biopharma companies. The royalties we own allow us to share in the top line, the sales of biopharma products. Importantly, from a top-line revenue perspective, we're no different from any biopharma company. While we benefit from strong IP protection, as well as the product upside often derived from new indications, at the same time, we have no or substantially lower exposure to many common industry challenges, like early-stage development risk, therapeutic class constraints, high research and development costs, and high fixed manufacturing and marketing costs.
This results in Royalty Pharma's unusually high EBITDA margin of over 90% and net margin of over 70%. Historically, we have been able to consistently grow at double digits, both our top line and bottom line. For more than two decades, we have been able to compound growth. When compared to biopharma companies, our growth dynamics stand out on: one, magnitude of growth, which is superior to most companies; two, diversity of growth, which makes our growth more consistent and predictable because it is less reliant on pure products, unlike most companies; three, duration of growth, given the very long IP duration of our portfolio, twice as long as many large pharmas. We took Royalty Pharma public in June 2020, and we trade on Nasdaq with the ticker RPRX.
Royalty Pharma's core focus is to provide capital to those at the forefront of discovering life-saving therapies and enable institutions to reinvest capital back into the biopharma ecosystem to accelerate future innovation. This is a powerful and enduring value proposition that is necessary for the success of innovators in life sciences. Turning over to ProKidney, I have had a personal interest in therapies that have the potential to improve long-term outcomes in people with chronic kidney disease (CKD) because my son was born with urinary reflux. I became aware of the cutting-edge science behind ProKidney's REACT because at Boston Children's Hospital, where my son had surgery shortly after birth, a team led by Anthony Atala did the basic early research behind ProKidney cell therapy. In 2014, I was approached by Anthony Atala and Tim Bertram, who asked if I would be interested in an investment to fund REACT.
At the time, REACT had not yet started human clinical trials, so I declined. By 2017, my son's renal function was declining, and around that time, inRegen, ProKidney's predecessor, had concluded a Phase I trial in diabetic CKD patients. I reached out to Tim and asked if they could consider running a clinical trial in patients with impaired kidney function caused by urinary conditions, not diabetes. inRegen and I agreed to collaborate and split the cost of the trial, about $3 million, on a 50/50 basis. I worked with Tim and the nephrology teams at Children's Hospital of Philadelphia and Mount Sinai to design a trial. We filed it with the FDA. The FDA approved the trial, and I went back to inRegen to discuss the launch of the trial. inRegen declined.
I offered to pay 100% of the cost of the trial. Tim indicated that the owner of inRegen had become very negative about biopharma, given the incoming Trump administration and its negative position on the pharma industry. I pushed back with no success, and eventually, they asked if I would be willing to acquire the company. I said I would at cost, indicating I would not be willing to pay a premium. I reached out to Carlos Slim and his family, whom I knew well, who had expressed an interest in kidney research, given a genetic predisposition to kidney issues in the Slim family. He said, "If you ever see something interesting in kidney, give me a call." We partnered and acquired the company and changed its name to ProKidney.
When we acquired the company, they were launching a 40-patient Phase II trial in diabetics with Stage 3 and Stage 4 CKD. I felt uncomfortable investing in a rather small trial that I felt could yield inconclusive data. I asked Tim to check with statisticians, and based on their feedback, we decided to double the size of the trial to 80 patients and make it randomized, multicenter, and to follow up with patients for much longer, up to 2 years after being treated with REACT, to get a better feel for the duration of clinical benefits. We ran the trial, an 80-patient trial that was randomized 1:1 and ran it in 15 hospitals. That allowed us to randomly create an active cohort of about 40 patients that had been injected with REACT, their own progenitor cells, and started to improve their kidney function.
Another 40 patients were enrolled in a deferred cohort and were not treated for a year. These patients were maintained on the best standard of care and followed for 12 months before being offered the possibility to cross over and be injected. The superior design created two groups of around 40 patients each with similar characteristics: one group that was treated and improved, and another that was not treated for a year and continued to decline. This design then allowed us to measure the magnitude of difference in renal function between the two groups, as well as the duration of benefit. Many Phase I and Phase II companies have data from smaller single-arm trials that were run in a single or a few centers, and the data rarely exceed a year of follow-up.
ProKidney has generated unprecedented clinical data from a randomized trial that enrolled 81 patients from 15 hospitals, and we have up to 24 months of follow-up data. This is somewhat rare and should meaningfully reduce the remaining clinical development risk. In a disease in which kidney function progressively declines and patients inevitably reach dialysis, the stabilization of kidney function would be enough for REACT to achieve the status of a disease-modifying blockbuster product, likely making it a widely successful product from a patient uptake and commercial perspective. Our data to date, unprecedented in CKD, appear to meaningfully improve renal function in many patients, an improvement that has been sustained for up to 24 months. We are seeing improvements in: 1) gaining renal function; 2) stabilization to a slight decline in albuminuria or proteinuria; and 3) improvements in other CKD comorbidities such as anemia and bone and mineral dysfunction.
Importantly, REACT's clinical data impacts a wide range of a patient's clinical parameters because it has the potential to repair the organ, in contrast to most other products that impact only one clinical parameter. Notably, ProKidney's REACT was awarded the coveted RMAT designation by the FDA, the equivalent of breakthrough designation for small molecules and biologics, which materially de-risks the remaining clinical development and FDA approval process. To achieve this result, ProKidney shareholders, the Slim Family and I, have supported the company, investing around $200 million to date. ProKidney has also benefited from an additional $200 million that was invested before the existing shareholders, the Slim Family and I, acquired the company. This capital was invested in the science and in the development of the manufacturing process of the cell admix and the delivery of the product safely into the kidney with a minimally invasive procedure.
Existing shareholders, the Slim Family and I, are also committed to investing an additional $50 million in the PIPE. Finally, if approved, ProKidney's REACT will address one of the largest unmet medical needs in human health, potentially delaying dialysis, the medical treatment that represents the number one category of expenditure by most healthcare systems. Furthermore, from a pharmacoeconomic perspective, it is extremely rare for a new treatment to have the potential to reduce existing costs already borne by healthcare systems around the world. In fact, the launch of the vast majority of novel disease-modifying medicines, many that treat rare diseases afflicting small patient populations—many of which I know well since we have invested in them through Royalty Pharma—generally adds significant cost to already stretched healthcare budgets.
What is so unique and exciting about ProKidney's REACT is its ability to benefit patients by delaying dialysis while reducing significant costs that are already in the system. Thank you. Back to you, Chamath.
Thanks, Pablo. Let's jump in. I think it's important, starting on page 4, to really understand what we're dealing with. In most cases in biotech currently, we don't really get the chance to work on large disease categories, and there are a lot of reasons why that is. Without belaboring them, the point here is that chronic kidney disease is a condition with a very large patient population. In fact, if you start looking on page 5, what you can see is that the chronic kidney disease market is really quite substantial. Unfortunately, in the United States, as of 2020, approximately 38.5 million Americans suffered from the disease. When you include Western Europe, that population almost doubles to almost 75 million total people.
Over the course of the next two decades, what we see just in the United States and Western Europe is that this disease is estimated to affect more than 90 million people by 2040. When you deal with population sizes that big, the thing that we can also expect is that an enormous amount of money is spent treating CKD all around the world. On page 7, what we've done is we've broken out the United States population, and we've started to look at the actual costs. Within Medicare, there is some transparency that they give us in terms of how much they spend in supporting this disease. The answer is that an enormous amount of money is spent to support these 38.5 million people.
Just within Medicare, around $80 billion a year is spent on chronic kidney disease. Now, that's unfortunately just the beginning of this disease burden, because at the end of chronic kidney disease, when your kidneys have effectively failed, you are then put on end-stage renal disease or dialysis. That is yet another $50 billion that is spent. When you add these two things together, chronic kidney disease begins a journey that costs Americans around $130 billion a year just in public insurance. If you then extrapolate that to include the cost of CKD and end-stage renal failure for private insurers, the costs increase between 2x and 4x. What that means is on a yearly basis in America, we spend somewhere between a quarter of a trillion dollars and half a trillion dollars a year dealing with this disease.
If you take a big step back, the real thing that surprised me is that CKD has no known cure, and that the current standard of care merely slows down your expected eventual loss of kidney function. If you're an individual, and many of us know these people—in fact, in my own family, my father suffered from chronic kidney disease brought on by diabetes. He then spent 10 years on dialysis. Unfortunately, he passed away six years ago. It's a disease that we all understand as a slow-motion train wreck in many ways. Essentially, what happens is patients continue to slowly lose kidney function on whatever existing therapies exist. Despite the fact that these therapies are not that efficacious, those therapies still exhibit multi-million dollars' worth of sales.
In fact, what you can see here on this slide on page 9 is essentially the performance, both physiologically and financially, of the three most prevalent drugs that are prescribed for patients suffering from CKD. I think this is a good opportunity to reintroduce Pablo and have him talk to you about his view of these drugs from the context of Royalty Pharma when he underwrote one of these drugs and bought one of these royalties.
Thank you, Chamath. What we see here is the clinical data from three large, well-run trials on SGLT2s. This is interesting for me because at Royalty Pharma, over the last 10 years or so, we have invested close to $2 billion in patients with CKD. We actually invested close to $1 billion in DPP-4 inhibitors, which are approved and became a $10 billion-plus category. Drugs like Januvia, Janumet from Merck, Onglyza, and Tradjenta from Lilly are used to treat CKD patients. What we see here are SGLT2s. At Royalty Pharma, we actually, at some point many years ago, considered funding the phase III trial on canagliflozin, the drug on the left. We had discussions with the developer, J&J. It did not happen, but eventually we did invest in dapagliflozin, and today we collect a royalty on dapagliflozin.
These are drugs I'm very familiar with. What's interesting to note here is that in each of these cases, you have placebo-controlled trials with about 4,000-7,000 patients, depending on the trial. You can see that the patients have the very typical decline that you see in stage 3, 4 CKD patients, where they're losing between 8 and 10 points of function per year. That's the gray lines you see in each of these graphs. These patients continue to decline over time. What you then see is the effect of the SGLT2s. When patients take these drugs, what we can see here is that the slopes of decline are attenuated a bit.
It is between 1 mL and 2 mL, this is milliliters per minute, of eGFR over a 24-month period, highly beneficial for these patients. It delays dialysis a little bit, but this is the best that today's best drugs can do. Also noteworthy is the fact that these drugs are all approved, generating significant sales and are forecasted to reach $10 billion+ in sales by the middle of this decade. It's important also to keep these drugs in mind because when we look at the effect of ProKidney's REACT, it is obviously a more significant improvement in function, stability to actually a gain in kidney function versus an attenuation of the loss of kidney function. Thank you. Back to you, Chamath.
Great. Thanks, Pablo. If you take a big step back, knowing that these drugs are not that effective, the real opportunity for us is to answer the holy grail question in medicine, which is: How can you find a solution that is ultimately disease-modifying? The economic reason for doing that sits in a very complementary way with the human and ethical reason, obviously, which is that economically, there are enormous payoffs. On page 11, what you can see is just a study of six very meaningful breakthroughs in medicine over the last number of years. In each of these cases, what we see are drugs that have been proven to be disease-modifying in a very conclusive way in their own category, whether that's cystic fibrosis or SMA, Graves' disease, et cetera.
In all of these cases, what's interesting to note is that by being disease modifying, two things happen. The first is that you have these really large competitive moats based on how unique you are to build a large and very predictable revenue stream. The second is that because of your uniqueness, you also tend to get an enormous amount of pricing power that you inherit. This is a quite unique relationship that happens specifically in this class of drug. The opportunity for us was to diligence ProKidney and to try to figure out whether their early data was directionally trending towards one of these very unique and special disease-modifying solutions for, again, what is an enormously large disease population.
Because if we could show that their solution, which is called REACT, is not just stopping the progression of CKD, but also drives meaningful improvement, and that we could see that scaling into a phase III trial and hopefully an eventual FDA approval, it really would be a first of its kind and quite a revolution in science. Starting on page 13, what we can start to do now is give you a very high-level readout of some of the clinical data that allowed us to really get comfortable, excited, and then eventually underwrite this deal. To do that, I'd like to introduce Kishen Mehta, who is my partner in the Social Capital Suvretta Biotech SPAC business, and he'll give you a sense of his readout from this perspective.
Thanks, Chamath. As part of our due diligence, we focused on three questions: Is the REACT product safe? Is it clinically active in impacting chronic kidney disease progression? And is the benefit seen to date relevant for patients given the existing standard of care? From a safety perspective, we believe the question has, to a large degree, been answered through large Phase I and Phase II programs, which include multi-year follow-up. The REACT product has been safe and well-tolerated to date, with a profile in line with or even a little better than standard biopsy. As Tim will walk you through later in the presentation, over 100 patients have been treated with REACT, with follow-up in some cases of more than two years post the last cell injection. The cells, once in place, do not seem to cause any reaction in the patient.
The next question was, is it clinically active? Thanks to Pablo, Tim, and the ProKidney team, we have a well-designed Phase II randomized controlled data set, which we believe points to the clinical activity of REACT. As you see in the graph on the side, the REACT-treated or active patients demonstrate a meaningful and statistically significant difference in eGFR trend than the untreated standard of care patients. In addition, active patients demonstrated a compelling change in the slope of their eGFR graph from pretreatment. We view these relative trends on eGFR, which include good long-term follow-up for a Phase II study, as substantial. On the next slide, we see the eGFR trends for the entire treated Phase II population. This included patients randomized to receive REACT upfront and those that crossed over after one year to receive REACT.
When looking at these data, which is the broadest way to evaluate Phase II, the average eGFR trend is upward sloping. While this is an average and not all patients will benefit from the treatment, we do believe that on average, this represents a trend that suggests a potentially multi-year delay in the need for end-stage renal care and dialysis, which gets to the last question. Is the benefit seen to date relevant for patients in light of existing standard of care? We believe that if these data are replicated in Phase III, REACT will represent a major step change in the treatment of advanced CKD and meaningfully impact how the medical community and patients think about kidney disease progression.
As Pablo walked you through previously, regarding SGLT2s, CKD is a slowly progressive disease where the best outcome to date has been to alter the slope of decline and potentially delay the progression to dialysis by a few months or longer. We do not diminish these contributions as we, patients and physicians, agree on the high value of every month of benefit that can be obtained. However, we believe that more can be done to help CKD patients live with better kidney function and will look to the Phase III REACT data to confirm the work done to date. With that, I would like to turn it back over to Chamath, who will walk you through the revenue opportunity in more detail.
Thanks, Kishan. As Kishan said, this data starts to show this really disruptive ability to not just slow the progression of the disease, but in many cases to improve kidney function, even in an all-comers kind of situation. What we wanted to do, though, was take a step back and say, "Well, if this disease-modifying capability is proven in a phase III clinical trial, how would we size the population? How would we think about an initial go-to-market? Who would be the patients that would be the first at the front of the line to be able to use this solution?" The way that we thought about that was in the following way. As we talked about earlier, there are about 38.5 million Americans with CKD, about 15% of the entire United States adult population.
Of that, we sub-segmented to individuals specifically with CKD in stages 3 and 4, and from that, we further sub-segmented to those who suffer from CKD in stages 3 and 4, specifically because of diabetes or hypertension. We think that ultimately that is the initial population pool. Within that, there are about 8.3 million people who suffer from CKD because of diabetes and 5.1 million people who suffer from it because of hypertension. We believe that within that diabetic population, and specifically if you have an eGFR between 20 and 50, that is likely where the most value exists initially for ProKidney and REACT. What does that 4.4 million-person population represent in terms of potential long-term revenue?
Well, one way to think about it is to sensitize these 4.4 million people for every 1% of that market that we acquire. That is to say, around 44,000 patients. If you think about the pricing power that we would have if we are disease-modifying, one way to think about the revenue potential is by looking at those other six drugs that we looked at previously. Again, just to remind you, in those six examples, when you had a disease-modifying solution, not only did you have the ability to have very little competition, you also had tremendous pricing power. In those six examples, the median price was $360,000 per patient.
Now, if we apply that same metric here as a thought experiment, what that would mean is that for every 1% of the population we acquire at that same median price point, that would result in around $16 billion of revenue per 1% of the market that we attract. That being said, I think there's a very good argument to be made that it's not clear whether we would have the ability, nor should we price at that upper bound, because it could be deemed relatively arbitrary. We could also consider how much money we save the system because we could make a very good claim that we should be able to capture some percentage of these savings in a value-based care model. This slide on page 17 starts to demonstrate that.
If you think about what happens when somebody gets to the end of chronic kidney disease, as we indicated before, they start dialysis or ESRD. When you do that, if you're on public Medicare, the cost to Medicare is around $100,000 per year, and the average patient is on dialysis for about five years, which means the lower bound of cost is about $500,000. If you're on private insurance, however, the cost can be up to $400,000. Over that same five years, what that means is the cost can be upwards of $2 million.
The point is that if we can actually take CKD patients in stage three and four, stop the progression of that kidney loss, stabilize, and in some cases improve, what we actually do is we have the ability to defray up to $2 million in costs in the system. That again is a different way of backing into how we could price. We think that pricing in the hundreds of thousands could be quite reasonable upon approval. Now, all of that revenue potential and market sensitivity was really focused on the United States. The bigger point is much more important, which is that this is a global disease. Wherever you see large middle classes, large growing GDP, poor eating habits, you have chronic kidney disease, you have diabetes and hypertension, and you have end-stage renal failure.
If we can find a solution that works meaningfully and compellingly in the United States, the obvious markets are not just Western Europe, but also China, Latin America, the Middle East, Japan, et cetera. On page 18, you'll see that when you add up these populations, we're talking about hundreds of millions of people all around the world who could be potential patients of ProKidney and REACT. To summarize our investment thesis and how we came to this conclusion, what does ProKidney represent? It represents a very novel solution to a high-acuity, large global unmet medical need, where the disease population is measured in the hundreds of millions of people. As you will hear, it's a very novel platform with broad potential in kidney disease, which uses your own cells to help heal you.
Third, what you will also hear is that there are some very strong scientific underpinnings. This is 17 years of research and broad phase II clinical trials that have been funded internally by the principals in order to get to this stage. Based on that compelling proof-of-concept phase II data, we were able to receive this very unique designation called RMAT from the FDA, which is essentially a form of breakthrough and fast-track innovation that also gives us the ability for an accelerated approval specifically designed for these kinds of molecular therapies. Then the last thing is that we have a comprehensive plan to achieve the goals that we would need in order to build the capacity to be able to manufacture our REACT solution at scale for our patient population.
The last thing I'll say is that we've also spent a lot of time with the team. You've just heard from Pablo. Pablo is an incredible executive who's had a multi-decade career in identifying very compelling and disruptive solutions in biotechnology, underwriting them from first principles from both a scientific and financial perspective, which he's done at scale and with success. I found it quite compelling that he essentially did that for ProKidney off his own balance sheet and has supported this endeavor for both ethical, societal, and financial reasons for the last many years. You will now meet Tim Bertram, who is the CEO and has really been the pioneer of finding a meaningful solution to CKD.
Tim is an incredible scientist and deeply understands the physiology of the kidney and its mechanism of action. He has been doing this for almost two decades, which is incredible. I think that what we've brought together with ProKidney, Social Capital, and Suvretta is a very good balance of deep science underwriting, deep financial underwriting, and a very credible go-to-market team that has a track record of finding these kinds of compelling solutions. With that, I'd like to introduce Tim Bertram, the CEO of ProKidney, to walk you through the mechanism of action and our clinical trial results and to go into the REACT solution in more meaningful detail.
Thank you, Chamath. REACT is a new generation of disease-modifying treatments for chronic kidney disease. I would like to introduce you to REACT by covering its mechanism of action, clinical and regulatory developments, and how we make REACT. REACT starts with a standard biopsy conducted in an outpatient procedure. In the United States, over 100,000 kidney biopsies are performed each year. Once a biopsy is taken, it is shipped to ProKidney's manufacturing facility in North Carolina, where we use a proprietary process to grow the kidney's progenitor cells from each patient's biopsy. We then select the active cells involved in the normal repair and restorative healing processes of the kidney. Once these cells have been grown and processed, they are formulated into a final product and frozen. Only one biopsy is needed to make 5-10 REACT doses prepared for each patient.
This entire process takes approximately 10 weeks from biopsy to injection. Once the doses have been tested for identity, purity, and potency, they can be shipped frozen to the clinical site for injection. After thawing, the product is injected back into the patient's kidney using a small 25-gauge non-cutting needle. Up to 800 million progenitor cells are injected into the kidney. Injection is a simple procedure done under conscious sedation on an outpatient basis. The injection procedure takes about 45 minutes with recovery from sedation in about 2 hours. The kidney is composed of approximately 26 different cell types. Many of these cells form the nephron, which is the functional unit of the kidney. The nephron is composed of a filtering portion called the glomerulus and a tubular segment that is involved in the metabolic functions of the kidney.
Some cells are involved in the maintenance, repair, and restoration of damage that can be incurred from diseases such as diabetes and hypertension. After more than a decade of research, our scientists were able to identify three cell progenitors that could restore and repair nephrons damaged by disease. These cells were combined to form REACT, a cellular admixture that can reactivate the kidney's natural healing processes. These progenitor cells form the mechanistic basis for the stabilization and improvement of kidney function in chronically diseased kidneys. To understand the mechanism of this repair, we looked to see where the progenitor cells localized after being injected into diseased kidneys. Cells were labeled to allow microscopic visualization. You can see in the images in the lower right, the blue-labeled REACT cells go to damaged regions of the nephron.
When they integrate into the damaged areas of the glomerulus and tubules, they replace the damaged cells and remain there for up to six months, guiding the repair and restoration of the diseased nephrons, downregulating inflammation, and remodeling the scarring process. Once we knew that the three progenitors could repair damaged nephrons, we looked at the potential of REACT to repair other areas of kidney damage. We used four different animal models of chronic kidney disease caused by diabetes, hypertension, and acute-on-chronic injury. If the chronic kidney disease was untreated in these models, the disease progressed to renal failure. When REACT was injected after the animals developed severe chronic kidney disease, we saw that the REACT-treated animals would live while most of the untreated control animals would die of kidney failure.
REACT-treated animals had many structural improvements of the kidney, including repair of damaged nephrons, reduced scarring, reduced inflammation, and multiple functional improvements, including the ability to control blood pressure and maintain phosphorus and calcium metabolism. These effects could be attributed to the repair of the damaged nephron, resulting in restoration of glomerular filtration, tubular metabolism, vitamin D3 production, and release of erythropoietin to control erythroid homeostasis. Let's now consider the effects of REACT in patients with chronic kidney disease caused by type 2 diabetes. CKD can be caused by many diseases, including diabetes, hypertension, and congenital anomalies. ProKidney is currently evaluating REACT in the United States as part of a global phase III trial for chronic kidney disease caused by type 2 diabetes. We are also conducting a phase II trial with patients who have congenital anomalies of the kidney and urinary tract.
For our discussion today, I will focus on ProKidney's lead indication for patients with diabetic kidney disease stages 3 and 4. I would now like to share with you the effects of REACT from the RMCL-002 phase II trial in patients who have diabetic kidney disease stage 3-4 and are at very high risk of progressing to kidney failure. This trial is a multicenter 1:1 randomized study of type 2 diabetic patients with chronic kidney disease stage 3-4 who have lost between 50% and 80% of their kidney function. Function is measured by estimated glomerular filtration rate levels, and eGFR ranges from 20-50 mL/min. 81 patients were enrolled and placed on maximally tolerated standard of care medications, including angiotensin receptor blockers, sodium-glucose cotransporter-2 or SGLT2 inhibitors, and other medications to control their diabetes and hypertension.
The average eGFR for all patients was 33 mL/min, and 40% of the patients in this study had CKD stage 4. After meeting the key entry criteria, a routine biopsy was taken from the kidney, and the patients were randomly assigned to one of two groups. If assigned to an active group, they were injected with two REACT doses 6 months apart in the same kidney that was biopsied. Alternatively, they were assigned to the placebo-controlled cohort that would remain on best standard of care for 1 year. At the end of that one-year standard of care therapy time period, they were crossed over and injected with two doses of REACT 6 months apart in the same kidney that was biopsied. Both patient groups were followed for 2 years after the second injection of REACT.
REACT is demonstrating a robust efficacy and safety profile in this interim analysis of the phase II trial. 50% of REACT-injected patients had improved renal function, of which 80% were projected to never progress to end-stage renal disease. This estimate of risk of progression to kidney failure is based on two independent models evaluating changes in estimated glomerular filtration rate, gender, age, and clinical outcomes based on the rate of kidney function decline. Using the same predictive models that assess the risk of progressing to renal failure, a majority of patients in the placebo-controlled group were projected to progress to end-stage kidney disease, even though they were maintained on maximal standard of care for one year. Other kidney improvements in the REACT-injected patients included reduction of anemia and hyperphosphatemia.
REACT was also shown to have a robust safety profile, and the injection procedure had fewer side effects than a standard biopsy. Kidney function in both cohorts was measured by estimated glomerular filtration rate from screening to the last scheduled follow-up examination available for this interim analysis. In the REACT-treated patients, you can see the improvement in renal function after both REACT injections. REACT-injected patients are observed in the blue line. The average eGFR for the REACT-treated patients improved from 32.8 at injection to over 38 mL/min at the 18-month follow-up. In sharp contrast, patients in the placebo-controlled cohort being maintained on best standard of care, including SGLT2s, had progressively declining kidney function from an average of 32.5 to 28.2 mL/min at the one-year follow-up. The results from the placebo-controlled patients are shown in the purple line.
As can be seen in the gray boxes between the lines, there are substantial differences in the average estimated glomerular filtration rate between the REACT and placebo-controlled patients at each time sampling, beginning at the time of the second injection of REACT and progressing to the last reported follow-up. REACT's effects on kidney function, as measured by estimated glomerular filtration rate, and estimates of kidney damage, seen as protein in the urine and measured by a urine albumin-creatinine ratio (also called UACR), are demonstrated. eGFR is shown in the red and blue lines, and urine protein levels are the numbers placed above the gold bars. At the time of injection, patients had an average estimated glomerular filtration rate of 32.5 mL/min and severe proteinuria of over 300 mg/g as measured by the UACR assay.
As the average eGFR increased over time, the proteinuria stabilized or decreased to an average of under 200 milligrams per gram. This suggests the improved renal function is linked to the effects of REACT on the kidney, including a stabilization or reduction of proteinuria, which is a surrogate marker of kidney damage, such as inflammation and scarring. If we now consider other kidney functions, such as the production of vitamin D3 and erythropoietin, we can see that REACT stabilizes, restores, and may repair comorbidities of diabetic kidney disease, including the anemia and hyperphosphatemia observed commonly in these patients. Patients can be seen to have a progressive decrease in their hemoglobin prior to REACT injection and then a progressive improvement after injection. Similarly, phosphorus can be seen to have a slow but steady increase before REACT injection, followed by a decrease after injection.
These observations are consistent with the mechanism of action for REACT as defined in the animal models. To evaluate the potential of REACT in patients with very severe chronic kidney disease and risk of kidney failure leading to the need for dialysis, ProKidney conducted a study in patients with chronic kidney disease stage 4 having estimated glomerular filtration rates of 15-20 mL/min. This group of patients had an average eGFR of 17.5 mL/min. It is generally considered that patients with an eGFR of 15 mL/min or less are progressing to renal failure and can be referred for dialysis. Notice that these very sick patients also had quite high levels of proteinuria, as shown by UACR levels that were over 2,500 mg/g at the time of injection.
Even with this lower kidney function and extent of kidney damage, REACT reduced the decline of renal function by almost 50%, potentially adding months of dialysis-free living and stabilizing the amount of protein being lost in urine. For over 7 years, ProKidney has evaluated REACT's effect on diabetic patients with chronic kidney disease stages 3 and 4. We have completed over 150 injections. In this time period, we have provided 100% of the REACT doses to each patient, and there have been no product-related adverse events. Adverse events that were observed have been typical for patients suffering from type 2 diabetes mellitus and diabetic kidney disease stages 3 and 4. In these studies, the REACT injection procedure has been shown to have fewer related side effects than a standard kidney biopsy.
This highlights the robust safety profile of REACT, and these significant safety findings have recently been published in the journal Kidney International Reports. Clinical outcomes from this study have been shared with both the Food and Drug Administration and the European Medicines Agency. Based on these results, the Food and Drug Administration awarded ProKidney's REACT the Regenerative Medicine Advanced Therapy, or RMAT, designation. This assignment for cell therapy is equivalent to breakthrough designation awarded for drugs advancing against severe diseases with few other standards of care available. Also, ProKidney has worked with both agencies to define a phase III program. This registrational program will include randomized controlled trials in a patient population at very high risk for end-stage kidney disease that is caused by type 2 diabetes. These trials will be sham-controlled and involve up to 1,500 patients.
Treated patients will have a REACT injection in both kidneys. These patients will be followed for two years and then rolled over into a long-term follow-up study to evaluate the safety and durability in support of premium pricing for this product. We launched the Phase III program in the U.S. in January of this year. We are planning for an interim analysis in 2024, with a commercial launch to follow after regulatory review. During the two-year period while we conduct the blinded, sham-controlled trials in the U.S. and around the world, we will be conducting four other Phase II clinical trials. We plan to progress the current trial in CKD3-4 patients and enroll an open-label extension of the RMCL-002 study to establish long-term characterization of REACT's durability and safety.
We will also complete two other studies: the REGEN-003 trial in late-stage CKD4 patients with estimated glomerular filtration rates of 15-20 mL/min, and the REGEN-004 trial in patients with congenital anomalies of the kidney and urinary tract. Additionally, we will complete enrollment and report results of another trial in diabetic kidney disease patients, which will evaluate the effects of a REACT injection in both kidneys and define REACT redosing based upon eGFR and UACR triggers. We anticipate this last study to be a surrogate for the outcomes we might expect with the phase III program, which is being done by injecting REACT into each kidney. After reviewing interim RMCL-002 clinical trial outcomes, the FDA guided ProKidney to conduct a time-to-event randomized sham-controlled registrational program. The phase III program would be conducted in type 2 diabetic patients with diabetic kidney disease stage 3-4.
The primary endpoint for the program would be a four-component composite evaluating a 40% reduction in estimated glomerular filtration rate, an eGFR of less than 15 mL/min or chronic dialysis, an increased UACR of 30% and greater than 30 mg/g, and mortality caused by kidney or cardiovascular failure. Because RMCL-002 is a randomized controlled trial being conducted in a similar patient population that will be studied in the phase III program, we conducted an ad hoc time-to-event statistical analysis of the RMCL-002 results obtained at this interim analysis. In the Kaplan-Meier graph to the left, placebo-controlled patients receiving the best standard of care for diabetic kidney disease are shown on the black line. These patients are gathering adverse events at a greater rate and more frequently than REACT-treated patients shown in the blue line.
As can be seen in the lower right, REACT reduced the risk of triggering a component of the primary endpoint by 60% in patients with an average eGFR of 33 mL per minute, resulting in a hazard ratio of 0.4 with a low p-value. It is noteworthy to compare the hazard ratio for REACT used in patients at high risk of end-stage renal disease to recently reported SGLT2 used in healthier patients with average eGFRs of 43-56 mL per minute, also using a composite endpoint. ProKidney controls the REACT supply chain from biopsy to injection. To ensure the highest quality product, all manufacturing is conducted in ProKidney manufacturing facilities. ProKidney's bioprocess and quality manufacturing procedures have been developed over the past 15 years using patented processes that have been reviewed by both the FDA and the European Medicines Agency.
Over the past seven years, 100% of REACT doses have been manufactured, shipped, and injected in all REACT clinical trials. ProKidney's manufacturing facilities have been inspected by the European Medicines Agency and considered phase III commercial-ready. We are conducting advanced bioprocess research and development for the manufacturing process to ensure commercial cost of goods supports a robust business model. The manufacturing process starts with a biopsy and ends with an injection into the patient's kidney. The entire process from biopsy to injection takes a total of 10 weeks. 5-10 doses are manufactured from each patient's biopsy. All manufacturing is conducted to the highest quality and regulatory standards to ensure the best product is provided for each patient. Our manufacturing facility has been inspected by regulatory agencies from the U.S. and EU and is approved for phase III and commercial manufacturing of REACT.
ProKidney has a staged manufacturing strategy to ensure we can deliver all products for the Phase III program and be prepared for early commercial launch. In preparation for commercialization and market ramp-up, we are initiating plans for a launch facility that would be production-ready after Phase III registration. Additional plants will be planned and developed after launch to address up to 65,000 patients with CKD per year. Commercial facilities will be designed to optimize the cost of goods and large-scale supply chain efficiencies. Proceeds from this capital raise will be used to support the company through registration. Our current funding requirements include capital for continuing the Phase III program, planned and ongoing Phase II programs, commercial readiness, and capital expenses. Financial needs are approximately $450 million, which will take us to mid-2024 for the interim analysis of the Phase III program.
An upsized capital raise of $700 million will allow for increasing manufacturing capacity and expanding sales and marketing. Thank you for your attention and interest in the ProKidney story. I will now turn it back to Chamath to discuss the transaction overview with you. Chamath?
Thanks, Tim. To summarize, what do we know the problem to be? Well, again, just to recap, 75 million people suffer from CKD and ESRD in the United States and EU. More than 12 million people develop CKD in the United States and Europe every year. What is our goal? Our goal is to find a solution that obviously slows and stabilizes, but ideally reverses the decline of kidney function so that we can delay or prevent dialysis and renal transplantation. Tim and his team have built a solution called REACT, which utilizes this proprietary autologous cell therapy taken from the patient's own kidney. Ultimately, that results in three specific cell types that help promote the regrowth of all kidney function.
What you've heard is that we are building a financing plan and a capital plan that allow us to scale a very large phase III clinical program, monitored very closely, obviously, and in partnership with the FDA and EMA. We have conditional approval potential based on this interim data analysis that could be possible in 2024, but realistically, we're targeting commercial launch in 2025. The goal is to ultimately treat millions of diabetic CKD patients worldwide and meaningfully reduce the number of people on dialysis or who require transplantation each year. Specifically, in terms of the transaction, the pre-money equity value of this business is $1.75 billion. The pro forma equity value is around $2.64 billion with all the capital that comes in. There's up to $250 million in the SPAC's trust account.
There's also a $575 million PIPE that we have raised. Affiliates of DNAC, including myself, have committed approximately $155 million, and existing ProKidney investors have committed at least $50 million. Existing ProKidney equity holders will roll over 100% of existing outstanding equity, and they will hold around 66% of the pro forma equity in the combined company. Around 12% of the pro forma equity will be held by DNAC's sponsors and public shareholders, and 22% of the pro forma equity will be held by the PIPE investors. Lastly, there is an earn-out for ProKidney's existing management and equity holders of 17.5 million shares that will trigger in three installments of 5.8 million share increments at $15, $20, and $25 per share.
Which is to say that as they perform and create equity value for everybody, they will be able to participate in those gains as well. Lastly, as Tim has said, but to reiterate, the point of all of the capital right now is to make sure that we fully fund this phase III trial of REACT, that we can make some early progress in manufacturing and commercial build-out, and have some money as well for some other general corporate purposes, so that on the presumption of a successful phase III trial and approval in 2025 or thereabouts, we can hit the ground running and really bring this solution to as many millions of patients as possible. With that, I would like to thank you for tuning in and your support.