So look, I just was in a meeting earlier today, and I heard there were seven hundred and thirty-five publicly traded biotechnology companies in the United States, right? So what differentiates Protara from any of those? I think, you know, look, I think obviously all of us are in it for the good of patients. All of us are in it because we're profoundly impressed by science and medicine. Our approach at Protara has always been focused on trying to uncover assets, where an application of modern scientific understanding, whether it's assays or even manufacturing or regulatory paths, can sort of breathe new life into previously explored mechanisms of action.
In our world, the program that we'd most love to be able to emulate is thalidomide, which became Revlimid, a $6 billion a year hematological cancer treatment. And with TARA-002, we think we might be pretty close to finding that next Revlimid. A quick note on the pipeline, as you can see here, these are all mid- to late-stage development programs, all of which have been de-risked by data produced previously. In the case of 002, this is a drug that has been used for oncology indications in Japan for almost fifty years. The patient safety database of the predecessor compound in Japan numbers in the tens of thousands. So tens of thousands of oncology patients have been treated successfully with the drug that we are currently interrogating in non-muscle invasive bladder cancer.
In the case of IV Choline, there we have a PK-based endpoint. Again, that's PK-based endpoint for approval of a drug that could ostensibly treat 40,000 patients in the United States alone, and finally, OK-432, the predecessor of TARA-002 in Japan, and I'll get into the backstory a little bit to try and clear the air. That is the standard of care for lymphatic malformations in Japan, where about 500-700 patients, all in the pediatric setting, are treated every year with the exact same compound as 002, and it's been the standard of care in Japan since the mid-1990s.
So we're talking thousands and thousands of patients with known mechanism of action, and where we have conducted primary research to take the understanding of both IV Choline and 002 into the modern setting of immuno-oncology and into the modern setting of liver metabolism. So obviously, NMIBC, if you are in the world of oncology or around the world of oncology, NMIBC has sort of leapt to the forefront of a lot of investors' mind frame with the IPO of CG Oncology earlier this year. We are squarely in that space, but before I talk about how we're in that space, I think it's important to just spend a little bit of time on TARA-002 .
I mentioned TARA-002 was probably the first ever approved immuno-oncology agent utilized in the cancer setting, although at the time in Japan, no one knew it. They just knew that it worked. Basically, TARA-002 is a genetically distinct strain of Strep pyogenes, so a bacteria that drives a TH1-type immune cascade, turbocharging the immune system and activating your host immune system against oncology targets. For us, that's in non-muscle invasive bladder cancer, but for Chugai Pharmaceutical before us, where you know they are still you know distributing OK-432 in Japan, there's approvals that exist to this day in lung, gastric, head, neck, and thyroid cancer. And again, it is the standard of care in lymphatic malformations in Japan as well.
We have worldwide rights, ex Japan, which means we can pursue any indication for any target in any geography outside of Japan. Talked about the mechanism of action. It looks a lot like BCG, which is the standard of care in non-muscle invasive bladder cancer in the front-line setting. BCG is a bacterial therapeutic in the same way that 002 is a bacterial therapeutic, although each of us drive different pattern recognition pathways. In the case of BCG, the underlying bacteria is Mycobacterium bovis. It's a TLR4 activator. What we know about 002, because of that primary modern lens that we've applied to it, is that it's a TLR2 activator.
and so we are generating a lot of the same upregulation of key pro-inflammatory cytokines, but we do it preferentially for TNF-alpha, Interferon-gamma, and IL-12, whereas BCG preferentially upregulates IL-6, which we do as well, not in the same way. So I'm gonna try and get through the NMIBC conversation fairly quickly. We released data in April of 2024, very preliminary three-month data in 16 patients with NMIBC in both the front-line and second-line setting. And there, we're hoping to demonstrate activity, which we did. Now we are generating a dataset of more expansive data in longer-term patients and in a far broader set of patients, and we have guided the street to expect us to release that interim data in the second half of this year at a urology medical conference.
Really quickly on NMIBC, for those of you that don't know, it is the sixth most prevalent cancer in the United States, fourth most prevalent among men. There are 725,000 patients with bladder cancer in the United States. Now, this is why we think about bladder cancer and non-muscle invasive as sort of like an indolent chronic disease that looks like ulcerative colitis, as opposed to something like pancreatic cancer, where you are articulating success in the number of months where there's progression-free survival. Here, the mortality rate of NMIBC is about 10%, but the recurrence rate is about 80% over a three-year timeframe. So you're living with a very refractory disease, that if left untreated, can progress, and so it looks a lot, as I said, like a chronic NMIBC indication.
I’ll summarize the data here by saying this data that we produced in April 2016 in 16 patients, this is the floor of efficacy that we can expect to see out of 002. Because, a, these patients were only treated for three months. Our current ADVANCE-II registrational design study follows these patients for 60 months. They’re given administration, and then at three months, if they are non-complete responders, they are given another induction course, and then they’re given maintenance therapy out to 24 months. So what we see here is that, you know, across a number of different patient types, we’re at about a 43%-50% complete response rate. That’s not competitive in the current environment, where competitors are at about 60%, 65% at a landmark six months.
But these patients here have not benefited from reinduction. Part of our protocol says that non-complete responders who are reinduction eligible would get another induction course of six doses, Q weekly, over six weeks. And what we've seen from competitors with the immunologic agents in this setting is that that reinduction has driven a 54% salvage rate. In the case of CG Oncology and in ImmunityBio, they both had 54% salvage. And what we know about our drug is that because of its kinetics, continued administration of the drug is likely to drive a pretty significant salvage rate, and we'll talk about that in our interim data release at the end of the year. A key point about 002 relative to competitors. It is a very well-tolerated and safe drug.
The majority of all the AEs are Grade 1, and anything better than a grade or higher than a Grade 2 AE was not associated with treatment. You know, in the NMIBC setting, what we're seeing is a migration away from near-term response rates to long-term durability. By the way, that's a fabulous thing for the patients out there who are living with NMIBC or waiting to have an NMIBC recurrence. Durability means longer-term stability of these patients, and our non-clinical work, I won't get into it here, but I'll show you this picture. On the left, you see vehicle. On the right, you see 002.
This is in a well-validated MB49 BCG-unresponsive mouse model, and it's very clear that while it takes some time for the peak therapeutic effect of 002 to kick in, once it does, that effect tends to be durable. And as we think about where we might stack up in the competitive landscape, that durability is something that we are predicting will be a true benefit to us as we look at longer-term data in patients at the end of this year and into next year as well. As we think again about a constant drive towards innovating and differentiating in an increasingly busy field of competitors, one of the things that we want to lean on is: where are we able to do something that competitors can't? So we know that reinduction is an important part of all immunotherapy and NMIBC.
We know that prolonged dosing through maintenance is an important piece of treating these patients and sustaining response rates. But what we can do that none of our competitors can do, and for which we draw along a huge history in Japan, is we can administer our drug systemically. 002 is an inactivated bacteria. All the other viral or bacterial therapeutics in the non-muscle invasive setting are attenuated. It means you can do one systemic administration. For those of you that remember the TB scar, you were only able to do that once, right? TB vaccine is Mycobacterium bovis. It's the same drug that is BCG. We can administer systemically over and over again without driving sepsis, without driving immune cascade or cytokine storm.
So if you think about the urologic setting, where patients are administered drugs through the urethra several times a year, if you could swap out an intravesical transurethral administration of a drug for a systemic intramuscular dose, that could potentially set this setting on its ear. And so as we move into 2025, we've already launched a study of with a priming dose of 002, where we give one systemic dose, and then three weeks later, commence our intravesical administration course. As we learn more and more about how these non-muscle-invasive bladder cancer patients respond to that systemic dose, we will continue to push the boundary of how many systemic doses we can administer versus an intravesical administration. And again, imagine never having to go and administer a drug through the urethra again for non-muscle-invasive bladder. That would be pretty amazing.
When you think about our product as it stacks up against competitors, it's important to remember that 80% of all intravesical drugs are administered in the community setting. That means these are uro-oncology, oncologic surgeons for whom workflow and for whom patient flow matters. If you're over here on the right, which is CG Oncology's drug, that's about a three-hour you know, administration timeframe. Versus us, it's five minutes to reconstitute our drug in saline, and then five minutes through catheter. It's not a cystoscope, it's a catheter, meaning that a nurse can administer this drug, and the doctor just has to pop in and say, "How you doing?" It's like a visit to the dentist. When you're talking about busy surgical practices in the community, that ease of administration is very important.
To summarize, there are a lot of elements about the 002 story that makes us excited for the data that we'll be releasing in December or November of this year. And then as we think about where we stack up as a competitive product. We like that we have no overlapping toxicities with any of the other monotherapy products out there. We can administer systemically, and we're safe, well-tolerated, and easy to administer. So I'm gonna spend a couple of minutes before Q&A on our two rare disease programs. We put two press releases out today, one on each of the two programs. I'm gonna try and get through these quite quickly. IV Choline Chloride, choline is the root substrate for phosphatidylcholine, which is the most ubiquitous phospholipid in the body.
If you are on parenteral nutrition, meaning you receive parenteral support, which is nutrients and fluids exclusively through intravenous means, you do not get choline in your intravenous nutrition diet. And what we know is that for these patients, this is heavily associated with multiple disease sequelae, including liver disease, muscle and bone wasting, neurological dysfunction, and a number of other sequelae. And, again, there's been a huge amount of literature produced that says that for parenteral support patients who do not get choline in their diet, up to 60% of them go on to develop end-stage liver disease. And that's. We're learning more and more about some of the other medical sequelae as well. Here's what's important about IV choline. I'm gonna try and summarize it as quickly as I can.
There are 40,000 patients in the United States who are on long-term parenteral support. We just released data today from a long-term prevalence study that we conducted over two years, looking at up to 700 patients retrospectively and 100 patients prospectively, where we released data that suggests that 78% of patients on parenteral support are choline deficient. So 78% of patients that are just showing up every day, getting their nutrition via an IV line, are deficient in one of the most important phospholipid precursors that exists. And of those, 63% have long-term liver dysfunction, whether that's steatosis, cholestasis, or hepatobiliary injury. So we're releasing a poster at ESPEN today in Europe, in Milan, that details this finding.
But what it says to us is that of the 40,000 patients that are on parenteral support in the United States, about 80% of them are likely to need choline substrate replacement therapy. So here's what I'd like to leave you with, is the FDA has cleared us to run a pivotal study, which we are launching as we speak, in parenteral support patients, 120 patients, where all we have to do for approval is demonstrate increase in serum choline. So again, that's a PK-based endpoint. We don't even have to hit a target. We don't even have to hit a physiologically normal level. All we have to do for approval is demonstrate an increase in serum choline concentrations. And when you give something intravenously, which choline is administered intravenously, it tends to drive an increase in serum of that agent.
So very quickly, phase II work that we did previously suggests that after one dose in parenteral support patients, we bring choline levels back up to physiologic levels. And over on the right, we show that patients versus placebo that receive choline supplementation show a dramatic improvement in steatosis, and that when that treatment is discontinued, they move back to placebo. So again, this is a 40,000 patient addressable market where the approvable endpoint is PK. We have intellectual property to 2041 that's Orange Book listable. And in our view, this is probably, you know, a several hundred million dollar rare disease opportunity for us that, you know, where the, where we believe that the regulatory hurdle is not as hard as it can be for others.
Finally, not very many drugs out there that are not approved are recommended in guidelines, and yet choline is by both the American and the European physician associations for parenteral nutrition. So they're already asking for our drug to be on guidelines before we even have commercialized it. 002 lymphatic malformations. Very quickly, today, we released data from the first cohort of our phase II study, showing that we achieved complete response rates in two pediatric patients after one dose of 002. So a child like this, in our study, two of them are now in this category of complete response after one dose.
What we know, again, this is the standard of care in Japan, and previous phase II work done here in the United States shows that versus just observation, 69% of all kids treated with this drug achieved a complete or substantial response. That's a significant medical benefit for kids that are school-aged and running around with large malformations of the head and neck and perhaps the, you know, other parts of the body. And when you look at specifically these more balloon-like macrocystic lesions, in the data, 84% of patients with that lesion type achieved a complete or substantial response. So with my last sixteen seconds, I want to talk just about where we are from in terms of catalysts. It's a lot to digest.
There are a lot of programs, but the way I would argue is that at our current cash, there are multiple opportunities for value creation across the oncology platform, as well as the rare disease platforms, and multiple catalysts in 2025 and 2026. We have $80 million on the balance sheet, which is enough to carry us into 2026, and just to give a sense of what our capital structure looks like, if you take pre-funded warrants, preferred and common, you're looking at about 30,000 common share equivalents. So again, the story for us is multiple shots on goal, low regulatory hurdles in some, and huge addressable markets in the others. So I apologize, I'm out of time. Happy to take questions. Justine is here. Pat's here. I'm here.
Thank you for attending, and have a great conference. Thank you so much, Jesse, for the great presentation. We really appreciate you being here and the time and effort that went into preparing it.