The largest data set ever generated in lymphatic malformations of all types, generated by the University of Iowa in a 27-center, investigator-led study that looked at over 550 patients. As we move into registration with FDA, in addition to the study that we're undertaking and where we'll be releasing data before the end of the year, we'll be able to utilize that data set and our experience in Japan to put together a registration package that we hope will be enough to drive towards an accelerated approval. Very quickly, we have received the majority of investor interest in our NMIBC program. I'll talk again here on kind of what's new. As you all know, we are in the standard sort of BCG-unresponsive single-arm open-label study in CIS patients plus or minus papillary disease. A quick note on our mechanism of action.
We get a lot of questions, you know, are you basically a BCG 2.0? What we tend to say is, we are like a cousin to BCG, but we are not exactly like BCG. BCG is a TLR4 activator. TARA-002 is a TLR2/NOD2 activator, and so there are some significant differences between us and BCG. We are administered in exactly the same protocol as BCG. We are as easy to utilize as BCG. There's no special handling for TARA-002. There's no thaw time. In fact, from the refrigerator, where we have demonstrated three-year stability at refrigerated temperatures, from refrigerator to catheter is a matter of minutes, and then it's roughly a 15-minute administration time via catheter, not a cystoscope.
The physician doesn't have to be in the room, and that patient, unlike BCG or unlike any of the other immune-mediated therapies that are either approved or under investigation, those patients can get off the table and go home. There's no post-administration protocol, no urine bleaching, no special handling. The adult children of these elderly patients don't have to monitor the parent for BCGosis. As this field moves to approved marketed products, that's the kind of product profile that will drive adoption, assuming that we're through a threshold of efficacy. One other key point that differentiates TARA-002 from BCG is the fact that we upregulate a number of cytokines preferentially that are not as highly upregulated with BCG. Note, specifically TNF-alpha, interferon-gamma, IL-12, those are all known to be significant oncolytic immune-activating cytokines that we preferentially upregulate relative to BCG. One final note, we down-regulate IL-8.
IL-8 is associated with recurrence and is actually upregulated by BCG. That reinforces this notion that there is a market for BCG-refractory patients because BCG itself drives a cytokine pathway that is associated with recurrence. I'll quickly talk about what our strategy is in NMIBC before I move on to the rare disease programs, and talk about when you'll see data from Protara Therapeutics on the NMIBC program. We are currently enrolling and accelerating enrollment in our Advanced II study. This is, again, the standard single-arm open label design that FDA continues to support for the BCG-unresponsive CIS patient population. We will publish interim data in February, in sort of concurrent with a urology-focused medical conference. The data set will be a minimum of 25 BCG-unresponsive patients who are at a minimum six months evaluable.
You'll get six-month data, 12-month data, and a handful of patients that have demonstrated even longer-term durability. That's the next time point that we'll publish data there. In terms of what's new, we have been for some time relaying to our investor community that because we have so many similarities to BCG in terms of administration and the fact that you're not re-educating a staff on administration, we have been looking at the naive setting and in fact have generated data in approximately 31 naive patients. The question there is, do you want to go head-to-head with BCG? I don't. Is there an opportunity to address that sort of earlier line of treatment in a way that presents TARA-002 as an alternative to BCG?
We have been in dialogue with FDA and demonstrated to them via a seven-year claims data analysis from Optum Health that approximately 35% of patients who are BCG eligible do not get BCG either because they can't, don't tolerate, refuse, or are contraindicated. To give a sense of what that looks like, the claims data suggests to us that every year approximately 10,000 to 12,000 patients who are BCG eligible in the United States do not get BCG, and what they get instead is either Gem, chemo, mito, chemo, cisplatin chemo, or Gem dosi. One of the arguments that we would like to make to the FDA, and this is again active dialogue, is can we run a study in a BCG alternative setting in either front-line or second-line patients who can't get, don't tolerate, refuse, or are contraindicated for BCG?
A study design would be a randomized controlled study, and we've asked FDA to allow us to compare to chemo. Again, not to replace BCG, but to replace what patients are given if they don't get or can't get BCG. We'll be able to provide feedback on the FDA's engagement with us before the end of the year, and we'll provide an interim update at the SUO conference in December in our ongoing 31-patient BCG-naive proof of concept study, where the last time we put data out was at AUA in April. Just to give a sense, in those 21 patients, we demonstrated a complete response at any time at the six-month time point of 70+% and a complete response at 12 months of 40+% in that sort of BCG-naive setting.
We'll be able to talk about a regulatory pathway if it exists and that particular patient population's responses in longer term to TARA-002. That's sort of the NMIBC program. I'm going to move through just a reminder that as some of our competitors are moving towards approval and the narrative around the NMIBC opportunity starts to incorporate what are the product characteristics and how those characteristics drive adoption, we'd be remiss if we didn't talk about the profile of TARA-002 in terms of safety in these patients. We've had no treatment-related grade 3 adverse events. The most common reported side effects in our study so far have been related either to the instrumentation of a transurethral administration or flu-like symptoms, which in our mind are indications of the activity of the drug.
Very safe, and again, an incredibly easy administration, and efficacy that to date is either better than or in line with the other products that are in development. This shows the impact of some of the approved products as well as some of the investigational products that we are lumped in with. Incredibly easy administration time. I'm going to move with nine minutes left past our IV Choline Chloride program. Just a quick update on that. IV Choline Chloride is a phospholipid substrate replacement therapy for patients who are on parenteral support.
Patients who are on parenteral support receive all of their nutrition via central line, and as a result of that, undergo a number of metabolic sort of perturbations because if essentially you and I eat food, it goes through first pass metabolism through the small intestine, large intestine, and then the liver, and then eventually makes its way into the bloodstream. For these patients, nutrition is introduced in the bloodstream and it goes backwards. We see a number of different sort of metabolic deficiencies in these patients, and the most notable is IV choline, or rather choline levels. Choline is the precursor to phosphatidylcholine. As you may know, that's the most ubiquitous phospholipid in the body. What we're doing is we're essentially replacing a metabolic precursor that these patients don't get.
You will have seen that in enzyme replacement therapies where that lack of that nutrient or that activating ligand in a metabolic pathway is absent because of a genetic deficiency. Here, it's absent because the patients don't get it or they can't absorb it. We are enrolling a pivotal study as we speak, for IV Choline Chloride where our primary approval endpoint is demonstration of elevated choline levels in serum at the eight-week time point. Again, we are introducing a compound intravenously and then for approval measuring whether or not there's an elevation of that compound in serum. We'll obviously look at some of, as secondaries, but not in a hierarchical way because the FDA hasn't required that. We'll look at medical endpoints. Here, you know, when you think about phospholipids, you ought to think about liver dysfunction, and that's the most common sequelae associated with parenteral support.
We will be looking at a number of different liver endpoints. Steatosis is measured by MRI PDFF, but also LFTs, alk phos, bilirubin, and a number of other functional endpoints where lack of phosphatidylcholine is implicated in various organ systems. There we'll be able to talk about interim data from this study in the middle of 2026. Look forward to that. I do want to spend the rest of my time on lymphatic malformations. We're hearing a lot of interest in this field, and I want to talk about how it is that we sort of set up in this increasingly interesting opportunity. TARA-002 is the standard of care, as I said, in Japan for lymphatic malformations that are macrocystic in nature.
Essentially, as you probably have heard from some of the other folks that are looking at microcystic lymphatic malformations, these malformations are driven by somatic mutations in the PI3K mTOR pathway, resulting in significant malformation or overgrowth of lymphatic vasculature, for lack of a better term. The other folks that are out there in lymphatic malformations treat microcystic disease. Microcystic disease is essentially a malformation that has very limited luminal space in the malformation, right? It's fleshy and thick. A topical approach is appropriate in those patients. Those represent, from our real-world evidence, about a third of all incident cases. We address macrocystic lymphatic malformations, and I'll show you exactly what that looks like. These are patients that were treated in the University of Iowa investigator-led study that I mentioned earlier.
550 patients, all pediatric, and these are patients that were treated with the drug that we are manufacturing and interrogating in the clinic today. You can see the balloon-like structure, and you can see the significant reduction in volume of those structures. To give you a sense, this is after a maximum of four doses. Right now, we are treating patients exactly like this across three different age strata, from 18 years old all the way down to six months old. We'll be putting out interim data from that study before the end of the year, where the protocol for these patients is one dose every eight weeks apart, up to four doses. What I can tell you is that we have yet to see a patient that has required the full four doses.
That should give you a sense of where we might be in terms of response rates when we talk about these patients in interim analysis. We've talked about the University of Iowa study, and that's because it is the most robust contemporary study conducted in lymphatic malformations. This really illustrates the difference between us and the folks that are looking at microcystic. We work in macro. We do not work in micro. You can see that on the right-hand side chart. What I like about that right-hand side chart is when we are addressing the patients that are macrocystic, we are achieving complete response in 62% of those patients and clinically meaningful response in 84% of those patients. Our objective is to replicate that data as we continue our study. This is the study design. Currently, we are in our final safety cohort, right?
We had three safety sentinels at different age strata. As we clear safety with the safety monitoring board, those patients at those age strata are enrolled in an evidence or an expansion population for efficacy. We are fully enrolled, or we have reached full enrollment, in the safety sentinels and are increasingly enrolling patients in the expansion as well. We often get the question, kind of, where do you fit in the broader LM situation or the broader LM market? On the left-hand side, we try to delineate what we've learned both from the Iowa study as well as from real-world data. The incidence for lymphatic malformations, you know, we believe is somewhere around one in 2,000, one in 4,000 live births. Somewhere around 1,800 patients per year incident. Of those, about a third are macrocystic, a third are macrocystic dominant mixed, and a third are microcystic.
If you look at the prevalence, and remember for us where we're, you know, introducing a cure model, the prevalence of patients that have lymphatic malformations are going to be those macrocystic patients that have foregone treatment or lymphatic malformation patients that are microcystic that remain sort of in the prevalence pool. This number we understand is low compared to what some of the other folks in this setting are talking about. This is what we kind of have observed from our real-world evidence. Once we prosecute this program and drive towards an approval, the question is, is where else might we take this? We are PRV designated, and obviously on an approval, we'll be able to, you know, we'll be awarded a PRV and then be able to sell that.
As we think about other maxillofacial cysts, where our drug OK432 has demonstrated efficacy in a, you know, greater than 10, you know, N of 10, case study, there are millions of patients in the United States where just these five alone, thyroglossal duct, salivary mucoceles, ranula, branchial cleft cyst, auricular hematoma, these are all indications where OK432 has demonstrated equivalent efficacy to what it has demonstrated in the lymphatic malformation setting. If you add up the epidemiology of just these five indications in the United States, it represents 12.5 million addressable patients on top of lymphatic malformations. For TARA-002 in the maxillofacial cystic-oriented setting, we start with lymphatic malformations and then we move into what might be a significantly larger patient population. At all points, we'll be able to lean on data that has already been demonstrated in Japan or in the United States.
Significant opportunities exist across the portfolio. Just to wind it up, we have $146 million of cash on our balance sheet as of the end of the second quarter. That's sufficient to carry us into 2027 and through multiple catalysts in 2026 across all three programs. There are a number of ways to win as we continue to push these programs forward. With that, I'll open it up for 27 seconds of questions.