Say clinically they have dementia with Lewy bodies, but they have no evidence of AD pathology on top of it. Within the last three years, this test has become established as a way to act as a surrogate for that PET scan and use that to say that if you're low enough on the test, you have enriched for, you are unlikely to have AD pathology on top of the DLB that, based on the clinical criteria you have already.
These are the patients who we are focused on, this pure DLB population, and who we are going to go forward with through phase III and ultimately to the market. Now, there are some who would say then, okay, it's already third most common, you've cut this down further. But the point of this slide is that there's still many patients who do have pure DLB. It's 175,000 patients with diagnosed pure DLB in the system today in the U.S. Again, high unmet medical need, no approved therapies.
There are symptomatic therapies, but they don't target the underlying disease process. People have a response, it's transient, and they progress relatively rapidly despite that, and so that's the unmet need, and then if you combine that with no approved therapies and it is a specialty disease, it's generally managed by neurologists, diagnosed and managed by neurologists, this is a very significant commercial opportunity, and we are the one company that has a drug with clinical proof of concept.
That the drug is clinically active and demonstrating efficacy against a substantive, significant clinical endpoint, the Dementia Rating Scale that I'll talk about in a few minutes, so there's a lot of science behind this. This is the one slide I'll show. Our drug is an inhibitor of this enzyme called p38 alpha, or the alpha isoform of p38 MAP kinase. It is a link between that kinase in the nerve cell ends up being what links alpha-synuclein, which is the protein that underlies Lewy bodies.
Think of it as an amyloid beta of Alzheimer's disease. It's alpha-synuclein. It's what makes up Lewy bodies. It's a key trigger of the disease pathogenesis, but it's linked with neuroinflammation. And then on the right-hand side, that activation leads to a variety of different molecular steps that leads to synaptic dysfunction and the loss of, in the most important cell type for DLB, the cholinergic neurons in the basal forebrain.
These are neurons that produce a neurotransmitter, acetylcholine, that is a key regulator of cognitive motor tasks. This is what goes awry, the function of these nerves due to the alpha-synuclein and the neuroinflammation. The science and all the references are down below, and there are more, most of them from independent academic labs. The mechanism by, or the path steps that leads from what's on the Alpha-synuclein neuroinflammation to ultimately reduce acetylcholine release is p38 alpha.
Our drug then, through inhibiting p38 alpha in preclinical studies, fully reverses those deficits in cholinergic function and cholinergic degeneration in that part of the brain. That's published in Nature Communications, so in a major scientific journal.
In our phase 2a study that's also been published, including in Neurology, the major clinical neurology journal, we showed that that was translatable into humans, that you could see the same types of effects on endpoints and outcomes that are linked to the cholinergic system on both cognition and dementia severity, as well as on motor function in patients with dementia with Lewy bodies.
But it's in that study that we first looked at using that blood test, p-tau181. We did so retrospectively in this context because the test didn't exist when we first ran the study. We went back and what we saw was, in fact, that all the clinical activity we're seeing, or a major portion of it, was limited to that group of patients. And it's on that basis that we have, we focused the next study, which is a phase 2b study, which we reported out results over the past few months, the AscenD-LB study.
We focused that in patients, we tried to enrich for using that blood test for patients who did not have AD co-pathology. The cutoff we actually used is shown on the left is less than 27.2 in a very specific version of that assay.
But otherwise, again, these patients were. It was 159 patients with DLB by consensus clinical criteria. So the initial focus of the study was in a placebo-controlled phase, 16-week placebo versus neflamapimod, 40 milligrams t.i.d., which is a dose we had identified out of phase II A, as well as in studies in AD as should be an efficacious dose or a therapeutically active dose. That initial analysis of that 16-week period we reported in December top-line results.
There was not an effect, which surprised us, very different than what we had in phase 2A and all of our clinical data. It turns out that the problem was in that batch of capsules that were manufactured as a single lot that we now know, but now today, not before, what the issue was, but that batch of capsules underperformed in terms of delivering drug to the bloodstream.
In fact, it was acting more as 40 mg twice a day, which we know is an ineffective dose rather than 40 mg t.i.d. Fortunately, we were able to rerun the same experiment because in the interim, we had introduced a new batch of capsules, a different batch of capsules that did not have the same problem. In fact, we discovered in January that we hit the target blood concentrations.
Then ultimately in March, at another 16-week endpoint in that extension study, showed now the results of effectively low-dose neflamapimod versus therapeutic dose of neflamapimod. Those results, I will then walk you through. The primary endpoint, and this is just to show the dosing groups going from the initial group of patients or the last group of patients, and green are the ones who got that effective dose of, or therapeutically targeted effective dose of capsules, which is DP batch B versus A.
W hich did not achieve the targeted blood concentrations. In the first 16 weeks, we had a rich group of patients who were both receiving either the first batch, low dose, or the second batch, the high dose. And so we reported out the data as a direct comparison. And that's the next set of data.
Primary endpoint is the dementia rating scale, CDR Sum of Boxes, the gold standard for evaluating dementia severity and clinical progression in dementia. Again, in the placebo-controlled phase, in all participants, or in what is today now the best definition of AD pathology or not.
This has been a moving target, but the paper that came out over the summer, in fact, validates that 21 picogram per mL is the best cutoff. You can see that there is no significant difference between the dark blue and the lighter blue in the top panels between placebo and neflamapimod. Though there is a trend in the patients who we are targeting favoring the capsule, but all consistent with that drug batch A just simply did not hit efficacious blood concentrations.
When you go down to the extension phase, all participants, or even more dramatically in the strictly defined no AD pathology group, the green bars are lower than. That's so less progression on CDR Sum of Boxes. In fact, in the ones without AD pathology who are below that, more strictly defined cutoff looks close to flat in terms of CDR change over time. So basically, when we hit therapeutic blood concentrations, there's evidence of significant effect on clinical progression on that dementia severity scale.
And if you look at across a variety of different secondary and exploratory endpoints, we didn't know what would hit upfront because some of these had not been tested even in phase II A. But you see everything trends in the right direction. And then when you look at, again, the ones who are with the more strictly defined population on multiple endpoints, your 95% confidence interval doesn't cross zero.
So there's a significant improvement when you hit therapeutic concentrations across CDR Sum of Boxes, CGIC, motor function with the Timed Up and Go test, working memory, again, pretty much across the board. And it's really based on this. This is, I would say, is the number one key opinion leader based in Newcastle in DLB in the world.
This was really very striking, persuasive data, really very little other evidence, Alzheimer's or DLB of a trial that shows such consistent effects with the statistical robustness and magnitude effect that we're seeing in the 16-week time point. So we also reported out longer term to the full end of the study, which is 32 weeks of extension. The point of coming back to this slide is that after week 16, almost all the patients, 90% of the patients in the end who completed were on drug batch B.
So we don't have a comparison anymore. But we do have patients on that batch A, that old capsules who actually got it during the placebo control phase and continued on. So we have more data beyond 16 weeks, but you have to take into account the full study. And the only way you can do that when you have variable lengths of treatment is to do a Kaplan-Meier analysis, survival curve analysis. And to do a Kaplan-Meier analysis, you have to look at dichotomous outcomes, whether you progress or not.
And for CDR Sum of Boxes, that's defined by a 1.5 increase in the CDR Sum of Boxes, because if you do that, you are significantly worse off. You have progressed. And when you do that analysis, either in all participants or in those ones who are below that strictly defined cutoff, clear cutoff effect with drug batch B when you hit therapeutic blood concentrations. In the green line is drug batch A overlapping with the blue line in placebo.
Again, a little bit of a trend when you look at the strictly defined AD co-pathology favoring the drug batch A, but red line clearly different and separate out as early as week eight. If you look at, in particular, the target population, hazard ratio 0.35 means 65% reduction in risk of progression against placebo, which you can make in this comparison as well, a 74% reduction with drug batch B compared to placebo.
We also reported out in that 32-week data on a plasma biomarker, which is considered to be the best marker of the underlying disease process. In DLB, placebo goes up, that's worse. Drug batch A may be a little bit better, but a profound reduction and a clear cutoff effect with drug batch A, B, I'm sorry, A minor effect, B all the way out.
So significant clinical progression, clinically meaningful reduction, multiple endpoints across the board, and supported by a biomarker effect. And the next step is really then go to regulatory agencies. And our plan is to present the trial, which is a 24-week clinical trial, approximately 300 patients, placebo against neflamapimod. The 24-week treatment duration is based on, this is what the ICH requires. As long as you can show clinically meaningful benefit, they have to approve you with a 24-week clinical trial.
And what our 32-week data in particular demonstrates is that we can show a clinically meaningful benefit within a 24-week treatment standpoint, which is why we say those results in particular substantially do as the phase III trial we planned. So that's the whole story. And I think our next major milestone is going to be, we're planning on meeting with the FDA.
We are on track to meet with the FDA and getting feedback within the fourth quarter, and we look forward to coming back and meeting with many of you when we have that feedback.
Thank you very much. If anyone has any questions, just raise your hand. I'll come bring the mic over.
I'm wondering about your financing plan to execute,
So we are financed as a company through to the third quarter of next year at this point in terms of our cash runway. That does not include the phase III trial.
We will need to, our phase III trial estimates, because this is not Alzheimer's disease again, it's not thousands of patients, 18-month duration. Our estimate is in the $50 million-$75 million range for that study outline, includes the extension part beyond the 24-week because you need to do that through to drug approval, probably closer to the $70million-$75 million range at this point. We would do that after we have the feedback from the FDA. So later this year into first half of next.