Yeah, of course. Great. Thank you so much for joining us today. My name is Julian Pean. I'll be moderating this discussion. I'm joined here by John Alam, CEO of CervoMed, who's going to be giving a presentation. And with whatever time is remaining, we'll do a brief Q&A. Thanks so much.
Thank you, Julian. Good afternoon, everyone. My forward-looking statements. CervoMed is a Boston-based public company developing oral therapeutics for neurodegenerative diseases. We are the leader today in terms of developing the first treatment for the major neurologic indication of Dementia with Lewy Bodies. Two quick background business slides. One is in terms of the management team and leadership team. I think across the board, in terms of the leadership team, board of directors, scientific advisory board, highly experienced industry leaders in terms of drug development, science, and building companies around success in clinical development. From a business standpoint, from a financial standpoint, we're in great shape. We did a pipe in the spring with that. At the end of last quarter, we had more than $46.7 million in cash, as well as remaining grant funding.
We're financed in terms of cash runway out through the end of 2025, with success in a phase II-B clinical trial next month, which we are anticipating. We would bring in through a structured step in that pipe investment within 180 days of that announcement, up to an additional $99.4 million, which would fund us towards the clinical phase of the phase III program in Dementia with Lewy Bodies that we are anticipating starting in the middle of next year. Otherwise, what I will be talking to you about is our program in Dementia with Lewy Bodies, which is a major neurologic indication. It's the third most common degenerative disease of the brain after Alzheimer's and Parkinson's disease, very high unmet medical need with no approved therapies, and a specialty disease. This is a significant commercial opportunity. We are positioned to be first to the market.
We're the only ones with positive phase II clinical data, and it's clinical data that's been published in high-profile journals, and we are coming to the primary efficacy analysis in a phase II-B clinical study in Dementia with Lewy Bodies. This is the study which I will describe in more detail and the rationale for this, but this is one of the major potential value inflection points across the industry within this year. This is one of the most important clinical trial data readouts within this year. It is definitively designed to be a definitively demonstrated proof of concept that the drug works and is efficacious in the treatment of Dementia with Lewy Bodies.
Now, most of my presentation then is to talk about Dementia with Lewy Bodies and fundamentally, what are the reasons to believe that we would be successful and what type of success we would have within this trial. Before I get to that, just a little bit of news that is perhaps more of the most recent news that are validating in terms of the potential of our drug within Dementia with Lewy Bodies. One of them is a prize, the Prix Galien, that we were awarded earlier this month as the best pre-revenue biotech company in the U.S. And we believe it is very much around the advances we have made in Dementia with Lewy Bodies. A second is on the right-hand side, which was the two oral presentations we had around our program at the major clinical trials meeting for Alzheimer's disease and related dementias like DLB.
We were the only company outside of Lilly and AC Immune who have approved drugs in Alzheimer's disease. We were the only company with actually two oral presentations, which we believe, which I believe points to the fact within the academic and clinical community in dementia research, the recognition of the advances we have made and the potential within the clinical trial readout that's coming next month. So what does fundamentally distinguish our program? This is our drug neflamapimod and the RewinD-LB study, which is a phase II-B clinical study of that drug in Dementia with Lewy Bodies. From many of the things that we see before are these three points. We recognize very much that within the investor community, there is a track record of trials such as this that read out negatively. But fundamentally, there are three things that stand out in terms of our program.
Number one, we have done a lot of science and some deep understanding of a mechanism that fundamentally aligns our drug and demonstrates that neflamapimod targets the specific mechanisms that drive disease expression and progression in Dementia with Lewy Bodies. I think very specifically matching of the drug and mechanism with the disease process. Second, our focus on early-stage Dementia with Lewy Bodies. This is a patient population that represents about half of all patients with DLB. These are patients whose disease is driven by a functional deficit. They're sick neurons that are not working well, but they're still there. This is ahead of significant neurodegeneration, and it is a unique within the overall neurodegenerative disease space. It's a unique group of patients that have the capacity to actually be treated and respond and show and actually do better, show reversal of clinical disease progression.
It's data we're seeing, and we are uniquely focused within the space on these patients, the early-stage Dementia with Lewy Dodies patients, and third, uniquely in terms of a trial of this size and stage, we have significant clinical data and extensive clinical data, both in Alzheimer's disease that helps us define the pharmacology and dose response, as well as, more importantly, even in Dementia with Lewy Bodies, with effects on clinical endpoints and biomarkers that informed on the design, and we believe gives us a very high probability of success in terms of the trial, which will, again, read out next month. To introduce you to some of you to Dementia with Lewy Bodies, this is the third most common chronic neurodegenerative disease after Alzheimer's disease and Parkinson's disease, 700,000 patients in the U.S. alone, of which half are in that early-stage population who we are focusing.
So 350,000 patients that we would address with success in our ongoing clinical trial. Two other points to make about DLB. It is a very high unmet medical need if you compare it to early Alzheimer's disease in particular, significantly higher healthcare costs, lower quality of life, higher caregiver burden, and the disease progresses faster. The second point I would make is that Dementia with Lewy Bodies, with the current clinical criteria, is actually well identified. The diagnosis is very specific. A patient who meets the clinical criteria today, they will have a high probability of having Lewy bodies underneath. And they are, more importantly for us, they will have disease in the area of the brain that we are targeting, which is called the Basal Forebrain Cholinergic System.
It's for that reason that as opposed to what we hear about in Alzheimer's disease, we don't need to do additional testing to identify and diagnose these patients and include them in our clinical trial. The clinical diagnostic criteria actually define exactly the patient population that exactly defines a patient with dementia with underlying Lewy bodies as pathology. From a mechanism of action standpoint, a pathogenesis standpoint, the key target here is a part of the brain that's shown in red there, the basal forebrain cholinergic complex. This is where the major site of the production of a neurotransmitter, the major neurotransmitter acetylcholine. It's involved in regulating a wide range of cognitive and motor tasks, and particularly in terms of synchronizing different parts of the brain to get optimal cognitive and certain motor tasks, such as walking.
It is the region of the brain that is where the primary pathology is in Dementia with Lewy Bodies. It's the region of the brain that fundamentally what goes wrong that causes the clinical symptoms in Dementia with Lewy Bodies. On the right-hand side is how our drug works. Our primary mechanistically, our target is a protein called p38 alpha. But p38 alpha is a regulator of what has been identified as the major target for this pathogenic process in Dementia with Lewy Bodies and other degenerative diseases of the basal forebrain. The protein Rab5, through inhibiting neflamapimod, our target p38 alpha, it inhibits the entire cascade and reverses the disease process within that part of the brain in well-demonstrated animals. The other way to think about this drug is we are downstream of neuroinflammation.
We block the effects of inflammation on this part of the brain, on the cholinergic system. And by blocking the effects of neuroinflammation and reversing the effects of neuroinflammation, we treat the disease process within this part of the brain. This has all been well demonstrated in animals and mechanistic studies, most of it coming out of the academic laboratory of Professor Ralph Nixon at NYU Langone, but validated in a number of different systems. Again, in animals, we reverse the cholinergic degenerative process. We improve cholinergic and fully reverse the deficits that the animals have due to that disease. We've then taken that, done studies in Alzheimer's disease, demonstrated the relevant pharmacological activity in terms of inhibiting those specific steps in the pathway, in particular in lowering spinal fluid levels of total tau and phospho-tau.
Also, with MRI studies, we've actually shown we can increase the size and reverse the atrophy in that part of the brain, as well as improving the functional connectivity of that part of the brain. And then otherwise in Dementia with Lewy Bodies, again, in published data, shown effects on both cognitive and motor aspects of the disease, and then been able to, as I'll show you, been able to identify within the broader population how to identify those early-stage patients and get an optimal treatment result. So then from a biological standpoint, we are targeting that early-stage population. And what that early-stage population represents is where the disease is confined to the Basal Forebrain Cholinergic System. Other parts of the brain, in particular the hippocampus, are spared. Because of that, in this patient population, we can get a great response.
And that's what we saw in the phase II-A study. As patients advance, this is the more half the patients who have more advanced disease, they develop neurodegeneration elsewhere, particularly in the hippocampus. Because of that, we believe we're still treating the cholinergic aspect of the disease, but we have less effects. And the way we can get optimal effects and we can do the most patients for is that early-stage population where we fully match our drug mechanism with the disease process in that patient population. And what that allows for is in these early-stage populations is an actual reversal of clinical disease progression. And that's shown in the blue line at the top.
That's what we saw in the phase II-A study, some improvement and then stabilization going forward from there, which gets us out of the trap that has always been in Alzheimer's disease that you're very familiar with, that all you can do is slow disease progression and slow future decline. That requires large trials, long trials to show drug effect, and even at the end of that, the effects are minimal because you've never made them. It's hard to get separation if you're too far down in the neurodegenerative process. The early-stage Dementia with Lewy Bodies population, whose disease is confined to that part of the brain, fundamentally behaves differently. If you have a drug like ours, you can restore function. You can demonstrate efficacy in phase II . You can go to the market with a six-month phase III trial. We know that from discussions with the FDA previously.
If you can show a clinically meaningful effect in DLB, you can get approved on six months. Because of that, your phase II work, you can definitively show efficacy and fully de-risk phase III from an efficacy standpoint. So this is our phase II-A clinical study, again, published in Nature Communications in September of 2022. So it was a 16-week placebo-controlled study, 91 patients randomized to either placebo or neflamapimod. In the neflamapimod group, patients got either 40 mg b.i.d. or 40 mg t.i.d., a higher dose level. I'll tell you upfront, the lower dose did not actually achieve what we were hoping to get in terms of blood concentration and was largely ineffective. And if you look at the efficacy data on the blue column, the first two columns are the data including that low-dose group.
So this is the intent-to-treat analysis, including all patients in which we have efficacy data on. We see significant effects on overall dementia severity as well as on motor function measured by specifically in terms of gait, measured by the Timed Up and Go test, dementia severity by the gold standard test, the Clinical Dementia Rating Sum of Boxes or the CDR Sum of Boxes. And we see positive effects versus placebo, p-values of 0.023 and 0.044 on those endpoints. In that analysis, in the ITT analysis, we did not see effects on certain cognitive tests, but we do see that when we look at the high dose alone against placebo. This is the fundamental reason we learned in terms of dose. We're dropping the 40 mg, the lower dose group going forward.
We've identified an optimal dose group dose with the 40 mg three times a day dose in the right-hand side. Now, that was a primary publication. There's a secondary analysis that was contemplated in the protocol, but we could not do upfront, which is to be able to identify the early-stage patients and separate them away from the advanced disease patients. The blood test for that was first published around in about a year after the study was initially completed. It's called p-Tau181. It's plasma blood levels of phosphorylated tau at position 181. You can use that with certain cut-offs to identify the ones who have elevated, have advanced disease. Those are the more ones advanced, more progressed. They have significant neurodegeneration. Their expectation would be less effect there. That is indeed what we see.
If you look at on the left-hand side on this slide, I'm showing you again the prior data at the high dose versus placebo, good effects on cognition, CDR sum of boxes, Timed Up and Go test, moderate size effect size. When you look at the early-stage patient populations, the magnitude of effect there, it goes up roughly doubles. We also see an effect on the memory test down at the bottom. This in terms of magnitude of effect, this is unprecedented activity in dementia trials, Alzheimer's disease, DLB, any of these chronic CNS diseases. We see significant effects on most of these endpoints, even with relatively small numbers. This is a really nice, very clean result that comes from excluding the patients with the advanced disease, decreasing the heterogeneity, and really focusing on our drugs treatment on the most responsive patient population.
And this is the patient population we're focused on going forward. And the final set of data coming out of that phase II-A data is on a blood biomarker also of neurodegeneration now. This is measuring directly the rate and the severity of the neurodegenerative process. Again, something we could not have done even two years ago. But it's come out in the literature recently, particularly in DLB, but it occurs in a range of neurodegenerative diseases, a very specific and sensitive marker of the neurodegenerative process, including in terms of degeneration within the cholinergic system. But for DLB, this is really the one and only marker that's been identified to assess the underlying disease process, neurodegenerative disease process. And on that marker, we see a significant effect that's shown with neflamapimod treatment, shown on the left-hand side.
In the placebo group over the 16 weeks of the trial, there's a modest increase, while there is a decrease in neflamapimod treatment, and that difference is significant with a p-value of 0.015, and very interestingly, that effect correlates to the clinical outcome in terms of the CDR sum of boxes and overall dementia severity. If we look on the left-hand side of the right-hand figure, the patients who have a reduction in GFAP levels, four of the nine patients actually show an improvement, and none of the patients worsen. There's really no examples in the literature in CNS disease, and particularly in neurodegenerative disease, where you can correlate a biomarker of the disease process to the clinical outcome. It's more evidence that, number one, we're acting on the underlying disease process.
Number two, there's a very robust clinical effect that's mediated by that effect because you wouldn't see such a correlation unless there was a clear-cut efficacy driven by drug administration. Now, it's acknowledged that it was a phase II-A study, exploratory study. First study, we did not have a predefined hypothesis. So we're not claiming the drug, there's efficacy, that the drug works. You need to run a confirmatory study, which is there's a predefined primary endpoint with a sample size calculation to be able to say that you have demonstrated true proof of concept and demonstrated efficacy. That's this trial, the RewinD-LB study, which was initiated last August, completed enrollment in June of this year, 159 patients enrolled. And last patient, last visit for the primary efficacy analysis, which is at the 16-week of the double-blind placebo-controlled study, happened in October.
The data readout will happen in the coming weeks in December. The study otherwise is a replication of phase II-A in that it's a 16-week double-blind placebo-controlled study. There is an open-label extension, but the primary efficacy is at 16 weeks. The primary outcome measure is the dementia rating scale, CDR sum of boxes, the gold standard for looking at dementia progression and severity. Importantly, we are excluding the advanced disease patients using that blood biomarker p-Tau181. Simplest way to think about is this study going to read out positive in my mind is that at the 40 mg t.i.d. in these patients in the phase II-A study with about 15 patients per arm, we showed a significant effect. In this study, we're going up on the numbers to 80 patients per group. I can give you a statistical analysis of that.
There's very high statistical power, but just straightforward, if we have the same types of effects that we saw in Phase II-A, this study should read out positive. It's the basis of our with using all of the information we had, the signal we had, we're able to design a study that we think has a very high probability of success. At the end of that, again, if we see the same types of effects, we will demonstrate true proof of concept that the drug has efficacy in the treatment of Dementia with Lewy Bodies in a clinically meaningful way. A significant effect on CDR sum of boxes is inherently clinically meaningful by the nature of the scale and how hard it is in certain respects to show effects on CDR sum of boxes.
Again, if we saw the same effect we saw in Phase II-A, trial should read out positive. But with that, because Phase III will then be a replication of the Phase II-B, it's going out to 24 weeks, larger numbers. But all of that works in your favor in terms of being able to show a treatment effect. This study should substantially, if not fully, de-risk from an efficacy standpoint the Phase III trial. And that's a fundamental reason at that point, along with the fact that this is a very high-value indication. Having a trial that is de-risked in terms of getting to approval, there's still time and money involved. But the primary risk in our business is the drug going to work or not?
Once you've de-risked that in a major indication like this where there's no approved therapy, specialist disease, high medical need, high pricing leverage, it's a very valuable asset, and the company should be valued accordingly, so this is where we are. This is where we're going forward. We've had a great year. We've met all of our milestones since we've gone public, actually, in over the last 15 months or so. What's remaining is report out the top-line results, which we will otherwise present at scientific meetings and publish in the first half of next year. The first scientific presentation will be in January, at the end of January, and then meet with the FDA, finalize phase III programs, and move into the phase III study. Again, thank you very much for everyone listening. I know we have a few questions.
Again, the hugely important data readout coming up in the next few weeks. And what the distinguishing points here are what we believe is going to make it that there is a high probability of success within this trial. And what is fundamentally different about this trial readout relative to a lot of the readouts that you've been seeing over the last few years.
Excellent. Awesome. Thank you so much for the presentation. That was really enlightening. I guess just with a couple of minutes we have left, can just ask a couple of questions about the upcoming trial. I guess so totally understand the hypothesis of going after patients with low p-Tau earlier on the progression curve. Is there anything else that you guys are doing to further homogenize the patient population with respect to inclusion criteria to give yourself the best chance at success in this upcoming readout?
So when you think in terms of this is probably one of the best demonstrations of combination of targeted therapy and personalized medicine. You had to think about more broadly dementia, which is how most people have when they go after Alzheimer's disease, they're really just going after dementia broadly. What we've done is within the broader realm of dementia, we've focused in first on Dementia with Lewy Bodies to begin with. That brings that down to 15% of the population of dementia. And what that defines, and again, are the patients with dementia that's driven by disease in the cholinergic system. There's a very nice, almost one-to-one relationship between Lewy body pathology in the cortex, and if it shows up in the spinal fluid, then with having disease in the cholinergic symptoms and having the symptoms of Dementia with Lewy Bodies.
And then out of that, so that's the biggest cut from an inclusion-exclusion criteria is being very specific to the criteria for Dementia with Lewy Bodies. And then being able to identify the patients who it is really AD pathology, and it's hippocampal atrophy. It's disease in the hippocampus that we're segregating out with the p-Tau181. That removes actually the remaining heterogeneity in terms of the patient population. This is, I think, if you compare it to what people think in terms of Alzheimer's disease, this population is very homogeneous in terms of their underlying pathogenesis. It's Lewy bodies. In terms of their underlying pathology, it's cholinergic system. It's a very clean patient population. And then what we have to that is a drug that matches that clean patient population. And I think that's really the difference from everything that I think has come before us.
And we're building on and it's not that we're smarter. We're building on what people have been trying to do in Alzheimer's disease. This is exactly what they've done in Alzheimer's disease. They've gone with anti-amyloid focused on the amyloid PET scan positive and trying to get more homogeneous pathogenesis. But I think at the end of the day, it is still very, very heterogeneous. And the other problem you have is that when you go to where there's not a lot of neurodegeneration in Alzheimer's disease, and that's the nature of the hippocampus, you don't have a lot of clinical signal to see drug effects. And DLB just stands out in that. And we've taken the same concepts, and it just fundamentally works better in DLB to get this homogeneous population, lots of clinical signal.
But underlying it, it's a very common disease pathway, which I just fundamentally don't think exists in Alzheimer's disease otherwise.
Excellent. Great. Well, thank you so much. We're up on time. Appreciate the presentation. Best of luck.
Thank you to everyone listening. Thank you to Stifel for having us here.
Of course. Thanks.