Hi, everyone. Thanks for joining our 46th Annual Healthcare Conference. I'm Vishwa Shah, part of the biotech team here with my colleague Stacy Ku. It is my pleasure to introduce Christopher Missling, the CEO of Anavex. Thank you so much for being here.
Thank you very much for the very kind introduction and also very kind invitation. I'd like to share with you Anavex Life Sciences. We are a public company, so I'd like you to read this. We're focusing on dedication on patients to get them a potential solution with an innovative oral potential solution, which we hope to improve their lives. We focus on central nervous system, one of the biggest unmet needs today. We'd like to do this with the transformational science through personalized oral medicine. We believe that we're aiming for improved patients' outcome, developing convenient oral personalized treatments. We also have a strong IP protection and a strong team and board as well. One of the biggest unmet needs today is dementia, Alzheimer disease.
It's in exponentially almost increasing over time because the correlation with developed nations, better quality of life, you live longer. One of the things which correlates the highest with Alzheimer is aging. That's why this is exponentially increasing and expected to reach 139 million worldwide dementia cases. The costs are staggering, of course. One of the things we have done, we finished our phase II-B/III study in blarcamesine with blarcamesine, an orally once-daily treatment. You see a picture of that drug here in the slide. What we noticed was that overall in the ITT population, a very solid response rate of the key primary endpoint ADAS-Cog13 with 36% improvement. That was further increased to almost 50% in a pre-specified population in 48 weeks only.
What is also exciting about the trial was that we did demonstrate a really reliable safety profile with no ARIA, no imaging neurological adverse events, no associated neuroimaging adverse events. Also, we did not record any drug-related deaths in the study. That includes the open label study as well, which was up to 192 weeks. We also observed something which is pathologically known by now that the brain shrinks over time in Alzheimer, and a very nice data demonstrate significant slowing of this brain atrophy. We're able also to look at the biomarker outcomes in this phase II-B/III , and we saw a corroboration with the plasma, Abeta 42 ratio significantly as well.
We learned by now that one of the key requests from patients with dementia and Alzheimer's in general is really a simple oral solution. There's just no propensity for them taking them out of their normal habitus and home care or home stay. They just wanna take something which is orally once daily, which makes it also easier for the caregivers, for the family members to begin with. That's been corroborated that there's a request for very convenient, accessible oral solution, and we would, of course, fit that request. I'll give you a little background where we stand. We are in discussions right now with regulatory agencies in the key markets. We also have a solid IP protection up to 2040. Our operations does not have any debt.
We are fully cash funded, the current estimated cash utilization rate expects us to be able to progress for more than three years without any additional cash requirements. Again, in summary, we think blarcamesine represents a convenient oral once daily commercially scalable potential medicine. We're not limited to Alzheimer's. We have also with blarcamesine a broader pipeline assessed. We have finished a phase II study in Parkinson's disease dementia, which gives us the inclination now to start a Parkinson's study a bit more later about that, as well as rare diseases where we have done some interesting work and received very intriguing results in Rett syndrome, which was tested orally clinically, and in other indications of the autism spectrum disorder like Fragile X syndrome, which is the largest portion of autism spectrum.
We also saw a very nice correlation of biomarkers which also corroborated in humans, and we're planning a study accordingly there as well. Infantile spasm and Angelman syndrome is also where we have very solid preclinical data where we might also engage in at a later point. Also allow it to highlight that we have a broader pipeline in Anavex. We have also another oral drug called ANAVEX 3-71, where we just completed after a phase I study, a solid phase II study in patients with schizophrenia, and we like to move that forward as well. We have frontotemporal dementia, preclinical data, and we have received orphan designation by the FDA for FTD.
Again, you see the franchise is orally oriented with blarcamesine, a simple capsule, and for the rare diseases, a different formulation, which also allows to separate for later in the market for different pricing reasons, liquid formulation with different doses. Overall, the pipeline looks like balanced with geared towards potential commercialization eventually. Let me explain quickly the mechanism because that's really at the core of our pipeline. Autophagy declines with aging. It's one of the key elements I'd like you to take away today. In the same time, cellular stress increases with aging. In pathology, this is strengthened or even stronger. Autophagy declines even further significantly, and stress increases significantly.
What is really intriguing is that our drug blarcamesine is able to reactivate neural Autophagy if it's impaired, and at the same time is able to counter cellular stress. That is what blarcamesine does. Basically, is able to any point in time during this decline to intervene. Before I go into more details about this, I wanna quickly also share with you what is coming up in the milestone section. We expect a review of our re-examination with the EMA in this first half. We also are planning to start Alzheimer's study. One is in within the ACCESS-AD, which is a European funded situation with multiple Alzheimer-oriented franchises and care supporters for working on Alzheimer solution in Europe.
We are planning a phase II-B/III study in Parkinson's, which is longer than six months, probably 12 months. We are planning a Fragile X study I mentioned, and also another rare disease which we have not disclosed yet. Subsequent, you will see very soon three publications which have been submitted and will be expected to be published.
One is a precision medicine publication from the phase II-B/III study, blarcamesine in Alzheimer's disease, a specific publication about a new gene, which we identified in the GWAS analysis called COL24A1, a gene in the ECM, extracellular matrix, relevant to the response to blarcamesine, a Fragile X study where I mentioned we saw a very nice correlation of EEG biomarker correlating both in humans and in animals, giving us confidence to move forward with that in the clinic. Let me now give you what is important to understand the mechanism. It's really, like, important to understand that Alzheimer's disease pathology is today defined by a beta and tau. However, it's a very good point of view to start to define those two as potential biomarkers of the pathology.
The question, are they the best targets of this complex pathology? We learn now, recently learned that the impairment of autophagy actually precedes both beta-amyloid and tau tangles, and therefore anticipates the neurodegenerative process in Alzheimer's disease. If we're able to go further upstream, that's maybe more advantageous than trying to target further downstream. That's been just recently published, the exact mechanism how blarcamesine interacts within the autophagy flux and is able to restore what is an impaired lysosomal consolidation by joining forces with another protein called GABARAP. It's been really nicely published and explained to its detail that blarcamesine is able to activate sigma-1, and with that activation, joining GABARAP, forming a function which is basically able to replace LC3 if it's not functional or any other reason why the lysosomal binding cannot take place.
Just to, for you to background, what we're talking about is a recycling of the cells. Neurons cannot get rid of their trash, so to speak. They have to recycle it inside in the system, and that is called autophagy. If that's impaired, you can imagine that the neurons will eventually die, become impaired, and then die. That's why it's so important to have that autophagy flux always going. It's really nice to be able to confirm that exactly mechanism with blarcamesine to restore the autophagy and enhancing the function again of the brain function very upstream. I mentioned briefly before the pathology of Alzheimer's is highly correlated with the brain shrinking and the ventricles in the middle, they are enlarged. The holes are built in the brain.
This is really one of the key features that Alois Alzheimer identified in his patient in his autopsy. We're able to show that almost in all regions of the brain with blarcamesine compared to placebo, a stopping or declining of this atrophy, procedure or process, which is also considered the de facto neurodegeneration pathology. In the whole brain, in the total gray matter, in the parietal lobe, temporal lobe, limbic lobe, insular cortex, frontal lobe. It's really nice to see that in almost all regions of the brain, a significant reduction of this atrophy, which is a clear sign of pathology.
Now, I'd like to go what I referred to as the really exciting data of the phase IIb/3 trial, where we saw that in the trial measuring the key endpoints, ADAS-Cog13 and the CDR-SB, key endpoints that I used in this pathology in early Alzheimer's disease were significant. Not only that, but also shown the consistency of that, the pre-specified population, which I mentioned before, which the sigma-1 population wild type, and this represents 70% of the overall population in the overall population genetically identified with databases, but also was consistent with our population in the trial itself. It is nice to see that since we activate sigma-1, the expectation would be, would those patients with a completely functional sigma-1 gene do better, responding better to blarcamesine?
The answer is given you here clearly yes, because the ADAS-Cog13 moved from two points for ITT to -2.3, the CERAD box moved from 0.48 to -0.6. It's nice to see that ITT was highly significant already in the ITT population, but the sigma-1 wild type did just a little bit better, that is consistent with the mechanism of action again. What is also important here to notice already for the ITT population, for all patients, that this data was clinically meaningful. That means a recent publication asked the question, what defines clinically meaningfulness in Alzheimer's? The answer that it has to be a delta of at least two points in the ADAS-Cog, we definitely demonstrate that, as you can see, with -2.3.
Again, I wanna point out that the consistent safety profile of the drug, and we were able to also adjust the titration to have a more tolerable outcome of dizziness, which was the most often observed adverse event in this trial, by extending the titration period. Again, we did not see any ARIA in this study. Now mentioning the long-term effect of the drug, we saw that in the extension study, which went up to 992 weeks, we found the ability to compare this open-label, you know, extension data with the ADNI population, which is a matched population specifically. You see very nicely that the blarcamesine arm holds up quite nicely and consistently over this 144 weeks compared to the ADNI group, which is declining significantly.
When you calculate what really is what it means for patients and for caregivers, what can be communicated to them is how much time can you say that there is no change in the decline? That is what is called or calculated as time saved. The calculation of that results in 18 months roughly or 1.5 years of time saved. I have to share with you my grandfather and grandmother, they both were afflicted by Alzheimer's dementia, and I'm sorry that they passed. I wish we had had that drug at that time approved. That would have allowed to have more quality time together in this moment when a patient is afflicted by this terrible disease. Nice to demonstrate the ability to also prolong quality life over that period.
That data is for ITT patients. That is for all patients in the trial. What is the future? We demonstrated, and was recently published by a third party investigator, that if you give this drug blarcamesine to animals and then make them sick with Alzheimer pathology, those animals never developed the cognitive impairment. Those who did not get the treatment but get a placebo, however, did in the water maze. If you basically export that into the future, we have to demonstrate that of course in humans, but it gives the potential that this could be eventually also prophylactic taken eventually. I really move to what I regard as the most exciting part of this presentation, which is the moving from a disease which has been always considered, especially in CNS, as a all or nothing.
Why don't we think about can we learn something from oncology, which is also the area I worked before joining Anavex. This is like the shift from chemotherapy to immuno-stimulation by looking at the profile of patients and their genetic make up, what they could basically be able to get if they are have a certain homogeneous make of genetically. What we found was an interesting outcome, which you already have a first snippet from the sigma-1 wild type. We found another gene joining the wild type sigma-1, and that is this COL 24A1 . We found that combined wild type groups were able to demonstrate the goal of almost approximating normal aging, normal healthy aging in adults with that population identified as we call precision medicine.
What is very intriguing is that this result is not accidental. It's very consistent also with the autophagy mechanism, because those two genes are required for proper sigma-1 activation and collagen presence in autophagy flux. It's really nice to see that consistency explained. Just to give you a snapshot of what it means potentially, there's a publication which took non-cognitive impaired participants, which are considered prodromal because they had some A-beta in the brain, but were not cognitive impaired. The trajectory of them is the orange line, is a very barely detectable decline over one year. Comparing this to this blarcamesine-treated ABCLEAR 3 cohort, which is the defined wild type sigma-1 and collagen, you see almost identical decline.
While the placebo arm that is the gray line is declining, accordingly to also consistent with the natural history study. It's really nice to see this consistency of effect over time. I wanna mention that the baseline of the participants in our trial was much worse. They're more advanced in Alzheimer pathology. Despite that, we were able to shift them up to almost no decline. Mathematically, that represents a 48.7% clinical benefit over placebo, which is extremely exciting. To give you another way of looking at the data, which I just demonstrate to you, is for all the endpoints in the trial, the clinical endpoints.
You see here both ADAS-Cog13 as well as ADCS-ADL. It was a key endpoint in this trial. The figures on the boxes are basically jumping out in this cohort, what we refer to ABCLEAR cohort, clearly meaningful and also unprecedented almost. It's worth basically identifying that as key results for this patient population, what that could mean for patients. Not only the endpoints are important, but also what patients most are affected by is the quality of life. This is patients' quality of life. It's not like an observation of somebody's quality of life.
This is what is the scale and the questionnaire of what the assessment is done through for a participating patient, the physical health, the energy, the mood, living situation, memory, family, marriage, friends, ability to do things, ability to money, dealing with life as a whole. All these are a specific questionnaire, overall, it's consolidated in the QOLAD result. What you see here is a snapshot of these cohorts. One is the ITT on the left or a trend towards improvement versus placebo. In the middle of the precision medicine result. On the right is the ABCLEAR 3 result , the strongest. It's not only interesting to see the separation, but also what you see on the right side of the slide that the end of the trial, the quality of life was better than at the baseline.
That means they're not the net improved quality of life. I think that's something you can definitely articulate as a physician, or caregiver to your participating person with Alzheimer's. Last but not least, I wanna remind again the convenience aspect of blarcamesine, not only for the patients, because again, they're very inflexible. They don't wanna be taken around. They really wanna have a stable place where they are and enjoy their life. We heard from patients who told us, "We're not interesting in this antibody injections, whatever," because just the trip to the site or wherever they have to go is so disrupting and stressful that they rather wanna have just one hour with quality of life with their families. This how sensitive they are to disruptive and moving around.
The oral blarcamesine would allow for a individual patient focus. For the families also, they don't need to spend time and take times off to ship, you know, the grandmother or grandfather around. It's less stress for them and also less financial strain, and again, no impact on their work schedule. For the physicians, they don't have to become project managers. They have to coordinate PET scans, they have to coordinate MRIs, they have to coordinate lumbar puncture. It's a really simplified oral solution without PET, MRI, and lumbar puncture follow-up because of the safety concerns of the antibodies, which we would not encounter.
Last but not least, we are communicating and working with care advisory supportive groups and educate them about blarcamesine, engage the community, and expand the knowledge what really matters for the patients and for the resilience of this population, and develop a strategy together how to move forward. Regarding coming back to the overall product portfolio again, we're addressing really large markets. We can see here on this slide, not only Alzheimer's, which is, by the way, very balanced between U.S. and Europe in terms of numbers of population. Also, the other indications are very large in number, Parkinson's disease, schizophrenia, and of course, also the rare diseases with Fragile X being a very large population as well.
Again, I wanna mention we have strong IP protection, and I think the one of the key patents up to 2040 without any extension. A quick snapshot on the financial side. We have round about over $131 million in cash today. We have no debt, and we utilized round about $39 million as of last year, and we're expecting this to be potentially similar this year, if not a little bit more. With that, you can calculate a runway run about of three years. We also like to mention we are supported for non-dilutive funding by Michael J. Fox Foundation and the International Rett Foundation, which we're very thankful for. In summary, we like to again point out we have late-stage Alzheimer's program with a scalable commercial opportunity in a large market with huge unmet medical need.
We have emerging body of evidence. blarcamesine is potentially highly efficacy in this genetically defined large Alzheimer's population through precision medicine. The autophagy platform offers opportunity through expansion into broader CNS space 'cause this increase of stress is all correlated, autophagy impairment to this other indication as well. Last but not least, we have a strong financial position and long-term IP.
Stay tuned for more updates. Thank you very much. If you'd like to have more information, please go on our website, www.anavex.com. Thank you very much.