Good morning, everyone, again. Welcome to the Needham Healthcare Conference. It's my pleasure to be hosting Christopher Missling in our next session for Anavex Life Sciences. Why don't I turn it over to Christopher for taking us through the company's story, and we'll have some time at the end for some Q&A. Christopher?
Thank you very much, and thank you for the very kind introduction. So, like, we share with you Anavex Life Sciences. We're a public company, so I'd like you to read the forward-looking statement. So if you're grappling with a CNS disease, take comfort in knowing that we are pushing, and we're dedicated to pushing the boundaries of scientific discovery with novel oral small molecules tailored to potentially offer you hope and relief. We're addressing one of the largest unmet needs, which is Alzheimer's, dementia in general, and it's exponentially rising around the world. And that is because it's a complex disease, and a complex disease might require also a more, specific and upstream approach to address this complexity of this pathology. So in summary, there's a cumulative cost of over $20 trillion for dementia care expected in the future, and it's from 2015 to 2050.
1 in 3 Medicare dollars will be spent on people living with Alzheimer's and other dementias by 2050. 11 million is the number of Americans providing unpaid care for people with Alzheimer's and other dementias. What we're trying to do to target these markets using differentiated and transformative precision medicine, which we'll explain, throughout this presentation. Again, we also believe that we are positioned to capitalize on this significant growth in market opportunities to treat these diseases especially, but also other indications of CNS globally. To give you an overview of the investment highlight, we are in the stage of regulatory submission right now, a platform company with novel central nervous system mechanisms, which we also explain a bit later. We are meeting with regulatory authorities to discuss now the full data of the phase II-B/III study in Alzheimer's disease.
With the aim to bring Alzheimer's therapy to patients in Europe, Asia Pacific, and the U.S. This includes potential approval pathways, which are based on available efficacy results, also of surrogate biomarkers. The good news is we are very good with our cash, and we have enough cash on hand to run our operations with all the planned studies for at least four years. We have no debt on our balance sheet. We believe that our oral drug, blarcamesine, which is taken once daily, demonstrated superior clinical safety and efficacy compared to the monoclonal antibodies, lecanemab, but also another drug in the monoclonal antibody class, donanemab. This is also shown our drug to show reduction and slowing of neurodegeneration in early Alzheimer's disease, the indication which we covered with our drug in our phase II-B/III study.
So in summary, blarcamesine, ANAVEX 2-73, is an orally, once daily, convenient, scalable treatment, which also differentiates to the antibody therapies. We also have good international protection of the patents for our product candidates. It's important to be also able to differentiate between our Alzheimer's franchise or Parkinson's franchise, which requires an oral, once daily, solid formulation, to the rare disease franchise, which is for children or patients who have a hard time swallowing. And they prefer a solid oral formulation, which we developed. And so we're also able to separate these two formulations from a marketing perspective in the future. And also because they will have different price points to not interfere with the respective markets and branding strategy. So on the left side, you see the oral solid formulation for Alzheimer's, Parkinson's disease, and Parkinson's dementia.
In the middle, you see for blarcamesine the oral liquid formulation for the indications of Rett syndrome, Fragile X syndrome, infantile spasm, Angelman syndrome, and other indications which we might develop in the rare disease space. We also have another drug, ANAVEX 3-71, which we just started a study in schizophrenia, which also uses an oral solid formulation. So a simple capsule. The oral administered candidates also offer significant potential for clinical benefit relatively to the costly and logistically much more challenging biological antibodies, which also present additional safety concerns. And we know, for example, from the antibodies for Alzheimer's disease, lecanemab, that there's a black box warning. That means there's a warning that this drug could cause deadly outcome, and that is in a black box. That's why it's called in their label black box warning.
Which, which is caused by ARIA, and we did not notice in our study any ARIA. So now we believe we're really well positioned to expand our transformative precision medicine platform and capitalize on significant market opportunities. Let me share with you the mechanism, which is really important to understand, because this very complex disease or diseases require probably a further upstream approach rather than a singular target, like only A-beta blocking or tau blocking by itself alone. We believe the pathology is much more complex. The good news is we're activating the body-owned defense mechanism, as the body would do, to push back on cellular stress in order to restore cellular homeostasis. That includes also reduction of A-beta .
Reduction of tau and reduction of inflammation, if it's too high in the body or in the brain, and also activate the recycle mechanism in the body, which is called autophagy, which is impaired also in Alzheimer's disease and Parkinson's disease and other diseases. We've demonstrated with blarcamesine that happens very nicely in many animal models which we tested. Endogenously, the activators, which is the way the body responds to these cellular stress signals, is depleted because of chronic cellular stress caused by Alzheimer's disease, Alzheimer's disease, or Parkinson's. At the same time, in rare diseases, where the chronic element is since birth by a genetic dysfunction, so the proteins are not properly folded or properly expressed because the gene is faulty. It's constant cellular stress, chronic.
Requires an upregulation of sigma-1, which is triggered by endogenous small molecules in the body to activate the sigma-1. If they are depleted, though, there's not enough sigma-1 activation visible or available to the body to fight this imbalance. We can now provide from the outside the sigma-1 activation with small molecules, because the sigma-1 is a G- coupled receptor. What's very intriguing is that the sigma-1 target binding affinity is so specific that even when patients carry a variant receptor, so a mutation of the sigma-1, that still powerful effects are observed. All patients, regardless of genotype, stand to benefit. So that's important to understand the mechanism of our drug.
And indeed, when we measure the expression level of the sigma-1 in patients which are treated with our drug, we see, compared to placebo, a correlation of the outcome of the clinical outcome with the expression level of the sigma-1 mRNA in the body, in the blood. So it's very nice to see that logic that we activate sigma-1. The activation of sigma-1 is visible and measurable. And this activation correlates with the clinical benefit in Alzheimer's disease, in Parkinson's disease, and in Rett syndrome. So in a nutshell, in all the studies we have performed so far where we measured the mRNA expression level. And we were also able to confirm that fidelity of the sigma-1 receptor with another biomarker of the sigma-1, which is because some patients have a variant.
We noticed, though, those with a variant, which are the minority, run about 10% or less sometimes. They are not able to show as a strong signal as those who carry a non-variant of the sigma-1 receptor. And it's logical. It's a bit the analogy of two cars with the same brand. But one car has a flat tire. So the car with a flat tire is running not as quickly as the car with fully inflated tires. So that was a confirmation and shows the fidelity of the signal of the benefit of the sigma-1 activation. We noticed in Alzheimer's disease, Parkinson's disease, and Rett syndrome patients in clinical studies with our small molecule, ANAVEX 2-73, or blarcamesine. I also now like to move further to discussing briefly the upcoming updates, which are near term, expected.
Among them is data from the full data of the Alzheimer's phase II-B/III study, AD-004. It will be published in an upcoming peer-reviewed journal. We also are in the process. We initiated for full regulatory submission of blarcamesine in Europe at the EMA. We're also expecting to start several studies, one of them in Parkinson's disease, in Fragile X, and a new rare disease. We continue to provide clinical and scientific, both clinical and preclinical papers updates in medical journals. I also like to point out that we've demonstrated with blarcamesine and ANAVEX 3-71 the ability of these mechanistic approaches to not only treat the pathology once it has arisen, but also when there is a need for prevention. So we noticed that the drug also shows the ability to prevent the pathology to express itself.
So in animal models, we noticed that animals never developed the overt dementia in the mouse models, both for ANAVEX 2-73, blarcamesine, as well as ANAVEX 3-71, our second drug in the pipeline. So it's nice to see this ability also to go further upstream, if needed, down the road. So we have multiple clinical milestones and promising pipelines with potential progress towards commercialization, given our late-stage pipeline. And of course, among them is the most advanced indication is Alzheimer's disease. And others to follow, as you can see from this chart. I like to quickly now run through the programs itself and dedicate a bit more time on the Alzheimer's data, which we have so far captured. So we ran through several studies in Alzheimer's disease, which again impacts families tremendously in nearly every aspect of a person's life as it progresses.
35 million people worldwide live with Alzheimer's these days. The most recent data from the Alzheimer's Association indicates that the Alzheimer's pathology has now increased in the U.S. to 6.9 million in the U.S. alone. So it's an increase ramping of this indication with unmet need. We have the ability to replace the kidney, the hips, the knee, and heart, but we cannot replace the brain. So it's still a huge unmet need in the pathologies we are facing. We completed a phase I study. We completed a phase II study, and we completed a phase II/III study. We're now in the stage 4 of ongoing regulatory submission for blarcamesine.
We are planning, after phase I in ANAVEX 3-71 , also a study eventually in ANAVEX 3-71 , which, however, is starting the first study in schizophrenia, given its mechanism of action of M1 agonist and sigma-1 agonist. When we look at Parkinson's disease as well as Alzheimer's, are still unmet need. The motor impairments are in patients which ranges from tremors to of their extremities and goes to the head and stiff limbs and inability to relax muscles during the episodes. And what's also noticeable, up to 80% of those patients with Parkinson's eventually develop and experience dementia with Parkinson's. So that's something which we like to focus on down the road in addition to Parkinson's, to also explore the Parkinson's dementia indication. And that's why we're planning right now a study in Parkinson's disease, a phase II/III, as well as a late-stage study in Parkinson's disease dementia.
In Rett syndrome, we have now completed threee studies of efficacy, two in adults and one in pediatric patients. We really have to face that fact that the key features of Rett syndrome are really, extremely heartbreaking, because this heartbreaking, because the families don't know right away that a patient has Rett syndrome. The child is born a happy girl at the moment, seems to be, and after normal infancy, when nothing is really noticed, the impairment starts to kick in. So instead of starting to walk, there's no walking. So starting to talk, there's no talking. And then the parents go, after developing and bonding with the girl, to the physician, and they find out that the patient, the girl, has Rett syndrome, which is, associated with key features of loss of expressive language, loss of fine motor skills, impaired ability to walk, and repetitive hand movements.
Then they have to deal with this for their life, unfortunately. They run about 350,000 patients with Rett syndrome worldwide. Round about 10,000 to 11,000 patients are expected or estimated to exist in the U.S alone. So it's still an unmet need. We have noticed in our phase II and phase III study in Rett syndrome a very interesting observation in our real-world evidence, a positive feedback from patients with Rett syndrome's families. The voice of the patients should be heard, which say, "We did get a surprise. Once with her mobility, we heard a noise from our family room. Next we looked, and Madeline had climbed 12 steps upstairs to a bedroom by herself." That happened with our drug in our study, after open label treatment. So knowing that the patient was on the drug.
Another quote Jane said, "Within a week starting the Anavex open-label extension, she only had one seizure, and then she went three months without a seizure." So there are some additional, real-world evidence observation and witness comments on RSAA/parents' stories if you'd like to see more of them. What's also interesting, after our EXCELLENCE study , 91% of the patients completed the EXCELLENCE study continued into the 48-week open-label extension. And to date of the pediatric patients who completed the open label, 93 have joined the Compassionate Use program, which we started for all studies so far. Those, after the studies finished, the parents and the patients and the physician requested to stay on ANAVEX 2-73 and blarcamesine, and we opened the Compassionate Use pathway for them to continue to stay on study drug.
That also was chosen by the majority, including the phase III AVATAR study in adults. And as of today, we can say that some patients have been now on blarcamesine for more than four years, combined with the OLE open label extension and Compassionate Use, a very strong vote of confidence to our drug. And we continue to complete our due diligence on the previous studies. And we are planning now an additional study in Rett syndrome, since this would require to move forward with this program. We also want to now move to the next important or most important indication and most advanced, which is Alzheimer's disease. We completed the phase II-B/III studies in Alzheimer's disease, early Alzheimer's disease, to be exact. And we had key co-primary endpoints was ADAS-Cog13 and ADCS-ADL.
The secondary key endpoint was CDR-SB, which was also supported by additional biomarkers of pathology, including structural and functional MRI, which measures the brain volume, as well as many biomarkers, including Aβ42/40 ratio, tau, and other biological markers of the pathology. We also included the prespecified genetic variant biomarker, which I was referencing before, related to the mechanism of action for sigma-1, which is specific. So in this study, we measured the brain volume changes, and it's a clear feature of pathology. It's in every Alzheimer's book described that healthy patients, healthy people, have a fully developed brain with not many gaps in the brain, which you can see nicely on this picture on the left side.
And the Alzheimer's pathology manifests with brain volume loss, which is very intuitive, that if you lose matter of the brain, like muscle loss, you have less ability of being a fast runner. And the same is with the brain. If you lose your brain volume, the mass of the brain, there is an impairment expected. And as a matter of fact, Alzheimer's disease pathology is really correlated with the loss of brain volume, also called atrophy in Alzheimer's disease, which you can see the black holes showing up in the right side of this picture. And very intriguingly, after 48 weeks of treatment, we noticed not in the placebo arm of the treated patients, but in the active arm of blarcamesine treated patients, in almost all regions of the brain, are stopping or the attenuation or even partially reversal of this shrinking of the brain.
And that includes the whole brain, the gray matter, the parietal lobe, the frontal lobe, the limbic lobe, the insular cortex, and the temporal lobe. All areas of the brain which are very clearly manifestations where pathology of Alzheimer's disease is described and known. It's the entire brain, of course. Very intriguing to see this clear message of an attenuation or stopping or delaying of this pathological clear pathological sign of Alzheimer's pathology. Now I want to move to another biomarker of pathology, which is the amyloid beta accumulation in the brain, which is clearly since Alois Alzheimer noticed that in the brain of the first patient, that the accumulation takes place over time, probably accumulates over many years, and eventually then is measurable or visible with PET scan.
But more elegantly, it can be also captured with measuring in the blood by what is called plasma Aβ42/40 ratio. And that has been now shown to be identical. And because it's more convenient to the patient and requires less resources than the PET scan, it's important to know that's equivalent to a PET scan of the brain, which requires a contrast medium, which is not very preferred for patients because of a foreign substance is injected in the body of a patient. But the Aβ plasma 40/42 ratio is a simple blood test. And what we have noticed is that with the blarcamesine treatment, we noticed an improvement of the Aβ42/40 ratio. That means an improved or reduction of the Aβ in the brain, which is the correlation of this 40/42 ratio. It's counterintuitive.
So in the blood, the Aβ42/40 ratio increase represents a decrease of the Aβ pathology in the brain. On the left side, you see the clinical worsening of the placebo arm slightly, further clinically worsening in 48 weeks. And then countering with blarcamesine, you see an improvement of this ratio, which is significant. And interesting enough, because it was published, we put it in this slide to put it in perspective, the same measure, 42/40 ratio of Leqembi, and seeing and noticing that we seem to have a stronger signal in a shorter period of time than Leqembi. But that also needs to be put in perspective with potentially different assays here. But it's important to be aware of that our data clearly shows a very nice separation of the Aβ pathology against placebo.
And now I would like to point out something extremely relevant and new, which is the recent guidance from the FDA related to early Alzheimer's disease, exactly spot on the target population of our phase II/III study. And it's important to be aware that until recently, before this guidance came out several weeks ago, the requirement for an FDA approval was always a co-primary endpoint in Alzheimer's disease, and co-primary endpoint of a cognitive and a functional endpoint. So either, together, ADAS-Cog and ADCS-ADL. And interesting enough, or very encouragingly, this new issued guidelines from the FDA now states, and the reason for that is that the pathology in early Alzheimer's is so slowly moving, and it's so subtle that the activities of daily living, the ADCS-ADL, often cannot be measured well enough as an impairment.
So the new guidance requires not anymore a co-primary endpoint, but one cognitive endpoint alone is sufficient for a primary endpoint for approval for an indication or a study in early Alzheimer's disease. We believe that this opens another possible pathway for us to move forward. And we're encouraged by this new development, as you can imagine, since it would allow us to have an intriguing discussion with the agency, since we have now demonstrated clearly that we met the primary endpoint of ADAS-Cog13 with a score of minus 1.783 and a p-value of 0.0226, which even is less than the required measure of 0.05. We also were significant CDR-SB, which captured both cognition and function. And we also mentioned before that we demonstrated a significance in two additional biomarker classes of pathology.
One is the Aβ 42/40 ratio, as well as the reduction of brain volume and stopping of the brain volume and attenuation of the atrophy or the reduction of the brain volume, with up to 0.0005 p-value. We also observed that the drug was generally safe and well tolerated. The next steps are now to initiate. We already initiated the regulatory submission for the oral blarcamesine for Alzheimer's disease to the European Medicines Agency, EMA, in Europe. We're starting now also to explore the first commercial activities and examining innovative strategies to effectively engage with patients, providers, and payers. You will see more of that, as we progress this year. I mentioned before, we're expecting the full data to be published in an upcoming peer-reviewed journal.
Also, what is very important, almost the majority of the patients in our phase II-B/III Alzheimer's disease study are now in an open-label extension study lasting at least 96 weeks, which is called the ATTENTION-AD study. Also, I want to quickly point out the differences to other studies which have been now in the visible data because they were published, among them to put in perspective our data with our oral once daily formulation to a more complex administration with additional possible black box warning or safety challenges. For example, the donanemab data showed a much weaker ADAS-Cog13 score of -1.35 over 76 weeks. So much longer duration was needed to have a score of that magnitude. ANAVEX 2-73 blarcamesine reached already much quicker, much sooner a separation in the identical population, by the way.
So it's very nice to be able to compare that almost head to head, in this study from a population perspective with a much larger score of -1.78. And again, a minor score means a better cognitive signal than placebo. Again, once daily orally. And we see also for the comparison to Leqembi, which did not use ADAS-Cog13. That's why we cannot compare it. But they used CDR-SB. We also are in a better position because we reached earlier, 6 months earlier, a similar separation to placebo than Leqembi. Again, with a simple oral once daily scalable drug. We also like to point out we are well positioned to for future expansion and worldwide commercial rights because we own them and we also have a strong IP foundation.
We are now exploring commercial activities and we're examining innovative strategies to effectively engage patients, providers, and payers. I mentioned you will see more of that because of the high demand from Alzheimer's disease patients and families for easy access and scalable treatment options. There's also the intended to reduce the need for complex procedures for the treatment of people with Alzheimer's disease. We have noticed that Leqembi, after seven months of heavy marketing, was not able to get more than, I think, 2,000 patients on study drug, which is for a disease of the size of 6.9 million, a very, very humble number. And again, we believe that blarcamesine orally once daily versus the challenges of biological antibodies, intravenous antibodies, might be a better solution. We also like to point out in this slide the additional indications we are covering with our portfolio. I mentioned Alzheimer's disease.
So the number in the U.S has risen. It used to be 6.5 million patients today. But it has now been increased. And we just picked up these numbers a week ago from the Alzheimer's Association publication that was now indicating the number has increased to 6.9 million patients in the U.S alone. There are 7.8 million patients with Alzheimer's in Europe. And the largest number is in Asia with 23 million and globally 35 million. So you understand this indication is globally a problem and increasing.
And for that reason, a scalable, simple solution like a patient goes to the physician, the physician assesses the pathology without complex PET scans or other measures of CSF measures in the spinal tap or other painful potential procedures, and then gives the patient something to take orally once daily for a year or more and assesses the effect of this in the patients. So this is the unmet need, really, for this indication. And that also translates to Parkinson's disease, of course, in the same way. And schizophrenia is also an unmet need. We have also frontotemporal dementia, the rare disease franchise, further on the bottom of this slide, and Rett syndrome and Fragile X. I mentioned before we are aiming to bring these lead therapies to patients in Europe, Asia, and the US following regulatory submission discussions.
We also like to point out we have wide international patent protection up to 2039 for our product candidates. Last but not least, I like to point out that we have enough cash runway for the next foreseeable future. We believe that we have four years of runway, since we have our cash position of $143.8 million as of last quarter, which was December 31st. We used $27.8 million in the last fiscal year. So you can easily make the calculation if that stays at that level. We might have a little increase, of course, this year because of our activities.
But in general, we believe that we are sufficiently funded for four years, with our sustainable and also very efficient cash management, which is also thanks to non-dilutive funding from foundations like the Michael Fox Foundation, which we like to thank very much for, as well as the International Rett Syndrome Foundation and some government funding as well. So this would not happen without a team. We're grateful for that. Especially like to highlight our VP, Head of Biostatistics, which has worked with the FDA for 27 years in the neuro division, where all the Alzheimer's studies and other neuro CNS drugs have been approved in the past, Kun Jin. And also like to highlight the strong Scientific Advisory Board, which we have, backing us in our endeavors.
I like to highlight especially the Chairman of the advisory board, Marwan Sabbagh, which has been very efficient and effective in leading us, since the Alzheimer's study came out. Now I want to close out with, again, summarizing where we are with our precision medicine platform and novel central nervous system platform to improve chance of clinical success. Given our biomarker data, we have several promising differentiated therapeutics, with challenging CNS diseases and high unmet need. We achieved multiple clinical milestones, and we're progressing now from a research-focused to a commercial stage company to bring therapies to patients around the world. We believe we have a good position to expand worldwide commercially, with a strong IP foundation, with our orally administered candidates. We have sufficient cash for the next four years. In summary, the key Anavex inherent advantage is really the platform scalability.
When you look at the biggest challenge of the society and Medicare and the rising cost of the Medicare system, you need equitable and accessible drugs for the diverse population and maintaining sustainability within the global healthcare system, which we believe we could offer with our orally administered drugs. With that, I like to give back. If you have further questions, please contact us at www.anavex.com. Thank you and appreciate your listening in.
Hey, Christopher, thanks for that thorough presentation. I have two questions here for you. Firstly, can you talk about the relevance of sigma-1 receptor as a target across kind of the range of indications that you're pursuing? Is it more relevant in some diseases than others?
Excellent questions. It's really a question we can only answer in the clinical setting, ultimately. In the preclinical setting, it's not only our work, but it has been now demonstrated that the sigma-1 activation is really so, beneficial in many pathologies of the CNS spectrum from rare diseases, which I mentioned, Rett syndrome, infantile spasm, Angelman syndrome, but also other diseases like Huntington disease and ALS, but also other diseases of pathology like, Alzheimer's and Parkinson's, which we have, of course, tested in the clinic, but have been started in the preclinical setting. There is also the ability to potentially address the activation of sigma-1 in indications like depression and, other impairments, which are more subtle. So it's really a lot of data, preclinical data, to indicate that the upstream activation of sigma-1 is beneficial to push back on imbalances, which are then causing this pathology.
And when we look at the big picture of the papers which are coming out every other week, we notice that there's an influx of lessons learned that the complexity of the ability to address complex diseases is really always captured by the sigma-1 activation, by the body-owned defense mechanism. And it's shown that sigma-1 even goes into the nucleus to restore chromatin remodeling. So it's really fascinating to see the ability to restore inflammation and also enhance biological activity like possibly longevity or possibly also infections and increase the body-owned resilience to infections. So it's so interesting and enriching and stimulating to see what the science so far, and we have probably not yet even understood completely in how many further potential the sigma-1 activation might find.
But to answer your question, it's really ultimately in the clinical setting where we can state with certainty that preclinically there might work very well for all indications and preclinical models have the inherent imprecisions. But in the clinical setting, it might very well be that the sigma-1 activation is perfect or the best for Alzheimer's and also for Parkinson's, but maybe not for depression. You know, so it's so hard to find out until we test it in all these indications. But we are in the process of working through our list, as you can see, with schizophrenia with 3-71 and Alzheimer's and Parkinson's with 2-73.
Okay. Looks like we are unfortunately out of time. I'd like to thank you for taking the time to take us through the story. I wanted to thank our listeners for joining it as well. Thank you so much.
Thank you, again.