Here to present proteins that can help in haploinsufficiencies, where there are deficiencies in the with the disease caused by the disease. It has enabled us to create a number of potential first-in-class modifying new disease new medicines for diseases. With zorevunersen entering phase III later this year, we have a program in autosomal dominant optic atrophy, or ADOA, that'll be entering the clinic later this year as well as programs in Rett syndrome and SYNGAP1 with our partner, Acadia Pharmaceuticals. And we believe that our unique platform opens up the potential for 6,500 additional potential disease haploinsufficiencies, where we could have a disease-modifying effect. Looking at our pipeline, as I mentioned earlier, we have a program in zorevunersen that's heading into phase III. It'll be entering phase III next year.
You also can see our pipeline in SYNGAP1 and Rett syndrome, as well as an undisclosed program with Acadia. They will be providing an update on those programs either later this year or next year, but in ADOA, we have STK-002 entering the clinic later this year. We'll be providing the update when we have our first patient in, so our first program for zorevunersen, we're looking at Dravet syndrome, so Dravet syndrome is a severe genetic epilepsy. It is characterized. One in every 16,000 babies are born with Dravet syndrome. There's approximately 35,000 patients affected across the sort of six major countries we've listed here, and it is characterized by long, sustained, rather severe, seizures that occur starting at one year old in different patients and continue through the life of the patient. We'll talk a little bit more about that.
The effects of Dravet, so the seizures I mentioned, you have patients who are getting seizures anywhere between several a day up to hundreds of seizures a day, including drop seizures, which can be quite extreme. Despite all of the anti-seizure medicines out there, 90% seizures are still not adequately controlled, so those are still patients refractory to seizure treatments. Approximately 20% of children and adolescents will not even reach adulthood due to SUDEP that they may encounter during their lives. When you look at the effects of Dravet, it goes well beyond seizures. I've had the opportunity to meet families. We spent a lot of time with families in the Dravet Foundation, and what you'll find is parents and caregivers who are monitoring their children or their loved ones for every...
They have to stay within an hour of, sorry, within a foot of them in case they have a drop seizure. They're staying, they're monitoring 24/7 . They're sleeping next to their children because they're afraid that they could die in their sleep. And so what we find is, despite all the great drugs that are out there right now, there truly is a need for a disease-modifying drug. And when we look at the ASMs on the market, and when you talk to the families, Fintepla has been a really important development for patients. But again, you find the need for a disease-modifying approach. And what we found with zorevunersen, with our approach is, and this really kind of states what our platform can do, when the haploinsufficiency that occurs here, this is a haploinsufficiency of the SCN1A gene.
So what ends up happening is it results in 50% less protein that stokes protein expression in the NaV1.1 channel. What happens with these patients is we find that about the age of one, they start to have seizures, and by the age of two, their brain will no longer develop beyond that from a cognition and behavioral perspective. What we have found with our approach is that by stoking the healthy allele, the healthy gene, and not the dysfunctional one, we're able to increase production in that gene of 50%-80%, even up to 100%. That then helps cover for this haploinsufficiency, hence being disease-modifying. What we've done to understand these patients and understand what they, what the seizure frequency looks like, we've conducted a natural history study over two years.
What we found is, as you can see here, that despite all the medications listed on the right and the improvements that have been made in anti-seizures for these patients, there's still a number of patients who remain refractory to the treatments, and therefore, there really is a need for better treatment. One thing we found in the natural history data, and this was had never been done before, we found that we looked at basically the Vineland-3. So the Vineland-3 is a measure of, it's an adaptive behavior scale. It's used to understand how the brain, the cognition and behavior occur over time. What you can see here is these patients suffer from a severe deficit in areas like receptive communication, expressive communication, personal skills, fine motor.
And so using this, we were able to identify the fact that, again, the need for a disease-modifying treatment that could actually improve cognition and behavior would be truly meaningful for patients. So that then brings us to zorevunersen. Most of you may have seen, but earlier this year in March, we produced some exciting data from our phase I/IIa study, where we looked at a number of different doses, your typical phase I study, where you've got a large range of doses, anywhere from 15 mg all the way up to 70 mg. And what we found is at, on top of all of the other anti-seizure meds that patients were on, at three months, we saw an 85% reduction in patients who were given the 70 mg loading doses and 74% reduction at six months.
Keep in mind, this is on top of standard of care. This is on top of some of these patients on four to five different ASMs or on GI disorder drugs. And so you can imagine this is a quite profound effect that we saw. What we've also seen is in our OLE study, so we have an open-label extension study that we've been conducting, with patients having been on the drug for as long as even three years. We've seen durable reductions in seizures and meaningful improvements in measures of cognition and behavior over the twelve months, which I'll show you momentarily.
From a safety perspective, this is an antisense oligonucleotide, so there are gonna be some CSF level elevations, but we have not seen any that have been clinically meaningful, nor different from any other ASOs that are out there on the market. What I would say is that the single and multiple doses of 70 mg were generally well tolerated. When we look at some of the data now, this is, we're gonna walk you through some of the seizure data we've seen. Basically, it's 70 mg doses, and here what we're showing is three loading doses and then maintenance doses. This is how to really sort of think about it. If you'll hear our various management team members and clinical team talk about it, at the end of the day, Dravet is not a neurodegenerative disorder.
It is a disorder where the synaptic connections at the neuronal level are not acting correctly, they're dysfunctional. And so what happens is, as we mentioned, at two years old, the brain stops development from a cognition and behavior perspective. With our drug, what we've seen is, and we believe that providing a loading dose is a way to sort of jumpstart those synaptic connections, get the brain sort of rewired and working correctly, and then over time, you're maintaining that with dosing every four or so months, based on the half-life of the drug. And what you can see here, what you're looking at is the orange and red lines represent the 30 mg and 45 mg dose levels. And you saw that we saw patients that had seizure reductions all the way down to 50%.
But when you look at most important is 7 mg, two or three dose loading schedule, you see a marked deepening in the anti-seizure reduction level, so we are seeing reduction levels, as I highlighted earlier, between 75% and 85% in these patients, again, despite being on all their other drugs, so that green line has us very, very excited for what we're gonna be doing in our phase III, and we could see these reductions in seizure frequency even with just one dose, so on the left side, you can see with seven and eight patients counted, that we saw after three months and six months, 43%, 57% reductions in seizure frequency in these patients.
When we look at the 70 mg, two or three dose, that's where you see the 74%- 85% that I had alluded to earlier. These are, again, very exciting data when you think about the seizure burden on these patients. And when we look at across these two and three doses of zorevunersen, we saw 80% of patients treated with these doses experienced a greater than 50% reduction in seizures. What we've highlighted here, and this is an individual patient. Each bar represents an individual patient. You have a number of patients who are actually reaching complete seizure freedom, and you're also seeing in patients across from two to five to three, all the way up to even 17 years old, an effect here.
When people ask, "Is there an age relation in terms of, does the brain get so far where a patient might be too far gone, so to speak, in terms of their brain development?" We're actually finding that, again, because this is not a neurodegenerative disease, this is about synaptic connections, we're actually able to, again, rewire these brains potentially, in these patients, even at a later age. It may take more time, but that's something we're actually, we're obviously investigating as we think through our phase III plans. Here we see the durable reductions in seizure frequency over time. So this is now data from our OLE studies. As I'd mentioned, we've got patients who have been on drug for over three years now. There are about 81 patients that we're still tracking in this study.
What you can again see here is the 30 mg and 45 mg doses are lowering seizures even up to 50%. But importantly, the 70 mg doses are getting patients down. Again, 70 mg loading, plus a dose of 45 mg maintenance. You can see the marked improvement and deepening we saw of the effect on these patients in terms of the seizure burden. Very, very exciting for us. Now, turning to the disease-modifying aspect. So what we are pursuing as a company is the treatment of Dravet syndrome, not seizures associated with Dravet syndrome. And what you can see here is disease-modifying. This is really what is important to us.
What you saw earlier when we saw in natural history, we saw deficits, we saw the declines in cognition and behavior from patients who are already on standard of care. With our drug, what we saw in the OLE, this is at 30 mg and 45 mg, we actually saw improvements, meaningful improvements in all these different areas according to the Vineland-3 subdomains for the patients. If we think back to what this is like for the caregivers, this is extremely important. Having met a family, for instance, I got to meet a patient who is eight years old with the brain of a two-year-old. The parents have put the child on all possible medications, but you can see as the patient interacts with the parents, he is literally functioning like a two-year-old.
If you think about it, if we have the ability to actually set the brain development on some kind of a level where instead of flatlining, even if it comes up not to normal levels, but even somewhat, and you can increase the ability for a patient, for a child or an adult, to piece several words together, even that can make a meaningful difference for these caregivers and for these patients. So again, we're very, very excited about the disease-modifying potential of our drug. And when we look at this across two different sets, I've mentioned caregivers a lot, but from a clinical perspective as well, when we look at the natural history study that we conducted versus these OLE patients, basically, what we're looking at here is the dark bars represent the natural history, orange bars represent the patients on zorevunersen....
And the lower the bar, the more the improvement we can see across these different areas. And you can see the improvement on the Vineland score from a clinical perspective is quite meaningful, and also from a caregiver perspective. And so when we think about this, this totality of data, we're extremely excited about the fact that we've seen the seizure reductions, both at lower doses and the higher doses of our drug, and the fact that it's safe, so we can feel comfortable dosing at the higher levels. We can see through the OLE that we have the effects on cognition and behavior. And now, at this point in time, it's all about meeting with the regulatory agencies to figure out what the phase II registrational study will look like. But we anticipate there being 70 mg loading doses, followed by 45 mg maintenance doses.
We are currently coordinating this across the EMA, the FDA, and the PMDA in Japan, which will obviously takes time to coordinate a global study. We plan on coming back to the street with updates before the end of the year in terms of what the regulatory pathway looks like going forward. Our second program will be having a patient entering the clinic, as I mentioned, in the next few months, you know, by, before the end of the year. This is an autosomal dominant optic atrophy, ADOA. This is a severe progressive optic nerve disorder. It's 60% to 65% to 90% are caused by haploinsufficiency, where these patients lack an OPA1 gene or the, insufficient amount of OPA1 gene. The OPA1 gene is actually the one of the- is a, a very metabolically active gene.
It determines a lot around the structure of the mitochondria. And what we found is that by stoking, similar to what we showed with zorevunersen, by stoking the healthy gene, we're able to increase the OPA1 protein levels by 50%+. And so when you look at the patient population, this is one out of every 30,000 people are affected by this. And when you look at the actual what the impact is for patients, 46% of them will actually go be registered legally blind. I'll walk you through that in a moment. So there's no approved disease-modifying therapies for ADOA. So what ends up happening with these patients is you'll have children who are in school, who struggle with reading the chalkboard or with sight, and they suffer from...
They lose central field, and they have to basically rely really on their peripheral vision. This is all based on the retinal ganglion cells being dysfunctional. What we found is, through one intravitreal, we plan to test this in phase I. We will dose a patient with an intravitreal injection. It's once a year, and we will see that we believe that we can improve the acuity for these patients, the visual acuity for these patients over time, and so that this could be the actual only... This could become the only disease-modifying therapy for ADOA. At this current time, what they'll do is they'll give a child glasses or try other methods for improving vision, but they cannot improve the central vision, the central field of vision that they lose over time.
This depicts what a child or a patient will see on the left side with healthy, versus on the right side with the optic neuropathy. The body of data we have is preclinical, obviously, heading into our phase I study. What we've shown is that the increase in the OPA1 protein, ATP-linked respiration, ADOA patient fibroblast. We've shown dose-dependent increases in OPA1 protein expression in rabbit retina and NHP, which obviously are important animals to look at when evaluating ophthalmic disorders. We've identified an NHP model, which is a disease model for ADOA, so we'll be looking at that to see what kind of data we can produce in those monkeys. We've also seen it's well-tolerated for up to 29 days after the intravitreal injection in rabbit.
We feel that the safety profile in NHPs and rabbits is similar to other intravitreal oligos. As I mentioned, the phase I Osprey study will begin later this year. As we come to the end of the presentation, I want to remind everyone of our upcoming milestones. We'll be providing the regulatory update on zorevunersen on the phase III study at the end of this year. We'll anticipate kicking that off next year. We are going to initiate that phase I in STK-002 for ADOA. We'll have our first patient in, we anticipate, by the end of this year. We have our Acadia collaboration, which has gone well over the last three years, and we'll continue to execute there and await the update from Acadia Pharmaceuticals.
We have $282 million in cash and marketable securities. We have cash runway through 2025, and so we're a strong cash position. We feel well positioned to launch the phase III, provide the updates to Wall Street, and continue to run the company. You know, when we think about this from a commercial perspective, if this were to become the first disease-modifying medicine for these patients, there's quite a bit of opportunity here globally to serve an unmet patient need. There's an incredible burden on the healthcare system right now. You have families where their children are so severe, they're going to the ER on a weekly basis. The ER doctors know them by first name.
So if you can imagine a drug that could reduce the seizure burden, increase the cognition and behavioral abilities of these children and adults, it will create a much more efficient spend on for the healthcare system as we give our patients zorevunersen in place. So thanks, all, for the time, and I'll open that up to Q&A.
Yeah. Thanks very much, Tommy. Yeah, so the floor is open for Q&A if you have any questions. Yes.