I'm Anish Bhatnagar, CEO of Soleno Therapeutics. Soleno is based in the San Francisco Bay Area. We're in Redwood City, California. We're now about 140 people. We used to be about 20-some, about 18 months ago. We have a recent approval for a drug called VYKAT XR. It's for the treatment of hyperphagia in patients with PWS, Prader-Willi syndrome, four years and older. It's a significant unmet need. I'll walk you through that. The approval was based on a long phase III program, which I will walk you through as well. The drug itself is based on a known pertinent molecule but has significant IP protection, potentially into the mid to late 2030s. The drug had breakthrough and fast-track designation. It's also orphan designated in the U.S. and in the EU. Significant commercial opportunity.
We estimate greater than $2 billion in the U.S., as well as a significant opportunity outside of the U.S. as well. We have a strong balance sheet, approximately $300 million, $290 million at the end of last quarter. The disease itself, Prader-Willi syndrome, PWS, is a genetic disease. It is a neurobehavioral and metabolic disease. It's something that happens to 1 in 15,000 live births. It happens spontaneously. It is not inherited. It happens by chance, and it happens at the same frequency regardless of geography or ethnicity. The same sort of birth incidence numbers that you see here will apply to Asia as well as other geographies. It's a disease which is diagnosed, at least in the Western world, right around the time of birth. The reason that happens is that these patients are born with very low muscle tone. These babies are floppy babies.
At birth, they will typically be sent to the NICU where they'll have a bunch of tests. One of those tests is going to be a genetic test for PWS. Within the first few weeks of life, the parents will know that this is a child with Prader-Willi syndrome. They'd also be told, at least until now, that not much could be done for them. The only thing that can be done is they're put on growth hormone because they're all growth hormone deficient. They have short stature. As they grow older, by the age of about three or four years old, they start to show more of an interest in food. They start to develop a disproportionately high amount of body fat and low lean body mass.
By the age of seven or eight, they will all, virtually all of them, will develop the hallmark symptom of the disease, which is hyperphagia. Hyperphagia is an insatiable desire to eat. This is not you or I feeling hungry. This is the brain telling these people they are starving even as they eat. The reason for that is that their satiety switch in the hypothalamus does not exist. They do not know that they are full. They will eat whatever comes their way: 20 cookies, four pizzas. They will eat themselves to death. One of the catastrophic outcomes that is possible in these situations is a gastric rupture. They will literally eat till their stomach bursts. It is a terrible disease. The only thing that has been done until now is restriction of access.
These children, these adults live in situations with locked refrigerators, locked trash cans, locked pantries. As you can imagine, if food is being restricted, when your brain is telling you you're starving, they tend to develop significant behavioral abnormalities. They'll have aggression. They will have depressive episodes. They'll be highly anxious. In general, cognitively, they are impaired. Average IQ is in the range of 70-80. It's a terrible situation. It is also a disease of the families because to take care of these patients, families will have to often give up jobs. One person will have to give up a job. They'll have to stay with them, make sure that if they're going to school, they don't have access to food, et cetera. Divorce rates are very high, and unaffected siblings will have PTSD.
It is something that has not seen a treatment since 1956 when it was first described. Numerous companies have tried. The first drug approved is our drug, VYKAT XR. It is based on a known pertinent molecule called diazoxide. It is a diazoxide salt called diazoxide choline, which allows the drug to have a much higher absorption as well as be formulated into a once-a-day tablet formulation that makes it a lot more tolerable based on the data that we have generated. The indication is for the treatment of hyperphagia in adults and pediatric patients four years of age and older with Prader-Willi syndrome. This is important because four and up is when you expect to see hyperphagia. Children younger than four will almost never have hyperphagia. It is the first treatment to be approved.
It is a clinical program, which I'll walk you through briefly, that has shown the significant improvements in hyperphagia with the drug. We believe that it can become the foundational therapy for patients with PWS. The clinical program, and we've presented these data in many different forums in a lot more detail, but briefly, this is a program that started in 2018. It started with what we call C601 or the Destiny PWS study, which was a randomized double-blind placebo-controlled study in 127 patients enrolled in the U.S. and U.K. at 29 sites. The challenge with the program was that C601 did not meet its primary endpoint, and I'll come to that in a second. All those who completed 601 were given the ability to roll into an open-label extension study called 602.
Patients were on 602 for between three and five years when we randomized them into a withdrawal study. It was a placebo-controlled randomized withdrawal study. At the end of that, when they completed that, we allowed them back into an open-label drug, which is called C614. We presented bits and pieces of these data along the way. If you start from the left of the slide, C601, as you can see, the curves are, while they are starting to separate with placebo in gray worsening, we did not see significance. What we realized after the fact was that in the middle of 2020, when we announced the data, was really when COVID had started. The endpoint in all of these trials has changed from baseline and hyperphagia, which is a subjective endpoint.
When we did the analysis retrospectively of excluding the COVID-affected data points, which is about 20%-30% of the data, we saw the trial was indeed significant for the primary as well as all the key secondary endpoints. We then, while the patients were in 602 in the open-label extension study, had a prolonged dialogue with the FDA on how we could get the drug approved. Their contention to begin with was that we needed to do a new study. Our contention was we should not be needing to do a new study because the data showed that the drug worked. What you are seeing here, if you look at these numbers, at the end of 602, you are seeing a number of 9.3. At the left end of the slide, you are seeing a number of 23. The hyperphagia score goes from 0 - 36.
The median baseline value is close to 23 when the program started, which is severe hyperphagia. What you're looking at at the end of 602 when we did the randomized withdrawal was a score of nine. These patients would not even qualify for a hyperphagia study because the typical baseline is 13. We had seen a tremendous effect. Nevertheless, the FDA wanted to see additional control data. We were able to negotiate doing a randomized withdrawal using only the patients who were currently on the study. You see the 602 RWP data where the gray line is showing significant separation from the blue line. In those 16 weeks, we saw a statistically very significant worsening of the placebo patients with a p-value of 0.002. That was the basis for our submission to the FDA.
While we did that, we allowed the patients to go back on drug in a study called C614. As you see there, we are back to 9.4. After a year of starting drug, everyone is back. This is about as convincing an evidence of efficacy as you would expect to see. You give the drug, there is an effect. You take the drug away, the effect goes away. You give the drug back, the effect comes back. In my mind, there is very little argument that this is a drug that really does work. From a safety perspective, which is important, this is a drug that is based on a known pertinent molecule.
We have an extensive amount of data available from the trial program where more than 100 patients were treated for more than a year, 440 total person-years of experience overall at the time we submitted, and more than six years of continuous exposure in many patients. It is extensively studied. The safety profile was generally consistent with what has been seen with the pertinent molecule, although it appears to be more benign in many cases. The most common adverse events to look at are hypertrichosis, which is increase in body hair, edema, and hyperglycemia. These are typically grade 1-2, typically self-limiting. Sometimes they will need a dose adjustment. Sometimes they will need a treatment with a drug like an oral antidiabetic. We have had a couple of serious AEs that are more notable are in the label.
One is erythema multiforme, and the other is DKA, which has happened in one patient each. As I said, we've presented this data pretty extensively. We have engaged with the advocacy community very significantly over time. We support their local meetings, et cetera. We now have a community council where several members of the community sit in and provide advice on our programs or our initiatives, et cetera. These actually include some adults who have PWS. We also partner with the advocacy organizations on helping them with issues that are not specifically drug-related, but things like the assessment of the disease or the disability, which gets them other benefits. We are very intertwined with the advocacy groups, and they have been extremely helpful to us in the process of the trials as well as the approval process. From a commercial perspective, this is a large commercial opportunity.
It is not ultra-rare. It is 1 in 15,000 live births. If you translate that into claims, if you look at claims data, you translate into prevalence, we see about 12,000 patients in the data today. Traditionally, this was thought of as about 10,000 patients, and that was based on an academic paper that was published a few years ago from the University of Colorado where they admitted that this was likely to be the lower bound of prevalence. Indeed, that is the case as we look at claims data. As there is a more specific code for PWS, we see about 12,000. We see the TAM as being about 10,000 out of that.
What you're doing is excluding those who are either less than four years of age or older than four but not hyperphagic yet or have significant comorbidities that would not allow them to be on drug. So TAM of about 10,000, fairly concentrated market. We see about 300 healthcare providers either directly prescribing to or influencing the prescriptions of about 4,000 or about 40% of the TAM. So fairly concentrated. The diagnosis rates, at least in the Western world, are very high. We see 85%-90% of people who are diagnosed at birth today. Why do we think the launch will be successful? The clinical program has shown very robust evidence of efficacy. If you look at all our published data, there's comparisons to natural history that have been very significant.
There have been changes from baseline over one year and three years that are published that are very significant. There is other data that we will be presenting at an upcoming conference called United in Hope where you will see more evidence of efficacy. We have invested significantly in our commercial infrastructure starting about a year and a half ago when we got the pivotal data. We have a strong analytics team. We have significant account profiling that already happened at the time of birth. Our field force teams, the key attribute for them is rare disease experience. Virtually all of them have been deeply embedded in the rare disease world. From a payer access strategy, we invested early in that as well. As you can imagine, this is not a disease that payers were familiar with.
What we saw was that the moment you talk to them about the disease, it was not difficult for them to grasp. The unmet need was obvious, the fact that nothing else exists. Given the rarity of the condition, there's a low-budget impact. We see this as something that should resonate with payers. As I said earlier, we are deeply engaged with the advocacy community. We have disease state awareness work that's going on. We have education campaigns that are going on. We have a strong presence at all relevant medical conferences during this time. When we think about our launch, we segment the patients by age in general. You'll see based on this slide why we do that.
The segmentation of younger versus older is typically, in our minds at least, based on an age of 25 because at 26, you're going to transition out of your parents' insurance. It is highly likely that until the age of 25, you are living at home with parents. The attributes of that population that are different from the older population are that these are people who are living with their families, who are being cared for a lot better. They are seeing healthcare providers more. They are seeing healthcare providers four to five times a year, which is significant. The primary point of care for these people is pediatric endocrinologists. This is kind of a legacy thing because of growth hormone use. Growth hormone is typically provided by, prescribed by, and dose-modified by pediatric endocrinologists. They are the primary caregivers.
As they transition to adulthood, we see, A, there is this increase in desire for independence in these patients, even though in general, it is not possible for them to be independent. The most independent they would get is living in a group home, perhaps, where there might be one caregiver for a handful of people, but they would still need that kind of care. We see that the prescribers will change from pediatric endocrinologists to adult endocrinologists in general or psychiatrists. Or sometimes we will see geneticists who are seeing patients all along the lifespan. In general, the primary care point is endocrinology. From a reimbursement perspective, critical things that we think have made a difference will continue to make a difference. One is that the need for treatment of hyperphagia is something that people have found easy to understand.
When we talk to payers, even though this is a disease they're not familiar with, they quickly recognize the need for treatment. This is a low-budget impact issue because the numbers are not large. The clinical data is convincing. We have found that the randomized withdrawal data has resonated very significantly with payers. It is the only FDA-approved treatment for hyperphagia. When you look at the alternative of living in a home with locked refrigerators and locked pantries and locked trash cans, it is easy for payers to understand why this is something that they should be doing. We have a patient services team, which is also very good. This is a very experienced team of people. It's called Soleno ONE. It's a single specialty pharmacy, which we are able to control tightly. Soleno ONE was live on the first day of launch.
The first prescription was sent out by April 14, so about two weeks after we got approved. We think the drug is positioned to be the standard of care in PWS today. It is obviously the first one approved. The key elements of the label are there are no exclusions for severity of hyperphagia. There was a lot of discussion around, is it going to be just for severe hyperphagia? No, there are no exclusions around that. There are no box warnings. There are no REMS. There are no contraindications. Interestingly, it is clearly stated in the label that it should not be substituted with diazoxide oral suspension, which was also a question that we were asked. The early metrics that we provided as of May 6, which was the first, I think, 26 or 27 days of launch, there were 268 start forms from 131 prescribers.
We did say that the value proposition seemed to be resonating with both commercial as well as government payers. This is an interesting stat of the 131 prescribers because often in rare disease launches, you will see a handful of KOLs putting out large numbers of prescriptions. What we are seeing here is very interesting because it is a very broad-based prescription paradigm, somewhat unexpected, but pleasantly so. Regarding Europe, the unmet need remains the same. As I said earlier, the birth incidence of PWS is the same regardless of geography or ethnicity. The problem in Europe is as big as the problem here. We estimate just in the EU4 plus U.K., there are about 9,500 patients. Obviously, in the EU27, the number will be larger than the U.S. We also announced in May that we had submitted and the EMA had validated the submission of the MAA.
From an IP perspective, there's three families of patents that we are prosecuting in all major markets. The primary cases on all have issued. The salt polymorph patent has a primary expiration at the end of 2026. With PTA and PTE, if applied, it has the potential to go to 2034. We have two families of method patents, which have primary expirations in the 2035 timeframe with the ability to be extended into the late 2030s. From a cash perspective, as of the end of March, we had $290 million in the bank, which included $50 million in debt and a total fully diluted share count of 55 million shares. Thanks for listening. Happy to take questions.
Yeah. Are you able to share any insights into?
Yeah. Could you share some insights into the competitive space? What competition is coming up behind you?
There's two late-stage programs. The latest stage program is Acadia. Acadia is working on a drug called carbetocin. It's an intranasal three-times-a-day product. It's a drug that was developed many years ago by Ferring. It's actually used in pregnancy and delivery-related complications in its intravenous form. This is intranasal. Ferring did a phase II study. They put it on the shelf. It was bought by a private company called Levo. They ran a three-arm study, two doses versus placebo. There was an inverse dose response. The higher dose did worse than the lower dose. The FDA asked them to do a new study. They submitted. There was an adcom. It was voted down 12 to 1. They got a CRL. The company went under. Acadia bought it. They're running a study of the lower dose versus placebo.
They have said that they would be reporting data towards the end of the year. We will see what that looks like. The other program is Aardvark, which is a bitter taste receptor-related drug, which is a new mechanism of action. The data that they have publicly shared is open-label data, short-term data. It is hard to interpret that data in a PWS setting, in my opinion. I believe they will be starting a phase III study soon.
Just to follow up, you obviously have a very strong trial, especially patients not on the drug. Do you think the competitors will have to show the same kind of data?
The FDA does not require that, as you know, right? The FDA requires placebo-controlled studies in most settings like this. I think the challenge becomes doing the trials. Can you do a trial that is placebo-controlled if a drug is approved? I think that is probably the bigger challenge. I do not think the need is from the FDA's perspective. There may be a need from a payer perspective later. Maybe there is a step-through depending on pricing, etc. From a regulatory perspective, no.
All right. Thank you.