Hello everyone, good morning and welcome to the Jefferies 2024 Global Healthcare Conference. It is my pleasure to now introduce Jim, the CFO of Soleno. This will be a 20-minute presentation, and we will leave a few minutes at the end for any Q&A.
Thank you very much. Good morning and welcome. My name is Jim Mackaness. I'm the Chief Financial Officer for Soleno Therapeutics. For those who are not familiar with Soleno, we're based in the San Francisco Bay Area, California, about 80 folks, and we're focused on a single asset, DCCR, for the treatment of Prader-Willi syndrome. Earlier this year in June, we submitted our NDA for DCCR in PWS, and we're notified in August by the FDA that it was accepted to file, and we have a PDUFA date of December 27th of this year. The NDA was submitted based on the top-line data from the randomized withdrawal period, which were reported out in September of 2023. For DCCR, we think we have extensive IP protection, three families of patents that have been prosecuted in all major pharma markets throughout the world.
DCCR also has a Breakthrough and Orphan designation in the U.S. and the EU, as well as Breakthrough and Fast Track in the U.S. Overall, for PWS, even though it's a rare disease, it's a fairly large rare disease, and we see it being a $2 billion market opportunity in the U.S. We find ourselves very well positioned with a strong balance sheet of over $285 million exiting Q3 to allow us to basically execute on our strategy. By introduction to PWS, this is a genetic, rare genetic disease. It's due to the loss or lack of expression of genes on chromosome 15. Birth incidence about one in 15,000. It appears to basically be prevalent throughout the world, no geographic or ethnicity differences, and it equates to about 10,000 patients in the U.S.
We've done some claims analysis, I'll come back to, that says we've identified about 10,000 patients here in the U.S. The key characteristic is hyperphagia. This is this insatiable drive to eat. This isn't like you or I feeling hungry. This isn't where we might eat one pizza. This is where if these people are not monitored, they'll eat two, three, four pizzas. They'll rummage through trash cans for food. They'll eat things like frozen chicken, and if left unmonitored, the possibility is they'll eat to the extent of stomach rupturing and death, so these folks need to live closely monitored throughout their lives, and this leads to a situation where they have very low quality of life, and particularly also it impacts their caregivers very negatively. The caregiver burden is highest, basically the same height as someone dealing with someone living with Alzheimer's.
92% of siblings indicated moderate to severe PTSD, so a very low quality of life situation. We have an opportunity with DCCR to change what it means to live with PWS. We would be the first to market to treat hyperphagia, the key symptom, and we believe our clinical programs demonstrate the ability to significantly reduce that impact on their lives and become a foundational therapy. DCCR, diazoxide choline in extended-release tablet form, was intentionally engineered with the goal of basically having a choline salt from its parent molecule, diazoxide. The key thing here is to extend absorption throughout the GI tract. This allows for daily, stable intraday circulation of the drug in the blood system and basically improved therapeutic benefits. The mechanism of action that DCCR is working on is the KATP channel. This is the potassium ATP channel.
This is found in numerous tissue sites throughout the body, most notably in the hypothalamus, where it basically reduces the NPY and AGRP secretion, resulting in reduced hyperphagia. It's also found in other areas of the central nervous system, where it reduces hyperinsulinemia and improved insulin sensitivity within the fat cells, reducing in fat mass, and also in pancreatic cells, where basically we have reduced insulin secretion, and all of these together are what we believe are creating the therapeutic benefit, so we've been studying DCCR in a phase three clinical program. It initially started with C601. This was a multi-center randomized double-blinded trial. It had folks recruited in from the U.S. and the U.K., 127 patients in all, 120 completed, and those patients were offered the opportunity to go into the C602 open-label extension trial.
So we read out the results back in June of 2020, and you can see from the middle column; this is all data, and so what you can see here is the primary endpoint was not statistically significant. Now, the primary endpoint for hyperphagia is using an HQCT questionnaire, the Hyperphagia Questionnaire for Clinical Trials. This is a questionnaire that's nine questions scored from zero to four, so your maximum score is 36, and on average, the score was 21 for people going into the clinical trial, and it's given every two weeks, so at the end of the set of June 2020, we did the results. It was not statistically significant. However, as we progressed into July, August, and September, if you remember, we're all becoming much more aware of the impact of COVID, how it's disrupting all of our lives.
In fact, the FDA was signaling to sponsors to be very careful about the impact of COVID on clinical trials and to the extent that they were guiding people to use a March 1st cutoff date to avoid the impact. We went back and we re-ran all our statistical analysis, and you can see on the right-hand column, the results basically with the data that was collected through March 1st. In this situation, you can see the primary endpoint is now statistically significant along with all three secondary endpoints. We took this back to the FDA and basically said, "Hey, look, if we remove the COVID-impacted data, we think we've got a positive trial." They came back and they said they could not remove the fact that it could be an artifact.
Meanwhile, while we were doing that, we had our patients on the open-label extension trial. So we explained that we could go and basically find clinical evidence from one year of data on the open label, and we could compare it to patients who were doing the PATH for PWS. This is an ongoing study evaluating the natural history of subjects in PWS. So we went through the exercise. We got a third-party CRO to do all the statistical analysis and basically to compare those on drug for one year with patients who were basically in the natural history study. And so here are the results from that. So you can see on the left-hand side, for patients on drug up to 52 weeks, a continued improvement of being on DCCR. Their HQCT scores were now coming down by approximately 10 points.
So if you remember, I said on average the score was 21 for the patients in the trial. So now on average, they're basically about 10 and 11. This would mean they wouldn't actually qualify to go into a clinical trial studying hyperphagia. You have to be at least 13 on that scale. So significant improvement in their disposition. You can also see on the right-hand side comparing with PATH. So DCCR is green, PATH is blue. So at 26 weeks, statistically significant improvement, and same for 52 weeks. If we look across other domain behaviors, you can see statistical improvement at the end of one year from baseline across all the behaviors that are measured: aggressive behaviors, anxiety, compulsivity, et cetera. Statistically positive.
Again, comparing these results to those on PATH, you can see across all domain behaviors, again, statistical significance for those on drug compared with basically natural history. Looking at the weight, again, those on PATH were putting on more weight than if on drug. And particularly the lean mass, basically those on drug were getting lean muscle mass compared with fat mass improvements. Finally, on the metabolic markers again, statistical improvement across all of the four metabolic markers we were looking at at the end of one year. And if you look at the safety profile, as I mentioned, diazoxide choline is a salt of diazoxide, so it's very well known. It's a safety profile generally consistent with prior experience with diazoxide. The most common adverse events reported were hypertrichosis, hirsutism, peripheral edema, and hypoglycemia. Most were grade one or two and none were grade four or higher.
This is just a picture to give you a little bit of a visual impression of what's going on. As we mentioned, now we know a lot about hyperphagia, so we control food intake as best we can, but for some patients, they obviously still can present being fairly overweight. But as you can see, one year in, significant changes in body composition, significant improvements in lean muscle mass. So we went back to the FDA after we conducted the C602 one-year data, and now the FDA basically was saying that we didn't have to do a new clinical trial, but they still were requiring more controlled data. So this led us to go back and propose the randomized withdrawal trial.
You can see on the right-hand side what happened was basically we took 77 patients that were still in our open label, randomized them into the randomized withdrawal phase, and at the end of that, they were able to go over C614. At the time, the FDA said they believed that the results had the potential to support our NDA submission. We went through and completed the trial, and we read out in September 2023, and as you can see the results here, highly statistically significant for that primary endpoint, that HQCT questionnaire score.
Also, if you look at the separation, this is exactly the type of visual impression you'd expect to see or hope to see, where basically what you have is those on the blue line are those patients in the placebo, so they have a steadily worsening effect as time moves on, and they're removed from drug for a longer period of time, whereas those that continued on drug, the green line, much more stability in results. Sometimes we get asked, you know, are the impacts one or two questions specific? If you remember, I said the HQCT was a nine-question questionnaire, but you can see across all nine questions, those that are on placebo significantly worsening during the trial. Secondaries, this was not powered for the secondaries, but strong trending in the secondaries for the CGI-S and the CGI-I.
Also, if you look at the PWS domain behaviors again, all of these, you see those on placebo indicated worsening. Looking at weight, you can see those that were taken off drug, significant increase in weight, and also the BMI again, change in BMI, worsening BMI for those that were on placebo. So with regards to the regulatory status, you know, as I mentioned, we were granted Breakthrough, Fast Track, and Orphan designation. Recall I mentioned we submitted the NDA in June based on these results. It was accepted to file in August. Priority Review has been granted. We recently communicated that the FDA does not plan to hold an advisory committee, and the PDUFA date has been set for December 27th of this year.
Meanwhile, we've been working very diligently with the scientific and patient advocacy groups along our journey with a growing body of clinical evidence presented at medical and scientific conferences. There was recently some papers presented in Liverpool just over the weekend. Independent town halls created by parents of children to explain the benefits. An independent FDA-led patient-focused drug development meeting last year at PWS USA. And when we did submit our NDA, the PWS Advocacy Coalition submitted a petition with over 14,000 signatures in support, requesting that the FDA accept for filing and grant Priority Review, which indeed happened. I did mention we have extensive IP protection on DCCR. Three families of patents, as I mentioned. You're in the central one here. You see the method of composition patent that lasts through 2026 with patent term adjustment that gets us through to 2029.
And if we choose patent term extension on that, that would give us exclusivity through 2034. So we obviously have orphan in the U.S., orphan in Europe, an opportunity to have patent extension through 2034. Also on the method patents, regarding to the label, if we get the label, certain indications within one of the method patents might also be applicable, and that could give us exclusivity through 2039. So turning our attention to the commercial side of the equation, the U.S. market opportunity I mentioned is a very attractive opportunity. We've done extensive claims data analysis already, identified over 10,000 patients in the U.S. One of the key things there is PWS presents itself in such an awful way that there is a very high diagnostic rate that happens with newborns. So 85% of diagnoses are made within the first year of life.
And again, there's no therapy out there for the hyperphagia. So when we've done our research so far with healthcare providers, 95% of HCPs state a willingness to prescribe DCCR. Also somewhat common with other rare diseases, we find a concentration, if you like, of KOLs and what we believe will ultimately be high prescribers. So there's 300 HCPs, primary treaters for 2,100 PWS patients. And we also think they have an influence on additional prescribers to reach a further 2,000 patients. Also looking at the patient population, we're seeing it really segment into two groups. So the younger patients being less than 25 years, the onset of hyperphagia typically happens after four, but before 12, and virtually everyone with PWS will basically end up with hyperphagia.
These patients are typically in a home setting, and we're going to be focusing on the pediatric endocrinologists to basically access this market segment. Greater than 25 still need that supervision, but a little bit more fragmented. But what we are seeing is we are seeing that often these people will end up in homes. The burden on the family is just too great, so they're going to PWS homes. So there's about 1,000 adult patients, we believe, in the U.S. in various homes, and we're going to focus targeting on that. And you'll see our basic call point move towards the adult pediatric, sorry, adult endocrinologist and psychiatrist in this situation.
When we talk to caregivers, healthcare providers, and patients, they really come back and they echo the fact that the ideal therapeutic profile for a drug would be one that basically significantly improves hyperphagia as durable improvement in cardiometabolic markers, body composition. These are reduction in PWS-related behaviors and a well-tolerated safety profile. We believe that DCCR has an opportunity to address that profile. The pathway to a successful launch we believe will be based on a robust clinical program that we have. We have over five years of data to be able to leverage. I've already mentioned we're already doing extensive analytics to understand the patients, identify the patients, identify the healthcare providers, identify the payers, already starting to talk to the payers, and continuing to engage with stakeholders, patient advocacy groups, and really understanding the needs of the community.
While we've been focused on the NDA, a lot of work's gone on the other side of the house to basically build teams, infrastructure, and programs to commercialize DCCR. Within the supply chain, we've identified a 3PL and specialty pharmacy. I mentioned we're doing market access, payer engagement. We've got some MSLs in the field. Marketing is getting up to full steam on disease state education. I've already mentioned the analytics. We're starting to recruit the field force, obviously continuing our ongoing and deep engagement with patient advocacy and putting some drug safety profiles into play. I did mention that there's opportunity beyond the U.S., so just briefly to touch on Europe. Again, we've already done early work here, confirmed high unmet need, strong thought leaders in this market opportunity, estimated to be about 9,500 diagnosed PWS patients in the EU, 4,000 in the U.K.
So our plan here is to move the regulatory ball forward. We're planning to submit an MAA in the first half of 2025. And all of this is made possible by the fact that we mentioned early on, we believe we have a very strong balance sheet, $285 million of cash at the end of Q3 to allow us to execute on the strategy, which is to basically continue to seek approval for DCCR in the U.S., then commercialize with our own commercial organization and basically execute upon regulatory approval in Europe. And that brings us to the end of the presentation. Question. Thank you. Yeah, really interesting. Thank you. Did you see a difference in terms of clinical data between pediatric and adult populations? You mentioned those were the two key buckets of patients.
No, when we presented the clinical data, and you can see in a number of the publications, not really a noticeable difference between the age groups in the performance. You mentioned the European commercialization. Are you guys going to do it yourselves, or are you looking to partner? Yeah, so it's a question on would we do it ourselves within Europe. So most recently, we've always said we'd be looking for a partner. We have mentioned that we thought it was good to keep momentum going, so that's why you're seeing us moving forward on the regulatory. We're still open to partnership, if you like, so that's definitely our predisposition. But at the same time, we're trying to make sure that we continue to take the necessary steps to keep the momentum going.