Hi, good afternoon, everyone. It's my pleasure to welcome Anish Bhatnagar, CEO of Soleno Therapeutics.
Thank you, and thank you all for being here this afternoon to listen to our story today. My name is Anish Bhatnagar. I'm the CEO of Soleno Therapeutics. For those of you who don't know us, Soleno Therapeutics is based in the San Francisco Bay Area. We're in the rare disease space. We have a recently US FDA-approved drug called VYKAT XR. This is for a rare disease called Prader-Willi syndrome. It's the first drug for the space. We are working in a market that is multi-billion dollars as part of the TAM. We are in the midst of a geographic expansion with the submission of the MAA in Europe. We have IP protection into the mid-2030s, and we have a strong balance sheet, and as of the last quarter, we are profitable. The disease that we are treating, Prader-Willi syndrome, is genetic, but it's not inherited.
It happens spontaneously, one in 15,000 live births, translates to about 12,000-15,000 people in the U.S., and about 400,000 globally. It's a disease which has a hallmark characteristic of hyperphagia. Hyperphagia is an insatiable desire to eat. It's your brain telling you you are starving while you eat. It has a constant impact on many parts of people's lives, and it's life-threatening as something that PWS people face as a novelty. Hyperphagia causes several effects on families, on patients, as well as on the health care system. It is disruptive. The behaviors that you see are significant. They can lead to aggression. They can lead to emergency room visits. They can lead to police being called in schools. The only way these patients live is under constant surveillance by restricting access to food. You're locking refrigerators, locking pantries, and that's how they live.
This is how it will be for the rest of their lives. Many of them will not live at home, but will live in group homes where, again, food security is paramount in order to make sure that these people will not eat themselves to death. The caregiver burden is significant. In fact, certain measurements measure it to be higher than that of giving care to Alzheimer's patients. More than 90% of unaffected siblings are said to have PTSD. From a health care system impact perspective, there are several times more hospitalizations depending on your age. If it is a younger age group, it is even more. If it is older patients, it is slightly less, but significantly more than the general population. Hyperphagia, in the words of those who have PWS, in the words of those who have babies, children, adults with PWS, can be described in many different ways.
All of these, as you can see, occupy the person's mind completely. They are unable to function in ways that do not involve food. Aggressive behaviors are not uncommon. These patients tend to be able to manipulate their way into accessing food in many situations. As a disease, PWS affects many parts of the body. It has significant comorbidities and several times more incidence of severe events such as heart failure, diabetes, venous thrombosis, atrial fibrillation, and pulmonary embolism. All of these, as you can see, happen several times more in patients with PWS. Average life expectancy is in the 30s. These patients will generally die of respiratory or cardiovascular complications, many of which are directly related to hyperphagia, so accidents, choking, et cetera. These are the reasons why VYKAT XR, the drug that we have, is a significant commercial opportunity.
One in 15,000 live births, translating to about a TAM of 10,000 patients. Total claims data shows us about 12,500 patients. The TAM excludes those who are either less than four years of age, more than four years of age and not hyperphagic yet, or those who have significant comorbidities. This is an interesting disease because the diagnostic rates are very high. In the U.S. and in the rest of the Western world today, approximately 85%-90% of patients will be diagnosed around the time of birth. The reason that's the case is because these patients are born with very low muscle tone. As soon as they are born, they will be in the NICU. The doctor will run a number of tests. One of the tests will be a genetic test for Prader-Willi syndrome.
These families will know that they have a child with PWS, but they'll also be told that not much can be done for them until now. As a market in the U.S., it is a concentrated market with about 300 health care providers either directly treating or influencing the treatment of about 4,000 patients. The unmet need is high across the world, and we see that more so in the U.S. in some ways. The clinical program that led to the approval of DCCR, which was the development name of the drug, involved a series of studies. The phase III initial study, C601, was a randomized double-blind placebo-controlled study that ran from 2018 through 2020. It was followed by C602, which is an open-label extension study, followed by randomized withdrawal of patients from this open-label study, and then the return of those patients to C614.
It is important to understand why we did things the way we did. If you look from one side of the slide to the other, you will see that C601, which was a 13-week study, did not meet its primary endpoint. The reason we believe was because when we reported data from the study, the pandemic had just started. For several reasons, the data was skewed. When we did the COVID-adjusted analyses, we did see significance. We had a long process of back and forth with the FDA, which lasted about two years or slightly more than that, during which we kept patients on drug. If you look at the second box that says C602 OLE, you see that hyperphagia scores continue to go down, and they go down very significantly.
We negotiated with the FDA that if we did a randomized withdrawal of these patients, so in a blinded manner, take the drug away from half the patients, if the effect went away, then that would potentially be approval. The C602 RWP, which you see there, shows you that that's exactly what happened. In a highly statistically significant manner, we saw that the withdrawal of drug led to worsening of hyperphagia. At the end of that study, all patients went back to open-label drug. As you can see, their hyperphagia scores went down again.
What you see from the top, where the average scores were about 22 out of a score of 0 to 36, so pretty severe hyperphagia, to the time when they have been on drug, they're in the range of 8 or 9, which basically means that they're actually not eligible for any hyperphagia studies at the time. A very meaningful decrease in hyperphagia. The side effect profile, based on prior work with DCCR, based on the known molecule that this drug is based on, we know that the three most common things were hypertrichosis, or increases in body hair, edema, or fluid retention, and hyperglycemia. This is the table from the US Prescribing Information. What we see is a safety profile that was what we would have expected based on DCCR prior work and the profile of diazoxide. We saw that treatment modifications were generally not needed.
Most of the adverse events were grade 1 to in severity. The serious AEs were limited. What we have seen since launch is most common adverse events being similar to what we saw in the clinical program. Based on these data, VYKAT XR was approved and indicated for the treatment of hyperphagia in adults and pediatric patients four years and older with Prader-Willi syndrome. The approval, obviously, first to market drug, robust clinical data, and with the hope that this will be standard of care going forward. We have continued to engage with leading advocacy organizations as well as professional organizations. We have extensively presented data over the last year, numerous posters and presentations, different congresses in the U.S. and elsewhere, and a lot of additional presentations amplifying the data for DCCR.
We have worked side by side with the advocacy community, which is a very influential community in this space. There are two major advocacy organizations in the U.S., the Foundation for Prader-Willi Research and PWSA USA, and in Europe, PWSA UK and FPWR UK and the International Prader-Willi Syndrome Organization. We have engaged with them. We have worked with them on Capitol Hill to advocate with them. We have co-organized numerous events. We have worked with what we call the Community Council. This is a number of patients and caregivers who we work with to create materials around educating for the disease. We have sponsored and worked on approximately 60 different events with these organizations over the year. Commercially, we have seen significant traction.
As of the end of the third quarter, we had a robust launch, so more than 1,000 start forms or 10% of our TAM, 494 unique prescribers, which is a huge number given the fact that a lot of these patients are treated at very concentrated centers, 764 active patients on drug, and a discontinuation rate for AEs of about 8%, which is very reasonable in this setting. Our commercial teams are working to make sure that this progress that we have had can continue. The three key areas that they're stressing on, one is activation of health care providers to work on the depth as well as the breadth of treatment, to enable patient access, to make sure that reimbursement remains as robust as it has been, and to optimize treatment outcomes by educating both health care providers as well as patients and their families.
All rare disease launches have their own challenges. We have an interesting situation because it is the first-ever treatment for hyperphagia in PWS. Our health care providers are working to incorporate this into their workflows. Our teams have engaged extensively with the KOLs to generate real-world evidence and to establish guidelines for the use of the drug. We have seen significant broad adoption with almost 500 prescribers in the first six months. We credit that to the education as well as the omnichannel efforts of our teams. We are in the process of extending this into the community using virtual sales teams, sales teams, and predictive targeting. A couple of interesting things to point out here. One is our expert on demand program.
If you have a patient who has to be put on drug and you're not sure what to do, you're a community treater, or you have a patient who's having a problem, you can call one of our experts. They will spend a half an hour on the phone with you and work through with you on how to best deal with the situation. Similarly, the caregiver webinars are a really interesting way for us to work with caregivers, work with patients to make sure they're comfortable with the treatment. We have a number of people who have signed up to be advocates for themselves and for the drug. Examples of this, we had a recent webinar where a patient who has been on VYKAT XR for some time took questions from one of our experts and from the audience to talk about their experience with VYKAT XR.
About 80 families had logged into that. We've had some in-person events, the first one of which happened in Philadelphia. Approximately 60 families were there. The education continues and has led to what we think is excellent adoption from a reimbursement perspective as well. More than $130 million lives covered. We have seen reimbursement from all channels, whether it's commercial, whether it's Medicare or Medicaid. We have seen payments come through from 40 different state Medicaid programs. The top three national PBMs have favorable policies that have already been written. We think this is because of a few things. One is that we believe there is a recognition of the unmet need. A lot of education went into this pre-launch. There is a recognition that this is a need that needs to be treated. The budget impact is low, given this is a rare disease.
The clinical program is robust. The data is believable. Providers and payers have agreed to that. This is the only available treatment for Prader-Willi syndrome. The education piece also extends to caregivers and patients. We have a team called the PACE team, which is the Patient and Community Educator Teams. These are nurse educators. The idea is that everyone should have a nurse educator assigned to them. If you have a question about treatment, about expectations for treatment, if you have questions about adverse events, they will be able to answer that. They will route the calls to the physicians as needed. They obviously cannot provide medical advice, but will be available to you in case needed. A lot has been seen already in terms of efficacy.
We have an ongoing marketing campaign which was worked on in conjunction with health care providers, with advocacy organizations, as well as families. It is called Making Space for What Matters. The idea is that these patients, they are taken over by the thoughts around food. When you can have a child who has a plate of food and says they are full, if you have meltdowns that can resolve quickly, if you are not anxious around food, these might seem like small things, but for these families, they are a really big deal. There are adults who are having effects that are also very interesting. For example, we have an adult who lives in a group home in the Midwest. She is probably about 40 years old. Her family is much older, lives in Florida. Their biggest challenge is traveling to bring her back home.
The reason they have to bring her back home until now is that the plane has been turned around a few times because of her food-related behaviors on the flight. This patient is now able to travel alone. These are the sort of changes which are very meaningful, and we are seeing a lot of them. In terms of international expansion, Europe, there are approximately 9,500 patients that we have seen in primary claims in the EU4 + UK. It is just as high an unmet need as it is in the U.S. There is strong thought leader support. We have seen centers of excellence that see virtually all patients in certain countries. We announced submission and validation in May 2025 of the MAA. We recently talked about the fact that we received day 120 questions and that we are working on the responses as we speak.
We believe that an approval decision is likely around Q2 of next year. From an IP perspective, there are three families of patents that we prosecute in major markets. The Salt Polymorph patent has a primary expiration at the end of 2026, with patent term adjustment and extensions if applied to that. It can go to 2034. A very interesting recent patent issued and now listed to the Orange Book has to do with methods of treating hyperphagia and food-related behaviors, which has an expiration in 2035. We have contemplated new IP, which we have not discussed details of, but has the potential to extend it further. From a financial perspective, as of September 30, we had about $550 million in the bank. Our net revenue in the third quarter was $66 million, and we had a positive net income of $26 million.
We also announced a share buyback, an accelerated share repurchase program, a few weeks ago for $100 million. I'll leave you with one thing, and those on the webinar are not able to see this picture, but this tells you why we do what we do. It's an email that we got from a father of a patient with Prader-Willi syndrome. It's a picture of a full plate of food and an empty chair at a dining table. The caption is, "I guess dinner could wait tonight." Thanks for listening.