Greetings. Welcome to Soleno Therapeutics' randomized withdrawal period of Study C602 top-line results. At this time, all participants are in listen-only mode. A question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero from your telephone keypad. Please note, this conference is being recorded. At this time, I'll now turn the floor over to Brian Ritchie with LifeSci Advisors. Brian, you may now begin.
Thank you, operator. Thank you all for joining us this morning. With me on today's call are Soleno's Chief Executive Officer, Dr. Anish Bhatnagar; the company's Chief Financial Officer, Jim Mackaness; and Dr. Jennifer Miller, Professor of Pediatrics in the Division of Endocrinology at the University of Florida. This morning, Soleno issued a news release announcing top-line results from the company's randomized withdrawal period of Study C602, evaluating DCCR tablets for patients with Prader-Willi syndrome. Please note that certain information discussed on the call today is covered under the safe harbor provision of the Private Securities Litigation Reform Act. We caution listeners that during this call, Soleno management will be making forward-looking statements. Actual results could differ materially from those stated or implied by these forward-looking statements due to risks and uncertainties associated with the company's business.
These forward-looking statements are qualified by the cautionary statements contained in Soleno's press release issued today and the company's SEC filings, including in its annual report on Form 10-K and subsequent SEC filings that it has made. This conference call also contains time-sensitive information that is accurate only as of the date of this live broadcast, September 26th, 2023 . Soleno undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call. Finally, during today's Q&A session, we ask that you please direct all questions to Anish, and he will request that Dr. Miller elaborate as appropriate. Now, I'd like to turn the call over to Anish. Go ahead, Anish.
Thank you, Brian, and good morning to you all. Thank you for dialing in today. As you all probably know, Soleno is in late-stage clinical trials for DCCR, which is a once-a-day oral tablet for the treatment of PWS. Prader-Willi Syndrome, or PWS, is a rare genetic disease that happens spontaneously in about one in 15,000 live births, with the same birth incidence regardless of geography or ethnicity. Translates to about 10,000-20,000 patients in the U.S. and approximately 400,000 globally. The most significant unmet needs relate to its hallmark symptom, hyperphagia, a life-threatening, insatiable desire to eat. In spite of several drugs having been tested in late-stage clinical trials, none have been successful, and no treatments exist for hyperphagia.
Children and adults with PWS require lifelong supervision, and families need to ensure access to food remains restricted, translating into locked refrigerators, pantries, et cetera. People with PWS have varying levels of cognitive impairment and can have significant behavioral problems. We conducted a phase III study of DCCR from 2018 to 2020. The study was called Destiny PWS, or C601. Although the top-line analysis did not show a statistically significant improvement in hyperphagia with DCCR, key secondary endpoints showed significant improvements, and it's worth remembering that the COVID pandemic started in early 2020. When we analyzed the data, excluding the pandemic-affected data points, we saw evidence that the study was positive for the primary as well as the key secondary endpoints.
We have publicly also shared long-term data covering a one-year period, showing very significant improvements from baseline and hyperphagia and all behavioral aspects of PWS, as well as an improvement in metabolic endpoints. We've also shared data comparing matched patients on DCCR to those in PATH for PWS, which is a natural history study being conducted by FPWR, which is the Foundation for Prader-Willi Research. These analyses also show statistically significant benefits with DCCR relative to natural history. While being on DCCR, kids have been mainstreamed in schools, and some have even gone to four-year colleges. We have discussed these data with the FDA, and they have asked us to generate additional control data. They've acknowledged that data from a randomized withdrawal of patients who were on our long-term open label study, C602, if positive, have the potential to support an NDA submission.
We are sharing those data today. The FDA has agreed that the primary endpoint of the randomized withdrawal study is changed from baseline and hyperphagia, measured using the Hyperphagia Questionnaire for Clinical Trials, or the HQCT. It's a nine-question questionnaire, with each question having a zero to four response. The worst possible hyperphagia score is 36. The result of this primary analysis was highly statistically significant, with a P value of 0.0022. This represents a difference of five points between DCCR and placebo, which is clinically meaningful, highly significant. I think it's important to point out that even with a study as small as 77 patients, which is approximately half the size of typical phase III studies being designed today. We are seeing such statistical significance.
In addition, we are seeing strong trends towards significance in the two secondary endpoints, which measure investigator assessments of participants' overall severity of illness and change in condition. The Caregiver Global Impression of Severity showed a P value of 0.07, and a Caregiver Global Impression of Improvement had a P value of 0.09. In addition, all six behavioral domains that we track for PWS showed the placebo group to be worse than DCCR at the end of 16 weeks. These domains include aggressive behavior, anxiety, compulsivity, depression, disordered thinking, and rigidity- irritability. And finally, there is further objective evidence of efficacy, with the placebo group showing a statistically significant increase in weight with a P value of 0.035. The same significance was seen in BMI, with a P value of 0.036.
People have now been on DCCR for between two and four years before the start of the randomized withdrawal study, and the safety profile is consistent with what we have known all along. No new safety signals for DCCR were identified in the randomized withdrawal study. We believe that these results are unprecedented in the world of PWS clinical trials. This is the first phase III study to show statistical significance in the difficult endpoint of hyperphagia while maintaining an acceptable safety profile. In addition, all other behavioral data was observed to be moving in the same direction. Those patients who were on placebo, being worse across the board. This was a difficult study to conduct for many reasons. It was very difficult for the patients and their families to be on a drug for years, and then for some of them to be withdrawn from it.
We cannot thank them enough for participating. The investigators on the study had the tough job of watching some of their stable patients go back to not doing so well. The advocacy organizations, the Foundation for Prader-Willi Research, and PWSA USA, and many individual advocates, have been supportive of us in this study and continue to be supportive. And finally, the exceptional team at Soleno successfully executed this complex study across 25 sites in the U.S. and U.K., while at the same time initiating an open-label study for completing subjects. Virtually all completing subjects have either rolled into that open-label extension study or will do so shortly. Thank you to all of you. Our work is not done, but this was a big step.
We look forward to working on our plan of submitting the NDA to the FDA next year, and finally, if approved, bringing a treatment to market for hyperphagia in PWS. I have with me today Dr. Jennifer Miller, Professor of Pediatrics at the University of Florida. As many of you know, she's one of the world's foremost authorities on PWS and follows by far the largest cohort of patients with PWS anywhere in the world. She's the principal investigator for the DCCR studies at the University of Florida and has the largest number of enrolled subjects in this study. Dr. Miller, you've had a chance to take a quick look at these data. What is your perspective on these? How do you think they impact the PWS community?
Oh, I think it's great data. You know, I've said since the 601 program that this drug was extremely effective and had a significantly positive impact on the lives of the individuals with Prader-Willi, as well as their families. I've just seen it be so life-changing in so many ways. I know that COVID impacted the outcome of the C601 study, which was truly unfortunate, but the data from this randomized withdrawal trial are very positive and support my belief that the drug works. The effect size of five points on the HQCT is very clinically meaningful, and I could tell that from all of my patients, as could their parents, if they were possibly on placebo. It's great to see the supportive trends in the secondary endpoints, as well as the supportive trends on the behavioral endpoints.
Again, these were very observable during the trial, and I'm thrilled that everything was moving in the right direction, with the placebo subjects worsening on all counts and the DCCR patients improving. The increase in body weight in the placebo group really just confirms this. The Prader-Willi community has been waiting a very long time for these data, and I know the whole community is absolutely beyond thrilled to see it. It's been a long time coming, and we're very glad to see these results.
Thank you, Dr. Miller. Brian, we can take a couple questions.
Thank you. If you'd like to ask a question at this time, you may press star one from your telephone keypad, and a confirmation tone will indicate your line is in the question queue. You may press star two if you'd like to remove your question from the queue. For participants that are using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. One moment please, while we poll for questions. Once again, that's star one. Thank you. Thank you. Our first question is in the line of Kristen Kluska with Cantor Fitzgerald. Please proceed with your questions.
Hi, this is Rick on for Kristen. Thank you for taking our questions, and congrats to the whole team on the data. In terms of endpoints in the randomized withdrawal trial, what is considered kind of the most meaningful in the caregiver community?
Yeah. So you know, it's something that what we focus on is what is the FDA most concerned about, and that is hyperphagia. As you may know, there was a recent externally led PFDD meeting at the PWSA conference in June. And there was a lot of conversation around other challenging behaviors, endpoints, et cetera. I think there is a reasonable belief that hyperphagia remains perhaps the most important. But there are several other things, like the behavioral domain that I'm referring to, in particular, things like anxiety, which I think are very meaningful to the PWS community.
Great. Could you also talk a little bit about the treatment settings in which you expect PWS patients to potentially be reached, you know, pending, you know, getting to the market, such as through primary care physicians or endocrinology clinics? Just sort of how you're thinking about that path.
Yeah, we think that in the U.S., the primary prescribers are going to be pediatric endocrinologists with some psychiatrists as well as geneticists. As you know, there's probably about just north of 1,000 pediatric endocrinologists in the U.S., and we think that the primary prescription will be from them. I think follow-up prescriptions could be out in the community as well, because from what we know of DCCR until now, this is something that we do understand. The safety profile is well understood. Dr. Miller, anything further to add to that?
No, I think that's very accurate, although I would add that I think that they should all continue to be followed by pediatric endocrinologists or endocrinologists in general, as they are now for all their other endocrine medications.
Thank you. Maybe just one more question for us. What other data could we be looking forward to, potentially other endpoints in upcoming publications, and any potential for presenting randomized withdrawal data at upcoming medical meetings? Thanks again, and congrats.
Thanks for the questions. There, you know, there'll be a little more detail coming up. There's a Foundation for Prader-Willi Research Conference coming up in the next few days, so we'll probably have a little more granularity in the data then. But I don't expect, you know, vast, vast amounts of new data coming out for now.
Thank you.
you'd like to ask a question at this time, you may press star one from your telephone keypad. We'll pause a moment to assemble the queue. Thank you. Our next question is from the line of Leland Gershell with Oppenheimer & Co . Please proceed with your question.
Hey, good morning, and our congratulations on these terrific data. Wanted to ask, you know, with respect to, you know, next steps. You know, clearly you'll be filing NDA. Wanted to ask, you know, Anish, about your plans, you know, as you head toward commercial, what that's going to look like for Soleno in terms of, commercial organization and potential spend there, and how we should think about kind of the go-to-market strategy overall. Thank you.
Yeah. Thanks, Leland. You know, as you can imagine, we have started doing some of the pre-commercial work. You know, we've started looking at claims data. We're doing early pricing work. We're looking at prescription paradigms, et cetera. So the work has started. We expect to accelerate some of that as we get closer to NDA submission. We think that a commercial organization for a drug for PWS is not large. We think it's a pretty finite organization because the primary prescribers are not that many pediatric endocrinologists. So as we look to that size, we think that it's an organization that we could relatively easily develop over the next year or so as we get close to commercializing the drug. Stay tuned for details, and we're taking it one step at a time. Thank you for the question, Leland.
Okay, then if I could also ask, with respect to ex-U.S., I know that originally you had planned for Destiny PWS to also serve as support for registration in Europe and maybe other territories. I don't recall if you had discussions with the European regulators as you went through the more recent, you know, randomized withdrawal and so forth with the FDA. Just wondering where things may stand in terms of your outlook on, you know, EMA and maybe other geographies. Thanks.
Yeah, good question. So you correctly point out that, our interactions, regulatory interactions, really have focused on the U.S. FDA for the randomized withdrawal, so we have not discussed it with, the EMA. However, I believe that the strength of these data is such that we should be able to submit, for a marketing, for an MAA with the EMA as well. Remains to be seen, but that is certainly our intent at this time.
Terrific. Okay, great. Well, congrats again, and I look forward to seeing the drug get to market. Take care.
Thank you. Dr. Miller, I have one question here for you. What do you think a drug like DCCR could mean for people with PWS?
You know, I think for anyone who doesn't live with Prader-Willi on a daily basis, it's pretty close to impossible to imagine how difficult it is to live with a child or a young adult with this condition. On a daily basis, I hear parents say, "I can't do this anymore." It's just really, really hard and literally every aspect of life that you can imagine. To me, by far, the most important thing that this could mean is normalizing lives for not only the patients but their families as well. I've seen that my patients who have been on DCCR long term have been able to start living in households with unlocked pantries, without cameras on, that to monitor the kids' access to food. The adults can go and buy groceries on their own and prepare their own meals.
They can go to parties and school dances. They can go to sleepovers. They can travel with their high school sports teams. They can do anything that any other kid or person can do, and that is absolutely life-changing. They don't need to live in fear anymore of getting a call from the school or even the police because their child was violent or caught stealing food from a store. It's just, it's been remarkable, and I've said from the beginning that DCCR can and is making a massive impact on these individuals' lives, and I can't wait to see it make an impact on the lives of so many people affected with this syndrome. And I hope we can bring it to as many patients as possible, as soon as possible.
Thank you.
Thank you. If you'd like to ask a question over the phone, you may press star one at this time. Thank you. Thank you. Our next question is from the line of Debjit Chowdhury with Guggenheim. Please proceed with your questions.
Hey, good morning, team. This is Robert on for Debjit. Huge congrats on the data set, and thanks for taking our question. From us, I am curious in the strong trends that were shown in the secondary endpoints of CGI-S and CGI-I, and I'd love to get your view on what that could mean for the patient community. Thank you.
Yeah. So as you know, these are endpoints that are the doctor's impression of... The CGI-S is how severe is the disease relative to a typical patient with PWS. And the CGI-I is, compared to baseline, how much has the patient improved or worsened? So they're both meant to be sort of holistic views, which are not driven just by hyperphagia or just by behaviors or anything like that. As you can imagine, this is a 77-patient study, which is very small, so we are quite thrilled to see these positive trends in even the small study. And I think what this means is that it's not visible just to the caregivers who are filling out the HQCT. It's also visible to the clinicians who are seeing them only twice in person and the rest on telemedicine.
Even that, they're able to tell that the placebo patients are doing worse.
That's great. Once again, congratulations. Thank you.
Thank you.
Thank you. At this time, I'll hand the floor back to Anish for closing remarks.
Thank you, operator. Thank you all for dialing in today. This is, you know, a significant day for us. It's been a long journey, and we're really happy with the data today, and we look forward to continuing the journey, submitting the NDA, and hopefully having an approved product for hyperphagia in PWS, as soon as possible. So thank you all for listening.
Thank you. This will conclude today's conference. You may disconnect your lines at this time. We thank you for your participation.