Operator
Greetings. Welcome to Soleno Therapeutics Randomized Withdrawal Period of Study C602 Top Line Results. [Operator Instructions] 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.
Brian Ritchie
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 26, 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.
Anish Bhatnagar
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 1 in 15,000 live births, with the same birth incidence regardless of geography or ethnicity, translates to about 10,000 to 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 has 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 bearing levels of cognitive impairments 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 1-year period, showing very significant improvements from baseline in hyperphagia and all behavioral aspects of PWS as well as an improvement in metabolic endpoints. We've also shared data comparing match 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 benefit with DCCR relative to natural history. While being on DCCR, kids have been mainstreamed in school and some have even gone to [ the colleges ]. We have discussed these data with the FDA, and they have asked us to generate additional control data. They have 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 in hyperphagia, measured using the hyperphagia questionnaire for clinical trials or the HQ-CT. It's a 9-question questionnaire with each question having a [ 0 to 4 ] 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 5 points between DCCR and placebo, which is clinically meaningful, highly significant. I think it's important to point out that even with the study, a smaller 77 patients, which is approximately half the size of typical Phase III study being designed today, we are seeing such statistical significance.In addition, we are seeing strong trends towards significance in the 2 secondary endpoints, which measured 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 6 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 2 years and 4 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 are 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 a 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 subject, 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 and PWS. I have with me today, Dr. Jennifer Miller, Professor of Pediatrics of the University of Florida. As many of you know, she's one of the world's foremost authorities in PWS and follows by far the largest cohort of patients with PWS anywhere in the world. She's a principal investigator for the DCCR study with 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 the impact of PWS community?
Jennifer Miller
I think it's great data. I've said since the C601 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. And 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 5 points on the HQ-CT 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 support of 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. And 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.
Anish Bhatnagar
Thank you, Dr. Miller. Brian, we can take a couple of questions.
Operator
Thank you. [Operator Instructions] Thank you. Our first question is from the line of Kristen Kluska with Cantor Fitzgerald.
Rick Bienkowski
This is Rick on for Kristen. 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?
Anish Bhatnagar
Yes. So 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 domains I'm referring to, in particular, things like anxiety, which I think are very meaningful to the PWS community.
Rick Bienkowski
Great. Can you also talk a little bit about the treatment settings in which you expect PWS patients potentially be reached pending getting to the market, such as through primary care physicians or endocrinology clinics just sort of how you're thinking about that path?
Anish Bhatnagar
Yes. 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 would 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?
Jennifer Miller
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.
Rick Bienkowski
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.
Anish Bhatnagar
Thanks for the questions. There will be a little more detail coming up. There is the 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 vast amounts of new data coming out for now.
Operator
[Operator Instructions] Thank you. And our next question is from the line of Leland Gershell with Oppenheimer & Company.
Leland Gershell
Congratulations on these terrific data. [ Though ], I want to ask with respect to next steps, clearly, you'll be filing NDA, I want to ask you an issue about your plans 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?
Anish Bhatnagar
Yes. Thanks, Leland. As you can imagine, we have started doing some of the pre-commercial work. 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.
Leland Gershell
Okay. And 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 randomized withdrawal and so forth with the FDA. Just wondering where things may stand in terms of your outlook on EMA and maybe other geographies?
Anish Bhatnagar
Yes. Good question. So you correctly point out that our interaction -- 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 marketing for an MAA with the EMA as well remains to be seen, but that is certainly our intent at this time.
Leland Gershell
Terrific. Okay, great. Well, congrats again and look forward to seeing the drug get to market. Take care.
Anish Bhatnagar
Thank you. Dr. Miller, I have one question here for you. What do you think the drug like DCCR would mean for people with PWS?
Jennifer Miller
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 just 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 normalized in 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 -- 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 sleep-overs. They can travel with their high school sports teams.They can do anything that any other kid or a 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 effective with this syndrome. And I hope we can bring it to as many patients as possible as soon as possible.
Operator
[Operator Instructions] Thank you. And our next question is from the line of Debjit Chattopadhyay with Guggenheim.
Robert Finke
This is Robert on for Debjit. Huge congrats on the data set. 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.
Anish Bhatnagar
Yes. So as you know, these are endpoints that are the doctors' impression of the CGI-S is how severe is the disease relative to a typical patient with PWS. And the CGI-I compared to baseline, how much has the patient improved or worsened. So they're both meant to be sort of holistic view, 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 we're filling out the HQ-CT. 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.
Robert Finke
That's great. Once again, congratulations.
Anish Bhatnagar
Thank you.
Operator
Thank you. At this time, I'll hand the floor back to Anish for closing remarks.
Anish Bhatnagar
Thank you, operator. Thank you all for dialing in today. This is 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 and PWS as soon as possible. So thank you all for listening.
Operator
Thank you. This will conclude today's conference. You may disconnect your lines at this time. We thank you for your participation.
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