Good morning, everyone. Welcome to our Piper Sandler Healthcare Conference. It's day three of our conference. My name is Yaz Rahimi. I'm a senior biotech analyst at Piper. Thrilled to have the team from Soleno. Anish, thank you so much for being here with us. I think a good place to start off is what sparked the interest of the FDA to move the PDUFA date from December 27 to March 27. I think in the press release, it had some wording around some material data or I can't remember the exact wording, but if you could just tell us, did they see anything in the submission process that said, "Wait a second, we need extra time"? Right. So firstly, thanks for having us. Always a pleasure to be here. In terms of the rationale for extension of the PDUFA, as we said, the FDA deemed certain submissions that were done at the time to be major amendments. And that in FDA speak is need more time for review. We know that this has been kind of a robust back and forth with them. There's been a good number of questions coming from them. We've been responding to them in a timely manner. We believe that at the time, the information that was in front of them to be reviewed just needed more time. And we were literally days before Thanksgiving. So with a month left with the original PDUFA, it was one week of Thanksgiving, one week of Christmas, effectively two weeks left for review. So as I've said before, I was surprised, but not shocked. Okay. I think the second question that has come up is right around Thanksgiving, Applied Therapeutics received a CRL letter, different indication, different drug, different division, but they also had an extension that they had received, and that extension was November 27. So a number of investors have been kind of trying to figure out, like, "Hey, they got an extension. We thought that was a positive, and then they got a CRL." What does that mean for Soleno? I would love to hear your thoughts on that because that has come up quite a bit over the last week or so. I will say that I had not quite focused on Applied as much as I have now. Now that I've reviewed the publicly available information around it, I can say that the similarities seem to me purely procedural. Yes, there were these two acts which were similar, the extension of the PDUFA as well as the cancellation of the Adcom. As I review the available data, et cetera, I feel like we're very different in terms of data sets. We had a positive, highly statistically significant phase three study on a pre-specified primary endpoint, which had been agreed upon by the FDA. We are in a different division. We feel like that's where the similarities sort of end. We don't feel it to our parallel situations. I have seen some of the more recent information around the warning letter. As you know, we do not comment on our ongoing review. Given sort of the acuteness of the situation, what I would like to say is that we have had inspections, and we have not had any 483s. I won't go into any more detail, but I will say that what you've seen with those warning letters is not who we are. Okay. Thank you. Maybe let's talk about a little bit. I don't know if you can comment on whether you are in label negotiations with the agency or now with the PDUFA extended. Maybe it's too early to have those discussions. So generally, label negotiations are in the weeks before PDUFA date. So we obviously have not commented on whether we are in negotiations or not. But hypothetically speaking, you would expect to be in those conversations just prior to PDUFA. Okay. And I think you guys have always been clear to say that the label is going to be PWS patients age four and above with hyperphagia. Has that changed in your perspective on who could be the label? What we've said is that's a desired label, so we don't know what the label will be, but what we have said is that we expect it to mirror the key inclusion/exclusion criteria closely, and the key inclusion/exclusion being the diagnosis of PWS, the age of at least four years, and the presence of hyperphagia, so we expect that to be a base case scenario, but obviously it remains to be seen where it goes. Have you had your 180-day safety? The 120-Day Safety Update went in on time. That's driven by the date of submission, and that went in on time. Okay. And is it just safety, or is it a combination of? It is meant to be a safety update, yeah. That has already been completed and submitted? Correct. Okay. All right. And that was not the piece that said, "There's only two weeks left. We need more time. If you look at the number of days, that would have gone in earlier. But when you get information requests from the FDA, they come in with different windows for sending in responses. Some of them could be a couple of days. Some of them could be a couple of weeks. Some of them could be a couple of months. So what that means is that on a given week, you could have multiple responses going in. So I would say that it's probably one of those situations that led to the belief that they need more time. Okay. Before we transition into understanding preparation for the PWS market, how do you foresee your communication and disclosure is going to look like between now and March 27? I know everybody's constantly asked the same questions over and over again. So what can you say, what can't you say, and how do you think about communicating with the Street? I fully expect you to continue to ask the questions that you've been asking, but that doesn't mean we'll respond. Yeah. We'll have to see. I mean, we've always been good about reporting material information and being very honest in our reporting. We continue to do so, and we will continue to do so. But again, we also have been very careful about not trying to analyze the review in public. The review is a review. We don't want to give out information that is specific to the review. And I would not expect that to change. Okay. And maybe one last question. Sorry. Do you know is there an optionality of an Adcom being on the table between now and March 27? I would say theoretically, yes, but we have not been asked to prepare for one. It's not been conveyed to us that it's back on the table. So I would say that our internal assumption right now is that there is no Adcom. Okay. So let's start off on the PWS market. I think it's estimated there are about 10,000 diagnosed PWS patients in the U.S. What is the data to support that number? This is from claims data, so we've done, and you know where this started. There's an academic abstract out of the University of Colorado, which talks about 9,000 patients diagnosed, and when we look at the claims data, we see at least that many, so I think it's a reasonable assumption right now to say there's approximately 10,000 diagnosed based on claims data. Okay. And what percentage of them would fall within that population study and then DCCR that is over age of four with hyperphagia? So we think that 10%-15% of them will fall into a category which is below four years of age or may have uncontrolled diabetes or something like that. If you take, let's say, 85%-90% of that diagnosed patient population, that is your TAM. Okay. And that's also over the age of four then, yeah? Yeah. Correct. Is there a number of undiagnosed patients, and what efforts are being done to increase awareness? I I could expand into that. So I would say that today, the number of undiagnosed patients should be very low if you're below, say, 10 years of age because the age of diagnosis in a place like the U.S., it's believed that about 85%-90% of patients are diagnosed around the time of birth. So if you do have undiagnosed patients, and I'm sure there are some, they're likely to be older. So these are likely to be patients who are substantially older, may not have genetic diagnoses of PWS, and may be living with a provisional diagnosis only. We see some of that in the claims data. We'll be refining that further. But you should expect to see eventually some undiagnosed patients. Okay. And could you maybe talk about, as you looked into the claims database around the 10,000 patients, where they're located? Are these patients, I guess, question one, distributed sort of all around the U.S.? Are there certain centers of excellence where you have really concentrated areas? That's sort of one. And then two is, what specialties are seeing PWS patients that you would need to be focusing on in terms of your launch? So the population of PWS patients is sort of distributed, as you would expect the population of the nation to be. There is no predisposition based on geography or ethnicity. So we see these patients everywhere. There are some exceptions. For example, there are some areas where very prominent KOLs live. So we know that families have moved there. Florida is a good example. The University of Florida is the largest PWS center in the world. And we see a concentration of people in the Southeast, so Florida, Georgia, those sort of areas. We also see similar concentrations in places like Texas and New York City, but nothing that's sort of extraordinarily different about it. In terms of the physician population that's targeting that is serving these patients, the most obvious one is pediatric endocrinology. When you look at these patients who are younger, virtually all of them are going to pediatric endocrinologists. The reason is predominantly the fact that they are all on growth hormone. In order to get growth hormone prescriptions, changes in doses, et cetera, that's where you would go. That we know is our primary healthcare provider population that we'll be targeting. As these patients grow older, they start to see more adult endos and psychiatrists. In many situations, the pediatric endocrinologists are able to continue to see these patients, but often they have to transition to adults. I would say our primary population of physicians is pediatric endocrinologists. The secondary population is a combination of adult endos, psychiatrists, and geneticists. How large is the pediatric endocrinology group? It's north of 1,000 of them. But if you look at the distribution of the patients, in the claims data, we see that about 300 of these healthcare providers are either directly prescribing or influencing the prescription of about 40% of the patient population. So it's a pretty concentrated market. Okay. And could you talk about what activities is going to be ongoing? Or how many sales members do you have? Sales team do you need to hire for targeting the specialties? And what is the ramp of hiring going to look like between now and the launch? We have stated that we believe the sales force is about 30 people. Initially, when the PDUFA was December 27, the plan was to bring our salespeople on board at the time of approval, have them ready to go with hire at the time of approval. With the delay, what we are going to be able to do is prepare a little bit better. So the salespeople for the key geographies will actually be coming on board shortly. And the rest of them, most of them have been interviewed already and will be making offers contingent upon approval for the rest of them. Okay, so a small group of leaders, like five? The sales leadership is already hired. Most of our sales leadership is already hired. In fact, we recently hired the person from Acadia who launched DAYBUE to head up the sales organization. Obviously a big hire for us. It goes along with the rest of our hires who all come from places like BioMarin, Albireo, and various other mainstream rare disease companies. We think that probably I don't have an exact number for you today, but the key geographies, several of them will see the sales reps be hired shortly. How much awareness exists for DCCR currently among the patient community and physician community? I think the patient community, this, as you know, is a very engaged community. Many of them are engaged directly with advocacy organizations like the FPWR and PWSA. Many others are part of Facebook groups and other social media channels where they very actively talk to each other. Many of them are involved with state and federal government advocacy, so they're involved through that. So all of those people who are involved at any level of advocacy, they know about DCCR. Those who are connected with them probably have heard about DCCR. So we think there is a substantial number of patients that are aware. We do see that a lot of the advocacy is driven by younger families, patients, families with younger kids. So those, for many reasons, remain the sort of initial target for us. How big is the group, the PWS group, that already has a good awareness, you think? It's hard to give an exact number, but I would say that it's probably in the few thousand range. Given the fact that the number of families who are members of these advocacy organizations are about that many, I would say that's at least the number who have some awareness of the drug. And how do you think about? I think a lot of investors in Street thinking of DCCR launch very similar to Omav, right, where as soon as Omav got approved, physicians were getting tons of inbounds immediately around wanting to get into an appointment, wanting to write. And so I guess, is it fair to make a similar prediction that there's going to be a very strong early bolus of patients that are going to want to be on the drug? Or is there some differences between the FA population versus the PWS patients that don't expect those sort of Reata-like uptake in the first few months or almost on the first few weeks, yeah? What we know is that there is a lot of interest. What we don't know is how that translates into a bolus because that's something that is not driven purely by family interest. It's also driven by the ability of these physicians to absorb that many patients, to bring them in, to put them on drug, et cetera. I would say that I think our confidence remains in the ultimate size of the market and in the fact that many patients are targets for this and many patients will take the drug eventually. We are a little hesitant to give you bolus numbers because that's not something that we're able to control. We can tell you that there's a lot of interest from the physicians as well as the families, but we're working with them, with the physicians, et cetera, to understand how we can best support more patients getting on drug faster, but remains to be seen what that looks like. Okay. Could you also talk about what work is being done to understand the size of the market in Europe and what do you project it to be in part one and part two? Where will you be in your regulatory filings in Europe? We have stated that we intend to file in Europe in the first half of next year. We have started to do work to understand the market, to kind of quantify the numbers. In the first cut, we actually see the market to be quite meaningful. If you look at EU4 and U.K., the numbers are similar to the U.S. It's a pretty significant market, even just in the main geographies. We expect that because there's no difference with geography and ethnicity, the numbers in the EU27 will be substantially north of what they are in the U.S. It's meaningful. It's meaningful not just in Europe, but also in the other ex-U.S. geographies. We continue to do our diligence on figuring out what the best way to target those various geographies is. I think we had the pleasure of having you at our conference maybe about a month ago. You spoke about sort of when you engaged with the European agency way back as you designed your studies. Could you share the feedback, right, what their thoughts were on a placebo-controlled study versus a randomized withdrawal? I think there's just what investors are trying to figure out is how will they view the data package versus the U.S. agency? Yeah, it's a fair question, and as we've said in the past, our main engagement with the European regulators was when we initially designed our program in the 2016, 2017 timeframe. We proposed both to the FDA as well as the EMA a six-month study. The FDA wanted us to do a shorter study. The EMA wanted us to do a longer study. We did the shorter study, and in our back and forth with the EMA, we pointed out to them that it's not entirely feasible to do these long-term placebo-controlled studies in indications like PWS. And one of their recommendations was to consider a randomized withdrawal of patients to get long-term efficacy data, so we have interestingly landed there for different reasons that they initially envisioned, so we expect that this data set should be acceptable to them. Okay. That's very helpful. And maybe another bucket of questions related to launch is pricing, right, how we should be thinking. What work has Soleno done in engaging with payers and understanding what sort of the expected price range that would be feasible, yeah? So our access team is at this point almost fully hired. So we are in conversations with larger providers. We've done advisory boards with payers. And obviously, part of the discussions have been what is the tolerance in terms of price. What I can tell you is that there is no pushback in terms of coverage for the drug. I think even though payers are not familiar with PWS as a disease, if you take 20 minutes to explain it to them, this is not difficult to understand as an unmet need that needs treatment. So I don't expect that to be a challenge. From a pricing perspective, as we've said in the past, we're not able to give you a number, obviously, but we work in sort of the broad bracket of the lower end being one of the Amylyx type of situations, which is $140K, the high end being the DAYBUE type of situation, which is $540K plus, and in the middle, you have situations like SKYCLARYS at about $370K and setmelanotide at about $360K, so we expect to play in this range somewhere. We'll give you the exact numbers closer to the time we launch. Okay. And you would expect the prior authorization would be as simple as a genetic diagnosis, right? And how do you quantify with hyperphagia since, I guess, I assume physicians don't use hyperphagia questionnaires. So is it just as simple as an observation of a physician just saying, "Yep, this patient is morbidly or is obese and reports overeating"? What will be the clinical quantification of hyperphagia? We'll see what it ends up being, but I think it's not unreasonable to assume that prior auths are kind of the norm these days for any significant drug. So we would expect prior auths, and I expect it to be as simple as a genetic diagnosis of PWS or a diagnosis of PWS and the presence of hyperphagia. You're right that clinicians don't use the hyperphagia questionnaire on an ongoing basis, and we don't expect that to be part of a prior auth. It'll partly be driven by the label as well. So we'll see what the label states. Okay. Very helpful. In terms of the label, one of the things that sometimes comes up is DCCR safety looks very clean. The only thing that could come up is maybe a need of glucose monitoring. I guess one question is, do you expect the use to be restricted to only non-diabetics? Do you think it could probably label being diabetic and non-diabetic with a glucose monitoring? How do you foresee? What was the reminders? What was the population? How was glucose monitored? And what would the implication be? The phase 3 studies did not exclude patients with diabetes. In fact, we had patients with diabetes, treated patients with diabetes that we treated with DCCR, and they did well. Most of them did well. I think we expect that patients will see glycemic excursions. We expect some patients will see more excursions than others, and we would support the idea that uncontrolled diabetics should not be on the drug, but we don't see any reason why we should exclude diabetics, so we think that eventually the patient population will reflect what we treated in the clinical trial, which is all comers other than patients who have uncontrolled diabetes. When you refer to the U.S. with the 10,000 patients, what percentage would you count as like a minor group that is uncontrolled? Hard to say. When we look at the literature, we see about most of the literature suggesting that about 20-ish% of patients are diabetic. The prevalence of diabetes goes up as you grow older and more obese, and in some populations, even more than 50%. However, it's hard to come to a number on how many are uncontrolled diabetics of the 20%. So we expect it to be a minority. And obviously, once the treatment is available, we think physicians, endocrinologists will be incentivized to better control their diabetics and perhaps put them on drug. Okay. And what do you do in terms of glucose monitoring? Do you think it's just a standard glucose test? Yeah. I mean, in our trials, we've done a few things. We've given some people glucometers to take home. So if you need more close monitoring, that can be done at home. Any lab will be able to do a fasting glucose and A1C level as well. So we think some combination of these will be needed. But again, it'll depend on the patient, and the physician will have to decide how close the monitoring needs to be. Okay. Wonderful. And just maybe the last question, the cash and cash runway for the company, especially as you're going to be getting ready for commercialization of your sales team? As of the end of the last quarter, we had about $285 million in the bank. We think that's a good chunk of change. It allows us to launch successfully. Assuming reasonable sales estimates, we should be able to be cash flow positive with this. Wonderful. Can't wait for the approval. Congrats on a very successful 2024, and can't wait for a great year ahead. So that's, I think, a need for a great discussion.