Good morning, everyone. Tyler Van Buren here, Senior Biotech Analyst at TD Cowen. Thank you very much for joining TD Cowen's 46th Annual Healthcare Conference. For our next session, very excited to be hosting a fireside chat with Soleno Therapeutics. It's my pleasure to introduce Anish Bhatnagar, CEO, and Meredith Manning, the Chief Commercial Officer of Soleno. Anish, Meredith, it's a privilege to have you both here with us. Thank you very much for joining me. Thanks for having us, Tyler. Before we get into the questions maybe we'll give you the opportunity to start with some high-level comments on Soleno and the VYKAT XR launch, especially given the recent earnings announcement and updates, on the franchise and in Q4 heading into this year. Thanks, Tyler. As most of you I'm sure know, there's a rare disease space. We have launched a drug, the first ever drug for hyperphagia in Prader-Willi syndrome, VYKAT XR. We've had a tremendous launch. We've had about $190 million in revenue in the last three quarters. We are in the process of expanding the VYKAT franchise. We recently talked about the next indication, which is glycogen storage disease. We think it's a high probability of success. It's something that makes a lot of sense, no FDA-approved therapies, et cetera. Yeah, looking forward to the conversation. Just to follow up on that and staying at a high level, now that you guys are three quarters or three-plus quarters into launch, what's been the biggest learn-as-you-go insights, as you bring, you know, the first approved therapy for Prader-Willi syndrome to patients? I think the most interesting thing has been that it's sort of verification that this is a big market. You know, it's. We knew going in that the claims data were telling you that there's a lot of patients out there, and we've seen that pan out. What we've also seen pan out is interest from the community, interest from the physicians. If you look at our number of prescribers, you know, more than 600 prescribers is something that no one had really thought would be possible that quickly. That's been very rewarding, and the other thing that's been very interesting is our reimbursement, our coverage. We're seeing, you know, more than 180 million lives covered. We're seeing payments from more than 45 Medicaid. We're seeing Medicare be one of our best payers. We're seeing all the large PBMs remove new-to-market blocks. Overall, it's been great. Maybe we'll move to start forms. Can you know, discuss how that's progressed over the course of the launch and what your expectation is for start forms moving forward in Q1 and subsequent quarters? Yeah, as we all know, we had a huge bolus to begin with, not one we were expecting, but very large bolus, and we've seen meaningful numbers for the rest of the year. The fourth quarter was about 200+ start forms, which we think we're getting towards steady- state. We've said publicly that we expect to do about 1,000 over nine to 12 months. It's really driven by two major factors. One is, you know, we ask our sales team to do a bottoms-up assessment on what they can do. The other is we know that the larger practices are crowded, unable to insert people sort of at will, and that they'll be seeing patients every six to 12 months. When that time comes, they'll offer drug to them. That's what drives that number. Okay. 1,000, nine to 12 months, should we expect $250+ a quarter, or could there be some lumpiness between quarters as we look out over the course of the year? Yeah, we discourage people from looking at quarters. We prefer people look at the year. There's definitely lumpiness to be expected. Has what you've seen so far in January and February, given you confidence in reaching that 1,000 over the next nine to 12 months? Not really commenting on the quarter. I had to ask. Sure. As we think about start forms translating to revenue, what does that timeframe look like in terms of start form to actually getting drug to titrating up to the full dose and the full price and really adding to sales? Meredith, do you want to take that? Yeah, happy to take that. We've stated that the typical turnaround time that we're looking at is anywhere from 30 to 45 days. I would just share the pathway of the way that a start form comes in to our specialty pharmacy. Sorry, there's a little bit of feedback. Thank you. Comes into our specialty pharmacy. First, you know, we work on the benefits verification, and then making sure that the families are coached up and ready to get started. Once we make sure that the payers have the ability to reimburse, then we move forward, and shipping is pretty easy. We're very pleased with the way that Panther is able to get the product VYKAT XR out to the patients very quickly. As we've mentioned, we've been very successful at the reimbursement. The overwhelming majority are on paid versus free, but we do have a comprehensive program that if there are people who need either a quick start or a bridge or free drug, that we have that available as well. Just to follow up on the PSFs from Q3 to Q4, was there holiday-related seasonality in Q4 that impacted that start form number? Is that something that we could see reverse in the new year? You know, I think seasonality for sure, especially, you know, food-related holidays like Christmas, Thanksgiving, et cetera, are meaningful for this population. I do think that there's peculiarities that are specific to the disease itself. I'm not sure that they're so seasonal. You know, you have situations within families, you know, high divorce rates. You know, we had a recent example of a patient who had a script but did not start because the parents divorced. We see situations like this, which we find peculiar to this disease state. Yes, while there is seasonality, I think there's other things that happen in this disease state that are very specific to it. Maybe you could just elaborate what you're seeing in terms of persistence or discontinuations and what you expect that to look like over the long term. Yeah. The discontinuation numbers we said for adverse events, as of the fourth quarter launch date were about 12%, overall about 15%. We have said in the past that we expect long-term discontinuation rates to be in the 15%-20% range. You know, the one thing that we're tracking is in the trials we saw discontinuations to be earlier in the process. If you stayed on drug for about, you know, 6 months or so, you were likely to stay on drug long term. That's a metric we're watching very carefully. Early indicators are that is indeed the case here, but we'll watch that carefully. Okay. The discontinuations are primarily due to adverse events early on. You're not seeing discontinuations due to efficacy yet? How are you thinking about as patients get to kinda six to 12 months on treatment, especially for those that may not have as good of a response as others? Overall, we feel that if you stay on drug, a vast majority will have a response. We see that. We see responses coming on early. We see them deepening over time. I think there's this narrative about the six to 12 months. I think it's more related to the fact that our data shows maximal effects in those six to nine or six to 12 months. We see efficacy coming on early. I think it'll be unusual for someone to stay on drug for a year and not see efficacy. Okay. In terms of determining max benefit or response in a patient, do you think a doctor really needs six months, or it's really that kind of first full year, 12 months that's required to determine that? I mean, honestly, I don't think it's the doctor as much as the family, because these are really observed behaviors, and while some of them could be observed in clinic, generally they're observed by the caregivers. The doctor might ask the relevant questions, but the answer really comes from the caregivers. Okay. Maybe you could just give us the latest on coverage, where you're at in coverage and when you expect to reach, peak coverage. As Anish had mentioned, we're at the end of Q4, we were at over 180 million lives covered. We've looked at the various sources that you all probably look at, MMIT, to track the covered lives. As Anish mentioned as well, we have over 45 state Medicaid programs that either have a policy or have covered. I think that we also mentioned in our earnings call that we're probably going to, after Q1, stop reporting out on the covered lives. As you'll notice in rare disease programs, Medicare Part D doesn't usually list the product or the medicines on their formulary because they don't want populations going and searching for specific plans. If you look at MMIT, it's gonna be underreported, and most rare disease stop at around 60% covered. We're very pleased. We've had really strong coverage in Medicare. We mentioned about the 45 states in Medicaid. All of our top national PBMs last year removed the new-to-market block. We're super pleased. Also early trends last year looking at reauthorization were very strong. We haven't had any issues with that. What needs to be accomplished to get some of these last payers on board over the next few months? Yeah. The majority of them are really just some state Medicaid of the last couple of states. They just take time. They go through the P&T and the DUR, you know, Drug Utilization Review. It's just timing on those. Maybe you could discuss the latest on the average weight and price per patient that you all are seeing? As we've said in the past, the clinical trial weight was about 61 kg on average, 30.5 years of age. What we have seen over time, we've said a vast majority of patients are between four and 26 years of age, and therefore on average heavier than what we have seen. We've talked about the WAC being north of about $500. Overall we feel that we have started to see older patients come in, so the patients will be heavier, on average perhaps. We don't expect large step-ups though. We see this more as sort of a gentle cadence moving upwards. Okay. On average, how many patients titrate all the way up to the maximal dose or their optimal dose? How long does that take? We're tracking that information. I think it's fair to say that a vast majority of them will get to where they need to. In the clinical trials, for example, virtually everyone did. We're tracking it carefully, but right now I'd say a good majority is getting there. Obviously, some of the more experienced doctors, they'll pause titration if they see, some safety events and then allow it to recover and then go back to titrating. Assuming there's no pause, remind us how long that should take for the average patient. It's about six weeks. Six weeks. Yeah. All right. Gross-to-net, should we still expect it to be somewhere in the range of 15%-20%, or could that continue to grow over time or? As we have said, we expect it in the long term to be that. We have seen it to be somewhat lower until now. As we pointed out in the first quarter, you should expect it to be higher for the reasons that we have discussed. One is new policies coming in and, you know, needing to provide free drug for a period of time, and the other is copays resetting. As you know, for commercial payers, we do pay for the copays, so we expect the gross trend to be higher in the first quarter. What% of patients are on free drug, and how long on average does it take to move them from free drug to paid drug? We're not giving full percentages, but the vast majority are on paid. As many people might know, if you start a Medicare patient on free drug, you have to carry them out through the full year. Medicaid, you can actually convert onto paid and then commercial. We work through that on a day-by-day, week-by-week basis, but we've been really quite successful at converting to paid. I would add that a lot of the free programs are actually short-term. There's three programs that we have. One is Quick Start, One is Bridge, and the third is actual like true free drug. Mm-hmm. That category is actually very small at this time. Mm-hmm. Maybe just, we could touch on the prior authorization process. What's that been like for most doctors? I think if you've heard any of the interviews, they're all quite surprised at how smooth it's gone. Kudos to our market access and medical team for really laying the groundwork with the payers. As we've said before, a lot of the reauthorizations that are coming in with the policies are anywhere from six months to 12 months, with the majority sitting around 12 months. As I mentioned, some of those patients who had 6 months reauthorization in November and December have gone through quite well. Just following up on discontinuation, how many patients are you seeing discontinuing and then coming back onto drug or being reintroduced? This is starting to happen. I think it's a steady stream of people coming back. Interestingly, you know, one would expect that if you had a more severe adverse event that led to discontinuation, you might not want to, but we've actually had a meaningful number come back on drug or want to come back on drug in spite of serious reaction. Okay. As you've noted, well over 600 prescribers, many with few patients. Maybe you could talk about your plan to kind of reach these prescribers that may be less familiar with VYKAT XR as well as the patients and just your educational efforts and events that you all are hosting. Yeah. We have really placed a large emphasis and in the field team that we have gone to market with in the go-to-market launch, focusing on those who are high-volume prescribers. At the same time, we recognize that there were a lot in the community with regard to the long tail. We've put into place other teams like hybrid teams who are able to generate leads and pass that off to our sales team. We did that early on at launch, and we've seen that to be very effective. That raises awareness across the community, especially in those settings where they may not be as steeped into PWS. We have our MSL team and the medical affairs team who is really putting a lot of resources towards educating across both academic settings as well as the community settings. When we look at the metrics of awareness and growing awareness, it's very strong. We're also looking at the knowledge around VYKAT XR, and that's really a proxy for comfort, and we're seeing that grow as well. When you host these events, are you seeing like an uptick in prescriptions immediately following those events? How do you assess kinda return on investment and return on time with respect to your promotional efforts? Yeah. I think you're speaking about the patient events. Yeah. We both have the patient webinars where usually we have one of our top PWS experts talking and dialoguing with a family caregiver. We actually had a patient who came on and did a webinar. The other events that we have are the live patient events. We actually had one last year in October in Philly. We just did one last weekend in North Carolina, and we had two physicians join that as well. It's early, but we are hearing of patients who reach out to us, families who reach out to us and say, "Thank you for hosting that. Because of that, I went in and I asked to be prescribed VYKAT XR," and said, "I'm not leaving until I get it." It's been very successful. Before we get to, ex- U.S. and, the newly announced, pipeline indication, just in the U.S., What's your latest thoughts on the ultimate market opportunity for VYKAT XR? How large of a drug do you think it will be over the long term? I think the numbers speak for themselves, and the claims data itself at the time of launch, we said we were seeing confirmed 12,500 cases, which is a very meaningful number. Even if you were to assume a very modest penetration of that, this is a very large drug. The math is not that difficult to do. Turning to Europe, you responded to Day 120 questions. I think you said Day 180 were expected maybe the day after you reported earnings. Presumably you've got those questions. Are there any comments you could provide with respect to those questions and maybe even how you've responded or how you plan to respond, and next steps? I can acknowledge that we've received the questions. We're processing them right now. It'll take us some time. Were you surprised by any of them? No comments. Fair enough. How do you think about the opportunity in Europe, and your ability to launch VYKAT XR there without a partner? Let me talk about the opportunity. I think it's very meaningful. If you just look at the EU 4 plus U.K., you're seeing about 9,500 patients based on primary market research. When you look at prevalence estimates, we're seeing north of 15,000 in the EU 27. It's a very meaningful market. I think it is interesting that in many ways it's a lot more structured than what we see in the U.S., particularly in markets like France and Germany. Centers of excellence really drive it. We've started to work on a team, and I'll let Meredith deal with some of that. Yeah. I think it's as Anish had mentioned, a very attractive opportunity. Right now we're working on looking at the workload and the number of sales force that we need. We already have some of our medical team and the MSLs who are already starting and talking with KOLs and understanding the market landscape and doing market development activities. I think that what we're very pleased about is by those who are watching us in Europe and seeing the success that we've had here in the U.S. and getting to know the PWS community, that's very special. You have a lot of individuals who are very expert in rare disease and wanna join Soleno. Just to follow up on the structured comment, you mean like the infrastructure, like the treatment infrastructure, the practices, it's easy to identify the practices and the institutions that you need to go after. Is that fair to say relative to the U.S.? I think the U.K. might be an exception, but other than that, yes. Got it. Is that fair? Yeah. A little more concentrated. You know, if you look at Germany, they have more of the established centers of excellence than the U.S. although the U.S. is growing. We've commented a couple times where we're hearing, like even here in Boston Children's, finally got approval to set up their PWS clinic really recently. That's a little bit already established in Europe. Is the diagnosis rate in Europe similar to the U.S., or could it be better given what you just mentioned? It varies by country. If you look at France, there's published data that shows within the first couple of months, diagnosis happens really early. We've already done market research where other countries, there's some work that we need to do, but really strong advocacy across the physicians. I think not this past December, but December of 2024, we were able to bring together, I think it was almost 60 thought leaders across Europe. The great thing is that they're a tight community, and they share, and they share best practices. Assuming approval in Europe, you guys are committed to launching it yourselves as opposed to partnering, or is partnering still an option? You know, it remains an option. There's a lot of interest, but I think the ongoing challenges or uncertainty with MFN certainly makes us believe that it's best to have control. Not made the final decision yet, but we are certainly thinking more in that direction. Yep, that makes sense. Certainly hearing that from other companies as well. Okay. Maybe moving to the new indication GSD1 that you announced during Q4 earnings. Can you just elaborate on that indication, the mechanistic rationale to pursuing that indication with VYKAT XR and if there's been any thing observed historically in terms of case studies or clinical experience? glycogen storage disease, in particular Type 1, is a terrible condition. It's a situation where your body is not producing enough glucose or having enough glucose in the blood and leads to potentially fatal hypoglycemic episodes. The way these people survive is by taking multiple feeds of uncooked cornstarch during the day so that their glucose levels remain high enough. It is not a great way to live life if you speak with one of these families. People have been able to survive, and they live fairly normal lives, so they don't have the sort of comorbidities that we see in PWS, but it's a very tough way of living. Multiple efforts have been initiated to try and deal with this. The only one that's bear fruit to some extent is the Ultragenyx gene therapy. The data from that phase III study, it's now in front of the FDA, shows that there is a very modest decrease in cornstarch use from about five to about four times a day, which is pretty modest. In addition, about 20%-30% of those patients have antibodies to AAV, so they will not be candidates. In addition, there are known problems with AAV therapies related to the liver, and the liver is a primary target organ in GSD. It leads to a situation where these 3,000-4,000 people in the U.S. are really in dire need of a treatment option. Interestingly, there is very limited case reports that have been published from a very long time ago that show that the parent molecule can actually be used effectively. I've spoken with a KOL who has actually used that molecule in the past successfully, but could not continue to use it because of its side effect profile, given its multiple times a day use and very high doses. We think VYKAT XR has the opportunity to provide a very meaningful solution. Mechanistically, it makes a lot of sense because as you know, the drug decreases the secretion of insulin from the pancreas as a direct effect. What we need to do is to do exactly that, raise blood glucose levels just enough, so we can titrate the dose very carefully, get these people to where they need to be with a once daily dose. What's the status of initiating a study, and what might that look like in terms of timeline to data? Something we need to discuss with the FDA. The process has started. As we have said, we expect to start the process as we speak and start a trial later this year. We'll keep you posted on study design as we get more clarity from the FDA. Okay. Just in general, what about life cycle extension, strategy for VYKAT XR? Is that something that you all continue to think about? Could we get an update on that front anytime soon? We continue to think about it. There are some interesting options, and, yes, you should think of an update in the coming quarters. Great. Maybe to close out, I'll ask you what you believe is the most underappreciated aspect of the Soleno story by investors right now. I think you have to look at the market. You have to look at the fact that when we talk about patient numbers, these are not prevalence estimates. These are real patients. There is a very meaningful market out there. Each patient is very valuable. We don't need a very high penetration of this TAM to be a very meaningful drug. Meredith, anything you wanna add? I would just say that, you know, there's a high unmet need, similar to the numbers, but I think we've been very pleased with the interaction with the advocacy organizations and the community, and they're very receptive and just very appreciative of the approach that we've taken. I think that that tightness with the community will continue the momentum that we have. Wonderful. Anish, Meredith, thank you very much for your time. Thank you. Thank you, Tyler.