All right, good morning, and thank you for joining Guggenheim's 2025 Healthcare Innovations Conference. I am Debjit, one of the therapeutic analysts here, and my privilege to welcome our next presenting company, Soleno Therapeutics. Joining us are Anish Bhatnagar, CEO, and Jim Mackaness, CFO. Thank you so much, gentlemen, for braving the weather and the travel issues to making it here. Thanks for having us. I would otherwise ask you to do a quick intro, but I do not think you need an intro at this point. Let's get into the Q&A. Sounds good. Just had what we thought was a pretty phenomenal quarter, but obviously the stock reacted very differently. What do you think is the disconnect here? Yeah, good question. I want to give the backdrop of what you said was a phenomenal quarter because we agree. We doubled our revenues to $66 million. We were cash flow positive. We had a very meaningful number of start forms, a large number of active patients, a discontinuation rate, which is very reasonable. Overall, we agree this was a phenomenal quarter, and it was in a space, hyperphagia, and PWS where nothing has been launched before. As far as we're concerned, the disconnect appeared to be that people were expecting to see more or different from start forms from the perspective of what the business might look like going forward. From our perspective, start forms, we were clear, do not expect to see the same as Q2, but expect to see a steady increase over time. That's exactly what we saw. We also indicated that there is a continuing cadence of that level of start forms going into this quarter as well, which we think is what we need to build a business going forward. We do not see any reason to have the sort of reaction that we did. Let's drill into the start forms. You've had basically two full quarters of launch. You have 10% of the market. What should be the cadence that, or how should we think about the cadence of new start forms going forward? Is the bolus done? It's going to be more the steady state looks more like the third quarter, or it's going to be substantially lower going forward? If you remember what we said before launch, we said we do not know if there is going to be a bolus, but based on our conversations with physicians, especially the large practices, we see this as a cadence of steady increase in numbers of patients on drug over time. We did have a bolus, and we think that bolus tended to sort of peter out early in the third quarter, but we saw what we expected to see, which is a steady stream of start forms going forward. In terms of what we expect to see, it is hard to give actual numbers because this is the first drug to be launched for this space. What we have said is that we got 10% of the TAM in the first six months. Even if conservatively we get 10% of the TAM in nine to 12 months again and again and again, this is a very meaningful market. This is going to be a billion-dollar drug in not very long. Got it. Before we go back into this quarter thing, you just announced a $100 million buyback program. What prompted that? Just thoughts on the timing of that? Yeah, it was very clear that the market was undervaluing the opportunity. We see the opportunity here as being substantial and being very different from what the stock was representing. We saw it as an opportunity given where we are with generation of cash and cash at hand. It was the right thing to do. Let's go back to the start forms thing. You said early in the third quarter, it sort of normalized. What are you capturing now as we go towards the end of the year? Do you expect significant seasonality in the holiday season? For example, did you have any seasonality during the summer vacations? It's a good question because as we try to give some color on the cadence of start forms, we said that August and September tended to be lower than July. For us, that could have been a function of summer because from what we understand, a lot of these kids, these young adults, go to multi-week sleepaway camps during the summer. It was not clear to us what it would look like. Similarly, it's not clear to us what Thanksgiving and Christmas will look like because, as you know, there are very different connotations of food for these people. Again, remind you, first drug to be launched in the space, we are learning as we go. When you look at the start forms in the early third quarter, in the early fourth quarter, we see the cadence is similar to the third quarter. Jim, you and I have talked about this in terms of the start forms, which can be captured externally. How accurate are that data set versus what you guys are actually monitoring? Yeah, we've got our analytics team looking at that. We're still trying to piece together all of it because we don't actually understand the projection that it's throwing off. We know that Panther, who's our specialty pharmacy, blocks scripts. We understand that the tracking service, if you like, is getting it from a number of different sources and then is trying to come up with an algorithm to throw it off. We know it's not a complete, it's a smaller set, obviously, than the whole claims data. We know that, so it doesn't represent everything. As I said, at the moment, whatever image is coming off is not what we're seeing internally. We're still trying to work on it a little bit more, but it seems very confusing to us. To provide a little more color, the scripts that you're talking about, the Symphony data that you're talking about, suggests at times a flattening of new treatments or number of the patients on drug. What we can categorically tell you is that both of those are increasing. Got it. That's helpful from a clarity perspective. With respect to the discontinuation rate, that ticked up a little bit. When are you capturing the discontinuation? Is it happening very early once a patient starts, or is it happening later in the course? What's driving that discontinuation? I would say a majority of discontinuations happen either during titration or completion or just completion of that. Think of it as the first couple of months as the time when a majority of them happen. I think it's fair to say that a good number of them happen because of side effects, peripheral edema or hyperglycemia being the more common ones. We've also said that in the recent quarter, some of them did happen due to non-serious events. We think that some of this is education. It's physician education. It's education of families. We're paying a lot of attention to that. We know that if you're an experienced physician, if you're someone who has been using the drug and treats the disease on an ongoing basis, you have a solid understanding of what to do with the drug, how to titrate it if there's a problem, et cetera. If you are a physician who does not have significant experience, you may not have seen it. There is an active education process. There are peer-to-peer events that are happening today. There is experts on demand. If you're a pediatric endocrinologist with no experience in this space, you can call an expert who will talk to you for half an hour, walk you through your patient and what you could do to titrate better, take care of adverse events, et cetera. A lot of activity in that space. We do think this is a space where we need to educate better, and we're doing that. With respect to efficacy, how long does that actually take in a real-world setting now that it's been out in the market for, call it, eight, nine months? Yeah, I want to provide a little bit of clarity there because there's this narrative out there that, oh, six months is what it takes to get efficacy. That's actually not true. The data shows that you get maximal effects in six to nine months. It's fair to expect people to start seeing efficacy before that. Maximal effects can take more time. For a situation like this, for families like this who have patients in such dire straits, you can imagine that even small changes can be very meaningful. We are now seeing stories across the board of patients who are having life-changing events. We will see more of that. The other thing we're doing is making patients and families available to others in the form of webinars and in-person events to talk about what therapy is like. What is it like to be on drug for a while? If there is a side effect, what did they do to get over it? The patients who have dropped out, is there an effort to bring them back on the drug with more education, or how should we think about that? Yeah, so that's the one big difference from the clinical trial setting where if you discontinued, you were gone. You were not in the trial. In the commercial setting, that is not the case. We have indeed started to see people come back to drug. There are, I would say, more than a handful of people now who have gone off drug for whatever reason, probably looked around and realized the fact that the disease comes back pretty quickly when they're off drug and have come back to drug. Yes, there is an effort to educate better, and we think we'll see more of those. Got it. Given the disease by itself has a huge number of comorbidities, is there a realization on part of the community and of treating physicians? There has just got to be more attention paid to this than randomly prescribing or titrating very fast. Yes. I think, again, there's a difference between KOL practices, people who understand the disease and the drug, and those who don't. I would say there is an increasing realization that this is a complicated disease. There's a lot of comorbidities there, and you have to watch. There are some patients who will sail through with a titration scheme that is exactly as written. There are others who will need more care. What percent of the market do you think are on the overweight, obese side where we have seen more of the severe AEs happen? What specifically are you doing to address that? Because that adds more noise, and it does not help the rest of the patients or families who want to get on the drug. Yeah, I think it's a fair comment that having a serious AE will discourage people whether or not it's relevant to them or not. It's hard to put a number to what percent of patients are obese, but I can tell you in our clinical trial setting, for example, about half the patients were obese. What happens often, and you can see this even in situations like oncology, when a new drug gets approved, often physicians have this gut reaction to put your worst patients on it. Nothing works for so-and-so. Let me try this. We have an effort ongoing to explain to people that that may well be the case, but you need to think through how you treat these people with respect to titrating better. Yes, another area of education, which is happening today. From a titration perspective, you do not necessarily, or the physicians do not necessarily have to adhere to what is on the label. Correct. You can take it slow. Do you have a sense of how your weight is currently trending from, let's say, August? Is there more of a concentrated effort to titrate slower and not have patients drop out? It depends on the patient. As I said, many patients will sail through. In our clinical trial population, we had virtually no problems with titration. It is really a function of patients. There is no sort of concerted effort that every patient needs a different titration. I think by and large, the way the label is written is correct. There needs to be a realization that there are specific patients who might need more care. On the cardiopulmonary side, is there a specific program that you're sort of implementing right now? Again, it depends on the patient. We do not think that across the board there is a need to have a specific kind of screening. Screening is something that denotes population-wide stuff that is not needed. There are certainly patients who, if you are 300 kg and you have congestive heart failure and bad diabetes, you are definitely a patient who deserves a good look by an expert before you put on the drug. Is there a point of no return from a treatment perspective that some patients you just should not treat no matter what? I'm sure. When we talked about our TAM, and you remember that our claims data actually shows about 12,500 patients, we've said our TAM we think is about 10,000. That delta includes patients who have significant comorbidities who we don't think are candidates for the drug. The initial plan was to go after the 300 high prescribing HCPs. What percent of that number is currently captured in your end of 3Q numbers? More than half of them have written. The interesting thing there is that even though we talk about our top 300, it's not that the distribution of patients is even across the top 300. I would say the top maybe 30, 40, 50 practices have a lot more patients than, let's say, the 250th practice out of the top 300. I would say that a vast majority of the large practices have already written. If you looked at across the board at the top 300, then we're more than half of them. You pointed out the physician education or peer-to-peer education. Has that started delivering dividends as yet, or is this still very early? Number two, would you be adding more boots to the ground than was originally planned just to address the overall safety profile? We absolutely think that we're seeing returns from the work that we put in. The physician-to-physician interactions are two main ways. One is that we've identified speakers, bureaus, experts who have experience with the drug. There are events being hosted where for an evening you could get together with eight other physicians, have a conversation with them, answer questions for them. The other is the physician on demand. We have people who've signed up, experts who've signed up to be sounding boards, if you will. For a 30-minute call or a 15-minute call, you can get an opinion from someone else. Got it. So we talked about this a little while back. 10% of the market already in for six months. Next year at this time, do you think Soleno can be 20% + of the market? 12 months out? Yeah. I think one of the things perhaps to help with that is you were talking about the KOLs. And one of the things listening to the commercial team is an example of a pro forma account, if you like, is you talk to the doc, and particularly they'll say of the number they thought they were going to put on drug, they're maybe like one-third of the way through. A lot of that was the bolus coming in, et cetera, et cetera. They have managed our expectations to say, look, I'm one-third in, but I really anticipate bringing my patients on the next two-thirds and three-thirds in the normal cadence of the patients showing up in my clinic. That kind of underpins the idea that over a period of time duration, we think this steady start form rate plays out over the next nine, 12, 18, 24 months. That allows us to go deep in those accounts. Then, as you mentioned, all of those communication things are helping us go broader across the HCPs sort of in the community where they may have more like a 1Z, 2Z number. That combination is kind of what really sort of gives us the confidence of what we think happens with that steady-state start form going forward. Got it. Let's switch to Europe for a second. The 120-day questions from Europe are already in. Thoughts around the next steps there? The way this works is you get the questions, you respond to them, and those responses are currently being worked on. The EMA then looks at those responses and sends a subsequent set of responses at day 180, which will be somewhere in the first quarter. You have a decision at approximately a year from validation. Europe does work differently. You have the concept of clock stop. While you're answering questions or back and forth, you have the ability to stop the clock, if you will, and then restart it with the EMA. Overall, we're guiding people towards a decision in Q2. Any showstoppers from your side from Europe? No, we think that the nature of questions that we got was similar to what we had been discussing with the FDA for the couple of years back and forth. We think that we were able to prevail with the FDA, so we should be able to prevail with the EMA. How are you planning for an eventual European launch? As we have said, we have interest from various parties. We have not made a decision on whether to partner it or not. We do think that MFN brings in a little bit more complexity. We did raise enough money to launch it ourselves if we needed to. We have started hiring in Europe, at least at the headquarter level. We have started thinking through a launch sequence, which would start with Germany. We will be ready to launch ourselves if we need to. Is that going to be a more concentrated market, or at least that's what we have seen with other rare diseases, as opposed to how it's in the United States? Yeah, definitely. We've been doing groundwork there. What we see in places like France, Germany, Italy, et cetera, is that care is centered around centers of excellence. There are experts. France is a good example that virtually every patient with PWS is seen at one of the centers of excellence. Got it. Anybody from the audience has any questions? Nope? Rana? Yeah, just regarding MFN, and I may be misunderstanding this. If this is considered an orphan drug as opposed to a mass market drug, do you see that the risk of being different there? I may be misunderstanding this. I think the problem is that nobody quite understands MFN, and they haven't really been very specific. There is the thought that orphan drugs will perhaps be excluded from MFN, but they haven't been clear. Going back to the U.S. launch then, the coverage sort of expanded to now 132 million lives covered. How do you see that cadence going through? Yeah, we're hoping that so the most you get is about 80% in terms of lives covered. We're hoping that in 12 -1 8 months post-launch, we should be around that number. What we have seen from a coverage perspective is pretty extraordinary. Our coverage team says they've never quite seen something like this in a rare disease setting. We've seen payments already come through from about 40 state Medicaid programs. We have three largest PBMs already have policies in place. We're seeing payments come through Medicare as well. It's been quite gratifying to see that, I think partly or in large part because of the pre-approval education, disease state education that was done by our teams. I think I touched upon this before, but you think the weight in the commercial setting is still trending higher than where it was in the clinical trials? Yes, I think that remains the case. We think that over time, one can expect the weight to trend up, just as we have said, that we expect older patients to come online. Should we sort of assume most of these patients are on 300+ mg, or they'll titrate to that kind of a dose or higher? As you know, these are weight bands, right? The lowest weight band would be a much smaller dose. The 61 mg would be the 200+ dose. The next weight band would be the 300+ dose. What you are looking at is weight bands that could be higher than the 61 kg without getting into the specifics of the weight. Got it. Any other thoughts before we close this? No, appreciate the time. Thanks for the invite, and looking forward to continuing the launch. Good luck, and hope to see fewer disruptions, especially from Facebook posts. Thanks, Debjit. Thank you very much. Appreciate it. Thank you so much, Anish. All right. Thank you, Jim.