Hi, good morning, everybody. Welcome to day one of Cantor's Global Healthcare Conference. Very happy to have Dr. Anish Bhatnagar, the CEO of Soleno . It's kind of become our tradition here to kick off the three-day conference by hosting you first, and last year was a very, very special moment, as actually it was the day you announced your very positive randomized withdrawal data for DCCR and Prader-Willi syndrome. So thank you so much for being here.
Thank you for having me. Great to be here.
Can you believe it's been a year?
I can. It's been intense, but it's been good, and thanks for starting us off on the right foot exactly a year ago.
Yeah, it's been such a great year to see the progress and to see all, frankly, investors in the community learn about what Prader-Willi syndrome is, too. I think that's been something refreshing from my end, but let's jump right into it. So... Apparently, I'm not loud enough, so- Excuse the interruption. Okay. So very recently, the FDA approved your NDA filing for DCCR. You got priority review, and your PDUFA is on December 27th, indicating that there will be an AdCom. To date, what level of data and information is currently in the FDA's hands?
Right. So the FDA has our NDA, which consists of everything starting from what we believe to be our pivotal evidence of efficacy, the one study which is adequate and well controlled. That's the randomized withdrawal period for 602 . In addition to that, they have what we believe to be confirmatory evidence from all the other studies that we have done, starting with the 601 study, which was the first Phase III study, particularly its pre-COVID analysis. The long-term efficacy data, which at this point is an average of about four years, and the patients who went on randomized withdrawal, the comparison to natural history, you know, we have published these data around the comparison to the PATH for PWS study. So all of that is in their hands.
We've done patient interviews along with the 601 , 602 studies, that's in their hands, and obviously everything else that goes with an NDA, which has to do with CMC, which has to do with the quality, manufacturing, etc. So lots of stuff to review, a brief review period, and, you know, it'll be fairly intense, I assume.
Yeah. Well, congratulations on that progress so far. And you've been transparent with us for, you know, essentially since the time these data came out and you were talking about submitting, that you were gonna prepare in case an AdCom was asked for. And I know you've been doing a lot of work since that time. Can you help us understand what you're doing to prepare for this AdCom, what a mock panel is gonna look like for the company?
Sure, so as I've said in the past, we typically, the way this works is that you sign up with one of these three or four organizations that helped you prepare for an AdCom. That's what they do, so each of them has supported companies through 60, 80 AdComs, so they supposedly know what they're doing. The idea is for them to be involved as early as possible in the process, so in our case, we had them involved from the time we were working on the NDA documents. The idea is to look at messaging. The idea is to make sure that what we are saying in the documents comes across the same way when we do the AdCom.
The idea is for them to poke holes in the story, for them to look at the data with fresh eyes and ask the questions that we might not have asked, and then stay with us through the time that we are preparing for the AdCom with critiquing slides, creating slides, and eventually hosting mock panel, panels, where the idea is to bring in people who may have a profile that's as similar as is possible to the people who will be on the ultimate panel. All of that's in process. Mock panels are supposed to look like, exactly like the panels that will happen, and that's the intent. They get done in a way that kind of completely recreates the idea of an actual panel.
As part of that panel, how do you anticipate that patients, caregivers, the community are gonna help at this event? Clearly, they see a strong need, and I would encourage everybody to read the 130 -page petition that was filed. There was really powerful anecdotes, both on patients that were on the trial, but also those that would love to take a shot at it if the drug is approved.
So we're preparing from our end, and from what we can see from a distance, the advocacy community seems to be very enthusiastic as well. So you've seen the petition. We have heard anecdotally that they reach out to the FDA in the ways that they can as patient advocates. And if you look at the FPWR websites, they have a description of how you can help in an AdCom, and they're sort of quarterbacking the effort to have people go and speak at the AdCom, etc. So I have no doubt that there will be many people who would want to speak. There's not much that we can directly do to facilitate that, but we see that the advocacy community is pretty active.
You remember that they have been through this once before with the Levo AdCom, so they're familiar with it. The outcome was not what they desired, so everyone's hoping for a different outcome this time.
Yeah. Would also recommend anybody to view the town hall videos on YouTube if you're trying to get a sense of what this therapy did for patients. So separately, you'll be working with the psych division. In your opinion, are they familiar with Prader-Willi syndrome? Do you think there's a lot of education that needs to be required for them to truly understand the manifestations?
... I think they're quite familiar at this point. So if you remember many years ago, Zafgen was one of the companies in this space, and they were the last company that is-- that was in the metabolic division. At the time, it was determined, based on a lot of pushing from the advocacy organizations, that the primary endpoint needed to be hyperphagia. And at that point, to the best of my knowledge, all applications for PWS have gone to the psych division. So they've seen a lot. They have seen, you know, the phase III study designs for a lot of these companies.
Obviously, with Levo, there was a pretty concentrated education on the unmet need and the disease, and if you look at the advisory committee transcripts, or if you listen to the advisory committee, it's pretty clear that they are saying the right things as far as the disease is concerned. I would say since then, the couple other things that have happened are, one is the PFDD, the Patient-Focused Drug Development meeting that happened in June of last year, which was attended by people as senior as Patrizia Cavazzoni. So yes, I would say there is a clear realization of the unmet need, and I think it's a lot more than it used to be.
Okay, and simultaneously, ahead of your December PDUFA date, the company has grown in size pretty substantially to prep for a launch. What does that team look like today? And then, are there any other hires we can expect potentially after an approval decision?
So when we got data, which is a year ago today, I think we were about 27, 28 people. We are 70-some people now, so it's been a rather intense period of hiring. The early hires were really to assist with expediting the NDA filing, and we hired people around the CMC side, regulatory quality, et cetera. But soon after that, the hiring really has been focused on commercial and adjacent functions. So at this point, our Chief Commercial Officer has been on board for the last few months. Her leadership team is almost completely filled out, so you know, we have heads of market access, we have heads of marketing. Our med affairs team, the leadership team, is fully filled out. We're now hiring for field roles for medical, so MSLs, et cetera.
We expect the commercial hiring to continue through approval, and we expect the salespeople, the sales force that we're expecting to hire, to come on board right around the time of launch. You will see more hiring, not a massive amount, but all of it is gonna be in the commercial and adjacent spaces.
This is a kind of a rare disease that fits a lot of the buckets that people look for. The patients are easily identified, you know, at a pretty young age that you experience hyperphagia and get diagnosed with this. Patients are constantly meeting with physicians, but in terms of thinking about a commercial launch, how do you think about finding these patients through their doctors, but then also the young adults that are maybe living at specific places that are meant for patients, where there's a little bit of oversight in terms of making sure their eating habits?
Yeah. So I'd say there's two different categories here. The more obvious one to approach, identify, and therefore, treat, is going to be the younger patients who are living with their families and seeing their doctors, we estimate four to six times a year. So they have many more touch points. They're typically seeing pediatric endocrinologists. They are getting different things managed at a time. As they grow older, they are seeing more psychiatrists because of their psych symptoms. So those are the patients that we think are sort of lower-hanging fruit for us. When you come to the patients living in group homes, slightly different in the sense that they don't have any level of parental supervision on an ongoing basis, but they do typically have very involved family members.
What we have noticed is that the people who run these group homes are actually very interested in the drug, and the reason is that these are not, you know, massively profit-making enterprises because of how expensive it is to take care of situations like this. So you're looking at one-on-one care for these people. So if you can ease the situation enough that you don't need one-on-one supervision, it could make a very big difference. So we have seen a lot of interest from those providers in group homes, and we think the best way to approach that patient population is to work with the providers, who will then talk to the families.
We have specific people that we are planning to hire and have already hired at least one of them, who has experience in these spaces, who understands these group homes and this kind of care, and they will be the ones who will be leading these conversations.
I had the opportunity to go to a few rare disease conferences this year, and something I really didn't appreciate is how these communities really know each other very well. I mean, there were instances where people never met in person, and they approached each other because they knew them from a Facebook support group. Is that the case with Prader-Willi syndrome? Is the patient community very much intertwined? Are they all up-to-date about the different things in development, including your recent positive data?
There is definitely one element of the population which is very plugged in, so these are families that go to all the conferences. Every year, they will go to the FPWR conference, they will go to any PWSA conference that happens, so they know each other. These kids hang out together, and well, we have seen something similar. We have, in fact, had hosted an event recently where a number of families were there, and there were some kids who had never met each other, and you're right, they-
Yeah
... they kind of tend to blend, and it's, it's great to see that. So it is a community which is very tightly knit. It is a community that realizes that their problems are very similar to each other's.
Yeah.
So I think that brings them closer together.
Yeah... they can relate with each other.
Exactly.
Hard to explain these things to some people when you don't experience them. So in the trial, the hyperphagia questionnaire was the primary endpoint, but you were very successful on a number of other endpoints, including some hormones, some body weight, and then some behavioral changes. But the question I have for you is, commercially, how is one gonna determine success for this drug?
Good question, because you're right that the questionnaire that is the endpoint in the clinical trial is not used on an ongoing basis, so this has been a topic of discussion that we've had with some of the physicians who treat these patients, and what we hear is that they all have their own way of kind of approximately getting that information. So if you think of the nine questions in the questionnaire, you can kind of make them more qualitative and ask the questions around: "Hey, how is, how is so and so doing around food? Are they getting very upset these days, or is it better now? You know, last time we talked, they were, they were trying to get to the trash can in the middle of the night.
Have they done that recently?" So I think at the end of the day, even though the questionnaire is not administered as a questionnaire, we see physicians asking approximately the same questions to get to an answer. So I think when you think about reauthorizations and stuff like that, in many situations, these are physician notes saying that, you know, the patient's doing fine, patient's doing better, et cetera. So we expect that something similar will happen based on the, loosely speaking, the questionnaire itself.
Okay. And then is there a domain that people care about the most, or is it frankly that if you're helping with hyperphagia, secondarily, you're gonna see the other anecdotes improve as well?
Our data suggests that is the case. So when we have seen improvements in hyperphagia, we have seen improvement across all behavioral domains. So whether it be aggression, destructive behaviors, even depression in some cases, anxiety for sure. So we have seen that. It may not be the case in every situation, but we've also noticed that different patients may have different things that bother them the most, caregivers, not necessarily patients. So, for example, you may have a situation where one child is extremely anxious, and the caregiver may not identify that as true hyperphagia. But if you question it further, it's actually anxiety around food. So even in those situations, we believe that if you sort out the hyperphagia, the anxiety will decrease. So different...
You know, this was borne out in the PFDD, the Patient-Focused Drug Development Meeting, where there are themes which are common across patients, but there are themes which are very different across patients, too.
Okay. And going back to the commercial landscape, is it your understanding that there are areas where there's, like, pockets of patients, or is it more diverse across the U.S.? Of course, Florida is one place in particular that we're aware there's a lot of PWS patients.
What we know is that there is no predisposition with geography or ethnicity. So PWS happens by chance, spontaneously, in one in 15,000 live births, almost regardless of where you are, et cetera. So the prevalence numbers tend to reflect that, at least across a given country, because healthcare is relatively similar. So we see it track population centers, and if you look at the concentration of patients, and, you know, as we have talked about claims data, when we see the claims data, we're able to identify the 9-10,000 patients that people are talking about. So they are very much there, and they very much track with the sort of population distribution, with exceptions like Florida.
We have also seen that there is a small number of physicians who are prescribing to a very large proportion of these patients, and those same physicians also appear to have influence over prescription of even more patients. So, for example, there's about three hundred physicians in the nation who seem to have either direct prescription or influence over prescriptions of almost 400 patients. It is a very concentrated patient population in that way, but not from a geographical perspective.
Okay, got it. Well, I started off by saying this does fit a lot of buckets that you'd like, a disease where the patients are identified pretty easily. There's no standard of care, so really, you'd be the first here. But that said, how should we frankly be setting expectations and not getting overly excited about what the opportunity can look like?
I think you have to realize that healthcare delivery is complex.
Yeah.
And getting on any treatment is complex, particularly expensive treatments. That said, we do think that when you have a situation of a rare disease with a significant unmet need and no treatments available, we don't think there's going to be pushback from payers for payments. The question more is, how quickly can you schedule patient visits to go to these physicians? How quickly can you get coverage in place? So I would say you should temper your expectations on speed, but you should be as bullish as you've been in terms of actual patient numbers. We think that there's a lot of patients. We think there's a lot of demand, ultimately.
Okay. And, all of us in rare disease land tend to like to look at comps of drugs that are in different indications but can kind of tell a story similar to what the potential for this could be. Are there any that come up as it relates to comps for what DCCR can look like?
... The challenge with comps in rare diseases is that every rare disease ends up being different.
Yeah.
You know, you can try to come up with a comp, and you will definitely be wrong because, you know, the incidence, the prevalence is different, who's seeing them is different, the treatment landscape is different. But that said, our commercial teams are looking carefully at any comp that might exist to figure out what was done right and what was just wrong, what was done wrong. So we're taking the learnings from those comps and hope to incorporate those in how we create our messaging. So I don't have a precise comp to give you, unfortunately.
Okay.
but what I can say to you is that we're learning from what's been done.
Yeah. Yeah, maybe just on that note, Anish, I've seen a lot on LinkedIn. You're a huge advocate for the rare disease space in general, even beyond the work that Soleno is doing, along with another of other great companies I cover here that really have the same mission as you. So maybe just in your level of expertise in following this field, why are we all of a sudden getting more enthusiastic about the potential for rare diseases, and what are the biggest question marks going forward for this space?
I think we're getting more enthusiastic for different reasons, and one is humane. You know-
Yeah
... this just doesn't make sense to be in a situation where there's so much work that's gone into other stuff and not enough into rare diseases. So that's one big reason. You know, these are clear, unmet needs where not enough work has been done. The other is I think commercial. I think people see the commercial opportunity in rare diseases as well, which is okay, as long as you're doing it for the right reasons. And then I believe the IRA also has an impact on the interest in rare diseases. So I think in a lot of ways, rare diseases have become a very interesting space for many people.
Well, thank you for your support in helping-
Thank you for yours, yes.
... some of these patients beyond what you're doing. So, yeah, so tell us about the balance sheet. What does this get you through? How are you feeling? Are you pulling your CFO's hair out these days, or is he pretty happy?
I think my CFO is pretty happy, as you can see right now. I think at the end of last quarter, we had almost $300 million in the bank, so we are a lot more comfortable than we were when we were sitting here last, Kristen. You might remember. So in terms of where it takes us, this is a substantial amount of cash for us. When we look at how we spend, we think that this will take us through launch and substantially through launch and potentially to a place where we can be cash flow positive.
All this together, I mean, you went from what was it? $50 million market cap when we were sitting here last time to-
We've been south of that.
To now,
We won't talk about it.
To now $2 billion. So why, why is it that, when investors look at your stock chart, they shouldn't say, "Oh, man, I'm too late getting in"? Why is it still a great opportunity to invest?
I think it depends on when you knew U.S.. I think a lot of people who knew U.S. back then when we were 50 or less will feel like they've missed the boat, and I get it. I think there's a psychological element to feeling like I could have bought then and didn't, but I think if you look at the space that we are in, the market opportunity that exists, the fact that there's no competitors on the market right now, you can easily justify valuations that are north of where we are today, so you know, you all do the math better than I do, but I think from my perspective, this is a drug that works in a disease that nothing else does.
So what do you think, folks are still missing or maybe, underappreciating outside of that market potential?
I feel a lot more appreciated now. I have to start by saying that. But, I will say that it's the overall market. It's the idea that you can actually reach that many people in a rare disease-
Yeah
... where nothing exists, so I think people who are digging in and really understanding the story are seeing it, but not everyone's there yet.
Okay. Please go ahead.
Two questions. I know it's early, for modeling purposes only, just tell me what kind of pricing assumptions I should use, and what's the dose of your drug per day, the pricing assumptions? And second, can you give us an update on your strategy for the rest of the world, Europe?
Some parts of that I can easily answer. Our dosing is an optimal dose of 4.2 mg per kg per day. Our tablets come in three strengths, 75, 150, and 25 milligrams. We try to get to 4.2 based on a combination of that. We achieve in pretty much every patient, a minimum of 3.3, and there's an upper limit as well, I believe, of 5.2, but I would use 4.2 mg per kg as the target dose. In terms of pricing, obviously, I don't have a number to give you, but we talk in large brackets at this time. We talk about the lower end of the bracket being something like Amylyx, which is, you know, $140-$150 when it was launched and when it was selling.
And we talk about a high end of something like Daybue, which is about $540 or so. And then there's others in the middle of the pack, like setmelanotide, in the range of about $360, Skyclarys in the range of about $370. So this is the range that we are working with. As you know, a lot of work goes into optimizing how we price, and that's ongoing right now. From a rest of world perspective, we have recently talked about the fact that we are planning to submit an MAA in Europe in the first half of next year. So we believe that the data set will suffice for approval there. We're planning to move forward. We are talking to people extensively about other geographies.
As I've said earlier, the birth incidence of the disease is the same regardless of geography or ethnicity. So, you know, wherever you are in the world, this is a real disease, and it's well-recognized because of its phenotypic characteristics. So there's believed to be 60- 70 countries which have mainstream advocacy organizations for PWS. So well-recognized, an unmet need. We're committed to trying to bring it to as many countries as possible, as quickly as possible. So we have internal efforts to identify what's the best way to do that. Stay tuned on that.
I'm looking forward to seeing you on stage at 8:00 A.M., September of twenty twenty-five. I think the story is just gonna keep getting better for here, from here. Thank you so much for your time and coming to our conference.