Great. Good afternoon, and thank you for joining Guggenheim's Second SMID Cap Conference. I'm Debjit, one of the therapeutic analysts here. And on stage with me today is Dr. Anish Bhatnagar, CEO of Soleno Therapeutics. Anish, thank you for your time. And maybe we can get started very quickly on the regulatory front.
Thanks, Debjit, for having me. Yes, things are moving along on the regulatory front. As you're all aware, we had a PDUFA delay in November. So the PDUFA was moved from December 27 to March 27. We think that was primarily because of the amount of information we were provided to them in response to their questions. So we have continued the back and forth, and we're hoping for a positive outcome at the end of March.
Any sort of new major questions from them? Obviously, they can't do any more amendments, right? There's only one push out.
That is my understanding, yes. And in terms of the back and forth, obviously not commenting on any of the specifics, but I don't feel like anything has been an extraordinary ask. I think these are good questions that one would expect to see in the context of an NDA review.
And how much of this three-month PDUFA push out was mostly logistics, given that it was right around the holiday season? And also, it was a relatively condensed review period.
So yes, we think those are the factors that played a part in it, the fact that the PDUFA was originally two months shorter than all the other priority reviews because the parent molecule is a known active substance, the fact that many of the responses that we had to them were due around the same time, and the extension happened when there was a month left in the PDUFA date, and that month included Thanksgiving and Christmas. So I think all of these things were factors. They did not point out anything specific in terms of safety, efficacy, or CMC-related issues.
Got it. And the inspections, those have happened. No formal 483s that we can track. Any updates on that side?
Same status. We have had inspections. No 483s have been issued.
Given the PDUFA as March 27, are you willing to comment on whether you are in labeling discussions currently, or?
That would be one we are not willing to comment on.
Typically, it happens four weeks before, roughly?
Yeah, I think in the weeks leading up to PDUFA.
But given that they've had a little bit of extra time, so it's almost like a six-month clock, do you think this will be on March 27, or could happen earlier than that?
We're not banking on anything earlier. We've spoken with our advisors, and they feel like sometimes some divisions will do it. So oncology is an example of one that does it. We're not banking on anything early.
OK. So setting aside the regulatory component here, you feel confident about the PDUFA date. How long do you think it'll take Soleno as a company to get drug in the channel?
We were ready even at the end of December. So there's some logistical steps that happen in terms of labeling drug with the final label, all that. But that should be a matter of weeks, not months.
So let's say PDUFA is on March 27, and by May, you should have product in the channels and potentially start booking sales?
Yes.
Cool. Anything that you see within the consensus estimates that give you a pause, hey, that's too high, first year of launch?
You know, I think the consensus estimates have not necessarily caught up with the PDUFA delay. So that's the one thing we would say. I think the models are still being looked at and updated. I think it's fair to say that if PDUFA is at the end of the first quarter, we start things in the second quarter, and we really be in earnest in the third and fourth quarters. So that's probably the best way to think of it.
If you think about the market size, depending upon who you ask, anywhere between 7,000- 12,000 patients, how many of those do you think will be on label?
So we've done extensive work now with claims data. And we feel really good about the at least 10,000 type of number. And we would think a vast majority of those are on label because the only ones that are not on label should be less than three years of age and those who have uncontrolled diabetes or no hyperphagia. So a vast majority of that approximately 10,000 should be on label.
Do you expect FDA to specifically put the age on the label, or just indicate patients with hyperphagia?
I think we expect the age, primarily because that was part of our inclusion-exclusion criteria. So my base case scenario would be that it's patients who have PWS, who have hyperphagia, and are at least four years of age. That would be my assumption.
Got it, and when you think about this market, how are these patients concentrated, or some patients are concentrated, how easy is it going to be for Soleno to find them and get medicine to them?
So, I think, like many markets, many rare disease markets, part of this is very concentrated. So, if you look at our corporate deck, you'll see a picture on there, which talks about approximately 300 health care providers either directly prescribing to or influencing prescription of approximately 4,000 patients. So, that's 40% of the TAM right there. We also know that we can see where these patients are, at least with three digits of the zip code in the claims data. And we can pinpoint which practices are seeing these patients. So yes, when you get out to community endocrinologists, primary care physicians, they might have one or two. But there are good ways to target them. Other than the salespeople in the field, we're going to have other providers who will target the group homes. Other employees will be targeting the group homes.
We will have inside sales looking at the accounts that are out there. And we'll have a lot more digital assets who will be targeting those accounts that don't have more than one or two patients. So we feel pretty good because there is a very strong component of advocacy here as well. We expect there'll be a strong pull from the families and caregivers who've been following the development of the drug over many years. So I think the ultimate demand will definitely be there. I know there's this curiosity about what is the bolus going to look like. That's harder for us to predict because access is something you need to sort out. It's not completely in your hands. And we'll have to see what the cadence is of these patients coming into the clinic, being able to be scheduled.
Obviously, we're not expecting final pricing from you, but the $300,000-$400,000 range seems about right?
No comments on specific pricing. And we've done a lot of research on price bands. We look at analogs. We look at incidence prevalence of various other diseases. I think you have to take a lot of things into account. And you also have to remember that this is weight-based dosing. So it's likely to be weight-based pricing. So it's not as granular as kind of one price fits all. So we'll be providing more detail on this around the time of approval.
Is there an age where patients are no longer hyperphagic?
You know, there's a theoretical nutritional phase IV where it is believed that patients are no longer hyperphagic. But we have not encountered a patient with true resolution of hyperphagia. We have now met patients who are 40, 45 years old and still living with hyperphagia. I think depending on your level of cognition, some of them understand it better, deal with it better. But they all live under supervised conditions because of food-related issues.
In these older patients, do you think there's going to be a challenge with compliance? I mean, I can understand the younger ones with families motivated to take it.
Interesting question because if you're in a group home, for example, then you probably have staff that's making sure that you're taking your drug because you're probably taking other medications as well. So this will be part of that. The other interesting thing about PWS is that these patients are obsessive-compulsive. So they actually want to be in a rhythm. They want to keep doing what they do. So whether it's going to school at a certain time, eating a certain meal at a certain time, or if it's being on a drug and taking that drug at a certain time. So we think there are some interesting aspects why compliance should not be as much of an issue.
Got it. And when you mentioned group homes, what percentage of that 10,000 patients are in group homes?
Our best estimate right now is about 10%.
Okay.
Remember, the group homes come in kind of different flavors. Some of them are PWS-specific, which means only PWS patients live there. The others are more kind of special care homes where different people with different kinds of disabilities live there, including the PWS. So the homes are spread all across the country. They come in different flavors.
The EU segment, obviously, did the PDUFA push out affect or change your plans or alter your plans with respect to CHMP?
No. We expect to submit in the first half of this year, and that remains on track.
What's the strategy going to be in Europe?
So we had initially been pretty categorical that we don't intend to have an ex-U.S. commercial infrastructure. But as we've done the work there, as we've understood the market there, we feel that it could be quite interesting to look at it ourselves, too. So for example, just the sheer prevalence of the disease, the EU4 plus the U.K. have the same number of patients as the U.S. does. When we look at pricing analogs, we see rare disease pricing as being a lot more attractive than other drugs. So we're right now kind of parallel tracking this. There is a lot of interest in ex-U.S. partnering. So we're looking at that as well but haven't made the decision yet.
I believe at time of launch, you wanted to be somewhere in the 125 kind of FTE. Does that include headcount for Europe, or is that purely focused on the U.S. launch?
Limited headcount for Europe is included in that, and we are almost there. I think we're at 120 right now.
Okay. So again, the PDUFA clearly did not push out, didn't impact your sort of hiring strategy.
No. In fact, we had intended to bring our sales force on contingent upon approval with the December PDUFA because there was just not enough time to do the hiring. With the push out, we have actually already hired about a third of the sales force, the ones that's targeting the key geographies. And the idea is that we will bring on the others contingent upon approval.
Thoughts on the IP situation? Do you think you can actually get to that 10-plus years, or still prudent to think about it as a seven-year life?
I think the seven years is kind of a starting case scenario. In our minds, there are many opportunities to go beyond that, and we've talked about this earlier, that even if you look at our salt polymorph patent, the composition of matter patents, with PTA and potential PTE could be in the 2034 time frame. We have two families of method patents that, without extensions, have primary expirations in the mid-2030s, so we think there's plenty of opportunity to be beyond that seven years.
So we've started tracking some additional future competition in Prader-Willi, primarily based on success you guys have had. Any thoughts on how that competitive landscape is setting up for you?
The only one that is late-phase is Acadia's drug, which, as you know, is carbetocin, which has been studied in two large randomized placebo-controlled studies. The FDA has turned it down, given it a CRL because there was an inverse dose response. It's a three-times-a-day product, which needs nasal delivery and temperature control. We think it's challenging. And the data that we've seen so far does not suggest significant efficacy. So I don't feel that it's competitively going to be too disadvantageous for us, even if approved. The last thing I saw was data in the mid-2026 time frame, I believe. So it appears to be delayed. That's really the only late-phase product that we are tracking.
Given that at this point, you are a single-asset company, how are you thinking about next steps for Soleno?
Several things. One is that we actively are evaluating other indications for DCCR. They fall in two categories. One is diseases like PWS, so diseases that have hyperphagia, potentially obesity associated with them. An example is Smith-Magenis syndrome. There's another class of diseases that have hypoglycemia associated with them. Example is GSD, glycogen storage disease. So that's sort of the first set of indications that we're looking at for DCCR. We're thinking about other ways of extending our work in PWS. We're looking at next-generation molecules, and we obviously are looking at other drugs to in-license as well.
Got it. Given that your expectations are for a pretty quick uptake, and that's kind of the feedback that we've got from physicians, are you thinking about in-licensing externally, or it'll become more of a DCCR-focused strategy?
Initially, it's a DCCR-focused strategy. We have to succeed in PWS. And I think we have to do more work with DCCR. I think we have to evaluate other new molecules in this space with similar mechanisms of action, which we are doing. And we are also looking at the possibility of in-licensing, but nothing that's imminent or urgent. This will come with time.
Got it. Any questions from the audience? We have time. Otherwise, I'll have to revert back to regulatory questions, which will be a no-go. No? Okay.
Thank you.
I do not want to push you on the regulatory side. I know you're sensitive to that. So good luck. And looking forward to March 27 or before.
As are we. Thank you.
Thank you so much, Anish. Appreciate the time.
Bye.