Okay, good morning, everyone. Welcome again to the Piper Sandler Healthcare Conference. This is David Amsellem from the Piper Pharma team, and we're delighted to have the team from Harmony: Jeff Dayno, CEO, Jeff Dierks, Chief Commercial Officer. Did I get your title right? Yes, sir. Okay. Thank you. Sandip Kapadia, Chief Financial Officer. So thanks, gentlemen, for joining us, and let's dive right in. There's, there's so much to talk about. I wish we had more than 25 minutes. So in terms of near-term dynamics on, on WAKIX, you've had pretty consistent growth, in the number of patients on, on treatment. So I, I guess, with that in mind, how are you thinking about the rest of this year, and into next year? This is not a guidance question. This is more of just a, a qualitative question about, the overall trajectory of the product, and I'll turn it over to you, Jeff. Yeah. Yeah. Yeah. Thanks, David. Thanks for the invitation. Great to be here. So let me first, you know, I want to emphasize and frame, I think, that Harmony continues to be a growth story. You know, you've heard me say this before, and, you know, and we're confident in that. The reason, it's due to the strength of our, sort of our core fundamental business of WAKIX and narcolepsy. You know, with regard to y ou know, we see the strong continued growth and momentum, and as we said, you know, we see that as a, a billion-dollar-plus opportunity in adult narcolepsy alone, and I think we're well on our way. And, you know, to give some of the proof points behind that, I'll, you know, I'll turn it over to Jeff. Sure. Thanks, Jeff, and thanks for the question, David. Yeah, we continue to be extremely pleased with the growth that we're seeing in WAKIX. We reported in the third quarter approximately 5,800 average number of patients on WAKIX, and that was approximately 350 patient increase sequentially from the second quarter. Mm-hmm. So, strong second quarter, that momentum continued into Q3, really driven by a continued strong top-line demand, new patient starts that offset the typical summer seasonality that you tend to have with fewer patient visits in the summertime. Mm-hmm. We continue to see strong product adoption, and I think the unique thing about the narcolepsy market, which we talk a lot about, is although it's a rare condition, there's about 80,000 diagnosed patient opportunity. Mm-hmm. And so as we're quickly approaching approximately 6,000 patients on product, you could see there still is a vast opportunity that remains in front of us, and we'll continue to tap into that opportunity each quarter as the market allows. Mm-hmm. I think what we've also seen in terms of, you know, analogs, as you look back to the oxybate analog back in the early 2000s. Mm-hmm, mm-hmm in terms of, you know, looking at growth trajectory moving forward. Yeah. There's a product that's been on the market for over two decades. Four years into their launch and where we are in our launch, we compare very favorably with respect to having more average patients on product. We have more unique prescribers of WAKIX today, four years in, than they do today, 20 years in. Mm-hmm. You know, oxybate's a great drug. Yeah. It's helped tens of thousands of patients, but it's continued to grow during its entire life cycle. Yeah. So we look at that as a very good harbinger, and it gives us a lot of confidence in WAKIX really being a potential billion-dollar opportunity. Good. Yeah, yeah. We've spoken to the broad clinical utility of WAKIX, you know, given the overall, you know, benefit-risk profile, you know, in terms of that sizable market opportunity of 80,000 diagnosed patients. Yeah. I want to just add- Yeah, go ahead. You know, obviously, the last quarter was really strong as well, with over $160 million in sales. So a really good, strong momentum, you know, versus prior year, versus the prior quarter, as, as we expect that to continue for you know, as we go into quarter four and as we enter, you know, another, another year, in 2024. I wanted to focus on your penetration into physician practices. So there's an audience of doctors who are in an Oxybate REMS, and there's an audience of physicians who are not in an Oxybate REMS. So can you talk to your penetration into both groups of physicians, and also just remind us what the size of those two respective audiences are? Sure. So the 80,000 diagnosed patient opportunity, they're really managed by approximately 9,000 healthcare professionals. Mm-hmm. There's about 9,000 doctors that see and treat almost 100% of the diagnosed narcolepsy patient opportunity. About 4,000 or so of those are Oxybate REMS-enrolled healthcare professionals, but there's another 5,000+ doctors that are not enrolled in the Oxybate REMS program and cannot prescribe an oxybate. And so when you think about those two distinct segments within the oxybate, healthcare professionals, we're highly penetrated in that audience, and probably is no surprise to you, David. These are sleep specialists. They've got larger narcolepsy patients that they're managing. They prescribe all the eligible treatment options, WAKIX, as well as the traditional scheduled, you know, medicines that are available. Mm-hmm. As we get into the 5,000 healthcare professionals that are not in the Oxybate REMS program, what we disclose in our third quarter earnings is we're about 25% penetrated in there. Okay. So more than 1,000 doctors that are not eligible to prescribe oxybate have already prescribed WAKIX in the first couple of years of our launch. And so as we think about growth moving forward, what we're seeing in the oxybate enrolled healthcare professionals is growth in the depth of prescribing, right? They have experience with WAKIX. They've got multiple patients on the product, but every quarter, they're finding new appropriate patients in their practice to prescribe, even with the availability of multiple generic and new formulations of oxybate. Mm. In the 5,000 healthcare professionals, you know, we continue to see new ads and new prescribers at a relatively consistent rate, going almost back to COVID. Within those 5,000? Within those 5,000. Yeah. Moving forward, we're seeing a balance of growth within both depth of prescribing in the Oxybate REMS-enrolled healthcare professionals, as well as breadth- Mm-hmm in the new prescribers. We've done research periodically throughout the year, and we've shared on our recent earnings call. We do what's called awareness, trial, and usage, or ATU research, every, you know, maybe 3 times a year, about 70 healthcare professionals that see and treat 3 or more narcolepsy patients under his or her own care. When we interviewed these individuals and asked those with WAKIX experience prescribing, 100% of the physicians that were surveyed said that they're going to continue to write the same or increase their prescribing in the next six months. Mm-hmm. Even more importantly, of those who have no experience prescribing WAKIX, more than 40% of those that were surveyed stated intent to prescribe in the next six months. We continue to see a really strong, you know, prescriber base, and gives us a lot of confidence in that future growth driver for the brand. Let's talk about payer dynamics. You know, this is a rare disease space, so there's a caveat here, but are dynamics relatively benign regarding payers? Are you seeing any evidence of a tougher payer landscape now that there's authorized generics of sodium oxybate? And do you envision the payer landscape at all changing once we see vanilla generics of sodium oxybate by the end of 2025? Sure. Well, I think the only, you know, sort of constant in managed care is change. Sure. I think that's very fair. But one of the unique things about WAKIX, given the overall unique product profile, it's, it's very insulated in terms of the current dynamics that are evolving, right? Mm-hmm. Within the oxybate vertical, there is churn, right? You've got multiple versions, you've got generic versions, and within the payer landscape, we are seeing them honing in on making one of those options available. So as we've had generics come to market, and we've had new formulations of oxybate, we've not seen any changes to the WAKIX formulary position. We've got positive, published formulary coverage for more than 80% of all insured lives across commercial Medicare and Medicaid. And even with the generic formulations being approved in the once-nightly oxybate, there are no plans that we're aware of that require WAKIX to step through any form of an oxybate. Mm-hmm. As we move forward into 2024, we've already had some of those discussions. Most payers have kind of finalized their plans, usually in Q4. We do not anticipate any changes- Okay to our formulary position moving forward. Okay. That's helpful. Yeah, Dave, so tough to move off, you know, a, you know, the only sort of non-scheduled approved agent for narcolepsy. You know, tough to sort of move that out of, you know, a sort of favored formulary position. Mm-hmm you know, given the overall benefit-risk profile. Okay. So there's been a lot of discussion about the Orexin Agonist, so I'd be remiss if I didn't ask you about the Orexin Agonist and how you're thinking about the potential impact of those agents to WAKIX and just on the treatment landscape in general, to the extent that one or more of these agents reach the market. What are your thoughts? I'll turn it over to you, Jeff. Yeah. So I'll, I'll keep it brief. So a lot of thoughts on that. Yeah. Very dynamic space- Yep I think, as people know, you know, the orexin agonist in those programs. So let me start. You know, obviously, really interesting target, you know, with regards to, you know, it's the potential mechanism of type 1 narcolepsy. So, you know, interesting target to begin with as the next, you know, novel therapies in narcolepsy. Mm-hmm. I think, you know, proof of concept has been established, you know, more around the EDS component- Yep still awaits to be seen on, you know, cataplexy. You know, and I think with all the emerging data, a lot of data that the World Sleep Congress and the recent announcement, you know, in terms of Jazz's four-for-one program. Mm-hmm. I think, you know, these programs are early. Mm-hmm. You know, they're early, and as we've seen, in the initial trials, you know, some good efficacy signals on EDS, but questions around, you know, some of the safety and tolerability and some of the signals that have been seen, whether it's molecule-based, whether it's target-based. So a lot of questions remain, but, you know, it's still a very exciting target. We watch, you know, this space very closely. Mm-hmm. I think that also, if and when they do come to market, it's gonna be at the end of the WAKIX life cycle, so, you know, when these eventually come to market, number one. Mm-hmm. And then also, it'll continue to be—narcolepsy will continue to be a polypharmacy market. Yep. So I think that, you know, even- Even Narcolepsy Type 1, because I've heard some KOLs who have been very excited about the orexin, saying, "This is gonna be transformative in NT1." You think this will be polypharmacy in NT1 too? I do. I do. Yeah. I do. I think that, you know, and I think that we've said this all along, you know, these symptoms are tough to treat. Sure. You know, as a neurologist who treated patients for 12 years and took care of patients, you know, with narcolepsy and IH and other sleep disorders, it's rare that monotherapy optimizes, you know, patients, you know, treatment and managing their symptoms. Mm-hmm. So I think even with orexin agonist, you know, if and when they come to market, it'll continue to be a polypharmacy market. And, at best, I think, you know, the lead program, you know, 2029-30 in terms of coming to market, so the impact on WAKIX, it'll be at the end of its, you know, life cycle, and, you know, we'll see how things play out. Okay. I do wanna talk about life cycle. Mm-hmm. Let's just talk about exclusivity runway for WAKIX. So now, no surprise, we have generic filers pending. Right. So that's to be expected here. The question I have here is: help us frame the best-case scenario in terms of exclusivity and your worst-case scenario in terms of WAKIX exclusivity. Yeah. So what I would say, yeah, in terms of our best case, let's start there, in terms of, you know, what we think with, you know, our IP landscape. You know, it takes us out, as we said, you know, it takes us out to March of 2030- Mm-hmm with regards to, you know, the polymorph patent and, you know, where patent term extension was applied to, so March of 2030. And then we're also working on pediatric exclusivity, which would provide an additional six months of protection, taking it to September of 2030. Okay. I think that that's our base case. Mm-hmm. You know, we believe in the strength of, you know, of our IP and plan to and are, you know, vigorously defending that. In terms of the, you know, the generic filers, the ANDA filers, as you said, you know, successful commercial business, we expected this to happen and we were prepared. So the, you know, initial ANDA filers came in- Mm-hmm you know, about six of them, and, you know, we've already filed suit to, you know, trigger the 30-month stay. And then, you know, now we'll sort of look at the claims, and, you know, that process, that long process will take place. And we'll see how that plays out. But our, you know, our base case assumption that we've, you know, spoken to is, you know, March of 2030 and potentially out to September of 2030. Okay, that's helpful. So, with all that in mind, you did announce or provide more details on the last call on two next generation- Yeah -forms of pitolisant. So, before I go into, you know, more specific questions about those two, and I have plenty, I wanted just to get a little refresher on the two formulations. What are the potential advantages? How do you see those advantages, and what kind of development program for both of you- Yeah you could envision? Yeah, sure, David. Yeah. Yeah. So I think that a nd I was gonna go there in terms of, Yeah you know, one of the answers in terms of the IP with regards to pitolisant, 'cause these are pitolisant-based assets- Sure are new formulations. You know, kind of lifecycle management, we have a novel molecule, you know, with sort of the first novel mechanisms of action, you know, in the market when we launched in over a decade for narcolepsy, and a successful commercial product. So in order to optimize that, working with our partner, Bioprojet, on new formulations. Mm-hmm. So at a high level, and I think, you know, we're now in the clinic, and we'll have more data first half of next year. So the first formulation is sort of a optimized formulation, an enhanced formulation of pitolisant, designed for an optimized PK profile. Okay. With that, we're working to increase, you know, the dosage range compared to where WAKIX is. That involves kind of a full development program- Mm-hmm and the opportunity to generate new IP- Mm-hmm -to extend the pitolisant franchise, not just to 2030, but out possibly beyond 2040. Mm-hmm. With that runway, we plan to do full development programs and look at new indications. Okay. You know, new indications, you know, So to be clear, that formulation would not be focused on narcolepsy? Well, one of our thoughts is possibly an expanded label in narcolepsy, and we've talked about looking- Okay at a fatigue indication Okay In addition to EDS and cataplexy. Fatigue is sort of emerging, you know, as another component, you know, of narcolepsy. So, you know, that's one, that's one idea, one part of the design of the program we're looking at. Okay. And then, you know, this would, you know, by design, a full development program, not come to market towards the end, you know, of the WAKIX life cycle. Okay. All right. So the other- Yeah So the other formulation we're working on is. It's more of a fast-to-market strategy in patients with narcolepsy. So, you know, what we're looking is a sort of formulation changes that could have some clinical differentiation and do an abbreviated development program in patients with narcolepsy- Mm-hmm Sort of consistent with a 505(b)(2) approach. Okay. And then have a new product offering during the WAKIX life cycle. And I think, you know, I'll turn to Jeff in terms of the thinking around that, why that could have value in the market. Well, if I may just interject and just ask one— Yeah I'm trying to tease out the difference between the two formulations. So they're both enhanced formulations. It looks like formulation one, the goal is to push the dose, and be able to confer potentially a better wakefulness-promoting effect without sacrificing tolerability. Is that a fair way to think about that? I think it's a fair way. Okay. And I think also by the formulation work is also looking to improve sort of the overall PK profile, some aspects of the PK profile- Mm-hmm you know, in terms of, you know, how that product would perform in the clinic. So we'll see when the data read out, you know, we'll have more information, and we'll be able to speak to that. So, so formulation two, what is different about that versus formulation one? I mean, you talked about a, you know, some degree of differentiation. Is that also a formulation where you can potentially safely push the dose? The second formulation is more a bioequivalence approach. I see. The PK profile would be similar bioequivalent. Okay. But then, you know, within that program, there's some clinical differentiation that we're working on in the clinic, you know, that would so it would be different to WAKIX. You know, a bioequivalent approach with other clinical features, you know, that we could get to, sort of fast to market through a 505(b)(2) approach. Understood. Sorry, go ahead, Jeff. No, it's a great question. Yeah. I think just given the lack of, you know, appropriate therapeutic options, that we see this as a significant opportunity to introduce something new to the marketplace. Yep. Especially in sort of the mid-WAKIX life cycle, it's likely in advance of the Orexin program, so there's likely not gonna be anything that's new out there for individuals in that mid-WAKIX life cycle. We have a mandatory hub model, so every prescription for WAKIX comes into one centralized location, so we have all of that patient information. They've opted in to be able to receive information from us. So at the time we get the approval of this new formulation, we have the ability to reach out to them and let them know that there's a brand-new treatment option. And David, you know this really well. The discontinuation rate that occurs across this category is very significant. There are patients constantly looking for new treatment options. Mm-hmm. We see this new formulation as a synergistic approach in increasing patients as opposed to converting from WAKIX to a new formulation. We see there's distinct patient populations for growth, and they're basically gonna be accretive for Harmony. Okay, that's helpful. Just going back to the formulation one- Yeah. I'll call it. You probably are not gonna be able to answer this, but I'll ask the question anyway. What new indications would you consider for that formulation? And, you know, you're working on Myotonic Dystrophy. Yeah. You have that study ongoing. That's gonna read out soon. Would myotonic dystrophy one make sense for that new formulation? I mean, you know, we think that it would, you know- Okay. with regards to, you know, where we are in sort of the runway for, you know, for pitolisant, that, as you said, the phase 2 proof of concept signal detection study- Mm-hmm. You know, will be reading out, you know, shortly before year-end. Yeah. And based on what we see there and where we are, you know, that is a program that we could pivot and have, you know, thought about, you know, pivoting to- Mm-hmm this, one of the new formulations, you know, with new IP, with obviously a longer runway. Okay. So we'd have much longer time in the market and could optimize, you know, that opportunity. In addition, as I said, you know, fatigue and narcolepsy in terms of an expanded label, potentially in an area we know well, and then other target indications would be consistent, you know, with our focus in other orphan rare neurologic disorders. Sure. So let's move to this study in IH. I'll start with just a process question. Are we going to see any updates on your analysis of the data before you meet with the FDA? And, I guess the second part of the question is, you did sound a note of confidence on the recent call in being able to move forward with a filing in IH. Can you also talk to that? Sure. Yeah, so let me unpack that- Yeah W ith regard to, yeah, our IH program- Yeah - and the phase 3 trial. So I think now that we've had time to, you know, review all the data and, you know, assess that. The reason, you know, the confidence in terms of a nd as we said from the start, even the top line, that when we look at the totality of the data- Mm-hmm you know, and we saw that a strong clinical signal with pitolisant and IH. You know, starting with, as we said in the initial open label phase, you know, an 83% response rate- Mm-hmm - which is pretty significant in a tough-to-treat population, with a mean improvement in the Epworth of almost 10 points. Right. So we acknowledge, you know, that during the randomized withdrawal phase, you know, we did not hit on the primary endpoint, but then 90%, almost 90% of the patients opted to go into the open-label extension, and we continue to collect data, both safety and effectiveness data. So when we look at the totality, you know, of the data, we think that there's a lot to work with, with regards to approaching the FDA, which is our next step. In addition, you know, when you look at, the overall benefit-risk profile compared to. There's only, as you know, one drug approved for idiopathic hypersomnia, you know, in XYWAV. And, and we look at the sort of the different product profile. And also, pitolisant has received orphan drug designation- Mm-hmm from the FDA. So we are putting all that together to engage with FDA in terms of the path forward. With regards to the rest of the data, you know, our plan is, first, we'll have those discussions with the agency, and then we'll be presenting sort of the data from the intern study at a future medical meeting. Okay, that's helpful. So I wanted to dig a little more into the trial here. So one difference in this trial versus the XYWAV- Yeah Trials, you had a 4-week randomized withdrawal period. With XYWAV, that was a 2-week randomized withdrawal period. And I'm not trying to say that, you know, that was the reason for the absence of separation, but I do want to ask you, why was that the case here? What was the rationale behind doing a 4-week randomized withdrawal period? Yeah. No, David, it's a fair question. Actually, it's in the other direction, and this is where we're digging in. Yeah. So the short answer is, it's because of the difference in the half-life, the PK profile. Sure. Pitolisant has a longer half-life than XYWAV- Mm-hmm than the oxybate products. That's why the XYWAV trial. B ecause when you randomize, you know, after the open-label phase, you randomize active to placebo, you need sort of decay in plasma levels in the placebo arm in terms of driving the difference. Mm-hmm. That's why pitolisant, longer half-life, and it was a 4-week randomized withdrawal to endpoint versus 2-week in the XYWAV trial. Mm-hmm. You know, given the, you know, the PK profile and plasma levels. That is where we are digging in a little further, because in addition to the PK, and where we expected plasma levels to, you know, decrease in the placebo arm, you know, we, we're looking at the potential in terms of pitolisant having a longer pharmacodynamic effect- Mm-hmm because it works through histamine modulation. The difference in the XYWAV trial, when patients were randomized to placebo, you quickly saw deterioration of almost up to 8 points worsening in the Epworth- Yeah - which is what we did not see in the trial with pitolisant. So, you know, we, The question is: Is there a longer pharmacodynamic effect? Mm-hmm. We did not see that lasting longer than the PK effect. We're digging into that to sort of better understand why there was not more separation. We expected placebo arm- Mm-hmm - to perform worse. Right. Even out, you know, to four weeks, where it we didn't see that separation. But you also saw a little, some degree of diminution of efficacy, for active drug, and I'm just wondering out loud, is that a nd I know this is a different population- Yep than narcolepsy, but is there w as that a surprising finding, number one? Do you see anything like that in practice where, you know, the effect of the drug over time does attenuate to some degree? Maybe if you can talk to that. Yeah. So that, that was a surprise to us in terms of, you know, we thought the pitolisant arm would hold a little more stable. There's a little movement, a couple points, in a randomized withdrawal phase. Mm-hmm. But that, you know, we did not expect that much movement. So in terms of your questions, we've not heard that in, you know, in terms of clinical practice in patients with narcolepsy, we've not heard that. We know that there's no evidence from the clinical data for narcolepsy, there's no evidence of tachyphylaxis. Mm-hmm. I think that even there, there was a real-world trial, long-term trial, the Harmony Tree study- Mm-hmm And out to a year, and in those patients that completed out to a year, 68% of the patients, they maintained effect. So we've not, in the previous clinical data, you know, we've not seen that, you know, you know, sort of that signal. And so I think that there's no evidence of that, you know, with regards to the previous data. Got it. Okay. Well, wish we had more time, lots to talk about, but we are out of time. Thanks so much for joining us, and thanks everyone in the audience. Great.