Harmony Biosciences Holdings Aktie

Good morning, everyone. My name is Bo, and I will be your conference operator today. At this time, I would like to welcome everyone to the Harmony Biosciences Second Quarter Financial Results Conference Call. [Operator Instructions] Please be advised that today's conference is being recorded. [Operator Instructions]

I would now like to turn the call over to Mr. Brennan Doyle, Head of Investor Relations. Please go ahead, sir.

Good morning, everyone, and thank you for joining us today as we review Harmony Biosciences' second quarter 2026 financial results and provide a business update. Before we start, I encourage everyone to go to the Investors section of our website to find the materials that accompany today's discussion, including a reconciliation of our GAAP to non-GAAP financial measures. At this stage of our life cycle, we believe non-GAAP financial results better represent the underlying business performance.

Our speakers on today's call are Dr. Jeffrey Dayno, President and CEO; Adam Zaeske, Chief Commercial Officer; Dr. Kumar Budur, Chief Medical and Scientific Officer; Peter Anastasiou, Chief Operating Officer; and Steve Mollichella, Interim Principal Financial Officer.

As a reminder, we will be making forward-looking statements today, which are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties. Our actual results may differ materially, and we undertake no obligation to update these statements even if circumstances change. We encourage you to consult the risk factors referenced in our SEC filings for additional details.

I would now like to turn the call over to our CEO, Dr. Jeffrey Dayno. Jeff?

Thank you, Brennan. Good morning, everyone, and thank you for joining us today. This was a defining quarter for Harmony Biosciences on 2 fronts. Commercially, WAKIX delivered record quarterly net revenue of $261.3 million, up 30% year-over-year and up 21% compared to last quarter, signaling a decisive rebound from the seasonal headwinds we discussed on our first quarter earnings call.

And importantly, on the R&D front related to our robust pipeline, today, we shared encouraging data from a Phase I single ascending dose or SAD study for BP-205 that reinforces its potential as a best-in-class orexin-2 receptor agonist. Revenue is on track to exceed $1 billion this year, and our opportunity with our orexin-2 agonist BP-205 is coming into focus with multiple data catalysts over the next 6 months.

The 2 key messages that I want you to take away from today's call are: first, continued strong growth for WAKIX on track for over $1 billion in net revenue for the year; and second, encouraging Phase I PK data for our potential best-in-class orexin-2 agonist BP-205 with multiple data catalysts coming in the next 6 months. The foundation upon which we continue to grow the business and advance our pipeline remains strong. We are a profitable, self-funding biotech company operating from a position of strength, a proven commercial engine now in its seventh year in the market, a robust pipeline centered around BP-205, our potential best-in-class orexin-2 agonist, a balance sheet with the capacity and a management team with the expertise and conviction to execute on meaningful business development opportunities and a multilayered IP strategy to protect the pitolisant franchise out to 2030.

We continue to run the business aligned around our 4 priorities focused on value creation, growing the WAKIX franchise in an evolving market, advancing our robust pipeline, transacting on strategic business development opportunities and protecting our IP estate around the pitolisant franchise.

Let me walk you through the highlights for each of these 4 priorities. First, the commercial performance this quarter was outstanding as we continue to grow the WAKIX franchise in an evolving market. Our record quarterly revenue of $261.3 million keeps us firmly on track to achieve more than $1 billion in net revenue in 2026, which is why we are confident in reiterating our full year guidance of $1 billion to $1.04 billion. WAKIX has a compounded annual growth rate of about 40% over the last 5 years, and there continues to be a large market opportunity for WAKIX with about 80,000 patients diagnosed with 90,000 to 100,000 individuals not yet diagnosed.

Turning to our pipeline and the focal point for this call, BP-205, our potential best-in-class orexin-2 agonist. Today, we shared encouraging data from a Phase I single ascending dose PK study for BP-205. Kumar will take you through the SAD data results later in the call. BP-205 is designed to deliver a differentiated profile as the most potent of the orexin-2 agonist currently in the clinic with excellent selectivity and now with clinical PK data demonstrating a predictable PK profile with the potential for once-daily dosing, along with a favorable safety tolerability profile.

These data strengthen our conviction that BP-205 could be a best-in-class orexin-2 agonist and reinforce our commitment to invest in the BP-205 development program. We will be initiating Phase II trials in the middle of next year to evaluate multiple CNS indications as we believe BP-205 could have broad clinical utility.

Next up for BP-205 is top line data from the multiple ascending dose study in Q4 and initiation of a Phase Ib study in sleep-deprived healthy volunteers in the third quarter with top line data readout expected early next year. Kumar will provide more color on BP-205 during his R&D update.

One additional comment on BP-205 and our exciting orexin opportunity. We have been leaders in the Sleep/Wake space for almost a decade now and are leveraging our expertise to accelerate our BP-205 development program toward multiple CNS indications and become a leader in the orexin space. In addition to organic growth, we have significant firepower to put forward business development for inorganic growth.

With approximately $963 million on the balance sheet, we have the capacity and the conviction to execute on meaningful transactions to drive long-term value. Peter will share more color around our BD strategy later in the call. Additionally, he will provide an update on our multilayered IP strategy and our efforts to protect the WAKIX franchise.

We have settled with 6 of the 7 ANDA filers and are confident in the strength of our IP estate, which supports WAKIX exclusivity to March of 2030, inclusive of 6 months of pediatric exclusivity for which we are on track to obtain.

In summary, this has been a defining quarter for Harmony Biosciences. We posted record revenue for WAKIX in its seventh year in the market and shared encouraging data for BP-205, which supports its profile as a potential best-in-class orexin-2 agonist. With multiple data catalysts coming for BP-205 over the next 6 months and our focus on business development, Harmony is poised to deliver meaningful long-term value creation as we drive toward delivering innovative treatments for patients living with CNS diseases and unmet medical needs.

With that, I will now turn the call over to Adam Zaeske, our Chief Commercial Officer, for a closer look at our Q2 commercial performance. Adam?

Thank you, Jeff, and good morning, everyone. The second quarter continued our strong growth and momentum trend. WAKIX delivered $261.3 million in net sales, up 30% year-over-year and up 21% over the first quarter, now in its seventh year on the market and firmly on pace for our full year guidance of $1 billion to $1.04 billion in net revenue. Last quarter, we saw a bit more pronounced seasonal market access headwinds that impact the industry every year, the elevated plan changes, planned switching and premium increases, which can delay patient starts, especially in January. But the underlying fundamentals remained steady and consistent.

This quarter, the demand-driven trajectory and patient additions continue. WAKIX achieved estimated average patients of 8,950 or an increase of approximately 450 patients from 1Q. This represents the highest 2Q increase in the history of the brand, the second highest increase all time and with 4 of the last 5 quarters achieving 400-plus patient additions, our growth and performance has never been stronger.

What's driving this continued performance is clear. WAKIX owns a highly differentiated position as the only non-scheduled treatment option for narcolepsy patients. With now 7-plus years of clinical experience, health care providers are highly aware of WAKIX and believe in its unique combination of efficacy, safety and tolerability with low drug-drug interactions as well as its broad payer coverage with more than 80% of lives covered. This makes WAKIX a familiar go-to option for any patient with narcolepsy and in any combination with other therapies in a highly polypharmacy market, and this will continue to remain true as the market continues to evolve.

Q2 was the first quarter after our field team expansions, which has expanded our presence by roughly 20% across field sales, remote sales and field reimbursement. This represents the largest expansion and increase in investment in the history of the brand. All of those physicians have been hired, trained and fully deployed. We also launched a new online portal, easing the process to prescribe WAKIX for health care providers and office staff. And we implemented changes to our reimbursement support process, which is already showing results with patients able to secure WAKIX faster and with higher success.

As a result, we see significant continued growth potential in a total narcolepsy population of approximately 170,000 at diagnosis rates still under 50% and brand penetration of about 20%. Looking ahead, we're excited about our 2 life cycle programs to extend and expand the franchise. Pitolisant GR builds on the WAKIX safety and tolerability profile and enables patients to start at a therapeutic dose. Pitolisant HD offers a new optimized formulation with up to 2x the highest labeled dose of WAKIX, all of the benefits of the GR formulation and potential for differentiated labeling regarding fatigue in narcolepsy and sleep inertia in IH.

Finally, our orexin program gives us the opportunity to deliver on the promise of efficacy with a favorable tolerability profile, once-daily dosing and potential use in a broad range of CNS indications.

To summarize, we continue to operate from a position of strength. We are on track to achieve more than $1 billion in net sales this year with a pipeline built to extend our leadership in Sleep/Wake for at least the next decade.

I'll now turn the call over to our Chief Medical and Scientific Officer, Dr. Kumar Budur. Kumar?

Thank you, Adam. Good morning, everyone, and thank you for joining us today. We continue to make good progress across all our pipeline programs, including 5 Phase III registrational studies in 5 distinct rare neurological disorders. The headline for R&D this quarter is BP-205, a potential best-in-class orexin-2 receptor agonist.

So let me start there. BP-205 is built on novel chemical scaffold that confers unique potency, selectivity and potentially avoids some of the molecular structure-related effects such as hepatic and cardiac toxicity. It is the most potent orexin-2 receptor agonist in clinical development with excellent selectivity for orexin-2 over orexin-1 receptors and over 150 other receptors of interest.

The high potency gives us the flexibility to use low doses and to pursue a broad range of CNS indications, including those with no obvious orexin deficiency. Today, we reported data from the single ascending dose portion of our Phase I study in healthy volunteers. In this randomized, double-blind, placebo-controlled study across 9 cohorts in men and women, each participant received a single dose of BP-205 or placebo with doses ranging from 0.2 milligram up to 6 milligrams. In total, 72 healthy volunteers participated in this study.

The SAD study in healthy volunteers was designed to characterize pharmacokinetics and safety tolerability profile. Within that scope, the data was very encouraging. Walking through the specific findings, BP-205 showed rapid absorption with a short Tmax in the range of 30 to 75 minutes pointing to the potential for rapid onset of efficacy. We observed a mean half-life of approximately 25 hours across dose group, which supports once-daily dosing and the potential for durable efficacy throughout the day and into the early evening.

Exposure was dose proportional Cmax and AUC across all doses, indicating predictable systemic exposures across the ranges tested. We saw no age or gender differences in PK parameters, which supports no dose adjustment for elderly or female patients. Finally and most importantly, BP-205 was generally safe and well tolerated with no serious or severe treatment-emergent adverse events reported, including no cardiovascular, hepatic or visual abnormalities.

The most common adverse events were headache, fatigue and diarrhea in approximately 10%, 4% and 3% of the participants, respectively. To our knowledge, we are the first company to share this level of granularity on orexin-2 receptor single ascending dose data, and we are doing so because we have strong conviction in BP-205 having the potential for a best-in-class profile.

What comes next? Multiple ascending dose study data analysis is ongoing, and we plan to disclose those data in Q4. The U.S. IND for BP-205 is now open and we'll be initiating our Phase Ib study in sleep-deprived healthy volunteers in Q3 with the top line data expected from this study in early 2027.

That study is a one to watch because it will provide the first signals of efficacy for BP-205 and provide a basis for comparison against other orexin agonist. Given the potential for broad utility of this profile, we will be initiating Phase II trials in multiple CNS indications in mid-2027.

Turning to our other programs and starting with next-gen pitolisant programs. We submitted the pitolisant GR NDA in the second quarter. The file is accepted for full review with a target PDUFA date of April 1, 2027. Approximately 80% to 90% of patients with narcolepsy experienced GI symptoms as part of the disease and pitolisant GR is designed to reduce the potential for GI AEs while also allowing patients to initiate treatment at a therapeutic dose of 17.8 milligrams without titration, an important clinical differentiation.

Pitolisant HD and optimized formulation of pitolisant with GR coating and high dose continues to advance in 2 Phase III registrational trials, ONSTRIDE 1 in narcolepsy and ONSTRIDE 2 in idiopathic hypersomnia with top line data expected in 2027 and anticipate PDUFA in 2028. These programs are pursuing differentiated labels, fatigue in narcolepsy and sleep inertia in IH, symptoms for which there are no currently approved treatments. Utility patents were filed for both pitolisant GR and pitolisant HD with the potential to extend the pitolisant franchise into the 2040s.

Moving on, the Phase III registrational study in Prader-Willi syndrome, the TEMPO study is actively recruiting patients and we now expect top line data in mid-2027. The delay in top line data is mainly due to limited prevalence of people living with PWS and also experiencing the level of sleepiness that meets the criteria to enroll in this study.

This study is designed with the input from the FDA, not only to meet the registrational requirements but also fulfill the second and last requirement for pediatric exclusivity, which gives us 6 months of additional regulatory exclusivity for WAKIX on the back end of the longest patent. And we remain on track to obtain pediatric exclusivity for WAKIX. We are also advancing the amorphous form of pitolisant license for Novitium, supported by an issued patent through 2042.

The current efforts are directed towards formulation optimization and ongoing Phase I PK study. Finally, our epilepsy franchise. EPX-100, our clemizole hydrochloride continues to advance in 2 global Phase III registrational trials, the ARGUS Study in Dravet syndrome and the LIGHTHOUSE Study in Lennox-Gastaut syndrome, with top line data expected in mid-2027 and anticipated PDUFA in 2028.

In summary, we are encouraged by the data we shared today for our orexin-2 agonist, BP-205, supporting its potential best-in-class profile and excited about the multiple data catalysts coming within the next 6 months for BP-205. We also continue to make progress on the 5 Phase III registrational clinical trials that we are conducting across our other pipeline programs, which will contribute to additional data catalysts in 2027 and target PDUFA date in 2028.

On behalf of Harmony, I want to thank the patients and the families for participating in our clinical trials, along with the investigators and site personnel for their dedication in advancing our clinical trials.

I'll now turn the call over to our Chief Operating Officer, Peter Anastasiou. Peter?

Thank you, Kumar. I want to provide a brief update on the final 2 objectives in our value creation strategy, transacting on business development and protecting the pitolisant franchise. In business development, we are primarily focused on assets with revenue potential in the 2028 to 2032 time frame. We are prioritizing products in Phase III, in registration or on the market. We plan to leverage our core competencies and are directing our search and evaluation efforts in Sleep/Wake, epilepsy, rare orphan CNS and broader CNS indications.

We are considering a variety of deal types, including M&A and licensing. With approximately $963 million on the balance sheet, we have both the capacity and the conviction to transact. You should not expect that we will allocate all of that capital on one transaction.

Instead, we will likely engage in multiple transactions and together, they can be transformative for Harmony. With regard to protecting pitolisant, our IP estate is multilayered across formulations, methods of use and next-generation applications, and it supports WAKIX exclusivity into March 2030, inclusive of 6 months of pediatric exclusivity. There is the potential for Harmony to extend the pitolisant franchise through other formulations into the 2040s via additional patents and applications.

With respect to ongoing litigation, we have settled with 6 of the 7 ANDA filers, and we have 2 active legal proceedings with the lone remaining ANDA filer. The first is the ANDA litigation with AET, where we are defending our polymorph 197 patent and the method of use 947 patent. The bench trial has concluded and the post-trial briefs are public. Harmony requested and the judge has called for closing arguments from both sides on October 22 this year.

In April, Harmony and Novitium filed a new patent infringement lawsuit against AET Pharma US and its marketing partner, Sandoz, alleging infringement of the 920 patent covering an amorphous form of pitolisant hydrochloride. We are confident that we will prevail in both of these legal proceedings, enabling us to maintain exclusivity for WAKIX into March 2030.

I will now turn the call over to our Interim Principal Financial Officer, Steve Mollichella. Steve?

Thank you, Peter, and good morning, everyone. This morning, we issued our second quarter 2026 earnings release and filed our 10-Q, where you will find details of our financial and operating results. We delivered strong financial results that reflect continued demand for WAKIX and our disciplined approach to managing expenses across the business. For the second quarter of 2026, we reported net revenue of $261.3 million compared to $200.5 million in the prior year quarter, representing 30% growth.

Performance in the quarter reflects the continued robust demand for WAKIX. Cost of product sold was 24.2% of net revenue compared to 19% 1 year ago. This year-over-year increase was primarily driven by new royalties related to the Novitium license agreement, which we signed in Q1 of this year. We reported total operating expenses of $108.8 million for the second quarter compared to $114.2 million in the prior year quarter.

The decline in expenses was primarily driven by the $15 million upfront fee we paid to CiRC in Q2 of 2025, with no corresponding amount in the current year period. This was partially offset by continued investments in R&D and the ongoing commercialization of WAKIX. Net income for the second quarter was $75.4 million or $1.28 per diluted share compared to $39.8 million or $0.68 per diluted share for the prior year period.

Finally, we ended the second quarter with $962.5 million of cash, cash equivalents and investments and $155 million in debt. We expect cash flow generation to continue to be strong in the coming quarters. That said, our intent is to deploy our cash towards strategic business development opportunities and to continue to invest in the growth of our pipeline and diversification of our commercial portfolio.

And with that, I will turn the call back over to Jeff for his closing remarks. Jeff?

Thanks, Steve. In closing, this was a defining quarter for Harmony Biosciences, centered around 2 key accomplishments. We delivered record quarterly net revenue for WAKIX and are on track to achieve greater than $1 billion in revenue for the year. And importantly, we took a big step forward in our orexin-2 agonist development program, sharing encouraging Phase I PK data for BP-205, which supports its potential best-in-class differentiated profile.

And coming soon, MAD data in Q4 and data from a sleep-deprived healthy volunteer study for BP-205 early next year. We have been leaders in the Sleep/Wake space for almost a decade now and are leveraging our expertise to accelerate our BP-205 development program toward multiple CNS indications and become a leader in the orexin space.

We continue to drive the business around our 4 priorities focused on value creation, grow WAKIX in an evolving market, advance our robust late-stage pipeline with our potential best-in-class orexin-2 agonist, BP-205 as the centerpiece of our pipeline with multiple data catalysts coming over the next 6 months, transact on strategic BD opportunities, and lastly, protect the pitolisant franchise based on our multilayered patent estate and robust IP strategy that gives us confidence in defending the WAKIX franchise out to March 2030. We believe that when we execute on these 4 priorities, Harmony is well positioned to bring innovative treatments to patients living with CNS diseases while driving sustained long-term value for shareholders.

Thank you for your attention. I will now turn the call back over to the operator for Q&A. Operator?

[Operator Instructions] We'll go first this morning to Pete Stavropoulos at Cantor Fitzgerald.

Congratulations on the progress. My question is around the clinical program on BP-205. Congrats on the SAD data. Good first step. And I'm curious on how the short Tmax relatively long half-life and high potency could translate into a differentiated clinical profile from both efficacy and safety standpoint, especially compared to other orexin-2 receptor agonists that are either BID or split dose? And how do you think they impact the use in the broader CNS indication?

Pete, thank you for your question. Yes, with regards to BP-205, we are excited about the emerging clinical profile with the Phase I SAD data. I'll turn to Kumar to provide perspective on short half-life and the rest of the profile and the potential clinical relevance.

Pete, thanks for the question. So you asked 3 questions, Tmax, half-life and potency. Let's start with Tmax. The time to maximum concentration was very short, 30 to 75 minutes. And this is a very desirable feature because it results in rapid onset of efficacy. And that's especially important when you look at central disorders of hypersomnolence where patients are sleepy. And within central disorders of hypersomnolence, if you look at indications such as idiopathic hypersomnia, for example, who have sleep inertia, again, short Tmax is very helpful.

And also beyond central disorders of hypersomnolence, if you look at indications such as ADHD, again, a short Tmax will be very helpful. In terms of half-life, first and foremost, the longer half-life will facilitate QD dosing, which is always preferable from a patient perspective.

And in terms of efficacy, it does help sustain wakefulness in the later part of the day and in early part of the evening. And if you look beyond NT1, for example, in NT2, idiopathic hypersomnia and other central disorders, where there is no obvious deficiency of orexin, what we are trying to accomplish there is look at the higher cascade mechanism of orexin receptor agonist and depend on the downstream impact on histamine, norepinephrine, dopamine and serotonin.

so having a longer half-life dosing to steady state will be helpful in both hypersomnolence disorders and non-hypersomnolence disorders, the broader central nervous system disorders. Finally, the potency. We have always talked about the importance of potency. In fact, we have been talking about the importance of potency since we first disclosed our in vitro data in October 2024. And we are very impressed with the potency of BP-205. This continues to be the most potent orexin-2 receptor agonist in clinical development. It gives us the flexibility to use low doses across all 3 central disorders of hypersomnolence and by extension, other broad CNS indications as well.

Just a quick follow-up. How do you -- were you able to confirm target engagement? Do you know if BP-205 is actually activating the orexin-2 receptor in CNS?

Yes, Pete, great question. Yes, in our single ascending dose study, probably you are referring specifically to insomnia and [ polyuria ], we did not see those [ EAEs ], but it's single ascending dose study, so there is some limitation in extrapolation of the safety and tolerability profile. We are not disclosing our multiple ascending dose data today because the data analysis are still ongoing. But in our multiple ascending dose study, we dosed for 15 days in healthy volunteers. What I can say is we did see some target engagement mechanistic EAEs such as insomnia and polyuria. But this is transient and none of them were either serious or sustained. And we'll disclose full MAD data sets in Q4.

Yes. Thanks, Kumar. Pete, I just want to add additional -- a few additional comments with regards to the half-life, just frame of reference. I think as you may be aware, neuropsych drugs that in the market that are dosed once-daily typically have half-life in the range of about 15 to 25 hours. So just an important sort of context with regards to the half-life we're reporting today, 25 hours. One interesting analog is actually WAKIX.

WAKIX half-life of about 20 hours dosed once-daily in the morning, convenient dosing for patients. So frame of reference with regards to a half-life of 24 hours. And importantly, as Kumar said, maintaining the physiologic tone of the orexin system when dosed to steady state, another important component of the PK profile. Thanks, Pete.

We'll go next now to David Hoang at Deutsche Bank.

Congrats on the quarter and the data update today. So first question, I was wondering if you could just comment a little bit on the selectivity of your orexin, BP-205 for the orexin-2 receptor versus orexin-1. I think you have some preclinical data in the presentation and how that might compare against other orexin molecules out there? And maybe just -- if you could just elaborate on the importance of potency versus selectivity. So that's my first question.

Thanks, David. Let me just a brief comment. I think that comes down to a threshold effect. So a threshold effect with regards to selectivity, after which there's really no incremental benefit. And then Kumar can provide sort of the data behind that.

Yes, David. In terms of the selectivity, you are probably referring to the in vitro data that is in the slide deck. We have over 600-fold selectivity for orexin-2 receptors over orexin-1 receptors. Potency and selectivity, they go hand in hand. If you look at the half [indiscernible] at orexin-2 receptor, EC50 is 0.015 nanomolar. And for orexin-1 receptor, it's 9.01 nanomolar. So that's over 600-fold selectivity.

That's a lot of selectivity. We also look at selectivity over 100 other receptors of interest. And we saw greater than 1,000-fold selectivity over there. Now what it implies from a clinical perspective, based on the preclinical data, we have a predicted maximum therapeutic dose. If you look at that dose, we will have 140-fold margin over the maximum predicted efficacy dose in humans.

And typically, in central nervous system disorders, you work with a selectivity of around 20, 30-fold and having 140-fold margin over orexin-1 receptor is pretty good, a lot more selectivity than we will ever need. And if there is ever a concern about EAEs related to orexin-1 receptor agonist, we just disclosed the single ascending dose study, granted that it's single ascending dose study, we actually did not see anything to say that the drug is interacting with orexin-1 receptors. And the same was true with the preliminary MAD safety tolerability data as well.

Great. And then my follow-up question pertains to pitolisant HD. I understand the top line data would be next year. Can you just help maybe set some expectations for us? What would you -- what will you present in the top line data for pitolisant HD? And what's your level of confidence in getting a differentiated label?

Right. David, in terms of the top line data for pitolisant HD, we are on track for top line data for both narcolepsy and idiopathic hypersomnia in 2027 and PDUFA date in 2028. Let me start with narcolepsy. Pitolisant HD is an optimized formulation of pitolisant. So milligram to milligram is just not the same as, for example, WAKIX formulation, also has GR coating and it's higher dose. And we have data to show some linear correlation between exposure and efficacy.

So to start with, when it comes to excessive daytime sleepiness, we anticipate to see a larger effect size. And then we will also be pursuing a differentiated label for narcolepsy by targeting symptoms of fatigue. So that's narcolepsy. When it comes to idiopathic hypersomnia, we had disclosed a lot of data from our INTUNE study. So we will not just be targeting excessive daytime sleepiness in idiopathic hypersomnia. We will have a high level of confidence, but we'll also be targeting sleep inertia, a very important symptom in patients with idiopathic hypersomnia for which there are no approved treatments. And again, at last year's SLEEP Meeting, we showed the effectiveness of pitolisant in treating sleep inertia as measured by Sleep Inertia Questionnaire.

Thanks, Kumar.

We'll go next now to Graig Suvannavejh at Mizuho.

I wanted to get back to the orexin candidate. And in particular, can you talk more about the novel scaffold you're using for BP-205 and in particular, how different and what is that specific difference versus scaffolds used by other orexin candidates that directly translate or at least you believe directly translate to a potential differentiated profile in both efficacy and safety tolerability? And then I have a follow-up.

Yes, Graig, thank you for your question. And I'll turn it over to Kumar, but I think that's where the differentiated profile for BP-205 begins with that differentiated scaffold and chemical structure. Kumar, can you provide some more detail around that.

Yes. Graig, I'm not a medicinal chemist, but I'll try to explain to the best of my ability. When the orexin-2 receptor agonist was being developed, you may remember that there were some EAEs that were caused because of reactive metabolites, for example, liver function test abnormalities. So Teijin from who Bioprojet licensed and we sub-licensed, this drug was designed to stay away some of the molecular structure-related EAEs, especially when it comes to hepatotoxicity and cardiac toxicity. So what we did was instead of going with the typical pyrrolidine sulfonamide bicyclic moieties, which is a typical structure, they stayed away from it.

And what it really provides is instead of this 3-dimensional crystal structure, the structure is much more flat, and that is supposed to give us more potency and also help us with some of the structure-related EAEs. And we saw that. We saw that in our preclinical profile, where we showed very high potency. In fact, BP-205 was effective at a dose of 0.03 mg per kg in the narcolepsy transgenic mice model, the lowest dose that was ever used to test.

And we saw the same profile in our single ascending dose study in terms of short Tmax, in terms of longer half-life and the safety and tolerability profile to the extent we can extrapolate based on the single ascending dose is very favorable. So overall, very encouraging data, both from a nonclinical perspective and from a limited data that we have on the clinical side.

Okay. And then I think there are many of us who are excited about the potential for BP-205 to be differentiated. But I think a question that I get often from investors is really relates to kind of developmental time lines and how far you might be behind, say, Takeda or some of the other players. So can you comment on maybe broadly speaking, how we should think about the clinical development program and kind of what's next in terms of time lines?

Yes. So Graig, I think at a high level, as you can hear today, we are -- have the conviction to move quickly and accelerate the development time line. So while we may not be first to market with regards to NT1 or with regards to NT2 or IH or the other hypersomnias, but importantly, looking at broader CNS indications, as we said, we'll be initiating multiple Phase II trials mid next year.

And we believe with our experience, our know-how in the space, we'll be able to accelerate those development programs and potentially be first or second to market in some of the broader indications. So we have that commitment. We have that experience to move the program forward across multiple CNS targets, and we're building that momentum. And as we shared, multiple data catalysts coming over the next 6 months.

And I would just add, Graig, that as we've seen in many therapeutic categories, the first or second asset isn't necessarily the best asset. And so we believe we've shown today some initial clinical data that supports that this is a differentiated profile that can be well set up to be best-in-class, not just in hypersomnolence indications, but importantly, in broader CNS indications where features like the potential for rapid onset of action, potential for once-daily dosing are going to be very important. And so first isn't necessarily best, and we believe that we are developing what's emerging to be the best profile.

Yes. Thanks, Peter. Excellent.

We go next now to David Amsellem at Piper Sandler.

A couple for me. So I wanted to drill down more on Graig's question on different indications. So we already have a glimpse of potential other indications. There's Alkermes with an ADHD program and also fatigue in MS and Parkinson's program. Obviously, there are other potential indications across mood and cognition, for example. So given the business model, which is focused historically on rare, how are you thinking about these broader indications, particularly in these larger markets that are much more promotion intensive, and your willingness to dive into, say, mood or cognition where you're going to need considerably more commercial infrastructure? So that's number one.

And then number two is, sorry if I missed this, but wanted to get a better flavor for your IP estate on BP-205, when the composition IP expires and talk to additional patents that issued or pending.

Thanks, David, for your question. So let me start, and I'll turn it over to Peter some thoughts. So in terms of the opportunity with BP-205, and we're also working with our partner, Bioprojet on additional orexin-2 compounds. So there's a backup and then additional compounds based on novel chemical scaffold that we talked about. So I think that now we are looking at optionality.

So we're looking at optionality as we advance the program with regards to, obviously, the hypersomnias and some of those programs are further ahead, but the broader CNS indications that you alluded to, I think there is a lot of activity in the space around some of the targets, you mentioned ADHD, MS fatigue, et cetera. So we actually have worked with our partner, Bioprojet, on some preclinical models and emerging evidence in what potentially could be the best of those targets with regards to preclinical proof-of-concept.

So we are looking broadly with optionality and accelerating the development program opportunity, realizing that in indications in the orphan rare space, there's one opportunity there and then other orexin-2 compounds to go broader with a different commercial model. And I'll turn it over to Peter, any additional comments.

The only thing I would add is on your question about appetite. The appetite is strong, and I think it is based on the foundation that we just talked about that this asset has the potential to be effective in both Sleep/Wake indications and the broader indications. And in particular, that's where the potency, I think, really helps us, because many of those broader indications are not indications where there's orexin deficiency.

And so having the most potent asset, I think, sets us up well from an efficacy perspective. And in terms of your question on appetite for investment commercially, et cetera, certainly, Adam can chime in. But we have that appetite as well. Many of us have significant experience in many of those categories. Even though the organization doesn't have experience in those categories, many of us within the organization do. And we, I think, have clearly established with the fact that we're on track to achieve $1 billion in revenue that we have the commercial wherewithal. So to be able to scale up from that very strong commercial footprint we already have to take advantage of opportunities in these broader markets is something we're prepared to do and quite confident we can do.

IP.

And then you asked about IP. The IP goes to 2043 with the potential for additional patent term extensions on top of that.

And the composition patent expiry, is that 2043? Isn't it earlier?

No, that's 2043, with again, the potential for patent term extension add-ons.

We go next now to Ami Fadia at Needham & Company.

Maybe a follow-up to the last couple of questions. As you think about sort of navigating the competitive landscape with this first orexin asset, BP-205, and some of the backup compounds that you talked about, how would you think about prioritizing either rare indications versus the larger markets with your first sort of initial program? Because I would assume that [ you'd want in ] each of the different markets and appropriately develop each asset catered to a different market. So maybe if you could sort of talk about how -- maybe your current thoughts around how you're prioritizing around those. And then maybe if I could squeeze in a question on WAKIX. With the strong patient adds that we saw this quarter, if you could comment on how you anticipate the cadence of patient adds in the remainder of the year?

Ami, thanks for your questions. With regards to the first one and prioritizing, I think it's a combination of multiple factors. I think as Peter alluded to, we have the ability and the conviction to pursue multiple CNS indications, both the hypersomnias and these broader CNS indications, understanding in terms of price point of an orphan rare indications such as narcolepsy and IH. So I think it's a combination of timing. But again, we feel first to market may not be best.

So there's still opportunity in hypersomnias off of the strong foundation and the strong base and business that we've built in that space with WAKIX, but also excited about the broader CNS indications, accelerating those efforts, multiple Phase II trials beginning mid next year and then investing in those Phase II studies, letting the data inform our opportunities going forward.

And as Peter alluded to, with the commercial experience to broaden that footprint, broaden that effort, towards those opportunities. So I think we've got optionality, multiple opportunities in both the hypersomnias, broader CNS indications and are moving the program forward to generate data covering both of those areas to inform our decisions on Phase III development and eventual commercialization.

And I can speak to patient adds. Ami, good to hear from you. So we are very pleased with the performance we saw in 2Q, achieved 8,950 average patients, that's up 450 in the quarter. That is the second highest quarterly increase in the 7-year history of the brand. So very, very strong. And we've now seen 4 of the last 5 quarters actually achieving 400-plus patient adds. So the momentum is there. We're carrying that into Q3, and we'd expect that growth to continue through the end of the year, similar to what we've seen in prior years for WAKIX, very steady growth, very steady momentum, and we expect that growth to continue. Hence, confirming full year guidance at $1 billion plus in net sales, $1 billion to $1.04 billion for the year. Thanks for the question.

We'll go next now to Patrick Trucchio with H.C. Wainwright.

Congrats on the progress. This is Luis in for Patrick. I'm curious about the next steps for the BP-205 program. So what efficacy data would give you confidence to advance to Phase II? What are the key gating items? Is there a minimum threshold that the FDA requires? What would be a go/no-go decision for you?

Luis, thanks for the question. So I think the next steps, and then I'll hand it over to Kumar. So as we said, multiple data catalysts coming over the next 6 months, the MAD data that will read out in the fourth quarter, importantly, initiation of the sleep-deprived healthy volunteer study this quarter, data early '27.

Obviously, the mechanism of action is proven. So with regards to -- we anticipate a strong outcome in the sleep-deprived healthy volunteer study. The opportunity is also demonstrating at lower clinical doses, at lower clinical doses, which could provide a very good risk benefit profile, similar to what Kumar alluded to in the preclinical model at the lowest doses, demonstrating sustained wakefulness. So that is the opportunity with regard to the sleep-deprived healthy volunteer data. And then from there, Kumar, additional thoughts.

Yes. Sure. Luis, thanks for this question. Just building on what Jeff mentioned, the sleep-deprived healthy volunteer study, that's when we will see the first signals for efficacy. We anticipate strong and sustained response from the sleep-deprived healthy volunteer study, and that is based on the profile that we saw in our nonclinical studies and also the early profile, the PK profile that we are seeing in our single ascending dose study.

In terms of your question regarding go/no-go gating decisions, those kind of things, as Jeff was alluding to, in NT1, the mechanism of action is established. There is orexin deficiency, you get an orexin-2 receptor agonist and you see efficacy. But beyond that, that's where the profile of BP-205 becomes extremely important in terms of potency, in terms of selectivity, in terms of half-life and also the safety and tolerability profile, the initial safety and tolerability profile that we shared today.

We believe all of these features are -- continue to support our belief that BP-205 is a best-in-class orexin-2 receptor agonist that will be helpful not just for central disorders of hypersomnolence, but beyond that, including many other broader central nervous system disorders.

Thanks, Kumar.

We'll go next now to Jason Gerberry with Bank of America.

This is [ Chi ] on for Jason. I have a question on BP-205 and a follow-up as well. I'm curious, can you talk about the shape of the PK curve? Should investors interpret the rapid Tmax as a high Cmax as well or peak concentration? Or does the PK curve have a flat peak-to-trough profile? And then I have a follow-up after this.

Yes. Thank you. Thank you for the question. We haven't disclosed all the data because typically, we disclose the full data set at a scientific meeting. But to your point in terms of Tmax and Cmax, is Tmax that's when we saw the maximum concentration of BP-205 and the Tmax varied in the range of 30 to 75 minutes.

Okay. And my follow-up question is on the extended half-life relative to other clinical programs or other clinical orexin clinical programs. And I think those programs seem to have roughly around 10 hours of half-life or less. So I'm curious, do you think you've thread the needle between having a long enough half-life for a once-daily dosing and also having exposure level low enough at nighttime? Can you talk about dosing strategy to mitigate insomnia and early insight from the Phase I MAD portion given you have talked about insomnia and polyuria as signal of target engagement earlier on the call?

Yes. Good question. In terms of half-life, look, we don't know the half-life or the exact half-life of the other programs because no one has shared the data in a comprehensive way like what we are doing in our SAD study. So I can only comment on BP-205. The terminal half-life that we saw in the single ascending dose study was approximately 25 hours. If you look at the drugs that are administered once a day, for example, the half-life ranges anywhere between 14 to 20-plus hours.

I just mentioned earlier, the half-life of pitolisant is 20 hours, and it's dosed once a day. So based on what we know about the PK profiles of the drugs that are dosed once a day, we are confident that this profile fits QD dosing, which is preferable from a patient perspective. And it will also help to sustain wakefulness in the afternoon and in the early part of the evening.

In your -- to your question about the long half-life and potential for EAEs, I mentioned earlier in our single ascending dose study, we did not see insomnia or polyuria that are some of the mechanistic target engagement-related EAEs. But in our MAD study, where we did dose for 15 days in healthy volunteers, we did see some insomnia and polyuria, but neither of them were neither severe nor sustained. So the emerging profile that we are seeing is very much supportive of QD dosing, helping the patients through the day and without necessarily carrying the effect into night, resulting in undesirable EAEs.

We'll go next now to Danielle Brill with Truist.

Maybe a bit of a follow-up to the prior one. So you've confirmed insomnia and polyuria in your MAD study and understanding you're not giving numbers today, but just wondering if you could maybe provide some directional color ahead of the data. Specifically wondering if investors should expect incidence rates to track similarly to peers in the 50% to 60% range, whether we should expect a dose response? And understanding there were transient events, did these resolve despite continued dosing? Or did they fade over time as tolerance improved? And should we -- what should we expect in terms of discontinuation?

Danielle, thanks for the question. All great questions. But at this point in time, those data are still being analyzed, and we plan to provide a comprehensive MAD data in the fourth quarter of this year. I can't comment anything beyond than what I already said, which is, yes, we did see insomnia, we did see some polyuria, these were transient, not sustained or severe.

Okay. Maybe as a follow-up, could you frame -- you talked a lot about how metrics that would support the best-in-class profile of BP-205. Could you frame on the safety front, how you would define a best-in-class profile?

All right. So from a safety perspective, there are things that are class-related that we expect based on the mechanism of action. And there are things that are off target depending on the chemical structure of the compound, right? From a class-related EAEs, I already mentioned what I can mention on this call, which is from a single ascending dose study perspective, we did not see cardiovascular, hepatic or visual disturbances. Specifically mentioning just because based on the development program from other sponsors, we have seen in the past some hepatotoxicity and some visual disturbances.

In terms of off-target effects, we already talked about the selectivity, 600-fold selectivity over orexin-1 receptor agonist. And we already talked about the potency and the efficacy. Ultimately, what it comes down to is the product profile, the product profile based on efficacy, safety and tolerability and ease of use.

Based on the data that we have as of today, the nonclinical and early clinical, high potency, longer half-life, short Tmax, seeing some on-target target engagement EAEs, transient, not sustained, not severe, no off-target effects and once-a-day dosing. We are actually very, very confident with the emerging product profile for BP-205.

Thanks, Kumar. Yes. So I think, Danielle, just to add, overall benefit risk based on efficacy, safety, tolerability, as Kumar said, and also the opportunity with BP-205 are lower clinical doses given its potency, both in NT1 and other disorders that don't have orexin deficiency. So that opportunity in terms of threading the needle, if you will, of a favorable benefit risk profile is what we are working towards and what BP-205 is designed to deliver. So more data to come, but excited about the emerging profile and our opportunity in the broader orexin space.

Thank you. Ladies and gentlemen, that's all the time we have for questions this morning. Dr. Dayno, I'd like to turn things back to you, sir, for any closing comments.

Thanks, operator. My thanks to all of you for being on the call today, for your interest in Harmony Biosciences and our opportunities ahead. Again, strong commercial performance this quarter and excited about our opportunity, BP-205 and in the orexin space. Thank you, and have a great day.

Thank you, Dr. Dayno. This does conclude today's Harmony Biosciences second quarter 2026 financial results conference call. You may now disconnect your line, and have a wonderful day, everyone.

All right. Welcome, everyone. Good morning, and thanks for joining us here at the Goldman Sachs Global Healthcare Conference. We're thrilled to be joined by the team from Harmony Biosciences today.

And maybe I will start by allowing you guys to give a brief introduction to yourself. And just talk about the new strategic vision that you recently unveiled at the most recent earnings call.

Yes. Good morning, Corinne. Good morning, everyone. Thank you for the invitation on behalf of the Harmony team. So with regards to where we are sort of at Harmony, it's really an evolution of the strategy, and we think that we are identifying sort of 4 main strategic pillars, which we think that's how we'll be valued or judged in terms of the performance and to drive long-term value.

So the first is really protecting the pitolisant franchise to the 2030s. And we feel we have a strong position with regards to our IP that we can sort of dive into in terms of where we are there. The second main strategic pillar of value creation is really to continue to grow the WAKIX franchise while protecting the IP out to 2030. So we're on track to $1 billion-plus opportunity this year in narcolepsy alone and continue to extend that with the next-gen formulations.

The third strategic pillar is really our pipeline and driving more value from our pipeline with our late-stage programs and now really, it's all about the orexin -- sort of the orexin opportunity. That's obviously a very large opportunity, a lot of excitement about that. And we feel we have a potential best-in-class orexin and we can spend a little time on that opportunity.

And then last is sort of BD, business development. And with our strong balance sheet, a renewed emphasis and the conviction to really transact in BD to build out the pipeline and expand the commercial portfolio. So that's sort of the framework how we think we will be sort of valued and judged and when we execute on those 4 pillars to drive long-term value for our shareholders.

Great. Maybe we'll talk about the litigation quickly and get that one out of the way. I guess, recently, you had a lawsuit with Novitium that you filed against AET, and it helps to kind of map to that goal you set about protecting the WAKIX franchise to 2030. Could you just talk about that update and then the confidence that you derive from there in the IP?

Absolutely. I think, again, we feel really strong and confident in the strength of our IP out to 2030. And I think Peter can sort of expand on the licensed Novitium patent and this multilayered strategy with regards to protecting our IP.

Yes. Just real quickly to introduce myself. I'm Peter Anastasiou. I'm the Chief Operating Officer. I was on the board for the last 3 years. So I've been an active participant in the Harmony story for the last 3 years, and I joined the management team about 2 months ago. But just to clarify on the IP, we have 2 cases that are going on.

One is the ANDA that had the court case in February. That continues and we feel very strongly about our ability to prevail in that litigation. But in addition to that, during that trial, AET and Sandoz introduced a significant amount of evidence that they are infringing upon a polymorph -- or excuse me, amorphous patent that we have exclusively licensed from Novitium. So at that time, we decided in April, together with Novitium, that we would file lawsuit defending our rights from infringement. And so that is at the beginning of the trial that has its own course of 24 to 30 months. Then you have to add appeals to it. It's another 18 months.

So that's why we feel so confident, as Jeff said, that we will have IP through March of 2030. And that is because if the court cases go to their full extreme, we feel very strongly in our ability to win. But also because of the strong hand we have, we believe it also enables a settlement to be reached. And so either way, the clear message is 2030 -- March of 2030 is our IP.

Right. Inclusive of the 6 months of pediatric exclusivity.

Great. All right. We're going to come back to the WAKIX franchise, but I know that one of the key areas of focus for you guys right now is the orexin. So I wanted to start there in terms of products. Maybe on that front, you acquired orexin-2 agonist a couple of years ago now. How are you thinking about the class of agents and their potential in narcolepsy, particularly given a relatively crowded set of therapies?

Yes. So obviously, the orexin space is a really exciting one. And as I said, we feel in BP-205, we have a potential best-in-class. So maybe to take a step back, the reasons why we're excited about that. And then I think the team can expand on where we see that class going and our opportunity. So BP-205, what is unique? It has a unique chemical structure and chemical scaffold, which differentiates from the other orexin-2 compounds in the clinic. And based on that, it drives the attributes of this compound. So the first is potency and being the most potent orexin-2 agonist in the clinic right now and potency matters with regard to the ability to have lower doses and drive greater efficacy, but also acceptable safety tolerability profile.

So a lot of it comes down to sort of a risk-benefit assessment in terms of what that profile will be. In addition to potency, there's excellent selectivity of the orexin-2 receptor over orexin-1 and as the preclinical data have shown, and we're now in the clinic in terms of to bear that out, potential for once-daily dosing and a very clean in terms of the safety tox data that we've demonstrated there.

So I think with that, the potential not only for sleep-wake disorders. But again, beyond NT1, which is a disorder of orexin deficiency, when you move into NT2 and IH and then these broader CNS targets where there's a lot of discussion around, potency really matters to be able to have enough potency to drive efficacy with acceptable safety tolerability.

Okay. Obviously, this is a key piece of why you guys acquired that asset. And maybe you could just put a bit of a finer point on exactly how you think that could play out in terms of clinical differentiation and meaningfulness with respect to the specific side effect profile that you could see here.

Yes. So I think that it's the ability to dose lower and drive strong efficacy. And based on the preclinical data that we've seen and we're now in the clinic, with regards to sort of side effects that are on target in terms of lower percentages of those side effects and minimizing and avoiding the off-target effects. And I think that where we're seeing the class, Peter, from a commercial perspective where we see those opportunities.

Yes. Just rarely in a new class is the first entrant the best entrant. And so we believe we have the best entrant for all the reasons that Jeff mentioned. I would add one more, and that is the once a day. One of the things that we hear is split dosing is a challenge for some of these patients, especially in the open-label phases of the clinical trial. So we believe pretty strongly that we're going to be once a day.

And so we believe we're going to be bringing into the market the best offering among the orexins and it does give us the chance to take advantage of all the opportunities that exist in the space, not just in narcolepsy, but also in those other broader indications because of the features of the drug, particularly the potency.

Right. As we approach these orexins actually entering the market here, do you anticipate any impact to your WAKIX franchise in narcolepsy?

I can answer that. The short answer is no. And I can point to a couple of things. So when we were the first new mechanism to come out about 7 years ago, we had incredible growth and still do, but it didn't impact the growth of the oxybate, that's because this market has a high degree of unmet need. Doctors use polypharmacy as more the norm than the exception. These patients are highly heterogeneous and so having multiple mechanisms to treat these patients is really kind of the standard. And so we expect that will continue.

WAKIX has been on the market now 7 years. It has an established efficacy and safety profile. Doctors are comfortable with it. They know the value that it brings. And so we expect it to be resilient in the marketplace and continue to grow even with the orexins coming.

Great. And you're pointing to sharing Phase I data in healthy volunteers this year. As you think about the hypothesis you just laid out, what kind of results would kind of push that -- advance that kind of hypothesis?

Yes. So where we are in the clinic. So we are in the clinic with healthy volunteer Phase I PK data. So we're right around the corner from the single ascending dose data that we'll be sharing in the first opportunity we have. And really, that will confirm sort of the profile of the potential for once-daily dosing that we saw kind of from the preclinical PK data. And we want to confirm that in the clinic with healthy volunteers.

And then later this year, the multiple ascending dose data in healthy volunteers, we'll be sharing those data. And importantly, we'll be submitting an IND shortly and then we'll be doing the sleep-deprived healthy volunteer study this year or early next year. And that will be the first sort of signal in terms of signals of efficacy in that model potentially at lower doses and once-a-day doses with BP-205 compared to some of the other orexin programs in the clinic, where they started with once-daily dosing and except for Takeda, which is BID and NT1 and then other programs went to sort of the split dosing paradigm.

So we feel we have the potential once-daily dosing at lower doses to drive strong efficacy and those sets of data will bear that out.

Okay. So as you think about the metrics you'll be sharing with these updates near term, what should investors be paying attention to? And how would we think about the right benchmarks as we assess those results relative to the broader [indiscernible]?

So I think it's looking for a favorable PK profile of short Tmax in terms of time to onset and then a half-life that can support once-daily dosing and minimize in terms of the on-target effect of insomnia.

It's also worth noting that as far as we know, the competition hasn't shown some of those early PK data. So they're not out there. And so we intend to share ours. And so I think it will be viewed positively and really shows the potential we're talking about is starting to bear itself out in the clinic.

Okay. In terms of safety and tolerability, I guess, when would you expect those sort of events to emerge? And so at what point can we say pretty definitively this does have the better tolerability profile you're guiding to?

Yes. So obviously, the more patients that you accrue in the clinic and the clinical trials. So I think we'll get initial signals with regards to what we're seeing, especially in the sleep-deprived healthy volunteer study, the Phase Ib study. And then when we move into sort of Phase II and accruing more patients, we'll get a pretty good read with regards to what we believe will be a favorable safety tolerability profile.

Okay. So once you get past that, maybe you could speak to the broader development strategy that you're [Technical Difficulty] what indications are you planning to prioritize here?

Peter and Glenn, I think we all have a lot of thoughts on this. So obviously, the initial targets in the sleep wake space, which started this whole opportunity. And remember, beyond NT1, these are not disorders of orexin deficiency, which is where we think a more potent compound can be beneficial. So I think that we have that opportunity and then these broader CNS targets, the potential in cognition, in ADHD, in mood disorders, fatigue, and really where we are now.

So we're working with our partner, Bioprojet, beyond BP-205 for additional compounds, the orexin-2 agonist because you'll need. If you're going into sleep wake and orphan rare, you'll need other compounds, follow-ons if you go to broader CNS indications, different commercial models, different price points. So we are assessing all those opportunities, and I think we said later this year, we'll be providing kind of an update of the development strategy. If you want to add anything?

No, I would just emphasize that we are committed with our partner, Bioprojet, to aggressively develop this and to take advantage of the variety of indications that this asset could be targeted for. And as Jeff said, later this year, we'll give a substantive update on some of those specifics.

Okay. We'll look forward to that. Maybe in terms of the ability to look at other people providing proof of concept in different indications versus doing it yourself, how are you going to prioritize which indications you kind of take a lead on?

Yes. So I think being a little behind, we've always said, we're learning from some of those other programs. But in addition, we're also working with our partner, Bioprojet, at the bench in terms of preclinical models in some of these broader CNS targets that I mentioned. So we will also have those data to inform our strategy. And the other opportunity that out there is there is a potential for synergistic mechanism between an orexin-2 agonist and pitolisant, and histamine-3 antagonist.

So we are also looking at preclinical models to the potential for synergy between pitolisant and an orexin agonist. And that could afford an opportunity sort of down the road for fixed dose combination drug development. We're also working on that opportunity with our partner, Bioprojet.

The only other thing I just wanted to put in some perspective, that while we can concede that we won't be first in NT1 because of the aggressive development approach, that we plan to take, there's a real chance we could be first or second in some of these other indications. And so that's, I think, one of the other areas of differentiation with the compound.

Yes. It's a good point. So how do you think about balancing where you're going to invest dollars in? And how important is being kind of first to market in some of those other indications versus kind of following in more established indications for the category?

I think the most important thing is the profile and a strong profile can succeed in any market even if you're fourth, fifth, sixth. We won't be. But that's the most important part. But if you can see that all these drugs will be good in NT1, where we think we can really shine is in these other areas, and that's where we intend and believe we can be first or second with also the best profile.

Yes. And in terms of the investment, we now -- we see the opportunity and have talked about investing in a broader orexin development program. We're also looking at the rest of our pipeline and reassessing in terms of where can we drive the greatest value from the pipeline programs and a broader orexin program.

Great. So you mentioned the development learnings that you can take away from leaders in the class. So maybe we could talk about the commercial launches that we start to expect over the course of the next couple of years. What will you be watching in terms of their commercial progress? And how are you going to take that learning into account as you think about your own?

Do you want to...

Okay. I think several things. First and foremost is what does the profile look like in the real world. We all know that for all drugs, the clinical environment is not the same as the real-world environment. Clinical environment, patients are very homogeneous. There's no comorbidities. There's very strict rules around what concomitant meds you can take and not take.

So the real-world profile, I think, for any drug is critically important. So some of the long-term efficacy that is unknown about these competitive products will remain to be seen, the long-term tolerability when you get into broader patient populations. So those are clearly some of the things that we're looking for, but also things like price. So it's -- depending -- there's a lot of rumors out there about what Takeda will price that makes a big impact on the payer access situation and patients' ability to get those.

So those are a number of things that we'll be watching. But at the end of the day, all we can control is what we do with WAKIX. And so we're continuing to be focused on driving that long-term efficacy -- short- and long-term efficacy, short- and long-term tolerability. It's the only unique mechanism that's in the market beyond the oxybates and has its own place carved out because of its unique mechanism, even in the face of orexin. And it's also still the only nonscheduled product. So that's where we'll be focusing. But of course, we'll be paying attention to some of these other factors.

With respect to figuring out indications on the orexin, I think what you're going to see is a process. You see a pretty broad effort on Phase II, and then we'll have the data dictate. But the selection of the targets will really be determined by our strength, right? So we're looking for areas with great pricing, kind of niche where we can address it with our sales force and value with respect to our hub and the way we get reimbursement for patients and treat patients.

Yes. I think the opportunity for WAKIX remain -- we still believe that it will continue to be a polypharmacy market. I know there's a lot of debate around that. But chronic CNS disorder, difficult to treat symptoms, often you need multiple mechanisms to really control these patients. So as Peter said, WAKIX has been in the market 7 years, well-established our commercial model. So I think there continues to be that opportunity. Pricing, obviously, in terms of place and therapy will have an impact.

And while that's happening, we'll be aggressively advancing our orexin-2 agonist programs. sleep wake looking at Phase II proof of concept in these other targets and sort of guide -- let the data drive us and guide us in terms of what the best opportunities will be.

Yes. In terms of prioritizing R&D, what we're going through over the next couple of months is just looking at our entire portfolio of products and figuring out where we're getting our best return. The last thing we want to do is not have enough money to fund the most exciting opportunities in front of us. So we're going through that process. We're going to really test the P&L pretty hard just to make sure we're fully funding everything into 2030.

Can I ask a follow-up on that point, which is that as you're doing this, I imagine you're also taking into consideration what Harmony's real strengths are. So as you think about the core competencies of the business and like what are those? And how do they inform the development strategy and prioritization that you're undertaking as well?

Yes. No, it's a great question. So I think our core competencies are really a lot of expertise in the CNS arena, I think, and not just sleep wake but epilepsy and other target indications, including some of the broader ones based on our R&D team and their sort of backgrounds and their experience. So I think that is an important part, along with obviously the commercial prowess and the strong commercial engine that we've developed the unique commercial model.

So we would be able to apply that to other orphan rare CNS indications, other rare indications outside CNS. So I think that will all inform as we move forward with the orexin program the best.

Maybe talk a little bit about our partner as well. I appreciate. That's a key advantage as well.

Yes. So that's a good point. So Bioprojet, our partner, who are the innovators of WAKIX, of pitolisant, actually the principal scientist, Jean-Charles Schwartz, discovered the histamine 3 receptor. So the seat of the science sits there. So they're really strong at the bench in terms of their basic R&D and preclinical models. And that's who we are collaborating with in terms of advancing the orexin program. So they have a lot of strength there. And it provides kind of our research arm working with them closely on the orexin opportunity.

I would just add, I think, at this point, we've established ourselves as the leader in the sleep wake market across all facets, commercial certainly, but also R&D advocacy. We know the KOLs. We know the advocacy groups. They know us. We've been obviously successful in the market and expect that, that's one of our superpowers, and will continue to be as we introduce GR and HD, but also the orexin as well.

Right. So one of the things you mentioned that list was the commercial prowess. It's a good segue to WAKIX. You've guided to reaching blockbuster status this year. I guess what does that embed with respect to patient growth? And how are you guys continuing to deliver such good kind of patient growth this well into the commercialization of the product?

Sure. I'll let Peter expand on that when it's a long history with his commercial expertise.

Yes. I mean it all starts with the product. Again, I know we keep repeating it, but it is the only unique mechanism relative to the oxybates. It has its own place carved out. It's a known efficacy and safety profile. And then of course, we have demonstrated strength in commercial and so we don't take anything for granted. There is a strong growth trajectory, but we are constantly innovating and sometimes incrementally, sometimes more so.

So we recently expanded our footprint both in the sales force, but also in specialty pharmacy and hub, our field reimbursement managers, getting to more prescribers, helping more patients get through the process from a prescription to a paid Rx for rare disorders, especially at this type of price point and higher, there's a lot of support that's needed. And so we're constantly innovating and tweaking our model to be able to help with that and it's paying dividends. We had strong growth last year. We're on track to hit the $1 billion, and we're seeing some very strong growth this year as well. And so we expect that to continue.

Yes. So you followed the story for a while. And we've always said this -- it's a unique profile. It's the first and only nonscheduled product. And when I saw those data from the abuse liability study readout, I realized this could be something special. And remember, it's still a large market for an orphan rare condition, it's still a sizable market. We continue to sort of tap into that.

[ 90,000 ] patients that are undiagnosed and untreated.

So it continues to grow. Top-line demand is strong, and we believe we can continue to drive that. And then into the next-gen new formulations of pitolisant.

Thank you for the segue. I wanted to talk about life cycle management. So at a high level, maybe you could just talk about where you see the gastric-resistant and high-dose formulations sitting within the context of the broader franchise.

Yes. So latest update on that and then I can turn it to Peter in terms of strategy, the commercial strategy. So as we've said that we were going to be submitting the NDA for pitolisant GR in the second quarter. So we've submitted the NDA, and we are on track for target PDUFA first quarter next year. We see that as a significant opportunity right around the corner to extend the pitolisant franchise out to March of 2030, which is our base case LOE. Also pitolisant GR and HD have utility patents filed to 2044 as well. In terms of the commercial opportunity, I think Peter can expand on that.

As good of a product as WAKIX is, as we've said, there are ways to -- and back to the point about constantly innovating and adding additional value, we believe that GR can be an incremental step forward even already on a great profile with WAKIX. And the main area is because of the GR coating, we believe it's going to be very helpful for narcolepsy patients because narcolepsy patients have a high degree, 80% to 90% of them. This is irrespective of WAKIX, just as part of their disease, they have a high degree of GI symptoms that kind of co-travel with their disease. So they're always very sensitive to GI side effects.

So having the GR formulation will certainly help that. But also what that enables us to do is, right now, there's a 2-step titration with WAKIX and so by having the GR formulation, it should help us avoid the first step in the titration and get right to a therapeutic dose from the very first day of treatment. And so these are incremental advancements on an already good profile, very strong profile. And so we plan to launch it in Q1, and we think it will be helpful to patients. And also, as Jeff said, because of its IP, be helpful long term beyond 2030.

Great. On the high dose, could you speak to what you view as clinically meaningful in terms of incremental efficacy you could achieve at a higher dose? And I know one of the areas you've spoken to is kind of showing benefit on fatigue. So maybe you could embed that in the answer to this question.

Yes. I think the bar is demonstrating what's clinically meaningful in terms of the 2- to 3-point improvement over WAKIX, the label data on the Epworth Sleepiness Scale. So we have data from the development program in terms of dose response. And we feel at about 2x the current maximum label dose with pitolisant HD, which is also -- it's also a unique formulation. So it's not bioequivalent. It's got greater bioavailability milligram per milligram, and we're at about 2x the highest label dose currently for WAKIX.

So we feel we can drive clinically meaningful benefit improvement, 2 to 3 points at a minimum on the Epworth reduction in cataplexy and then the Phase III trial in narcolepsy is also including fatigue as a secondary endpoint. And in terms of demonstrating improvement in fatigue, so differentiated labeling in about 60% to 70% of patients with narcolepsy also experience fatigue as another sort of debilitating symptom.

Okay. So how do you think about what portion of patients are going to be good candidates for a switch if you deliver on that kind of profile?

Yes. If I can add just one thing before we answer that question is the idiopathic hypersomnia program that we're pursuing, which is not an indication that WAKIX has, but it will be an indication that HD has. So that's even additional differentiation. And even in the face of generics post 2030, we think that, in addition to all the things that Jeff said, will help WAKIX HD continue to be a thriving formulation because it has an indication generic WAKIX won't.

Sure. Okay. So maybe on that, the percentage of patients that are currently on WAKIX that you think would be good candidates to switch to high dose assuming the profile you just described.

Yes. We certainly haven't guided a specific, but I think we point to pretty frequently the Xyrem Xywav analog as something that we believe we can achieve or do better with a switch. And so we believe that there is more benefits to both the GR and the HD then Xywav gave over Xyrem. So I think with more differentiation in those 2 formulations, we think we can do that and possibly better.

And maybe some comments on the commercial model, so the opportunity we have, starting with GR.

Yes. So again, this product is not distributed in retail pharmacies. It's a closed distribution network of specialty pharmacies and a hub that manages all this data. And so we have data on all the patients, all the prescribers for WAKIX. And so that's also something that we can leverage to be able to share the benefits of both GR and HD with patients that are currently on the product as a potential switch opportunity. But just as important, patients who maybe have tried WAKIX in the past and have left WAKIX for some reason to bring them back with one of these 2 new formulations.

Yes. So I think the opportunity to extend the pitolisant franchise is right around the corner with the NDA submission for GR and the target PDUFA in first quarter next year, really starting in terms of to extend the franchise and then the HD program, currently Phase III, as Peter mentioned, both narcolepsy and the IH study. And then for IH, we're also looking at, in addition to excessive daytime sleepiness, sleep inertia as a unique sort of endpoint to get data in the label and have differentiated labeling for the IH program as well.

Okay. Great. I wanted to quickly talk about business development. You've got quite a bit of cash on the balance sheet, and you have talked about business development as being a key pillar. So maybe you could just talk about the areas of focus with respect to indication, size of the asset, stage of development, and I'll let you guys kind of go from there.

Yes. So from a BD perspective, I think the strategy continues to evolve. And as I mentioned upfront, renewed emphasis and conviction to transact, especially with a very strong balance sheet, continue strategic and thoughtful. We've gone deep in several opportunities, but I think for the right reason, have not pulled the trigger yet. Glenn can expand on the current thinking and where we are in business development.

Yes, obviously, I like a big balance sheet. So you have the optionality of doing transformative, something transformative. I think that term scares a lot of people. So that's not really our inclination to do something that's transformative. What will most likely happen here is we're going to do a series of smaller transactions, all playing into our strengths in terms of niche neuroscience opportunities.

Our biggest emphasis are on those products that could -- that are complementary to what we're selling right now that would contribute to revenues in the 2028 to 2032 time frame. And the reason we kind of picked that time frame is, obviously, we have to deal with the threat of orexin between now and 2030 and then post 2030, you have an LOE to deal with. And at that point in time, we're just beginning, hopefully, for the takeoff of the orexin for our own orexin program. So that seems to be the sweet spot in terms of revenues.

Okay. In terms of capital allocation priorities, how do shareholder returns kind of rank relative to...

I heard that question last time that you asked in terms of shareholder returns. We're very cognizant of shareholder returns because we're all shareholders, and I certainly want our employees to think of it that way. And so it has to make sense, obviously, from a return on investment perspective. I think it would help if it was obvious to investors. But in terms of share repurchase, it continues to be my strong belief that we can do better for shareholders investing in the business, either our orexin program or with BD than it would be to return cash to shareholders today. I'm not ruling that out, but that's where the priority is right now.

Yes. And we don't think it's either/or. We think the opportunities are both investing in good BD opportunities as well as this broader orexin program that we're really starting to accelerate and focus on and maybe some of the other strategic filters in BD in terms of what the types of deals that we...

I mean the Centessa deal was a blessing in some ways because we're able to really show folks what a transformation to a biotech entity really would look like. So here we are a company that is fighting it out to generate $1 billion of revenues. And we're sitting on close to $1 billion of cash, and we sell at a market cap of $1.7 billion. We are undervalued. But then you look at Centessa being bought in a range of $6 billion to $8 billion. You can see how transformative 1 molecule that's unique can be to an organization. So obviously, if we can identify that molecule either through a BD deal or our own portfolio, we can create tremendous value for folks, particularly with 205 or orexin agonist.

Yes, of course. Maybe in the last minute we have here, I just want to give you a chance to talk about the epilepsy data we'll expect later next year? And just what should we be looking for there?

Yes. So EPX-100 currently in Phase III for both Dravet and LGS. On target for top line data next year in 2027, it's really similar to some of the long-term extension data that we shared last year at the AES meeting showing, I think, the profile of efficacy, about 50% responder rate in terms of kind of the bar of entry for showing good efficacy, but more importantly, with a very good safety tolerability profile. The profile of EPX-100 clemizole hydrochloride is very similar to another product in the polypharmacy market, strong efficacy with a very favorable safety tolerability profile. And that product is called WAKIX, with regards to the broad clinical utility and the overall benefit risk proposition in a polypharmacy market.

We know there's a lot of competition in that space, but we feel with EPX-100, we can have a very strong product profile and strong offering for both Dravet and the opportunity in LGS.

Beautiful. With that, I think we're at time this morning. Thanks everyone who joined us here and online.

Thank you.

Hello, and thank you for standing by. My name is Mel and I will be your conference operator for today. At this time, I would like to welcome everyone to the Harmony Biosciences First Quarter 2026 Financial Results. [Operator Instructions] Thank you.

I would now like to turn the call over to Brennan Doyle, Head of Investor Relations. Sir, please go ahead.

Thank you, operator. Good morning, everyone, and thank you for joining us today as we review Harmony Biosciences first quarter 2026 financial result and provide a business update. Before we start, I encourage everyone to go to the Investors section of our website to find the materials that accompany our discussion today, including a reconciliation of our GAAP financial measures.

Our speakers on today's call are Dr. Jeffrey Duyno, President and CEO; Adam Zaeske, Chief Commercial Officer; Dr. Kumar Badur, Chief Medical and Scientific Officer; Glenn Reicin, Chief Financial Officer; and Peter Anastasiou, Chief Operating Officer.

As a reminder, we will be making forward-looking statements today, which are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties. Our actual results may differ materially, and we undertake no obligation to update these statements even if our circumstances change. We encourage you to consult the risk factors referenced in our SEC filings for additional details.

I would now like to turn the call over to our CEO, Dr. Jeffrey Dayno. Jeff?

Thank you, Brennan. Good morning, everyone, and thank you for joining our call today. I want to start by highlighting what we have built at Harmony. We are a profitable, self-funding biotech company that continues to operate from a position of strength.

We have an exceptionally strong commercial engine, which continues to drive WAKIX growth now in year 7 on the market. We have recently solidified our IP position around the pitolisant franchise through a multilayered approach. We have a robust pipeline centered around BP-205, our potential best-in-class Orexin-2 agonist. And we have a very strong balance sheet with the capacity and conviction to execute on meaningful business development opportunities.

With this solid foundation in place, we are now turning our focus on 4 key pillars of value creation for shareholders. In support of this next phase of growth, we have brought in 2 new members to our management team who further strengthen our ability to execute as we scale.

First, I am pleased to welcome our new Chief Financial Officer, Glenn Reicin. Glenn is a seasoned biopharmaceutical executive with extensive experience across publicly traded and privately held companies, guiding them through key growth inflection points. With his experience as a sell-side analyst, investor and biotech CFO, Glenn brings a strong track record of success in strategic planning, capital markets and fundraising.

Next, welcome to Peter Anastasiou, our new Chief Operating Officer, who brings more than 30 years of experience in the industry and comes into this role after having served on Harmony's Board of Directors where he contributed strategic insights across the business during a period of continued growth and operational evolution.

Most recently, Peter served as Chief Executive Officer of Capsida Biotherapeutics and previously held multiple leadership roles at Lundbeck, including President of U.S. and Canadian Operations, and U.S. Chief Commercial Officer for its psychiatry and neurology franchises.

I am excited to welcome both Glenn and Peter to the Harmony team. Their combined experience meaningfully strengthens our leadership bench and positions us well to execute on our 4 strategic pillars of value creation, which I will now walk you through.

The first pillar is to protect the pitolisant franchise into the 2030s. We are committed to protecting the pitolisant franchise through a multipronged strategy that is based on strong intellectual property protection and exclusivity.

Pitolisant's IP estate is multilayered, covering different formulations, methods of use and next-generation applications, which support WAKIX exclusivity into 2030, inclusive of 6 months of pediatric exclusivity with potential IP protection of the franchise into the 2040s via additional issued patents and pending patent applications.

In January, we also acquired an exclusive license from Novitium for certain IP, including their issued patents out to 2042, covering an amorphous form of pitolisant hydrochloride, which provides us with new development opportunities.

With regard to the ANDA litigation and the trial that took place in February, we have settled with 6 of the 7 ANDA filers, maintaining LOE until March of 2030, inclusive of 6 months of pediatric exclusivity.

During the trial in February, AET, the one remaining ANDA filer who has not settled, stated that their product contains an amorphous form of pitolisant hydrochloride rather than a crystalline form covered by our 197 polymorph patent. After learning that, Harmony, along with Novitium, recently filed a patent infringement lawsuit against AET Pharma U.S. and Sandoz, alleging infringement of a patent covering an amorphous form of pitolisant hydrochloride.

This suit is a new action, different from the legal proceeding of the ANDA litigation trial that took place in February, which is ongoing and is being presided over by the same judge. Based on this legal activity, we remain confident in the strength of our IP estate and continue to vigorously protect it through this multipronged strategy.

Second, we are dedicated to the continued growth of the pitolisant franchise in an evolving market. In Q1, we delivered $215.4 million in net product revenue, up 17% from $184.7 million in the same period last year. This performance reflects continued strong demand, offset by market access headwinds observed every Q1 following 3 of the strongest consecutive quarters in Harmony's history.

The average number of patients in Q1 was approximately 8,500, and we exited the quarter with approximately 8,600 average patients on WAKIX. These patient numbers are in a market of 80,000 diagnosed patients with narcolepsy, showing the significant market opportunity that remains to support continued growth of WAKIX and the pitolisant franchise. Based on this, we are reiterating our full year net revenue guidance of $1 billion to $1.04 billion.

In addition to the continued growth of WAKIX in the market, our next-gen pitolisant formulation programs are advancing. Pitolisant GR remains on track for NDA submission this quarter with a target PDUFA date in Q1 2027, and is positioned to extend the WAKIX franchise and our leadership in narcolepsy.

Pitolisant HD is enrolling in 2 ongoing Phase 3 registrational trials, one in narcolepsy and in idiopathic hypersomnia, or IH, designed to expand the franchise with differentiated labeling. We have also initiated a new development effort with the amorphous form of pitolisant that we licensed from Novitium. This gives us an opportunity to pursue broader CNS indications, and Kumar will share more color on this new opportunity later in the call.

Our third pillar of value creation is driving value from our robust pipeline, led by BP-205, our potential best-in-class Orexin-2 agonist. We do not believe our current valuation reflects the strength of our pipeline, especially related to our highly potent and selective Orexin-2 receptor agonist, BP-205.

This program is on track for top line data readout from our Phase 1 clinical PK single ascending dose study in the middle of this year. Built on a novel chemical scaffold with strong preclinical PK, safety, efficacy and tox data, BP-205's potential product profile could position it as a highly competitive Orexin-2 agonist, not just in narcolepsy and other central disorders of hypersomnolence, but also for broader indications outside of sleep/wake that are not due to Orexin deficiency for which potency matters.

Overall, our robust late-stage pipeline consists of 5 ongoing Phase 3 registrational trials across 5 distinct CNS indications, including the 2 Phase 3 registrational trials with EPX-100 in the rare developmental and epileptic encephalopathies. Kumar will provide more detail on BP-205 and our other pipeline programs during his R&D update.

And our fourth value-creating pillar is a renewed emphasis on business development. We are focused on opportunities with revenue potential in the 2028 to 2032 timeframe, prioritizing assets that are in Phase 3 development in registration or on market, and we are maintaining our therapeutic areas of interest that include sleep/wake, epilepsy, rare orphan CNS disorders and CNS adjacencies beyond rare diseases.

With about $870 million on the balance sheet, we are moving with urgency to deploy our capital and have clear conviction to execute on strategic business development opportunities. In summary, I've outlined 4 pillars of value creation that we believe matter most to investors and will serve as the framework by which our performance will be measured. Next, the team will share with you the highlights of how we are executing on each of these strategic pillars.

With that, I'll turn the call over to Adam Zeskey, our Chief Commercial Officer, for an update on our commercial performance. Adam?

Thank you, Jeff, and good morning, everyone. We're off to a strong start in the first quarter with WAKIX delivering $215.4 million in net sales, representing 17% year-over-year growth, now in its seventh year on the market, which is in line with the growth required to achieve full year guidance of between $1 billion and $1.04 billion.

WAKIX achieved approximately 8,500 average patients in the first quarter. The Q1 typically has lighter patient additions due to seasonal dynamics the entire industry experiences every year. This year, we saw slightly higher market access headwinds than previous years with a higher level of plan changes, planned switching by consumers and higher premium increases, which can delay patient starts.

That said, we're coming off our strongest ever 3 consecutive quarters of patient adds. First quarter demand was actually higher than the first quarter in 2025 and was in line with our recent performance and expectations. In March, we saw a higher level of new prescriptions in all but 2 months in 2025, and we exited the quarter with 8,600 patients on WAKIX.

The driving force behind this continued performance is clear. WAKIX owns a unique and highly differentiated position as the only non-scheduled treatment option for narcolepsy patients. After 7-plus years of clinical experience, health care providers are deeply aware of WAKIX.

They believe in its combination of efficacy, safety and tolerability and low drug-drug interactions as well as its broad payer coverage, making it a familiar go-to option for any patient with narcolepsy and in any combination with other therapies in a highly polypharmacy market. And this will continue to remain true as the market continues to evolve.

We've now also completed our field team expansion, which has expanded our presence by roughly 20% across field sales, remote sales and field reimbursement. This represents the largest expansion and increase in investment in the history of the brand. All of those positions have been hired and are in place as of April 1.

In Q2, we will launch a new online portal using the process to prescribe WAKIX for healthcare providers and office staff, and we will execute significant changes to our reimbursement support process, helping patients to secure a WAKIX dispense faster and with higher success rate.

Looking to the future, we're excited about our 2 life cycle management strategies to extend and expand the pitolisant franchise. Pitolisant GR will build on the strength of WAKIX safety and tolerability profile and allow patients to gain faster results by starting at a therapeutic dose. Pitolisant HD, or high dose, will bring a totally new optimized formulation to the market with up to 2x the approved dose of WAKIX, all of the benefits of the GR formulation and differentiated labeling regarding fatigue in narcolepsy and sleep inertia in IH.

We're also excited about our orexin compound as we see an opportunity remains for Harmony to deliver an orexin that delivers on the promise of efficacy with a better safety and tolerability profile, once daily dosing and indications across NT1, NT2 and IH.

To summarize, we're on track to achieve $1 billion plus in net sales this year, and we're excited about our pipeline with multiple assets that will extend our leadership in sleep/wake for at least the next decade.

I'd like to now turn the call over to our Chief Medical and Scientific Officer, Kumar Budur, to discuss the advancements in our clinical development programs. Kumar?

Thank you, Adam. Good morning, everyone, and thank you for joining us today. Q1 2026 was a quarter of continued progress across our pipeline. We have 5 ongoing Phase 3 registrational clinical trials across 5 distinct CNS indications, and I'll walk you through the key updates.

As just noted, orexin is one of the most exciting areas in sleep/wake and broader neuropsych indications. I'd like to start with the progress we are making with our Orexin-2 receptor agonist, BP-205, an asset we believe has meaningful potential that is not yet reflected in how our pipeline is being viewed today.

BP-206 with its unique chemical scaffold has demonstrated compelling preclinical potency, selectivity, safety and efficacy and the potential for once-a-day dosing all supportive of a potential best-in-class Orexin-2 receptor agonist. It is the most potent Orexin-2 receptor agonist in clinical development and demonstrated weight promoting asset at the lowest dose tested in the transgenic mouse model for narcolepsy.

The high potency gives the flexibility to use low doses and treat all 3 central disorders of hypersomnolence that is NT1, NT2 and IH with the same compound. BP-205 also have high selectivity for Orexin-2 receptors over Orexin-1 receptors and 150 other receptors of interest. We continue to dose healthy volunteers in our Phase 1 SAD/MAD PK study in Europe, and we remain on track for Phase 1 SAD PK data in mid-2026.

We are also on track for U.S. IND submission in mid-2026 and commence sleep deprived healthy volunteer study in the second half of this year. As we make progress with our lead asset, DP-205, targeting central disorders of hypersomnolence, we are also working on preclinical experiments in broader neuropsych indications targeting mood, ADHD, cognition and fatigue.

Now moving to pitolisant and the life cycle opportunities, beginning with Pitolisant GR. We remain on track for NDA submission in Q2 2026 and a target PDUFA date in Q1 2027. About 80% to 90% of patients with narcolepsy have GI symptoms related to the pathophysiology of narcolepsy itself.

Pitolisant GR is designed with enteric coating meant to reduce the potential for GI side effects in patients prone to GI symptoms. Pitolisant GR demonstrated bioequivalence to WAKIX in our pivotal D study and it also allows patients to start at the therapeutic dose range of 17.8 milligram without titration, an important clinical differentiation.

Pitolisant HD continues to advance in 2 Phase 3 registration trial: ONSTRIDE 1 in narcolepsy and ONSTRIDE 2 in idiopathic hypersomnia. We anticipate top line data in 2027 and a target PDUFA date in 2028. These programs are pursuing differentiated labels, fatigue in narcolepsy and sleep inertia in IH, addressing symptoms for which there are currently no approved treatments. Both Pitolisant GR and Pitolisant HD have utility patents filed until 2044.

We are also optimistic about the novel amorphous form of pitolisant we recently licensed from Novitium supported by an issued patent through 2042. We believe this could enable new modes of delivery and broaden pitolisant's potential in larger CNS indications. We are currently optimizing formulation with the goal of commencing a Phase 1 PK study.

On pediatric exclusivity for WAKIX, the top line data from the Phase 3 TEMPO study in Prader-Willi syndrome is anticipated in second half of 2026, a key requirement for achieving pediatric exclusivity, which gives us additional 6-month regulatory exclusivity at the back end of the longest patent for WAKIX.

Moving to our epilepsy franchise. EPX-100 continues to advance in 2 global Phase 3 registrational programs, the ARGUS study in Dravet Syndrome and the LIGHTHOUSE study in Lennox-Gastaut Syndrome. We recently presented Encore safety and effectiveness data at the AAN meeting from the open-label extension study in Dravet Syndrome that showed clinically meaningful reduction in seizures and a favorable safety and tolerability profile.

We now have sites actively enrolling patients in India and China in addition to North America and Europe to accelerate recruitment. We anticipate top line data in first half of 2027 and a target PDUFA in 2028.

Finally, on behalf of Harmony, I would like to thank all the patients and their families who are participating in our clinical trials as well as the clinical investigators and site personnel for their dedication and commitment in helping us advance our development programs.

I now turn the call over to the newest member of our team, CFO, Glenn Reicin, for an update on our financial performance. Glenn?

Thank you, Kumar, and good morning, everyone. I'm delighted to join this organization and help contribute to the growth and significant value creation. And I should mention that I was drawn to Harmony by the strength of its commercial foundation and self-funding financial model that positions us to build and grow from a place of strength.

This morning, we issued our first quarter 2026 earnings release and filed a 10-Q where you'll find the details of our financial and operating results. We delivered solid financial results that reflect the continued underlying demand for WAKIX and our disciplined approach to managing expenses across the business. For the first quarter of 2026, we reported net revenues of $215.4 million compared to $184.7 million in the prior year quarter, representing 17% growth.

Performance in the quarter reflects the strong underlying demand for WAKIX, partially offset by the seasonal market access headwinds the industry sees at the start of every year. Cost of goods of products sold was 20.7% of net sales and compares with 17.3% one year ago. This year-over-year increase in cost of products sold as a percentage of net revenue was almost entirely driven by new royalties related to the Novitium license agreement, providing new development opportunities in broader CNS indications

We reported total operating expenses for the first quarter of $133.6 million compared to $96.5 million in the same quarter in 2025. The growth in expenses reflects continued investment in R&D and ongoing investments in the commercialization of WAKIX in narcolepsy. These operating expenses also include the costs associated with upfront licensing fees of $32 million or $0.45 per share on a fully tax basis related to the amorphous license agreements. Without these costs, operating expenses were up around 5%.

GAAP net income for the first quarter of 2026 was $32.5 million or $0.55 per share. This compares with $45.6 million or $0.78 per share. Of course, that includes $0.45 in costs related to the in-license of the amorphous form of pitolisant and new development opportunities.

We ended the first quarter with $870.5 million in cash and cash equivalents cash flow generation in the quarter was muted by the licensing fees and a large reduction in accrued expenses and a modest reduction of debt. We ended the quarter with $160 million in debt.

Cash flow generation will reaccelerate in the coming quarters. That said, it's our intent to deploy cash into business development with the objectives of enhancing revenues in the 2028 to 2032 timeframe, consistent with our 4 key pillars of value creation for shareholders.

And with that, I'd like to turn the call over to Jeff for his closing remarks. Jeff?

Thank you, Glenn. And again, welcome to the team. In closing, I have shared with you our 4 pillars of value creation that we feel matter most to investors and will serve as the framework by which our performance will be measured.

First, protect the pitolisant franchise into the 2030s. Second, continued growth of the pitolisant franchise in an evolving market. Third, drive value from our robust pipeline centered around BP-205, our potential best-in-class Orexin-2 agonist. And last, a renewed emphasis on business development with our goal to transact. We believe when we execute on these 4 strategic pillars, we will be well positioned to bring innovative treatments to patients with unmet medical needs while driving sustained long-term value for our shareholders.

Thank you for your attention. I will now turn the call back over to the operator for Q&A. Operator?

[Operator Instructions] We have the first question comes from the line of David Amsellem of Piper Sandler.

I have a few questions on BP-205. Just give us a road map on how to think about data milestones as we move through '27, particularly in healthy sleep-deprived volunteers. And then secondly, why not just move right into actual narcolepsy 1 and narcolepsy 2 and IH patients in a Phase 1 B, just given that it's become a pretty crowded landscape just as a way to expedite development. I wanted to get your thought process there.

And then lastly, with other indications, mood, ADHD, cognition, fatigue, as you alluded to, can you talk about early-stage work that you're going to be doing over the next 12 to 18 months that could help you decide what paths to take in terms of the non-sleep break indications?

David, thank you for your question. With regards to BP-205, first, let me frame overall our excitement around the potential opportunity we have with our Orexin-2 agonist. And it's really based on, as you've heard us say, the novel chemical scaffold and really the highest potency of any Orexin-2 agonist in the clinic. With that, it gives sort of the differentiated features with a product profile likely to be best-in-class.

With regards to timing of the development program and other indications, first, the issue with indications outside sleep/wake and central disorders of hypersomnolence, the opportunity there is that those are not based on a state of orexin deficiency. And in those conditions, potency matters where we think we would have a significant opportunity, not just with BP-205, but other compounds that we're working on with our partner, Bioprojet.

So now I'll ask Kumar to sort of provide what the timeline looks like on the current development program. Kumar?

Thank you, Jeff. David, you asked several questions, so let me try and answer one by one. In terms of data milestones, we are on track to receive single ascending dose clinical PK data in the middle of this year. We also continue to dose patients in multiple ascending dose study, the food effect study, things like that, that are important before we go to the later clinical stage of development.

In terms of your question, why not go straight into clinical proof of concept rather than sleep-deprived healthy volunteer study? Great question, David. One thing to remember is BP-205 is the most potent orexin receptor agonist in clinical development. So it's good to get a nice bracket around the dose range before we go into clinical proof-of-concept studies. And also another thing to remember is this is not going to add to the timeline. This is done in parallel with the multiple ascending dose study and the data we need that before we go into clinical proof-of-concept studies.

You also talked about the other indications as we are very excited about the profile of BP-205, most potent orexin receptor agonist, and Jeff alluded to some extent in his response, it's very important that potency translates into efficacy, and we saw that in our preclinical animal models. And in other indications, it becomes all the more important because we'll be depending on some of the downstream effects of the orexin receptor agonist in conditions like mood, fatigue, cognition, ADHD. We are conducting several preclinical experiments right now. And as the data becomes available, we'll be able to disclose. I hope that answers all of your questions. Thanks, David.

Yes. And David, final comment on that. I think as I've discussed with the team, given the potential value of this class of compounds, it's our intent to invest in this program with regards to where we are now on additional compounds and look at the broad opportunity with not just BP-205, but other compounds that we're working on. Thanks, David.

[Operator Instructions] Next question comes from the line of Ami Fadia from Needham.

Maybe one main question and a follow-up. You gave us some sense about the litigation versus AET Sandoz and then there seem to be 2 trials here. Can you talk about kind of what we can expect in terms of next steps with regards to how the litigation might proceed and over the course of the next couple of months?

And then a follow-up on the orexin question from earlier. With the sort of higher potency that you've highlighted, how do you see it being differentiated in the sleep/wake area relative to the other orexins that are in development? And then can you elaborate a little bit more on the other indications? Do you see that other indications such as ADHD, mood, fatigue, et cetera, being ones where you would study it as a combination treatment with other assets? Or do you see it being developed both as a monotherapy and then also explore other combinations?

Let me address your first question, and then I'll have Kumar address the follow-up on BP-205. So I want to take a minute or 2 to provide clarity with regards to the IP situation and around the WAKIX and pitolisant IP estate.

Before I provide some detail, I first want to be clear about our position. We believe in the strength of our IP, and we continue to vigorously protect it. And it's based on a multipronged strategy with pitolisant IP estate, which is also multilayered. So with regard to some of the detail to provide clarity. So recall, we settled with 6 of the 7 ANDA filers. AET was the one remaining party who went to trial in February. That legal process continues. It's currently in post-trial briefs, and that part of the process will be completed towards the end of May.

So during the trial in February, AET and Sandoz stated that the product will contain an amorphous form of pitolisant hydrochloride rather than a crystalline form, which is covered by our 197 polymorph patent. And they did that in an effort to work around that IP. So we believe that AET and Sandoz infringed our 197 patent and during the trial, they also admitted to the facts that they infringed the 920 amorphous patent that we licensed from Novitium.

Based on that, when we learned about the trial, that is when Harmony Novitium recently filed the patent infringement lawsuit against AET Sandoz, alleging infringement of the 920-patent covering an amorphous form of pitolisant hydrochloride. So that suit is a new and separate action, different from the legal proceedings of the ANDA litigation that took place in February, which is ongoing. And that new suit is also being presided over by the same judge. That is a new legal proceeding, which is just getting started.

So based on this multipronged strategy, the different factors that I just mentioned, we remain confident in the strength of the IP estate, again which is multilayered with multiple components, enabling exclusivity into 2030, inclusive of 6 months of pediatric exclusivity.

Kumar, over to you.

Thank you, Jeff. Good morning, Ami. So in terms of potency, you may have heard me talk about it many, many times in the past as well why potency matters with Orexin-2 receptor agonist. It matters because it gives us the ability or the flexibility to use low doses to target all 3 central disorders of hypersomnolence. How it could potentially manifest itself in a clinical setting? Well, with low doses, we'll be able to avoid the off-target EAEs. That's number one.

The number 2 is having a high potent drug. As you know, the doses required for NT2 and IH are relatively larger based on the data that we have. So it provides us an opportunity to use the same compound to treat all 3 central disorders of hypersomnolence, NT1, NT2 and IH rather than use different compounds or go to high doses, which may actually result in some EAEs.

In terms of the combination, that's a great question, Ami. There is a scientific rationale to potentially realize synergistic effect by combining pitolisant, which is a histaminergic drug with an orexin agonist because the neurocircuitry is such that orexin acts at a higher level and the neuronal connections between the orexinergic neurons and histaminergic neurons in tuberomammillary nucleus is very well established. So this is something that we are very interested in, and we are looking into.

We have the next question comes from the line of Graig Suvannavejh form Mizuho.

I've got 2. My first, just if we could just talk about the WAKIX ramp right now. My apologies, I was a bit late on the call. I know that you're reiterating the guidance for this year and that you added 100 net patients. Should we expect the balance of the year to pretty much reflect what we've seen in the past in terms of second quarter, third quarter and fourth quarter dynamics? Or is there anything this year as the product matures that we need to be aware of?

And then just secondly, going back to the ongoing litigations that are ongoing. I was curious if you could provide a sense of in terms of the timing of when you decided to sue on the second lawsuit on the potential Novitium IP that you licensed in. I was curious as to why you chose to sue when you did versus perhaps waiting for the outcome of the original IND litigation on a view that, at least based on our work, I think there's still a potential chance that you would win.

With regards to WAKIX performance, let me just sort of frame and then over to Adam for more commentary. So I think we're off to a strong start with good strong demand that continues for the WAKIX franchise as well as through the quarter, we saw good momentum coming out of the first quarter, exiting with about 8,600 average patients. So with that, we're on track to achieve full year guidance of over $1 billion.

And I think Adam can provide more color on the continued growth of the WAKIX franchise.

Thanks, Jeff. Graig, thanks for the question. So in the first quarter, we achieved $215.4 million in net sales. That represents about 17% growth year-over-year. And that is exactly the growth level that we need to achieve in order to hit our full year guidance of $1 billion to $1.04 billion for the full year.

Graig, as you know, and we've talked about this before, we typically see seasonal headwinds in the first quarter as we start the year related to market access and payer changes. And we saw that again this year, no surprise. So plan changes, consumer switching plans, increases in premiums. These are factors that can delay some patient starts as we start the new calendar year. And we saw that again this year. That said, underlying demand remains very strong. We're just coming off 3 consecutive quarters of record growth, and we saw the same level of demand in terms of new prescriptions and new patient starts, consistent with that recent performance.

And actually, first quarter demand this year was even higher than it was a year ago. And in March, we saw the highest demand that we've seen in all but 2 months in 2025. So the momentum is there. To answer your question directly, yes, we would expect the remainder of the year to play out similarly as we've seen really in the last 6 years in terms of WAKIX performance. And that this first quarter is just down to the typical start of the year market access headwinds.

Great. With regards to the second question on the timing of our lawsuit with Novitium with regard to the amorphous patent, I want to take the opportunity to welcome Peter and not to see you to the Harmony team, our Chief Operating Officer, who is working very closely with me on all the matters related to IPA and the litigation. Peter?

Yes. Hello, everyone. It's a pleasure to be on the call with you. I look forward to meeting those of you I don't know in the very near future.

To answer your question in terms of timing, first, let me just say, we agree with you that we believe we will prevail in the ANDA case. And so this filing of this lawsuit in no way reflects our -- any other belief than that. It's an effort to make sure that we're asserting our full rights. So we believe that evidence was introduced that there is infringement on our polymorph patent, and we believe that our method of use patent is absolutely valid.

Having said that, during that trial, AET and Sandoz also introduced very clear evidence that they are violating the amorphous patent, the 920 amorphous patent, that we licensed from Novitium. So when you asked about timing, it was after those facts were entered into evidence in the trial that we, along with our partner, Novitium, decided that we were going to fully assert our rights to defend the IP for pitolisant. And as Jeff has said many times, this is a multilayered approach. And so that's why we filed suit in April.

And again, these are 2 different cases with 2 different time courses, and we believe that we will prevail in both cases, and that's why we have strong confidence in our exclusivity going into 2030, inclusive of the 6-month exclusivity.

Next question, we have the line of Pete Stavropoulos from Cantor Fitzgerald.

Congrats to Glenn and Peter on joining the team. Can you touch on EPX-100 for Dravet? The clinical data disclosed at AAN. Can you comment on baseline seizure rates and baseline antiseizure med use? Sort of how do they compare to the real-world patients and patients enrolled in other Dravet clinical trials? And with interim OLE efficacy data and safety data in hand, what's your view on the emerging benefit risk profile? How competitive do you believe the profile is? And where do you see it fitting into the current landscape?

Thanks for your question. Kumar?

Yes. EPX-100 clinical data that was presented at the recent AAN meeting, that's Encore data that we had already presented at the AAN meeting in December last year. Just to refresh, the data is from the open-label extension part of the Argus study, the Phase 3 pivotal registration study in Dravet syndrome. What the data showed is that in patients who had at least 6 months of exposure to EPX-100, we saw a median reduction of 50% in seizures as measured by CMS 28. And we also saw 50% of patients experiencing 50% reduction in seizures. Both of these measures are considered clinically meaningful.

Now the other side of the coin is safety and tolerability, which is extremely important in this patient population, given many of these patients are on 4 to 6 antiseizure medications and still have residual seizures. And that's exactly how EPX-100 was used in this study as adjunctive therapy. And on average, patients were on about 4 different antiseizure medications. It doesn't require any special monitoring, which is very important, [indiscernible], for example. The lab values were really fine. So there is no need to monitor liver function test as is often the case with some of the antiseizure medications.

And more importantly, the tolerability because a lot of these medicines do cause nausea, vomiting, abdominal graft, diarrhea in patients up to 20% to 30% in some instances. What we saw with EPX-100, the only AE of note was actually diarrhea in about 2% of the patients. So the combination of clinically meaningful efficacy, favorable safety and tolerability profile as an adjunctive therapy in a patient population known for refractory seizures positions EPX-100 very well from a clinician, from a prescribing algorithm perspective.

I hope I answered all of your questions.

Next question comes from the line of Patrick Tutcher from H.C. Wainwright.

I was hoping to get a little bit more detail on the BD strategy just in terms of the sort of the size and the disease areas that you would be most interested in, particularly as we think about CNS adjacencies beyond rare disease. And then separately, as we approach the BP-205 data in the middle of this year, I'm wondering if you can tell us what specific PK parameters and tolerability bar would validate the best-in-class claim.

Patrick, thank you for your questions. Let me first address the question on our BD strategy and then turn it over to Kumar for your second question.

So I first want to with regard to the renewed emphasis on business development, just take a minute on the strategy and our thinking there. So it's important to note, I think we have a renewed organizational commitment to transact with regards to business development. And this is from the management team to our Board and then obviously, the 2 members of the management team, Peter and Glenn, that bring very relevant experience doing deals and really strengthens the overall ability for us to move this forward and execute on this key priority.

Obviously, it's one of BD and the renewed emphasis is one of our 4 key pillars of value creation as we see the urgency and conviction to deploy our capital, put it to work to generate sustained value. So I want to ask Glenn to comment on thoughts on capacity, where we are there. And Peter, with regard to what's the strategic focus of what we are considering. Glenn?

Yes. I mean capacity, we can -- we actually have quite a bit given our cash balance and our ability to borrow as well. And obviously, not preferred, but we can always use stock. So we have quite a bit of capacity and size deals, I think, are not a limiting factor.

And with regard to strategic focus, it's really -- it's an evolution. It's an evolution of our strategy. It's a refinement. It's not a major pivot sort of in the road. And Peter, if you want to sort of highlight what we're thinking in that area.

Yes, absolutely. So there's a number of criteria that we're looking at. But I also want to say we're also willing to be opportunistic and keep an open mind to other opportunities as well. But in terms of the areas of focus, it is, of course, revenue potential, especially near-term revenue potential, especially in the '20 to '32 timeframe. So that implies something that's in the Phase 3 or registrational phase or even on market, quite frankly. And then we're big believers that the types of things we should look at are things that are related to our core competencies, and we feel we have many core competencies.

But clearly, in the sleep/wake space, we've demonstrated a lot of success and we'll continue to demonstrate success in that space. Also because narcolepsy is in the rare orphan CNS space, we believe that capability can be applied there. We've also been building an epilepsy presence. And so that's an area of focus for us in a variety of different epilepsies. And then certainly other things that are adjacencies to all of those within the CNS space that we believe we could leverage our core competencies.

And we are agnostic to deal type. We're looking at M&A. We're looking at licensing. We're looking at collaborations. So we have kind of a broad aperture in the way we're thinking about accessing and sourcing some of these deals. And then I will also say, while our focus is very heavily on near-term revenue, we are also, in parallel, looking at bolt-on opportunities that fit nicely within our current construct. And so that hopefully gives you some color.

And I'll also just end by saying we have a really strong BD team and really strong capabilities that we plan to mobilize and put into action with this renewed focus and commitment from not just this management team, but also the Board.

Yes. Thanks, Peter. Thanks, Glenn. In addition to the strong business development team, we also have a very strong commercial engine. So any of these potential bolt-ons or on-market opportunities, we've always wanted to utilize that commercial engine and put it to work in terms of generating more revenue. Kumar to BP-205?

Yes. Patrick, great question on the broader CNS indications. Although central disorders of hypersomnolence are the logical natural choice for Orexin-2 receptor agonist. We are also excited at the potential for Orexin-2 receptor agonist in broader CNS indications. And to a large extent, [indiscernible] acquisition of centers have validated the potential for this class of compounds. We are looking at mood disorders, cognition, fatigue, and ADHD in a preclinical setting.

In terms of your question regarding what kind of clinical PK data we would like to see, as we have mentioned earlier, BP-205 has demonstrated a potential best-in-class in the preclinical setting, high potency, great selectivity, favorable preclinical safety pharmacology and toxicology and potential for once-a-day dosing. So in the clinical PK setting, we'll be looking at Tmax, Cmax, AUC, half-life, safety and tolerability to the extent we can infer based on a single dose study.

Next question comes from the line of Corinne Johnson of Goldman Sachs.

Maybe as you look at business development, you've been highlighting the importance of relatively near-term revenues. But I'm curious where the path to earnings accretion factors in for deals that you might consider? And then separately, could you just expand a little bit on the newest pitolisant formulation and the types of delivery models that that formulation could enable?

Glenn?

Yes. In terms of earnings accretion, I think what you should -- it's hard to answer that one. What I will represent is, obviously, you have to be looking at returns on invested capital that are quite substantial, which would obviously have low to mid-teens. So that would be the main criteria over time. So we wouldn't be just doing a deal for the purpose of growth. We obviously have to have financial returns. I hope that answers your question.

And Corinne, with regards to the new amorphous form of pitolisant and so that was part of the value of the Novitium license. And we saw really an opportunity. We always talked about adjacencies beyond orphan rare with obviously this very strong product, differentiated molecule, WAKIX being very successful in the market in narcolepsy and opportunities to go broad. So with that, we saw new form and potential new formulations and modes of delivery to develop with the Novitium license, the amorphous form. And Kumar, additional thoughts on directionally where we're headed there.

Yes. Thanks, Jeff. Corinne, to answer your question, by the way, the physiochemical properties of our amorphous formulation could potentially lend itself to a different mode of oral delivery, resulting in a PK profile that may be more favorable to some of the indications that we plan to target within the broader CNS space. That's all I can say at this stage of development.

Right now, we are optimizing the formulation towards a Phase 1 PK study.

Next question comes from the line of David Hong from Deutsche Bank.

This is Sam on for David. Just a quick one on the OpEx front. Can you help us to think about the trajectory for OpEx for the rest of the year given the slight uptick in cost of products sold from the individual license and the step-up in R&D from the amorphous formulation as well?

Yes. So in terms of gross margins, obviously, they're going to be impacted by the Novitium contract. And then we obviously also have step-up royalties related to Bioprojet. But nothing abnormal beyond that year-over-year gross to net anticipate anything changing there.

With respect to R&D, we would, in fact, expect a ramp-up in R&D expense as we move forward on these trials and accelerate these trials. And then with respect to the rest of the P&L, I would not see substantial increase in run rates in terms of -- I hope that helps.

We have the next question comes from the line of So Youn Shim of UBS.

In 1Q, it seems like you saw more friction than usual in terms of access, which may have led to the softness in the patient numbers. Curious if you saw any changes in the discontinuation rate. And as a follow-up on the Orexin agonist program. So now there are several Orexin agonists that are either approaching approval or in late-stage trials in narcolepsy and IH. So for BP-205, although it has the most potency among the competitor Orexin compounds based on preclinical data, it seems like the flea space may be very crowded with a number of Orexin agonists by the time 205 launches. So just curious here, instead of going head-to-head in those core indications, could it make more sense to just prioritize other indication first where you might have a clear differentiation or even a first-in-class opportunity?

Yes. Thanks for your question. With regards to the Q1 dynamics, I'll let Adam share thoughts on that as well as in terms of the commercial perspective on the continued opportunity with BP-205.

Okay. Sure. Thanks, Jeff. Yes. So in 1Q, we typically see these market access-related headwinds. But to be clear, our coverage has not changed. We enjoy very broad coverage over 80% of lives in the U.S. And actually, that coverage was strengthened in 2025 with some improvements in some of our key payer accounts. So that remains the same. What happens is as consumers enter the new calendar year, sometimes they've got to go through co-pay resets. They've got to reestablish coverage or prior authorizations. Sometimes they switch plans. And that dynamic can simply just delay some of the patient starts, which is going to affect your average patients for the quarter. That's something that we see every year. It's really no surprise. And the -- I think you asked specifically around D.C. rate and persistency. Persistency on WAKIX has remained very, very steady for many years, and we have not seen any meaningful change in that dynamic for a very long time. So it's really just these delays in patient starts as we start the new calendar year.

And then from an Orexin standpoint, kind of a commercial perspective around BP-205, I think we're excited that there still is an opportunity to deliver an Orexin that can deliver on the promise of Orexin level efficacy, but potentially with a better safety and tolerability profile and once-a-day dosing across all 3 domains, NT1, NT2 and IH with a single compound. That's really where we're excited and where we're focused. Thanks, Jeff.

Sure. Thanks, Adam. And a final comment on BP-205 and the question. It's not sort of either/or. We see this opportunity in terms of the development program both looking at central disorders of hypersomnolence with BP-205 as well as the broader program that we are working on in addition to some of the broader CNS indications, as Kumar alluded to earlier. So not either/or, we will look to invest in this significant opportunity across the Orexin-2 agonist program.

We have the next question comes from the line of Jason Gerberry of Bank of America.

Just a question and a follow-up just on the WAKIX IP situation. So if AET does get a non-infringement, the decision in the second half, just wondering about thinking about scenarios and what actually are barriers to an at-risk launch in second half '27? And then as a follow-up, just can you talk a little bit about the diligence that you did just to ensure that the -- I guess, this arrangement survives any FTC scrutiny. If you can just describe a little bit of the history of the license with Novitium versus the settlement agreement that you reached with them during ANDA litigation.

Yes. So first, on your question with regard to AET and various scenarios. Just as a reminder, the 30-month stay ends in February. And so we would expect February of '27, to be clear. So we would expect that the judge will issue her ruling on the ANDA case somewhere around there. And then, of course, there's appeal opportunities that both parties have for adverse outcomes for either party. So fully expect that there would be appeals. Certainly, we would appeal if there was an issue there.

But then also, please keep in mind that this second trial just started, and it could take 24 to 30 months in and of itself plus an appeals process. And so that kind of gives you a sense of the timelines. And in our view, in almost every scenario, we end up with exclusivity that gets us into 2030, again, inclusive of the 6-month exclusivity. And so hopefully, that gives you some sense of the timelines and the impact. And again, we're going to vigorously defend and use every right that we have to defend our multilayer IP strategy, and that's what we're putting in place.

Thanks, Peter. And I would just add that in terms of AET and an at-risk launch, we really can't comment on other parties and what their decisions would be in that regard. And with regards to your question about the antitrust aspect, we obviously always consider that very closely. But most important to remember, when we saw the Novitium license and the amorphous form, the original opportunity we saw with a bona fide development program, which we've already initiated.

And that was the opportunity when we did that license in January before what we learned at trial in February. And we continue to pursue that business and development opportunity with the Novitium Amorphous license.

If I may just add to Jeff's point, just on the at-risk launch. Of course, there are legal remedies that we have access to that we would fully implement in that see how vigorously we are defending our intellectual property, and we would use every tool available.

That will conclude our question-and-answer session. I will now turn the call back over to Dr. Jeff Dayno, CEO, for closing remarks.

Thank you, operator, and thanks, everyone, for your interest in Harmony Biosciences, and have a great rest of your day.

Thank you. Ladies and gentlemen, that concludes today's call. Thank you all for joining. You may now disconnect.

Good morning, everyone. I'm Ami Fadia, biotech analyst here at Needham. It's my pleasure to be hosting the Harmony Bioscience team today. I have with me Jeff Dayno, who's the CEO of the company; along with Kumar Budur, Chief Scientific Officer; and Adam Zaeske, Chief Commercial Officer. Thanks, all 3 of you for taking the time to be with us today.

Maybe if I could ask Jeff, if you could kick us off with some opening remarks, some priorities for this year, and then we can take it from there?

Yes. Sure, Ami. Yes, Ami. And on behalf of the Harmony team, thank you once again for the invitation to Needham's Virtual Healthcare Conference. And we are very excited for what is coming this year, that sets us up for both near-term and long-term growth and value creation. As for some of our key priorities, just to sort of walk through, starting with WAKIX. So we are on track to achieve over $1 billion in net revenue for WAKIX in its sixth year on the market, which provides us with a very solid foundation, I think, as many are aware.

In our pitolisant next-gen programs, pitolisant GR gastro-resistant is on track for NDA submission this quarter to extend the pitolisant franchise with a target PDUFA date in the first quarter of next year, 2027. For pitolisant high dose or HD, we're in the clinic with 2 Phase III registrational trials, one in narcolepsy, one in idiopathic hypersomnia or IH. And these are designed to expand the pitolisant franchise with target PDUFA dates both in 2028 and utility patents filed out until 2024.

These programs are also designed to evaluate new labeling for unique indications such as fatigue in narcolepsy and sleep inertia in IH. Kumar can tell you more about our new formulation of pitolisant that we acquired through a license to an issued patent that goes out to 2042.

And this will give us an opportunity to explore pitolisant in broader CNS populations, in which fatigue is a prominent symptom. And there is a scientific and a mechanistic rationale to this strategy and this approach. And we're also excited about this new opportunity.

So there's a lot going on in the pitolisant franchise, but we are very excited about our advancing orexin program with BP1.15205, for which we are on track for top line data from the Phase I single ascending dose PK trial in healthy volunteers midyear followed by an IND submission in midyear. Then we'll initiate a Phase I PK trial in sleep-deprived healthy volunteers, which will provide us some initial data on signals of efficacy as well as safety tolerability, along with dose ranging for a Phase II proof-of-concept study.

Another priority that I want to remind everyone is our development program in the developmental and epileptic encephalopathies with EPX-100. Two Phase III trials are advancing, in Dravet syndrome and one in LGS, with top line data anticipated from both of those in '27 and target PDUFA dates in 2028.

So I think this all adds up to Harmony really having a robust late-stage pipeline in CNS with 5 Phase III trials towards 5 distinct CNS indications, driving multiple catalysts over the next few years. And then finally, business development, a very high priority for us with over $880 million on our balance sheet. And we are always actively pursuing strategic BD deals to both build out our pipeline, looking for commercial opportunities to expand our commercial portfolio to drive even greater value creation. So a high-level summary of what's coming and advancing in '26, and we're excited about the status of our business and future opportunities.

Excellent. Thank you so much, Jeff. Maybe we can dive into some of these topics. Maybe starting with WAKIX. Could you help us understand the setup for the product for this year. With your guidance of over $1 billion in revenue, what are some of the initiatives that you're focused on? And what are some of the metrics that you're tracking to make sure that this drug is continuing to sort of grow this year and into future years?

Adam?

Yes. Thanks, Ami, and thanks for hosting us this morning. Good morning, everyone. As you can tell from Jeff's comments, it's exciting times at Harmony and especially with the performance of WAKIX, we're really pleased with the momentum we're seeing as we finish 2025. As you know, Ami, we typically see patient additions of 100 to 400 patients a quarter. And for the last 3 quarters, we've seen 400 to 500 patient adds in the last 3 quarters, really, really strong growth and momentum carrying us into '26. And what's driving that is the core differentiation of WAKIX as fundamentally a unique product profile, the only non-scheduled treatment option available for patients.

But we also have a very experienced team now, several years of positive track record of consistent performance, broad access. And in 2025, we continue to make improvements to how we are bringing WAKIX to the market. So we continue to refine our sales force excellence, promotional mix and messaging. We added a couple of payer wins in 2025. And we continue to make improvements in our processes that support patients that get to a dispense event faster and with higher success. And so those are some of the elements and tweaks that we're making in '25 to really fuel that momentum and performance.

And as we move into 2026 now, we're actually expanding our teams. So we're expanding our field sales, our remote sales as well as our field reimbursement teams across the board on average of about 20%. So it's a meaningful expansion. We've affected that expansion in first quarter. So all those folks are now in place. They've been hired, they're in training, enroll, and we expect continued strong performance this year and now with an expanded team, hopefully continuing that momentum through 2026 to achieve, as you said, the guidance of $1 billion plus in net revenue for the year.

So you obviously have been demonstrating that this drug can continue to grow so many years into the launch. So I think that's really impressive, and you continue to invest more behind the asset. I think some of the investor concerns or sort of focus seems to be around one of the ANDA filers that's outstanding. Can you talk about where the process is at with respect to that litigation? And what are the next steps with regards to the hearing and how you're thinking about reacting depending upon the hearing?

Yes, Ami, at a high level to share what I'm able to. So 2 processes running in parallel, sort of the legal process, the trial as that continues to play out. And then obviously, our efforts towards settling with the ANDA filers. And I think as we have shared, we've settled with 6 of the 7 ANDA filers with LOE to September of 2029 and then along with pediatric exclusivity for which we're on track to achieve, taking it to March of 2030.

So I think reflective of those settlements, reflective of our strong IP position that we believe in, and I think we are well positioned in terms of that process of settling to continue to see that through. With regards to the trial, post-trial briefs were submitted last Thursday. So after the initial trial, the briefs went in and that process continues to play out. So -- and we can't obviously predict the timing or the outcome of the process, but we follow that closely and really focus on the settlement process as we achieved thus far and trying to secure that for the WAKIX franchise.

And as I alluded to, while that's happening, our focus is on the next-gen programs. Pitolisant GR right around the corner out ahead of the LOE with regards to a target PDUFA first quarter next year. And then we've got a very exciting opportunity with a new formulation that an exclusive license to a new formulation issued patent to 2042 that is unique and different from the areas we work in and looking in these broader CNS populations. I think Kumar shared a little bit of that on our last earnings call, where fatigue is a prominent symptom such as fatigue in MS, fatigue in Parkinson's disease, a strong scientific and mechanistic rationale and positive proof-of-concept data for pitolisant in fatigue from our Phase II proof-of-concept study in type 1 myotonic dystrophy with a strong signal and a dose response. So aside from the backdrop of the current sort of trial and other activity, we see continued opportunity with the pitolisant franchise.

So I think that's a great segue. I kind of wanted to dig a little bit further into the Pitolisant GR formulation, and you mentioned the PDUFA date in early next year, first quarter. Can you help us understand how that impacts the overall target addressable market, how it helps you bring back some patients that might have not been able to tolerate WAKIX. Help us sort of quantify that a little bit.

Go ahead, Adam.

Yes, sure. I can jump in on that. So with the GR formulation launching early next year, I mean, that's right around the corner, we're excited about this. We see significant patient benefit here. GR coding addressing the fact that means 80% of patients with narcolepsy have the potential for GI symptoms related to the disease, not necessarily related to WAKIX, but related to the disease and the underlying mechanism of the disease. So GR coding makes sense, especially for a product's whose foundation is not only strong efficacy, but a really, really strong safety and tolerability profile. And we believe that it adds to that foundation.

You also have the opportunity that patients can start at a therapeutic dose. So no titration required, which will help get patients to patient outcome faster and more effectively. And so with that profile launching early next year, what we see is the opportunity that any new patients that would have been prescribed WAKIX would be prescribed the new GR formulation, and we tested this in research. Physicians are very open to this. It makes sense. It makes intuitive sense. And then also, we have an opportunity to recontact previous patients. So in our unique model, we actually secure consent upfront with -- for all patients prescribed WAKIX and we have the ability to recontact them over time. This is actually a significant patient population. We can identify those patients that may have discontinued over time for various reasons and educate them, make them aware that the GR formulation is now available. There may be something that they want to speak with their physician about. Historically, we've thought about the GR as between $300 million and $500 million opportunity, and we're excited to launch that early next year.

So through your unique distribution process, you've been able to get some information about why certain patients might have discontinued if they were willing to share the reason and you can maybe go back and contact those patients.

Yes, exactly. And what's important to remember in this class, patients tend to cycle through combinations of treatments frequently. So we see patients discontinue on WAKIX and then restart, discontinue. And that's also the same with other therapies in the class. Now not only will they have the benefit of the GR coding, but if they decide to restart, there'll be no titration. They can start immediately at that therapeutic dose. And so it makes it a little bit smoother and easier for them.

Can you talk about the high-dose formulation? What is the strategy with that? And we are expecting data from the study in 2027 for that. How does that fit into your sort of life cycle management strategy here?

Yes, sure. Happy to speak about that. The HD -- think of the HD as a totally new branded launch, a highly differentiated product. It carries with it the benefits of the GR formulation. So the coding as well as started at a therapeutic dose. But now you have up to 2x the approved dose of WAKIX. So hopefully bringing improved efficacy and better patient outcomes. And we're pursuing unique indications in narcolepsy and IH with the HD formulation.

So you have something that's truly differentiated with indications that no other brand has with up to 2x the dose of WAKIX and the benefits of GR. This is a 2028 PDUFA, highly differentiated new brand launch. And I should mention, historically, we've talked about the HD as a $1 billion-plus opportunity. And both of these formulations, the GR and the HD have utility patents out through 2044. So also really extends the franchise and our runway to continue to benefit patients with our pitolisant franchise overall.

Yes. And Ami, one more point just to add about HD. As opposed to GR, which is based on a demonstration of bioequivalence, it's -- this is also a unique formulation. This is an enhanced formulation with a different PK profile, greater milligram per milligram greater exposure with demonstrated Kumar and the team, safety margins well beyond going 2x the highest label dose. So driving efficacy, driving unique indications. And really, as Adam said, sort of a new branded launch as opposed to GR more as a line extension near term as we build to a truly differentiated product in pitolisant HD.

Yes. I definitely want to also talk about the new -- sort of the new formulation that you disclosed at your last earnings call, which is meant to address fatigue in indications like MS and Parkinson's. Could you elaborate on the mechanism behind this and how you identified MS and Parkinson's as the focus indications to go after? And how we can -- what we can expect with regards to the development time lines around that formulation?

Yes, absolutely. Kumar?

Sure, sir. Thank you.

Good morning Ami. Thank you for hosting us today. So the new formulation of pitolisant, if we take a step back and look at fatigue in general, this is something that we have been thinking about for a while now. That's mainly because fatigue is a multidimensional concept as opposed to excessive daytime sleepiness, for example.

Fatigue has emotional, physical and cognition aspects to it. And the histamologic mechanism of action because of the way it works, not just on the histamine circuitry, but also the downstream norepinephrine and serotonin mechanism of action, it is uniquely positioned to address all 3 aspects of fatigue. And that's exactly what we saw when we did our Phase II proof of concept in myotonic dystrophy, where about 90% of the patients have significant fatigue.

In that study, we showed that pitolisant not only improved fatigue in a clinically meaningful way, but it also showed a dose response. Not only that, we also studied fatigue in patients with residual excessive sleepiness in OSA. In fact, that actually is in the label in Europe, where pitolisant is marketed as Osavate for residual excessive daytime sleepiness in patients with sleep apnea.

So when we have this opportunity to get our hands on this new formulation with an issued patent until 2042, there were certain features of this formulation, which lends itself better to treat fatigue in broader indications. And so that's when we decided to go ahead and pursue indications like fatigue in MS, fatigue in Parkinson's disease. We prioritized fatigue in MS because this is where fatigue is very well characterized. More than 80% of patients with MS have some kind of fatigue and more than 50% of patients with MS have significant fatigue.

Folks have done some work in terms of how to measure fatigue in these patients. There is some longitudinal data for fatigue in MS. And based on the pitolisant profile that we know and some of the work that has been done in the past in the preclinical space, that was logically our next first indication for a broader indication like MS. So that's where we are. In terms of where we are in terms of our clinical development right now, we are optimizing the formulation. The next step would be to do a Phase I PK study, and we'll take it from there.

Got it. Okay. I want to step back and think about the competitive landscape here for a second before we move on to BP1, your own orexin. And I wanted to get your thoughts on how you're thinking about the landscape that's evolving with the first orexin that will get approved later this year, which is the Takeda product. How do you see that impacting WAKIX in the near term? Now we know that, that's approved or expected to get approved just in NT1. So how do you see that impacting the WAKIX utilization in the near term? And then maybe stepping back, how do you see that impact with the entry of other orexins over time, how do you see WAKIX being positioned in the market? And maybe we can talk about the 2 sort of life cycle assets, the GR and HD formulation, how does that help you navigate that competitive landscape over the next couple of years?

Yes. Ami, before I turn it over to sort of Adam in terms of market impact of the emerging orexins and Kumar on our development program, I just comment that, it is obviously, incredibly exciting space, so much attention and activity around the orexin development programs for good reason, novel mechanism, really the first new novel mechanism coming to central disorders of hypersomnolence and probably more, and we can talk about that a lot as well since WAKIX launched, -- and I just -- we are very active in this space, following the programs, our own development programs, other activities with our partner, Bioprojet, looking at even indications beyond sleep wake. So just wanted to emphasize that comment, and then I'll turn it over to Adam and Kumar on further thoughts of impact and then our development program.

Sure. Happy to jump in. As you can imagine, Ami, this is a question we've spent quite a bit of time thinking about and analyzing and conducting market research. We're excited about Orexin's new treatment option for patients. And in the research, what we see is, yes, there's definitely excitement and interest based on the efficacy profile. There's also some remaining questions around some of the adverse events and tolerability. As you've seen, there's pretty high rates of insomnia up to 60%, frequent urination, visual disturbances in some cases and of course, limited long-term data. So there's definitely interest to try. But I think this is going to be a gradual approach to trial. And as we learn more, we'll see how physicians end up utilizing orexins as a new treatment option.

In terms of impact, we're still -- as in narcolepsy, we're still less than 50% diagnosed and even less treated. So hopefully, with the awareness that the orexin class brings, we'll see an improvement there for patients. We also have seen over the last, let's say, 5 or 6 years, an expansion of brand utilization, but brand utilization is still, what, around 20% of the class. So we would expect a new brand launch to expand brand utilization as well. And that's actually what we've seen historically as new brands come in, they tend to expand brand utilization rather than steal share from other brands. That's the polypharmacy approach, which is the hallmark of this class.

Clearly, we've seen in research and our discussions with health care providers, they will prefer to continue that approach. And so we would expect an expansion of brand utilization as well. And then when it comes to treatment selection, WAKIX, we believe, will continue to grow in the face of orexin because it's going to continue to offer something that's totally different and unique than any other treatment option when you look at the totality of efficacy and safety tolerability. So really good efficacy, but exceptional safety and tolerability and extremely clean profile that allows WAKIX to be added on to virtually any combination of therapies in a polypharmacy market. And that profile is going to continue to be the case with WAKIX now with 7 years of clinical experience, and it's going to continue to be differentiated versus all other competitors, including orexins.

So that's where we see physicians are really familiar with WAKIX, 7 years of clinical experience. It's a go-to add-on therapy in a polypharmacy market, and we expect that to continue.

Yes. Ami, from a development perspective, from a clinical, medical and scientific perspective, I'm very fascinated with the orexins and I'm even more fascinated with our own orexin because of several distinguishing features. This continues to be the most potent orexin receptor agonist in clinical development.

The potency we are talking about is at 0.015 nanomolar levels. And this does offer a benefit of targeting all 3 central disorders of hypersomnolence at very low doses with the same drug and limit the off-target AEs. In addition, we also have a novel chemical scaffolding that helps not just with its potency, but also helps with some off-target AEs that were answered with earlier orexin receptor agonist like LFT abnormalities or QT prolongation.

On top of it, we have excellent selectivity. The preclinical safety data has been very clean. And also the preclinical PK profile is supportive of potentially once-a-day dosing regimen. We started dosing patients in the fourth quarter of last year. We are on track to get full clinical PK data in single ascending dose study in healthy volunteers. And after that, we plan to submit the IND and kind of the sleep deprived healthy volunteer study, which will help us to bracket the dose range, and then we'll immediately move on to the next stage of development.

Kumar, do you think the potency can help differentiate on some of the adverse events that I think Adam had mentioned and yes, those are the most common adverse events that we have seen with orexins, which is insomnia, polyuria. Do you think that a more potent molecule can help reduce -- meaningfully reduce those adverse events that we're seeing, which are on-target adverse events?

Great question, Ami. That's something that we'll have to wait until we get the clinical data. We know that having a large potency, high potency like this will definitely help us to go with a much lower doses and target NT1, NT2 and IH. The emerging data has shown that you need a much more potent drug to target NT2 and IH or go really high on the dose, that's when you end up seeing many of the off-target EAs the other sponsors have disclosed to some extent like visual disturbances and hypersalivation, things like that.

So the on-target effects, that's something that we need to wait for the clinical data. But the off-target AEs, clearly we will be able to manage that with a very high potent orexin receptor agonist at very low doses.

Yes. Yes, Ami, the other interesting part of this is, as we look at this conversation and the interest in orexins beyond central disorders of hypersomnolence, some of these new targets that are cognition, mood, et cetera. So when you move away from NT1, which is a disorder of orexin deficiency, where obviously, the main efficacy has been proven, but then NT2 IH and then these other potential indications around cognition, mood, ADHD and probably others to be discussed in the future that we are also looking at and contemplating and doing some work with our partner. They are not disorders of orexin deficiency. So having a potent compound, as Kumar said, and dosing flexibility may also be very relevant as this sort of platform play kind of evolves, if you will.

Yes. I mean you have the benefit of taking some learnings from some of the other companies that are running clinical trials. And I'm just sort of curious what type of data you believe you need to generate with either BP1 or what you need to see to sort of lay out a path for your own asset in terms of which indications you're going to go after and how you're going to elucidate its differentiated profile.

Yes. Take Kumar.

In pharma in general, in drug development in general, the first asset is not necessarily the best asset, right? More often than not, it's the fourth or the fifth asset that ends up becoming the best-in-class asset. And to some extent, we are seeing this play out here as well. And we already incorporated many of the learnings from the previous compounds. I mentioned about going for a new scaffolding rather than the typical [pyridine] sulfonamide bicyclic moieties.

And the reason for that is to exactly avoid some of the off-target structural related AEs like abnormalities in LFTs or cardiac abnormalities like Q-T prolongation, and we successfully accomplished that. The second thing was potency. Potency was extremely important for all the reasons that we discussed earlier, and we achieved that with 205 compound. In fact, we did disclose this data at the last year meeting, where in the arsenic mouse model of narcolepsy, our 205 demonstrated wakefulness at the lowest dose we ever tested in this particular mouse model, 0.03 mg per kg.

So it is playing up as we had hoped for based on pretty much the drug design, the medicine chemists here at [indiscernible] worked based on what was seen with the earlier compounds. In terms of clinical development, we'll be looking at efficacy, safety, tolerability, the dosing frequency and the dose range that will help us determine how to go about with the next indications. And based on what we are seeing, we believe we should be able to target NT1, NT2 and IH with the same drug with very low doses and with a very favorable benefit risk profile. Obviously, we need clinical data to demonstrate that. And we'll get there soon.

Yes. That makes sense. Great. I wanted to switch gears to your epilepsy program, EPX-100. At AES last year, you disclosed data from its open-label ARGUS study -- well, the open-label portion of the ARGUS study. And we saw that it demonstrated a 50% median reduction in CMS-28 from baseline, and we saw a reduction or a response in at least 50% of the participants.

Based on the data that you've disclosed so far, and of course, a lot of the differentiation comes on the safety side of things as well. How do you see it positioned in the market? We know that there are other drugs that are also in development. So how are you thinking about its market positioning from a commercial standpoint?

From a clinical perspective, right, you're absolutely right, the data that you just mentioned. That's clinically meaningful efficacy. We need to hit the efficacy bar and a 50% median reduction compared to baseline is considered as clinically meaningful by all clinicians who deal with these patients. And it's important to remember that this is adjunctive therapy. This is on top of about 4 to 6 antiepileptic medications these patients are already taking.

So in this context, it is considered as very clinically meaningful. And then the other aspect of the equation here is tolerability and safety. One of the biggest challenges that patients have with all the medicines that are approved in this space is tolerability and safety. Even the most recently or more commonly used medications like, for example, Fintepla and Epidiolex, they have significant issues with appetite suppression in a patient who is already cachectic, has some feeding difficulties, about 20% to 30% in some instance of nausea, vomiting, abdominal grams and diarrhea. With EPX-100, the only GI AE that we saw of any clinical relevance was diarrhea in just over about 2% of the patients. In terms of safety, we do not have to do any of the looking in safety monitoring. For example, with Epidiolex, you need to check with LFTs every so often because of unpredictable elevation in liver function tests.

With Fintepla, for example, it's important to do echocardiogram on a regular basis. In fact, it's part of the REMS program. We don't see the need for any special medical monitoring. So the benefit-risk profile is very differentiated with EPX-100 compared to anything that is approved thus far.

Yes. And maybe I don't know if this is a good time to also get a sense of where in the treatment paradigm in the real-world setting, do you see it being used? And -- so if a patient is not achieving goal, then this is another option that can be considered for being added on top of existing therapy.

Yes, that's exactly what happens, Ami, in this particular space. It's a chronic condition. These patients have treatment refractory seizures. In fact, with all the medicines that are approved in this space, about 50% of the patients still have seizures that are not adequately controlled with the existing treatments. And this is being studied as an adjunctive therapy that is an add-on therapy, and we see it as being used as an add-on therapy on top of everything else these patients are currently on.

Yes. I know we have just a couple of minutes left. I wanted to talk about sort of the balance sheet. And I think Jeff mentioned at the beginning of our conversation that you have over $800 million in cash. And certainly, over the last couple of years, you have executed on deals to bring in different assets into the mix. Has anything with regards to your strategy or approach to thinking about what type of assets you would pursue changed over the course of the last year? And at this time, are there certain types of drugs or things that you could add on to your existing portfolio that would be more interesting than others?

Yes, Ami, I think thank you for that question, sort of an important priority for us. I think that our core strategy has really not changed in terms of the core strategy. I think we've sort of opened up the aperture a little with regards to what we're looking at across the BD landscape. But we still -- our sweet spot is in orphan rare CNS and neuropsych targets, and we sort of look across the landscape for opportunities there.

More recently, and given our capacity, we're open to looking at broader potentially assets with broader indications outside orphan rare, what we call sort of adjacencies to our core strategic franchises in sleep wake and the rare epilepsies. And then importantly, again, given our capacity and where we are in our evolution, not just pipeline assets, but on market as well, which I think is probably the most recent sort of evolution of our thinking because we have the capacity. We have a strong commercial engine and a strong commercial team, as you're aware.

And I think the ability to add another product to their bag and beyond just WAKIX and the pitolisant franchise where there's a good strategic fit. So that is the current thinking. And looking at both strategies, whether we do sort of tuck-ins, if you will, or string of pearls in smaller opportunities, but also open to something more transformational. We have the capacity. We have the experience and the know-how across the team. If we see something larger that is a good strategic fit, is a smart business development deal for us. We are also looking really across the spectrum of those opportunities.

Okay. That's very helpful. I think we're almost out of time. So this is a good opportunity for me to thank you all for taking the time to have this conversation with me and look forward to our future conversations. Thank you so much.

Ami, thank you on behalf of the team. Thank you so much for the invitation. Always enjoy our conversations. Thank you.

Thanks, guys. Thanks.

Good morning. My name is Angela, and I will be your conference operator today. At this time, I would like to welcome everyone to Harmony Biosciences' Fourth Quarter and Full Year 2025 Financial Results Conference Call. [Operator Instructions] Please be advised that today's conference may be recorded. [Operator Instructions]

I will now turn the call over to Matthew Beck from Astr Partners. Please go ahead.

Thank you, operator. Good morning, everyone, and thank you for joining us today as we review Harmony Biosciences' fourth quarter 2025 financial results and provide a business update.

Before we start, I encourage everyone to go to the Investors section of our website to find the materials that accompany our discussion today, including a reconciliation of our GAAP to non-GAAP financial measures. At this stage of our life cycle, we believe the non-GAAP financial results better represent the underlying business performance.

Our speakers on today's call are Dr. Jeffrey Dayno, President and CEO; Adam Zaeske, Chief Commercial Officer; Dr. Kumar Budur, Chief Medical and Scientific Officer; and Sandip Kapadia, Chief Financial and Administrative Officer.

As a reminder, we will be making forward-looking statements today, which are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties. Our actual results may differ materially, and we undertake no obligation to update these statements even if circumstances change. We encourage you to consult the risk factors referenced in our SEC filings for additional details.

I would now like to turn the call over to our CEO, Dr. Jeffrey Dayno. Jeff?

Thank you, Matt. Good morning, everyone, and thanks for joining our call today. I want to start off by recognizing the entire Harmony team for another outstanding quarter and a remarkable year in 2025. Our fourth quarter results reflect strong, sustained execution and have positioned us to achieve blockbuster status for WAKIX this year.

In Q4, we delivered $243.8 million in net product revenue, up from $201.3 million in the same period last year, driven by continued strong demand for WAKIX based on its broad clinical utility and ongoing executional excellence by our commercial team. Q4 '25 marked the third consecutive quarter with approximately 400-plus average patient adds, the first time in franchise history. This quarter's net patient adds brings us to approximately 8,500 average patients on WAKIX. With 80,000 diagnosed patients with narcolepsy, there continues to be a large market opportunity to support strong growth.

For full year 2025, WAKIX generated $868.5 million in net product revenue, representing strong year-over-year growth and extending to 6 consecutive years of revenue growth and profitability. Looking ahead to 2026, we are guiding WAKIX' net revenue to blockbuster status of $1 billion to $1.04 billion for the first time in franchise history, underscoring the durability of the WAKIX brand and the strength of our commercial engine.

On the IP front, we have made good progress towards the goal of securing the WAKIX franchise. We recently settled with 3 generic filers, resulting in us having settled with 6 of the 7 ANDA filers. Based on these settlements, generic entry would occur no sooner than March of 2030 if we are granted pediatric exclusivity, which we are on track to obtain. As for last week's trial, we remain confident in the strength of our IP, and we'll continue to vigorously defend it as the legal process and trial continues.

In addition to the strong growth of WAKIX, we are advancing the next generation pitolisant franchise. Pitolisant GR will extend the WAKIX franchise and our leadership in narcolepsy as a line extension of WAKIX with its broad clinical utility. We are on track for NDA submission in Q2 this year with a target PDUFA date in Q1 2027. Pitolisant HD is designed to expand the pitolisant franchise into unique indications in orphan rare diseases, addressing unmet medical needs.

And we now have an opportunity to explore a new pitolisant formulation to pursue broader indications in CNS patient populations in which fatigue is a prominent symptom. This strategy is a mechanism-based approach as fatigue is mediated through histamine circuits in the brain, and pitolisant works by upregulating histamine transmission in the brain, along with other neurotransmitters. This work is supported by newly licensed IP with patent protection until 2042. And we are excited for the opportunity to explore broader CNS indications with pitolisant. Kumar will provide more color on this opportunity later in the call.

Our robust late-stage pipeline continues to advance with 5 ongoing Phase III registrational trials towards 5 distinct CNS indications, and we are making good progress. These trials set us up for multiple catalysts over the next few years and if successful, meaningful long-term value creation. Kumar will provide more details on the progress of our pipeline programs, and the timing of these important catalysts during his R&D update.

In summary, Harmony enters 2026 with powerful momentum, a clear path to blockbuster status for WAKIX in narcolepsy alone; record revenues and a large market opportunity that remains in narcolepsy for continued growth of WAKIX; a life cycle management strategy that we are advancing to extend the success of WAKIX; expand next-generation pitolisant into unique indications in orphan rare CNS disorders along with our new opportunity to explore broader CNS indications with a new formulation of pitolisant driven by a mechanism-based approach; and a robust late-stage pipeline with 5 ongoing Phase III registrational trials toward 5 distinct CNS indications.

All of this reinforces our belief that we have built something rare in this industry, a profitable, self-funding biotech company with a strong balance sheet, well positioned to build out our pipeline and expand our commercial portfolio to drive long-term value creation.

With that, I'll turn the call over to Adam Zaeske, our Chief Commercial Officer, for an update on our outstanding commercial performance. Adam?

Thank you, Jeff. 2025 marked a year of unprecedented and record-setting performance for WAKIX and that performance continued in the fourth quarter. In Q4 of 2025, WAKIX continued its remarkable trajectory with the third consecutive quarter of approximately 400 or more average patient adds. The first time this has been achieved in the history of the franchise. This level of sustained momentum speaks directly to the strength of the brand and the consistency of our execution.

What's driving this performance is clear. WAKIX maintains a unique, highly differentiated position as the only non-scheduled treatment option, which continues to fuel broad clinical adoption. Brand awareness, perceived efficacy, tolerability and stable payer coverage remain exceptionally strong. And we've sharpened our commercial fundamentals from field deployment and call planning to refine messaging, targeted promotion, new payer wins and better patient support processes that shorten time to dispense and boost conversion.

The compelling value proposition of WAKIX combined with continued strategic adjustments and strong operational execution are delivering results, giving us confidence heading into 2026. In addition, right now, we are expanding our field-based teams by almost 20% across our field sales, field reimbursement and remote sales teams, and we've already made progress in hiring for these roles.

This investment will increase our presence in the market and demonstrates confidence in our continued growth. We will launch a new online portal to enable easier and faster access for patients, and we're continuing to deploy process improvements to further improve time to dispense and success rate, and we'll continue to look for opportunities for additional improvements and efficiencies moving forward.

We're also extremely excited about the recent FDA approval of WAKIX for the treatment of cataplexy in pediatric patients 6 years of age and older with narcolepsy. This approval further demonstrates the clinical value of WAKIX for pediatric patients who experience cataplexy and gives their health care providers the option of prescribing WAKIX to address excessive daytime sleepiness, cataplexy or both in people's 6 years of age and older living with narcolepsy.

Our commercial teams were well prepared ahead of this approval and with robust promotional strategy and began executing on those plans from the day of approval. With all of this momentum, we've announced full year revenue guidance for WAKIX to achieve blockbuster status of between $1 billion and $1.40 billion in revenue in narcolepsy alone.

Looking ahead, pitolisant GR and pitolisant HD give us the opportunity to extend and expand the franchise with differentiated formulations that address important unmet needs, while fully leveraging the commercial engine we've built. Early feedback from market research with health care providers and payers has been highly encouraging, and we're preparing the organization to drive the next phase of growth as these assets come to market.

In short, our commercial performance has never been stronger. The fundamentals are sound, execution is disciplined, and we have a clear path to sustained growth.

Now I'd like to turn the call over to our Chief Medical and Scientific Officer, Kumar Budur, to discuss the advancements in our clinical development programs. Kumar?

Thank you, Adam. Good morning, everyone, and thank you for joining us today. Q4 2025 capped a year of significant scientific and clinical progress for Harmony, and we are entering 2026 with one of the most robust late-stage CNS pipelines in the industry. We now have 5 ongoing Phase III registrational clinical trials across 5 distinct CNS indications underscoring the breadth and depth of our development programs.

I'll start with updates for our Sleep/Wake franchise. I'm pleased to highlight a new indication for WAKIX that the FDA approved on February 13. The FDA approved WAKIX for cataplexy in patients 6 years of age and older. This is another important milestone for WAKIX, and it is now approved for both excessive daytime sleepiness and cataplexy in adults and children 6 years of age and older. This approval also advances our efforts towards achieving pediatric exclusivity for WAKIX, which is an additional 6 months of regulatory exclusivity at the back end of the longest pattern for WAKIX. The data from the ongoing Phase III study in Prader-Willi syndrome, the TEMPO study is the other requirement for pediatric exclusivity, and we are on track for the top line data from the TEMPO study in the second half of this year.

Across our next-gen pitolisant program, pitolisant GR continues to advance as a fast-to-market strategy after demonstrating bioequivalence to WAKIX in a pivotal bioequivalent study and has the ability to initiate treatment at the therapeutic dose range at 17.8 milligram, eliminating the need for titration, which is an important differentiation. We remain on track for an NDA submission in Q2 2026 and target PDUFA in Q1 2027. Pitolisant HD, our enhanced formulation with an optimized PK profile and a higher dose remains on track for top line data in 2027 and PDUFA in 2028.

The Phase III registrational clinical trials in narcolepsy and IH, that is the ONSTRIDE 1 and ONSTRIDE 2 studies are ongoing. ONSTRIDE 1 is a prospective placebo-controlled parallel-arm double-blind randomized clinical trial comparing pitolisant HD and placebo. This is an 8-week study, evaluating excessive daytime sleepiness via subjective and objective endpoints, that is ESS and MWT, and we are also evaluating cataplexy and fatigue in this study.

On Slide 2 is also a prospective placebo-controlled parallel arm double-blind, randomized clinical trial comparing pitolisant HD and placebo. This is an 8-week study, evaluating symptoms of idiopathic hypersomnia via IHSS and sleep inertia via sleep inertia scale. The sample size for each of these studies is approximately 200 patients, and both programs are pursuing differentiated labels, fatigue in narcolepsy and sleep inertia in idiopathic hyperthermia. Both the GR and HD formulations have utility patents filed extending and expanding the pitolisant franchise potentially into the 2040s.

We are also very excited to announce the opportunity to explore broader CNS indications with a new formulation of pitolisant with an issued patent until 2042. As we have discussed in the past, the histaminergic mechanism of action of pitolisant is uniquely positioned to address all 3 different dimensions of fatigue: physical, emotional, and cognizant, and we have already generated clinical data to support the utility of pitolisant to treat fatigue.

We plan to evaluate this new formulation for fatigue in broader indications with fatigue in multiple sclerosis of the lead indication and explore other opportunities such as post-stroke fatigue and fatigue in Parkinson's disease. Our current efforts are focused on formulation optimization and new modes of delivery and towards the Phase I PK study.

Beyond pitolisant, our orexin-2 receptor agonist BP1.15205 is enrolling in our Phase I clinical study. We are on track for Phase I PK data in mid-2026. As we have previously shared, BP1.15205 has demonstrated compelling preclinical potency, selectivity, safety and efficacy, positioning it as a potential best-in-class orexin-2 receptor agonist.

Moving on to our epilepsy franchise. EPX-100 continues to advance in 2 global Phase III registrational programs. Enrollment is ongoing in both the Dravet syndrome and the Lennox-Gastaut syndrome programs, that is the ARGUS study and the LIGHTHOUSE study, respectively. The top line data is expected in first half of 2027 and PDUFA in 2028.

We recently label extension part of the Phase III study in Dravet syndrome at the AES meeting in December 2025, which supported a differentiated product profile for EPX-100. The effectiveness data in patients who had at least 6 months of exposure to EPX-100 showed clinically meaningful reduction in seizures, approximately 50% median reduction in seizures as measured by CMS-28. In addition, we saw at least 50% reduction in seizures in half of the patients. EPX-100 was found to be generally well tolerated with no additional laboratory or special monitoring requirements with some participants exposed to EPX-100 for more than 2 years and approaching 3 years.

Finally, on behalf of Harmony, I would like to thank all the patients and their families who are participating in our clinical trials as well as the clinical investigators and site personnel for their efforts and commitment in helping us to advance our development programs.

I'll now turn the call over to our CFO, Sandip Kapadia, for an update on our financial performance. Sandip?

Thank you, Kumar, and good morning, everyone. This morning, we issued our fourth quarter earnings release and filed our 10-K, where you'll find the details of our fourth quarter and full year 2025 financial and operating results. Our financial performance is also shown on Slides 15 through 17.

We finished the year with great momentum across the business, delivering strong growth across several of our key metrics, positioning us well as we head into 2026. We delivered another year of double-digit top line growth as we reported net revenues above the top end of our previous guidance range.

We continue to be a profitable cash-generating company, funding the growth and advancement of our pipeline fully with the strength of our balance sheet. Our strong financial performance, combined with a solid balance sheet, including approximately $882.5 million in cash, cash equivalents and investments positions us well as we continue to invest in the advancement of our robust late-stage pipeline and look for additional value-enhancing opportunities to further build out our pipeline and add to our commercial portfolio.

We reported net revenues of $243.8 million for the fourth quarter of 2025 compared to $201.3 million in the prior year quarter, representing a growth of 21% and also our highest quarterly revenues to date. Performance in the quarter reflects the sustained strong underlying demand for WAKIX.

We also reported total operating expenses for the fourth quarter of $136.7 million compared to $91.1 million for the same quarter in 2024. The growth in expenses was related to investments in our R&D to advance our late-stage pipeline, investments in the commercialization of WAKIX and narcolepsy as well as ANDA litigation and settlement expenses during the fourth quarter of 2025.

Non-GAAP adjusted net income for the fourth quarter of 2025 was $33.4 million or $0.57 per diluted share compared to $64.2 million or $1.10 per diluted share in the prior year quarter. We believe non-GAAP adjusted net income better reflects the underlying business performance. Please see our press release for a reconciliation of GAAP to non-GAAP results.

We ended the fourth quarter with $882.5 million in cash, cash equivalents and investments. The balance reflects robust cash generation of $348.2 million from operations in 2025, providing us with the financial flexibility to execute on our growth strategy.

Looking ahead to our expectations for 2026. As previously disclosed, we are reiterating our guidance for WAKIX net revenue of $1 billion to $1.04 billion. We believe this guidance reflects our strong expectations for 2026 and demonstrates that we are on track to achieving blockbuster potential for WAKIX in narcolepsy alone.

As you think about phasing of revenues for the first quarter of 2026, we expect to see the typical seasonal dynamics that the industry as a whole experiences each year in Q1. This includes higher gross to net deductions due to insurance plans resets and higher co-pay obligations, along with potential for drawdown in trade inventories. With respect to expenses, we expect significant increases in investments in R&D as we advance our pipeline with 5 ongoing registrational Phase III programs, along with plans for a sixth Phase III study anticipated to start later this year. Finally, business development is a high priority, and our intention is to deploy capital to expand our pipeline and commercial portfolio.

In summary, I'm pleased with our strong financial performance in 2025. We once again delivered a year with strong top line growth, maintained healthy operating margins, while continuing to generate significant cash. This positions us well as we enter 2026 with a potential for significant value generation.

And with that, I'd like to turn the call back over to Jeff for his closing remarks. Jeff?

Thank you, Sandip. In closing, I'm incredibly proud of what the Harmony team accomplished in 2025, but that is behind us, and we are now focused on 2026 and excited for what is ahead. Growth of the WAKIX franchise, guiding WAKIX to blockbuster status in 2026, extending the WAKIX franchise with pitolisant GR's target PDUFA date in Q1 2027, expanding the pitolisant franchise with the advancement of the Phase III trials with pitolisant HD in unique orphan rare CNS indications; a new opportunity to explore broader CNS indications with newly licensed IP and a new formulation of pitolisant and advancing our robust late-stage pipeline with 5 ongoing Phase III registrational trials toward 5 distinct CNS indications.

It is the cost of these achievements that we continue to operate from a position of strength and drive significant momentum. This momentum reinforces our confidence that we have built something rare in this industry, a profitable, self-funding biotech company with a strong balance sheet, blockbuster commercial product, a pipeline positioned to deliver significant long-term value and the capacity, experience and commitment to generate even greater value through the pursuit of smart business development opportunities.

Thank you, and I will now turn the call back over to the operator for Q&A. Operator?

[Operator Instructions] We'll take our first question from Pete Stavropoulos with Cantor Fitzgerald.

Actually, I'm going to go to one of your earlier-stage assets, EPX-100 for Dravet and the clinical data disclosed at AES in December. Can you just comment on the baseline seizure rates and the baseline antiseizure med use? How do they sort of compare to the real-world patients? And then how do you compare to patients in other Dravet clinical trials? And with the interim OLE efficacy and safety data in hand for those that have at least 6 months of exposure, what's your view on the emerging benefit risk profile? How competitive do you believe the emerging profile is? And where do you see it fitting into the current landscape?

Pete. Thanks for your question, and I'll turn it over to Kumar to respond.

Thank you for the question. These patients who participated in our Dravet syndrome study had treatment-resistant seizures. They were, on an average, approximately about 4 antiseizure medicines. And their baseline seizures, I don't remember the exact number what the baseline seizure was, but I can provide that information, but that was comparable to what we have seen in other studies as well.

In terms of the value proposition, Pete, I mentioned on the call, the efficacy that we saw in this study. The effectiveness data showed that we had at least about approximately 50% median reduction in seizures. And we also saw 50% reduction in seizures in about 50% of these patients. What's important is to see this alongside the safety and tolerability profile. We did not see significant nausea, vomiting, abdominal pain, diarrhea, that is commonly seen with other medicines, including suppression of appetite.

In fact, the only GI, AE of note was diarrhea, which was seen in about 2% of the patients. Liver function tests also remain normal, which is an issue with some of the approved drugs. And EPX-100 doesn't require any special monitoring. And also the ease of use is also very important here. Our liquid formulation BID dosing regimen is much more better suited in this patient population for patients and caregivers compared to some of the other drugs that are in development, which have a TID dosing regimen. Thank you, Pete.

Thanks, Kumar.

And one follow-up, if okay. A question on the orexin-2...

Go head, Pete.

Can you hear me?

Yes.

Yes. So for the orexin-2 receptor agonist, you're going to have data midyear-ish. What's the PK/PD and safety bar that you look for in the Phase I to move this program into later-stage studies? And where do you sort of see your orexin-2 receptor agonist fitting into the emerging landscape?

Yes. We are dosing the -- sorry, we are dosing subjects right now in our Phase I PK study. By mid-2026, we will see clinical PK data, safety and tolerability data. We don't anticipate to see anything different than what is already seen with other orexin receptor agonist in this class. And we are making progress on advancing this to the next stage of development, which is sleep-deprived healthy volunteer study, we plan to commence in the second half of this year.

And in terms of how it fits with the competitive landscape, look, Takeda is ahead. They have submitted an NDA, and the others are in Phase I and Phase II studies. And our goal is to really accelerate the clinical development by leveraging some of the learnings that we have from other development programs that are ahead of us without compromising the quality of data.

Congrats on the quarter.

Thanks, Pete.

Thanks, Pete.

And we'll move next to David Amsellem with Piper Sandler.

Two for me. One on the orexin, I just wanted to clarify, are we going to get multiple ascending dose data in the second half in sleep-deprived healthies? And how are you thinking about indications here given that you have a number of companies that are looking at narcolepsy and IH? Are you thinking beyond narcolepsy and IH? Or is that going to be your core focus for the orexin program? That's number one.

And then number two, sort of a hypothetical here, but to the extent that with the patent case, if you were to not prevail and there was an earlier-than-expected loss of exclusivity, how do you think about cash conservation and ultimately trying to bridge from the LOE to your next set of development stage assets and commercialization of them?

David, thanks for your questions. With regards to the orexin-2 agonist, just to comment. In terms of target indications, I think we're contemplating broadly in addition to the primary targets in terms of our overall orexin-2 program, other opportunities beyond primary disorders of hypersomnolence. So I think that is part of an overall development strategy.

With regards to the emerging data, first, I just want to clarify, in terms of the PK profile, in healthy volunteers, single-dose study, we are looking to confirm the expected profile of once-daily dosing, with regards to the initial data that will read out.

And Kumar multiple ascending dose on sleep-deprived healthy volunteers?

Yes. The single -- the multiple ascending dose study, David, will follow the single ascending dose study. And in parallel, we plan to conduct a sleep-deprived healthy volunteer study. In terms of the indications, as Jeff was mentioning, we are keeping an open eye and looking at everything, not just central disorders of hypersomnolence, but other potential neuropsychiatric disorders, including several aspects of cognition, mood and other things. We will pursue single-ascending, multiple-ascending dose study because that's something that we need to do regardless. And then we will evaluate the competitive landscape and decide which way to go.

And David, with regard to your second question, with regards to the ongoing litigation. I think as you're aware, I think it's premature. I'm not going to speculate on the future outcome of the trial. But I'd point you to the recent progress that we made in settling with 3 of the generic filers. So that currently, it brings the total number of settlements to 6 of the 7 ANDA filers. We feel good about how that positions us going forward. Based on these settlements, generic entry stands at March of 2030, if we're granted pediatric exclusivity, which we're on track to obtain.

With regards to our cash position and how we stand, I'll ask Sandip.

Yes. Look, I think we're in a very strong cash position. You saw we generated close to $348 million cash last year. We have $880 million of cash on the balance sheet. So I think we're really well positioned to continue to drive innovation, but -- to build our pipeline and be able to fund many -- of all the programs that we spoke about today generally. And we continue to have a solid position as a company.

We'll move next to Jay Olson with Oppenheimer.

Congrats on the progress. Can you talk about any gating factors to filing the pitolisant GR NDA next quarter? And then separately, can you just talk about the pace of enrollment in your Phase III narcolepsy and IH studies for pitolisant HD, considering you've got some competitors also enrolling their studies?

Jay, thanks for your question. We're excited about pitolisant GR. It's sort of right around the corner in terms of NDA submission.

Kumar, any gating items to that or how are things looking?

Nothing. Things are looking good. We are on track to submit the pitolisant GR NDA in second quarter of this year. As always, the final things that are needed for NDA submission, that's what we are working on. And we are on target for PDUFA in Q1 of 2027.

In terms of your question regarding the enrollment for pitolisant HD in narcolepsy and idiopathic hypersomnia studies, you're absolutely right, Jay. There is a competition for patients. We are very much aware of it. But we also have been in this field for a long time. We know the sites; we know the investigators. We have conducted studies in this patient population. So we are confident with our current time line, which is top line in 2027 and PDUFA in 2028.

Yes. Thanks, Kumar.

Great. And with regard to the...

Yes. Sure. With regards to pitolisant GR, I just want Adam to comment on how he sees the opportunity and how the commercial team is preparing for that.

Great. Thanks, Jeff. Preparation is definitely underway, looking for PDUFA in 1Q '27, that will have us launching several years before LOE with an opportunity to extend the WAKIX franchise. This is a fast-to-market line extension strategy that provides a GR coding to pitolisant and allows patients to start right at the therapeutic dose. So another layer of additional protection for a product that's already perceived is highly well tolerated and the addition of starting at a therapeutic dose, which has hopefully the benefit of securing faster patient outcomes.

The strategy here is really focused on new patients that would have been prescribed WAKIX as well as previous patients that we have the ability to recontact because we secure consent right upfront anytime there's a patient referred for WAKIX therapy. Both of those are tremendous opportunities, and we look forward to executing on that launch beginning in 1Q ' 27 next year.

We'll take our next question from Graig Suvannavejh with Mizuho.

This is Ryan on for Greg today. A couple of quick questions for me. I'm wondering if you could comment on the increase in SG&A that we saw in the fourth quarter, the dynamics behind that? And then any updates that you might have on EPX-200 and when we might hear more about that program?

Okay. Sandip?

Yes. Just regarding the expenses in the fourth quarter, I mean, as I mentioned on the call, I mean, we did see an increase in expenses, largely driven by the R&D investments as we start up our Phase IIIs for both IH and narcolepsy in the HD program, continued cost in terms of investments for WAKIX in narcolepsy commercialization there. And then I also mentioned that we did have ANDA litigation and settlement expenses in the fourth quarter. So that the team could be prepared for the trial, which happened a few days ago as well. So again, those are the key drivers for our expenses.

And as I mentioned, going forward, I think the key thing to note in terms of expenses is as we'll have 5 registrational studies ongoing this year and potentially 6 ones planned for later this year, we will see some increases also in the R&D expenses as we go into 2026.

Thanks, Sandip. Kumar?

Regarding liquid lorcaserin, which is EPX-200, we are doing some pre-IND-related work right now. Ryan, as you know, lorcaserin is more selective for 5-HT2B. And this drug probably has one of the largest safety and tolerability database out there, including a long-term cardiovascular outcome study. And also there is a lot of efficacy data in several DEEs with this compound. Our goal is to leverage all of the data that is already available and pursue an accelerated development program and hopefully bring a new medication to patients with Development and Epileptic Encephalopathies.

Thanks, Kumar.

And we'll go next to Danielle Brill with Truist Securities.

This is Alex on for Danielle. Two little detailed questions. One follow-up on Jay's question on ONSTRIDE 1 and 2. Have those begun enrolling patients? Just we haven't seen any indication in [ clintrials.gov ]. And then on the OpEx expenditure, you mentioned the impact of some of the settlements and litigation. Was that primarily in the general and administrative line item? Just kind of curious how that run rate we should expect moving forward?

Okay, Kumar?

ONSTRIDE 1 and 2 studies, as we have mentioned in the past, we started initiating sites towards the end of last year, and it will be posted on clinicaltrial.gov, typically within 21 to 30 days after the first subject is enrolled. We are at different stages of site initiation, site activation, sites are getting prepared to enroll the patients.

Yes. And regarding the expenses, yes, most of them -- they were all under G&A in terms of the ANDA litigation and settlement expenses. Some of it tend to be onetime expenses and some will continue as we kind of continue with the litigation process.

We'll move next to Corinne Johnson with Goldman Sachs.

Maybe I know you can't speak too much about the details of ongoing litigation, but you could help us understand kind of the time line for decisions that are expected next, what process you kind of could anticipate for appeal for a situation like this? And also kind of remind us the regulatory exclusivity time lines that you have?

And then I know you've talked about the litigation or the settlements you have kind of with 6 of 7 of these other generic manufacturers. But can you clarify what the impact this litigation might have on potentially like acceleration clauses in those settlements? I think those are pretty standard, but not sure if they're included here.

Yes, Corinne, thanks for your question. So with regards to the timing of the judge issuing a rule, it's really -- it's hard to know and can't really speculate. This is an ongoing legal process. And it's hard to know when that will complete and come to final decision. As a reminder, there is -- in the meantime, there is a stay that's in place that extends to February of 2027.

And then based on the outcome of the trial, obviously, an appeals process is available to both sides. I think we know that the litigation process as well as the appeals process takes time. And with that, while this was happening, again, I think pointing back to the progress we've made on the settlements in terms of 6 of the 7 generic filers being settled, we feel that positions us well going forward with regards to the overall process.

In the meantime, there are other things going on with regards to -- as we just spoke to, pitolisant GR and extending the franchise. And that's -- we remain -- with regards to last week's trial, we remain confident in the strength of the IP, and we will continue to vigorously defend it as the legal process plays out after the trial.

Kumar, in terms of regulatory exclusivities? So in terms of our regulatory exclusivities of where we are with regards to -- I mean, ODE with regards to EDS takes us to March of '26 and for cataplexy to October '27.

And we'll take our next question from Patrick Trucchio with H.C. Wainright.

Just a couple of clarification questions and then a follow-up. First, I think you reiterated 2026 WAKIX guidance of $1 billion to $1.04 billion. What level of average patient growth is embedded in that range? And how much incremental contribution do you expect from the newly approved pediatric cataplexy indication in 2026?

Patrick, thanks for your question. Adam, what -- respond to the patient growth supporting that?

Yes. Thanks for the question. So for 2026 guidance, exceeding basically $1 billion or blockbuster status. The underlying patient growth is consistent with what we've seen this year. So we expect that momentum to continue. We're really excited to see the third consecutive quarter of more than 400 patient adds in the quarter. We've never seen that before in the brand. We believe that's a strong foundation and momentum carrying us into '26, and we expect that to continue.

You're going to see the regular and normal seasonality that you're going to -- that we've seen over the last several years. Q1 tends to be a little bit slower as the start of the calendar year with payer resets and what have you. So we expect that seasonality to continue. But the underlying sort of average performance, we'd expect to continue the momentum we saw in 2025. Hopefully, that covers the question.

Yes. That's helpful. And then just as it regards to the broader CNS strategy with MS fatigue, I'm wondering, first, can you elaborate on what existing clinical data supports pitolisant's efficacy in fatigue? And what's the development time line for your Phase I -- what is the development time line for the Phase I PK study?

Patrick, regarding this new formulation, this is something we are very excited about. It's a new formulation with an issued patent until 2042. We have mentioned in the past about our interest to pursue fatigue based on the histaminergic mechanism of action. We have also said that fatigue is not an any-idimensional construct. It's a multidimensional construct with physical, somatic and cognition symptoms. And how pitolisant with its unique mechanism of action working at tuberomammillary nucleus and the downstream effects on serotonin and norepinephrine is uniquely positioned to treat fatigue.

To your question about clinical data, Patrick, we actually showed the efficacy data in fatigue with pitolisant in our myotonic dystrophy study, where we saw clinically meaningful improvement in symptoms of fatigue, and we also saw a dose response. Similarly, we also saw clinical efficacy data in fatigue in patients with residual exclusivity and sleepiness with OSA.

So on with all of these data points, we plan to pursue broader CNS indications where fatigue is a prominent symptom, and we have identified fatigue in MS as a lead indication because it's very well characterized very well-known and about 80% of patients with MS have fatigue with more than 50% having clinically significant fatigue. In terms of where we are with the development program, right now, the focus is on formulation optimization and looking at potentially other modes of delivery and prepare for a PK study, clinical PK study. That's where we are. Thank you.

Great.

And if I could just jump in, I neglected to answer the second part of your question around the pediatric cataplexy opportunity. So just a quick couple of words on that. We're really excited about the approval of pediatric cataplexy. We now have approval for EDS and cataplexy in both adult and pediatric populations, basically anyone over 6 years of age.

The pediatric patient population represents about 5% of the total narcolepsy population, just to give you an idea around scale of the opportunity. But really, we see this as -- look, this is an important addition to the label. It provides greater flexibility for health care providers and their ability to treat these patients. It's important new information that we will educate those health care providers on.

And it -- I think reinforces WAKIX as an appropriate treatment for peds as well as having just broad clinical utility across almost all patients with narcolepsy. So our teams are really well prepared ahead of the approval. As I mentioned, we had a robust promotional and execution strategy ready to go, and we began executing on those plans really from the day of approval. Thank you for the question.

We'll go next to Jason Gerberry with Bank of America.

This is Pavan Patel on for Jason Gerberry. Just a couple of questions for us. The first is, I know you guys mentioned expanding the field sales and reimbursement teams in 2026. So maybe if you can just help us understand how much of this investment is dedicated to the core in narcolepsy market versus preparing for new launches like pitolisant GR in the future?

And then the second question is with regards to BD. Maybe if you can speak to the BD as a capital allocation priority versus share repurchases or other things and how you're planning to diversify beyond the pitolisant franchise ahead of an important IP outcome, providing clarity on the full commercial asset.

Yes. I didn't catch the first part of the question, if you could repeat that.

I did.

Yes. Why -- yes, go ahead.

Okay. Adam, go ahead.

Yes. The first part of the question was around the expansion. What does that look like and how much of that is related to core growing -- basically growing WAKIX versus preparing for GR. I mean the short answer on that last piece is 100% of the investment expansion is around continuing to grow WAKIX today. Our plans for how we will launch GR will take form kind of as we progress through the calendar year this year and approach that PDUFA date in 1Q '27.

I'll remind that we were really pleased with the performance we saw in '25, really record-setting performance. And that was based on continuing to tweak some of the fundamentals around our sales execution, marketing promotional mix and messaging, adding some payer wins and supporting patients.

As we enter '26, we triggered an expansion of our field-based teams. That's what you were asking about. Overall, it's about a 20% increase in total field-based personnel. So we see full increase in our share of voice. Also gives us the opportunity to rebalance territories that we want to do about every 18 months to 2 years. With our field sales teams, we're seeing that expansion more than 10%, field reimbursement more than 50%, our remote sales teams more than 10%. So it's really meaningful, and we're excited about that opportunity. We've posted those roles. We're already in the process of hiring. We've already identified several of those candidates. So we expect those folks to be in place by the end of this quarter. That's our plan. Thanks for the question.

Thanks, Adam. And with regard to the second question on business development, business development remains a high priority for us, obviously, with a very strong balance sheet, and we want to deploy that capital and invest in the business.

As we said, the sweet spot, the focus continues to be orphan rare CNS opportunities, late-stage development as well as commercial on market. We have the capacity to do that. Obviously, we have a strong commercial engine. We'd like to build out the commercial portfolio. Dedicated business development team and we're also looking -- and we've said this before, adjacencies, broader CNS indications. Obviously, we shared today a new opportunity that we're very excited about based on newly licensed IP with a new formulation of pitolisant where we see a significant opportunity around fatigue and broader CNS populations. So we are focused and committed to those efforts, deploy our capital towards business development.

Sandip, any thoughts on capacity?

Yes. Look, I think we're in a very strong position. We have over $880 million in cash on the balance sheet as of last quarter. And just to your question, I mean, not only obviously, we're looking at business development, but of course, we also have $150 million capacity on the share buyback. So we're always looking at opportunities to drive value for shareholders and that's something that we think we have the optionality as a company as to move forward there.

We'll go next to So Youn Shim with UBS.

Congrats on the great year. I have 2 questions, if I may. First, so it seems like the settlement for generic entry with the 3 additional ANDA filers are now 4 months early, March 2030, if pediatric exclusivity is granted from the prior settlement agreement of July '30 -- July 2030. So I just wanted to check if I'm understanding it correctly. Does it mean without the pediatric exclusivity, the generic entry would start no earlier than September 2029 now?

And my second question is on Prader-Willi syndrome indication for WAKIX. So the Phase III reading out second half of this year, potential PDUFA in 2028. Here, I was wondering what are you envisioning opportunities from the PWS? It would support the pediatric exclusivity for WAKIX and delay generic entry too. But on just the PWS indication itself, the runway would just be about 2 years from launch if approved. Are you thinking of trying the PWS with the pitolisant HD as well?

So Youn, thanks for your questions. With regards to your first one about the timing of the settlement, you are correct in terms of without the pediatric exclusivity market entry would be September 2029. But we are on track, making very good progress towards pediatric exclusivity, which would take it to March of 2030. One of the important components of that, obviously, after the peds narcolepsy data is the Prader-Willi program, both for potential indication. But the larger market opportunity, I think, as you're aware, is the 6 months extension with the peds exclusivity.

Kumar, further thoughts on that?

Yes. With -- So Youn. With PWS in the U.S. alone, there are approximately 15,000 patients with Prader-Willi syndrome. About half of these patients have significant excessive daytime sleepiness for which there are no drugs approved. So if we are successful with this study, we will go for an indication really addressing high unmet need in this patient population.

And in terms of pitolisant HD being a potential option to pursue PWS, that's not how we are thinking right now, but that option is always open to us. Thank you.

And we'll take our next question from David Hoang with Deutsche Bank.

So maybe on the new pitolisant formulation, could you talk a little bit about what characteristics and profile you expect to see with that product? How is it different from, let's say, pitolisant HD? And are there characteristics that lend itself to MSLT related conditions?

And then maybe a second question just around the IP estate for some of these life cycle management products. So could you just summarize again for us the IP that you either currently have or expect to obtain for pitolisant GR, HD and then the new formulation?

Kumar, it's on the new opportunity.

Yes. David, thanks for the question. Regarding the new formulation, as we evaluated this opportunity, there might be some potential options for us with this new formulation that could potentially differentiate itself in terms of the PK parameters that probably will lend itself better for the treatment of fatigue in larger indications. Obviously, once we complete the human PK study, that's when we will get to know how exactly this will play out in humans, and that will help us determine the next step.

But for now, we are really excited about this particular formulation because, as I mentioned earlier to the other question, this is a very unique opportunity for us to pursue fatigue in a broader CNS indication.

And David, in terms of your second question about the IP estate, just briefly as a reminder, pitolisant GR and pitolisant HD utility patents filed out to 2044. This new formulation of pitolisant and the opportunity there is actually an issued patent that we have a license to out to 2042. So formulation work continues on.

As Kumar mentioned, the potential of other modes of administration, looking at the potential some of these patient populations where there's swallowing dysfunction and other methods of delivery, but an issued patent out to 2042.

And we'll take our last question from Ami Fadia with Needham & Company.

This is Poorna on for Ami. Are there any recent updates for the enrollment from the ARGUS and the LIGHTHOUSE studies? And just in case I missed this, what are the targets for the recent sales force expansion? And when do you see that impact coming through?

Poorna, ARGUS and LIGHTHOUSE study, they continue to enroll, and we continue to make progress. We are on track for top line data in the first half of 2027 and PDUFA in 2028.

And the second question, just to clarify.

Just want to understand when do you see the impact from the sales force expansion coming through?

Adam.

Yes. Thank you, Ami. And there was a question around the targets as well. We did add some targets, but let's say it was about 5%. So not a huge add. It's really improving our share of voice and rebalancing territories targeted at the existing target base that we've been targeting for some time. And when would we expect to see that impact? Obviously, we -- as I mentioned, we'd like to get those folks on board and in place by the end of this quarter. And so from the impact standpoint, I guess you would expect to see the impact from that point forward.

Thank you. I'm showing no further questions. I would now like to turn the call back over for any closing remarks.

Thank you, operator, and thanks, everyone, for joining our call this morning for your interest in Harmony Biosciences, and have a great rest of your day. Thank you.

This does conclude today's Harmony Biosciences fourth quarter and full year 2025 financial results conference call. You may now disconnect your lines, and have a wonderful day.

Hi, everyone, and welcome again to the 44th JPM Healthcare Conference. I am Sherry Yang, an Associate from the Healthcare Investment Banking Group, and it's a pleasure to be introducing Harmony Biosciences.

Today, we have Jeff Dayno, President and CEO on stage with me for the presentation and Sandip Kapadia, CFO. Kumar Budur, Chief Medical and Scientific Officer; and Adam Zaeske, Executive VP and Chief Commercial Officer in the audience. Please join me in welcoming Jeff to the podium. Thank you.

Thank you, Sherry. Good afternoon, everyone. And on behalf of the Harmony team, I want to thank JPMorgan for the invitation to present again at this year's conference. I'm really excited to be here with all of you to share Harmony's outlook, a very great outlook for 2026.

Our forward-looking statement, please refer to our website for our latest SEC filings. The theme is momentum. Harmony enters 2026 with significant momentum and propelled by 3 key drivers. First WAKIX performance with 5 years of consecutive growth and profitability, our 2026 guidance points to over $1 billion in net revenue, which means that WAKIX is on track to achieve blockbuster status this year.

Driver #2, a robust late-stage pipeline. With 5 Phase III programs in the clinic advancing towards 5 distinct CNS indications, which will set us up for multiple catalysts over the next few years. And the third driver, our strong financial profile. Harmony is a profitable self-funding biotech company with a strong balance sheet, the ability to bring in new assets, additional assets to build out our pipeline further as well as expand and diversify our commercial portfolio.

We have the expertise. We have the proven commercial engine, and we have the conviction to deliver on our growth strategy. So let me share with you how our momentum is going to propel us throughout this year to deliver on this growth strategy. First, I want to start with some highlights of the overall Pitolisant franchise. Grow, extend and expand our leadership position in sleep/wake by addressing unmet patient needs.

So let me break this down for you. Starting with WAKIX, the foundation of the Pitolisant franchise. The first and still the only product approved for narcolepsy that's not scheduled as a controlled substance, which sort of translates into a very differentiated product profile, a strong overall benefit risk proposition. And that has led to broad clinical utility in this large market.

And going into year 7 on the market, WAKIX is on track to achieve $1 billion plus in narcolepsy alone and blockbuster status. Then turning to PITOLISANT GR or gastro-resistant formulation to extend the Pitolisant franchise. So the gastro-resistant coding and formulation is designed because about 90% of patients with narcolepsy have GI symptoms, GI disturbance, not related to the meds they take, but related to the underlying disorder, the underlying condition.

So the GR formulation is meant to minimize the impact on those GI symptoms and minimize the worsening. We've also demonstrated with the dose optimization study the ability to start at a therapeutic dose and no need for titration. So with PITOLISANT GR we are on track to extend the Pitolisant franchise with a focus on new patients, and patients that may have been on WAKIX before may have discontinued, for which through our single patient hub and those patients opting in, we can reach out and recontact them with a new treatment option.

And lastly, the main value driver. PITOLISANT HD or a high-dose formulation of Pitolisant with a novel formulation and optimized PK profile that is designed to drive greater efficacy in an area, where about 75% of patients still have residual symptoms in this chronic neurologic disorder with refractory symptoms. So with PITOLISANT HD can generate greater efficacy.

In addition to expand the franchise, we're looking at unique indications in these Phase III development programs. In narcolepsy, in addition to EDS and cataplexy, looking at a fatigue indication and the programs are designed to demonstrate benefit on fatigue, which occurs in about 60% of patients with narcolepsy.

In our program in idiopathic hypersomnia, or IH, in addition to the symptoms of excessive sleepiness we're pursuing an indication, an unique indication in sleep inertia, 1 of the core symptoms in IH. So the plan is drive a differentiated label, a differentiated product in the market and expand the Pitolisant franchise with new patients, previous patients and then patients that are on WAKIX with a greater value proposition.

In some market research that we've done with both HCPs and payers, they see this product profile as clinically superior and would switch their patients with this greater value proposition greater efficacy and a unique indication in fatigue. With utility patents filed out to 2044 we have the ability to extend and expand the Pitolisant franchise to the mid-2040s.

The LOE for Wakix is Q1 2030 plus we are on track to obtain pediatric exclusivity, an additional 6 months of regulatory exclusivity that would take the LOE to Q3, 2030. PITOLISANT GR is on track. We're working on the NDA to submit the NDA second quarter this year with an anticipated PDUFA date in Q1 of next year 2027.

We're making good progress in PITOLISANT HD, the high-dose program. We initiated the 2 pivotal Phase III trials, 1 in narcolepsy, 1 in idiopathic hypersomnia, last quarter, fourth quarter last year and are on track with the anticipated PDUFA date in 2028. So what that gives us is 2 meaningfully differentiated product profiles building off of the success of WAKIX with the anticipated PDUFA dates prior to LOE in 2030 advancing differentiated product profiles to strengthen our leadership position in sleep/wake.

The Pitolisant franchise and WAKIX continues to grow. Again, you're going into year 7 in the market. The net revenue -- full year net revenue for 2025, $868 million, coming in over our guidance range of $845 million to $865 million. And then for this year, setting WAKIX up and our guidance of $1 billion to $1.04 billion, WAKIX on track to reach blockbuster status this year. We have been talking about that for a couple of years with the significant growth and momentum, but we look to this year to achieve that goal.

And after WAKIX being 1 of the most successful orphan rare drug launches, we see continued momentum, continued strong underlying demand. The new net patient ads in fourth quarter last year of 400 patients. And what you see here, we have shown 3 consecutive quarters of 400-plus new patient adds in the WAKIX brand in year 6 on the market, the first time we've ever seen this with WAKIX and with that, a significant large market opportunity remains.

With 80,000 patients diagnosed, we ended last year at an average of 8,500 patients. With 80,000 patients diagnosed with narcolepsy in the U.S., significant market opportunity remains and another 90,000 not yet diagnosed. In a market of polypharmacy, we see significant opportunity ahead for WAKIX and the next-gen formulations.

This is being driven by our strong commercial engine. And I think what I'm most excited about, I'm proud of the commercial team, proud of the performance. But what I'm most excited about are some of the improvements and enhancements we made in the second half of last year and especially what's to come this year.

So last year, in year 6 in the market, we had some new payer wins -- on top of strong formulary access, about 80% of lives covered, we had additional and new formulary wins. We strengthened our operations at -- we have a single patient hub. We added some staff, some new initiatives to help the patient experience from prescription to dispense, be more efficient, and that has shown benefit with regards to the commercial performance.

And then this year, so we after really fine-tuning in the execution last year. This year, the theme is about investing and expanding in the commercial operation, expanding on our field teams, and we're also going to be launching an online portal for e-prescribing, which will also drive efficiency in the process for HCPs, which will also benefit patients.

With Pitolisant GR, we are on track to extend the Pitolisant franchise. And as I mentioned, anticipate PDUFA date in the first quarter of 2027. This is a fast-to-market strategy based on the demonstration of bioequivalence to the WAKIX formulation, which we have demonstrated and reported out. As I also mentioned, we've shown that patients can start with on PITOLISANT GR at a therapeutic dose without the need for a titration dose.

So possibly reaching clinical benefit quicker and the overall patient experience enhanced in that regard. NDA submission, second quarter this year and utility patents filed out to the mid-2040s to extend the Pitolisant franchise. And with PITOLISANT HD we have the opportunity not only to extend, but to expand this franchise.

PITOLISANT HD is different. It's an enhanced formulation, a new and unique formulation of Pitolisant with an optimized PK profile and a higher dose. About 2x the label dose. So it's designed to drive greater efficacy, again, in a market where residual symptoms, refractory symptoms not uncommon, even on polypharmacy. The program is also designed to deliver differentiated label, a differentiated product profile, fatigue indication in narcolepsy and sleep inertia and idiopathic hypersomnia.

We're making very good progress. We initiated 2 Phase III registrational trials in the fourth quarter last year ONSTRIDE 1 for adult patients with narcolepsy ONSTRIDE 2 adult patients with IH. And we anticipate top line data readouts from both of those studies in 2027 also utility patents on the HD out to the mid-2040s.

Okay. So not seeing pictures of patients. So -- this is why we do what we do. Those shadows are pictures of patients with narcolepsy that are not here. But -- and Harmony, this is why we do what we do to help patients living with narcolepsy as well as other rare neurological disorders based on what we're working on in our pipeline.

So let me turn to our robust pipeline. And this is an innovative late-stage pipeline. We have programs of Phase III program in Prader-Willi Syndrome. I just shared highlights with you of our Pitolisant, our next-gen Pitolisant programs with GR and HD.

Our Orexin 2 receptor agonist program, early phase but in the clinic and advancing. And then our rare epilepsy development programs led off with EPX 100 in Dravet syndrome and Lennox-Gastaut syndrome or LGS. In the developmental epileptic encephalopathies.

We're driving momentum across the pipeline, setting us up for multiple catalysts over the next few years. So BP1.15205, our Orexin 2 agonist. And the excitement here is Phase I clinical PK data anticipated in the middle of this year. And last year, at the Sleep meetings and the World Sleep Congress, we also presented some of the preclinical data to share the profile from the preclinical safety and efficacy data in a transgenic mouse model of narcolepsy.

And what we showed was single oral dose administration a significant and dose-dependent increase in total wakefulness at the lowest doses reported in that model, 0.03 milligrams per kilogram, which proves out and consistent with this being the most potent of the Orexin 2 agonist compounds that are being -- currently being worked on.

So along with the preclinical efficacy and safety profile, the other feature is the unique structure, the unique chemical scaffold, different than the other compounds. So with all this, and as we go into the clinic, we're excited about the potential for a best-in-class Orexin-2 agonist and further opportunity in the sleep/wake space in the central disorders of hypersomnolence.

Turning to our epilepsy programs, EPX 100. So first half 2027, anticipating top line data from an ongoing global Phase III trial, the ARGUS study in patients with Dravet syndrome. But importantly, last month at the American Epilepsy Society Meeting, we shared some of the clinical data from the open-label extension phase of the ARGUS study in patients that had been on EPX-100 for at least 6 months.

And what we demonstrated was clinically meaningful reduction in seizures in the condition of patient population with refractory seizures on top of multiple other medications 3, 4, 5 other anti-seizure medications with a median reduction on top of that of about 50% in countable motor seizures, the primary end point.

And there's also an overall 50% response rate, both of these clinically meaningful with regards to efficacy. But what the EPX 100 offers is a product profile and the potential to offer an unique risk-benefit proposition with the current therapies in the market, it's not just about efficacy, but especially in polypharmacy, safety and tolerability.

And the profile that is emerging with EPX 100, so a very safe, well-tolerated profile. No need for additional laboratory monitoring, example is Epidiolex, a treatment for Dravet where you have to monitor LFTs. No need for special safety monitoring, another approved product for Dravet [indiscernible] that requires in the REMS program and echocardiogram at baseline in every 6 months to assess for cardiac valor disease.

So none of these aspects on the safety and tolerability profile for EPX-100 as the Phase III trial advances. In addition, the chance to offer convenient dosing regimen, BID, as opposed to some of the other products out there for both patients and caregivers as well. EPX-100 is 1 of the most advanced of the 5-HT serotonin agonist programs in the Developmental and Epileptic Encephalopathies Space or the DEES.

It has an established and validated mechanism of action through a highly predictive preclinical model known as the Zebrafish model, actually developed out here in San Francisco, Scott Baraban at UCSF. And we are also in Phase III global registrational trials with EPX-100 in patients with Lennox-Gastaut syndrome and we anticipate top line data readout from this global study in the first half of 2027 as well.

So let me line up for you the catalysts at Harmony that we see coming and our path to long-term value creation. This year, top line Phase III top line data readout from the Pitolisant program in Prader-Willi syndrome. The importance of this is not just on track for an indication, but this will represent the second and final of 2 data sets that we need to obtain pediatric exclusivity, the additional 6 months of regulatory exclusivity on the back end of the longest patent.

And we are on track, and we'll have the top line data readout this year. And then the Orexin 2 receptor agonist program, we're excited to share the Phase I clinical PK data around mid-2026 this year, but then looking to next year when it gets really exciting. The PDUFA date, first quarter of next year for PITOLISANT GR.

And then Phase III top line data readouts for 4 orphan rare CNS indications for PITOLISANT HD Phase III top line data readout in both narcolepsy and IH, in our epilepsy program with EPX-100, top line data readouts for both Dravet syndrome and LGS -- that positions us going into 2028, just a couple of years away for 4 anticipated PDUFA dates and if successful, HD PDUFA date in narcolepsy and IH, EPX-100 in both Dravet and Lennox-Gastaut. And in addition, the Prader-Willi program with Pitolisant that anticipated PDUFA date there.

So what you see here is our pipeline is poised to deliver significant value through both the extension and expansion of the Pitolisant franchise and our innovative EPX-100 epilepsy asset. And finally, with strong cash generation, prudent investments and responsible expense management, we've established a very strong financial profile at Harmony. And this driving value for our shareholders, consistent revenue growth and profitability.

And as I shared with you, guiding this year to $1 billion to $1.04 billion, WAKIX is on track this year to achieve blockbuster status. And importantly, everything I shared with you, the pipeline programs, the commercial -- strong commercial engine, the expansion of the field force is being fully funded off of our balance sheet. And it also leaves us significant capital for business development, to continue to build the pipeline, grow the enterprise. So we're poised for value creation.

So in closing, I shared with you the momentum coming into 2026 in these 3 main drivers: commercial performance with WAKIX on track to achieve blockbuster status. Our pipeline advancing with 5 Phase III registrational programs advancing towards 5 distinct CNS indications, setting us up for multiple catalysts over the next few years and a strong financial profile, a strong balance sheet as we look to deploy the capital to bring in new assets, build out the pipeline, expand the commercial portfolio.

And with this momentum at Harmony, we're poised to deliver on our promise to patients, while creating meaningful value for our shareholders. Thank you for your attention. Thank you for your interest in Harmony. I'll invite members of my team up for the Q&A. Thank you.

Yes. So thank you, Jeff. You shared a lot of very exciting developments for 2026. What are you most excited about?

All of it, everything -- so no, I think that really excited to see the continued growth of WAKIX in narcolepsy. And it's really across the 3 drivers: the advancement of the pipeline and the opportunities there, especially with the next-gen Pitolisant formulations. Proud of the commercial teams and continue to fine-tune what they're doing there and looking for further growth with those opportunities.

And then -- and lastly, our strong financial profile, which gives us the ability to grow the enterprise even further. We're very active on the BD front scouring the landscape and looking for strategic, thoughtful opportunities to even generate further value creation.

And now moving on to WAKIX. You've built a very nice franchise with WAKIX already with a $1 billion potential. Can you help explain how the Pitolisant strategy is extending and expanding that franchise with GR and HD?

Sure. So I think that -- set up to the next gen is really starts with, I think, the market opportunity, as I alluded to. So we ended the year with about 8,500 average patients but there's still a large market opportunity with 80,000 patients diagnosed and another 90,000 not yet diagnosed.

And then with that and the very unique differentiated product profile with WAKIX strong commercial execution. I think that's what gives us the opportunity. And I want to turn to Adam to sort of share his thoughts on what lies ahead with the commercial team.

Yes. So let's talk about '25 and then in '26. So the history of the brand WAKIX has had very steady performance over the last 6 years, generally adding between 1 and, let's say, 400 patients in a quarter. Prior to this 2025 we'd only seen a 400-patient quarterly add twice in the history of the brand. In 2025, we saw that 3x, 3 consecutive quarters of 400-plus patient adds. That is momentum, I think, was the word that you used.

And it's a function of the market opportunity, highly differentiated product strong team with a lot of experience. Many of our team members have been with us since launch, but it's also about focus on the fundamentals. So really in 2025, sales force effectiveness, updating the call plan, reach and frequency, adjusting promo mix, these types of fundamentals. We enjoy broad formulary coverage. We added new coverage wins in 2025.

We support patients well, but we improved that process as well. We added staff, we improved that process to make sure that patients get to a dispense faster and with a higher probability of success. That type of execution is going to continue in 2026 in addition to continued investment and expansion. So we are in the midst right now of expanding our field sales team, expanding our field reimbursement team, expanding our remote sales team.

We'll be launching an online portal to support health care providers and patients and other significant changes to continue to improve that process to support patients and getting to a dispense event. So that momentum is going to continue in 2026, and that's why we feel confident in the guidance for 2026 that we will achieve $1 billion in net revenue this year.

Thank you. Now moving on to R&D. Regarding your next potential launch of the Pitolisant GR, can you share any additional color on the current status of the NDA submission?

Sure. Kumar?

Yes. We are on track for NDA submission in Q2 of this year with the potential PDUFA date in Q1 of 2027. Pitolisant GR, it's a faster market strategy by demonstrating bioequivalence to WAKIX formulation, which we already did. And in addition, we conducted a small study a dosing optimization study, where we demonstrated that Pitolisant GR can be initiated at 17.8 milligram the therapeutic dose without going through the titration of 8.9 milligrams.

So 2 distinct -- distinguishing features. We are on track for NDA submission, PDUFA in Q1 2027. And also, we have filed utility patents for Pitolisant GR with potential patent extension all the way into 2044, thereby extending the Pitolisant franchise all the way into mid-2040s.

You've guided to are starting the narcolepsy and the IH studies with PITOLISANT HD in Q4 of 2025. Can you share more color on the study rationale and the designs?

Sure. I will turn to Kumar. Yes, I think a lot of thought went into study designs with PITOLISANT HD to optimize those opportunities. And Kumar can share some highlights of the trial designs.

Right. I mean, PITOLISANT HD. This is an optimized formulation of pitolisant with doses up to 2x the highest labeled dose for WAKIX along with the gastro-resistant coating, 2 studies, 2 Phase III registrational studies, 1 each in narcolepsy and idiopathic hypersomnia. Both of these studies were initiated in fourth quarter of 2025. We anticipate top line data in 2027 with PDUFA 2028.

In terms of study design, the first study, narcolepsy, we are running it ONSTRIDE 1. This is a prospective placebo-controlled, double-blind, randomized controlled trial comparing PITOLISANT HD with placebo. The primary objective here is to evaluate excessive data and sleepiness and the key secondary objectives are to evaluate cataplexy and fatigue.

The second Phase III registrational study that is in idiopathic hypersomnia branded as ONSTRIDE 2 is also a prospective placebo controlled, double-blind, randomized controlled study comparing PITOLISANT HD with placebo. The primary objective here is to evaluate idiopathic hypersomnia symptoms we have idiopathic hypersomnia symptoms scale. And the secondary objective is to study sleep inertia, another core symptom of idiopathic hypersomnia, for which there are no approved treatments.

Thank you. You mentioned in your presentation the top line readout from the Prader-Willi study. Can you provide your thoughts on the unmet need and the opportunity for the pediatric extension and exclusivity?

Sure. Yes. So in terms of the Prader-Willi study, there's kind of 2 opportunities there. So Prader-Willi is a disorder. So fundamentally, it's a disorder of hypothalamic dysfunction. And in the hypothalamus, it is both [ hungeratety ] switch, and that's what drives sort of the main symptom of Prader-Willi.

And I think most of you are familiar with the hyperphagia. But right next to that is the sleep/wake switch. So there's a lot of sleep to service in about 50% of patients with Prader-Willi syndrome. And that's the opportunity with regards to Pitolisant looking at Prader-Willi for improvement in excessive day from sleepiness. And then some of the downstream effects related to the behavioral symptoms, looking at irritability of some of the secondary endpoints.

So that's the opportunity towards the indication. And then Kumar can sort of also expand on the pediatric exclusivity opportunity with that study.

Right. I mean we are in Phase III for Prader-Willi syndrome with Pitolisant. This was based off of a positive proof-of-concept study, the results of which were disclosed a couple of years ago. High unmet need, as Jeff mentioned, about half of the patients with Prader-Willi syndrome have significant excessive data and sleepiness and the histaminergic mechanism of action is uniquely situated, is uniquely placed to help with excessive data and sleepiness in this patient population, top line data in the second half of this year.

And if it's positive, we will quickly move to NDA submission and potential PDUFA in 2027. In terms of the [ PEDS ] exclusivity, regardless whether the study is positive or not, this will fulfill the second and the last requirement for us to get [ PEDS ] exclusivity, which is 6 months of additional regulatory exclusivity for WAKIX formulation on top of the longest exclusivity for Pitolisant, which is currently at Q1, 2030. So at 6 months, it takes us to Q3 2030. And there's a significant opportunity, significant commercial opportunity for WAKIX.

Thank you. And now moving on to the Orexin assets. Why do you believe the Harmony's Orexin asset is best-in-class? And when do we expect clinical data?

So the Orexin space, I think, as you're all aware, a very interesting, exciting space, a lot of discussion around that. I think Kumar can share with you why we feel we have a potential best-in-class Orexin 2 agonist based on some of the features, what we've seen in the preclinical data and what's in store in the clinical program.

There is a lot of excitement about Orexins and we are excited as well with our own Orexin-2 receptor agonist. BP1.15205, we believe, based on the data that we could potentially be the best in class. #1, it continues to be the most potent Orexin receptor agonist that's out there. The potency is in terms of nanomolars n fact, it's 0.015 nanomolars to be precise, good selectivity, good safety data in the preclinical models and potential for once a day dosing.

The efficacy in the preclinical model, Jeff was talking earlier, it was demonstrated, we're at a dose of 0.03 mg per kg in transgenic mice model of narcolepsy, we saw significant improvement in wakefulness, which is the lowest dose that is tested in this particular model of narcolepsy.

And in terms of the clinical data.

Well, in terms of clinical data, we started dosing in clinic in single ascending dose healthy volunteer study in fourth quarter of last year, mid-2026 we plan to present the clinical PK data, along with safety and tolerability. And in parallel, we also plan to conduct a sleep-deprived healthy volunteer study. And we'll disclose the data when they are available.

Thank you. And now moving on to financials. You provided guidance today. Can you tell us some of the puts and the takes of achieving your overall guidance?

Sure. Sandip?

Yes. Look, we're very excited about the guidance this year, as Jeff said, guidance on top line revenue of $1 billion to $1.4 billion for this year with Orexin narcolepsy. And the key drivers are a lot of the things that we I mean we have great momentum coming out of Q4 of this year -- I mean last year, we had $868 million in sales, 21% growth overall, really quite remarkable for a product at year 6 of commercialization to still be growing at 20-plus percent growth.

So we have great momentum, not only from a top line perspective. But also, if you take a look at the net patient adds as Adam shared, we've seen great momentum of 400-plus add in the last 3 quarters, 1 of some of the strongest trends we've seen. And a lot of it is really driven by the unmet need in the space and in the total number of patients.

I mean, we still have opportunity 80,000 patients that have been diagnosed with narcolepsy and we're about 8,500. So really significant opportunity to continue to grow the brand. And we look forward to executing on it this year and achieving that $1 billion plus that we've been talking about for several years.

Thanks, Sandip. Adam, any additional color?

I think Sandip explained it very well, absolutely. We believe we have that significant market opportunity remaining with a highly differentiated product very effective team that has a lot of experience, and that is essentially what is fueling the growth momentum this 2025 and into '26.

And then just last question for me. You have a very healthy balance sheet, as you mentioned in your presentation. You're very profitable with $770 million on the books at the end of Q3. How are you thinking about capital deployment and allocation?

Yes. So obviously, we've been very fortunate with regards to our profitability and the success of the WAKIX franchise. So I alluded to it. Business development is a top priority with regards to putting our cash to work off the balance sheet and investing in new opportunities. So we have a dedicated business development team. They're always scouring the landscape for good opportunities, we have a clear strategy in terms of our sweet spot in the orphan rare sort of neuro site space, also looking at some adjacencies, larger indications in neurology, if the opportunity is, right.

We have been -- we spent a lot of time as a management team and with our business development team doing diligence. We've gone deep on several, and the plan is to deploy that capital drive greater value through building out the pipeline. We have a little more focus now on commercial assets on market to diversify the commercial portfolio. And I think that's sort of the initial thinking and where the focus is. Sandip, any?

No. I think we're well positioned. Like I said, we continue to generate positive cash flow every quarter because at the end of quarter 3 last year, we had over $770 million on the balance sheet and more highly profitable. So we're really looking at opportunities to continue to redeploy that capital to drive value for shareholders. But we're going to be disciplined and thoughtful about how we do it. So that makes sure there's a good synergy with everything that else that we're doing, and we're going to stay very focused to CNS.

Thank you. And that concludes our presentation. Please join me in thanking the management of Harmony.

Thanks, everyone.

Good morning. My name is Madison, and I will be your conference operator today. At this time, I would like to welcome everyone to Harmony Biosciences Third Quarter 2025 Financial Results Conference Call. [Operator Instructions] Please be advised that today's conference may be recorded. [Operator Instructions]

I will now turn the call over to Matthew Beck. Please go ahead.

Thank you, operator. Good morning, everyone, and thank you for joining us today as we review Harmony Biosciences third quarter 2025 financial results and provide a business update.

Before we start, I encourage everyone to go to the Investors section of our website to find the materials that accompany our discussion today, including the reconciliation of our GAAP to non-GAAP financial measures. At this stage of our life cycle, we believe non-GAAP financial results better represent the underlying business performance.

Our speakers on today's call are Dr. Jeffrey Dayno, President and CEO; Adam Zaeske, Chief Commercial Officer; Dr. Kumar Budur, Chief Medical and Scientific Officer; and Sandip Kapadia, Chief Financial and Administrative Officer.

As a reminder, we will be making forward-looking statements today, which are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties. Our actual results may differ materially, and we undertake no obligation to update these statements even if circumstances change. We encourage you to consult the risk factors referenced in our SEC filings for additional details.

I would now like to turn the call over to our CEO, Dr. Jeffrey Dayno. Jeff?

Thank you, Matt. Good morning, everyone, and thank you for joining our call today. I want to start off by saying how proud I am of the Harmony team and their exceptional performance this quarter. It reaffirms Harmony's reputation for executional excellence. As we have shared, Q3 was a very strong quarter for Harmony. We reported $239.5 million in net revenue for the quarter, representing 29% growth year-on-year. And with this momentum, we recently raised our net revenue guidance for the year from $820 million to $860 million, taking it up to $845 million to $865 million. We had robust cash generation of $106 million, bringing our balance sheet to $778 million as of September 30.

But what I am most proud of is that this performance was driven by the highest number of quarterly patient adds for WAKIX since our launch with an average of 500 patients added this quarter, resulting in an average of 8,100 patients on WAKIX at the end of Q3. Our Chief Commercial Officer, Adam Zaeske, will next be providing more color on some of the things his team is doing to drive this strong momentum in our WAKIX business. There are many different ways to measure impact. Delivering innovative treatments to patient populations living with unmet medical needs is a very meaningful one. With this sustained momentum, we believe WAKIX is rapidly approaching a $1 billion-plus blockbuster status in narcolepsy alone.

Along with our very strong commercial business, Harmony also has a robust late-stage pipeline with multiple catalysts coming over the next several years. We continue to have firm conviction in our pipeline and full confidence in our R&D team to successfully execute on these programs. In fact, the IND for pitolisant HD, our pitolisant high-dose formulation has been submitted to FDA, and we are on track to initiate 2 Phase III trials, one in narcolepsy and in idiopathic hypersomnia or IH before the end of the year. Kumar will provide an update on our pipeline programs later in the call, including an update on the RECONNECT study in Fragile X syndrome.

Turning to our balance sheet. With over $778 million in cash and cash equivalents, a disciplined approach to capital deployment and a team with extensive industry experience, Harmony is well positioned to strategically pursue value-enhancing assets to add to our pipeline and build a broader product portfolio. That is our intent and a key component of our vision to become the leading patient-focused CNS company, delivering innovative treatments that can help even more patients living with unmet medical needs.

We believe that we have built something rare in our industry, a profitable, self-funding biotech company with an innovative catalyst-rich pipeline poised to deliver meaningful value for both patients and our shareholders. It is because of this unique profile that we continue to execute from a position of strength. And coming off of our exceptional Q3 performance, we believe that Harmony is one of the most compelling growth stories in biotech today.

With that, I'll turn the call over to Adam Zaeske, our Chief Commercial Officer, for an update on our outstanding commercial performance. Adam?

Thank you, Jeff. Harmony's Q3 2025 results were the strongest we've seen since launch. WAKIX delivered $239.5 million in net sales for the quarter, representing nearly 30% year-over-year growth in its sixth year on the market. WAKIX achieved a record increase in approximately 500 average patients for the quarter. This represents the highest quarterly increase we've ever seen and comes after the Q2 increase of approximately 400 average patients, which has only been achieved twice previously. As a result, WAKIX achieved approximately 8,100 average patients for Q3, exceeding our previous guidance of achieving nearly 8,000 patients by a full quarter. The foundation of WAKIX performance has always been the unique position WAKIX owns as the only nonscheduled treatment option, resulting in its broad clinical utility.

WAKIX enjoys extremely high brand awareness, is perceived as efficacious and well tolerated and is supported by broad payer coverage that has remained consistent for years. In addition to this, I'd like to highlight some recent areas of focus. We have adjusted our field sales deployment, call plan and messaging and continue to deliver sound sales execution. We've refined our promotion and messaging. We've secured important new payer coverage wins, which continue to expand our already broad payer coverage. And we have made improvements in how we support patients moving from a WAKIX prescription to dispense, reflected in higher rates of conversion and shorter times to dispense.

Much of what we're focused on are the fundamentals from sales execution, marketing and promotion, payer coverage and patient support. The adjustments we are making are delivering results, and we will continue to look for additional opportunities in all areas moving forward. As we look to the fourth quarter of 2025, we expect continued growth in average number of patients and momentum. As a result, we recently raised our full year revenue guidance of $820 million to $860 million to the high end of the range between $845 million and $865 million, and we are rapidly approaching achieving $1 billion plus in annual revenue from narcolepsy alone.

Looking to the future, the pitolisant GR and HD formulations each target significant unmet patient needs while extending our growth potential with utility patents filed through 2044. Early feedback from physicians and payers on the HD formulation has been particularly encouraging, and we will be able to leverage our commercial infrastructure to drive the next phase of growth through our pitolisant franchise formulations.

In summary, the performance of our business has never looked better, fueled by a highly differentiated product, a focus on fundamentals and excellent execution across the organization. We are confident in our continued growth and performance moving forward.

And now I'd like to turn the call over to our Chief Medical and Scientific Officer, Kumar Budur, to discuss the advancements in our clinical development programs. Kumar?

Thank you, Adam. Good morning, everyone, and thank you for joining us today. We continue to make good progress in R&D with 3 Phase III registrational studies ongoing and anticipate up to 5 Phase III registrational studies in 5 distinct indications by the end of the year. And we have some important updates to share on the next-gen pitolisant programs.

Starting with our Sleep/Wake franchise, we continue to make significant progress across our next-gen pitolisant programs. I'm pleased to report that we have submitted the IND for pitolisant HD to the FDA. The pitolisant HD program, an enhanced formulation with an optimized PK profile and higher dose, targeting enhanced efficacy for excessive daytime sleepiness and pursuing a differentiated label with an indication for fatigue in narcolepsy is on track for Phase III initiation in Q4 2025.

Similarly, the Phase III study with pitolisant HD in patients with idiopathic hypersomnia is also pursuing a differentiated label with an indication for sleep inertia, and we are on track for initiation in Q4 2025. The target PDUFA dates for both programs are in 2028. The other next-gen pitolisant formulation, pitolisant GR, is designed to minimize the potential for treatment-related GI side effects, especially since almost 90% of patients with narcolepsy experience comorbid GI symptoms. In addition, pitolisant GR also provides an ability to start at the therapeutic dose range at 17.8 milligrams, eliminating the need for titration, an important differentiation.

To demonstrate this, we conducted a dosing optimization study, which is now completed. We are excited to share that in this study, patients with narcolepsy started pitolisant GR at 17.8 milligram and 100% of the patients, that is all 46 of 46 patients were able to initiate pitolisant GR at the therapeutic dose of 17.8 milligram with no safety or tolerability issues. In addition, 98% of the patients who received pitolisant GR 35.6 milligram at week 2 tolerated the higher dose well. No new AEs or SAEs were observed from this study. Pitolisant GR is a fast-to-market strategy designed to demonstrate bioequivalence to WAKIX formulation. The top line data from the pivotal BE study is on track for Q4 2025 with a target PDUFA in Q1 2027.

Utility patents have been filed for both pitolisant GR and pitolisant HD with potential exclusivity to 2044, securing long-term franchise value. Beyond pitolisant, our Sleep/Wake portfolio continues to advance with BP1.15205, a highly potent orexin-2 receptor agonist demonstrating best-in-class potential in preclinical studies. At the recent SLEEP meeting in Seattle and World Sleep Congress meeting in Singapore, we presented comprehensive preclinical safety and efficacy data that demonstrated efficacy at very low doses across all parameters of interest in a standard transgenic mouse model. We are on track to dose the first subject later this quarter, and we anticipate sharing clinical data in 2026.

In the Neurobehavioral franchise, as we have already disclosed, the ZYN002 Phase III RECONNECT study in Fragile X syndrome did not meet the primary endpoint of improvement in social avoidance, mainly due to higher-than-expected placebo response. This is disappointing for Harmony and for the Fragile X syndrome community who continue to wait for approved therapies. The in-depth review of full data set is ongoing, and we plan to share additional information in the near future.

The ZYN002 program in 22q deletion syndrome has been paused pending the full review of the RECONNECT data. In our Epilepsy franchise, we continue to actively enroll patients in 2 global Phase III registrational trials with EPX-100, the ARGUS study in Dravet syndrome and the LIGHTHOUSE Study in Lennox-Gastaut syndrome. EPX-100, our clemizole hydrochloride is a 5HT2 serotonergic agonist and works we are enhancing serotonergic tone, an established mechanism of action for developmental and epileptic encephalopathies. In addition, it has a unique safety and tolerability profile and the emerging safety profile is supportive of no requirements for additional laboratory or special safety monitoring compared to some of the drugs commonly used in these disorders.

We will be presenting some of the efficacy data from the ARGUS open-label extension study and the safety tolerability data on EPX-100 at the upcoming American Epilepsy Society Meeting in December.

Finally, on behalf of Harmony, I would like to thank all the patients and their families who are participating in our clinical trials as well as the clinical investigators and site personnel for their efforts and commitment in helping us to advance our development programs.

I'll now turn the call over to our CFO, Sandip Kapadia, for an update on our financial performance. Sandip?

Thank you, Kumar, and good morning, everyone. This morning, we issued our third quarter 2025 earnings release and filed our 10-Q, where you'll find the details of our financial and operating results. We delivered strong financial results in the third quarter with our highest quarter-to-date in revenues and cash generation. Our financial performance and profile positions us well to continue advancing our growth strategy for the remainder of 2025 and beyond. We reported net revenues of $239.5 million compared to $186 million in the prior year quarter, representing a growth of 29% year-over-year.

The growth was driven by very strong demand for WAKIX as demonstrated by our record increase in average number of patients, along with an increase in trade inventories of a few days as we head into the fourth quarter. We reported total operating expenses for the third quarter of $114.3 million compared to $81.6 million for the same quarter in 2024. The expenses during the third quarter of 2025 included investments to advance our late-stage pipeline, a $15 million milestone for the completion of the enrollment of the ZYN002 trial as well as continued commercialization of WAKIX in narcolepsy.

We also continue to show solid net income growth. Non-GAAP adjusted net income for the third quarter of 2025 was $63.5 million or $1.08 per diluted share compared to $57.3 million or $0.99 per diluted share in the prior year quarter. We believe non-GAAP adjusted net income better reflects the underlying business performance. Please see our press release for a reconciliation of GAAP to non-GAAP results. As previously mentioned, Harmony ended the third quarter with approximately $778 million in cash, cash equivalents and investments. The balance reflects strong cash generation, resulting in an increase of $106 million in the third quarter. We continue to actively pursue value-enhancing strategic opportunities to deploy our capital to expand our portfolio and drive value for shareholders.

Looking ahead, in 2025, our strong performance through Q3 gives us increasing confidence in our full year outlook. We recently raised our revenue guidance from $820 million to $860 million to $845 million to $865 million. These results also gives us confidence that we are rapidly approaching blockbuster status for WAKIX in narcolepsy alone. With respect to expenses, we expect continued investment in R&D as we advance our late-stage pipeline with the start of 2 Phase III studies for our pitolisant HD programs. As a result, we expect to have 5 ongoing Phase III registrational programs by the end of the year. In addition, we also expect a milestone of $4 million in Q4 related to the initiation of our Phase I trial in our orexin-2 agonist program.

In summary, we had very strong results for this quarter, along with positive momentum going into Q4. That, along with our strength of our balance sheet, puts us in a solid position to accelerate our growth strategy and drive value for shareholders.

And with that, I'll turn the call back over to Jeff for his closing remarks. Jeff?

Thank you, Sandip, and my thanks to everyone for joining our call today and for your interest in Harmony Biosciences. In closing, I am very proud of our team's exceptional performance in the third quarter and energized by our progress.

Let me highlight a few key points to leave you with. First, we delivered a very strong quarter with 29% year-on-year revenue growth, driven by a record number of an average of 500 new patient adds for the quarter. With this sustained momentum, we believe WAKIX is rapidly approaching a $1 billion-plus blockbuster status in narcolepsy alone. Looking ahead, our late-stage pipeline remains robust, and I continue to have strong conviction in our pipeline programs, which are making excellent progress. Lastly, we continue to strengthen our unique profile of being a profitable, self-funding biotech company with an innovative catalyst-rich pipeline poised to deliver meaningful value for patients, providers and shareholders alike. We believe that this is what makes Harmony one of the most compelling growth stories in biotech today.

Thank you. And I will now turn the call back over to the operator for Q&A. Operator?

[Operator Instructions] And we will take our first question from Ami Fadia with Needham.

[ Congratulations ] on the strong third quarter. My first question is just around kind of your guidance. You've obviously raised your guidance. And even if we look at the year-to-date performance compared to the full year 2024, there's certainly acceleration in the new patient adds this year. So if you could sort of elaborate on how you see the trajectory of WAKIX evolving? It's certainly several years into the launch, but it appears that there is acceleration here. So if you could comment on how you see that evolving into 2026 and if that can be sustained? And then I have 1 or 2 other questions.

Ami, thank you for your question. I'm going to turn it over to Adam to speak about in terms of the trajectory of patient adds and the strong fundamentals there. And then Sandip can comment on kind of our thoughts and position on guidance. Adam?

Yes. Thanks, Jeff. Ami, thanks for the question. So yes, performance is going to be driven fundamentally by patient adds. And as you saw, we're extremely pleased with the quarterly increase in average patients of 500. We haven't seen that high of an increase ever since launch. And it comes on the back of a solid Q2 increase of 400 patients, which we had only seen twice previously. And the last time we saw an increase of 400 patients was, I think, early in 2022. So we're very pleased with the underlying performance of the brand and the fundamentals remain strong and that momentum we expect to carry forward into Q4. But Sandip, do you want to share your thoughts on that?

Yes. No, absolutely. As mentioned on the call, I mean, we recently raised our guidance from $820 million to $860 million to $845 million to $865 million. As reflected in the guidance, we saw really good strong demand, as Adam just talked about. We did also see a slight increase in trade inventory during the quarter, which obviously had an impact. As you may recall, in Q2, it was the opposite. We saw a bit of a drawdown. Again, it's typical wholesaler ordering patterns. Thing is it's hard to predict these things as we go into Q4, but we feel very good about the top line demand growth because ultimately, that's what helps drive revenues at the end of the day.

And so what we're seeing, we're very optimistic about top line growth in terms of patient adds as we go into the next quarter. And with regard to revenues, it's really just a question of where we end up with trade inventory sometimes at year-end, it's hard to predict. So again, it's going to be a very strong year, well ahead of our original guidance, again, ahead of our guidance in terms of net patient adds for the year. We had originally guided to about 8,000 patients, and we're well ahead of that as well by year-end. So really, we're going to see great momentum going into the end of the year on top line demand and certainly going into 2026. And of course, we're rapidly approaching blockbuster status for WAKIX.

Yes. Yes, Ami. And I would just add that I think, obviously, we're very pleased with the recent trends, and we're following them in terms of how that will sustain us going into the future. But underlying fundamentals remain very strong. Pleased with, obviously, some of the things Adam has done with the commercial team, and that positions us well going forward.

Great. And my next question was just for Kumar. With regards to the GR formulation, can you give us some color on what were the GI AEs seen with the GR formulation and how did the grade or frequency of those AEs compared to the in-market WAKIX sort of titration in the initial dosing period?

Yes. Ami, thanks for the question. What we are disclosing right now is no new safety or tolerability issues were observed with the pitolisant GR formulation, no serious AEs were observed. The safety and tolerability was, in general, consistent with the established safety tolerability profile of pitolisant GR. We will be disclosing the full data set in upcoming meetings. Haven't decided when exactly. But what's important from the pitolisant GR formulation, Ami, is we initiated 46 patients with narcolepsy with pitolisant GR at 17.8 milligrams. And all of those patients were successfully able to tolerate 17.8 milligrams and about 98% of the patients who went to get 35.6 milligram after 1 week of pitolisant GR, 98% of them were able to tolerate pitolisant GR 35.6 milligram.

And this is an important differentiation because if you look at the medicines that are approved for patients with narcolepsy, every one of them, including pitolisant has some level of titration and getting rid of the titration will have the patients to start at the therapeutic dose range, potentially can experience efficacy earlier, potentially less number of dropouts and potentially better overall patient experience.

If I could just squeeze in one more other quick question. If you could just elaborate on some of the details of what we should expect from the ARGUS open-label extension data at AES in December?

Yes. Thank you, Ami. Yes, we do -- we will be presenting some efficacy data on EPX-100 from the ARGUS open-label extension study. And we'll also be presenting safety and tolerability data from EPX-100 from the same study, ARGUS double-blind randomized study and also the open-label extension study. You'll see the overall efficacy, the safety, tolerability offers an overall very unique benefit risk profile for patients with developmental and epileptic encephalopathies. In this particular instance, particularly the data that we'll be sharing is in patients with Dravet syndrome.

And we will take our next question from David Amsellem with Piper Sandler.

Just a couple for me. First, I wanted to get your latest thoughts on biz dev and M&A, particularly in light of the failure of Zygel. Are you thinking more expansively regarding acquisitions? Are you open to more of a sizable transaction, perhaps a market-ready or commercial stage asset? Just trying to get a sense philosophically for where your heads are at. That's number one. And then number two, looking a bit longer term regarding WAKIX with the introduction of the first orexin agonist coming potentially before the end of '26, and I know it's just NT1, how are you thinking about the trajectory of WAKIX beyond '26, specifically in '27 with oveporexton potentially in the market?

David, thanks for your questions. So first, with regards to biz dev and our sort of thinking there. I mean, it really hasn't changed. We have always been focused on business development, being strategic, thoughtful in how we deploy our capital as we have built out our pipeline, obviously, the Zynerba acquisition and then Epygenix. I think at this point, despite the Fragile X data readout, it doesn't really change our strategy. We have a dedicated BD team focused on sort of search and evaluation. And at this point, it really is our intent with our strong balance sheet to pursue innovative assets to build out our pipeline to grow our product portfolio.

We are actively evaluating several, and that is our plan, but the strategy remains the same. Our focus in orphan rare CNS disorders to be strategic within the current franchises, but also looking at adjacencies potentially in broader neuro indications where we could utilize the proven commercial engine. So the strategy remains the same. I think a bit more focused with regards to our intent to move forward with business development when we find the right opportunities for us. And I'll turn to Adam in terms of thoughts on WAKIX performance in the setting of emergent orexins. Adam?

Yes. Thanks, Jeff, and thanks for the question, David. Look, we're excited about orexins, obviously, because we have one of our own, but it's also an important potential new treatment option for patients. And we remain confident in our ability to grow and perform with WAKIX well into the future. And there's a couple of reasons for that. The first is just the approach to therapy in this market. The hallmark of treatment is polypharmacy. You have a high majority of patients that are on 2 or more therapies, and that will continue. We've recently verified that in market research that we've done speaking with physicians, and they expect that to continue as well.

But also, if you just look at the history of WAKIX, WAKIX performance has been extremely steady regardless of new entrants, whether it's brands or generics. And we would expect that to continue as well. In fact, if you look at kind of the narcolepsy market in total, any time there's been a new brand entrant, it tends to expand brand utilization. And we would expect a similar phenomenon with an orexin launch when those come to market. But we're also highly confident just because WAKIX is a highly differentiated product. It's the only nonscheduled treatment option.

Physicians will have had 7, 8-plus years of clinical experience by the time of orexins launch, and it holds a unique position in the minds of health care providers. They're highly familiar with it, provides strong efficacy and is -- and they believe it's very well tolerated. So it can be added to combinations of therapies across a very broad selection of narcolepsy patients, and that will continue as well. We continue to hold that position. So for those reasons, I think we're very confident in our continued growth and performance well into the future.

And we will take our next question from Graig Suvannavejh with Mizuho.

Congrats on the progress. One question for me, just going back to the 2025 guidance. It was nice to see a raising of the guidance. But if you do the math, it does imply fourth quarter sales for WAKIX in the range of, I think, $221 million to $241 million. And on a quarter-over-quarter basis, that's essentially flat or down on a quarter-over-quarter basis. So can you just provide more color on how we should be thinking about whether it's net patient adds or gross to net or seasonality when trying to model fourth quarter? I know you -- Sandip had mentioned some inventory could be a factor, but any other color would be great on the fourth quarter, especially given the great momentum on net patient adds.

Yes. Thanks, Graig, for the question. Again, I think we saw great demand in terms of top line growth that we expect to continue as we go from Q3 to Q4 as well. I think we did -- as I mentioned, we did see a few days of trade inventory increase in Q3, which impacted the sales positively. Just as I mentioned in Q2, it's quite the other way -- the other direction. Right now, I mean, we feel very good about the range that we've put out there. We recently raised it, as you mentioned. This gives us great confidence and I'm sure like every team, I mean, we'll do everything we can to certainly not only meet but potentially exceed the range as well.

Again, it's hard to predict again Q4 because there are typical variabilities as you come to Q4, especially around brand and holiday and so forth. So we feel good about where it is. It's very robust growth year-over-year. It's going to be a robust growth over prior year. And we see, again, WAKIX very quickly approaching blockbuster status as we go into '26 and beyond.

Great. If I could ask a follow-up. Just your net cash position is building quite nicely. I'm sure there are various views on how to deploy that cash. Wondering if maybe in an answer that might be slightly different from David's question on BD, what are your kind of current thoughts on how best to deploy that nicely accruing cash balance?

[ Sandip ]?

Yes, sure. I mean, look, we -- as Jeff mentioned, I mean, we continue to look for business development opportunities. I think that's been a strategy for us for many years now. And we see attractive opportunities out there that we could potentially transact. And we have, again, a continued growth in terms of cash. We had very strong cash generation last quarter of $106 million, $778 million at the end of the quarter. And I think that gives us increasing confidence that we -- but again, we're going to be, I would say, thoughtful in terms of how we deploy our capital. I think we certainly have multiple ways in which to drive value for shareholders. Certainly, more recently, we've been prioritizing business development. But in the past, we've also done share buyback as well as an opportunity. And again, at the right time, we'll look at various opportunities to drive value for shareholders.

Yes.

Graig, I'll just go ahead. No, no, I appreciate the question. I just want to reiterate, I think while one can never predict the timing in terms of business development transactions, as Sandip alluded to, we have optionality, but our focus and our intent is really to pursue innovative value-enhancing assets. We want to build our pipeline. We see that's where the value is going forward as well as build a broader product portfolio in terms of -- we have a strong commercial engine. We want to continue to utilize that with additional products. So that is our intent, and we have a strong balance sheet to execute on that.

And we will take our next question from Jay Olson with Oppenheimer.

Congrats on the quarter. Can you talk about your life cycle management plan for pitolisant GR and HD with regards to new patients? And then which patients currently on WAKIX are the best candidates to benefit from GR and HD? And then for your orexin-2 program, what would you like to learn from your Phase I study? And any lessons learned from the Alkermes and Takeda data at World Sleep?

Yes. Jay, thanks for your questions. Adam, our life cycle management strategy with regards to patients that would benefit from the formulation.

Yes, we're really excited about the 2 life cycle management formulations, the GR and the HD. GR is kind of a fast-to-market strategy. And the strategy there would be any patient -- any new patients that would have been prescribed WAKIX would be prescribed the new pitolisant GR formulation as well as we have the ability because we obtain consent from patients when they start WAKIX therapy. We would also be able to recontact patients that may have been on WAKIX previously but have discontinued to see if pitolisant GR could be an option for them to consider as well. So for GR, it's really around new WAKIX patients and previous patients.

And then where the HD comes in with a greatly differentiated profile, we would see the strategy there focusing on not only new WAKIX patients and previous patients, but also existing WAKIX patients. And that's where the transition potential comes in. And we've conducted market research around this. HCPs respond very favorably to the profile of HD. They view it as clinically significantly differentiated, actually superior. And in market research, they tell us they would consider transitioning the majority of their patients that maybe are better but not well. And so that's the strategy for HD. And then both formulations have utility patents filed through 2044. So it really allows us to expand and extend our Sleep/Wake franchise well into the future.

In terms of our [ orexin-2 ] agonist program and learnings from some of the other development programs.

Sure. Thank you, Jeff. Jay, thank you for the question. Yes, we are on track to initiate the Phase I study with our orexin-2 receptor agonist this quarter. As we have disclosed in the past, we will be starting a healthy volunteer single ascending dose study. And in parallel, we'll be conducting a sleep-deprived healthy volunteer study as well to bracket the dose a bit. And we are closely watching the data that came out of World Sleep Congress from other orexin receptor agonists, especially as it relates to dosing and the safety and tolerability profile alongside the efficacy.

We have one of the most potent orexin receptor agonists based on all the publicly available data, and it lends itself to target the central [indiscernible] on NT2 and idiopathic hypersomnia at very low dose, providing us the dosing flexibility to target these 3 indications. And we are also trying to see how we can accelerate our own program based on the data that is coming out from the other orexin receptor agonists. And you'll be hearing more from our own orexin receptor agonist when we initiate the first-in-human study. And we also anticipate to share some of the clinical data in 2026.

And we will take our next question from Pete Stavropoulos with Cantor Fitzgerald.

Congratulations on the progress. Could you just touch on EPX-100 epilepsy program? Any clinical data that has been generated and disclosed that sort of gives you confidence in the Dravet and LGS program? Any details on efficacy, durability and safety? And can you also give us a sense of how enrollment is going in the Phase III studies? Any granularity on timing of data or when you expect to complete enrollment?

Pete, thanks for your questions. I'll turn to Kumar for some more color on the EPX program.

Yes, Pete, thank you for the question. Yes, I mean, we are excited to share some of the efficacy data at the upcoming American Epilepsy Society meeting in December. As I mentioned earlier in the call, we will be sharing the data from the ARGUS open-label extension study, that's the study in Dravet syndrome. In terms of your question around recruitment and enrollment, yes, I mean, we continue to recruit patients in both ARGUS study and the LIGHTHOUSE Study, that's Dravet and LGS studies, and we anticipate to share top line data in 2026. We'll be providing more granularity in terms of time lines as to the progress with the enrollment.

And any thoughts on taking EPX-100 into other DEEs or other DEEs remain the focus of EPX-200?

Yes, Pete, great question. Thank you. Look, there is this discussion around DS, LGS pursuing separately versus going with a broader DEE indication, right? So there are pros and cons with each of these approaches. But right now, we are focused -- laser-focused on Dravet syndrome and Lennox-Gastaut syndrome. We want to keep it that way, mainly to maintain the homogeneity of the patient population and try to get to the top line data as soon as possible and try and help these patients with a product profile, which is very favorable, not just from an efficacy perspective, but also from a safety and tolerability perspective.

Yes. And Pete, maybe one addition just to remind everyone. So EPX-100, clemizole hydrochloride. So a first-generation antihistamine that was in the market for about 20 years with a proven safety tolerability profile. And in the overall sort of risk benefit in these sort of therapeutic options with other indicated agents such as Epidiolex and the need to monitor LFTs or FINTEPLA with echocardiograms required in the REMS program because of cardiac valvular disease, the risk there. So there is sort of a proven safety tolerability profile. And in the overall kind of risk benefit, we see the opportunity there as we go forward and generate efficacy data in both Dravet and LGS.

And we will take our next question from Danielle Brill with Truist Securities.

Congrats on the quarter. Maybe just 2 quick ones from me. Do you have any sense of what proportion of your 8,100 patient base is NT1 versus NT2? And then what findings, if any, in the Fragile X data set would make you consider reactivating the q22 (sic) [ 22q ] trial?

Danielle, thanks for your questions. Adam, breakdown of patients on WAKIX.

Sure. Thanks for the question. It's been very consistent actually for the last several years. We see about 45% of patients from NT1, 55% from NT2, and that's been very stable.

Okay. Kumar?

Yes. Danielle, thank you for the question. We are right now conducting an in-depth review of all the data from the RECONNECT study. As mentioned previously, the Fragile X syndrome study did not read out as expected, mainly because of the larger-than-anticipated placebo response. Right now, we are conducting a number of post-hoc analysis. It's very hard to say at this point in time what kind of data sets we need to see before we embark upon 22q deletion syndrome Phase III study. Once all these data sets are available, we will make a decision based on the data that we see. And we should be able to complete this work by the end of this year, and we should be able to provide some update on the Fragile X syndrome study itself and also the implications on 22q deletion syndrome early next year.

And we will take our next question from Corinne Johnson with Goldman Sachs.

This is [ Anupam ] on behalf of Corinne. Maybe one question for Kumar. Can you talk about the effect size you are powering for the Phase III pitolisant HD study to show on ESS scale? And what do you think a clinically meaningful difference would be in comparison to the current WAKIX in order to support the HD use? I think the WAKIX shown around 12- to 13-point final ESS score. Any color on that?

Thank you for the call -- thank you for the question. Look, I mean, pitolisant HD, it's an enhanced formulation -- it's an enhanced next-gen formulation. It's not just the high-dose, but it's also -- it also has an optimized PK profile. Based on the dose response that we have seen with pitolisant in the pivotal narcolepsy clinical trials and also the studies that we conducted in Prader-Willi syndrome and also in myotonic dystrophy and the dose -- and the exposure response data, some of the exposure response data that we have, we anticipate a meaningful increase in the efficacy from an excessive data and sleepiness perspective.

But it's also important to note that we are not just targeting excessive data and sleepiness. We are also targeting fatigue in patients with narcolepsy for which there are no approved treatments. And we are also targeting sleep inertia in patients with idiopathic hypersomnia for which there are no approved treatments. And we plan to accomplish all of this without compromising on the safety or tolerability profile of pitolisant. In fact, we conducted a Phase Ib study where we studied pitolisant up to 180 milligrams, which is up to 5x the maximum label dose of WAKIX. And the safety and tolerability profile in general was similar to what we see with WAKIX.

So what it means at the end of the day is a very unique benefit risk analysis with established safety profile, established tolerability profile, larger efficacy in excessive daytime sleepiness, targeting symptoms like fatigue in narcolepsy, targeting symptoms like sleep inertia in patients with idiopathic hypersomnia, all while maintaining the nonscheduled status and a very simple dosing regimen of taking pill in the morning. So that's what we plan to accomplish with pitolisant HD.

And we will take our next question from Patrick Trucchio with H.C. Wainwright.

I was wondering if you could elaborate a bit more on the sustainability and as well the drivers of the record approximate 500 patient add in the third quarter. And if we should expect those drivers to continue in the fourth quarter, but as well in 2026? And then separately, on pitolisant HD, I think you mentioned strong early feedback from physicians and payers. I'm wondering if you could elaborate on what's resonating most and as well the implications for the Phase III development program.

Patrick, thank you for your questions. Adam?

Yes. Thank you for the question. So we're really pleased with the momentum we're seeing in increases in patient adds, as you mentioned. And the drivers, look, I think it starts with WAKIX is a highly differentiated product. It's the only nonscheduled treatment option. And that is combined with strong execution across the organization. So if you think about sales effectiveness and execution, marketing and promotional excellence, payer coverage, patient support, we've made adjustments in all of these areas. And we're seeing those adjustments delivering the performance that you're seeing and have confidence that, that momentum will definitely carry forward in Q4 and into 2026.

Okay. And Patrick, your second question?

Yes. So around the HD. And so what resonates, what resonates is the promise of improved efficacy, the no titration starting at a therapeutic dose and unique indications, especially around IH and fatigue. We know that 60% of narcolepsy patients present with fatigue. This would be the only product that has the indication for fatigue in narcolepsy. And they view that as highly differentiated. So I mentioned the feedback from HCPs, but we've also done research with payers. And the response is that we would expect broad payer coverage for the HD product with minimal step edits for WAKIX or no step edits actually prior to LOE. And even after LOE, only some mentions of perhaps some step edits, but only for patients that have never had any experience on WAKIX before, which at this point, I guess we'll be at, what, 8-plus years in the market by then.

The vast majority of patients will have had some experience with WAKIX at some point in the past. And then, of course, any patient that presents with fatigue would also not be subject to any step edits through WAKIX even post LOE. So we would expect broad payer coverage pre and post LOE supporting the product and its uptake.

And we will take our next question from Jason Gerberry with Bank of America.

This is [ Bhavan ] on for Jason. Just 2 questions from us. The first is on EPX-100. You have 2 Phase III readouts expected in 2026. So maybe if you can just speak to what you've learned from the Fragile X syndrome as well as the prior idiopathic hypersomnia study about managing placebo response in these types of neurodevelopmental studies? And then the second question is on WAKIX. Can you just speak to where new patient growth is coming from? Are you activating new prescribers? Or is the growth primarily from deeper penetration within existing writers?

Thanks, Bhavan, for your question. Kumar, on EPX-100?

Yes. Thank you for the question. With the EPX-100, I mean, as you know, what we are studying here is the seizure frequency, which is slightly different from what we studied with ZYN002 in the Fragile X syndrome. Placebo response in general is part and parcel of all neuropsych trials, especially psych trials with behavioral endpoints like Fragile X syndrome. And we had multiple checks and balances within the study to manage the placebo response.

With the EPX-100, it's slightly different in the sense seizure frequency is much more observable and much more definitive compared to some of the behavioral symptoms. So these are 2 distinct indications with the distinct endpoints. But to your point, in general, yes, I mean, placebo response can happen in any clinical trials, and that's something that we are watching. And we have checks and balances with our EPX-100 ARGUS and LIGHTHOUSE clinical trials as well.

Okay. Adam?

Yes. And then in terms of WAKIX new patients, so the short answer to your question is we see both new patients from increased penetration of existing writers as well as the addition of new writers. We see quarter-over-quarter a pretty steady increase in new writers every quarter, and that's continued for the past several years, and we would expect that to continue. A little bit more detail. Remember, we call on actually more than 9,000 physicians, and that's 4,000 that are enrolled in the oxybate REMS programs, but also more than 5,000 that are not enrolled in oxybate REMS programs. We have the ability to call on both of those sets of physicians. And in both instances, we see increased penetration as well as new writers.

Yes. And I would just add -- yes. No, thank you for your question. Just to add at a higher level, just to remind everyone that this is a large market. So in terms of the continued growth of WAKIX, a highly differentiated product profile with broad clinical utility, the only nonscheduled product, which is meaningful as a former neurologist treating patients, very meaningful in terms of therapeutic options. But in a sizable market, 80,000 patients diagnosed. So as this market evolves and grows and more understanding, similar with the learning about fatigue as a prominent symptom in patients with narcolepsy, about 60%. So designing that into the pitolisant HD program. So I think that is the backdrop why we are confident, why the underlying fundamentals and the growth of WAKIX in narcolepsy and our excitement and confidence in the pitolisant HD program and pitolisant GR, I think that has a lot to do with it as well.

Yes, I think it's a great point, Jeff. I mean the fact that we're at 8,100 average patients now in a market of over 80,000 diagnosed patients, obviously, we have a lot of room to continue to grow.

Yes. And also in a polypharmacy market, I think as you're all familiar with, where any chronic neurologic disorders, it's rare that a single mechanism of action will be able to treat difficult-to-treat chronic symptoms. And I think this is what we're seeing as WAKIX continues to grow.

And we will take our next question from Ash Verma with UBS.

Yes. So maybe just I wanted to get your latest thoughts on how you're thinking about the overall pipeline and diversification. I mean we've seen 2 different setbacks recently, first on the IH side and then on Fragile X. What gives you the confidence that the subsequent pipeline programs have higher chances of success? And then on the WAKIX $1 billion guide, is that something that you can achieve in 2026 just at the pace at which you're going and where 4Q is annualizing at? With Takeda's orexin expected to launch in 2027, what's your level of urgency to hit the long-term guide before the competitor entry?

Yes. Thank you, Ash. Let me start with the first question about our pipeline. And I just want to reiterate that I continue to have strong conviction in our pipeline programs, Kumar's leadership in our R&D organization, which has a lot of experience and expertise. We don't have time, but if you look at each of -- if you look at the IH study, if you look at Fragile X, there are good reasons in terms of the outcomes that we've sort of talked about. In the ZYN002 program, in talking with KOLs, unfortunately, that pattern, programs where there were positive Phase II data and a lot of expectation because there are no approved treatments and a high placebo response rate kind of got into multiple Phase III programs, which is the reason why none have been successful. We have learnings from that, and we will take those learnings going forward. But I think I continue to have conviction in EPX-100, our other pipeline programs. And Kumar, any additional thoughts?

Yes, I think you covered it.

Okay.

Yes. And then thanks, Ash, for the question around achieving $1 billion in revenue. Obviously, it's a little bit premature to provide guidance for 2026 specifically, but we're seeing very strong momentum as you saw in Q3 and in Q2. We'd expect that momentum to continue in Q4 and well into 2026. And we're confident we will achieve $1 billion in revenue well before LOE. So confidence remains high.

And we will take our next question from David Hoang with Deutsche Bank.

So I want to ask on eligible patients for WAKIX -- sorry, pitolisant HD and GR. I think for HD, you mentioned new, previous and switch patients, I think, are all on the table. Just wondering what, in your mind, defines a good switch patient for going from WAKIX to HD? And then is switching -- would switching be an option for GR patients?

Thanks for the question. So I guess the switch patients, obviously, that's going to be determined by the health care provider, but we know that 75% of patients with narcolepsy continue to struggle with residual symptoms.

And so if we're able to offer the HD product with an improved efficacy profile, but the same safety and tolerability profile that they're very familiar with on WAKIX, we would expect HCPs to consider their patients that potentially could benefit from a boost in efficacy and feel confident that they won't be introducing any new safety or tolerability issues. And also any patients that present with fatigue. And as I mentioned before, we know that 60% of patients with narcolepsy do present with fatigue. Those would be prime candidates for the HD as well. And then for the GR, yes, I mean, a switch would be an option certainly for the health care provider. In terms of our strategy, we'll be focused on new patients and previous patients, as I mentioned before.

And I'm showing no further questions. I would now like to turn the call back for any closing remarks.

Thanks, operator. On behalf of the Harmony team, I want to thank everyone for joining our call today and for your interest in Harmony Biosciences. Have a great rest of your day. Thank you.

This does conclude today's Harmony Biosciences third quarter 2025 financial results conference call. You may now disconnect your line, and have a wonderful day.

Welcome to the Cantor Global Healthcare Conference. I'm Pete Stavropoulos, biotech analyst with Cantor. With us, we have Harmony Biosciences, a company I cover. Pleased to introduce Jeffrey Dayno and Sandip Kapadia. So welcome, and let's start off with a brief intro and a description of Harmony.

Yes, sure. Thanks, Pete. Thanks for the invitation on behalf of the Harmony team. Good to be here with you. Jeff Dayno, President and CEO of Harmony Biosciences, neurologist by training, 10 years in clinical academic medicine, 27 years in the industry now and through many different from big pharma to evolving biopharma and biotech. And I've been with Harmony since the beginning when we launched the company in October 2017. and really excited for the opportunity of growing the company, growing the pipeline ahead. And with me, Sandip Kapadia, Chief Financial Officer. Sandip?

Yes. No, I mean, similarly, 25-plus years in the industry in biotech, both combination of large pharma as well as biotech as well and been here for the last 4 years. So...

I'm just going to ask what do you like better? Large pharma or biotech.

Biotech.

Biotech, much more dynamic, more exciting.

In terms of -- no, it's great to be here. So overview of Harmony for those not familiar, as I mentioned, launched in the fall of 2017. And really, the theme is we continue to be kind of a growth story from sort of our commercial franchise and the successful launch and commercialization of WAKIX in narcolepsy. That continues to grow in a sizable market of about 80,000 patients diagnosed with narcolepsy. From there, we have the next-gen pitolisant programs that are advancing and excited about those opportunities. We can dive into those. And really, the story from there over the past 2 years is building out our pipeline. And I think if you look at our pipeline, sort of robust late-stage catalyst-rich pipeline.

And if you look across the industry, in the orphan/rare neuro space, we think it's one of the most exciting pipelines in that space given the opportunities that we are working on. In sleep/wake, we obviously have WAKIX, our commercial product, the next-gen products and then an early phase orexin 2 agonist in that pretty exciting space. pretty exciting. And then we also have a rare epilepsy franchise based on our acquisition of Epygenix Therapeutics. And we've got EPX-100 in the clinic, a serotonin agonist in Phase III trials for both Dravet syndrome and Lennox-Gastaut syndrome. And those are advancing in Phase III in those rare epilepsy patient populations. And then I think an exciting in terms of our neurobehavioral franchise, the third of our 3 orphan/rare neuro franchises. And based on the acquisition of Zynerba Pharmaceuticals, we brought in ZYN002, and we are in our pivotal Phase III program and on track for top line data readout later this month in Fragile X syndrome.

So if we take a step back in terms of our pipeline, 8 assets across 13 development programs, up to 6 in Phase III by the end of the year. Each of these 3 franchises have peak sales opportunities of $1 billion to $2 billion each. And this pipeline is poised to deliver one or more new product or indication launches each year over the next several years. And the one right ahead of us that we're very excited about is ZYN002 in patients with Fragile X.

And that's where we should start off with. So what is the biological and mechanistic rationale for 002 in Fragile X?

Yes. So in terms of -- if we look at ZYN002 and Fragile X, kind of break it down -- with regards to the mechanistic fit, I think the uniqueness, sort of the innovative product itself, and then we can look at the data. So let me just kind of walk through that. So Fragile X syndrome is the most common known cause of inherited intellectual disability and autism spectrum disorders. It's based on -- Fragile X is a defect in the FMR1 gene. And that defect causes a lack of production of FMR protein. So with regards to the effect on that is disruption of the endocannabinoid system in the brain. So ZYN002 works at CB1 receptors in the brain to sort of generate homeostasis and of the endocannabinoid system. And disruption in that system is what causes the neurobehavioral symptoms.

So the mechanistic fit is explained by the underlying pathophysiology of disruption of the endocannabinoid system and ZYN002, especially through transdermal delivery, which causes -- results in steady-state plasma levels helps to generate homeostasis and regulate that system.

In terms of the product, so we see ZYN002 as an innovative product because I think the analog that's often considered is a product called Epidiolex, which is in the market for the rare epilepsies. The difference is that product is a plant-based cannabidiol that has THC, which is not good for kids with Fragile X and also has some rate-limiting GI tolerability issues because it's delivered orally, and it also causes elevation in LFTs that you have to follow. So ZYN002 is a very different product profile. It's a purely synthetic pharmaceutically manufactured product devoid of THC. That has a patent-protected permeation enhanced gel formulation, and it's delivered transdermally through the skin, and that results in steady-state blood levels.

Those steady-state levels help regulate and control the endocannabinoid system. So we see there is a fit in terms of mechanistically, there's innovation in the product. And then if we look at the data with regards to where we are. So the Phase III RECONNECT trial that we are working towards top line data readout before the end of the month, what we're trying to do is replicate the positive findings from the Phase II CONNECT study. So Phase II CONNECT study in patients with Fragile X, over 200 patients, so a sizable study in the Fragile X community. And what it showed is in the subset of patients with complete methylation, and I'll come back to that, the importance, it showed a statistically significant and clinically meaningful outcome in the subset of patients with complete methylation of the FMR1 gene.

So the importance of that is the Phase III RECONNECT study is trying to sort of replicate those findings along with the learnings from the Phase II CONNECT study. So primary analysis in Phase III RECONNECT is in patients with complete methylation, right? We saw in Phase II CONNECT that patients continue to improve beyond the 12-week endpoint out to 16 weeks, which is consistent with the mechanism because if you are driving homeostasis of the endocannabinoid system, over time, patients continue to improve. So the endpoint in Phase III RECONNECT is out to 16 weeks in terms of the primary readout.

Rather than 12. Okay.

Rather than 12 weeks. Right. And then we also saw a dose response in the Phase II CONNECT trial. So for patients over 50 kilograms, we added a third dose, a higher dose to ensure that there was enough drug on board to drive a therapeutic response. So given those design sort of enhancements, the learnings from Phase II CONNECT into Phase III RECONNECT, we feel confident and have a high degree of conviction in terms of the readout of the Phase III RECONNECT trial.

All right. When you look at the data from the CONNECT trial, especially when you cut it by subgroup, was there a sufficient amount of patients who actually had fully methylated versus not? And so like is there a strong signal there and do you feel comfortable?

Yes. I mean I think that, again, Phase II CONNECT was a large study, over 200 patients. So as this area has evolved, the importance of sort of what's called the methylation status of the FMR1 gene was becoming kind of more recognized. So the importance is patients with complete methylation of the FMR1 gene have more severe symptoms. So there's little to no FMR protein, which is what stabilizes the endocannabinoid system. So that subgroup, which was about 80% in the Phase II CONNECT study is where you can show greater benefit, greater efficacy and it's more predictable. So about 80% in that study. And in the Phase III RECONNECT, we're looking for a similar target, about 80% of patients with complete methylation and then there will be about 20% of patients in that cohort with partial methylation.

The importance of that, Pete, is in discussions with FDA, the primary endpoint is in the subgroup of 80% with complete methylation around the social avoidance subscale. If we see similar trends in the 20% patients with partial methylation, then we'll have an opportunity potentially for a broader label in the entire Fragile X patient population. The importance of that is the backdrop here is that there are no approved therapies for patients living with Fragile X. So if successful, if we have positive data, and this is what we're excited about, we could be on the path to the first approved treatment for patients living with Fragile X.

And hopefully, they show some flexibility and directionality can have an impact on the label.

Yes. So we've had good interactions with the agency in terms of concurrence on trial design, on primary outcome, on the instrument that we're using to measure the social avoidance. And so we've made very good progress there.

So one question that I have when I was going through clinicaltrials.gov as well as CONNECT. So CONNECT had a placebo run-in period where the subjects needed to -- need a certain score on social avoidance and the irritability subscales. They were then sort of rescreened after 2 weeks and those that met the certain criteria, which included those thresholds on social avoidance and ability again and had no more than a 30% improvement during the placebo run-in with then randomized. And so how does that sort of impact the probability of success and you have the same run-in period for RECONNECT?

Yes. So you've done your homework in terms of the trial design. And so I think what you're describing is the placebo run-in phase of the trial. And it's not uncommon in neuropsych trials with regards to managing a placebo response. So using a placebo run-in to sort of manage and exclude placebo responders is a common approach. So we have taken the same approach in the Phase III RECONNECT trial in terms of using a placebo run-in phase. We've not -- we purposely haven't disclosed the details around that while the trial was being conducted because we didn't want to sort of upset the blind or give any indication of that. But when we present all the data, then we'll describe what the placebo run-in phase look like and the criteria. And it will be similar to what you saw in the CONNECT study.

Which I believe was 33 or so patients.

It's about -- yes, 30% placebo response.

Okay. Walk us through the primary endpoint. Help us understand what the ABC FCS subscale 1 social avoidance is as well as the key secondary, which is the durability score. And what's clinically meaningful for these scales or subscales?

Yes. So the primary endpoint in the Phase III RECONNECT trial is on social avoidance measured by -- so the ABC, aberrant behavior checklist community version for Fragile X, specifically for Fragile X and measuring the aspects of social avoidance. And that is what was used in the Phase II CONNECT study, carried forward to Phase III RECONNECT and in agreement with FDA. A clinically meaningful outcome is within a 3-point difference within patient difference on that scale.

In terms of the Phase III RECONNECT statistical analysis, right? It is a -- what would define a positive study being statistically significant is a placebo-adjusted 1-point difference between active and placebo on that scale. And that is also recognized as clinically meaningful, and that's how the study is powered and demonstrating stat sig on that outcome would define a positive study and I think a path forward towards regulatory approval.

Okay. What endpoints will be shared on the top line readout? And just help frame, which I guess you just did, what a positive outcome would be. But just sort of to take a step back, what exactly just can you describe what it is exactly social avoidance and like on the scale, like what are caretakers sort of looking for and how they're scoring it?

Yes. So a lot of it is a pattern of interaction in terms of these kids interaction. And there's the different components of that 5 or 6 different components of how they kind of interact with others in the environment. And then that kind of makes up that social avoidance subscale. In terms of top line data readout, I think traditionally, we'll be sharing the patient demographics to kind of describe the study population. And then really the primary outcome around the social avoidance, primary endpoint in the patients with complete methylation, some of the key secondary endpoints, the secondary endpoint around the irritability subscale and along with the top line safety and tolerability data, just to kind of give the top line readout of the main components from the study.

I mean, after that, as you know, kind of the full data set and the other outcomes will be shared at a scientific meeting.

And when you look at the CONNECT study and you look at the AE profile, anything concerning? Or do you expect to sort of replicate the same.

Nothing concerning. I think we're expecting the same. And in terms of the benefit risk profile, this product is well tolerated. Again, transdermal delivery. Another benefit of that interesting that some of the KOLs have pointed out, these kids have difficulty taking pills. So that mode of delivery through the skin that the parent or caregiver applies is actually a beneficial aspect. Randi Hagerman, who's one of the top KOLs at UC Davis, has pointed that out recently, and she was an investigator in the Phase II and Phase III trials. So I think that's another benefit there.

Okay. I guess before we move on, how many patients actually are there in the U.S.? And how many of them are actually fully methylated or what percentage of that?

Yes. So looking at the market opportunity. So the prevalence, the Epi data suggests about 80,000 patients with Fragile X in the U.S., about 60,000 patients identified through claims data and then 60% to 70% of patients with Fragile X are fully methylated. So I think that kind of identifies market opportunity there. And I also want to add, there is a follow-on opportunity with positive data readout, we've already been working with the FDA. There's another related condition called 22q deletion syndrome, also known as the Georgia syndrome, which is a related neurobehavioral disorder, similar symptom complex. Zynerba ran a small Phase II open-label study and generated positive signals, positive data. So we've already been engaging with the FDA an agreement around a Phase III pivotal trial design, primary endpoint.

So with positive data, then we're preparing to initiate a Phase III trial as well in 22q deletion syndrome. Both of these programs, we've had interactions with both FDA and EMA. And the importance of that is we have global rights to ZYN002. So with positive data and if we're successful, then we plan not only to file an NDA with the FDA, but we'll also, in parallel, work on preparing an MAA to submit to the European agency.

You've been consistently communicating with the FDA. And I guess one of the concerns with the new administration is -- you've had a lot of movement within the agency. Is it the same individuals that you're interacting with in the division for.

Yes. Actually, it has been. No, it's a great question given the current climate. So it's actually the same division in the psychiatry division that we've been interacting with. And it's also the same individuals we've been interacting with WAKIX, the original approval of WAKIX, pitolisant. And I think we -- Tiffany Farchione is the Division Director. So we've had a lot of regular interactions with that division, and they're very familiar with the ZYN002 program.

Okay. All right. Let's move on to WAKIX. Turning to your commercial success, a successful asset, also known as pitolisant. It continues to grow and it's tracking towards the other $1 billion revenue marker with continuous year-over-year growth. What levers can you pull for sustained and durable uptake until generic entry, which I believe is in 2030s?

Yes. So LOE first quarter 2030, but then -- and we are on track of obtaining pediatric exclusivity, which is important, providing an additional 6 months of regulatory exclusivity, which would take us to third quarter 2030. Big market, a lot of headroom for growth. I know Sandip, if you want to sort of comment on where that's coming from?

Sure. We're now in year 6 of commercialization of WAKIX, and it's been remarkably steady in terms of the growth. of the product over last quarter, quarter 2, we did a little over $200 million in sales, a 16% sales growth overall. So really tracking well. We expect continued growth for the balance of the year and tracking towards our guidance of $820 million to $860 million in terms of sales. Now with respect to some of the levers that you talked about, the business, there's still a large opportunity overall. It's about 80,000 patients that are diagnosed with narcolepsy.

We currently have about -- as of the end of the last quarter, which was a very nice patient add of approximately 400 net patient adds to about 7,600. So you can see there's still a lot of room for continued growth for WAKIX for many more years to come. And what's driving the growth is really -- it's a very differentiated profile. It's the only non-scheduled agent out there. And we have a remarkable team with strong payer access there. And we call on about 9,000 HCPs, which -- 5,000 of which are not in the Oxybate REMS. So we have a broader set of universe of physicians that potentially can also write WAKIX and schedule.

So there's still a lot of opportunity to grow in this polypharmacy market. There's a lot of headroom, as Jeff mentioned. And we have a broad prescriber universe in terms of continued -- so we see continued growth for not only WAKIX, but even next-gen formulations over many years to come.

So next-gen formulations and I guess, life cycle strategy, GR and HD formulations. How are you positioning them to sort of extend and expand the franchise? And what does this sort of mean for mitigating the loss of exclusivity risk in 2030 and preserving brand?

Yes. So I think at a high level, so the life cycle management strategy, so we see WAKIX as obviously a very successful product in the market. The unique product profile, the benefit risk proposition. And when we launched into the market in 2019, it was the first sort of novel mechanism of action in over a decade. And this profile has held up in terms of the continued growth. So what we're trying to achieve out ahead of the LOE in 2030, like you said, is kind of a two-pronged approach. Pitolisant GR, so the gastro-resistant formulation is really a quick-to-market opportunistic approach based on the demonstration of bioequivalence with a target PDUFA date in 2026.

So we're on track for reporting the top line data from the pivotal BE study in the fourth quarter this year. We're also doing a dose optimization study designed to demonstrate where you don't need the titration dose, so patients can start at a therapeutic dose and potentially experience clinical benefit faster. So that is, again, target PDUFA in 2026, near term, really meant to expand the base of patients on both WAKIX and pitolisant. And then the real value driver after that is the pitolisant high dose or pitolisant HD formulation. That is a new novel formulation of pitolisant with an optimized PK profile that has greater bioavailability, less variability in the PK profile.

And then we're going to take it up to a higher dose because when our partner, Bioprojet, did the original pivotal program, it was a pretty conservative approach to dosing, and we think they left some efficacy on the table with a product that's well tolerated. So HD, we're on track for initiating 2 Phase III trials in the fourth quarter this year, one in narcolepsy and in idiopathic hypersomnia.

I think the other important aspect in the programs, we're also looking to drive as much differentiation from the current WAKIX product. So the opportunity is in addition to EDS and cataplexy in the narcolepsy program, we're also going to investigate fatigue, the symptom of fatigue, which is distinct from EDS. And that occurs in about 60% of patients with narcolepsy. So it's a distinct symptom. And the relevance with pitolisant mechanistically is fatigue is mediated through histaminergic circuits in the brain. So -- and pitolisant is the only agent working through histamine. So that has potential benefit.

We demonstrated that a couple of years ago when we did a Phase II proof-of-concept trial in patients with myotonic dystrophy. And we saw positive signals not just in EDS, but also in the endpoint of fatigue. And those 2 symptoms are really prevalent and debilitating in patients with myotonic dystrophy, another rare neurologic disorder that we could potentially restart that program with pitolisant HD in patients with myotonic dystrophy. But first things first is on narcolepsy and idiopathic hypersomnia, and we're on track to initiate both of those studies in the fourth quarter.

Yes. And I'll just add a little bit to that in terms of our commercial capabilities, given our single hub model distribution capabilities, puts us in a great position to both leverage the GR formulation because we have the ability to contact every patient that essentially has been on WAKIX at one point or currently on WAKIX. And that gives us the opportunity to help potentially transition the business over the long term.

Okay. So I guess if you do show the differentiated profile and you hit down those endpoints, which would have a distinct profile overall, pricing. Would it be the same? Would you price it at a premium?

Yes. So yes, we haven't sort of disclosed sort of the strategy around pricing. I think the approach at a high level is we want to price it to ensure access and generate the value for the innovation of the product. And I think as we get closer, we'll share the thinking around the pricing strategy. I think if you look at the market, WAKIX currently is priced favorably to the market leader. It's a favorable formulary position. No payer is stepping WAKIX through an Oxybate product, which is a Schedule III restricted access REMS product. So we think there'll be good opportunity in terms of pricing and helping to transition the franchise from WAKIX to pitolisant HD in 2028, the target PDUFA for HD out ahead of the 2030 LOE.

Okay. All right. So I think we are out of time, but I will ask you, if we're sitting here a year from now, what would you like to say was your key value-creating events?

So a year from now, I think starting with, I think, ZYN002 in Fragile X syndrome with regards to if we are fortunate to report out positive data and then be on the path to NDA submission. I think with no approved therapies, we would anticipate an opportunity for priority review and then a target PDUFA date late '26. So I think we see that as an important driver of value as well as important for that patient community that has no approved therapies.

In addition, really advancing the pitolisant HD programs, advancing them both narcolepsy and IH, working towards transitioning the pitolisant franchise, another key value driver.

Lastly, we didn't even get to touch on strong balance sheet, favorable position, very active in BD. So I think the last component of that would be looking potentially can never predict business development.

Additional assets.

But there are opportunities out there given the market backdrop. So I think possibly looking back and having the opportunity to announce additional assets in the pipeline to further build that out and more shots on goal and driving future value creation.

How about the epilepsy studies?

And the epilepsy, so on track for top line data readout late '26, early '27. So another potential catalyst driving value.

And any updates on the orexin program, which I'm pretty sure you have interest in.

Yes. So orexin, yes, importantly. So we're excited about that molecule. So the update, we're on track for first-in-human studies later this year. In terms of Phase I studies, both healthy volunteers in a single ascending dose study, healthy volunteers sleep deprived in a dose-ranging study and then to report clinical data next year in 2026.

Look forward to all the updates. And thank you very much for attending our conference. Great.

Thank you, Pete.

Thanks, everyone.