Harmony Biosciences Holdings, Inc. Q3 FY2025 Earnings Call

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. Please be advised that today's conference may be recorded. 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 additions 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 the FDA, and we are on track to initiate two Phase III trials, one in narcolepsy and one 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 the 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 three Phase III registrational studies ongoing and anticipate up to five Phase III registrational studies in five 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 the 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 milligrams and 100% of the patients, that is all 46 of the 46 patients, were able to initiate pitolisant GR at the therapeutic dose of 17.8 milligrams with no safety or tolerability issues. In addition, 98% of the patients who received pitolisant GR 35.6 milligrams at week 2 tolerated the higher dose well. No new adverse events or serious adverse events were observed from this study. Pitolisant GR is a fast-to-market strategy designed to demonstrate bioequivalence to the WAKIX formulation. The top-line data from the pivotal bioequivalence 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 a 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 the 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 two 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 by 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 to help us 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 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 give 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 two Phase III studies for our pitolisant HD programs. As a result, we expect to have five 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?

And we will take our first question from Ami Fadia with Needham.

Congratulations on a strong third quarter. My first question is regarding your guidance. You’ve raised it, and when we compare year-to-date performance to the full year of 2024, there's clearly an increase in new patient additions this year. Could you elaborate on how you see the trajectory of WAKIX developing? It's been several years since the launch, but it seems like there is growth happening. Can you comment on how you foresee this evolving into 2026 and whether this growth can be maintained? I have one or two other questions as well.

Ami, thank you for your question. I'm going to turn it over to Adam to speak about the trajectory of patient adds and the strong fundamentals there. And then Sandip can comment on 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 going 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, and 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 adverse events seen with the GR formulation and how did the grade or frequency of those adverse events compare 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 adverse events were observed. The safety and tolerability were, in general, consistent with the established safety tolerability profile of pitolisant GR. We will be disclosing the full data set in upcoming meetings. 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 milligrams after one week of pitolisant GR, 98% of them were able to tolerate pitolisant GR 35.6 milligrams. 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 help the patients start at the therapeutic dose range, potentially can experience efficacy earlier, potentially fewer number of dropouts, and a better overall patient experience.

If I could just squeeze in one more 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 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, safety, and tolerability offer a 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, and 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 change our strategy. We have a dedicated BD team focusing on 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 is 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?

Thank you, Jeff, and thank you for the question, David. We are excited about orexins because we have developed our own, and it's also an important potential treatment option for patients. We are confident in our ability to grow and succeed with WAKIX moving forward, for a few reasons. Firstly, the treatment approach in this market is characterized by polypharmacy, with a significant number of patients using two or more therapies, a trend we expect to continue. Our recent market research confirms that physicians also anticipate this will remain the case. Additionally, WAKIX has demonstrated consistent performance regardless of the arrival of new competitors, whether they are brand names or generics, and we expect this trend to persist. Historically, when new brands enter the narcolepsy market, brand utilization often increases, so we anticipate similar outcomes with an orexin product launch. Furthermore, WAKIX is a highly differentiated offering as the only non-scheduled treatment option. By the time orexins are launched, physicians will have considerable clinical experience with WAKIX, which has solid efficacy and is believed to be well tolerated. This positions WAKIX favorably in the minds of healthcare providers, allowing it to be used in combination with other therapies for a wide range of narcolepsy patients. For these reasons, we are very confident in our sustained growth and performance in the future.

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

Congratulations on the progress. I have a question regarding the guidance for 2025. It was encouraging to see the guidance raised. However, if we look at the numbers, it suggests that fourth quarter sales for WAKIX will be between $221 million and $241 million. This indicates that on a quarter-over-quarter basis, the sales are essentially flat or may even decline. Could you elaborate on how we should approach modeling the fourth quarter? Specifically, should we consider net patient additions, gross to net, or seasonality? I understand that Sandip mentioned inventory might play a role, but any additional insights on the fourth quarter would be helpful, especially considering the strong momentum in net patient additions.

Yes. Thank you for the question. We saw strong demand for top-line growth that we expect to sustain moving from Q3 to Q4. In Q3, we experienced a slight increase in trade inventory, which positively influenced our sales. This was quite the opposite in Q2. Currently, we feel optimistic about the range we've set, which we recently increased. This boosts our confidence, and like every team, we will strive to not only meet but potentially exceed this range. Predicting Q4 is challenging due to typical variabilities associated with the quarter, especially relating to brand and holiday factors. However, we are confident in our robust year-over-year growth. We're expecting strong growth compared to the previous year, and WAKIX is rapidly approaching blockbuster status as we head into 2026 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?

Yes, certainly. As Jeff mentioned, we are actively exploring business development opportunities, which has been a key part of our strategy for many years. We see several attractive options that we could potentially pursue. Additionally, we are experiencing ongoing growth in our cash reserves, having generated a strong $106 million last quarter, resulting in a total of $778 million at the end of the quarter. This provides us with increasing confidence, although we will be careful in how we allocate our capital. We have different avenues to enhance shareholder value. Recently, we have been focusing on business development, but in the past, we have also considered share buybacks as an option. At the appropriate time, we will evaluate various opportunities to maximize value for our shareholders.

I appreciate the question. I want to emphasize that while predicting the timing of business development transactions is difficult, we have options. Our main focus is to pursue innovative assets that enhance value. We aim to build our pipeline, as we believe that’s where future value lies, while also expanding our product portfolio. We have a strong commercial engine that we intend to leverage with additional products. This is our goal, and we have a solid balance sheet to support 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 very excited about the two life cycle management formulations, GR and HD. GR is a fast-to-market strategy aimed at new patients who would be prescribed the new pitolisant GR formulation instead of WAKIX. Additionally, we have the ability to reach out to patients who were previously on WAKIX but stopped, to see if pitolisant GR might be a suitable option for them. So, for GR, the focus is on new and former WAKIX patients. The HD formulation, with its differentiated profile, will target not just new and previous WAKIX patients, but also those currently taking WAKIX. This presents a transition opportunity. Market research shows that healthcare professionals respond positively to HD’s profile, considering it significantly differentiated and superior. They have indicated they would contemplate transitioning a majority of patients who are better but not fully well. That's the approach for HD. Moreover, both formulations have utility patents filed through 2044, which allows us to enhance our Sleep/Wake franchise for the foreseeable 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 nervous system on NT2 and idiopathic hypersomnia at very low doses, providing us the dosing flexibility to target these three 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 the 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 the ARGUS study and the LIGHTHOUSE study, that's Dravet and LGS studies, and we anticipate sharing top-line data in 2026. We'll be providing more granularity in terms of timelines 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, that’s a great question. Thank you. There is ongoing discussion about whether to pursue Dravet syndrome and Lennox-Gastaut syndrome separately or to approach them with a broader DEE indication. Both strategies have their advantages and disadvantages. However, our current focus is on Dravet syndrome and Lennox-Gastaut syndrome. We want to maintain this focus primarily to ensure the patient population remains homogeneous and to expedite our top-line data, aiming to assist these patients with a product profile that is highly favorable in terms of both efficacy and safety.

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. 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 liver function tests 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 two 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 22q trial?

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.

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 analyses. It is very hard to say at this point in time what kind of data sets we need to see before we embark upon the 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 updates 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 the 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 has shown around a 12- to 13-point final ESS score. Any color on that?

Thank you for the question. Pitolisant HD is an advanced formulation that not only involves a higher dose but also features an optimized pharmacokinetic profile. Based on the dose-response observed in our pivotal clinical trials for narcolepsy, as well as studies conducted in Prader-Willi syndrome and myotonic dystrophy, we expect a significant increase in efficacy regarding excessive daytime sleepiness. However, it's crucial to highlight that our focus extends beyond just excessive daytime sleepiness. We are also addressing fatigue in narcolepsy patients, for which no approved treatments currently exist, and tackling sleep inertia in individuals with idiopathic hypersomnia, another area with no approved therapies. We aim to achieve these goals without sacrificing the safety or tolerability of pitolisant. Notably, our Phase Ib study examined pitolisant at doses up to 180 milligrams, which is five times the maximum label dose for WAKIX, and the safety and tolerability observed were consistent with what we see with WAKIX. Ultimately, this results in a very favorable benefit-risk profile, with established safety and tolerability, improved efficacy for excessive daytime sleepiness, treatment targeting fatigue in narcolepsy, and focus on sleep inertia in idiopathic hypersomnia, all while keeping pitolisant nonscheduled and maintaining a straightforward dosing regimen of taking a pill in the morning. This is what we intend to achieve 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 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 being 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, and 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, eight-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 two questions from us. The first is on EPX-100. You have two 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?

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. These are two 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. We have checks and balances with our EPX-100 ARGUS and LIGHTHOUSE clinical trials as well.

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. Thank you for your question. To provide some additional context, I want to emphasize that this is a significant market. Regarding the ongoing growth of WAKIX, it has a highly differentiated product profile with broad clinical utility, being the only nonscheduled product, which is especially important to me as a former neurologist treating patients. This creates meaningful therapeutic options. The market consists of approximately 80,000 diagnosed patients. As the market evolves and we gain more insights, similar to the understanding gained about fatigue as a prominent symptom in around 60% of narcolepsy patients, we are integrating that knowledge into the pitolisant HD program. This is why we feel confident about the underlying fundamentals and the growth of WAKIX in narcolepsy, as well as our enthusiasm for the pitolisant HD program and pitolisant GR, which are both significant factors in our outlook.

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 two 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 Q4 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?

Thank you, Ash. I'll begin by addressing the question about our pipeline. I want to emphasize my strong belief in our pipeline programs and in Kumar's leadership within our R&D team, which has significant experience and expertise. While we don't have time to cover everything, there are valid reasons for optimism regarding the outcomes of our studies, including the IH study and Fragile X. In the ZYN002 program, we've spoken to key opinion leaders, and unfortunately, we've seen that programs with positive Phase II data can fall short in Phase III due to a lack of approved treatments and a high placebo response rate, which has led to unsuccessful outcomes. We've learned from these experiences, and we will apply those insights moving forward. I still have confidence in EPX-100 and our other pipeline programs. Kumar, do you have any additional thoughts?

Yes, I think you covered it.

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.

I want to ask about eligible patients for pitolisant in HD and GR. For HD, you mentioned that new, previous, and switch patients are all potential candidates. I'm curious about what you consider to be a good switch patient moving from WAKIX to HD. Additionally, would switching be a possibility 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.