Harmony Biosciences Holdings, Inc.

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 Bioscience's third quarter 2025 financial results conference call. All participants have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. If you would like to ask a question at that time, please press star 1 on your telephone keypad. Please be advised that today's conference may be recorded. Lastly, if you should require operator assistance, please press star zero. 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 Bioscience's third quarter 2025 financial results and provide a business update. Before we start, I encourage everyone to go to the investor 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 Dano, President and CEO, Adam Zeske, Chief Commercial Officer, Dr. Kumar Budur, Chief Medical and Scientific Officer, and Sandeep 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 Dana. 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 to $860 million, taking it up to $845 to $865 million. We had robust cash generation of $106 million, bringing our balance sheet to $778 million as of September 30th. But what I am most proud of is that this performance was driven by the highest number of quarterly patient ads for WACIX since our launch, with an average of 500 patients added this quarter, resulting in an average of 8,100 patients on WACIX at the end of Q3. Our Chief Commercial Officer, Adam Zeske, will next be providing more color on some of the things his team is doing to drive this strong momentum in our WACIX 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 WACIX 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 Pitollasen HD Our pitolis and high-dose formulation has been submitted to 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 Zeske, 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.

Wacix delivered $239.5 million in net sales for the quarter, representing nearly 30% year-over-year growth in its sixth year on the market. Wacix achieved a record increase in approximately 500 average patients per 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, WACIX 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 WACIX performance has always been the unique position WACIX owns as the only non-scheduled treatment option. resulting in its broad clinical utility. WayKicks 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 executions. 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 WACIX 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 a billion dollars plus in annual revenue from narcolepsy alone. Looking to the future, the Pitolis and 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 Pertolison 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're 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 Badur.

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 registration studies ongoing and anticipate up to five Phase III registration studies in five distinct indications by the end of the year. And we have some important updates to share on the next-gen pitolocin programs. Starting with our sleep-wake franchise, we continue to make significant progress across our next-gen pitolocin programs. I'm pleased to report that we have submitted the IND for pitolocin HD to the FDA. The pitolocin 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 3 initiation in Q4 2025. Similarly, the phase 3 study with pitocin 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 producer dates for both programs are in 2028. The other next-gen Pitocin formulation, Pitocin-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, Pitolacin-GR also provides an ability to start at the therapeutic dose range at 17.8 milligram, eliminating the need for titration and 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 Pitolacin-GR at 17.8 milligram, And 100% of the patients, that is all 46 of 46 patients, were able to initiate pitulocin-GR at the therapeutic dose of 17.8 mg with no safety or tolerability issues. In addition, 98% of the patients who received pitulocin-GR 35.6 mg at week 2 tolerated the higher dose well. No new AEs or SAEs were observed from this study. Pitulocin-GR is a fast-to-market strategy designed to demonstrate bioequivalence to make its formulation. The top-line data from the Pivotal BE study is on track for Q4 2025 with a target BDUFA in Q1 2027. Utility patents have been filed for both Pitocin-GR and Pitocin-HD with potential exclusivity to 2044, securing long-term franchise value. Beyond beta-recent, our sleep-wake portfolio continues to advance with BP1.15205, a highly potent RXN2 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 ZYN-002 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 the full dataset is ongoing, and we plan to share additional information in the near future. The Z1-002 program in 22-Q 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 EPX100, the ARGUS study in Drouet syndrome and the Lighthouse study in Lennox-Gisthof syndrome. EPX100 Our chlamysol hydrochloride is a 5HT2 serotonergic agonist and works via enhancing serotonergic tone and 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 August open-label extension study and the safety tolerability data on EPX100 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, Sandeep Kapadia, for an update on our financial performance. Sandeep?

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 as 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 WCAGs 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 CYN-002 trial, as well as continued commercialization of WACICs and 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 99 cents 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 foliar output. We've recently raised our revenue guidance from $820 to $860 million to $845 to $865 million. These results also gives us confidence that we are rapidly approaching blockbuster status for Awakex and 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 Pitocin HD programs. As a result, we expect to have five ongoing phase three 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 one 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, Sandeep. 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 ads for the quarter. With this sustained momentum, We believe WCAGX 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. 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?

Thank you. And at this time, if you would like to ask a question, please press star 1 on your telephone keypad. If you wish to remove yourself from the queue, you may do so by pressing star 2. We remind you to please pick up your handset and please limit yourself to one question and one follow-up question. And we will take our first question from Amy Fadia with Needham. Please go ahead.

on the strong third quarter. My first question is just around kind of your guidance. You've obviously raised your guidance and, you know, even if we look at the year-to-date performance compared to the full year 2024, there's certainly acceleration in the new patient ads this year. So if you could sort of elaborate on how you see the trajectory of WCAG's evolving It's certainly seven 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 one or two other questions. Thank you.

Okay. Good morning, Ami. Thank you for your question. I'm going to turn over to Adam to speak about in terms of the trajectory of patient ads you know, the strong fundamentals there. And then Sandeep can comment on kind of our thoughts and position on guidance. Adam?

Yeah, thanks, Jeff, and good morning, Ami. Thanks for the question. So, yeah, performance is going to be driven fundamentally by patient ads. And as you saw, we were 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 Sandy, do you want to mention? Sure.

Yeah, no, absolutely. As mentioned on the call, I mean, we recently raised our guidance from $820 to $860 million to $845 to $865 million. You know, as reflected in the guidance, you know, 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. The thing is, it's hard to predict these things as we go into Q4, but, you know, 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 ads 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, you know, well ahead of our original guidance. and ahead of our guidance in terms of net patient ads 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, you know, we're rapidly approaching blockbuster status for AWAKEN.

Yeah, yeah. I mean, I would just add that I think, you know, obviously we're very pleased with the recent trends And we're following them, you know, in terms of, you know, how that will, you know, 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, you know, and that position as well going forward.

Great. Thank you. 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, you know, did the grade or frequency of those AEs compared to the in-market, you know, Regex sort of titration in the initial dosing period?

Yeah. Hey, good morning, Ami. Thanks for the question. What we are disclosing right now is no new safety or tolerability issues observed. with the Pitocin-GR formulation. No serious AEs were observed. The safety and tolerability was in general consistent with the established safety tolerability profile of Pitocin-GR. We will be disclosing the full data set in upcoming meetings. Haven't decided when exactly. But what's important from the Pitocin-GR formulation army is We initiated 46 patients with narcolepsy with Pitocin-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 Pitocin-GR, 98% of them were able to tolerate 17.8 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 Pitocin, has some level of titration, and getting rid of the titration will help the patients to start at the therapeutic dose range, potentially can experience efficacy earlier, potentially less number of drop-offs, and potentially better overall patient experience.

Got it. Thank you. 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. Thanks.

Thank you, Ami. Yes, we will be presenting some efficacy data on EPX100 from the Argus open-label extension study. And we'll also be presenting safety and tolerability data from EPX100 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 a 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 Drouet syndrome.

Thank you. Thank you, Ami. Thank you. Thanks.

Thank you. And we will take our next question from David Amsalem with Piper Sandler. Please go ahead.

Thanks. Just a couple for me. Wanted to get your latest thoughts on BizDev 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 oviporexin potentially in the market? Thanks.

Yeah, good morning, David. Thanks for your questions. So first, with regards to Biz Dev and our, you know, sort of thinking there, I mean, it really hasn't changed. You know, we have always been focused on business development, being strategic, thoughtful, and, you know, how we deploy our capital. You know, as we have built out our pipeline, you know, obviously there's an herb acquisition and then epigenetics. 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 search and evaluation. 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. 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 neuroindications where we could utilize the proven commercial engine So, the strategy remains the same. I think a bit more focused, you know, with regards to our intent to move forward with business development, you know, when we find the right opportunities for us. And I'll turn to Adam in terms of thoughts on WCAG's performance in the setting of emergent erections. Adam?

Yeah, 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 WakeX 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 two or more therapies, and that will continue. I recently verified that in some market research that we've done speaking with physicians, and I expect that to continue as well. But also, if you just look at the history of WCAG, WCAG's 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 WakeX is a highly differentiated product. It's the only non-scheduled treatment option. Physicians will have had seven, eight-plus years of clinical experience by the time of orexin's launch, and it holds a unique position in the minds of healthcare providers. They're highly familiar with it. It provides strong efficacy, 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. It will 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.

Okay, thank you.

Thanks, David.

Thank you. And we will take our next question from Greg Sivanovesh with Zoho. Please go ahead. Your line is open.

Hey, good morning. Thanks for taking my question and 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 WACICs in the range of, I think, 221 to 241. And on a quarter-over-quarter basis, that's essentially flat or down on a quarter-over-quarter basis. So it can just provide more color and how we should be thinking about whether it's net patient ads or gross to net or seasonality when trying to model fourth quarter. I know you, Sandeep, had mentioned some inventory could be a factor, but any other color would be great on a fourth quarter, especially given the great momentum on net patient ads.

Yeah, hi. Thanks, Greg, 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. You know, right now, I mean, we feel very good about the range that we've put out there. You know, we recently raised it, as you mentioned. You know, this gives us great confidence, you know, and I'm sure like every team, I mean, we'll do everything we can to certainly, you know, 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, Again, 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, weight cakes very quickly approaching blockbuster status, you know, 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?

Yeah, sure. I mean, look, 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 in the 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.

Thank you. Oh, Greg, I'll just go ahead. No, no, I appreciate the question. I just want to reiterate, I think, you know, one can never predict, you know, the timing in terms of business development transactions, as Sandeep alluded to. You know, we have optionality, but our focus and our intent is really to pursue, you know, 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, you know, that is our intent, and we have a strong balance sheet to execute on that.

Thank you.

Thanks. Thank you. And we will take our next question from Jay Olson with Oppenheimer. Please go ahead.

Oh, hey, congrats on the quarter, and thank you for taking the question. Can you talk about your life cycle management plan for Pitocin, GR, and HD with regards to new patients? And then which patients currently on WACICs 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 1 study, and any lessons learned from the Alkermes and Cata data at WorldSleep? Thank you.

Yeah. Good morning, Jay. Thanks for your questions. Adam, our life cycle management strategy with regards to, you know, patients that would benefit from those formulations.

Yeah, we're really excited about the two 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 new patients that would have been prescribed WAKIX would be prescribed the new Fetolizum 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 had discontinued, to see if Ptolems and GR could be an option for them to consider as well. So for GR, it's really around new WACIX 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 WACIX patients and previous patients, but also existing WACIX 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 a majority of their patients that maybe are better but not well. And so that's the strategy with 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.

Thank you.

In terms of our reference, we have learned from some of the other development programs.

Thank you, Jeff. Good morning, Jay, and thank you for the question. Yes, we are on track. to initiate the phase one 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 Rx interceptor agonists, especially as it relates to dosing and the safety and tolerability profile alongside the efficacy. We have one of the most potent Rx interceptor agonists based on all the publicly available data. And it lends itself to target the central dysfunctions on ND2 and idiopathic hypersomnia at very low dose, 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 Rx interceptor agonist. And you'll be hearing more from our own Rx interceptor agonist when we initiate the the first in human study, and we also anticipate to share some of the clinical data in 2026. Thank you, Jay.

Super helpful. Thanks again. Congrats on the quarter. Thanks, Jay.

Thank you. And we will take our next question from Pete Stavropoulos with Cancer Fitzgerald. Please go ahead.

Good morning, and congratulations on the progress, and thank you for taking my questions. Could you just touch on EPX100 epilepsy program? You know, any clinical data that has been generated and disclosed that sort of gives you confidence in the Dravet and LGS program? You know, 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? Thanks.

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

Good morning, Pete, and 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 August open-label extension study. That's the study in Druet syndrome. In terms of your question around recruitment and enrollment, yes, I mean, we continue to recruit patients in both ARG study and the Lighthouse study, the Struve and LGS studies, and we anticipate to share top-line data in 2026. We'll be providing more granularity in terms of timeline as we make progress with the enrollment. Thank you.

Any thoughts on taking 100 into other DEs or other DEs remain the focus of 200?

Yeah, great question. Thank you. There is this discussion around DS, LDS, pursuing separately versus going with a broader DE indication, right? So there are pros and cons with each of these approaches. Right now we are focused, laser focused. on Drouet 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. Thank you.

Yeah, and Pete, maybe one addition just to remind everyone. So EPX100, clemenzol hydrochloride, so a first-generation antihistamine, you know, that was in the market for about 20 years with a proven safety tolerability profile. And in the overall sort of, you know, risk-benefit in these sort of therapeutic options with other, you know, indicated agents such as Epidiolex and the need to monitor LFTs or Phentepla with the echocardiograms required in the REMS program because of cardiac valvular disease, the risk there. So, you know, there is sort of a proven safety tolerability profile. And in the overall kind of risk-benefit, you know, we see the opportunity there as we go forward and generate efficacy data in both Gervais and LGS.

Thank you very much and congratulations once again. Thank you.

Thank you. And we will take our next question from Danielle Brill with Truist Securities. Please go ahead.

Hi guys. Good morning. Congrats on the quarter and thanks for the question. Maybe just two quick ones from me. Do you have any sense of what proportion of your 8100 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 trial? Thank you.

Good morning, Danielle. Thanks for your questions. Adam, breakdown of patients when waking?

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.

Daniel, good morning, and 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 Frazer-Lex 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 3 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 Frazer-Lex syndrome study itself and also the implications on 22Q. early next year. Thank you, Danielle.

Thank you.

Thanks, Danielle.

Thank you. And we will take our next question from Corinne Johnson with Goldman Sachs. Please go ahead.

Hi, 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 3 pitalescent HD study to show on ESS scale? And what do you think a clinically meaningful difference would be in comparison to the current WCAGs in order to support the HD use? I think the WCAGs shown around 12 to 13 point final ESS score. Any color on that?

Hey, yeah. Good morning. Thank you for the call. Thank you for the question. Pitocin HD, it's an enhanced formulation. It's an enhanced next-gen formulation. It's not just the high dose, but it also has an optimized PK profile. Based on the dose response that we have seen with Pitocin in the pivotal narcolepsy clinical trials, and also the studies that we conducted in Prader-Willi syndromes and also in myotonic dystrophy, 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 daytime sleepiness perspective. But it's also important to note that we are not just targeting excessive daytime 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 pitolacent. In fact, we conducted a phase 1 study where we studied up to 180 milligrams which is up to five times the maximum labeled dose of vague eggs. And the safety and tolerability profile in general was similar to what we see with vague eggs. 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 exercise and sleepiness, targeting symptoms like fatigue and narcolepsy, targeting symptoms like sleep inertia in patients with idiopathic hypersomnia, all while maintaining the non-scheduled status and a very simple dosing regimen of taking pill in the morning. So that's what we plan to accomplish with Pitilessant HD. Thank you.

Okay. Thank you.

Thank you. And we will take our next question from Patrick Truccio with H.C. Wainwright. Please go ahead.

Thanks. Good morning. I was wondering if you could elaborate a bit more on the, you know, sustainability and as well the drivers of the record approximate 500 patient ad in the third quarter and if we should expect those, you know, those drivers to continue in the fourth quarter but as well in 2026. And then separately, on pitolis and HD, I think you mentioned, you know, 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.

Good morning, Patrick. Thank you for your questions. Adam?

Yeah, thank you for the question. So we're really pleased with the momentum we're seeing in increases in patient ads, as you mentioned. And the drivers... Look, I think it starts with Wacix is a highly differentiated product. It's the only non-scheduled treatment option. And that is combined with strong execution across the organization. So, you know, 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 significantly. 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?

Yeah, so around the HD. And so what resonates is the promise of improved efficacy. 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... and 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. Thank you.

Thank you. And we will take our next question from Jason Gerberry with Bank of America. Please go ahead.

Hey, guys. This is Bob on for Jason. Just two questions from us. The first is on EPX 100. You have two Phase 3 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 wake aches. 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? Thank you.

Thanks, Bobbin, for your question. Kumar on EPX100.

Yeah.

Hey, good morning, Warren. Thank you for the question. With EPX100, I mean, as you know, what we are studying here is the seizure frequency, which is slightly different from what we studied with Z1002 in the fragile X syndrome. Possible response in general, is part and parcel of all neuropsych trials, especially psych trials with behavioral endpoints like Frazer-Lake syndrome. And we had multiple checks and balances within the study to manage the placebo response. With EPX100, 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 two distinct indications with 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? Yeah, and then in terms of WCAG's 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 pretty steady increase in new writers every quarter, and that's continued for the past several years. We would expect that to continue A little bit more detail, you know, remember we call on actually more than 9,000 physicians, and that's 4,000 that are enrolled in the Oxibade REMS programs, but also more than 5,000 that are not enrolled in Oxibade 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.

Yeah, and I would just add, you know, Yeah, no, thank you for your question. Just to add, you know, at a higher level, just to remind everyone that, you know, this is a large market. So in terms of the continued growth of WACIX, a highly differentiated product profile with broad clinical utility, the only non-scheduled product, which is meaningful, you know, as a former neurologist treating patients, you know, 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 Tolson HD program. So I think that is the backdrop, why we are confident, why, you know, the underlying fundamentals and the growth of WACICs in narcolepsy and our excitement and confidence in the Pitocin HD program and Pitocin GR. I think, you know, that has a lot to do with it as well.

Yeah, 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.

Yeah. 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 WACUS continues to grow. Thank you.

Thank you. And we will take our next question from Ash Verma with UBS. Please go ahead.

Oh, hi. Yeah, thanks for taking questions from us. 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 5Galaxy. What gives you the confidence that the subsequent pipeline programs have higher chances of success? And then on the WCAG's $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 analyzing at? With the catered direction expected to launch in 2027, what's your level of urgency to hit the long-term guide before the competitor entry? Thanks.

Yeah, 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 and our R&D organization, which has a lot of experience and expertise. We don't have time, but if you look at the IH study, if you look at Fragile X, there are good reasons in terms of the outcomes. you know, that we've sort of talked about. In the ZYN002 program, in talking, you know, with KOLs, unfortunately that pattern, you know, 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, you know, kind of got into multiple Phase III programs, which is the reason why, you know, 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, you know, in EPX100, our other pipeline programs. And, Kumar, any additional thoughts?

I think you got it. Good. Thank you.

Okay. Yeah, and then thanks, Ash, for the question around achieving a billion in revenue. Now, obviously, it's a little bit premature to provide guidance for 2026 specifically, but... 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 a billion in revenue well before LOE. So confidence remains high.

Thanks, Adam. Thanks, Ash.

Thank you. And we will take our next question from David Huan with Deutsche Bank. Please go ahead.

Hi there. Thanks for taking the questions. So I want to ask on eligible patients for Tolacent 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 Waitix to HD, and then is would switching be an option for GR patients? Thanks.

Thanks for the question. So I guess the switch patients, obviously that's going to be determined by the healthcare 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 WACICS, 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 healthcare provider. In terms of our strategy, we'll be focused on new patients and previous patients, as I mentioned before.

Thank you.

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.