Harmony Biosciences (HRMY) Earnings Transcript

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DATE

Tuesday, Feb. 24, 2026 at 8:30 a.m. ET

CALL PARTICIPANTS

• President and Chief Executive Officer — Jeffrey M. Dayno
• Chief Commercial Officer — Adam Zaeske
• Chief Medical and Scientific Officer — Kumar Budur
• Chief Financial and Administrative Officer — Sandip S. Kapadia

TAKEAWAYS

• Net Product Revenue -- $243,800,000 for the quarter, a 21% increase, and highest quarterly revenues to date, reflecting sustained demand for Wakix.
• Full-Year Net Product Revenue -- $868,500,000, representing six consecutive years of revenue growth and profitability.
• Patient Adds -- Third consecutive quarter with approximately 400+ average patient adds, reaching about 8,500 average patients on Wakix.
• 2026 Wakix Revenue Guidance -- $1,000,000,000 to $1,040,000,000, positioning for potential blockbuster classification.
• Cash Position -- $882,500,000 in cash, cash equivalents, and investments at quarter end, supported by $348,200,000 in operational cash generation during 2025.
• Operating Expenses -- $136,700,000 for the quarter, up from $91,100,000, primarily driven by increased R&D investment, commercialization costs, and litigation/settlement expenses.
• Non-GAAP Adjusted Net Income -- $33,400,000 ($0.57 per diluted share), compared to $64,200,000 ($1.10 per diluted share) in the prior-year quarter.
• Wakix Franchise IP Settlements -- Six of seven ANDA filers settled; earliest possible generic entry is March 2030 if pediatric exclusivity is granted, otherwise September 2029.
• Wakix Regulatory Exclusivity -- Orphan Drug Exclusivity through March 2026 for EDS and October 2027 for cataplexy.
• Pediatric Approval -- FDA approved Wakix for cataplexy in patients six years and older, supporting pediatric exclusivity and market expansion.
• Field Force Expansion -- Approximately 20% increase in field-based personnel planned, targeting enhanced market presence, with hiring underway.
• Pitolisant GR (Gastro-resistant) -- NDA submission on track for Q2 2026; target PDUFA in Q1 2027 as a line extension for the Wakix franchise.
• Pitolisant HD -- Top-line data in 2027 and potential PDUFA in 2028; ongoing registrational trials in narcolepsy and idiopathic hypersomnia aim for differentiated labels in fatigue and sleep inertia.
• Phase III Pipeline -- Five registrational trials ongoing across five CNS indications, with a sixth anticipated to start later in 2026.
• EPX-100 -- Phase III Dravet syndrome study open-label data presented showed about 50% median seizure reduction for at least six months in half of patients.
• New Pitolisant Formulation -- Issued patent coverage to 2042; development focuses on broader CNS indications where fatigue is a core symptom, such as MS, post-stroke, and Parkinson's disease.
• Orexin-2 Receptor Agonist BP1.5205 -- Phase I PK data expected mid-2026; preclinical profile includes potency, selectivity, and safety.
• Business Development Priority -- Capital deployment focus on expanding orphan rare CNS and broader CNS pipeline and commercial assets, with $150,000,000 share buyback capacity acknowledged as well.

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RISKS

• Non-GAAP Adjusted Net Income Decline -- Non-GAAP adjusted net income decreased to $33,400,000 from $64,200,000 due to higher R&D, increased commercialization expenses, and litigation/settlement costs.
• Legal and IP Uncertainty -- Ongoing litigation with one ANDA filer creates uncertainty around the timing and outcome of generic entry; CEO Dayno said, "it is really hard to know and I cannot really speculate."
• Operating Expense Growth -- Elevated quarter-over-quarter cost increases are expected to persist with five ongoing and a potential sixth Phase III study planned for 2026.

SUMMARY

Harmony Biosciences (NASDAQ:HRMY) delivered record revenues and maintained profitability, driven by consistent Wakix demand and ongoing patient growth. Management reiterated guidance for blockbuster-level Wakix sales in 2026 and highlighted the approval for pediatric cataplexy as a catalyst for further expansion. Multiple key pipeline assets are advancing, notably pitolisant GR and pitolisant HD, with all targeted regulatory milestones clearly stated. The company reinforced its robust financial position, citing substantial cash reserves and strong cash generation, while laying out focused strategies for business development and field force expansion to support long-term growth.

• CEO Dayno stated, "we have built something rare in this industry, a profitable, self-funding biotech company with a strong balance sheet well positioned to build out our pipeline and expand our commercial portfolio to drive long-term value creation."
• The launch of a new patient portal and process improvements aims to further shorten time to dispense and improve conversion and access rates.
• Chief Commercial Officer Zaeske reported the 20% field force increase is entirely directed at ongoing Wakix growth, with additional team rebalancing for geographical coverage.
• Pitolisant GR's strategy focuses on new patients and re-contacting those previously on Wakix, aiming for launch prior to loss of exclusivity.
• Chief Medical and Scientific Officer Budur described the new pitolisant formulation as "a very unique opportunity for us to pursue fatigue in broader CNS indications," noting Phase I study preparations are underway.
• Chief Financial and Administrative Officer Kapadia highlighted that increased expenses in Q4 included one-time litigation costs and continued R&D scale-up, with further investment ahead as the late-stage pipeline expands.
• EPX-100's observed lack of significant GI side effects and no special laboratory monitoring requirements may provide a safety and convenience differentiation among Dravet syndrome treatments.
• Six of seven generic litigation settlements set earliest generic entry no sooner than March 2030 pending pediatric exclusivity, reinforcing near-term revenue durability.

INDUSTRY GLOSSARY

• ANDA: Abbreviated New Drug Application, a regulatory submission for generic drug approval referencing a branded product.
• PDUFA: Prescription Drug User Fee Act, which sets the target date (PDUFA date) for FDA action on new drug submissions.
• ORCA: Name of the Phase III clinical trial evaluating EPX-100 in Dravet syndrome.
• LIGHThouse: Name of the Phase III clinical trial evaluating EPX-100 in Lennox-Gastaut syndrome.
• Onstrike-1/Onstrike-2: Phase III clinical trials for pitolisant HD in narcolepsy and idiopathic hypersomnia.
• GR: Gastro-resistant, describing a formulation designed to withstand stomach acid and release medication in the intestine.
• HD: High Dose, describing a formulation of pitolisant developed for expanded CNS indications.
• PK: Pharmacokinetics, the study of how a drug is absorbed, distributed, metabolized, and eliminated in the body.
• CMS-28: A seizure frequency measurement scale referenced in the Dravet syndrome data.

Full Conference Call Transcript

Matthew Beck: Good morning, everyone, and thank you for joining us today as we review Harmony Biosciences Holdings, Inc. fourth quarter 2025 financial results and provide a business update. Before we start, I encourage everyone to go to the Investors section of our website to find the materials that accompany our discussion today, including a reconciliation of our GAAP to non-GAAP financial measures. At this stage of our life cycle, we believe the non-GAAP financial results better represent the underlying business performance. Our speakers on today's call are Dr. Jeffrey Dayno, President and CEO; Adam Zaeske, Chief Commercial Officer; Dr. Kumar Budur, Chief Medical and Scientific Officer; and Sandip S. 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.

Operator: Jeff?

Jeffrey M. Dayno: Thank you, Matt. Good morning, everyone, and thanks for joining our call today. I want to start off by recognizing the entire Harmony team for another outstanding quarter and a remarkable year in 2025. Our fourth quarter results reflect strong sustained execution and have positioned us to achieve blockbuster status for Wakix this year. In Q4, we delivered $243,800,000 in net product revenue, up from $201,300,000 the same period last year, driven by continued strong demand for Wakix, based on its broad clinical utility and ongoing executional excellence by our commercial team. Q4 2025 marked the third consecutive quarter with approximately 400 plus average patient adds, the first time in franchise history.

This quarter's net patient adds brings us to approximately 8,500 average patients on Wakix. With 80,000 diagnosed patients with narcolepsy, there continues to be a large market opportunity to support strong growth. For full year 2025, Wakix generated $868,500,000 in net product revenue, representing strong year-over-year growth and extending to six consecutive years of revenue growth and profitability. Looking ahead to 2026, we are guiding Wakix's net revenue to blockbuster status of $1,000,000,000 to $1,040,000,000 for the first time in franchise history, underscoring the durability of the Wakix brand and the strength of our commercial engine. On the IP front, we have made good progress toward the goal of securing the Wakix franchise.

We recently settled with three generic filers, resulting in us having settled with six of the seven ANDA filers. Based on these settlements, generic entry would occur no sooner than March 2030 if we are granted pediatric exclusivity, which we are on track to obtain. As for last week's trial, we remain confident in the strength of our IP and will continue to vigorously defend it as the legal process and trial continues. In addition to the strong growth of Wakix, we are advancing the next-generation pitolisant franchise. Pitolisant GR will extend the Wakix franchise and our leadership in narcolepsy as a line extension of Wakix with its broad clinical utility.

We are on track for NDA submission in Q2 this year with a target PDUFA date in Q1 2027. Pitolisant HD is designed to expand the pitolisant franchise into unique indications in orphan rare diseases, addressing unmet medical needs. And we now have an opportunity to explore a new pitolisant formulation to pursue broader indications in CNS patient populations in which fatigue is a prominent symptom. This strategy is a mechanism-based approach as fatigue is mediated through histamine circuits in the brain and pitolisant works by upregulating histamine transmission in the brain, along with other neurotransmitters.

This work is supported by newly licensed IP with patent protection until 2042, and we are excited for the opportunity to explore broader CNS indications with pitolisant. Kumar will provide more color on this opportunity later in the call. Our robust late-stage pipeline continues to advance with five ongoing Phase III registrational trials for five distinct CNS indications, and we are making good progress. These trials set us up for multiple catalysts over the next few years, and if successful, meaningful long-term value creation. Kumar will provide more details on the progress of our pipeline programs and the timing of these important catalysts during his R&D update.

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

All of this reinforces our belief that we have built something rare in this industry, a profitable, self-funding biotech company with a strong balance sheet well positioned to build out our pipeline and expand our commercial portfolio to drive long-term value creation. With that, I will turn the call over to Adam Zaeske, our Chief Commercial Officer, for an update on our outstanding commercial performance. Adam?

Adam Zaeske: 2025 marked a year of unprecedented and record-setting performance for Wakix, and that performance continued in the fourth quarter. In 2025, Wakix continued its remarkable trajectory with the third consecutive quarter of approximately 400 or more average patient adds, the first time this has been achieved in the history of the franchise. This level of sustained momentum speaks directly to the strength of the brand and the consistency of our execution. What is driving this performance is clear. Wakix maintains a unique, highly differentiated position as the only nonscheduled treatment option, which continues to fuel broad clinical adoption.

Brand awareness, perceived efficacy, tolerability, and stable payer coverage remain exceptionally strong, and we have sharpened our commercial fundamentals from field deployment and call planning to refined messaging, targeted promotion, new payer wins, and better patient support processes that shorten time to dispense and boost conversion. The compelling value proposition of Wakix combined with continued strategic adjustments and strong operational execution are delivering results, giving us confidence heading into 2026. In addition, right now, we are expanding our field-based teams by almost 20% across our field sales, field reimbursement, and remote sales teams, and we have already made progress in hiring for these roles. This investment will increase our presence in the market and demonstrates confidence in our continued growth.

We will launch a new online portal to enable easier and faster access for patients, and we are continuing to deploy process improvements to further improve time to dispense and success rate, and we will continue to look for opportunities for additional improvements and efficiencies moving forward. We are also extremely excited about the recent FDA approval of Wakix for the treatment of cataplexy in pediatric patients six years of age and older with narcolepsy. This approval further demonstrates the clinical value of Wakix for pediatric patients who experience cataplexy and gives their health care providers the option of prescribing Wakix to address excessive daytime sleepiness, cataplexy, or both, in people six years of age and older living with narcolepsy.

Our commercial teams were well prepared ahead of this approval, with robust promotional strategy, and began executing on those plans from the day of approval. With all of this momentum, we have announced full year revenue guidance for Wakix to achieve blockbuster status of between $1,000,000,000 and $1,040,000,000 in revenue in narcolepsy alone. Looking ahead, pitolisant GR and pitolisant HD give us the opportunity to extend and expand the franchise with differentiated formulations that address important unmet needs while fully leveraging the commercial engine we built. Early feedback from market research with health care providers and payers has been highly encouraging, and we are preparing the organization to drive the next phase of growth as these assets come to market.

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

Kumar Budur: Thank you, Adam. Good morning, everyone, and thank you for joining us today. Q4 2025 capped a year of significant scientific and clinical progress for Harmony, and we are entering 2026 with one of the most robust late-stage CNS pipelines in the industry. We now have five ongoing Phase III registrational clinical trials across five distinct CNS indications, underscoring the breadth and depth of our development programs. I will start with updates for our sleep-wake franchise. I am pleased to highlight a new indication for Wakix that the FDA approved on February 13. The FDA approved Wakix for cataplexy patients six years of age and older.

This is another important milestone for Wakix, and it is now approved for both excessive daytime sleepiness and cataplexy in adults and children six years of age and older. This approval also advances our efforts towards achieving pediatric exclusivity for Wakix, which is an additional six months of regulatory exclusivity at the back end of the longest patent for Wakix. The data from the ongoing Phase III study in Prader-Willi syndrome, the TEMPO study, is the other requirement for pediatric exclusivity, and we are on track for the top-line data from the TEMPO study in second half of this year.

Across our next-gen pitolisant program, pitolisant GR continues to advance as a fast-to-market strategy after demonstrating bioequivalence to Wakix in a pivotal bioequivalence study and has the ability to initiate treatment at the therapeutic dose range at 17.8 mg, eliminating the need for titration, which is an important differentiation. We remain on track for an NDA submission in Q2 2026 and target PDUFA in Q1 2027. Pitolisant HD, our enhanced formulation with an optimized PK profile and a higher dose, remains on track for top-line data in 2027 and PDUFA in 2028. The Phase III registrational clinical trials in narcolepsy and IH, that is the Onstrike-1 and Onstrike-2 studies, are ongoing.

Onstrike-1 is a prospective, placebo-controlled, parallel-arm, double-blind, randomized clinical trial comparing pitolisant HD and placebo. This is an eight-week study evaluating excessive daytime sleepiness via subjective and objective endpoints, that is ESS, MWT, and we are also evaluating cataplexy and fatigue in this study. Onstrike-2 is also a prospective, placebo-controlled, parallel-arm, double-blind, randomized clinical trial comparing pitolisant HD and placebo. This is an eight-week study evaluating symptoms of idiopathic hypersomnia via IHSS and sleep inertia via sleep inertia scale. The sample size of each of these studies is approximately 200 patients, and both programs are pursuing differentiated labels: fatigue in narcolepsy, and sleep inertia in idiopathic hypersomnia.

Both GR and HD formulations have utility patents filed, extending and expanding the pitolisant franchise potentially into the 2040s. We are also very excited to announce the opportunity to explore broader CNS indications with a new formulation of pitolisant, with an issued patent until 2042. As we have discussed in the past, the histaminergic mechanism of action of pitolisant is uniquely positioned to address all three different dimensions of fatigue: physical, emotional, and cognition, and we have already generated clinical data to support the utility of pitolisant to treat fatigue.

We plan to evaluate this new formulation for fatigue in broader indications, with fatigue in multiple sclerosis as the lead indication, and explore other opportunities such as post-stroke fatigue and fatigue in Parkinson's disease. Our current efforts are focused on formulation optimization and new modes of delivery and towards the Phase I PK study. Beyond pitolisant, our orexin-2 receptor agonist BP1.5205 is enrolling in our Phase I clinical study. We are on track for Phase I PK data in mid-2026. As we have previously shared, BP1.5205 has demonstrated compelling preclinical potency, selectivity, safety, and efficacy, positioning it as a potential best-in-class orexin-2 receptor agonist.

Moving on to our epilepsy franchise, EPX-100 continues to advance in two global Phase III registrational programs. Enrollment is ongoing in both the Dravet syndrome and the Lennox-Gastaut syndrome programs, that is the ORCA study and the LIGHThouse study, respectively. The top-line data is expected in 2027 and PDUFA in 2028. We recently presented the data from the open-label extension part of the Phase III study in Dravet syndrome at the AES meeting in December 2025, which supported a differentiated product profile for EPX-100. The effectiveness data in patients who had at least six months of exposure to EPX-100 showed clinically meaningful reduction in seizures, approximately 50% median reduction in seizures as measured by CMS-28.

In addition, we saw at least 50% reduction in seizures in half of the patients. EPX-100 was found to be generally well tolerated with no additional laboratory or special monitoring requirements, with some participants exposed to EPX-100 for more than two years and approaching three years. Finally, on behalf of Harmony, I would like to thank all the patients and their families who are participating in our clinical trials, as well as the clinical investigators and site personnel for their efforts and commitment in helping us to advance our development program. I will now turn the call over to our CFO, Sandip S. Kapadia, for an update on our financial performance. Sandeep?

Sandip S. Kapadia: This morning, we issued our fourth quarter earnings release and filed our 10-Ks, where you will find the details of our fourth quarter and full year 2025 financial and operating results. Our financial performance is also shown on Slides 15 through 17. We finished the year with great momentum across the business, delivering strong growth across several of our key metrics, positioning us well as we head into 2026. We delivered another year of double-digit top-line growth as we reported net revenues above the top end of our previous guidance range. We continue to be a profitable, cash-generating company, funding the growth and advancement of our pipeline fully with the strength of our balance sheet.

Strong financial performance combined with a solid balance sheet, including approximately $882,500,000 in cash, cash equivalents, and investments, positions us well as we continue to invest in the advancement of our robust late-stage pipeline and look for additional value-enhancing opportunities to further build out our pipeline and add to our commercial portfolio. We reported net revenues of $243,800,000 for Q4 2025, compared to $201,300,000 in the prior-year quarter, representing a growth of 21% and also our highest quarterly revenues to date. Performance in the quarter reflects the sustained strong underlying demand for Wakix. We also reported total operating expenses for the fourth quarter of $136,700,000, compared to $91,100,000 for the same quarter in 2024.

The growth in expenses was related to investments in our R&D to advance our late-stage pipeline, investments in the commercialization of Wakix in narcolepsy, as well as handling litigation and settlement expenses during 2025. Non-GAAP adjusted net income for Q4 2025 was $33,400,000 or $0.57 per diluted share, compared to $64,200,000 or $1.10 per diluted share in the prior-year quarter. We believe non-GAAP adjusted net income better reflects the underlying business performance. Please see our press release for a reconciliation of GAAP to non-GAAP results. We ended the fourth quarter with $882,500,000 in cash, cash equivalents, and investments.

The balance reflects robust cash generation of $348,200,000 from operations in 2025, providing us with the financial flexibility to execute on our growth strategy. Looking ahead to our expectations for 2026, as previously disclosed, we are reiterating our guidance for Wakix net revenue of $1,000,000,000 to $1,040,000,000. We believe this guidance reflects our strong expectations for 2026 and demonstrates that we are on track to achieving blockbuster potential for Wakix in narcolepsy alone. As you think about phasing of revenues for 2026, we expect to see the typical seasonal dynamic that the industry as a whole experiences each year in Q1.

This includes higher gross-to-net deductions, due to insurance plan resets and higher copay obligations, along with potential for drawdown in trade inventory. With respect to expenses, expect significant increases in investments in R&D, as we advance our pipeline with five ongoing registrational Phase III programs, along with plans for a sixth Phase III study anticipated to start later this year. Finally, business development is a high priority, and our intention is to deploy capital to expand our pipeline and commercial portfolio. In summary, I am pleased with our strong financial performance in 2025. We once again delivered a year with strong top-line growth, maintained healthy operating margins while continuing to generate significant cash.

This positions us well as we enter 2026 with the potential for significant value creation. And with that, I would like to turn the call back over to Jeff for his closing remarks.

Operator: Jeff?

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

It is because of these achievements that we continue to operate from a position of strength and drive significant momentum. This momentum reinforces our confidence that we have built something rare in this industry: a profitable, self-funding biotech company with a strong balance sheet, blockbuster commercial product, a pipeline positioned to deliver significant long-term value, and the capacity, experience, and commitment to generate even greater value through the pursuit of smart business development opportunities. Thank you, and I will now turn the call back over to the operator for Q&A.

Operator: Thank you. At this time, we will take our first question from Pete Stavropoulos with Cantor Fitzgerald. Your line is now open. Please go ahead.

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

Jeffrey M. Dayno: Good morning, Pete. Thanks for your question. I will turn it over to Kumar to respond.

Kumar Budur: Hey, good morning, Pete. Thank you for the question. These patients who participated in our Dravet syndrome study had treatment-resistant seizures. They were on an average approximately about four anti-seizure medicines, and their baseline seizures, I do not remember the exact number what the baseline seizure was, but I can provide that information. But that was comparable to what we have seen in other studies as well. In terms of the value proposition, Pete, I mentioned on the call the efficacy that we saw in this study. The effectiveness data showed that patients had at least about approximately 50% median reduction in seizures, and we also saw 50% reduction in seizures in about 50% of these patients.

What is important is to see this alongside the safety and tolerability profile. We did not see significant nausea, vomiting, abdominal pain, diarrhea that is commonly seen with other medicines, including suppression of appetite. In fact, the only GI AE of note was diarrhea, which has been in about 2% of the patients. Liver function tests also remained normal, which is an issue with some of the approved drugs, and EPX-100 does not require any special monitoring. And also the ease of use is also very important here.

A liquid formulation BID dosing regimen is much more better suited in this patient population for patients and caregivers, compared to some of the other drugs that are in development which have a TID dosing regimen. Thank you, Pete.

Pete Stavropoulos: And if I have one follow-up, if okay. Can you hear me?

Sandip S. Kapadia: Yes.

Pete Stavropoulos: Yeah. So for the orexin-2 receptor agonist, you know, you are going to have data mid-year-ish. What is the PK/PD and safety bar that you look for in the Phase I to move this program into later-stage studies? And where do you sort of see your orexin-2 receptor agonist fitting into the emerging landscape?

Kumar Budur: Yes. We are dosing subjects right now in our Phase I PK study. By mid-2026, we will see clinical PK data, safety and tolerability data. We do not anticipate to see anything different than what is already seen with other orexin receptor agonists in this class. And we are making progress on advancing this to the next stage of development, which is sleep-deprived healthy volunteer study we plan to commence in the second half of this year. And in terms of how it fits with the competitive landscape, look, Takeda is ahead. They have submitted an NDA, and the others are in Phase I and Phase II studies.

And our goal is to really accelerate the clinical development by leveraging some of the learning that we have from other development programs that are ahead of us, without compromising the quality of data.

Pete Stavropoulos: All right. Thank you, and thank you for taking my questions, and congrats on the quarter.

Kumar Budur: Thank you, Pete.

Operator: Thank you. And we will move next to David Amsellem with Piper Sandler. Your line is now open.

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

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

Jeffrey M. Dayno: Yes. Good morning, David. Thanks for your questions. With regards to the orexin-2 agonist, a comment. In terms of target indications, I think we are contemplating broadly, you know, in addition to the primary targets, in terms of our overall orexin-2 program, other opportunities beyond primary disorders of hypersomnolence. So I think that is part of an overall development strategy. With regards to the emerging data, first, just want to clarify, in terms of the PK profile, in healthy volunteers single-dose study, we are looking to confirm the expected profile of once-daily dosing with regards to the initial data that we will read out, and Kumar, notably multiple ascending dose and sleep-deprived healthy volunteers.

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

Jeffrey M. Dayno: And, David, with regards to your second question, with regards to the ongoing litigation, I think as you are aware, I think it is premature. I am not going to speculate on the future of the trial. But I point you to the recent progress that we made, you know, in settling with three of the generic filers, so that, you know, currently, it brings the total number of settlements to six of the seven ANDA filers. We feel good about how that positions us going forward. Based on these settlements, generic entry stands at March 2030 if we are granted pediatric exclusivity, which we are on track to obtain.

With regards to our cash position and how we stand, Sandeep?

Sandip S. Kapadia: Yeah, look, I think we are in a very strong cash position. You saw we generated close to $348,000,000 cash last year, have $880,000,000 cash on the balance sheet. So I think really well positioned to continue to drive innovation by our pipeline and be able to fund any of all the programs that we spoke about today, generally. And we continue to have a solid position as a company.

Operator: And thank you. We will move next to Jay Olson with Oppenheimer. Your line is now open.

Jay Olson: Hey, congrats on the progress and thank you for taking the questions. Can you talk about any gating factors to filing the pitolisant GR NDA next quarter? And then separately, can you just talk about the pace of enrollment in your Phase III narcolepsy and IH studies for pitolisant HD, considering you have got some competitors also enrolling their studies? Thank you.

Jeffrey M. Dayno: Good morning, Jay. Thanks for your question. We are excited about pitolisant GR. It is sort of right around the corner in terms of NDA submission. Kumar, any gating items to that or how are things looking?

Kumar Budur: Nothing. Things are looking good. Good morning, Jay. We are on track to submit pitolisant GR NDA in second quarter of this year. As always, the final things that are needed for NDA submission, what we are working on, and we are on target for PDUFA in 2027. In terms of your question regarding the enrollment for pitolisant HD in narcolepsy, idiopathic hypersomnia studies, you are absolutely right, Jay. There is competition for patients. We are very much aware of it. But we also have been in this field for a long time. We know the sites. We know the investigators. We have conducted studies in this patient population.

We are confident with our current timeline, which is top line in 2027 and PDUFA in 2028.

Jeffrey M. Dayno: With regards to the pitolisant GR, I just wanted Adam to comment on how he sees the opportunity and how the commercial team is preparing for that?

Adam Zaeske: Great. Thanks, Jeff. Preparation is definitely underway. Looking for PDUFA in Q1 2027. That will have us launching several years before LOE with an opportunity to extend the Wakix franchise. This is a fast-to-market line extension strategy that provides a GR coating to pitolisant and allows patients to start right at the therapeutic dose. So another layer of additional protection for a product that is already perceived highly well tolerated, and the addition of starting at a therapeutic dose, which has hopefully the benefit of securing faster patient outcomes.

The strategy here is really focused on new patients that would have been prescribed Wakix, as well as previous patients that we have the ability to recontact because we secure consent right up front anytime there is a patient referred for Wakix therapy. Both of those are tremendous opportunities, and we look forward to executing on that launch beginning in Q1 2027 next year.

Operator: Thank you. We will take our next question from Graig Suvannavejh with Mizuho. Your line is now open.

Ryan (for Graig Suvannavejh): Hi, everyone. This is Ryan on for Graig today. Couple of quick questions for me. I am wondering if you could comment on the increase in SG&A that we saw in the fourth quarter, the dynamics behind that? And then any updates that you might have on EPX-200, and when we might hear more about that program? Thank you.

Sandip S. Kapadia: Yeah. Just regarding the expenses in the fourth quarter, I mean, as I mentioned on the call, I mean, we see an increase in expenses largely driven by the R&D investments as we start up our Phase 3s for both IH and narcolepsy in the HD program, continued cost in terms of investments for Wakix in narcolepsy commercialization there. Then I also mentioned that we did have litigation and settlement expenses in the fourth quarter, so that the team could be prepared for the trial, which happened a few days ago as well. So, again, those are the key drivers for our expenses.

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

Jeffrey M. Dayno: Thanks, Sandeep. Kumar?

Kumar Budur: Hey, Ryan. Good morning. Regarding lorcaserin, which is EPX-200, we are doing some pre-IND-related work right now. Ryan, as you know, lorcaserin is more selective for 5-HT2C, and this drug probably has one of the largest safety and tolerability databases out there, including the long-term cardiovascular outcome study. Also, there is a lot of efficacy data in several DEEs with this compound. Our goal is to leverage all of the data that is already available and pursue an accelerated development program and hopefully bring a new medication to patients with developmental and epileptic encephalopathies.

Operator: Thank you. And we will go next to Danielle Brill with Truist Securities. Your line is now open.

Alex (for Danielle Brill): Hey guys, this is Alex on for Danielle. Thanks for the question. Two little detailed ones. One follow-up on Jay's question on Onstrike. I wanted to ask, have those begun enrolling patients? Just we have not seen any indication in ClinicalTrials.gov. And then on the OpEx expenditure, you mentioned the impact from some of the settlements and litigation. Was that primarily in the general and administrative line item? Just kind of curious how that run rate we should expect moving forward. Thanks so much.

Kumar Budur: Hey, good morning, Alex. On Onstrike-1 and -2 studies, as we have mentioned in the past, we started initiating sites towards the end of last year, and it will be posted on ClinicalTrials.gov typically within 21 to 30 days after the first subject is enrolled. We are at a different stage of site initiation, site doc activation. Sites are getting prepared to enroll the patient.

Sandip S. Kapadia: And regarding the expenses, yeah, most of them, they were all under G&A in terms of the ANDA litigation and settlement expenses. Some of it tend to be one-time expenses, and some will continue as we continue with the litigation process.

Operator: And thank you. We will move next to Corinne Johnson with Goldman Sachs. Your line is now open.

Corinne Johnson: Thanks. Good morning. Maybe I know you cannot speak too much about the details of ongoing litigation, but you could help us understand kind of the timeline for decisions that are expected in that, what process you kind of could anticipate for appeal for a situation like this, and also kind of remind us the regulatory exclusivity timelines that you have? And then I know you have talked about the litigation or the settlements you have, kind of with six of seven of these other generic manufacturers, but can you clarify what the impact this litigation might have on potentially, like, acceleration clauses in those settlements? I think those are pretty standard, but not sure if they are included here.

Thanks.

Jeffrey M. Dayno: Yeah, Corinne, thanks for your question. So with regards to the timing of the judge issuing a ruling, it is really hard to know and I cannot really speculate. You know, this is an ongoing legal process, and it is hard to know when that will complete and come to final decision. As a reminder, you know, there is a stay that is in place that extends to February 2027, and then, based on the outcome of the trial, obviously, an appeals process is available to both sides.

I think we know that the litigation process, as well as the appeals process, takes time, and, you know, with that, while this was happening, again, I think pointing back to the progress we have made on the settlements, in terms of the six of the seven generic filers being settled, we feel that positions us well going forward with regards to the overall process.

In the meantime, you know, there are other things going on with regards to, as we just spoke to, you know, the pitolisant GR in extending the franchise, and, you know, that is, we remain, you know, with regards to last week's trial, you know, we remain confident in the strength of the IP, and we will continue to vigorously defend it as the legal process plays out, you know, after the trial. Two more in terms of regulatory exclusivities, so in terms of our regulatory exclusivities of where we are with regards to, I mean, ODE with regards to EDS, you know, takes us to March 2026 and for cataplexy to October 2027.

Corinne Johnson: Thank you. Mhmm. August 2025.

Operator: Thank you. And we will take our next question from Patrick Ralph Trucchio with H.C. Wainwright. Please go ahead.

Patrick Ralph Trucchio: Hi, good morning. Just a couple of clarification questions and then a follow-up. First, I think you reiterated 2026 Wakix guidance of $1,000,000,000 to $1,040,000,000. What level of average patient growth is embedded in that range, and how much incremental contribution do you expect from the newly approved pediatric cataplexy indication in 2026?

Jeffrey M. Dayno: Good morning, Patrick. Adam, want to respond to the patient reporting that?

Adam Zaeske: Yeah. Thanks for the question. So for 2026 guidance, you know, exceeding basically $1,000,000,000 or blockbuster status, the underlying patient growth is consistent with what we have seen this year. So we expect that momentum to continue. We are really excited to see the third consecutive quarter of more than 400 patient adds in a quarter. We have never seen that before in the brand. We believe that is a strong foundation, momentum carrying us into 2026, and we expect that to continue. You are going to see the regular and normal seasonality that we have seen over the last several years.

You know, Q1 tends to be a little bit slower as the start of the calendar year with payer resets and what have you. So we expect that seasonality to continue, but the underlying sort of average performance, we would expect to continue the momentum we saw in 2025. Hopefully that covers the question.

Patrick Ralph Trucchio: Yes, that is helpful. And then just as regards to broader CNS strategy with MS-fatigue, I am wondering first, can you elaborate on what existing clinical data supports the efficacy in fatigue and what the development timeline to your Phase I PK study?

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

Your question about clinical data, Patrick, we actually showed the efficacy data in fatigue with pitolisant in our myotonic dystrophy study, where we saw clinically meaningful improvement in symptoms of fatigue, and we also saw dose response. Similarly, we also saw clinical efficacy data in fatigue in patients with residual excessive daytime sleepiness with OSA. So with all of these data points, we plan to pursue broader CNS indications where fatigue is a prominent symptom, and we have identified fatigue in MS as a lead indication because it is very well characterized, very well known, and about 80% of patients with MS have fatigue, with more than 50% having clinically significant fatigue.

In terms of where we are with the development program, right now, the focus is on formulation optimization, looking at potentially other modes of delivery, prepare for a PK study, clinical PK study. That is where we are. Thank you.

Adam Zaeske: Great. Thanks. If I could just jump in, neglected to answer the second part of your question around the pediatric cataplexy opportunities. So just a quick couple of words on that. We are really excited about the approval of pediatric cataplexy. We now have approval for EDS and cataplexy in both adult and pediatric populations, basically anyone over six years of age. The pediatric patient population represents about 5% of the total narcolepsy population, just to give you an idea around scale of the opportunity. But really, see this as, look, this is an important addition to the label. It provides greater flexibility for healthcare providers in their ability to treat these patients.

It is important new information that we will educate those healthcare providers on, and it, I think, reinforces Wakix as an appropriate treatment for peds, as well as having just broad clinical utility across almost all patients with narcolepsy. Our teams were really well prepared ahead of the approval. As I mentioned, we had a robust promotional and execution strategy ready to go, and we began executing on those plans really from the day of approval.

Operator: Thank you. We will go next to Jason Gerberry with Bank of America. Please go ahead.

Pavan R. Patel (for Jason Gerberry): This is Pavan Patel on for Jason Gerberry. Just a couple of questions for us. The first is, I know you guys mentioned expanding the field sales and reimbursement teams in 2026. So maybe if you can just help us understand how much of this investment is dedicated to the core narcolepsy market versus preparing for new launches like the pitolisant GR in the future? And then the second question is with regards to BD, maybe if you can speak to BD as a capital allocation priority versus share repurchases or other things and how you are planning to diversify beyond the pitolisant franchise ahead of an important IP outcome providing clarity on the sole commercial asset. Thank you.

Jeffrey M. Dayno: Yes. The first part of the question was around the expansion. Adam?

Adam Zaeske: What does that look like, and how much of that is related to core, basically growing Wakix, versus preparing for GR? I mean, the short answer on that last piece is 100% of the investment expansion is around continuing to grow Wakix today. Our plans for how we will launch GR will take form kind of as we progress through the calendar year this year and approach that PDUFA date in Q1 2027. I will remind that we were really pleased with the performance we saw in 2025, really record-setting performance, and that was based on continuing to tweak some of the fundamentals around our sales execution, marketing promotional mix and messaging, adding some payer wins, and supporting patients.

As we enter 2026, we triggered an expansion of our field-based teams. That is what you were asking about. Overall, it is about a 20% increase in total field-based personnel. So we see that as a really significant and meaningful increase in our share of voice. Also gives us the opportunity to rebalance territories that you want to do about every 18 months to two years. With our field sales teams, we are seeing that expansion more than 10%. Field reimbursement more than 50%. Our remote sales teams more than 10%. So it is really meaningful, and we are excited about that opportunity. We have posted those roles. We are already in the process of hiring.

We have already identified several of those candidates, so we expect those folks to be in place by the end of this quarter. That is our plan. Thanks for the question.

Jeffrey M. Dayno: And with regard to the second question on business development, business development remains a high priority for us, obviously, with a very strong balance sheet, and we want to deploy that and invest in the business. As we said, the sweet spot, the focus continues to be orphan rare CNS opportunities, late-stage development, as well as commercial on-market. We have the capacity to do that. Obviously, we have a strong commercial engine. We would like to build out the commercial portfolio. Dedicated business development team, and we are also, you know, looking, and we have said this before, you know, adjacencies, broader CNS indications.

Obviously, we shared today a new opportunity that we are very excited about based on newly licensed IP, with the new formulation of pitolisant, where we see a significant opportunity around fatigue in broader CNS populations. So we are focused and committed to those efforts, deploy our capital towards business development. Sandeep, any thoughts on capacity?

Sandip S. Kapadia: Yeah, look, I think we are in a very strong position. We have over $880,000,000 in cash on the balance sheet at last quarter. And just to your question, I mean, not only obviously we are looking at this, but of course, we also have $150,000,000 capacity on the share buyback. So we are always looking at opportunities to drive value for shareholders, and that is something that, you know, we have the optionality as a company to move forward there.

Operator: Thank you. And we will go next to So Yoon Shin with UBS. Please go ahead.

So Yoon Shin: Good morning. Thank you for taking my question, and congrats on the great year. I have two questions, if I may. First, so it seems like the settlement for generic entry with the three additional ANDA filers are now four months early, March 2030, if pediatric exclusivity is granted, from the prior settlement agreement of July 2030. So just wanted to check if I am understanding it correctly. Does it mean without the pediatric exclusivity, the generic entry would start no earlier than September 2029 now? And my second question is on Prader-Willi syndrome indication for Wakix. So the Phase III reading out 2028. Here, I was wondering what are you envisioning as opportunities from the PWS?

It would support the pediatric exclusivity for Wakix and delay generic entry too, but on just the PWS indication itself, the runway would just be about two years from launch if approved. Are you thinking of trying PWS with the pitolisant HD as well?

Jeffrey M. Dayno: So Yoon, thanks for your questions. With regards to your first one about the timing of the settlements, you are correct in terms of without the pediatric exclusivity market entry would be September 2029. But we are on track on making very good progress towards pediatric exclusivity, which will take it to March 2030. One of the important components of that, obviously, the peds narcolepsy data, is the Prader-Willi program, both for potential indication, but the larger market opportunity, I think, as you are aware, is the six months extension with the peds exclusivity. Kumar, further thoughts on that?

Kumar Budur: Yeah. Good morning, So Yoon. With PWS, in the U.S. alone, there are approximately 15,000 patients with Prader-Willi syndrome. About half of these patients have significant excessive daytime sleepiness, for which there are no drugs approved. If we are successful with this study, we will go for an indication really addressing high unmet need in this patient population. And in terms of pitolisant HD being a potential option to pursue PWS, that is not how we are thinking right now, but that option is always open to us. Thank you.

So Yoon Shin: I see. Thank you.

Operator: Thank you. And we will take our next question from David Timothy Hoang with Deutsche Bank. Your line is now open.

David Timothy Hoang: Hi, good morning. Thanks for taking my questions. So maybe on the new pitolisant formulation, could you talk a little bit about characteristics and profile you expect to see with that product? How is it different from, let us say, the pitolisant HD? And are there characteristics that lend itself to MS-fatigue and related conditions? And then maybe a second question just around the IP estate for some of these life cycle products. So could you just summarize again for us the patents that you either currently have or expect to obtain for pitolisant GR, HD, and then the new formulation? Thank you.

Jeffrey M. Dayno: Hey. Good morning, David.

Kumar Budur: Regarding the new formulation, as we evaluated this opportunity, there might be some potential options for us with this new formulation that could potentially differentiate itself in terms of the PK parameters that probably will lend itself better for the treatment of fatigue in larger indications. Obviously, once we complete the human PK study, that is when we will get to know how exactly this will play out in human, and that will help us determine the next step. But for now, we are really excited about this particular formulation because, as I mentioned earlier to the other question, this is a very unique opportunity for us to pursue fatigue in broader CNS indications.

Jeffrey M. Dayno: And, David, in terms of your second question about the IP estate, just briefly as a reminder, the pitolisant GR and pitolisant HD utility patents filed out to 2044. This new formulation of pitolisant, the opportunity there is actually an issued patent that we have a license to out to 2042. So formulation work continues on, as Kumar mentioned, the potential of other modes of administration, looking at, you know, the potential, some of these patient populations where there is swallowing dysfunction and other methods of delivery, but an issued patent out to 2042.

Operator: Thank you. We will take our last question from Ami Fadia with Needham and Company. Your line is now open.

Purna (for Ami Fadia): Hi, this is Purna on for Ami. Thank you for taking our question. Are there any recent updates for the enrollment from the ORCA and the LIGHThouse study? And just in case I missed this, what are the targets for the recent sales force expansion, and when do you see that impact coming through? Thank you.

Kumar Budur: Good morning, Purna. ORCA and LIGHThouse study, they continue to enroll and we continue to make progress. We are on track for top-line data in 2027 and PDUFA in 2028.

Adam Zaeske: And on the sales force expansion targets and impact timing, we did add some targets—about 5%—primarily to improve share of voice and rebalance territories within our existing target base. We aim to have the new hires onboarded by the end of this quarter, so you should expect to see impact from that point forward.

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

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

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

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