Good morning, everyone. I'm Ami Fadia, Biotech Analyst here at Needham. It's my pleasure to be hosting the Harmony Biosciences team today. I have with me Jeffrey Dayno, who's the CEO of the company, along with Kumar Budur, Chief Scientific Officer, and Adam Zaeske, Chief Commercial Officer. Thanks, all three of you, for taking the time to be with us today. Maybe if I could ask Jeff if you could kick us off with some opening remarks, some priorities for this year, and then we can take it from there.
Yeah. Sure, Ami. Yeah. Good morning, Ami, and on behalf of the Harmony team, thank you once again for the invitation to Needham's Virtual Healthcare Conference. We are very excited for what is coming this year. That sets us up for both near-term and long-term growth and value creation. As for some of our key priorities, just to sort of walk through, starting with WAKIX. We are on track to achieve over $1 billion in net revenue for WAKIX in its sixth year on the market, which provides us with a very solid foundation, I think as many are aware. In our pitolisant next-gen programs, Pitolisant GR, gastroresistant, is on track for NDA submission this quarter to extend the pitolisant franchise with a target PDUFA date in the first quarter of next year of 2027.
For pitolisant high dose, or HD, we're in the clinic with two phase III registrational trials, one in narcolepsy, one in idiopathic hypersomnia, or IH. These are designed to expand the pitolisant franchise with target PDUFA dates both in 2028 and utility patents filed out until 2024. These programs are also designed to evaluate new labeling for unique indications, such as fatigue in narcolepsy and sleep inertia in IH. Kumar can tell you more about our new formulation of pitolisant that we acquired through a license through an issued patent that goes out to 2042. This will give us an opportunity to explore pitolisant in broader CNS populations in which fatigue is a prominent symptom. There is a scientific and a mechanistic rationale to this strategy and this approach. We're also excited about this new opportunity.
There's a lot going on in the pitolisant franchise, but we are very excited about our advancing orexin program with BP1.15205, for which we are on track for top-line data from the phase I single-ascending-dose PK trial in healthy volunteers mid-year, followed by an IND submission in mid-year. We'll initiate a phase I PK trial in sleep-deprived healthy volunteers, which will provide us some initial data on signals of efficacy as well as safety, tolerability, along with dose ranging for a phase II proof-of-concept study. Another priority that I want to remind everyone is our development program in the developmental and epileptic encephalopathies with EPX-100. Two phase III trials are advancing, one in Dravet syndrome and one in LGS, with top-line data anticipated from both of those in 2027 and target PDUFA dates in 2028.
I think this all adds up to Harmony really having a robust late-stage pipeline in CNS with five phase III trials toward five distinct CNS indications driving multiple catalysts over the next few years. Finally, Business Development, a very high priority for us with over $880 million on our balance sheet. We are always actively pursuing strategic BD deals to both build out our pipeline, looking for commercial opportunities to expand our commercial portfolio to drive even greater value creation. A high-level summary of what's coming and advancing in 2026, and we're excited about the status of our business and future opportunities.
Excellent. Thank you so much, Jeffrey. Maybe we can dive into some of these topics, maybe starting with WAKIX. Could you help us understand the setup for the product for this year with your guidance of over $1 billion in revenue? What are some of the initiatives that you're focused on, and what are some of the metrics that you're tracking to make sure that this drug is continuing to sort of grow this year and into future years?
Sure. Adam?
Yeah, thanks, Ami, and thanks for hosting us this morning. Good morning, everyone. As you can tell from Jeff's comments, it's exciting times at Harmony, and especially with the performance of WAKIX. We're really pleased with the momentum we're seeing as we finished 2025. As you know, Ami, we typically see patient additions of 100-400 patients a quarter. For the last three quarters, we've seen 400-500 patient adds in the last three quarters, really, really strong growth and momentum carrying us into 2026. What's driving that is the core differentiation of WAKIX as fundamentally a unique product profile, the only non-scheduled treatment option available for patients. We also have a very experienced team now, several years of positive track record of consistent performance, broad access. In 2025, we continued to make improvements to how we are bringing WAKIX to the market.
We continued to refine our sales force excellence, promotional mix, and messaging. We added a couple of payer wins in 2025, and we continue to make improvements in our processes that support patients to get to a dispense event faster and with higher success. Those are some of the elements and tweaks that we're making in 2025 to really fuel that momentum and performance. As we move into 2026, now we're actually expanding our teams. We're expanding our field sales, our remote sales, as well as our field reimbursement teams across the board on average of about 20%. It's a meaningful expansion. We've effected that expansion in first quarter, so all those folks are now in place.
They've been hired, they're in training, in role, and we expect continued strong performance this year and now with an expanded team, hopefully continuing that momentum through 2026 to achieve, as you said, the guidance of a billion-plus in net revenue for the year.
Yeah. You obviously have been demonstrating that this drug can continue to grow so many years into the launch. I think that's really impressive. You continue to invest more behind the asset. I think some of the investor concerns or sort of focus seems to be around one of the ANDA filers that's outstanding. Can you talk about where the process is at with respect to that litigation and what are the next steps with regards to the hearing and how you're thinking about reacting depending upon the hearing?
Yeah, Ami, at a high level to share what I'm able to. Two processes running in parallel, sort of the legal process, the trial, as that continues to play out, and obviously our efforts towards settling with the ANDA filers. I think, as we have shared, we've settled with six of the seven ANDA filers with LOE to September of 2029, and then along with pediatric exclusivity, for which we're on track to achieve, taking it to March of 2030. I think reflective of those settlements, reflective of our strong IP position that we believe in, and I think we are well positioned in terms of that process of settling to continue to see that through. With regards to the trial, post-trial briefs were submitted last Thursday. After the initial trial, the briefs went in, and that process continues to play out.
We can't obviously predict the timing or the outcome of the process, but we follow that closely and really focus on the settlement process as we have achieved thus far, and trying to secure that for the WAKIX franchise. As I alluded to, while that's happening, our focus is on the next-gen programs. Pitolisant GR right around the corner, out ahead of the LOE with regards to a target PDUFA first quarter next year. We've got a very exciting opportunity with a new formulation, an exclusive license to a new formulation, issued patent to 2042, that is unique and different from the areas we work in.
Looking in these broader CNS populations, I think Kumar shared a little bit of that on our last earnings call, where fatigue is a prominent symptom, such as fatigue in MS, fatigue in Parkinson's disease, a strong scientific and mechanistic rationale, and positive proof-of-concept data for pitolisant and fatigue from our phase II proof-of-concept study in type 1 myotonic dystrophy with a strong signal and a dose response. Aside from the backdrop of the current sort of trial and other activity, we see continued opportunity with the pitolisant franchise.
I think that's a great segue. I kind of wanted to dig a little bit further into the Pitolisant GR formulation, and you mentioned the PDUFA date in early next year, first quarter. Can you help us understand how that impacts the overall target addressable market, how it helps you bring back some patients that might have not been able to tolerate WAKIX? Help us sort of quantify that a little bit.
Sure. Go ahead, Adam.
Yeah, sure, I can jump in on that. With the GR formulation launching early next year, I mean, that's right around the corner. We're excited about this. We see significant patient benefit here, GR coating addressing the fact that, I mean, 80% of patients with narcolepsy have the potential for GI symptoms related to the disease, not necessarily related to WAKIX, but related to the disease and the underlying mechanism of the disease. GR coating makes sense, especially for a product whose foundation is not only strong efficacy but a really, really strong safety and tolerability profile, and we believe it adds to that foundation. You also have the opportunity that patients can start at a therapeutic dose. No titration required, which will help get patients to patient outcome faster and more effectively.
With that profile and launching early next year, what we see is the opportunity that any new patients that would've been prescribed WAKIX would be prescribed the new GR formulation, and we tested this in research. Physicians are very open to this. It makes sense. It makes intuitive sense. Also we have an opportunity to recontact previous patients. In our unique model, we actually secure consent upfront for all patients prescribed WAKIX, and we have the ability to recontact them over time. This is actually a significant patient population. We can identify those patients that may have discontinued over time for various reasons and educate them, make them aware that the GR formulation is now available. It might be something that they want to speak with their physician about.
Historically, we've thought about the GR as between $3 million and $500 million opportunity, and we're excited to launch that early next year.
Through your unique distribution process, you've been able to get some information about why certain patients might have discontinued if they were willing to share the reason, and you can maybe go back and contact those patients.
Yeah, exactly. What's important to remember in this class, patients tend to cycle through combinations of treatments frequently. We see patients discontinue on WAKIX and then restart, discontinue, and that's also the same with other therapies in the class. Now, not only will they have the benefit of the GR coating, but if they decide to restart, there'll be no titration. They can start immediately at that therapeutic dose. It makes it a little bit smoother and easier for them.
Can you talk about the high-dose formulation? What is the strategy with that? We are expecting data from the IH study in 2027 for that. How does that fit into your sort of life cycle management strategy here?
Yeah, sure. Happy to speak about that. The HD, think of the HD as a totally new branded launch and a highly differentiated product. It carries with it the benefits of the GR formulation, so the coating, as well as started at a therapeutic dose. Now you have up to 2x the approved dose of WAKIX, hopefully bringing improved efficacy and better patient outcomes, and we're pursuing unique indications in narcolepsy and IH with the HD formulation. You have something that's truly differentiated with indications that no other brand has, with up to 2x the dose of WAKIX and the benefits of GR. This is a 2028 PDUFA, highly differentiated new brand launch. I should mention, historically, we've talked about the HD as a billion-plus opportunity. Both of these formulations, the GR and the HD, have utility patents out through 2044.
Also really extends the franchise and our runway to continue to benefit patients with our pitolisant franchise overall.
Yeah. Ami, one more point just to add about HD. As opposed to GR, which is based on a demonstration of bioequivalence, this is also a unique formulation. This is an enhanced formulation with a different PK profile. Milligram for milligram, greater exposure, with demonstrated, Kumar and the team, safety margins well beyond going two times the highest labeled dose. Driving efficacy, driving unique indications, and really as Adam said, sort of a new branded launch as opposed to GR more as a line extension near term, as we build to a truly differentiated product in Pitolisant HD.
Yes. I definitely wanna also talk about the new formulation that you disclosed at your last earnings call, which is meant to address fatigue in indications like MS and Parkinson's. Could you elaborate on the mechanism behind this and how you identified MS and Parkinson's as the focus indications to go after, and what we can expect with regards to the development timelines around that formulation?
Yeah, absolutely. Kumar?
Sure, Jeff. Thank you. Good morning, Ami. Thank you for hosting us today. The new formulation of pitolisant, if we take a step back and look at fatigue in general, this is something that we have been thinking about for a while now. That's mainly because fatigue is a multidimensional concept as opposed to excessive daytime sleepiness, for example. Fatigue has emotional, physical, and cognition aspects to it. The histaminergic mechanism of action, because of the way it works, not just on the histamine circuitry, but also the downstream norepinephrine and serotonin mechanism of action, it is uniquely positioned to address all three aspects of fatigue. That's exactly what we saw when we did our phase II proof of concept in myotonic dystrophy, where about 90% of the patients have significant fatigue.
In that study, we showed that pitolisant not only improved fatigue in a clinically meaningful way, but it also showed a dose response. Not only that, we also studied fatigue in patients with residual excessive sleepiness in OSA. In fact, that actually is in the label in Europe, where pitolisant is marketed as WAKIX for residual excessive daytime sleepiness in patients with sleep apnea. When we had this opportunity to get our hands on this new formulation with an issued patent until 2042, there were certain features of this formulation which lends itself better to treat fatigue in broader indications. That's when we decided to go ahead and pursue indications like fatigue in MS, fatigue in Parkinson's disease. We prioritized fatigue in MS because this is where fatigue is very well characterized.
More than 80% of patients with MS have some kind of fatigue, and more than 50% of patients with MS have significant fatigue. Folks have done some work in terms of how to measure fatigue in these patients. There is some longitudinal data for fatigue in MS, and based on the pitolisant profile that we know and some of the work that has been done in the past in the preclinical space, that was logically our next first indication for a broader indication like MS. That's where we are. In terms of where we are in terms of our clinical development, right now, we are optimizing the formulation. The next step would be to do a phase I PK study, and we'll take it from there.
Got it. Okay. I want to step back and think about the competitive landscape here for a second before we move on to BP1, your orexin. I wanted to get your thoughts on how you're thinking about the landscape that's evolving with the first orexin that will get approved later this year, which is a Takeda product. How do you see that impacting WAKIX in the near term? Now, we know that that's approved or expected to get approved just in NT1, so how do you see that impacting the WAKIX utilization in the near term? Maybe stepping back, how do you see that impact, with the entry of other orexins over time, how do you see WAKIX being positioned in the market? Maybe we can talk about the two sort of life cycle assets, the GR and the HD formulation.
How does that help you navigate that competitive landscape over the next couple of years?
Yeah. Yeah. Ami, before I turn it over to sort of Adam in terms of market impact of the emerging orexins and Kumar on our development program, just comment that, obviously, an incredibly exciting space. So much attention and activity around the orexin development programs for good reason. Novel mechanism, really the first new novel mechanism coming to central disorders of hypersomnolence and probably more, and we can talk about that a lot as well, since WAKIX launched. We are very active in this space, following the programs, our own development programs, other activities with our partner, Bioprojet, looking at even indications beyond sleep-wake. I just wanted to emphasize that comment, and then I'll turn it over to Adam and Kumar on further thoughts of impact, and then our development program.
Sure. Happy to jump in. As you can imagine, Ami, this is a question we've spent quite a bit of time thinking about and analyzing, conducting market research. We're excited about orexins, new treatment option for patients. In the research, what we see is, yeah, there's definitely excitement, interest based on the efficacy profile. There's also some remaining questions around some of the adverse events and tolerability. As you've seen, there's pretty high rates of insomnia, up to 60%, frequent urination, visual disturbances in some cases, and of course, limited long-term data. There's definitely interest to try, but I think this is going to be a gradual approach to trial, and as we learn more, we'll see how physicians end up utilizing orexins as a new treatment option. In terms of impact, in narcolepsy, we're still less than 50% diagnosed and even less treated.
Hopefully with the awareness that the orexin class brings, we'll see an improvement there for patients. We also have seen over the last, let's say, five or six years, an expansion of brand utilization, but brand utilization is still, what? Around 20% of the class. We would expect a new brand launch to expand brand utilization as well, and that's actually what we've seen historically. As new brands come in, they tend to expand brand utilization rather than steal share from other brands. That's the polypharmacy approach, which is the hallmark of this class. Clearly, we've seen in research and our discussions with healthcare providers, they will prefer to continue that approach, and so we would expect an expansion of brand utilization as well.
When it comes to treatment selection, WAKIX, we believe, will continue to grow in the face of orexins because it's going to continue to offer something that's totally different and unique than any other treatment option when you look at the totality of efficacy and safety tolerability. Really good efficacy, but exceptional safety and tolerability and extremely clean profile.
That allows WAKIX to be added on to virtually any combination of therapies in a polypharmacy market, and that profile is going to continue to be the case with WAKIX now with seven years of clinical experience, and it's going to continue to be differentiated versus all other competitors, including orexins. That's where we see physicians are really familiar with WAKIX, seven years of clinical experience. It's a go-to add-on therapy in a polypharmacy market, and we expect that to continue.
Yeah, Ami, from a development perspective, but from a clinical, medical, and scientific perspective, I'm very fascinated with the orexins, and I'm even more fascinated with our own orexin because of several distinguishing features. This continues to be the most potent orexin receptor agonist in clinical development. The potency we are talking about is at 0.015 nanomolar levels, and this does offer a benefit of targeting all three central disorders of hypersomnolence at very low doses with the same drug and limit the off-target AEs. In addition, we also have a novel chemical scaffolding that helps not just with its potency, but also helps with some off-target AEs that were observed with earlier orexin receptor agonists, like LFT abnormalities or QT prolongations. On top of it, we have excellent selectivity.
The preclinical safety data has been very clean, and also the preclinical PK profile is supportive of potentially once-a-day dosing regimen. We started dosing patients in the fourth quarter of last year. We are on track to get full clinical PK data in single ascending dose study in healthy volunteers. After that, we plan to submit the IND and conduct a sleep-deprived healthy volunteer study, which will help us to bracket the dose range, and then we'll immediately move on to the next stage of development.
Kumar, do you think the potency can help differentiate on some of the adverse events that I think Adam had mentioned? Yeah, those are the most common adverse events that we are seeing with the orexins, which is insomnia, polyuria. Do you think that a more potent molecule can help meaningfully reduce those adverse events that we're seeing, which are on-target adverse events?
Great question, Ami. That's something that we'll have to wait until we get the clinical data.
We know that having a large potency, high potency like this will definitely help us to go with a much lower doses and target NT1, NT2, and IH. The emerging data has shown that you need a much more potent drug to target NT2 and IH, or go really high on the dose. That's when you end up seeing many of the off-target AEs the other sponsors have disclosed to some extent, like visual disturbance, and hypersalivation, things like that. The on-target effects, that's something that we need to wait for the clinical data, but the off-target AEs, clearly, we will be able to manage that with a very high potent orexin receptor agonist at very low doses.
Yeah, Ami, the other interesting part of this is, as we look at this conversation and the interest in orexins, beyond central disorders of hypersomnolence, some of these new targets that are cognition, mood, et cetera. When you move away from NT1, which is a disorder of orexin deficiency, where obviously, the main efficacy has been proven, but then NT2, IH, and then these other potential indications around cognition, mood, ADHD, and probably others to be discussed in the future, that we are also looking at and contemplating and doing some work with our partner. They're not disorders of orexin deficiency, so having a potent compound, as Kumar said, and dosing flexibility may also be very relevant as this sort of platform play kind of evolves, if you will.
Yeah, you have the benefit of taking some learnings from some of the other companies that are running clinical trials. I'm just sort of curious what type of data you believe you need to generate with either BP1 or what you need to see to sort of lay out a path for your own asset in terms of which indications you're going to go after and how you're going to elucidate its differentiated profile?
Yeah, Kumar.
Yeah, Ami. In pharma in general, in drug development in general, the first asset is not necessarily the best asset, right? More often than not, it's the fourth or the fifth asset that ends up becoming the best-in-class asset. To some extent, we are seeing this play out here as well, and we already incorporated many of the learnings from the previous compounds. I mentioned about going for a new scaffolding rather than the typical pyrrolidine sulfonamide bicyclic. The reason for that is to exactly avoid some of the off-target structural-related AEs, like abnormalities in LFTs or cardiac abnormalities like QT prolongation, and we successfully accomplished that. The second thing was potency. Potency was extremely important for all the reasons that we discussed earlier, and we achieved that with the 205 compound.
In fact, we did disclose this data at the last Sleep meeting, where in the transgenic mouse model of narcolepsy, 205 demonstrated wakefulness at the lowest dose we ever tested in this particular mouse model, 0.03 mg per kg. It is playing out as we had hoped for, based on pretty much the drug design. The medicinal chemists here at Bioprojet worked based on what was seen with the earlier compounds. In terms of clinical development, we'll be looking at efficacy, safety, tolerability, the dosing frequency, and the dose range. That will help us determine how to go about with the next indications. Based on what we are seeing, we believe we should be able to target NT1, NT2, and IH with the same drug with very low doses and with a very favorable benefit-risk profile. Obviously, we need clinical data to demonstrate that.
We'll get there soon.
Yeah, that makes sense. Great. I wanted to switch gears to your epilepsy program, EPX-100. At AES last year, you disclosed data from its open-label ARGUS study, well, the open-label portion of the ARGUS study. We saw that it demonstrated a 50% median reduction in CMS-28 from baseline. We saw a reduction or a response in at least 50% of the participants. Based on the data that you've disclosed so far, and of course, a lot of the differentiation comes on the safety side of things as well, how do you see it positioned in the market? We know that there are other drugs that are also in development. How are you thinking about its market positioning from a commercial standpoint?
Right, tell me from a.
Clinical, yes, of course.
From a clinical perspective, right? You're absolutely right, the data that we just mentioned. That's clinically meaningful efficacy. We need to hit the efficacy bar, and a 50% median reduction compared to baseline is considered as clinically meaningful by all clinicians who deal with these patients. It's important to remember that this is adjunctive therapy. This is on top of about four to six anti-epileptic medications these patients are already taking. In this context, it is considered as very clinically meaningful. The other aspect of the equation here is tolerability and safety. One of the biggest challenges that patients have with all the medicines that are approved in this space is tolerability and safety.
Even the most recently or more commonly used medications like, for example, Fintepla and EPIDIOLEX, they have significant issues with appetite suppression in a patient who is already cachectic, has some feeding difficulties. About 20%-30% in some instances, nausea, vomiting, abdominal cramps, and diarrhea. With EPX-100, the only GI AE that we saw of any clinical relevance was diarrhea in just for about 2% of the patients. In terms of safety, we do not have to do any of the routine safety monitoring. For example, with EPIDIOLEX, you need to check with LFTs every so often because of unpredictable elevation in liver function tests. With Fintepla, for example, it's important to do echocardiogram on a regular basis. In fact, it's part of the REMS program. We don't see the need for any special medical monitoring.
The benefit-risk profile is very differentiated with EPX-100 compared to anything that is approved thus far.
Yes, maybe I don't know if this is a good time to also get a sense of where in the treatment paradigm, in the real-world setting, do you see it being used? If a patient is not achieving goal, then this is another option that can be considered for being added on top of existing therapy.
Yeah, that's exactly what happens, Ami, in this particular space. It's a chronic condition. These patients have treatment-refractory seizures. In fact, with all the medicines that are approved in this space, about 50% of the patients still have seizures that are not adequately controlled with the existing treatments. This is being studied as an adjunctive therapy, that is add-on therapy, and we see it as being used as an add-on therapy on top of everything else these patients are currently on.
Yeah, I know we have just a couple of minutes left. I wanted to talk about sort of the balance sheet, and I think Jeff mentioned at the beginning of our conversation that you have over $800 million in cash, and certainly, over the last couple of years, you have executed on deals to bring in different assets into the mix. Has anything with regards to your strategy or approach to thinking about what type of assets you would pursue changed over the course of the last year? At this time, are there certain types of drugs or things that you could add on to your existing portfolio that would be more interesting than others?
Yeah, Ami, thank you for that question, sort of an important priority for us. I think that our core strategy has really not changed. In terms of the core strategy, I think we've sort of opened up the aperture a little with regards to what we're looking at across the BD landscape. Our sweet spot is in orphan rare CNS and neuropsych targets, and we sort of look across the landscape for opportunities there. More recently, and given our capacity, we're open to looking at potentially assets with broader indications outside orphan rare, what we call sort of adjacencies to our core strategic franchises, in sleep-wake and the rare epilepsies.
Importantly, again, given our capacity and where we are in our evolution, not just pipeline assets, but on market as well, which I think is probably the most recent sort of evolution of our thinking because we have the capacity, we have a strong commercial engine and a strong commercial team, as you're aware. I think the ability to add another product to their bag and beyond just WAKIX and the pitolisant franchise where there's a good strategic fit, that is the current thinking, and looking at both strategies, whether we do sort of tuck-ins, if you will, or string of pearls in smaller opportunities, but also open to something more transformational. We have the capacity, we have the experience and the know-how across the team.
If we see something larger that is a good strategic fit, is a smart business development deal for us, we are also looking really across the spectrum of those opportunities.
Okay. That's very helpful. I think we are almost out of time, so this is a good opportunity for me to thank you all for taking the time to have this conversation with me and look forward to our future conversations. Thank you so much.
Ami, thank you. On behalf of the team, thank you so much for the invitation. Always enjoy our conversations. Thank you.
Likewise. Thanks.
Okay.