Good morning, everyone. I'm Ami Fadia, biotech analyst here at Needham. It's my pleasure to be hosting the Harmony Bioscience team today. I have with me Jeff Dana, who's the CEO of the company, along with Kumar Badur, Chief Scientific Officer, and Adam Zesky, 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, you know, 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. And, you know, we are very excited for what is coming this year. You know, that sets us up for both, you know, near-term and long-term growth and value creation. As for some of our key priorities, just to sort of walk through starting with wakex so you know we are on track to achieve over a billion dollars in net revenue for wakex in it in its sixth year on the market which provides us with a very solid foundation i think as many are aware in our patollicin next gen programs patollicin gr gastro resistant is on track for nda submission this quarter to extend the patollicin franchise with a target pidufa date in the first quarter of next year of 2027. for patollicin high dose or hd you know we're in the clinic with two phase three registrational trials one in narcolepsy one in idiopathic hypersomnia or ih and these are designed to expand the patollicin franchise with target pidufa dates both in 2028 and utility patents filed out until 2024 these programs are also designed um to evaluate you know new labeling for unique indications such as fatigue and narcolepsy and sleep inertia in ih kumar can tell you more about our new formulation of patolescent that we acquired through a license to an issued patent that goes out to 2042 and this will give us an opportunity to explore patollicin in broader cns populations in which fatigue is a prominent symptom and there is a scientific and a mechanistic rationale um to this strategy in this approach and we're also excited about the you know this new opportunity so there's a lot going on in the patollicin franchise but we are very excited about our advancing orexin program with bp 1.15205 for which we are on track for top line data from the phase one single ascending dose pk trial in healthy volunteers um mid-year followed by an ind submission in mid-year then we'll initiate a phase one 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 two proof of concept study. Another priority that I want to remind everyone is our development program in the developmental and epileptic encephalopathies with EPX100. Two phase three trials are advancing, one in Gervais syndrome and one in LGS, with top-line data anticipated from both of those in 27 and target PDUFA dates in 2028. So I think, you know, this all adds up to Harmony really having a robust late-stage pipeline in CNS with five phase three trials toward five distinct CNS indications, driving multiple catalysts, you know, over the next few years. And then finally, business development, a very high priority for us with over $880 million on our balance sheet. And we are always actively pursuing strategic BD deals to both build out our pipeline, looking for commercial opportunities to expand our commercial portfolio to drive even greater value creation. So a high-level summary of what's coming and advancing in 26, and we're excited about the status of our business and future opportunities.

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

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 WAKEX, we're really pleased with the momentum we're seeing as we finished 2025. As you know, Ami, we typically see patient additions of one to 400 patients a quarter. And for the last three quarters, we've seen four to 500 patient ads in the last three Really, really strong growth and momentum carrying us into 26. And what's driving that is the core differentiation of Wakex as fundamentally a unique product profile, the only non-scheduled treatment option available for patients. But we also have a very experienced team now, several years of positive track record, of consistent performance, broad access. And in 2025, we continue to make improvements to how we are bringing Wakex to the market. So we continue to refine our Salesforce 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. And so those are some of the elements and tweaks that we're making in 2025 to really fuel that momentum and performance. And as we move into 2026 now, we're actually expanding our teams. So we're expanding our field sales, our remote sales, as well as our field reimbursement teams across the board on average of about 20%. So it's a meaningful expansion. We've affected that expansion in first quarter. So all those folks are now in place. They've been hired. They're in training, in role. And we expect, you know, continued strong performance this year and now with an expanded team, hopefully continuing that momentum through that 2026 to achieve, as you said, the guidance of a billion plus in net revenue for the year.

yeah so uh you know you obviously uh uh have been demonstrating uh that this drug can continue to grow so many years into the launch so i think that's uh really impressive and you continue to invest more behind the asset i think some of the investor concerns or sort of focus seems to be around one of the anti-fighters 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. So two processes running in parallel, sort of the legal process, the trial as that continues to play out and then obviously our efforts towards you know settling with the andefilers and I think you know as we have shared we've settled with six of the seven andefilers with you know LOE to September of 2029 and then along with pediatric exclusivity for which we're on track to achieve taking it to march of 2030 so i think you know reflective of those settlements reflective of our strong you know ip position you know that um you know we believe in and i think we are well positioned in terms of that process you know of settling to continue to see that through um with regards to the trial um post-trial briefs were submitted last thursday so um you know after the initial trial um you know the briefs went in and that process continues to play out um so you know and we can't obviously predict the timing or the outcome you know of the process but we follow you know follow that closely and really focus on um the settlement process as we have achieved thus far um you know and uh you know trying to secure that um for the wakex franchise and you know as i alluded to while that's happening our focus is on the next gen programs um patola sent gr right around the corner out ahead of you know the loe with regards to a target padufa first quarter next year um and then we've got a very exciting opportunity with a new formulation that an exclusive license to a new formulation issued patents 2042 um that is unique and different from the areas we you know we work in and looking in these broader cns populations i think kumar shared a little bit of that in our last earnings call where fatigue is a prominent symptom such as fatigue and ms fatigue and parkinson's disease a strong scientific and mechanistic rationale and um positive proof of concept data for pitocin and fatigue from our phase two proof of concept study and type one myotonic dystrophy with a strong signal um and a dose response so um aside from you know the backdrop of you know the current sort of um trial and other um activity um you know we see continued opportunity with you

know the patollas and franchise so i think that's a great segue i kind of wanted to dig a little little bit further into the pitot-of-the-san GR formulation, and you mentioned the put-of-a-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 way kicks? Help us sort of quantify that a little bit.

Sure. Go ahead, Adam.

Yeah, sure. I can jump in on that. So with the GR formulation launching early next year, I mean, that's right around the corner. We're excited about this. We see significant, you know, patient benefit here. GR coding addressing the fact that, I mean, 80 percent of patients with narcolepsy have the potential for GI symptoms related to the disease, not necessarily related to Wacix, but related to the disease and the underlying mechanism of the disease. So, GR coding 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, so no titration required, which will help get patients to patient outcome faster and more effectively. And so with that profile launching early next year, what we see is the opportunity that any new patients that would have been prescribed Wacix would be prescribed the new GR formulation. And we tested this in research. Physicians are very open to this. It makes sense. It makes intuitive sense. And then also we have an opportunity to recontact previous patients. So in our unique model, we actually secure consent upfront for all patients prescribed Wacix, and we have the ability to re-contact 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 three and 500 million opportunity, and we're excited to launch that

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

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

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

Yeah, sure. Happy to speak about that. The HD, think of the HD as a totally new branded launch, a highly differentiated product. It carries with it the benefits of the GR formulation. So the coding as well as started at a therapeutic dose, but now you have up to two times the approved dose of wakex so hopefully bringing improved efficacy and better patient outcomes and we're pursuing unique indications in narcolepsy and ih with the hd formulation so you have something that's truly differentiated with indications that no other brand has with up to two times the dose of wakex and the benefits of gr this is a 2028 pedufa highly differentiated new brand launch and i should mention you know historically we've we've talked about the HD, you know, as a billion plus opportunity. And both of these formulations, the GR and the HD have utility patents out through 2044. So also really extends the franchise in our runway to continue to benefit patients with our patolicin franchise overall. Yeah. And Ami,

one more point just to add about HD, as opposed to GR, which is based on a demonstration of equivalence it's all this is also a unique formulation this is an enhanced formulation with a different pk profile um greater milligram for milligram greater exposure um with you know demonstrated kumar and the team you know safety margins um you know well beyond going two times the highest labeled dose so driving efficacy driving unique indications And really, as Adam said, sort of a new branded launch, you know, as opposed to GR, you know, more as a line extension near term as we build to a truly differentiated product in Pitocin HD.

Yes, I definitely want to 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 how we can, you know, 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. So, the new formulation of Pidolocent, if we take a step back and look at fatigue in general, this is something that we have been thinking about for a while now. That's mainly because fatigue is a multidimensional concept, as opposed to excessive daytime sleepiness, for example. Fatigue has emotional, physical, and cognition aspects to it. And the 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 and that's exactly what we saw when we did our phase two proof of concept in myotonic dystrophy where about 90% of the patients have significant fatigue. In that study we showed that pitolocent 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 pitolocent is marketed as OSAWAID for residual excessive daytime sleepiness in patients with sleep apnea. So 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. and so that's when we decided to go ahead and pursue indications like fatigue in MS, fatigue in Parkinson's disease. We prioritized fatigue in MS because this is where fatigue is very well characterized. More than 80% of patients with MS have some kind of fatigue and more than 50% of patients with MS have significant fatigue. Folks have done some work in terms of how to measure fatigue in these patients. There is some longitudinal data for fatigue in MS. And based on the pedolescent profile that we know, and some of the work that has been done in the past in the preclinical space, that was logically our next first indication for a broader indication like MS. So that's where we are. In terms of where we are in terms of our clinical development right now. We are optimizing the formulation. The next step would be to do a phase one PK study, and we'll take it from there. Got it. Okay. So I want to step back and think

about the competitive landscape here for a second before we move on to BP1, your own orexin. And I wanted to get your thoughts on how you're thinking about the landscape that's evolving with the first erexin that will get approved later this year, which is a Takeda product. How do you see that impacting Vakix 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 Vakix utilization in the near term? And then maybe stepping back, how do you see that impact and you know with the entry of other orexins over time how do you see wakex being positioned in the market and maybe we can talk about the the the two uh sort of life cycle assets the gr and hd formulation how does that help you navigate that

competitive landscape over the next couple years yeah yeah i mean before i turn it over to sort of Adam, in terms of market impact of the, you know, emerging orexins and Kumar on our development program. Just, you know, comment that obviously incredibly exciting space, you know, so much attention and activity around the orexin development programs for good reason. You know, novel mechanism, really the first new novel mechanism coming to central disorders of hyper somnolence and probably more and we can talk about that a lot as well since wakex launched um and i just you know we are very you know active in this space you know following the programs you know our own development programs other activities with our partner bioproge you know looking at even indications beyond you know sleep wake so um just wanted to emphasize that comment And then I'll turn it over to Adam and Kumar, 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 orexin's new treatment option for patients. And 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. So there's definitely interest to try, but I think this is going to be a gradual approach to trial. And as we learn more, we'll see how physicians end up utilizing Erexans as a new treatment option. in terms of impact you know we're still as in narcolepsy we're still less than 50 percent diagnosed and even less treated so hopefully with the awareness that the orexin class brings we'll see an improvement there for patients we also have seen over the last let's say five or six years an expansion of brand utilization but brand utilization is still what around 20 percent of the class so we would expect a new brand launch to expand brand utilization as well and that's actually what we've seen historically. As new brands come in, they tend to expand brand utilization rather than steal share from other brands. That's the polypharmacy approach, which is the hallmark of this class. Clearly, we've seen in research and our discussions with healthcare providers, they will prefer to continue that approach. And so we would expect an expansion of brand utilization as well. And then when it comes to treatment selection, way kicks we believe will continue to grow in the face of erexins because it's going to continue to offer something that's totally different and unique than any other treatment option when you look at the totality of efficacy and safety tolerability so really good efficacy but exceptional safety and tolerability and extremely clean profile that allows way kicks 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 wakex now with seven years of clinical experience and it's going to continue to be differentiated versus all other competitors including orexins so that's where we see you know physicians are really familiar with wakex 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 RxNs, and I'm even more fascinated with our own RxN because of several distinguishing features. This continues to be the most potent RxN 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 hypersomnolins at very low doses with the same drug and limit the off-target AAs. 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 OREX interceptor 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. So we started dosing patients in the fourth quarter of last year. We are on track to get full clinical PK data in single S&D dose study in healthy volunteers. And after that, we plan to submit the IND and kind of the sleep deprived healthy volunteer study, which will help us to bracket the dose range. And then we'll immediately move on to the next stage of development.

um do you think the potency can help differentiate on you know some of the adverse events that i think adam had mentioned and yeah those are the most common adverse events that we're seeing with the orexins which is insomnia um you know polycuria do you think that a more potent molecule can help reduce meaningfully reduce those adverse events that you're seeing which you know are on target

that was fence? Great question, Ami. There'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 you end up seeing many of the off-target AES, the other sponsors have disclosed to some extent, like visual disturbance, hypersalivation, things like that. So the on-target effects, that's something that we need to wait for the clinical data, but the off-target AES, clearly we will be able to manage that with a very high potent Rx interceptor agonist at very low doses.

yeah yeah yeah i mean the other the other interesting part of this is you know um as we look at this conversation and you know the interest in orexins um beyond central disorders hypersomnolence you know some of these new targets that are cognition mood etc so you know when you move away from nt1 which is a disorder of orexin deficiency or obviously you know the main efficacy has been proven but then nt2 ih and then these other potential air you know indications around cognition mood you know adhd and and probably others to be discussed in the future you know that we are also looking at and contemplating and doing some work with our partner um they're not disorders of erexin deficiency. So having a potent, you know, compound, as Kumar said, and dosing flexibility, you know, may also be very relevant, you know, as this sort of platform play

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

Yeah. Yeah, Kumar. Yeah, I mean, the informa in general, interact development in general, The first asset is not necessarily the best asset, right? More often than not, it's the fourth or the fifth asset that ends up becoming the best-in-class asset. And to some extent, we are seeing this play out here as well. And we already incorporated many of the learnings from the previous compounds. I mentioned about going for a new scaffolding rather than the typical bottled down sulfonamide bicyclic pomoides. And the reason for that is to exactly avoid some of the off-target structural-related AEs, like abnormalities in LFDs 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. 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 ever tested in this particular mouse model, 0.03 mg per kg. So it is playing out as we had hoped for based on pretty much the drug design, the medicinal chemists here at Biopresentation work based on what was seen with the earlier compounds. In terms of clinical development, we will be looking at efficacy, safety, tolerability, the dosing frequency, and the dose range that will help us determine how to go about with the next indications. And based on what we are seeing, we believe we should be able to target NT1, NT2, and IH with the same drug with very low doses and with a very favorable benefit-risk profile. Obviously, we need clinical data to demonstrate that. And we'll get there soon.

Yeah, that makes sense. I want to switch gears to your epilepsy program, EPX 100. At AES last year, you disclosed data from its open-label ARGUS study, well, the open-label portion of the ARGUS study and, you know, we saw that it demonstrated a 50% median reduction in CMS 28 from baseline and we saw reduction or a response in at least 50% of the participants. So based on the data that you've disclosed so far, and of course, a lot of the differentiation comes on the safety side of things as well, how do you see it positioned in the market? We know that there are other drugs that are also in development. So how are you thinking about its market positioning from a commercial standpoint?

from a clinical perspective right you're absolutely right the data that you just mentioned that's clinically meaningful efficacy we need to hit the efficacy bar and a 50 percent median reduction compared to baseline is considered as clinically meaningful by all clinicians who deal with these patients and it's important to remember that this is adjunctive therapy this is on top of about four to six anti-epileptic medications these patients are already taking. So in this context, it is considered as very clinically meaningful. And then the other aspect of the equation here is tolerability and safety. One of the biggest challenges that patients have with all the medicines that are approved in this space is tolerability and safety. Even the most recently are more commonly used medications like, for example, Fintapra and Epidalex. They have significant issues with appetite suppression in a patient who is already cachectic, has some feeding difficulties, about 20 to 30 percent in some instances of nausea, vomiting, abdominal cramps, and diarrhea. With EPX100, the only GIAE that we saw of any clinical relevance was diarrhea in just over about 2% of the patients. In terms of safety, we did not do not have to do any of the protein safety monitoring. For example, with epidemics, you need to check with LFTs every so often because of unpredictable elevation in liver function tests. With Finterklau, for example, it's important to do echocardiogram on a regular basis. In fact, it's part of the REMS program. We don't see the need for any special medical monitoring. So the benefit risk profile is very differentiated with EBX100 compared to anything

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

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

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

Yeah, Ami, I think, thank you for that question. Sort of an important priority for us. I think that our core strategy has really not changed, you know, in terms of the core strategy. I think we've sort of opened up the aperture a little with regards to, you know, what we're looking at across the BD landscape. But, you know, we still, our, you know, sweet spot is in orphan rare CNS and, you know, neuropsych targets. And we sort of look across the landscape for opportunities there you know more recently and given our capacity um you know we're open to looking at um broader you know potentially assets you know with broader um indications out you know outside orphan rare what we call sort of adjacencies to our core strategic franchises you know in sleep wake and and the rare epilepsies and then importantly again given our capacity and where we are in our evolution you know not just pipeline assets but on market as well uh which i think is probably the most recent sort of evolution of our thinking because we you know we have the capacity we have a strong commercial engine and a strong commercial team you know as you're aware um and i think the ability to um you know um add another product to their bag and you know beyond just Wakex and the Patulsan franchise where there's a good strategic fit. So that, you know, that is the current thinking. And looking at both strategies, you know, 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, you know, we have the experience and the know-how across the team if we see you know something larger that um is a good strategic fit um is a smart business development deal for us we are also looking really across the spectrum of those those

opportunities okay that's very helpful i think we're almost out of time so this is a good opportunity for me to thank you all for taking the time uh to have this conversation with me and, you know, 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.