Harmony Biosciences Holdings, Inc. (HRMY) Earnings Call Transcript & Summary

So this morning, we have the Harmony Biosciences management team with us today. Glad to have you all at the GS Healthcare Conference.

And so we just wanted to get started and talk about things that have been going on with Harmony. So maybe we can start with the commercial side of the business. So let's talk about WAKIX. It's now in its fifth year of launch, and this is the first year that the company has provided guidance. So would you've indicated some slowing with respect to new patient growth. Can you talk to us about the shape of the commercial trajectory from here?

Yes. First one, on behalf of the Harmony team, thanks for the invitation. And just to take a step back with regards to framing the whole business, we now have 3 orphan rare CNS franchises, led by our foundational franchise WAKIX in adult narcolepsy. But with that, the Sleep/Wake franchise and the opportunity there and our Behavioral franchise as well as the Rare Epilepsy franchise. So the bigger business looks at the 3 orphan rare CNS franchises, each with potential peak sales opportunities of $1 billion to $2 billion. Coming back to WAKIX in adult narcolepsy. I think Jeff can sort of frame where the growth opportunity is coming from after the successful launch and now year 5 in the market.

Sure. So I mean we've had a tremendous launch, probably one of the most successful rare orphan launches in the history of the industry. And our growth continues in the year 5. I know [indiscernible] as you shared, we're getting ready in year 5. We had a very strong first quarter, 30% growth quarter-over-quarter and obviously, with respect to guidance, maybe Sandip, if you want to add a little bit on how the first quarter shaped our view on guidance.

Yes. Look, I mean, as you mentioned, really strong growth in the first quarter, great coming in from even from last year where we had a over $582 million in sales as we came into this year. We feel very good about how we started, the momentum we're seeing this year, reaffirmed our guidance of $700 million to $720 million for the year and well on our way towards $1 billion in adult narcolepsy alone, so we feel good about the momentum and expect continued quarter-over-quarter growth for the balance of the year. And again, it's really quite amazing, especially fifth year of commercialization to have such strong double-digit growth.

And so to answer your question in terms about growth looking forward. So as we get into year 5, we still are demonstrating very strong durable growth. But as you know, in any product in year 5 of a launch, growth is going to evolve, right? And there's no difference for WAKIX. We demonstrated 30% growth. So still strong double-digit growth. And I think what gives us confidence moving forward [indiscernible] is that we've had the oxybate analog in this market for 2 decades, right, product that launched in early 2000s, been on the market for over 20 years. And when you look at their first 4, 5 years of launch relative to our launch, we've exceeded their patient goals every single year in the first 5 years. It's a good product. It's helped thousands of patients and has demonstrated really durable growth throughout its life cycle, gives us a ton of confidence in our ability to continue to grow because there's some unique dynamics in this marketplace that really make WAKIX a product that is appropriate for all adult patients living with narcolepsy. There are 9,000 health care professionals in this audience, 4,000 are enrolled in the oxybate REMS program, another 5,000 or not. So all of oxybate's growth, right, they generated $1.6 billion in net sales, came from 4,000 health care professionals and that patient opportunity. We have the ability to call on the full 9,000 audience because of the broad clinical utility, the nonscheduled status of WAKIX being not a controlled substance. So we can tap into the full diagnosed patient opportunity over our life cycle. We're growing in the non-oxybate REMS enrolled doctors. We're about 33% penetrated in that audience since our launch, but we're also growing in the REMS-enrolled oxybate. Even with the number of oxybate generics, once-nightly low sodium, we continue to see durable growth and depth prescribing in that area. So when you look at those 2 growth drivers, we feel really confident about our business. We expect strong double-digit durable growth through the remainder of the year. And we do see this as a $1 billion-plus opportunity in adult narcolepsy alone.

Great. So kind of thinking about targeting some of these prescribers that oxybates can go into. What do you think will be the key factors for success in terms of promoting WAKIX in supporting that growth?

Yes. I mean I think it starts with what Jeff alluded to, the broad clinical utility. So if you look at the product profile of WAKIX, it's really differentiated from what else is in the market, beginning with its unique mechanism of action and then the overall sort of benefit-risk proposition. I think that speaks to why the sort of the HCP universe includes both those docs that are in the oxybate REMS, and the additional 5,000 that are not sort of in the REMS program. They don't like writing scheduled products. And so the nonscheduled nature, WAKIX has the only FDA-approved product that's not scheduled for narcolepsy, speaks to sort of that differentiated profile. Along with the other factors, which I think when we looked at what the unmet medical needs were in the market, the WAKIX product profile sort of fit that when we looked at that early on.

Yes, I would say the key, [indiscernible], is probably just education, quite honestly. These are doctors that do not write traditionally scheduled medicines, right? So even with stimulants, wake-promoting agents, oxybate on the market, they've been hesitant to prescribe these medicines. So going in, it takes 6 to 8 calls to change the behavior from what we've seen. We launched in the middle of a global pandemic. So even in the first couple of years, maybe hindered our ability to get in front of some of these customers, but we've seen steady growth in this audience. And the unique thing about this, [indiscernible], it's a great question, is this is a very insulated group of health care professionals. As all of these oxybates come to the market, they cannot play in that space. So we have a very insulated opportunity to call on these health care professionals to be able to support these patients. And so that really is -- you're getting all these generics and once nightlys, it really provides a very unique and meaningful growth engine for us moving forward.

Yes. I think the other key piece, too, is the market. So even though narcolepsy is sort of an orphan rare disease, there's 80,000 patients with narcolepsy sort of diagnosed in the U.S. So the patient opportunity is there with regards to growth going forward.

Great. So there's been some evolution in the market since the launch of WAKIX, including generic oxybates. Maybe you can talk to us about that. What do you see the WAKIX opportunity in the context of these generics coming into the market?

Yes. I mean, I think it speaks to sort of the insulated aspect with regards to, we have a sizable segment of HCPs that don't participate in the oxybate REMS. So even with the introduction of the generic oxybates, we were able to tap into that prescriber brand from -- in that regard as well as I think Jeff alluded to, even the physicians that are in the oxybate REMS, we continue to penetrate in terms of depth of prescribing there. And I don't know if anything else to add?

Yes. So what I would say is, [indiscernible], when we came into the market in 2019, we came into a branded and generic space. There were already a number of generics in the marketplace. And I think for an investor that looks at this, most markets [Technical Difficulty] product A or product B. As Jeff shared, it's a large diagnosed patient opportunity, 80,000. Patients sadly don't take 1 [Technical Difficulty] typically, it's 2 or 3. And being a very unique MOA working through histamine being the only non-scheduled treatment option, WAKIX fits really well within that polypharmacy market. [Technical Difficulty] have risen. All brands have grown [Technical Difficulty] investment to drive education, drive diagnosis rates. And so we feel really good. Even with the introduction of generics, we've not seen any impact on our business. With the introduction of the once-nightly oxybate, we haven't seen any impact. And then even moving forward as we're looking for future products potentially being coming to the market, we think it's great for patients, right? Patients have the ability to get new options, and I think that we still remain very confident because every patient that comes into an office from health care professionals is WAKIX is part of every treatment decision. They may not be prescribed the WAKIX, but WAKIX is a part of every treatment decision. Whereas, oxybate, it's a different overall benefit risk profile, and it's limited to a subset of patients. And as I said, you look at that as an analog and their success, I have a lot of confidence in our ability to do as well.

Yes. And I think even our formulary position has remained strong even with the introduction of the generic oxybates, and so there really hasn't been any impact there either.

And you can see, just this past year, I mean, we've had competition for now well over 1.5 years and continue to grow every quarter fairly consistently. So we don't think from a -- as mentioned competitively, we don't see this as a competitive market [indiscernible] as new entrants come into the market as there's more share of voice as there's more education overall.

Maybe thinking beyond the narcolepsy opportunity. You've elected to pursue approval in IH. Could you maybe walk us through the conversations you had with the agency and what lead you to this decision?

Yes, sure. So we've met with the agency, and we had a Type C meeting and had good interaction with FDA with regards to the Phase III, the INTUNE study in idiopathic hypersomnia. We approach them with regards to looking at the totality of the evidence, totality of the data that was generated not just in the randomized withdrawal portion, where the primary endpoint did not meet statistical significance. But upfront with regards to a significant an 83% response rate and improvement in EDS and a significant over 9-point improvement in the Epworth scale. So a lot of patients sort of normalize. So a strong response in that part of the trial and then up to 90% of patients elected to go into the long-term open-label extension, for which we've been collecting more data that we were able to sort of discuss with the agency. So with totality of the evidence coming out of the trial as well as there's only 1 approved treatment in the market for IH, that being Xywav which is a Schedule III restricted access REMS product, we saw sort of the overall benefit-risk proposition as being strong. The agency acknowledged with regards to the limited restrictions and then we talked about the potential in an orphan rare [Technical Difficulty] flexibility, and we're able to have that discussion. So after meeting with the agency, [Technical Difficulty] all the data that we have, the data that's been generated in the open-label extension. We also have some real-world evidence and other real-world data that we can submit, so we made a decision to submit the sNDA for IH, and we're on track to submit it second half this year.

So could you provide an update on the pitolisant life cycle management activity you've taken on?

Yes, sure, happy to. So that's an area that we're really excited about. Given that WAKIX has been a very successful product in the market, with its first-in-class novel mechanism and a strong product, the overall product profile. But we see the opportunity for incremental benefit and incremental improvement with regards to these new next-gen formulations. And it's also in looking at narcolepsy patients, we also see an opportunity to address additional unmet medical needs in this patient population. So we have 2 programs with regards to what we're looking at. And one is what we refer to as a pitolisant HD or high-dose opportunity and that is a full development program, and that is designed to basically look at and optimize and improve PK profile of pitolisant and then with new IP and we have provisional patents out to 2044. So an opportunity to sort of extend the whole pitolisant franchise with an optimized PK profile and a higher dose. And what that will provide the opportunity is to sort of drive even greater efficacy compared to sort of where WAKIX is now. And we also identified that there's another symptom in patients with narcolepsy that's in about 60% of patients, and that's fatigue. So in addition to the excessive daytime sleepiness and cataplexy in this development program, we have the opportunity to improve upon efficacy in both EDS and cataplexy and then pursue a fatigue indication. And that's sort of the lead program in pitolisant HD. While that is in development, we also identified another sort of opportunity near term to address another unmet medical need and that's related to sort of nausea and GI disturbance in patients with narcolepsy. And that is a program we refer to as pitolisant GR, gastro-resistant, and that is an abbreviated development program based on demonstration of bioequivalence. And I think -- and Jeff, you can maybe share some of what we saw in terms of that unmet need in patients with narcolepsy.

Sure. So, [indiscernible], I mean, I think what we're taking is a holistic leadership approach to life cycle development and patient-centric drug development. WAKIX is a great drug, made a meaningful contribution in the market. But even with its contribution, there are still unmet needs in the market that we believe that we can look to help fill. Obviously, we're working on 2 next-generation versions of pitolisant. We have an orexin, which I'm sure we'll talk about. So looking at our ability to end up trying to meet the needs and really stay ahead of the science. So with the gastro-resistant formulation, what we saw in the data is of the 88% of type 1 narcolepsy patients have GI disturbances, and there's a relation in the loss of [Technical Difficulty] not activating the vagus nerve, which causes the moderation of the GI tract. We also know through a meta analysis that 1 in 5 patients experienced nausea on any one of the treatment options. And we also know in looking at retrospective database analysis, when you look at narcolepsy patients, nearly half of them are taking either a PPI or an H2 blocker as a prescription and we know even more taking over-the-counter medicine. So we know the GI disturbances there's a big opportunity to try to meet that. So the gastro-resistant formulation development program is something that we believe can really address an unmet need in the market, kind of help enhance some of the benefits of what we've seen with WAKIX and narcolepsy. But more importantly, the high dose really is the meaningful ability to drive enhanced efficacy. [Technical Difficulty] patients even on narcolepsy treatment still have residual symptoms that disrupt their life. We know that 60% of narcolepsy patients have untreated fatigue. Those 2 key areas are going to be drivers. So we're going to grow the base and foundation with WAKIX. We can expand that population with the gastro-resistant formulation, the traditional conversion to expand our leadership with the next-generation HD and then that leads us right into the orexin into the 2030s. And we believe we're going to have 2 very significant assets to be able to be in the market in the 2030s, while we continue to make the most out of WAKIX now.

Yes. So it's sort of an overall plan to extend the pitolisant franchise into the mid-2040s, and then with the orexin-2 agonist maintain a leadership position in the Sleep/Wake space.

Yes. So let's talk about the orexin-2 agonist you recently acquired. Could you talk to us about how you're thinking about the drug class, especially since it seems to be pretty crowded in the context of narcolepsy?

Yes. So I think, yes, the orexin-2 agonist target, we've been following that space for a while. So it really represents the next new target mechanism of action for treating narcolepsy. So we looked at a lot of the programs, and we did diligence on several of them, but we wanted to be sort of thoughtful and realizing that there are a lot of programs out there, and this may not be first-in-class, but we think we have the opportunity for a best-in-class asset. And with that, with our partner, Bioprojet, we in-licensed TPM-1116. And what is unique about this molecule is that it's highly potent and has good selectivity with regards to the orexin-2 receptor. Based on the preclinical safety data, it has a good safety profile and also the opportunity for once-daily dosing. So if you look at some of the other development programs and drug development is very iterative, so we continue to learn from the data that read out from the other programs. We think that this profile could be a best-in-class profile. And I think we're still learning. Even the data from the Takeda program, the Alkermes program that was presented at SLEEP last week continued to show that there's a lot more to learn in the development of the orexin-2 agonist.

And so what can you share us, like, what were your takeaways last week from their datasets?

I think the main takeaways were that really threading the needle between sort of dosing once daily versus twice daily. Some of the safety issues, insomnia continues to be sort of a prominent signal. So I think those programs will be adjusting the approach, and we'll learn from that. But the important aspect of this class, a lot of it's related to both potency and selectivity. And what we saw in TPM-1116, at least of what's publicly available, the most potent of the orexin-2 class from what's publicly available that we've seen with very good selectivity. And importantly, once daily dosing would be an important attribute as well.

And when could we see data from your orexin-2 agonist...

Yes. So we're looking for the next opportunity at a medical meeting in terms of sharing the data from the preclinical program and what we saw in diligence.

And then can you talk to us about the structure of the acquisition with Bioprojet?

Sure. Sandip?

Yes. Look, I mean, we structured it -- again, we did a license together. We licensed it from Bioprojet. We have rights to the U.S. and Latin America. While Bioprojet had rights outside, we're developed -- codeveloping the program together. We feel a great opportunity to bring both of our capabilities, both to a clinical development there. And just as a reminder, we paid $25 million upfront that will be recognized in Q2, along with the other acquisition that we also did with Epygenix. So all of that will certainly hit our financials in Q2, but we feel good about it. We've got very late-stage programs, for example, for example, for the Epygenix program that we also licensed in as well. And then, of course, the orexin is, obviously, an earlier program, but we'll share data in the coming years.

Yes. And I think where we are now is the plan is, as we shared, is that we plan on submitting an IND in sort of mid-2025 and then first in-human in the second half of next year.

Great. So maybe we can switch gears and talk about the epilepsy asset for Lennox-Gastaut and Dravet syndrome. So maybe to start, what was the impetus for the decision to get this asset and require this asset?

Yes. So I think with regards to our BD strategy and looking at sort of orphan rare neurology opportunities, we've been looking at the epilepsy space and have a lot of expertise in that area. And we saw in this program, a late-stage asset with EPX-100 in Phase III in the registrational trial for Dravet syndrome. I think with a proven mechanism of action, so clemizole hydrochloride sort of validated through the zebrafish model with regard to that's very specific to that mechanism of action. And given the profile given sort of the deal terms, we saw a very good opportunity for this late-stage program in Dravet and also right behind that is an opportunity for a Phase III program in Lennox-Gastaut, which is a bigger market opportunity. So that really, for us, helps to sort of create a foundation of an epilepsy franchise, whether it remains sort of in the orphan rare space so we could build upon that in terms of larger opportunities.

And it's somewhat of a crowded space. So maybe you could talk to us about where you see an opportunity to differentiate from other therapies in Lennox-Gastaut and Dravet syndrome?

Yes. So I think with regards to what's in the market for those, I mean, the main products that are currently available: Epidiolex, the original from GW Pharma, now that Jazz acquired, an oral cannabidiol, but really sort of has challenges with regards to tolerability, a lot of dose-limiting kind of GI issues. And then the other main product is Fintepla, still an effective product. But with regards to the safety profile, has a REMS program because of the risk of cardiac valve issues, valvulopathy as well as pulmonary arterial hypertension. So both of the products affective with regards to seizure reduction, but significant safety tolerability issues. What we see in EPX-100, the product profile, efficacy as good, if not a little better than these other products, but with the safety tolerability profile that's much more acceptable and the potential to contribute a new treatment option in especially the overall benefit risk profile compared to what's currently on the market.

And could you talk to us about what data you have for this asset so far?

Yes. So I think some of the Phase II -- the data in the Dravet syndrome, the open-label data, showed a strong efficacy signal. And now that sort of guided the registrational study that's ongoing.

Great. And then in terms of safety is an important consideration, as you just mentioned. So do we know anything about the safety of this asset compared to others in this space?

Yes. I think the overall, the safety-tolerability profile, the main side effects have been some sedation and nausea and sort of common -- other common side effects, but not very different from some of the dose-limiting effects that we see with Epidiolex in GI aspects as well as the cardiac aspect and the valvulopathy with Fintepla.

Great. So maybe you could talk about now Fragile X syndrome. So maybe you can describe to us the motivation behind acquiring this asset?

Yes. So I think the acquisition of Zynerba Therapeutics and ZYN002 was another -- we've been following the company in that program, and it was another opportunity for a late-stage asset in an orphan rare sort of neuro-behavioral condition in Fragile X with very sort of favorable deal terms with regards to that acquisition. And that really strong data coming out of the Phase II trial that informed the Phase III RECONNECT study that's ongoing now and on track for top line data readout mid next year.

And what's the preclinical evidence that the product is active and hitting the target?

So the preclinical evidence is based on the mechanism of action related to the endocannabinoid system. So ZYN002 is a purely synthetic cannabidiol. So even that product profile, it's devoid of THC. So it has the opportunity to be a nonscheduled product and it's also delivered transdermally. So compared to the oral cannabidiol products, such as Epidiolex, it bypasses first pass metabolism, so you don't have the GI tolerability issues and you don't have effects on liver enzymes that you see with Epidiolex. So with that, working on the endocannabinoid system, and it prevents the excitation of that system, that is what occurs in Fragile X in the mutation of the FMR1 gene.

And then do we have any clinical or preclinical evidence supporting this mechanistic rationale?

Yes. So the clinical evidence was strong from the Phase II, the CONNECT trial. So the Phase II CONNECT trial demonstrated that in patients with Fragile X, especially those with sort of the full methylation of the gene, where the symptoms are more severe, it showed a statistically significant benefit on some of the behavioral symptoms in Fragile X. So that data informed the design of the Phase III, the RECONNECT study that's ongoing. And we've looked at that. We also looked at dosing. And in the Phase III trial, there's a higher dose group based on weight. So I think the opportunity in terms of probability of success in that trial from the learnings of the Phase II CONNECT study.

Could you talk to us about the changes to the trial, if any that you've made, since acquiring the drug?

Yes. So we didn't make any changes to the design. I think Zynerba did some very nice work. They also met with FDA in the end of Phase II meeting after the CONNECT trial and I think gained agreement on the primary outcome and the overall study design. So no changes really needed to be made in the study. We just sort of brought it in and then applied kind of our clinical development machine, our ClinOps team to drive the study forward. We also have a very strong patient advocacy group in terms of raising awareness in the Fragile X patient community to continue to drive the enrollment in that study. And we're excited about that and on track for top line data readout mid next year.

Nice. Perfect. So what is the current status of litigation around the pitolisant [indiscernible] property?

So the current status, I think that we know that if we take a step back, WAKIX has been a very successful product in the market. So with that, we fully expected the ANDA filers. Whenever you have a very successful commercial product, you're going to see ANDA filers come. So we expected it, and we were ready for that. So with that, when they filed, we filed suit in terms of -- and initiated a 30-month stay. But I think more importantly, we believe in the strength of the IP and the WAKIX patent out to 2030. And the reason -- a couple of reasons for that with regards to -- it's based on the polymorph patent, and we know that polymorph patents have been upheld over the years. We also know that there's only 1 stable polymorph for pitolisant hydrochloride. It's been tested multiple times, and any other polymorphs revert to the single stable polymorph with regards to what the patent protects. It's been -- the whole IP landscape has been analyzed by many experts around the world as well as looking at trying to find the stable polymorph and no one has been able to identify that. And then I think lastly, we also know that the patent has been challenged in Europe, actually twice, and that challenge was not held up and was defeated. So I think based on what we've seen and what's happened over the years, that the IP holds up very strong, and we're confident in that out to 2030.

Great. I think that's all the time we have for today. I really appreciate you all coming out and speaking about Harmony Biosciences and giving us updates on what you've been working on.

Great. Thanks, [indiscernible].

Thank you.

Thank you so much.

Thank you.