Welcome to the Cantor Global Healthcare Conference. I'm Pete Stavropoulos, a biotech analyst with Cantor. With us, we have Harmony Biosciences, a company I cover. Pleased to introduce Jeff Dayno, CEO, and Peter Anastasiou, COO. Welcome, and let's just start off with a brief introduction of yourselves, a snapshot of Harmony, and touch on the milestones that will shape the company over the next six to 12 months.
Yeah, thanks, Pete. On behalf of the Harmony team, thanks for the invitation to present today. I'm Jeff Dayno, CEO at Harmony Biosciences. Briefly, neurologist by training, 12 years clinical academic medicine, 28 years in the industry. Started at Merck, Cephalon, ViroPharma, and joined Harmony at the beginning in October 2017 with incredible opportunity on the heels of WAKIX. Now as we build out the pipeline with the focus on BP-205. Great to be here today, and Peter?
Yeah. First of all, thanks for pronouncing my name right. It takes a Greek to pronounce another Greek's last name, so thank you. I'm Peter Anastasiou. I'm the Chief Operating Officer. I've been with the company officially since April, but prior to that, I was on the board for three years. I've been in the industry 30 years. First half of it was at big companies like Lilly and Company and Bristol Myers Squibb, and the last half has been with kind of smaller mid-size companies. I was President of Lundbeck North America. I was CEO of a company called Capsida Biotherapeutics right before I joined Harmony full time in April. It's a pleasure to be here.
All right. Let's start off with BD activity. You've been focusing on business development around assets that can potentially contribute to revenue in 2028 to 2032 timeframe. Can you define your strategy, target characteristics, timing, and sort of transaction size, your vision?
Sure. Pete, let me first frame in addition to BD, the Harmony story and where we are. We feel that we're kind of emerging in our second chapter of growth. Obviously, on the heels of WAKIX, very successful in terms of commercial product, and the franchise continues to grow. On track for over $1 billion in revenue this year, and then the next generation programs also advancing. I think that has given us the ability in terms of very strong balance sheet, approaching $1 billion on the balance sheet, to really self-fund the entire enterprise. Our pipeline programs, we'll talk about BP-205 and in terms of our organic growth, and then in terms of business development, the ability to be competitive in the market with really interesting BD opportunities.
The plan is to continue to build out the pipeline, as well as look to diversify the commercial portfolio with potential on-market assets. I'll turn to Peter to frame the strategic lens that we look through in terms of BD opportunities.
Yeah. First of all, we want to do value-creating deals. We're very careful and cautious to make sure that when we evaluate, we're quite active in evaluating a number of BD opportunities and have been for quite a while. We want to do things that create value. The types of things that we are targeting are products that could bring revenues in the 2028-2032 timeframe. The reason for that is to help bridge the WAKIX LOE. That also helps us bridge to the significant revenues we expect from BP-205, our orexin agonist that we'll talk about hopefully here in a couple of minutes. Targeting revenues in that 2028-2032 timeframe implies something that is late stage in terms of phase III, something that's under regulatory review, or potentially even something that's on the market.
In terms of therapeutic focus and indications, clearly anything in the sleep space is something that we know we can do. We consider ourselves the leader in the sleep space. Anything there would be right in the center of the bullseye in our sweet spot. We also have an emerging capability and experience in the epilepsy space, particularly DEEs, with what we're doing in terms of the clinical trials with EPX-100. Also those types of indications are rare CNS disorders, and we've clearly demonstrated our ability to be successful with rare CNS disorders in what we're doing with narcolepsy. As we develop our orexin-2 agonist, we are committed to exploring a number of different potential indications for it, including outside the sleep-wake space.
We haven't disclosed what those indications are, but that certainly would be an important area of relatedness in terms of our strategy, those indications that we're thinking about with BP-205 to also be doing activities in the BD front. Last thing I'll say is we're agnostic to deal types. We're certainly looking at M&A, but we're also looking at licensing deals. I'll remind you that the billion-dollar business that we've built, it was built on a licensing deal. We're kind of agnostic to deal types. Also, we are unlikely to spend our entire dry powder on one transaction. It's likely we'll do two or three transactions. That gives you some color, Pete, about how we're thinking about BD.
All right. As you do evaluate new programs, what characteristics make the asset strategically attractive?
Yeah. As I mentioned, I think what makes it attractive is the revenue timeframe in that 2032. We always want to do things that relate to things that are strengths of ours. As I mentioned, sleep-wake, but also rare CNS disorders. We clearly have the ability to do that, and so we've demonstrated that with what we've done with narcolepsy. Those are the areas of focus for us.
Yeah. In addition, as Peter said, building out the additional verticals with regards to the epilepsy business and with EPX-100 and looking at other potential assets in the epilepsy space. As we look to BP-205, the conversation's incredibly interesting, and it's accelerating pretty quickly. In addition to NT1, NT2, and IH, these broader CNS potential indications, yet unproven, but a lot of promise in that area that we will plan to pursue as well.
All right. We will get into that shortly. But in terms of a BD transaction, is this something we should hear an update in 2026 or likely a 2027 event?
Hard to-
No, please.
When it comes to BD, hard to predict timing. Suffice it to say, as Peter said, we have always been very active in the BD space. Once we became profitable, realizing we do not want to be a one-product company, and the mandate was always growth. As I said, on the heels and the foundation of WAKIX, I think we are in sort of the next chapter of our growth phase. But we have got a dedicated team. We have a lot of firepower. Peter joined the management team with all his years of experience, but hard to predict timing.
Okay.
But it is a high strategic priority for the company. Stay tuned.
Okay. Before we get into 205 program, it's an orexin 2 receptor agonist. Just sort of give us an overview of why target this system for sleep-wake, as well as for CNS disorders.
Yeah. In terms of the orexin system?
Yeah.
Okay. The orexin system, it's the next new novel target with regards to sleep-wake. Starting with NT1 is a disorder of orexin deficiency, loss of orexin neurons in the hypothalamus. Especially for NT1, it is a direct mechanistic fit. From there, the focus was really on the spectrum of disorders in the central disorders of hypersomnia, NT2 and IH. While they're not necessarily disorders of orexin deficiency, you can sort of boost that system, upregulate that system to drive wakefulness. In terms of orexin is the main neuropeptide that stabilizes the sleep-wake switch and drives wakefulness.
I just want to note, interestingly, that is at the top of the cascade in the hypothalamus. I am a neurologist by training, so I cannot help myself. Right below that is the histamine center. Orexin neurons actually synapse, connect to the histamine center, histamine being the main neurotransmitter that drives wakefulness. You have got that rationale and the innovation of the next novel mechanism of action. The broader CNS indications that have emerged as the potential kind of value creation for this class of compounds, the orexin biology is thought to have a role in some of those areas, such as cognition, ADHD, mood disorder, fatigue. There are some preclinical models in support of that, but it is still early in the space, and the evidence is still emerging on how that will play out for the orexin agonist.
Okay. Turning to BP-205, what differentiates that molecule from other OX2R agonists in development?
Yeah. BP-205, this is an orexin 2 agonist. We have been in the space, as Peter said, leaders in the sleep-wake space. We diligenced a lot of the orexin 2 programs. We did not see anything that was compelling enough. Then our partner, Bioprojet, came to us with this opportunity. The innovator of BP-205, Teijin Pharma, Japanese company, a lot of the orexin biology coming out of Japan. They worked with one of the individuals who founded the orexin system, Professor Masashi. The other team was at Stanford University, Emmanuel Mignot. He worked, and they were seeing the other programs in the clinic, and then they developed BP-205. It starts with, it has a unique chemical structure, a unique scaffold, and that allows for the attributes that we feel could be best in class. Number one, potency.
The most potent of the orexin 2 agonists currently in the clinic, which matters with regards to, especially when you go beyond disorders of orexin deficiency, which are all the other ones I mentioned except for NT1. Potency will matter in terms of effective dosing to find the sweet spot between efficacy and some of the safety tolerability issues that are still kind of playing out. So highest potency, very strong selectivity of orexin 2 over orexin 1, and then a profile looking potential for once daily dosing. In the preclinical safety pharmacology tox data, no evidence in terms of some of the safety issues from the reactive metabolites because of the unique structure that Takeda saw in its original lead program before they moved on to their follow-on compound.
You did touch on selectivity, but some investors point out that 205 has greater than 600 x selectivity for orexin 2 receptor versus orexin 1, whereas TAK-861 is 3,000 x more selective and Lilly's ORX1517 is 9,000 to 10,000 times more selective. So what do you say to those investors regarding selectivity, and how should they view this when thinking about the totality of the 205 profile?
Yeah, no, it's a fair question. I think the short answer is when it comes to selectivity, it's a threshold effect. So it's a threshold effect with regards to how much selectivity is enough in terms of orexin 2 over orexin 1. So I think if you set the bar, most of the approved products in the market in neurology, psychiatry, you're looking at selectivities for the target receptor of about 10, 20, 30-fold over other receptors, serotonergic mechanisms and other things like that. So 20, 30-fold at given the potency and then potency and selectivity sort of interact, given the potency that we see at the potential highest clinical dose, we would dose at 140-fold selectivity of BP-205 for the orexin 2 receptor over the orexin 1 receptor. So, again, threshold effect, plenty enough selectivity that we're very comfortable with in regards to that attribute.
And I would just add that we've screened 150 other receptors, and there's no appreciable effect on any of those. So this is very much a focused orexin 2 agonist.
Yeah. So once again, 150 other fold biologic receptors of interest, mainly from a safety tolerability perspective. And 1,000-fold actually selectivity over those receptors.
On last quarter's call, you disclosed 205 SAD data. Just help us understand that PK profile.
The SAD data that we shared our Q2 earnings cycle, I think the important attributes were short Tmax. So short time to onset of effect, in terms of the potential for rapid efficacy in that factor. So half-life of 25 hours with regards to the potential for once daily dosing, and I will come back to that. And the other was dose proportionality, which is important because predictable dosing in terms of dose proportionality and studied a range of 30-fold in terms of the doses in the single ascending dose study.
How does the Tmax actually compare to other orexin 2 receptor agonists?
Yeah.
In the clinic?
Yeah. In terms of some of the other programs, we haven't seen a lot of PK data. I think what we've seen in terms of oveporexton and Takeda's product that is approved, we've seen the label. It's with the DEA for the scheduling decision. It has a shorter Tmax, but we haven't seen a lot of PK data from some of the other programs.
Okay. You did touch on it, but could rapid Tmax translate to fast morning onset? Just sort of help investors understand the importance of this.
That is the potential. That's what that would suggest. The importance is condition like narcolepsy or IH, starting there. Important in terms of getting up in the morning dosing and then having that effect of stimulating wakefulness early and starting their day in terms of functional level. In IH, there's another unique symptom called sleep inertia in addition to the excessive daytime sleepiness. Sleep inertia is literally trouble taking a long time to wake up from sleep or from naps. So in that condition, rapid onset is a really important attribute to overcome the sleep inertia in patients with IH.
Okay. How do you think about the half-life? I believe it's about 25 hours. Considering that oveporexton is 23 hours and still BID, why are you confident that once daily dosing is possible?
It's a great question. You mentioned, yes, oveporexton 23 hours and BID dosing. I think it starts there. The message is it's not all about PK. When you look at PK, the default is you just sort of correlate directly to what the clinical effect could be. But with oveporexton at 23 hours, you're dosing in the morning when you wake up, and I think the label says about five hours later. You would expect that not being needed with that type of half-life. With BP-205, in a 25-hour half-life, we see the potential for once daily dosing. But in addition to the question, and the important question, what about insomnia and on-target effect? It's not just all about, as I mentioned, PK. There are other variables, and that plays into a pharmacodynamic effect.
The pharmacodynamic effect, because ultimately at the end of the day, it's the clinical data, it's risk-benefit, and how does that play out? Which is as you advance in the development program, that's what you're demonstrating. Pharmacodynamic variables, blood-brain barrier penetration for a CNS target, receptor dynamics, on/off time, et cetera. The analog we often refer to, Pete, is WAKIX. WAKIX has a 20-hour half-life, and the strong histamine mechanism wake-promoting effect, and the incidence of insomnia in the label is about 5%-6%. We feel where we are tracking, and obviously, the development program, the clinical data will bear it out. We have the potential for truly once daily dosing, especially at lower clinical doses, given the potency.
That's why we're excited about the emerging profile. Peter, any additional thoughts?
Yeah, I think I would step back for a second and just frame how we see our story evolving. Historically, because of the success of WAKIX, we have been largely viewed as a quarterly sales type of story. We are at the beginning of or the early stages of a re-rating of our stock. We are emerging from that specialty pharma world to really starting to get some appreciation for our pipeline, primarily on the back of BP-205, but also other assets that we can certainly talk about in our pipeline. As, of course, what we talked about early at the beginning, our ability to bring in more assets, given our significant balance sheet. So we're at the beginning of an evolution of a story that's going to continue to be fueled by the data that's going to be coming out.
We already have SAD data in Q4. We're going to have MAD data in early next year. We're going to have sleep-deprived healthy volunteer data. Then mid-next year, we're going to be starting multiple phase II studies to really explore the full potential of BP-205. When you take everything together that you asked about, we really believe that we have a best-in-class asset for all the reasons that we mentioned, between the novel scaffold, the once-a-day potential that we feel strongly about, the high potency, which is particularly relevant beyond NT1, because all those other diseases are diseases where they're not clear orexin deficiency. So having the most potent product in the clinic gives us the best chance to show efficacy in those other indications. I think the story is rapidly evolving with Harmony.
You did mention other indications, so how are you thinking about other CNS indications to move into? I think you said you're going to start several phase IIs in 2026.
Yep. I was going to go there. In addition to BP-205, realizing the opportunity in both narcolepsy and IH and orphan rare disorders, the conversation has quickly moved to these broader CNS indications where there's a lot of potential value. So it's also our plan, our intent, to build a portfolio of orexin-2 agonists, not just BP-205. Because to do that, you're going to need more than one product in the market, different price points, different commercial models, et cetera. So we're working with our partner, Bioprojet and Teijin, in terms of additional orexin-2 compounds. There are also other programs out there, as part of our BD assessment, looking at other potential opportunities. With that is the longer-term plan.
To get things moving, as Peter Anastasiou mentioned, mid-next year, we plan to initiate multiple phase II proof-of-concept studies in the hypersomnias in some of the other broader CNS indications. We are working with our partner, Bioprojet. We have not disclosed the targets yet, but as we get closer to that, we will do that. Those data will inform where we think the best opportunities could be in this significant emerging space with the orexin 2 receptor agonists.
Your current agreement with your partner gives you access to additional orexins, or would that need to be a new terms of the deal?
We are working on those specifics. We have the opportunity with our current partner and with Teijin, in terms of potential additional compounds. There are other programs out there as part of our BD work and diligence, we are looking at.
All right. $963 million in cash. How much of that is going to be allocated to the orexin program?
Probably a decent amount. We are excited about this space, and we're going to invest in it. But the question, are you going to do that? Are you going to do BD? We often get asked that question. The answer is we have the capacity to do both. We have the capacity to do both, given the strength of the balance sheet. We've been saying, very active in BD. It is a high priority. We see the opportunity in the orexin space. Starting with BP-205, other work to follow. We think that we can advance that aspect of our pipeline, be competitive. We're leaders in the field. We know the space. We're excited. I think significant investment there, enough left for value-creating BD opportunities, and that is the plan. We feel we are in the next chapter of Harmony's growth phase.
Okay. Last several minutes, just want to ask you about the ANDA litigation, where it sort of stands, and what's the timelines, and next steps for WAKIX IP litigation?
Yeah. Multi-layered IP strategy, lot of things going on. Peter will break it down for you.
Yeah, thanks. Just as a reminder, there's two active court cases. There's the ANDA, which has closing arguments coming up in October, which we think is a great sign, that the judge is still deliberating, and we have another opportunity to make our strong case on the two patents that are the subject of the ANDA. As a reminder, there's a polymorph patent that we believe that AET and Sandoz are infringing upon. The other one is they're trying to overturn or claim invalidity of our issued patent for method of use.
We feel strongly that AET and Sandoz are infringing upon our polymorph patent, and that the issued patent that we have from the United States Patent and Trademark Office is a valid patent. In our view, historically, judges don't like to overturn patents that have been issued by the United States Patent and Trademark Office, and they are presumed valid. We believe we're going to prevail in that case. On top of that, though, AET and Sandoz, in their effort to try to prove that they're not infringing upon our polymorph patent, introduced significant amount of evidence into the court case that they have an amorphous form. We have an exclusive license to an amorphous patent, and so we filed suit against them in April, defending our amorphous patent. We believe that between those two court cases, we will prevail.
But of course, we would love to find a mutually agreeable settlement, just like we did with the other six. In the meantime, we're vigorously defending our IP.
Right. How does the new suit against the AET help your IP posture and position?
Say that one more time.
How does the new suit against AET help your IP posture and positioning?
Well, it's definitely the multi-layered approach. We have multiple patents that protect WAKIX, and we are going to defend all of them that are applicable. They introduced evidence that was very clear that they are infringing upon this IP. That case is really at its infancy at the beginning. It just started in April. These court cases typically take two and half to three years. Then if you add appeals on top of that, you add another 18 months to that two and half to three years. That is why we believe whether you follow the court cases all the way out to their full resolution, you get into 2030 as the LOE date for WAKIX. Or we can get to that same place, to March of 2030, where we are at with our other six ANDA filers that we settled with.
Either way you slice it, we believe we have strong conviction in that 2030 date.
Okay. Last question. If we're sitting here a year from now, what would you like to say have been the key value creating accomplishments for Harmony during this past year?
In terms of a year from now, I think if you just frame where we are, continued growth of WAKIX, again, on track to over $1 billion this year and continued growth in our foundational franchise. Advancement of BP-205. A year from now, obviously the catalyst we talked about, the MAD data disclosed in Q4, the sleep-deprived healthy volunteer data early next year. Then we'll disclose a broad phase II, proof of concept program with BP-205 mid next year and the investment there.
In addition, I think what good would look like is announcing probably a BD deal or more than one BD deals to grow the pipeline further, possibly put into the bag of our very strong commercial engine, and identify moves that we've made over the year that are value-creating in terms of for the long term, starting with the base business, BP-205, and our Orexin opportunity, and then transacting on the business development front, bringing in smart, strategic, value-creating assets into the enterprise.
Awesome. Well, Jeff, Peter, thank you very much for taking the time to participate in our healthcare conference. Looking forward to all the progress.
Yeah. Thanks, Pete.
Thanks, Pete.
Thanks very much. Thanks, everyone. Thank you.