Harmony Biosciences Holdings, Inc. (HRMY)
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2024 Cantor Fitzgerald Global Healthcare Conference

Sep 17, 2024

Moderator

I think we will get started. So yeah, good afternoon. This has been a gauntlet of five presentations in a row, and that said, I'm really excited about introducing the next presenting company. Harmony Biosciences is what I call affectionately refer to as a rev gen. This is a company that has a revenue stream that is nearing a billion dollars, or certainly it is on a vector to get to a billion dollars within a reasonable period of time. They have a drug called WAKIX, which is very different than the other standard of care in narcolepsy, and because of that, we think that there's broader potential for this drug. Now, I rate the stock overweight rating, and it's a pleasure to introduce Dr. Jeff Dayno, the company's CEO.

We have Jeff Dierks, who runs the commercial operations, so we can ask him about how it's going, and then, of course, Sandip Kapadia, and you know, frankly, this is a company that's really built out its portfolio in the last year, so there's a lot to unpack here, so we'll get started, and we're gonna get started with a question for you, Jeff. You know, in the last year. You've been CEO for a couple of years now, almost. Not quite-

Jeff Dayno
CEO, Harmony Biosciences

Yeah, a little over a year and a half now.

Moderator

Yeah, yeah.

Jeff Dierks
Chief Commercial Officer, Harmony Biosciences

Yeah, yeah.

Moderator

And a lot going on, transformative period for Harmony. So in the last year, what are you most proud of having accomplished by your team?

Jeff Dayno
CEO, Harmony Biosciences

Yeah. Well, first of all, Charles, great to be here. Thank you for the invitation, and yeah, in sort of my tenure as CEO, I think the mandate was to, you know, build off the success of WAKIX, you know, in the commercial market and, you know, build out the pipeline and expand the pipeline and diversify the portfolio, which I think the team has been really hard at work, and this is what, you know, we are looking forward to sort of sharing, especially our upcoming Investor Day on October 1st.

Moderator

Yeah.

Jeff Dayno
CEO, Harmony Biosciences

You know, I think the takeaway message is that it's not sort of the same Harmony that people kind of knew before, you know, as we've really transformed, you know, the company and the pipeline.

Moderator

I would say not. I mean, it's a totally different Harmony than a few years ago.

Jeff Dierks
Chief Commercial Officer, Harmony Biosciences

Yeah.

Moderator

There's a few shekels in the bank.

Jeff Dierks
Chief Commercial Officer, Harmony Biosciences

Mm.

Moderator

There's some revenue stream. What is the current cash, Sandip?

Sandip Kapadia
CFO, Harmony Biosciences

Yeah, no, we're in a solid cash position, $434 million as of the end of last quarter, and continue, as you know, we're profitable, generating positive cash flow, so, you know, as you saw over the past year, we've been redeploying that capital. We can maybe chat about it later, but-

Moderator

We'll have to talk about how to calculate profitability later on, so you can help me out, but that's okay. That's nice to see.

Sandip Kapadia
CFO, Harmony Biosciences

Yeah.

Moderator

As a biotech analyst, I don't often have to deal with such nuances, but what is interesting is that in addition to generating cash quarter on quarter, you're generating revenue out of WAKIX, which is in a relatively mature market called narcolepsy. So Jeff, how do you see WAKIX positioned in the narcolepsy field?

Jeff Dierks
Chief Commercial Officer, Harmony Biosciences

Sure

Moderator

... treatment area?

Jeff Dierks
Chief Commercial Officer, Harmony Biosciences

It's been an amazing journey. You know, we're almost up on five years in the market, launching in November of 2019, after the approval in August of 2019, and we've really seen very strong, durable patient growth, revenue growth as well, guiding towards approximately $700-$720 million in net sales this year, guiding towards approximately 7,000 average patients at the end of the year. WAKIX is the only non-scheduled treatment option that's available, in terms of FDA-approved treatment options for patients and healthcare professionals, and we see WAKIX really finding a meaningful place in this audience. The vast majority of medicines, Charles, are used as add-on therapy. Sadly, this is very much a polypharmacy market.

Moderator

Sure

Jeff Dierks
Chief Commercial Officer, Harmony Biosciences

... where you're looking to manage symptoms of this very debilitating disorder. About 80% of WAKIX use is being used with something else, concomitantly with an oxybate, a wake-promoting agent, and a stimulant.

Moderator

Yeah.

Jeff Dierks
Chief Commercial Officer, Harmony Biosciences

But I think the one thing about WAKIX is it offers really broad clinical utility, which appeals to a broader patient base and a broader prescriber base.

Moderator

Mm-hmm.

Jeff Dierks
Chief Commercial Officer, Harmony Biosciences

A lot of the confidence that I have in our billion-dollar-plus opportunity is the fact that there are 9,000 doctors in this universe that see and treat 100% of the diagnosed audience. We can call on all of these individuals. We can tap into the full diagnosed audience, and we're really, you know, very pleased with the difference that we're making in the community so far. A lot more to do.

Moderator

Now, you mentioned 9,000 prescribers. You mentioned a broad clinical utility. Let's dig into that a little bit.

Jeff Dierks
Chief Commercial Officer, Harmony Biosciences

Okay

Moderator

... because the standard of care really has a challenging set of circumstances with regard to being scheduled, that being the oxybates, for the most part. I guess the question is, why do you think that being non-scheduled is a source of competitive advantage? Does it just make it easier to use, or prescribers and patients really want to go there first before they get to an oxybate?

Jeff Dierks
Chief Commercial Officer, Harmony Biosciences

Yeah, so I think there's two elements. I can, you know, turn it over to our CEO and practicing neurologist for the second part, but there is a threshold to prescribe, and you used a very good word when you talk to doctors that have started to pick up WAKIX. It is an easier product to write.

Moderator

Yeah.

Jeff Dierks
Chief Commercial Officer, Harmony Biosciences

It's an oral pill you take once in the morning. Because it's not scheduled, you can write it with refills. You can write it via telemedicine, the product shipped directly to your home. But what we've seen in this audience, there's about 9,000 doctors, as I said, that see and treat this audience, but only about 4,000 of them have enrolled in the oxybate REMS program, meaning only 4,000 of those 9,000 can actually prescribe any version of an oxybate. 5,000 have chosen not to.

Could be they don't like writing scheduled medicines, they don't have the staff to manage the REMS, but WAKIX is a treatment option that all 9,000 will consider for their patients. And I think part of it is the non-schedule status appeals to a broader audience. We're living in an era with the backdrop of the opioid epidemic, stimulant abuse.

Women tend to make a lot of the healthcare decisions in the family. It's utmost paramount for them that doctors are thinking about how do I reduce controlled medicines, and WAKIX works. It's very effective for both EDS and cataplexy. It's well-tolerated, and the non-scheduled status is really a very differentiated and meaningful driver for the product.

Jeff Dayno
CEO, Harmony Biosciences

Yeah, I think from a, you know, clinical perspective, that's what really drives, you know, what we refer to as the broad clinical utility-

Jeff Dierks
Chief Commercial Officer, Harmony Biosciences

Yeah

Jeff Dayno
CEO, Harmony Biosciences

... in terms of the broader, you know, prescriber base and that attribute, you know, in this market, you know, where all the other products are scheduled. And, you know, it does come down to being sort of easier to use and that threshold to prescribe, as Jeff, you know, mentioned, along with the strong efficacy profile-

Jeff Dierks
Chief Commercial Officer, Harmony Biosciences

Mm-hmm

Jeff Dayno
CEO, Harmony Biosciences

in both EDS and cataplexy.

Moderator

Really differentiated mechanism.

Jeff Dayno
CEO, Harmony Biosciences

Yes.

Moderator

So when you think about this profile.

Jeff Dayno
CEO, Harmony Biosciences

Yeah

Moderator

... this clinical profile of WAKIX, and it being approved and then gaining traction in the narcolepsy market, first of all, is it used by narcolepsy Type 2 patients as well as Type 1? And then I'm gonna ask you about idiopathic hypersomnia, but first, we'll answer those six questions.

Jeff Dayno
CEO, Harmony Biosciences

Yes, it's used by, yeah, it's prescribed for both, you know, patients with Type 1 narcolepsy as well as Type 2. I guess historically, about fifty-fifty-

Moderator

Mm.

Jeff Dayno
CEO, Harmony Biosciences

but now it's, it's evolving a little.

Jeff Dierks
Chief Commercial Officer, Harmony Biosciences

Yeah, what we've seen, Charles, is about half, approximately half of patients coming in to see a healthcare professional present with Type 1, half present with Type 2. WAKIX prescribing has been very consistent, although what we're seeing in the last year or so is there's more of a push towards Type 2. Because the vast majority of patients come in to see their doctor is the excessive daytime sleepiness, not the cataplexy.

Jeff Dayno
CEO, Harmony Biosciences

Yeah, yeah.

Jeff Dierks
Chief Commercial Officer, Harmony Biosciences

So it's much easier to diagnose, and so we are seeing a little bit more Type 2 diagnoses, and as a result, WAKIX prescribing is kind of mirroring the clinical presentation.

Moderator

Let me ask you an off-the-wall question about idiopathic hypersomnia versus narcolepsy Type 2. Like, there's one drug, and we're talking about it, oxybate, that is approved for idiopathic hypersomnia. Is it possible that some narcolepsy Type 2 patients are misdiagnosed, and that idiopathic hypersomnia is actually a bigger deal, a bigger issue, incidence, prevalence, than what the data suggests?

Jeff Dayno
CEO, Harmony Biosciences

Yeah, so the short answer is yes. The short answer is yes, and some of that, you know, is related to... So, you know, IH, or idiopathic hypersomnia, is another central disorder of hypersomnolence, and it's an adjacency to narcolepsy, as you're well aware, and it's a diagnosis of exclusion, so you're kind of going through the diagnostic, you know, sort of exercise and then ruling out other kind of aspects, you know, with regards to, you know, NT1, how that's defined, and then, you know, NT2, you know, which is a little more subtle.

So especially in hands of other kind of HCPs that may not be as experienced, you're not getting, you know, to the kind of critical components to ultimately make the diagnosis of IH by excluding other aspects, and mainly that comes down to the work in the sleep lab and a sleep study. So, so I think that it's also... You know, the narcolepsy market is well defined, is very well defined.

Moderator

Yeah.

Jeff Dayno
CEO, Harmony Biosciences

You know, oxybate's in the market over twenty years, and IH is still an evolving market. And then, you know, what you said is important, only one approved product-

Moderator

Yeah

Jeff Dayno
CEO, Harmony Biosciences

... to treat IH, and that being Xwav, that, you know, I think people are familiar with.

Moderator

Yeah.

Jeff Dayno
CEO, Harmony Biosciences

But you look at that product, you know-

Moderator

Yeah

Jeff Dayno
CEO, Harmony Biosciences

... it's a Schedule III restricted access REMS product.

Moderator

Mm-hmm.

Jeff Dayno
CEO, Harmony Biosciences

The dosing kind of paradigm, where you have to take it around 10:00 P.M., wake up three to four hours later, dose again.

Moderator

Not easy

Jeff Dayno
CEO, Harmony Biosciences

... in patients that are long sleepers. So that is the backdrop. Maybe I'll move to, you know, why we are pursuing the sNDA in idiopathic hypersomnia.

Moderator

Great idea. Great segue.

Jeff Dayno
CEO, Harmony Biosciences

So I-

Moderator

Was gonna ask.

Jeff Dayno
CEO, Harmony Biosciences

Yeah.

Moderator

Yeah.

Jeff Dayno
CEO, Harmony Biosciences

I think it's

Moderator

You ran a study, the INTUNE study.

Jeff Dayno
CEO, Harmony Biosciences

Right.

Moderator

Required some interpretation.

Jeff Dayno
CEO, Harmony Biosciences

Mm-hmm.

Moderator

You've gone to the agency-

Jeff Dayno
CEO, Harmony Biosciences

Right

Moderator

... and now you're pursuing a supplemental NDA.

Jeff Dayno
CEO, Harmony Biosciences

Correct, right, and we're on track. So we're on track to submit the sNDA in the fourth quarter.

Moderator

Yeah.

Jeff Dayno
CEO, Harmony Biosciences

But, you know, so the thinking is the backdrop we just talked about, you know, that there is still significant unmet medical need for the treatment of IH, you know, given only one approved, you know, treatment option, you know, that has, you know, kind of a profile that's a lot different than WAKIX. You know, WAKIX works, you know, through histamine, it's non-scheduled, and you take it once daily in the morning-

Moderator

Yeah

Jeff Dayno
CEO, Harmony Biosciences

... in patients who are long sleepers that have sleep inertia in the morning. So, you know, the product profile sort of, you know, sits that, you know, fits that patient population. You know, with regards to, you know, the strategy of the sNDA, as you mentioned, you know, we did a phase III trial, and we sort of, speak to that... And then we met with the FDA in terms-

Moderator

Mm

Jeff Dayno
CEO, Harmony Biosciences

... of, you know, what we saw in the study, and in the discussion, you know, based on kind of the backdrop of the treatment options, you know, we heard the potential for having some regulatory flexibility-

Moderator

Okay

Jeff Dayno
CEO, Harmony Biosciences

... you know, if we were to submit, you know, an sNDA, and that obviously we are pursuing. And, you know, the reason is, you look at, you know, the unmet medical need, you build the overall benefit-risk proposition, and through that, you know, we're looking at the totality of the data, so briefly, you know, in the phase III trial, we saw a strong signal in the open label dose optimization phase.

Moderator

Yeah.

Jeff Dayno
CEO, Harmony Biosciences

Yeah. We acknowledge that we didn't hit the primary outcome during just the four-week randomized withdrawal, and we have some good explanations related to-

Moderator

Yeah

Jeff Dayno
CEO, Harmony Biosciences

... pharmacodynamic effect in those that were randomized to placebo. And at the end of that, almost 90% of patients that were in the study and had the experience on pitolisant in the open label phase up front, went into the long-term extension.

Moderator

Mm-hmm.

Jeff Dayno
CEO, Harmony Biosciences

Now we've been collecting long-term safety data as well as efficacy data.

Moderator

Mm-hmm

Jeff Dayno
CEO, Harmony Biosciences

... you know, out past a year, and that's some of the data we're gonna be sharing at our investor day-

Moderator

Oh, okay

Jeff Dayno
CEO, Harmony Biosciences

... to show, sort of the strong signal we're seeing in terms of maintenance of effect, durability of effect-

Moderator

Yeah

Jeff Dayno
CEO, Harmony Biosciences

... and about two-thirds of patients, you know, remain in the study. So we take, you know, all the data from the trial. We also have some real-world evidence data with WAKIX that's been used off-label in Europe-

Moderator

Mm-hmm

Jeff Dayno
CEO, Harmony Biosciences

... for IH.

Moderator

Mm-hmm.

Jeff Dayno
CEO, Harmony Biosciences

We have the French Compassionate Use Program data, so putting all that together to build a strong, you know, benefit-risk proposition, in pursuit of the IH indication.

Moderator

So it's really multifactorial. It's not just about the data from INTUNE. It's not just about the setup relative to the current standard of care, if you will, the non-scheduled setup. It's not just about the clinical experience, although positive with regard to WAKIX being in the market for narcolepsy. It's also all the other things that you mentioned. So you have confidence to pursue an sNDA. You are going to file by the end of the year, you say. What is the rate-limiting step?

Jeff Dayno
CEO, Harmony Biosciences

I think that the rate-limiting step is we've just been collecting the data from the long-term extension-

Moderator

Okay

Jeff Dayno
CEO, Harmony Biosciences

... and then just doing those data cuts and really getting them sort of, the data sets in a compliant manner, to sort of finalize the preparation of the submission.

Moderator

Okay.

Jeff Dayno
CEO, Harmony Biosciences

We also recently learned of some of the data in Europe.

Moderator

Mm-hmm

Jeff Dayno
CEO, Harmony Biosciences

... the real-world evidence, and what's important-

Moderator

Okay

Jeff Dayno
CEO, Harmony Biosciences

... you know, in orphan rare disorders where there's a lot of unmet medical need, and we've seen examples of this, that, you know, real-world evidence can often sort of, you know, supplement and support your clinical trial data, you know, along with the ability for regulatory flexibility.

Moderator

Yeah.

Jeff Dayno
CEO, Harmony Biosciences

I think, as you may be aware, you know, I've served as the industry representative on FDA ad coms in the neurology division.

Moderator

Mm-hmm.

Jeff Dayno
CEO, Harmony Biosciences

So I've actually been sort of a front-row seat to sort of seeing how the agency, you know, looks at, you know, where to apply regulatory flexibility-

Moderator

Sure

Jeff Dayno
CEO, Harmony Biosciences

... the importance of real-world evidence. So we've been bringing, you know, all of the data that we have to bear to put into the sNDA submission.

Moderator

Let me ask you a question with regards to the agency and the discussion. Do you think it is aware that narcolepsy or that idiopathic hypersomnia is both high burden and then possibly misdiagnosed as narcolepsy Type 2?

Jeff Dayno
CEO, Harmony Biosciences

I think that they are. It's a really interesting question because I think that the agency is learning more and more about that, you know, in terms of the sleep disorders and the primary disorders of hypersomnolence. And the reason I say that is because there was recently a patient-focused drug development meeting with the agency.

Moderator

Mm-hmm

Jeff Dayno
CEO, Harmony Biosciences

... around idiopathic hypersomnia.

Moderator

Mm-hmm.

Jeff Dayno
CEO, Harmony Biosciences

And the voice of the patient report just was released.

Moderator

Okay.

Jeff Dayno
CEO, Harmony Biosciences

The FDA and the director of the psychiatry division, that's the division we're in, attended that meeting, and her staff.

Moderator

Mm-hmm.

Jeff Dayno
CEO, Harmony Biosciences

I think it's top of mind, you know, with regards to the burden of IH, the unmet medical need, and where new treatment options, you know, would be very helpful. 'Cause in addition to Xywav, the only approved product, the other agents that are commonly used are CII stimulants.

Moderator

Yeah.

Jeff Dayno
CEO, Harmony Biosciences

And the FDA is very aware of a lot of, you know, stimulant misuse and diversion.

Moderator

Yeah

Jeff Dayno
CEO, Harmony Biosciences

... and they are not approved for IH, obviously.

Moderator

Yeah. Yeah. So quick advertisement, October 15th, we are running a KOL call with a couple of members of an advocacy community that participated in that meeting-

Jeff Dayno
CEO, Harmony Biosciences

Yeah

Moderator

... for IH. So we'll be talking more about this.

Jeff Dayno
CEO, Harmony Biosciences

Okay.

Moderator

But we're looking forward to this sNDA because it has been a point of, you know, I'll call it, debate among investors. You know, you had the INTUNE results, and then is Wakix gonna see an expanded label? If you had to be a betting person, Sandy, probability of sitting here next year and talking about an approval in IH?

Sandip Kapadia
CFO, Harmony Biosciences

Oh, you're [audio distortion]

Jeff Dayno
CEO, Harmony Biosciences

I think the question is directed to you, Sandy.

Sandip Kapadia
CFO, Harmony Biosciences

I think it's more of a regulatory question, Jeff. No, look, look-

Moderator

Well, you're-

Sandip Kapadia
CFO, Harmony Biosciences

We're gonna do-

Jeff Dayno
CEO, Harmony Biosciences

I'm gonna have to-

Sandip Kapadia
CFO, Harmony Biosciences

We're gonna do everything we can to be-

Moderator

Okay

Sandip Kapadia
CFO, Harmony Biosciences

... you know, bring as much, you know, information to it, to give it the highest probability of success that we can believe.

Moderator

To Jeff Dierks, will you be able to commercialize a broader label with a capital-efficient effort?

Jeff Dierks
Chief Commercial Officer, Harmony Biosciences

Yes.

Sandip Kapadia
CFO, Harmony Biosciences

Yes.

Jeff Dierks
Chief Commercial Officer, Harmony Biosciences

When approved, the good news is IH. There's a high level of overlap with narcolepsy.

Moderator

Mm-hmm.

Jeff Dierks
Chief Commercial Officer, Harmony Biosciences

About 90% of the doctors that we currently call on our narcolepsy universe are RH, are IH doctors, and over five, six thousand doctors have already had experience with WAKIX. So we have existing sales footprint. The doctors know the drug, they know the dose, they know how to fill out the form. It's the same patient hub, it's the same specialty pharmacy distribution universe, so we will be ready to hit the ground running and be able to help this next group of orphan patients as soon as we get the approval.

Moderator

So I assume that that's a component of the growth picture and confidence behind the growth picture of WAKIX. How about the lack of traction or even despite generic oxybates being introduced, are you confident in WAKIX growth in the near term? Then we'll talk about pipeline.

Jeff Dierks
Chief Commercial Officer, Harmony Biosciences

Yeah, so we see WAKIX as a billion-dollar-plus opportunity in adult narcolepsy alone. If successful in IH, that's an accretive opportunity.

Moderator

Okay.

Jeff Dierks
Chief Commercial Officer, Harmony Biosciences

A lot of interest in the community, but given the fact it's a high-price specialty product, managed care is not covering things outside their indication. So if we're successful in the regulatory approval, IH is a significant opportunity. I know that some analysts have looked at that as maybe a $500 million-$750 million opportunity for Xywav. So that's something that would be purely accretive to the $1 billion-plus opportunity we see in adult narcolepsy.

Moderator

Okay. Future lies ahead. Jeff Dayno, what are you most excited about in terms of the pipeline?

Jeff Dayno
CEO, Harmony Biosciences

All of it.

Moderator

I wanted to ask you-

Jeff Dayno
CEO, Harmony Biosciences

Ev- ev- ev-

Moderator

one specifically, but I'm

Jeff Dayno
CEO, Harmony Biosciences

Yeah

Moderator

... I wanna know your-

Jeff Dayno
CEO, Harmony Biosciences

Every bit of it. No, so I.

Moderator

They're all your favorite children?

Jeff Dayno
CEO, Harmony Biosciences

I think they are.

Moderator

Okay.

Jeff Dayno
CEO, Harmony Biosciences

So I think that obviously, you can tell we're really excited, you know, what we've built over the past year. IH is a good example, because in addition to WAKIX and the sNDA submission, we have the next gen formulations-

Moderator

Yes

Jeff Dayno
CEO, Harmony Biosciences

... and specifically HD.

Moderator

Yeah.

Jeff Dayno
CEO, Harmony Biosciences

That, you know, we were gonna-

Moderator

High dose

Jeff Dayno
CEO, Harmony Biosciences

... we're gonna pr-

Moderator

HD, high dose.

Jeff Dayno
CEO, Harmony Biosciences

High dose.

Moderator

Yes.

Jeff Dayno
CEO, Harmony Biosciences

Pitolisant and high dose, yes.

Moderator

Yeah.

Jeff Dayno
CEO, Harmony Biosciences

Which we're gonna also pursue in idiopathic hypersomnia as well. Higher dose, provisional patents filed to twenty forty-four.

Moderator

Okay.

Jeff Dayno
CEO, Harmony Biosciences

A much longer runway, more time in the market. So what that represents is, starting with the pipeline, we're really extending and strengthening our leadership position in sleep-wake-

Moderator

Mm-hmm

Jeff Dayno
CEO, Harmony Biosciences

... our core franchise. You know, WAKIX, in its successful commercial product, managing the life cycle, the next gen formulations, and then we can then talk to our orexin-2 agonists that we in-licensed. So in addition to sleep-wake, you know, all of which are very exciting programs, we have two other orphan rare, you know, neuro franchises. So where we're sitting to frame the pipeline-

Moderator

Epilepsy and neurobehavioral.

Jeff Dayno
CEO, Harmony Biosciences

Neurobehavioral and epilepsy. Three orphan rare CNS franchises, each with potential peak sales opportunities of $1 billion-$2 billion.

Moderator

Mm-hmm.

Jeff Dayno
CEO, Harmony Biosciences

We've gone from sort of a single product company to now having eight assets in 13 development programs, three of which are in phase III currently, and we're on track to soon initiate a fourth phase III program in Lennox-Gastaut with EPX-100.

Moderator

Mm-hmm

Jeff Dayno
CEO, Harmony Biosciences

... before the end of the year. Importantly, the pipeline is poised to deliver at least one new product or indication launch each year over the next five years.

Moderator

Mm-hmm.

Jeff Dayno
CEO, Harmony Biosciences

So what we now have put together are the near-term catalysts in the pipeline and a foundation for durable revenue generation.

Moderator

Now, EPX-100, you just mentioned, and I, and I have to kinda go off script here, although I'm trying not to be on script. EPX-100, what is it? And, you say that you're gonna launch in Lennox-Gastaut, a phase III.

Jeff Dayno
CEO, Harmony Biosciences

Yeah, so EPX-100, it's actually a repurposed drug. It's clemizole hydrochloride.

Moderator

Yep.

Jeff Dayno
CEO, Harmony Biosciences

It's really interesting that, you know, it is a first-generation antihistamine-

Moderator

Mm-hmm

Jeff Dayno
CEO, Harmony Biosciences

... that was on the market from the late 1950s to the late 1970s, and then with a lot of, you know, exposure in the market and no real safety sort of signals, you know, identified, and I can come back to that, that was just taken off the market when the second-generation antihistamines came along. But importantly, you know, working through, sort of, you know, 5-HT serotonin mechanisms, it was actually, put into one of the preclinical models for the rare epilepsies-

Moderator

Mm-hmm

Jeff Dayno
CEO, Harmony Biosciences

... what are referred to as the developmental epileptic encephalopathies-

Moderator

Yep

Jeff Dayno
CEO, Harmony Biosciences

... called the zebrafish model.

Moderator

Yep.

Jeff Dayno
CEO, Harmony Biosciences

And showed a very strong signal, which is very predictive of clinical efficacy. And then the, you know, Epygenix sort of went to work, you know, on this program and starting with Dravet syndrome-

Moderator

Mm-hmm

Jeff Dayno
CEO, Harmony Biosciences

... you know, that currently in a late-stage registrational trial, and then assessing for that. The bigger market opportunity is LGS-

Moderator

Yeah

Jeff Dayno
CEO, Harmony Biosciences

... which we'll be initiating-

Moderator

Yeah

Jeff Dayno
CEO, Harmony Biosciences

... the phase III.

Moderator

But the mechanism seems to have a really interesting effect size for Dravet. It gives you confidence that it may work in LGS.

Jeff Dayno
CEO, Harmony Biosciences

I mean, I think it's, you know, so there's some read-through to LGS based on that mechanism.

Moderator

Yeah

Jeff Dayno
CEO, Harmony Biosciences

... although it's, there's a little more heterogeneity-

Moderator

Yeah

Jeff Dayno
CEO, Harmony Biosciences

... in LGS compared to Dravet. So I think, you know, you need to sort of design, you know, the phase III trials accordingly and in terms of how it's powered, to be able to demonstrate that, you know, efficacy signal.

Moderator

Beyond doing an LGS study, would you consider a broader, DEE's, study?

Jeff Dayno
CEO, Harmony Biosciences

We would, yeah. I mean, we're just getting started. You know, we did-

Moderator

Okay

Jeff Dayno
CEO, Harmony Biosciences

... the acquisition, you know, this spring, brought it in, and the phase III for Dravet's was in line, so we're carrying that forward. We anticipate top-line data in 2026, initiating you know, the LGS phase III pivotal study. But in terms of the... as the field emerges and, you know, some of the other sponsors and the work that they're doing, you know, the potential of a basket trial in-

Moderator

Right

Jeff Dayno
CEO, Harmony Biosciences

... in broad DEEs-

Moderator

Right

Jeff Dayno
CEO, Harmony Biosciences

... is absolutely sort of in, you know, in consideration.

Moderator

In your sights. That's what I'm thinking about.

Jeff Dayno
CEO, Harmony Biosciences

Yeah.

Moderator

Why don't we then move to ZYN-005. Is it ZYN00-

Jeff Dayno
CEO, Harmony Biosciences

002.

Jeff Dierks
Chief Commercial Officer, Harmony Biosciences

2.

Moderator

002, sorry.

Jeff Dayno
CEO, Harmony Biosciences

That's okay.

Moderator

Fragile X.

Jeff Dayno
CEO, Harmony Biosciences

Yeah.

Moderator

phase III ongoing now. When to read out, and what gives you confidence in that recently in-licensed-

Jeff Dayno
CEO, Harmony Biosciences

Yeah

Moderator

... candidate?

Jeff Dayno
CEO, Harmony Biosciences

Yeah, so I know that-

Moderator

Or acquired candidate.

Jeff Dayno
CEO, Harmony Biosciences

Yeah. I know you know this story a bit-

Moderator

Yeah

Jeff Dayno
CEO, Harmony Biosciences

... and we're really excited about that, one of the near-term catalysts with, on track for top-line data mid-next year. So with regards to... And this is why I say, you know, all of these programs we're excited about in the pipeline. So ZYN002 is another novel innovative product. It's a purely synthetic cannabidiol-

Moderator

Yep

Jeff Dayno
CEO, Harmony Biosciences

... devoid of THC.

Moderator

Transdermal.

Jeff Dayno
CEO, Harmony Biosciences

Transdermal.

Moderator

Yeah.

Jeff Dayno
CEO, Harmony Biosciences

Bypasses first-pass metabolism-

Moderator

Yeah

Jeff Dayno
CEO, Harmony Biosciences

... and then you don't have, you know, sort of the, the GI tolerability issues as well as LFT issues. Similar to, you know... There, there's a product in the market, Epidiolex-

Moderator

Yeah

Jeff Dayno
CEO, Harmony Biosciences

... which is a plant-based cannabidiol, you know, where you have about 20%-30%, incidence of, you know, GI side effects-

Moderator

Yeah

Jeff Dayno
CEO, Harmony Biosciences

... and you have to monitor LFTs.

Moderator

Yeah.

Jeff Dayno
CEO, Harmony Biosciences

You know, you don't have that, those issues with ZYN002.

Moderator

Nor the peanut oil-

Jeff Dayno
CEO, Harmony Biosciences

Yeah

Moderator

... that you're swallowing.

Jeff Dayno
CEO, Harmony Biosciences

Correct. Correct.

Moderator

Yeah.

Jeff Dayno
CEO, Harmony Biosciences

I think that you know, when we did the diligence, and we saw. You know, as you're familiar, the phase II study, called the CONNECT trial, while it did not hit on the primary outcome, when you really dig in and look at the data, a pre-specified ad hoc analysis in a subgroup of patients that were called fully methylated, so the genetic defect in terms of the full methylation, where patients have more severe symptoms-

Moderator

Yeah

Jeff Dayno
CEO, Harmony Biosciences

... you know, in that subgroup, you saw a statistically significant outcome, number one.

Moderator

Mm-hmm.

Jeff Dayno
CEO, Harmony Biosciences

The other learnings from that trial that were designed into the pivotal phase III RECONNECT study that's ongoing, in terms of the dose response and then the need for a higher dose in patients with higher body weight.

Moderator

Mm-hmm

Jeff Dayno
CEO, Harmony Biosciences

... and then the duration of the trial because the effect continued to improve over time.

Moderator

Mm-hmm.

Jeff Dayno
CEO, Harmony Biosciences

Right? So those three elements, more of the study population, phase III RECONNECT, will be fully methylated-

Moderator

Yeah

Jeff Dayno
CEO, Harmony Biosciences

... about 80% of the patients, higher dose in a body weight, I think over 40 kilos, and then a longer out to, you know, 18 weeks in the trial, with regards to looking at the primary outcome.

Moderator

All enhanced signal-to-noise, for sure.

Jeff Dayno
CEO, Harmony Biosciences

Correct. Correct.

Moderator

Yeah.

Jeff Dayno
CEO, Harmony Biosciences

Right, and that, that's what, you know, gives us, you know, sort of confidence in terms of the probability of success, and as I mentioned, you know, looking to a near-term readout, you know, mid-next year.

Moderator

Okay. So we'll look forward to that one. I was actually involved in Zynerba earlier on in my career, and so, hopefully, that one will gain traction here soon, but definitely not in our model, at this point.

Jeff Dayno
CEO, Harmony Biosciences

Yeah

Moderator

... but the future lies ahead.

Jeff Dayno
CEO, Harmony Biosciences

Yeah.

Moderator

Now, you know, I wanted to save the best for last, if you will, because it's very topical, and this is the orexin-2 receptor agonist space become quite interesting and, in fact, in the last week or so, resulted in over $200 million worth of investor money being put to work for a company called Centessa, which I don't cover. But you, too, have an orexin-2 receptor agonist. Can you tell us a little bit about it, where it came from, and why you think it may have competitive advantage?

Jeff Dayno
CEO, Harmony Biosciences

Sure, so the orexin-2 agonist that we in-licensed with our partner, Bioprojet, TPM-1116, so it came from a company called Teijin Pharma, and, you know, based in Japan, and you know, a lot of the orexin biology, a lot of the Japanese, you know, companies are very strong in orexin biology. What's most interesting about Teijin, that the individual who discovered the orexin receptor in Japan, Professor Yanagisawa-

Moderator

Yes

Jeff Dayno
CEO, Harmony Biosciences

... worked with Teijin on this program. So you had the, Japanese group discovering the orexin receptor, and around the same time, the group from Stanford-

Moderator

Mm

Jeff Dayno
CEO, Harmony Biosciences

... also made the discovery, and they gave it the name hypocretin. So that's where the two different names come from. So Professor Yanagisawa worked with Teijin to optimize this library of compounds-

Moderator

Mm-hmm

Jeff Dayno
CEO, Harmony Biosciences

... towards the, you know, the orexin-2 receptor, and so I think that's where it came from. We in-licensed it with our partner, Bioprojet, and what we saw in the diligence, you know, was a profile that is very differentiated and the potential to be best-in-class, starting with a unique chemical scaffold.

Moderator

Okay.

Jeff Dayno
CEO, Harmony Biosciences

So a different sort of chemical library series than some of the other orexin-2 agonists in the clinic.

Moderator

Mm-hmm.

Jeff Dayno
CEO, Harmony Biosciences

From what we've seen publicly available, you know, potential as being the most potent.

Moderator

Okay.

Jeff Dayno
CEO, Harmony Biosciences

At our upcoming Investor Day, 'cause none of these data have been publicly disclosed yet, we will be sharing some of this new data on the orexin program. We'll be sharing data from the long-term extension in IH and some of the data in the ZYN002 program, so you know, some new data and updates, you know, on these programs.

Moderator

A lot to look forward to. Can't wait-

Jeff Dayno
CEO, Harmony Biosciences

Yeah

Moderator

... for that October 1st-

Jeff Dayno
CEO, Harmony Biosciences

Yeah

Moderator

... Analyst Day.

Jeff Dayno
CEO, Harmony Biosciences

Yeah.

Moderator

First ever for you for a long time or ever, that I can-

Jeff Dayno
CEO, Harmony Biosciences

This is our first.

Moderator

Yeah.

Jeff Dayno
CEO, Harmony Biosciences

Yep, and then in addition, on TPM-1116, we also have PK, you know, preclinical, sort of preclinical PK data that would suggest, you know, the potential for once-daily dosing, which is-

Moderator

Yeah

Jeff Dayno
CEO, Harmony Biosciences

... important.

Moderator

Important. Where would you go first, into a narcolepsy patient or a normal human volunteer?

Jeff Dayno
CEO, Harmony Biosciences

So to-

Moderator

To look clinically-

Jeff Dayno
CEO, Harmony Biosciences

Yeah

Moderator

... at the drug?

Jeff Dayno
CEO, Harmony Biosciences

Yeah, so great question. I know a lot of debate. I mean, the orexin-2 agonist space has generated a lot of interesting sort of-

Moderator

Yep

Jeff Dayno
CEO, Harmony Biosciences

... discussion. I think if you go into healthy volunteers, you can probably execute faster.

Moderator

Yeah.

Jeff Dayno
CEO, Harmony Biosciences

If you go into actual patients, it may take a little longer, but the quality of the data may be better. So a little too early to say, but I think we have both options available to us. We're very experienced, you know, in this space.

Moderator

Yeah.

Jeff Dayno
CEO, Harmony Biosciences

And we know that we are now working on IND-enabling studies, so the plan is to file the IND mid-next year.

Moderator

Okay

Jeff Dayno
CEO, Harmony Biosciences

... and quickly move into the clinic, first in human, second half of next year, and then look to sort of accelerate the development program, you know, based on the strength of our, you know, R&D team and-

Moderator

Sure

Jeff Dayno
CEO, Harmony Biosciences

... the experience in this area.

Moderator

We look forward to seeing that emerge. Unfortunately, we're pretty much out of time. Any other questions from the audience before we call it? Jeff, thank you. Jeff, thank you.

Jeff Dierks
Chief Commercial Officer, Harmony Biosciences

Sure.

Moderator

Sandip.

Jeff Dayno
CEO, Harmony Biosciences

Thank you.

Moderator

Great to see you folks.

Jeff Dayno
CEO, Harmony Biosciences

Yeah. Thank you, Charles.

Moderator

Thanks for sharing this story. I'll see you on October 1st.

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