Harmony Biosciences Holdings, Inc. Common Stock Piper Sandler Virtual CNS Symposium

Thanks again. Yeah. Thank you.

David, thanks for having us, and thanks to the Piper team. Just wanted to say a couple introductory comments. Obviously, we just had our earnings last quarter, and there were really two key, last week, our quarterly earnings. There were two key themes. First is the record quarter we had in terms of performance for WAKIX, and I think that's really important for a few reasons. One, clearly shows the important role that WAKIX has in the marketplace and will continue to have in the marketplace, and that it's growing this much in the seventh year on the market. Clearly, it's got an important role in the treatment of narcolepsy, but also, I think, speaks to the commercial execution and the capabilities of our team. Importantly, it pays for our pipeline.

That really strong performance allows us to bring forward products like BP-205, which was the other area of focus for our earnings call last week and the emerging data, the first clinical data that we have with BP-205, and I know Kumar will cover some of that. But it's certainly that WAKIX performance is an enabler for us to pay for that product, but also other products in the pipeline and also enables us to be able to do business development transactions, which is a high priority for us.

Yeah. Thank you, Peter. Hey, David. Good afternoon, and thank you for having us. Let me start with that 205. We have been getting a lot of questions, especially in the light of the preclinical data that we presented last year, especially, more importantly, the clinical data, the initial clinical data that we presented at the earnings call last week. So I'll provide a comprehensive overview of 205, and that will hopefully answer a lot of questions. Let me start with the chemical scaffolding, the chemical structure itself. BP-205 has a novel chemical scaffold that gives it some unique attributes, like high potency, and avoids some of the molecular structure-related AEs, like hepatotoxicity or cardiotoxicity. Then it also gave us very high potency in the range of 0.015 nanomolar. This continues to be the most potent orexin 2 receptor agonist in the clinical development.

Beyond that, it also has excellent selectivity. The preclinical data, the safety pharmacology and toxicology studies were clean, and the preclinical data showed that it could potentially be dosed once a day. This data was shared at the sleep meeting last year and also at the World Sleep Congress last year. Now, fast-forward, we are in the clinic now. We shared single ascending dose study last week at our quarterly earnings call. Just an overview on the study design itself. It is a standard single ascending dose study, double-blind, randomized, placebo-controlled study, men and women, healthy volunteers. 72 subjects participated in this study. We studied dose range from 0.2 milligram all the way to 6 milligram, so about 30 folds. What we saw in the single ascending dose study is it reinforced our belief that BP-205 has the potential to be the best-in-class orexin 2 receptor agonist.

Starting with the Tmax, we saw very short Tmax, 30 to 75 minutes, which points to rapid onset of efficacy. We saw Cmax and AUC that were dose proportional from 0.2 milligram all the way to 6 milligram. We saw a long half-life of 25 hours, which will potentially lend itself to once-a-day dosing, help with wakefulness in the later in the afternoon, early evenings, and especially the combination of the high potency and longer half-life is very well suited for indications outside of NT1, where there is no orexin deficiency, where we depend on the higher cascade mechanism of action of BP-205 for the downstream effects on histamine, norepinephrine, dopamine, and serotonin. Apart from that, safety tolerability. We did not see any cardiovascular, hepatic, or visual disturbances.

The AEs of note were headache, fatigue, and diarrhea in about 10%, 4%, and 3% of the patient population respectively, or healthy volunteers respectively. In terms of next step, we have completed dosing in the MAD study.

We did disclose some safety tolerability profile from the MAD study. We did see some target engagement AEs in our MAD study, like insomnia and polyuria. But the insomnia was neither severe nor sustained. We will disclose the full data set in the fourth quarter. The PK analysis is still ongoing. Finally, we have opened our IND in U.S. We will be commencing sleep-deprived healthy volunteer study, and the top-line data will be available in early 2027, and we are on course to initiate multiple phase II studies in product CNS indications.

That is correct, David. Okay.

Look, if there is an ability to dose once a day, that is always preferable from a patient's perspective, convenience, compliance. Pitolisant, for example, has a half-life of 20 hours. It's dosed once a day in the morning upon awakening, and patients love it, and prescribers like it.