Was target engagement confirmed for BP-205, specifically if it's activating the orexin-2 receptor in CNS?

Kumar Budur stated that while SAD data didn't show specific mechanistic AEs like insomnia/polyuria, the ongoing MAD study (dosed for 15 days) did observe some transient, non-serious insomnia and polyuria, indicating target engagement. Full MAD data will be disclosed in Q4. “in our multiple ascending dose study, we dosed for 15 days in healthy volunteers. What I can say is we did see some target engagement mechanistic EAEs such as insomnia and polyuria. But this is transient and none of them were either serious or sustained.”

Comment on BP-205's selectivity for orexin-2 vs. orexin-1, comparing it to other orexin molecules, and the importance of potency vs. selectivity.

Kumar Budur highlighted over 600-fold selectivity for orexin-2 over orexin-1, and over 1,000-fold selectivity over 100 other receptors. He explained that potency and selectivity go hand-in-hand, and the high selectivity (140-fold margin over orexin-1 at predicted max therapeutic dose) is more than sufficient to avoid orexin-1 related AEs, which were not observed in SAD or preliminary MAD data. “We have over 600-fold selectivity for orexin-2 receptors over orexin-1 receptors. Potency and selectivity, they go hand in hand.”

Discuss the novel scaffold for BP-205, how it differs from other orexin candidates, and how this translates to a differentiated efficacy/safety profile.

Kumar Budur explained that the novel scaffold avoids typical pyrrolidine sulfonamide bicyclic moieties, leading to a flatter structure designed to prevent molecular structure-related AEs like hepatotoxicity and cardiac toxicity seen with other orexin-2 agonists. This design contributes to high potency and the favorable PK/safety profile observed. “instead of this 3-dimensional crystal structure, the structure is much more flat, and that is supposed to give us more potency and also help us with some of the structure-related EAEs.”

HRMY

Harmony Biosciences (HRMY) Q2 FY26 earnings call: guidance and Q&A

Earnings call· Jun 2026 (Q2 FY26)· Health Care· Aug 4, 2026

Source: earnings call transcript

Executive summary

Harmony Biosciences Q2 FY26 — Record WAKIX Revenue and Promising BP-205 Phase I Data

Harmony Biosciences reported a defining quarter with record WAKIX revenue, firmly on track to exceed $1 billion for the year, driven by strong patient additions. The company also unveiled encouraging Phase I data for its potential best-in-class orexin-2 agonist, BP-205, with multiple data catalysts expected over the next six months. Harmony maintains a strong balance sheet and is actively pursuing strategic business development opportunities while protecting its pitolisant franchise IP.

Highlights

WAKIX delivered record quarterly net revenue of $261.3 million, up 30% year-over-year and 21% quarter-over-quarter.
Reiterated full-year 2026 guidance for WAKIX net revenue of $1 billion to $1.04 billion.
BP-205 Phase I SAD study showed a predictable PK profile with potential for once-daily dosing and a favorable safety/tolerability profile, reinforcing its potential as a best-in-class orexin-2 agonist.
WAKIX achieved estimated average patients of 8,950, an increase of approximately 450 patients from Q1, the highest Q2 increase in brand history.
Ended the quarter with $962.5 million in cash, cash equivalents, and investments, providing significant capacity for strategic business development.

Concerns

Cost of product sold increased to 24.2% of net revenue, up from 19% a year ago, primarily due to new royalties from the Novitium license agreement.
Delay in TEMPO study (Prader-Willi syndrome) top-line data to mid-2027 due to limited patient prevalence and specific enrollment criteria.

Guidance & targets

Category	Target	Timeline	Confidence
WAKIX Net Revenue	$1.0 billion to $1.04 billion high materiality	Full-year 2026 · FY26	High
Pitolisant GR PDUFA Date	April 1, 2027 medium materiality	Q2 · FY27	High
Pitolisant HD Top-line Data (ONSTRIDE 1 & 2)	2027 medium materiality	Full-year 2027 · FY27	High
Pitolisant HD Anticipated PDUFA	2028 medium materiality	Full-year 2028 · FY28	High
TEMPO Study Top-line Data (Prader-Willi syndrome)	mid-2027 medium materiality	Mid-2027 · FY27	Medium
EPX-100 Top-line Data (ARGUS & LIGHTHOUSE)	mid-2027 medium materiality	Mid-2027 · FY27	High
EPX-100 Anticipated PDUFA	2028 medium materiality	Full-year 2028 · FY28	High
BP-205 Multiple Ascending Dose (MAD) Data Disclosure	Q4 high materiality	Q4 · FY26	High
BP-205 Phase Ib Study Initiation	Q3 high materiality	Q3 · FY26	High
BP-205 Phase Ib Study Top-line Data	early next year high materiality	Early 2027 · FY27	High
BP-205 Phase II Trials Initiation	mid-2027 high materiality	Mid-2027 · FY27	High
WAKIX Exclusivity	March 2030 high materiality	March 2030 · FY30	High
Pitolisant Franchise Extension	into the 2040s medium materiality	Beyond 2040	Medium

Segment performance

Segment	Revenue	YoY	QoQ	Margin
WAKIX (Pitolisant) Record quarterly net revenue driven by strong patient additions and differentiated profile as the only non-scheduled treatment for narcolepsy. Field team expansions and improved reimbursement support contributed to performance. Estimated average patients: 8,950Patient additions (QoQ): 450CAGR (last 5 years): 40%Payer coverage: >80% of livesNarcolepsy market penetration: ~20%	$261.3 million	30%	21%	—

Deals & partnerships

Novitium License agreement for amorphous form of pitolisant

Supported by an issued patent through 2042. Current efforts are directed towards formulation optimization and ongoing Phase I PK study.

CiRC Upfront fee payment $15 million

Upfront fee paid in Q2 2025.

Risks & headwinds

Increased cost of product sold Q2 FY26

24.2% of net revenue in Q2 FY26, up from 19% in prior year quarter.

Mitigation:Primarily driven by new royalties related to the Novitium license agreement.

Delay in TEMPO study (Prader-Willi syndrome) top-line data Mid-2027

Top-line data expected mid-2027 (delayed from prior expectation).

Mitigation:Due to limited prevalence of PWS patients and specific sleepiness criteria for enrollment. Study designed with FDA input to meet registrational requirements and secure pediatric exclusivity for WAKIX.

WAKIX IP litigation with AET Ongoing, with key event in Q4 FY26

Bench trial concluded, post-trial briefs public. Closing arguments scheduled for October 22, 2026.

Mitigation:Harmony is confident in prevailing in both active legal proceedings to maintain exclusivity for WAKIX into March 2030. Also filed a new patent infringement lawsuit against AET Pharma US and Sandoz covering an amorphous form of pitolisant hydrochloride.

What to watch in Q3 FY26

BP-205 Multiple Ascending Dose (MAD) data

Q4 FY26

Current Data analysis ongoing

Target Disclosure of full data, including target engagement AEs (insomnia, polyuria) and their characteristics.

Why it matters

Provides further insight into BP-205's safety, tolerability, and on-target effects, crucial for assessing its best-in-class potential.

Multiple ascending dose study data analysis is ongoing, and we plan to disclose those data in Q4.

Find out whether HRMY delivers this. Inve re-checks your case every morning.

Q&A highlights

How do BP-205's short Tmax, long half-life, and high potency translate into a differentiated clinical profile for efficacy and safety, especially compared to BID/split-dose orexin-2 agonists, and its impact on broader CNS indications?

Kumar Budur explained that short Tmax (30-75 min) suggests rapid onset of efficacy, beneficial for hypersomnolence and ADHD. Long half-life (approx. 25 hours) supports once-daily dosing and sustained wakefulness. High potency allows for low doses across CNS indications. Jeffrey Dayno added that neuropsych drugs with QD dosing typically have 15-25 hour half-lives, similar to WAKIX.

“The time to maximum concentration was very short, 30 to 75 minutes. And this is a very desirable feature because it results in rapid onset of efficacy.”

asked by Pete Stavropoulos · answered by Kumar Budur

2 min read 5 chapters

Detailed narrative

WAKIX Commercial Performance

WAKIX achieved record quarterly net revenue of $261.3 million, representing a 30% year-over-year and 21% quarter-over-quarter increase, keeping the company on track to exceed $1 billion in net revenue for FY26. This strong performance was supported by an estimated 450 new patient additions, bringing the average patient count to 8,950, marking the second-highest quarterly increase in the brand's history.

Management attributed this success to WAKIX's differentiated non-scheduled treatment option, broad payer coverage (over 80% of lives), and recent strategic investments in field sales, remote sales, and reimbursement support.

BP-205 Orexin-2 Agonist Development

Harmony Biosciences reported encouraging Phase I single ascending dose (SAD) data for BP-205, its potential best-in-class orexin-2 agonist. The study demonstrated a predictable pharmacokinetic (PK) profile with rapid absorption (Tmax 30-75 minutes) and a mean half-life of approximately 25 hours, supporting once-daily dosing.

BP-205 also showed a favorable safety and tolerability profile with no serious adverse events. The company expects to disclose multiple ascending dose (MAD) data in Q4 2026 and initiate a Phase Ib study in sleep-deprived healthy volunteers in Q3 2026, with top-line data anticipated in early 2027, providing the first efficacy signals.

Next-Generation Pitolisant Programs

The company continues to advance its next-generation pitolisant programs. The pitolisant GR New Drug Application (NDA) was submitted in Q2 2026 and accepted for full review, with a target PDUFA date of April 1, 2027. Pitolisant GR is designed to reduce gastrointestinal adverse events and allow for immediate therapeutic dosing without titration.

Additionally, pitolisant HD, an optimized high-dose formulation, is progressing in two Phase III registrational trials (ONSTRIDE 1 for narcolepsy and ONSTRIDE 2 for idiopathic hypersomnia), with top-line data expected in 2027 and anticipated PDUFA in 2028, targeting differentiated labels for fatigue in narcolepsy and sleep inertia in idiopathic hypersomnia.

Broader Pipeline and IP Strategy

Harmony's broader pipeline includes the TEMPO study for Prader-Willi syndrome, which now expects top-line data in mid-2027 due to recruitment challenges, though it remains on track to secure pediatric exclusivity for WAKIX. The epilepsy franchise's EPX-100 is in two global Phase III trials (ARGUS for Dravet syndrome and LIGHTHOUSE for Lennox-Gastaut syndrome), with top-line data expected in mid-2027 and anticipated PDUFA in 2028.

The company also emphasized its multilayered IP strategy, which supports WAKIX exclusivity until March 2030, with potential extensions for new pitolisant formulations into the 2040s.

Business Development and Financial Strength

Harmony Biosciences ended the second quarter with a strong financial position, holding approximately $962.5 million in cash, cash equivalents, and investments. This capital provides significant capacity for strategic business development, with the company prioritizing assets in Phase III, in registration, or already on the market, with revenue potential in the 2028-2032 timeframe.

The focus areas include Sleep/Wake, epilepsy, rare orphan CNS, and broader CNS indications, with a strategy to engage in multiple transactions rather than a single large acquisition.

Summary of the company's earnings call; see how call summaries are prepared. Not investment advice.