Favorable Phase 1 Data for Orexin-2 Agonist BP-205, Broader Pipeline Progress Headline Harmony's Q2 Update

Harmony Biosciences has reported positive topline findings from the single ascending dose (SAD) portion of its phase 1 clinical trial evaluating its investigational orexin-2 receptor agonist BP-205, with early data demonstrating favorable pharmacokinetic (PK) characteristics and an encouraging safety and tolerability profile in healthy volunteers. The findings, announced alongside the company's second-quarter 2026 financial results, support continued clinical development of the therapy across multiple central nervous system (CNS) indications.¹

According to the company, BP-205 achieved a time to maximum plasma concentration (T_max) ranging from approximately 30 to 75 minutes and demonstrated a mean half-life of roughly 25 hours across dose groups, findings that may support once-daily dosing. Investigators also observed dose-proportional increases in maximum plasma concentration (C_max) and area under the concentration-time curve (AUC), suggesting predictable systemic exposure across evaluated doses. Harmony reported no clinically meaningful differences in PK parameters based on age or sex.

From a safety perspective, BP-205 was generally well tolerated, with no serious or severe treatment-emergent adverse events (TEAEs) reported. The company also noted no cardiovascular, hepatic, or visual safety signals. The most commonly reported AEs included headache (approximately 10% of participants), fatigue (4%), and diarrhea (3%).

"The Phase 1 clinical PK and safety/tolerability data for BP-205 that we shared, together with preclinical data demonstrating the highest potency of any orexin-2 agonist currently in the clinic, reinforce our conviction that BP-205 has the potential to be the best-in-class orexin-2 agonist with broad clinical utility across multiple CNS indications," Jeffrey M. Dayno, MD, president and chief executive officer of Harmony Biosciences, said in a statement.¹

For context, BP-205 is an investigational selective orexin-2 receptor (OX2R) agonist discovered by Teijin Pharma and being developed through a partnership between Harmony Biosciences and Bioprojet. Orexin signaling plays a central role in regulating wakefulness, and OX2R agonists have emerged as a promising therapeutic strategy for sleep-wake disorders and other neurologic conditions characterized by impaired arousal. Harmony noted that BP-205 has demonstrated high receptor selectivity and potency in preclinical studies, characteristics the company believes may differentiate the therapy from other agents currently in clinical development.

Harmony said multiple ascending dose (MAD) data from the ongoing phase 1 study are expected during the fourth quarter of 2026. The company also recently opened its investigational new drug (IND) application in the United States and plans to initiate a phase 1b study evaluating BP-205 in sleep-deprived healthy volunteers during the third quarter of this year, with topline results anticipated in early 2027.

Additional Clinical Development Planned

Building on those findings, Harmony expects to begin phase 2 clinical trials in mid-2027 exploring BP-205 across multiple CNS indications, although the company has not yet publicly identified the initial target populations. Bruce C. Corser, MD, medical director of the Sleep Management Institute, said the emerging PK profile may provide clinical advantages if confirmed in later-stage studies.

"The potential for rapid onset of action and once-daily dosing, along with a favorable safety/tolerability profile, exceptional potency and high selectivity, suggests that BP-205 may have potential clinical utility in indications beyond orexin deficiency," Corser said in a statement.

Broader Sleep Franchise Continues to Advance

Beyond BP-205, Harmony highlighted continued progress across its sleep medicine portfolio. In July 2026, the FDA accepted the new drug application (NDA) for pitolisant gastro-resistant (GR) tablets, with a Prescription Drug User Fee Act (PDUFA) target action date of April 1, 2027. The investigational formulation is designed with an enteric coating intended to reduce gastrointestinal adverse effects and allow patients with narcolepsy to begin treatment at a therapeutic dose without dose titration.

Development also continues for pitolisant HD, an enhanced formulation currently being evaluated in the phase 3 ONSTRIDE 1 trial in narcolepsy and the ONSTRIDE 2 trial in idiopathic hypersomnia. Harmony expects topline data from both studies in 2027, with a potential regulatory submission anticipated the following year.

Elsewhere in its pipeline, the company said enrollment continues in the phase 3 LIGHTHOUSE and ARGUS trials evaluating EPX-100 (clemizole hydrochloride) for Lennox-Gastaut syndrome and Dravet syndrome, respectively. Topline data from both studies remain expected during the first half of 2027. Harmony also reaffirmed that the phase 3 TEMPO study of WAKIX (pitolisant) in Prader-Willi syndrome remains on track for topline results in mid-2027.¹

REFERENCES
1. Harmony Biosciences Announces Record Q2 2026 Revenue and Shares Initial Clinical Data for Its Orexin-2 Agonist BP-205 Reinforcing Potential Best-in-Class Profile. Harmony Biosciences. News Release. August 3, 2026. Accessed: August 4, 2026. https://ir.harmonybiosciences.com/news-releases/news-release-details/harmony-biosciences-announces-record-q2-2026-revenue-and-shares