HARMONY BIOSCIENCES HIGHLIGHTS NEW DATA, ROBUST LATE-STAGE PIPELINE WITH NEAR-TERM VALUE CREATION OPPORTUNITIES AND ITS BOLD NEW VISION AT INVESTOR DAY

BP1.15205 Data Indicates Potential Best-In-Class Orexin-2 Agonist Based on Highest Potency

New Data Shows Clinically Meaningful Sustained Efficacy of Pitolisant in Patients with Idiopathic Hypersomnia in Long-Term Extension Study; On Track to Submit sNDA in Q4 2024

Preliminary Data Establish Pitolisant Safety Up To 5x Current Highest Labeled Dose of WAKIX®, Establishing Safety Margins for Pitolisant-HD Development Program; Target PDUFA 2028

EPX-100 Data Demonstrates Favorable Preliminary Safety and Tolerability Compared to Select Approved Drugs for Rare Epilepsies

PLYMOUTH MEETING, Pa., Oct. 1, 2024 /PRNewswire/ -- Harmony Biosciences Holdings, Inc. (Nasdaq: HRMY), will be providing a comprehensive pipeline update at its Investor Day event today, showcasing new data from its orexin-2 receptor agonist, next-generation pitolisant programs, and long-term extension data from its pitolisant program in idiopathic hypersomnia. The company will also provide program updates from its strategic acquisitions in Fragile X syndrome (FXS) and rare epilepsies, which have strengthened its late-stage development pipeline. 

"Harmony Biosciences has transformed into an innovative, catalyst-rich, self-funding biotech company focused on patient impact and long-term value creation," said Jeffrey M. Dayno, M.D., President and Chief Executive Officer of Harmony Biosciences. "We strategically expanded and advanced our pipeline, with near-term catalysts positioned to deliver one or more new product or indication launches each year over the next five years, positioning Harmony to generate over $3 billion in potential annual revenue. Our expertise in CNS and proven track record of success, combined with our unique commercial model, provide a strong foundation to efficiently scale beyond sleep/wake. I am extremely proud of what the Harmony team has accomplished over the past year, and we are just getting started in our growth story."

The event will feature presentations from Harmony's executive leadership team and experts in the fields of sleep disorders, Fragile X syndrome and developmental epileptic encephalopathies, highlighting Harmony's expansion and diversification of its pipeline, continued commitment to innovation, and focus on driving value for patients and shareholders.

Key Highlights:

• Orexin-2 agonist program: New data show BP1.15205 (formerly TPM-1116) is based on a novel chemical scaffold and has demonstrated greater potency compared to all publicly disclosed data on orexin-2 agonists, with the potential to be best-in-class.
• Pitolisant in Idiopathic Hypersomnia: New data show robust and sustained efficacy of pitolisant in patients with idiopathic hypersomnia in the Long-Term Extension study; mean improvement in Epworth Sleepiness Scale (ESS) was ~9 points from baseline out beyond one year, with the majority of patients achieving normal levels of wakefulness.
• Pitolisant-HD program: Preliminary data confirm safety up to five times the highest labeled dose of WAKIX, establishing the safety margins for the pitolisant-HD development program. Market research indicates healthcare professionals view HD as a superior product profile and anticipate high uptake of pitolisant-HD for all patients, including patients on WAKIX. Payers also see value in the HD profile and anticipate broad access to pitolisant-HD both pre- and post-WAKIX LOE.
• Fragile X syndrome program (ZYN-002): A prespecified ad hoc analysis from the Phase 2 CONNECT-FX in Fragile X syndrome study (published in 2022) showed that patients with complete methylation of FMR1 gene showed a 40% median improvement in socially avoidant behaviors (p=0.027) on the Aberrant Behavior Checklist-Community FXS Specific (ABC-CFXS) Social Avoidance subscale; this and other learnings from this trial have informed the design and selection of the primary endpoint for the Phase 3 RECONNECT study, which is on track for topline data in mid-2025.
• EPX-100 development program: New safety and tolerability data on EPX-100, a potent, oral, centrally acting serotonin (5HT2) agonist currently in a pivotal registrational trial (ARGUS) for Dravet syndrome (DS), shows a favorable risk/benefit profile for EPX-100 compared to select approved drugs for DS and Lennox-Gastaut syndrome (LGS); topline data in DS is expected in 2026, and a pivotal Phase 3 trial for LGS is on track to initiate later this year.

The replay webcast and presentation slides from this event will be available on Harmony Biosciences' investor relations at https://ir.harmonybiosciences.com/.

About WAKIX® (pitolisant) TabletsWAKIX, a first-in-class medication, is approved by the U.S. Food and Drug Administration for the treatment of excessive daytime sleepiness (EDS) or cataplexy in adult patients with narcolepsy and for the treatment of EDS in pediatric patients 6 years of age and older with narcolepsy. It was granted orphan drug designation for the treatment of narcolepsy in 2010, and breakthrough therapy designation for the treatment of cataplexy in 2018. WAKIX is a selective histamine 3 (H₃) receptor antagonist/inverse agonist. The mechanism of action of WAKIX is unclear; however, its efficacy could be mediated through its activity at H₃ receptors, thereby increasing the synthesis and release of histamine, a wake promoting neurotransmitter. WAKIX was designed and developed by Bioprojet (France). Harmony has an exclusive license from Bioprojet to develop, manufacture and commercialize pitolisant in the United States.

INDICATIONS AND USAGEWAKIX is indicated for the treatment of excessive daytime sleepiness (EDS) or cataplexy in adult patients with narcolepsy and for the treatment of excessive daytime sleepiness (EDS) in pediatric patients 6 years of age and older with narcolepsy.

IMPORTANT SAFETY INFORMATION

ContraindicationsWAKIX is contraindicated in patients with known hypersensitivity to pitolisant or any component of the formulation. Anaphylaxis has been reported. WAKIX is also contraindicated in patients with severe hepatic impairment.

Warnings and PrecautionsWAKIX prolongs the QT interval. Avoid use of WAKIX in patients with known QT prolongation or in combination with other drugs known to prolong the QT interval. Avoid use in patients with a history of cardiac arrhythmias, as well as other circumstances that may increase the risk of the occurrence of torsade de pointes or sudden death, including symptomatic bradycardia, hypokalemia or hypomagnesemia, and the presence of congenital prolongation of the QT interval.

The risk of QT prolongation may be greater in patients with hepatic or renal impairment due to higher concentrations of pitolisant; monitor these patients for increased QTc. Dosage modification is recommended in patients with moderate hepatic impairment and moderate or severe renal impairment. WAKIX is contraindicated in patients with severe hepatic impairment and not recommended in patients with end-stage renal disease (ESRD).

Adverse ReactionsIn the placebo-controlled clinical trials conducted in adult patients with narcolepsy with or without cataplexy, the most common adverse reactions (≥5% and at least twice placebo) for WAKIX were insomnia (6%), nausea (6%), and anxiety (5%). Other adverse reactions that occurred at ≥2% and more frequently than in patients treated with placebo included headache, upper respiratory tract infection, musculoskeletal pain, heart rate increased, hallucinations, irritability, abdominal pain, sleep disturbance, decreased appetite, cataplexy, dry mouth, and rash.

In the placebo-controlled phase of the clinical trial conducted in pediatric patients 6 years and older with narcolepsy with or without cataplexy, the most common adverse reactions (≥5% and greater than placebo) for WAKIX were headache (19%) and insomnia (7%). The overall adverse reaction profile of WAKIX in the pediatric clinical trial was similar to that seen in the adult clinical trial program.

Drug InteractionsConcomitant administration of WAKIX with strong CYP2D6 inhibitors increases pitolisant exposure by 2.2-fold. Reduce the dose of WAKIX by half.

Concomitant use of WAKIX with strong CYP3A4 inducers decreases exposure of pitolisant by 50%. Dosage adjustments may be required.

H1 receptor antagonists that cross the blood-brain barrier may reduce the effectiveness of WAKIX. Patients should avoid centrally acting H1 receptor antagonists.

WAKIX is a borderline/weak inducer of CYP3A4. WAKIX may reduce the effectiveness of sensitive CYP3A4 substrates, including hormonal contraceptives. Patients using hormonal contraception should be advised to use an alternative non-hormonal contraceptive method during treatment with WAKIX and for at least 21 days after discontinuing treatment.

Use in Specific PopulationsThere is a pregnancy exposure registry that monitors pregnancy outcomes in women who are exposed to WAKIX during pregnancy. Patients should be encouraged to enroll in the WAKIX pregnancy registry if they become pregnant. To enroll or obtain information from the registry, patients can call 1-800-833-7460.

The safety and effectiveness of WAKIX have not been established for treatment of excessive daytime sleepiness in pediatric patients less than 6 years of age with narcolepsy.

The safety and effectiveness of WAKIX have not been established for treatment of cataplexy in pediatric patients with narcolepsy.

WAKIX is extensively metabolized by the liver. WAKIX is contraindicated in patients with severe hepatic impairment. Dosage adjustment is recommended in patients with moderate hepatic impairment.

WAKIX is not recommended in patients with end-stage renal disease. Dosage adjustment of WAKIX is recommended in patients with eGFR