Lorcaserin Hydrochloride

WAKIX® (pitolisant) Franchise Delivers Net Revenue of $239M in Q3 2025 (+29% YoY Growth) Record Increase in Average Number of Patients of Approximately 500 to Achieve 8,100 Average Patients in Q3 2025 Strong Cash Generation of $106M with $778M On Balance Sheet at end of Q3 2025 Pitolisant HD IND submitted; On Track to Initiate Phase 3 Trials in Narcolepsy and Idiopathic Hypersomnia in Q4 2025 Potential Best-In-Class Orexin 2 Agonist (BP1.15205) On Track to Dose First Subject in Q4 2025; Phase 1 Clinical Data in 2026 Late-Stage Catalyst-Rich Pipeline Advances with up to Five Phase 3 Programs by Year End Conference Call and Webcast Today at 8:30 a.m. ET PLYMOUTH MEETING, Pa. --(BUSINESS WIRE)--Nov. 4, 2025-- Harmony Biosciences Holdings, Inc. (Nasdaq: HRMY) today announced earnings of $239.5M for Q3 2025, representing 29% year-over-year revenue growth for WAKIX®. These results were driven by the highest ever increase in average number of patients of approximately 500 for the quarter, accelerating the trajectory toward blockbuster status for WAKIX in narcolepsy. The company continues to build on four consecutive years of revenue growth and profitability. With over $778 million in cash and investments at quarter end, Harmony has further strengthened its financial position, solidifying its unique profile as a profitable, self-funding biotech company with a robust, late-stage pipeline and strong long-term growth potential. “Our exceptional performance this quarter highlights the continued strength of WAKIX and significant market opportunity that remains ahead. I am incredibly proud of our team’s focus and executional excellence, as we delivered very strong results today, which positions Harmony for future growth,” said Jeffrey M. Dayno , M.D., President and CEO of Harmony Biosciences . “I continue to have firm conviction in our late-stage pipeline to deliver multiple catalysts over the next several years and, given our strong cash position, we intend to strategically pursue value-enhancing assets to add to our pipeline and build a broader product portfolio of innovative treatments that can help even more patients living with unmet medical needs.” Franchise Highlights Sleep/Wake Franchise WAKIX in Narcolepsy Net Revenue was $239.5 million for Q3 2025 Recently raised 2025 Net Revenue guidance from $820-$860 million to $845-$865 million Record increase in average number of patients of approximately 500 to achieve approximately 8,100 average patients in Q3 2025 Pitolisant HD (high dose) IND submitted to the FDA Phase 3 registrational trials in both narcolepsy and IH to initiate in Q4 2025 with target PDUFA dates in 2028 Higher dose and optimized pharmacokinetic profile designed for greater efficacy without compromising safety and tolerability profile Phase 3 registrational trial in narcolepsy designed for greater efficacy in excessive daytime sleepiness and cataplexy; includes endpoint on narcolepsy-related fatigue in pursuit of a differentiated label Phase 3 registrational trial in IH to include endpoint on sleep inertia in pursuit of a differentiated label Utility patents filed for pitolisant HD with potential exclusivity to 2044 Pitolisant GR (gastro-resistant) Designed to minimize the potential for treatment-related GI side effects as patients with narcolepsy commonly experience GI symptoms related to their underlying disease (up to 90%) Topline data readout from pivotal bioequivalence study on track for Q4 2025 Provides patients with the ability to start at therapeutic dose range without the need for titration Topline data from dosing optimization study showed 100% (46/46) of patients were able to initiate pitolisant GR at the therapeutic dose of 17.8mg Utility patents filed for pitolisant GR with potential exclusivity to 2044 Topline data from dosing optimization study showed 100% (46/46) of patients were able to initiate pitolisant GR at the therapeutic dose of 17.8mg Orexin-2 receptor agonist (BP1.15205) First-in-human study to commence in Q4 2025 with clinical data anticipated in 2026 Comprehensive and compelling preclinical safety and efficacy data presented at SLEEP and World Sleep Congress Potential to be best-in-class orexin-2 receptor agonist based on a novel chemical scaffold, preclinical potency, selectivity, safety and efficacy data, as well as its potential for once-a-day dosing Rare Epilepsy Franchise EPX-100 (clemizole hydrochloride) One of the most advanced development programs in the 5HT2 (serotonin) agonist class Enrollment ongoing for Phase 3 registrational trial in Dravet syndrome (ARGUS Study) with topline data anticipated in 2026 Enrollment ongoing for Phase 3 registrational trial in patients with Lennox-Gastaut syndrome (LIGHTHOUSE Study) with topline data anticipated in 2026 Presenting data from the ARGUS open label extension study at the American Epilepsy Society Meeting in December 2025 EPX-200 (lorcaserin hydrochloride) Proven mechanism of action in developmental and epileptic encephalopathies (DEEs) confirmed via non-clinical and clinical data Currently in the IND-enabling stage Neurobehavioral Franchise ZYN002 The ZYN002 phase 3 RECONNECT study in Fragile X syndrome did not meet the primary endpoint of improvement in social avoidance primarily due to a higher-than-expected placebo response rate; a review of the full data set is ongoing The ZYN002 development program in 22q11.2 deletion syndrome (22q) has been paused pending the full review of the RECONNECT data Third Quarter 2025 Financial Results Harmony Biosciences reported net product revenue of $239.5 million for the quarter ended September 30, 2025 , compared to $186 million for the same period in 2024, representing 29% year-over-year growth. This performance reflects both continued demand for WAKIX within the large narcolepsy market opportunity (approximately 80,000 diagnosed patients in the U.S. ) and the product's broad clinical utility. Our continued success has been driven by strong execution across the organization from sales effectiveness to marketing and promotion and supported by broad payer coverage and how we support patients over time. On a GAAP basis, net income for the quarter was $50.9 million , or $0.87 per diluted share, compared to $46.1 million , or $0.79 per diluted share, in Q3 2024. Non-GAAP adjusted net income, which we believe better reflects our core business performance, was $63.5 million ( $1.08 per diluted share) for the third quarter of 2025 versus $57.3 million ( $0.99 per diluted share) for the comparable 2024 period. Reconciliations of applicable GAAP financial measures to Non-GAAP financial measures are included at the end of this press release. Harmony’s operating expenses include the following: Research and Development expenses were $55.0 million in the third quarter of 2025, as compared to $25.4 million for the same quarter in 2024, representing a 117% increase; primarily driven by a $15.0 million IPR&D charge related to a clinical milestone achieved for ZYN002; Sales and Marketing expenses were $29.5 million in the third quarter of 2025, as compared to $27.6 million for the same quarter in 2024, representing a 7% increase; General and Administrative expenses were $29.8 million in the third quarter of 2025, as compared to $28.6 million for the same quarter in 2024, representing a 4% increase; and Total Operating Expenses were $114.3 million in the third quarter of 2025, as compared to $81.6 million for the same quarter in 2024, representing a 40% increase. As of September 30, 2025 , Harmony had cash, cash equivalents and investments of $778.4 million , compared to $576.1 million as of December 31, 2024 . 2025 Net Product Revenue Guidance Recently raised full year 2025 net product revenue range from $820-$860 million to $845-$865 million . Conference Call Today at 8:30 a.m. ET We are hosting our third quarter 2025 financial results conference call and webcast today, beginning at 8:30 a.m. Eastern time . The live and replay webcast of the call will be available on the investor relations page of our website https://ir.harmonybiosciences.com/. To participate in the live call by phone, dial 800-274-8461 (domestic) or 203-518-9814 (international), and reference passcode HRMYQ325. Non-GAAP Financial Measures In addition to our GAAP results, we present certain Non-GAAP measures including Non-GAAP adjusted net income and Non-GAAP adjusted net income per share, which we believe provides important supplemental information to management and investors regarding our performance. These measurements are not a substitute for GAAP measurements, and the manner in which we calculate Non-GAAP adjusted net income and Non-GAAP adjusted net income per share may not be identical to the manner in which other companies calculate adjusted net income and adjusted net income per share. We use these Non-GAAP measurements as an aid in monitoring our financial performance from quarter-to-quarter and year-to-year and benchmarking against comparable companies. Non-GAAP financial measures should not be considered in isolation or as a substitute for comparable GAAP measures; should be read in conjunction with our consolidated financial statements prepared in accordance with GAAP; have no standardized meaning prescribed by GAAP; and are not prepared under any comprehensive set of accounting rules or principles. In addition, from time to time in the future there may be other items that we may exclude for purposes of our Non-GAAP financial measures; and we may in the future cease to exclude items that we have historically excluded for purposes of our Non-GAAP financial measures. About WAKIX® (pitolisant) Tablets WAKIX, 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 Usage WAKIX 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 Contraindications WAKIX 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 Precautions WAKIX 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 Reactions In the placebo-controlled clinical trials conducted in 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 Interactions Concomitant 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 Populations There 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 required 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 <60 mL/minute/1.73 m2. Dosage reduction is recommended in patients known to be poor CYP2D6 metabolizers; these patients have higher concentrations of WAKIX than normal CYP2D6 metabolizers. Please see the Full Prescribing Information for WAKIX for more information. To report suspected adverse reactions, contact Harmony Biosciences at 1-800-833-7460 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. About Narcolepsy Narcolepsy is a rare, chronic, debilitating neurological disease of sleep-wake state instability that impacts approximately 170,000 Americans and is primarily characterized by excessive daytime sleepiness (EDS) and cataplexy – its two cardinal symptoms – along with other manifestations of REM sleep dysregulation (hallucinations and sleep paralysis), which intrude into wakefulness. EDS is the inability to stay awake and alert during the day and is the symptom that is present in all people living with narcolepsy. In most patients, narcolepsy is caused by the loss of hypocretin/orexin, a neuropeptide in the brain that supports sleep-wake state stability. This disease affects men and women equally, with typical symptom onset in adolescence or young adulthood; however, it can take up to a decade to be properly diagnosed. About Idiopathic Hypersomnia Idiopathic Hypersomnia (IH) is a rare and chronic neurological disease that is characterized by excessive daytime sleepiness (EDS) despite sufficient or even long sleep time. EDS in IH cannot be alleviated by naps, longer sleep or more efficient sleep. People living with IH experience significant EDS along with the symptoms of sleep inertia (prolonged difficulty waking up from sleep) and 'brain fog' (impaired cognition, attention, and alertness). The cause of IH is unknown, but it is likely due to alterations in areas of the brain that stabilize states of sleep and wakefulness. IH is one of the central disorders of hypersomnolence and, like narcolepsy, is a debilitating sleep disorder that can result in significant disruption in daily functioning. About ZYN002 ZYN002 is the first-and-only pharmaceutically manufactured synthetic cannabidiol devoid of THC and formulated as a patent-protected permeation-enhanced gel for transdermal delivery through the skin and into the circulatory system. The product is manufactured through a synthetic process in a cGMP facility and is not extracted from the cannabis plant. ZYN002 does not contain THC, the compound that causes the euphoric effect of cannabis, and has the potential to be a nonscheduled product if approved. Cannabidiol, the active ingredient in ZYN002, has been granted orphan drug designation by the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of FXS and for the treatment of 22q. Additionally, ZYN002 has received FDA Fast Track designation for the treatment of behavioral symptoms in patients with FXS. About Fragile X Syndrome Fragile X syndrome (FXS) is a rare genetic disorder that is the leading known cause of both inherited intellectual disability and autism spectrum disorder. The disorder negatively affects synaptic function, plasticity and neuronal connections, and results in a spectrum of intellectual disabilities and behavioral symptoms, such as social avoidance and irritability. While the exact prevalence is unknown, upwards of 80,000 patients in the U.S. and 121,000 patients in the European Union and the UK are believed to have FXS, based on FXS prevalence estimates of approximately 1 in 4,000 to 7,000 in males and approximately 1 in 8,000 to 11,000 in females. There is a significant unmet medical need in patients living with FXS as there are currently no FDA-approved treatments for this disorder. FXS is caused by a mutation in FMR1, a gene which modulates a number of systems, including the endocannabinoid system, and most critically, codes for a protein called FMRP. The FMR1 mutation manifests as multiple repeats of a DNA segment, known as the CGG triplet repeat, resulting in deficiency or lack of FMRP. FMRP helps regulate the production of other proteins and plays a role in the development of synapses, which are critical for relaying nerve impulses, and in regulating synaptic plasticity. In people with full mutation of the FMR1 gene, the CGG segment is repeated more than 200 times, and in most cases causes the gene to not function. Methylation of the FMR1 gene also plays a role in determining functionality of the gene. In approximately 60% of patients with FXS, who have complete methylation of the FMR1 gene, no FMRP is produced, resulting in dysregulation of the systems modulated by FMRP. About Clemizole Hydrochloride (EPX-100) EPX-100, clemizole hydrochloride, is under development for the treatment of Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS). EPX-100 acts by targeting central 5-hydroxytryptamine receptors to modulate serotonin signaling. The drug candidate is administered orally twice a day in a liquid formulation and has been developed based on a proprietary phenotype-based zebrafish drug screening platform. DS is caused by a loss of function mutation in the SCN1A gene, and scn1 mutant zebrafish replicate the genetic etiology and phenotype observed in the majority of DS patients. The scn1Lab mutant zebrafish model that expresses voltage gated sodium channels has been used for high-throughput screening of compounds that modulate Nav1.1 in the central nervous system. About Dravet Syndrome Dravet syndrome (DS) is a severe and progressive epileptic encephalopathy that begins in infancy and causes significant impact on patient functioning. DS begins in the first year of life and is characterized by high seizure frequency and severity, intellectual disability, and a risk of sudden unexpected death in epilepsy. Approximately 85% of Dravet syndrome cases are caused by de novo loss-of-function (LOF) mutations in a voltage-gated sodium channel gene, SCN1A1. DS has an estimated incidence rate of 1:15,700. About Lennox-Gastaut Syndrome Lennox-Gastaut syndrome (LGS) is a rare and drug-resistant epileptic encephalopathy characterized by onset in children between 3-5 years of age. The underlying cause of LGS is unknown and can be related to a wide range of factors including genetic differences and structural differences in the brain. As a result, patients experience multiple seizure types, including atonic seizures, and developmental, cognitive, and behavioral issues. LGS affects approximately 48,000 patients in the U.S. About Harmony Biosciences Harmony Biosciences is a pharmaceutical company dedicated to developing and commercializing innovative therapies for patients with rare neurological diseases who have unmet medical needs. Driven by novel science, visionary thinking, and a commitment to those who feel overlooked, Harmony Biosciences is nurturing a future full of therapeutic possibilities that may enable patients with rare neurological diseases to truly thrive. Established by Paragon Biosciences, LLC , in 2017 and headquartered in Plymouth Meeting, Pa. , we believe that when empathy and innovation meet, a better future can begin; a vision evident in the therapeutic innovations we advance, the culture we cultivate, and the community programs we foster. For more information, please visit www.harmonybiosciences.com. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including statements regarding our full year 2025 net product revenue, expectations for the growth and value of WAKIX, plans to submit an sNDA for pitolisant in idiopathic hypersomnia; our future results of operations and financial position, business strategy, products, prospective products, product approvals, the plans and objectives of management for future operations and future results of anticipated products. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: our commercialization efforts and strategy for WAKIX; the rate and degree of market acceptance and clinical utility of pitolisant in additional indications, if approved, and any other product candidates we may develop or acquire, if approved, including ZYN002 and EPX-100; our research and development plans, including our plans to explore the therapeutic potential of pitolisant in additional indications; our ongoing and planned clinical trials; our ability to expand the scope of our license agreements with Bioprojet Société Civile de Recherche (“Bioprojet”); the availability of favorable insurance coverage and reimbursement for WAKIX; the timing of, and our ability to obtain, regulatory approvals for pitolisant for other indications as well as any other product candidates; our estimates regarding expenses, future revenue, capital requirements and additional financing needs; our ability to identify, acquire and integrate additional products or product candidates with significant commercial potential that are consistent with our commercial objectives; our commercialization, marketing and manufacturing capabilities and strategy; significant competition in our industry; our intellectual property position; loss or retirement of key members of management; failure to successfully execute our growth strategy, including any delays in our planned future growth; our failure to maintain effective internal controls; the impact of government laws and regulations; volatility and fluctuations in the price of our common stock; the significant costs and required management time as a result of operating as a public company; the fact that the price of Harmony's common stock may be volatile and fluctuate substantially; statements related to our intended share repurchases and repurchase timeframe; and macroeconomic effects and changes in market conditions, including the impact of tariffs, inflation and the risk of recession. These and other important factors discussed under the caption "Risk Factors" in our Annual Report on Form 10-K filed with the Securities and Exchange Commission (the " SEC ") on February 25, 2025 , and our other filings with the SEC could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management's estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change. HARMONY BIOSCIENCES HOLDINGS, INC. AND SUBSIDIARY CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE INCOME (In thousands, except share and per share data) Three Months Ended September 30 , Nine Months Ended September 30 , 2025 2024 2025 2024 Net product revenue $ 239,455 $ 186,038 $ 624,677 $ 513,467 Cost of product sold 59,650 42,778 129,797 102,406 Gross profit 179,805 143,260 494,880 411,061 Operating expenses: Research and development 54,962 25,387 139,661 111,159 Sales and marketing 29,549 27,576 90,333 83,316 General and administrative 29,807 28,587 94,974 81,487 Total operating expenses 114,318 81,550 324,968 275,962 Operating income 65,487 61,710 169,912 135,099 Other expense, net (106) (124) (575) (228) Interest expense (3,621) (4,348) (11,103) (13,287) Interest income 5,730 4,932 16,070 14,065 Income before income taxes 67,490 62,170 174,304 135,649 Income tax expense (16,625) (16,077) (38,103) (39,631) Net income $ 50,865 $ 46,093 $ 136,201 $ 96,018 Unrealized income on investments 118 733 291 497 Comprehensive income $ 50,983 $ 46,826 $ 136,492 $ 96,515 EARNINGS PER SHARE: Basic $ 0.88 $ 0.81 $ 2.36 $ 1.69 Diluted $ 0.87 $ 0.79 $ 2.32 $ 1.66 Weighted average number of shares of common stock - basic 57,550,902 56,870,234 57,655,272 56,815,167 Weighted average number of shares of common stock - diluted 58,717,910 58,103,963 58,738,361 57,754,016 HARMONY BIOSCIENCES HOLDINGS, INC. AND SUBSIDIARIES CONSOLIDATED BALANCE SHEETS (In thousands, except share and per share data) September 30 , December 31 , 2025 2024 ASSETS CURRENT ASSETS: Cash and cash equivalents $ 646,999 $ 453,001 Investments, short-term 25,582 14,185 Trade receivables, net 100,651 83,033 Inventory, net 6,882 7,198 Prepaid expenses 23,308 13,714 Other current assets 35,378 8,121 Total current assets 838,800 579,252 NONCURRENT ASSETS: Property and equipment, net 1,440 1,257 Investments, long-term 105,831 108,874 Intangible assets, net 95,380 113,263 Deferred tax asset 157,075 190,398 Other noncurrent assets 9,692 6,156 Total noncurrent assets 369,418 419,948 TOTAL ASSETS $ 1,208,218 $ 999,200 LIABILITIES AND STOCKHOLDERS’ EQUITY CURRENT LIABILITIES: Trade payables $ 26,341 $ 13,744 Accrued compensation 14,935 18,776 Accrued expenses 161,302 120,640 Current portion of long-term debt 20,000 16,250 Other current liabilities 825 5,672 Total current liabilities 223,403 175,082 NONCURRENT LIABILITIES: Long-term debt, net 148,506 163,016 Other noncurrent liabilities 1,186 1,947 Total noncurrent liabilities 149,692 164,963 TOTAL LIABILITIES 373,095 340,045 COMMITMENTS AND CONTINGENCIES (Note 13) STOCKHOLDERS’ EQUITY: Common stock—$0.00001 par value; 500,000,000 shares authorized at September 30, 2025 and December 31, 2024 , respectively; 57,596,358 and 57,144,887 shares issued and outstanding at September 30, 2025 and December 31, 2024 , respectively 1 1 Additional paid in capital 696,348 656,872 Accumulated other comprehensive income 357 66 Retained earnings 138,417 2,216 TOTAL STOCKHOLDERS’ EQUITY 835,123 659,155 TOTAL LIABILITIES AND STOCKHOLDERS’ EQUITY $ 1,208,218 $ 999,200 HARMONY BIOSCIENCES HOLDINGS, INC. AND SUBSIDIARIES RECONCILIATION OF GAAP TO NON-GAAP FINANCIAL RESULTS (In thousands except share and per share data) Three Months Ended Nine Months Ended September 30 , September 30 , September 30 , September 30 , 2025 2024 2025 2024 GAAP net income (1) $ 50,865 $ 46,093 $ 136,201 $ 96,018 Non-GAAP Adjustments: Non-cash interest expense (2) 161 175 490 531 Depreciation 7 7 20 261 Amortization (3) 5,961 5,961 17,883 17,883 Stock-based compensation expense 10,824 11,448 34,668 32,845 Income tax effect related to non-GAAP adjustments (4) (4,338) (6,412) (11,599) (15,044) Non-GAAP adjusted net income (1) $ 63,480 $ 57,272 $ 177,663 $ 132,494 GAAP reported net income per diluted share $ 0.87 $ 0.79 $ 2.32 $ 1.66 Non-GAAP adjusted net income per diluted share $ 1.08 $ 0.99 $ 3.02 $ 2.29 Weighted average number of shares of common stock used in non-GAAP diluted per share 58,717,910 58,103,963 58,738,361 57,754,016 (1) Includes a $15,000 IPR&D charge related to a clinical milestone achieved for ZYN002 during the three and nine months ended September 30, 2025 . Includes a $15,000 IPR&D charge related to an upfront fee incurred upon closing the CiRC research collaboration agreement for the nine months ended September 30, 2025 . Includes a $1,000 IPR&D charge related to a preclinical milestone achieved for HBS-102 during the three and nine months ended September 30, 2024 . Includes a $25,500 charge related to an upfront license fee incurred upon closing the 2024 Bioprojet Sublicense Agreement and a $17,095 IPR&D charge related to the acquisition of Epygenix for the nine months ended September 30, 2024 . (2) Includes amortization of deferred finance charges. (3) Includes amortization of intangible asset related to WAKIX. (4) Calculated using the reported effective tax rate for the periods presented less impact of discrete items. View source version on businesswire.com: https://www.businesswire.com/news/home/20251104727906/en/ Harmony Biosciences Investor Contact: Matthew Beck 917-415-1750 matthew.beck@astrpartners.com Harmony Biosciences Media Contact: Cate McCanless 202-641-6086 cmccanless@harmonybiosciences.com Source: Harmony Biosciences Holdings, Inc.

“咳咳咳……”——无论是季节交替时的感冒，还是恼人的慢性咽炎，咳嗽都是我们身体最常见的“警报”之一。它既是一种保护性反射，帮助我们清除呼吸道异物，但持续、剧烈的干咳又会严重影响生活质量，甚至导致并发症。此时，镇咳药（Antitussives）便应运而生。 一、可待因（Codeine）：昔日的“镇咳之王” 1. 药物的诞生与传奇 l诞生时间： 1832年 l人物与故事： 19世纪的欧洲，化学家们正痴迷于从天然植物中分离活性成分。法国化学家 皮埃尔-让·罗比奎（Pierre-Jean Robiquet） 在研究鸦片（Opium）时，继德国化学家F. W. A. Sertürner于1804年分离出吗啡之后，于1832年成功分离出了另一种生物碱。他根据希腊语中代表“罂粟头”的“kōdeia”一词，将其命名为“Codeine”（可待因）。 l趣味讲解： 可待因和吗啡是“亲兄弟”，都来自罂粟。但相比于哥哥吗啡的“桀骜不驯”（强效镇痛、易成瘾），弟弟可待因性格要“温和”得多，其镇痛、镇静和镇咳作用都较弱，因此在临床上更多地被用作镇咳剂。 2. 体内“旅行”记（体内过程） l吸收与分布： 口服后在胃肠道吸收良好，能穿过血脑屏障，进入大脑的中枢神经系统发挥作用。 l代谢（特别之处）： 这是可待因最特别、也是最关键的环节。可待因本身镇咳作用较弱，它其实是一个“前体药物”。进入人体后，约有5%-10%的可待因会在肝脏中，通过一种名为CYP2D6的代谢酶，转化为我们熟知的吗啡。真正发挥强大镇咳和镇痛作用的，主要是这个转化后的吗啡。 l特别提醒： 人群中CYP2D6酶的活性存在巨大的基因差异。 l“快代谢者”： 体内CYP2D6酶活性超强，会迅速将可待因大量转化为吗啡，导致血液中吗啡浓度骤升，极易引发呼吸抑制甚至死亡等严重中毒反应。 l“慢代谢者”： 体内CYP2D6酶活性缺失或很弱，无法有效将可待因转化为吗啡，导致服药后几乎感觉不到镇咳效果。 l因此，儿童（尤其是12岁以下）、哺乳期妇女以及CYP2D6超快代谢者被禁用可待因。 3. 如何“止咳”？——药理作用与适应症 l药理作用： 可待因属于中枢性阿片类镇咳药。它的作用靶点是大脑延髓的咳嗽中枢。通过直接抑制这个“咳嗽司令部”的兴奋性，提高咳嗽阈值，从而强力地镇压咳嗽反射。 l适应症： 主要用于治疗各种原因引起的剧烈、无痰干咳以及其他镇咳药效果不佳的顽固性咳嗽。由于其镇痛作用，也常用于缓解伴有疼痛的咳嗽。 4. 是药三分毒——不良反应与注意事项 l主要不良反应： l常见： 嗜睡、头晕、恶心、呕吐、便秘（阿片类药物的典型副作用）。 l严重： 呼吸抑制（尤其是大剂量或用于易感人群时）、成瘾性（长期或大量使用可产生身体和心理依赖）。 l注意事项： l禁用于12岁以下儿童及哺乳期妇女。 l痰多的患者慎用，因其抑制咳嗽反射，可能导致痰液排出不畅，加重感染。 l驾驶、操作精密仪器或高空作业者慎用。 l属于处方药，且在多数国家被列为麻醉药品或精神药品进行严格管制。 二、右美沙芬（Dextromethorphan）：现代的“安全卫士” 为了寻找一种既能有效镇咳又没有可待因成瘾性和呼吸抑制风险的药物，科学家们开启了新的探索，右美沙芬便是这一努力的杰出成果。 1. 药物的诞生与传奇 l诞生时间： 1954年获得专利，1958年在美国被批准作为非处方药（OTC）上市。 l人物与故事： 右美沙芬的研发背景是美国海军和CIA资助的一项旨在寻找可待因无成瘾性替代品的研究。它的化学结构与吗啡类似，但空间结构不同（是吗啡类似物左啡诺（Levorphanol）的右旋异构体）。 l趣味讲解： 我们可以把可待因和右美沙芬想象成一对“镜像人”。它们化学结构很像，但就像左手和右手一样，空间构象不同。可待因（左旋为主）能与阿片受体结合，产生镇痛和成瘾性；而右美沙芬（右旋）几乎不与阿片受体结合，因此完美地避开了成瘾和呼吸抑制的“大坑”，只保留了镇咳的“武功”。 2. 体内“旅行”记（体内过程） l吸收与分布： 口服吸收迅速，同样作用于中枢神经系统。 l代谢（特别之处）： 与可待因相似，右美沙芬也主要通过肝脏的CYP2D6酶代谢，转化为其活性代谢产物右啡烷（Dextrorphan）。因此，同样存在个体代谢差异，并可能与其他通过CYP2D6代谢的药物（如某些抗抑郁药）发生相互作用。大剂量使用时，代谢途径饱和，可能导致药物蓄积和不良反应增加。 3. 如何“止咳”？——药理作用与适应症 l药理作用： 属于中枢性非阿片类镇咳药。它同样作用于延髓的咳嗽中枢，但作用靶点与可待因不同，主要是通过拮抗NMDA受体和激动Sigma-1受体来发挥镇咳作用。其镇咳强度与治疗剂量的可待因相当或略强。 l适应症： 广泛用于治疗各种急、慢性咳嗽，尤其是感冒、咽炎、支气管炎等引起的干咳。它是目前全球应用最广泛的非处方（OTC）镇咳药之一。 4. 是药三分毒——不良反应与注意事项 l主要不良反应： l常见： 治疗剂量下不良反应轻微，偶见头晕、头痛、嗜睡、胃肠道不适。 l滥用风险： 远超治疗剂量使用时（滥用），会产生分离性幻觉和欣快感，有一定滥用风险 l5-羟色胺综合征： 与单胺氧化酶抑制剂（MAOIs）或选择性5-羟色胺再摄取抑制剂（SSRIs）等药物合用时，可能引发罕见但严重的5-羟色胺综合征。 l注意事项： l痰多的患者慎用。 l对该药过敏者禁用。正在服用MAOIs的患者禁用。 l虽然安全性高，但仍需按推荐剂量服用，切勿滥用。 三、喷托维林（Pentoxyverine）：双管齐下的“多面手” 喷托维林，又名枸橼酸卡贝缩通，是另一位中枢性镇咳药，但它的“武功”更为多样。 1. 药物的诞生与传奇 l诞生时间： 1956年由比利时科学家Morren合成。 l人物与故事： 它的诞生没有太多传奇色彩，是药物化学家在系统性地寻找新型镇咳化合物过程中的一个成功案例。它于1962年在中国获批生产，也曾在日本等国广泛使用。 l趣味讲解： 如果说可待因和右美沙芬是专攻“司令部”的特种兵，那喷托维林就是一位既能空降“司令部”，又能干扰“前线通讯”的多面手。 2. 体内“旅行”记（体内过程） l吸收与代谢： 口服后吸收快，约1.2小时血药浓度达峰。半衰期较短，约为2.3小时。关于其详细的代谢酶和途径，现有公开的研究数据非常有限，不如可待因和右美沙芬那样清晰。 3. 如何“止咳”？——药理作用与适应症 l药理作用： 兼具中枢和外周双重作用的镇咳药。 l中枢作用： 抑制延髓咳嗽中枢，其镇咳强度约为可待因的1/3。 l外周作用： 具有一定的阿托品样作用（抗胆碱作用） 和局部麻醉作用。抗胆碱作用可以使支气管轻度扩张，减少分泌物；局部麻醉作用可以轻微麻痹气管和支气管的牵张感受器，从外周环节削弱咳嗽反射。 l适应症： 主要用于上呼吸道感染引起的急性干咳。 4. 是药三分毒——不良反应与注意事项 l主要不良反应： 主要与其抗胆碱作用有关，如口干、嗜睡、视力模糊、便秘等。偶有恶心、腹泻。 l注意事项： l青光眼和心力衰竭患者慎用或禁用，因为其抗胆碱作用可能加重病情。 l痰多者慎用。 l驾驶或操作机器者慎用。 四、苯佐那酯（Benzonatate）：另辟蹊径的“前线尖兵” 苯佐那酯是这四种药物中作用机制最独特的一位，它完全放弃了攻击大脑“司令部”，而是选择在“前线”解决问题。 1. 药物的诞生与传奇 l诞生时间： 1958年获得美国FDA批准上市。 l人物与故事： 它的化学结构与一种局部麻醉药——丁卡因（Tetracaine）相似。科学家们巧妙地利用了这一特性，将其开发成一种口服的、专门作用于呼吸道的外周镇咳药。 l趣味讲解： 苯佐那酯是一位“前线麻醉师” 或“隐形尖兵”。当肺部和气管里的“哨兵”（牵张感受器）因为刺激想要向大脑“司令部”报告（引发咳嗽）时，苯佐那酯提前到达现场，把这些“哨兵”麻醉了，让它们暂时“失声”。这样一来，大脑收不到信号，咳嗽自然就停止了。 2. 如何“止咳”？——药理作用与适应症 l药理作用： 纯粹的外周性镇咳药。它通过选择性地麻醉肺部、支气管和胸膜的牵张感受器，阻断了咳嗽反射弧的传入神经冲动。它不作用于中枢神经系统，因此完全没有中枢抑制、嗜睡和成瘾性等问题。 l适应症： 用于急性或慢性支气管炎、支气管哮喘、肺炎、肺癌等引起的咳嗽。尤其适用于不希望出现中枢抑制副作用的患者。 3. 是药三分毒——不良反应与注意事项 l主要不良反应： 总体耐受性良好。偶见头晕、头痛、皮疹、胃肠不适。 l注意事项（极其重要！）： l必须整粒吞服，切勿咀嚼或掰开！因为苯佐那酯是软胶囊，如果提前破裂，药物会直接接触口腔和咽喉黏膜，强大的局部麻醉作用会迅速导致口咽部麻木，可能引起窒息风险！这是其最危险的不良反应。 l属于处方药。 五、四大“镇咳侠”华山论剑：全方位大比拼 对比维度 可待因 (Codeine) 右美沙芬 (Dextromethorphan) 喷托维林 (Pentoxyverine) 苯佐那酯 (Benzonatate) 人物设定 镇咳之王 (旧时代) 安全卫士 (新一代) 双料特工 (中枢+外周) 前线尖兵 (纯外周) 作用机制 中枢性 (阿片类) 中枢性 (非阿片类) 中枢性 + 外周性 外周性 作用靶点 延髓咳嗽中枢 (μ-阿片受体) 延髓咳嗽中枢 (NMDA/Sigma-1受体) 咳嗽中枢 + 支气管感受器 肺/支气管的牵张感受器 镇咳强度 强 与可待因相当 约为可待因的1/3 有效，但数据不一 起效速度 较快 (30-60分钟) 较快 (15-30分钟) 较快 较快 (15-20分钟) 成瘾性 有 无 (滥用有风险) 无 无 中枢抑制/嗜睡 明显 轻微或无 有 无 核心不良反应 呼吸抑制、便秘、成瘾 超量致幻、5-HT综合征 口干、视力模糊 (抗胆碱) 咀嚼致窒息风险 药物管理 处方药 (麻醉/精神药品) 以前是非处方药 (OTC)；2024年我国将右美沙芬、含地芬诺酯复方制剂、纳呋拉啡、氯卡色林列入第二类精神药品目录 处方药 处方药 巧记与总结： l想找最经典、强效的（且遵医嘱），选可待因，但要时刻警惕它的“坏脾气”（副作用和成瘾性）。 l想找和可待因一样有效，相对更安全，右美沙芬是选择。 l如果咳嗽同时感觉气管有点紧、有点痒，想试试“多管齐下”的，可以考虑喷托维林，但要注意它可能让你口干舌燥。 l如果非常害怕犯困，或者想从根源上（肺部感受器）解决问题，苯佐那酯是独特的选择，但务必记住“一口吞，别咬破” 的铁律。 六、止咳药的未来：新药研发与趋势 传统的镇咳药虽然经典，但也存在作用靶点不精确、有效性有限等问题。进入2025年，镇咳药的研究已进入一个新纪元： 1.精准靶向治疗： 科学家发现，一种名为P2X3受体的“信号站”在慢性咳嗽的信号传导中扮演了关键角色。针对这一靶点的新药，如已经获批或正在进行临床试验的Gefapixant，为难治性慢性咳嗽患者带来了新的希望。这类药物直接作用于外周感觉神经，精准度更高，副作用更少。 2.新机制探索： 除了P2X3，针对TRP通道（如TRPV1，辣椒素受体）、神经激肽受体等新靶点的药物也在研发中，力求从更多维度“截断”咳嗽信号。 3.安全性优先： 对现有药物（尤其是可待因）在特殊人群（如儿童）中的风险认识不断加深，推动了更严格的临床指南和更安全的替代疗法的发展。 划重点！大白话总结 好了，说了这么多专业的，最后我们用大白话来总结一下： 1.可待因：是个“老前辈”，功夫很猛，专门去大脑里叫停咳嗽。但它脾气不好，会让你犯困、便秘，甚至上瘾，小孩和喂奶的妈妈绝对不能碰。它是被严格管制的处方药。 2.右美沙芬：是个“新秀”，功夫和老前辈差不多，也去大脑里管事，但它脾气好多了，基本不上瘾，也怎么不让人犯困。它是药店里就能买到的“明星产品”，治干咳很常用。 3.喷托维林：是个“多面手”，既能去大脑里劝架，也能在气管局部搞点“小动作”（放松气管、麻醉一下），但可能会让你口干。也是处方药。 4.苯佐那酯：是个“潜行者”，根本不去大脑，直接跑到你的肺里，把那些整天想“打小报告”引发咳嗽的神经末梢给“麻醉”了。它不让你犯困，但吃的时候千万要整个吞下去，不能咬破，否则会麻痹喉咙，有噎到的危险！这也是处方药。 最终建议： 咳嗽原因复杂，选择哪种药，最好还是听医生或药师的。尤其是对于剧烈、持续不愈的咳嗽，一定要先去看医生，明确病因再用药，切勿自行滥用镇咳药，以免掩盖真实病情。 重要参考文献： 1.Dicpinigaitis, P. V., Morice, A. H., Birring, S. S., McGarvey, L., Smith, J. A., Canning, B. J., & Page, C. P. (2014). Antitussive drugs—past, present, and future. Pharmacological reviews, 66(2), 468-512. (这篇综述系统回顾了镇咳药的历史、现状和未来发展) 2.Smith, S. M., Schroeder, K., & Fahey, T. (2014). Over-the-counter (OTC) medications for acute cough in children and adults in community settings. Cochrane Database of Systematic Reviews, (11). (这是一篇关于急性咳嗽OTC药物的权威Cochrane系统评价，对右美沙芬等药物的有效性进行了评估) 3.Chung, K. F. (2017). Taming the cough: new insights into the mechanisms of action of novel antitussives. Pulmonary pharmacology & therapeutics, 47, 33-36. (该文献探讨了新型镇咳药的作用机制，代表了未来的研究方向) 提醒：本文仅为医学/药学知识科普，旨在传播健康常识，不构成任何诊疗建议或用药指导。个体病情与体质存在差异，请勿自行效仿文中内容用药或调整治疗方案，具体医疗决策请务必咨询专业医生或药师，以免延误病情或引发不良后果。