FMRP

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) 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 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 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 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 <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 ZYN-002 ZYN-002 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. ZYN-002 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 ZYN-002, 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, ZYN-002 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 Statement: This presentation includes forward‐looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements other than statements of historical facts contained in these materials or elsewhere, including statements regarding Harmony Biosciences Holdings, Inc.'s (the "Company") future financial position, business strategy and plans and objectives of management for future operations, should be considered forward-looking statements. Forward-looking statements use words like "believes," "plans," "expects," "intends," "will," "would," "anticipates," "estimates," "may," "could," "might," "continue," "potential," and similar words or expressions in discussions of the Company's future operations, financial performance or the Company's strategies, but the absence of these words does not mean that a statement is not forward-looking. These statements are based on current expectations or objectives that are inherently uncertain. These forward-looking statements involve significant risks and uncertainties that could cause the actual results to differ materially from the expressed or implied forwarding-looking statements, including, but not limited to the risk factors discussed under the caption "Risk Factors" in the Company's Annual Report on Form 10-K filed with the U.S. Securities and Exchange Commission (the "SEC") on February 22, 2024 and its other filings with the SEC. While the Company may elect to update such forward-looking statements at some point in the future, it disclaims any obligation to do so, even if subsequent events cause its views to change. This presentation includes information related to market opportunity as well as cost and other estimates obtained from internal analyses and external sources. The internal analyses are based upon management's understanding of market and industry conditions and have not been verified by independent sources. Similarly, the externally sourced information has been obtained from sources the Company believes to be reliable, but the accuracy and completeness of such information cannot be assured. Neither the Company, nor any of its respective officers, directors, managers, employees, agents, or representatives, (i) make any representations or warranties, express or implied, with respect to any of the information contained herein, including the accuracy or completeness of this presentation or any other written or oral information made available to any interested party or its advisor (and any liability therefore is expressly disclaimed), (ii) have any liability from the use of the information, including with respect to any forward-looking statements, or (iii) undertake to update any of the information contained herein or provide additional information as a result of new information or future events or developments. Harmony Biosciences Investor Contact: Brennan Doyle 484-539-9700 bdoyle@harmonybiosciences.com Harmony Biosciences Media Contact: Cate McCanless 202-641-6086 cmccanless@harmonybiosciences.com View original content to download multimedia:https://www.prnewswire.com/news-releases/harmony-biosciences-highlights-new-data-robust-late-stage-pipeline-with-near-term-value-creation-opportunities-and-its-bold-new-vision-at-investor-day-302263357.html SOURCE Harmony Biosciences

技术背景 01 遗传学检测技术的更新迭代不断推动着人类对遗传病的理解，但由于现有技术的局限性，无法识别部分变异或尚未构建部分变异与表型之间的联系，故仍有约半数的遗传病未得到明确诊断。近十余年来，以纳米孔测序和单分子实时测序为代表的三代测序技术，弥补了二代测序的技术盲区，在串联重复序列分析、结构变异、单倍型分析等遗传学检测的各方面展示出其优势。 三代测序技术以长读长、高准确度、无GC偏好性和单分子分辨率的特点，可全面覆盖结构变异、同源重组、重复、假基因等各类变异类型，更适合用于复杂单基因隐性遗传病的携带者筛查与诊断。 图1 三代测序对比二代测序优势示意图 三代测序，即单分子DNA测序，有望弥补NGS的不足， 拥有良好的应用前景。2008年，Helicos公司推出了第一台真正意义上的单分子测序仪，但其高售价及短读长限制了其市场推广和应用。2009 年，太平洋生物科学公司(Pacific Bioscience，PacBio)的 单 分 子 实 时 测 序(single molecular real-time sequencing，SMRT)和牛津纳米孔科技有限公司(Oxford Nanopore Technologies，ONT)的纳米孔测序技术(Nanopore sequencing)推出并相继投入商用。目前，PacBio已经过RS、RSⅡ、Sequel、SequelⅡ平台升级，在通量、成本、测序周期、数据质量等方面逐步优化 。 表1 主流三代测序技术厂商的技术差异比较 临床研究 02 ✅ 地中海贫血 全国43家三甲医院成功实施地中海贫血基因图谱(TiGA)计划，已累计对超过十万例样本进行检测，揭示了大量新发现的大片段缺失与结构变异，发表了十余篇临床研究论文。证明该技术能够一次到位，精准检出传统方法无法检测的地贫基因变异。 完成的三代地贫临床回顾性研究及多中心临床前瞻性研究成果分别于2020年5月和2021年7月发表于分子诊断领域权威国际学术期刊Journal of Molecular Diagnostics(IF=5.568)。 ✅ 先天性肾上腺皮质增生症 2022年6月，三代CAH（先天性肾上腺皮质增生症）临床回顾性研究成果，发表于检验医学领域权威国际学术期刊Clinical Chemistry(IF=12.167)，这是运用分子诊断技术探索CAH分子机制的一次创新。该研究证明三代CAH检测技术与传统MLPA+Sanger+家系组合分析方法或生化分析方法相比，筛查更全面，检测更准确。 ✅ 脊髓性肌萎缩症 2022年6月，三代SMA（脊髓性肌萎缩症）临床回顾性研究成果，发表于分子诊断领域权威国际学术期刊Journal of Molecular Diagnostics（即时IF=5.568）。研究证明，三代SMA检测技术与传统检测方法相比，具有覆盖更全面，检测更精准的特点。 ✅ 脆性X综合征 2022年9月，三代FXS（脆性X综合征）临床回顾性研究成果——“Comprehensive analysis of fragile X syndrome: full characterization of the FMR1 locus by long-read sequencing （脆性X综合征的综合分析：长读长测序全面解析FMR1基因变异）”在检验医学领域国际权威学术期刊 Clinical Chemistry (《临床化学》,IF=12.167)在线发表。这是基于三代测序平台开发复杂基因变异疾病诊断新技术的又一次重大突破。 临床应用 03 地中海贫血、CAH、SMA、FXS这四种疾病是表型较为严重的复杂单基因病，其综合发病率不容忽视，但其存在大片段结构变异、复杂重组、假基因、动态突变等特殊变异。针对这些复杂基因变异疾病，NGS仍无法有效解决，通常需要结合Sanger测序、PCR法、MLPA法等进行检测，但传统的检测方法存在一定局限性。 三代地贫 检测范围：一次性实现α、β地贫相关致病性SNV、Indel、缺失型变异、三联体、四联体及融合基因的全面覆盖，助力α、β及α三联体复合β变异等三种类型的重度地贫的精准防控。 适用人群：新生儿基因筛查；孕前或孕早期携带者筛查；地贫临床全面诊断； 三代CAH 检测范围:检测CAH涉及相关基因的SNV/InDel/CNV、拷贝数异常、假基因、基因重排等变异的检测，能够精准区分真假基因。 适用人群：新生儿基因筛查；孕前或孕早期携带者筛查；CAH临床辅助诊断； 三代SMA 检测范围：检测SMN1和SMN2基因全长的拷贝数、SMN1 基因微小变异，提示2+0携带风险。 适用人群：新生儿基因筛查；孕前或孕早期携带者筛查；SMA临床辅助诊断； 三代FXS 检测范围：检测FMR1基因CGG重复数，并可准确识别AGG插入数目与位置，有助于精准评估具有前突变女性的遗传扩增风险。 适用人群：对于具有相关家族史(不明原因的智力障碍、发育迟缓、孤独症、卵巢早衰、迟发性小脑共济失调和震颤)的孕妇；有生育意愿的妇女；对于主动要求检测的女性； 兰卫医学 提供基于三代测序技术的单基因病筛查与诊断 面对临床基因筛查与诊断的需求，兰卫医学提供基于三代测序技术的地中海贫血、CAH、SMA、FXS这四种疾病的全面检测服务，为临床筛查、诊断提供检测、遗传咨询、报告解读的一体化方案。 参考文献 [1] 许伊云,许争峰. 三代测序技术在遗传病诊断中的应用进展[J]. 中华妇产科杂志,2022,57(09):707-711. [2] Milos P. Helicos biosciences[J]. Pharmacogenomics, 2008, 9(4):477-480. [3] Eid J, Fehr A, Gray J, et al. Real-time DNA sequencing from single polymerase molecules[J]. Science, 2009, 323(5910):133-138. [4] Branton D, Deamer DW, Marziali A, et al. The potential and challenges of nanopore sequencing[J]. Nat Biotechnol, 2008, 26(10): 1146-1153. [5] Midha MK, Wu M, Chiu KP. Longread sequencing in deciphering human genetics to a greater depth[J]. Hum Genet, 2019,138(11-12): 1201-1215. [6] Luo S, Chen X, Zeng D, Tang N, Yuan D, Zhong Q, Mao A, Xu R, Yan T. The value of single-molecule real-time technology in the diagnosis of rare thalassemia variants and analysis of phenotype-genotype correlation. J Hum Genet. 2022 Apr;67(4):183-195. [7] Liu Y, Chen M, Liu J, Mao A, Teng Y, Yan H, Zhu H, Li Z, Liang D, Wu L. Comprehensive Analysis of Congenital Adrenal Hyperplasia Using Long-Read Sequencing. Clin Chem. 2022 Jul 3;68(7):927-939. [8] Li S, Han X, Xu Y, Chang C, Gao L, Li J, Lu Y, Mao A, Wang Y. Comprehensive Analysis of Spinal Muscular Atrophy: SMN1 Copy Number, Intragenic Mutation, and 2 + 0 Carrier Analysis by Third-Generation Sequencing. J Mol Diagn. 2022 Sep;24(9):1009-1020. [9] Liang Q, Liu Y, Liu Y, Duan R, Meng W, Zhan J, Xia J, Mao A, Liang D, Wu L. Comprehensive Analysis of Fragile X Syndrome: Full Characterization of the FMR1 Locus by Long-Read Sequencing. Clin Chem. 2022 Dec 6;68(12):1529-1540. 本文由 市场中心 张敏智 提供

WAKIX® (pitolisant) Net Revenue of $172.8 Million for Second Quarter 2024; ~29% Growth Year-over-Year Next Generation Pitolisant High-Dose (HD) Program Advances Based on Pilot Pharmacokinetic (PK) Data with PDUFA Date Expected in 2028 to Extend Pitolisant Franchise Beyond 2040 WAKIX Patent Upheld Again - U.S. Patent and Trademark Office (USPTO) Issues Final Denial After Two Attempts to Challenge the WAKIX Patent Received U.S. Food and Drug Administration (FDA) Approval and Launched WAKIX for the Treatment of EDS in Pediatric Patients with Narcolepsy Providing the First and Only Non-Scheduled Treatment Option On Track to Submit Supplemental New Drug Application for Pitolisant in Idiopathic Hypersomnia (IH) in Fourth Quarter 2024 Reiterates 2024 Net Product Revenue Guidance of $700 - $720 Million Company to Host Investor Day in New York City on October 1st Conference Call and Webcast to be Held Today at 8:30 a.m. ET PLYMOUTH MEETING, Pa., Aug. 06, 2024 (GLOBE NEWSWIRE) -- Harmony Biosciences Holdings, Inc. (Nasdaq: HRMY), today reported year-over-year net revenue growth of 29 percent for the quarter ended June 30, 2024. In addition, with the goal of addressing ongoing unmet medical needs in the narcolepsy market, the next generation pitolisant-HD development program is advancing and on track towards an expected PDUFA date in 2028. “We made substantial progress and continue to advance our pitolisant high-dose development program, targeting a PDUFA date in 2028, giving us the opportunity to extend the pitolisant franchise beyond 2040,” said Jeffrey M. Dayno, M.D., President and Chief Executive Officer of Harmony. “In addition, we are executing on our late-stage pipeline across three orphan/rare CNS franchises, which we expect to deliver at least one new product or indication launch every year over the next five years, with multi-billion-dollar revenue potential extending beyond 2040. We also delivered another strong quarter of revenue growth for WAKIX, confirming our confidence in WAKIX being a billion dollar plus market opportunity in narcolepsy alone, while gaining the approval and launching WAKIX in pediatric narcolepsy.” Key Franchise Highlights: Sleep/Wake WAKIX Net Revenue of $172.8 million in the second quarter of 2024, representing 29% growth over the same period in 2023.The average number of patients on WAKIX increased by approximately 250 patients sequentially to approximately 6,550 for the quarter ended June 30, 2024.WAKIX patent upheld again. We announced that the USPTO has issued a final denial of the petition for reexamination, which was filed by a short seller. This denial is non-appealable and reinforces our confidence in the strength of our patents, the validity of the patent portfolio, and our ability to rigorously enforce the intellectual property rights protecting WAKIX.Received FDA approval for WAKIX for the treatment of EDS in pediatric patients 6 years and older with narcolepsy on June 21, 2024, and executed commercial launch July 1, 2024.On track to submit supplemental new drug application (sNDA) for pitolisant in IH in the fourth quarter of 2024.Pitolisant Gastro-Resistant (GR): On track to initiate Dosing Optimization study in the fourth quarter of 2024 and Pivotal Bioequivalence study in the first quarter of 2025. PDUFA date expected in 2026. Provisional patent filed with the potential for patent protection out to 2044.Pitolisant HD: Pilot PK data showed meaningful differentiation with at least a ~ 20% increase in relative bioavailability and a decrease in the variability of the PK profile compared to an equivalent WAKIX dose of 35.6 mg, the highest labeled dose. Formulation optimization work continues, and we plan to study up to two times the current highest labeled dose of WAKIX, where we expect to demonstrate a further increase in relative bioavailability and decrease in variability in the PK profile. An optimized PK profile, along with a higher dose, GR coating and targeting unique symptoms (e.g., fatigue in narcolepsy, in addition to EDS and cataplexy) is expected to provide a differentiated product profile and label compared to WAKIX. PDUFA date expected in 2028. Provisional patent filed with the potential for patent protection out to 2044.Patient enrollment is ongoing in Phase 3 TEMPO study in patients with Prader-Willi syndrome (PWS).TPM-1116, a highly potent and selective oral orexin-2 receptor agonist that will be evaluated for the treatment of narcolepsy and other sleep-wake disorders. IND enabling studies are ongoing and we expect to file an IND in mid-2025 and initiate first-in-human studies in the second half of 2025.Completed pre-clinical POC study for HBS-102 in PWS with encouraging initial results; final study report and results to be shared later this year. Neurobehavioral On track for topline data from the Phase 3 RECONNECT registrational trial of ZYN002 in Fragile X syndrome (FXS) in mid-2025.Phase 3 preparation ongoing for ZYN002 in 22q11.2 deletion syndrome (22q). Rare Epilepsy EPX-100 is a potent, oral, centrally acting serotonin (5HT2) agonist, currently in a pivotal registrational trial (ARGUS) for Dravet syndrome (DS) with topline data expected in 2026.Phase 3 trial for Lennox-Gastaut syndrome (LGS), expected to initiate later this year.EPX-200 is a potent, oral, centrally acting and selective 5HT2C agonist, and is currently in IND-enabling stage. Second Quarter 2024 Financial Results Net product revenues for the quarter ended June 30, 2024, were $172.8 million, compared to $134.2 million for the same period in 2023. The 29% growth versus the same period in 2023 is primarily attributed to strong commercial sales of WAKIX driven by continued organic demand tapping into a large market opportunity (approximately 80,000 patients diagnosed with narcolepsy in the US) and the broad clinical utility of WAKIX across the approximately 9,000 HCPs that we call on (about 5,000 of whom do not participate in an oxybate REMS program). The average number of patients on WAKIX increased by approximately 250 sequentially to approximately 6,550 for the quarter ended June 30, 2024. GAAP net income for the quarter ended June 30, 2024, was $11.6 million, or $0.20 earnings per diluted share, compared to GAAP net income of $34.3 million, or $0.56 earnings per diluted share, for the same period in 2023. The decrease in GAAP net income was primarily driven by a $25.5 million upfront licensing fee paid as part of the 2024 Bioprojet Sublicensing Agreement for TPM-1116 and a $17.1 million IPR&D charge related to the acquisition of Epygenix. Non-GAAP adjusted net income was $60.6 million, or $1.05 earnings per diluted share, for the quarter ended June 30, 2024, compared to Non-GAAP adjusted net income of $45.9 million, or $0.76 per diluted share, for the same period in 2023. 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 $63.6 million in the second quarter of 2024, as compared to $15.0 million for the same quarter in 2023, representing a 325% increase, primarily driven by a $25.5 million upfront licensing fee as part of the 2024 Bioprojet Sublicense Agreement and a $17.1 million IPR&D charge related to the acquisition of Epygenix;Sales and Marketing expenses were $28.5 million in the second quarter of 2024, as compared to $24.5 million for the same quarter in 2023, representing a 16% increase;General and Administrative expenses were $27.2 million in the second quarter of 2024, as compared to $22.8 million for the same quarter in 2023, representing a 19% increase; andTotal Operating Expenses were $119.3 million in the second quarter of 2024, as compared to $62.3 million for the same quarter in 2023, representing a 92% increase. As of June 30, 2024, Harmony had cash, cash equivalents and investments of $434.1 million, compared to $425.6 million as of December 31, 2023. Reiterates 2024 Net Product Revenue Guidance Expect full year 2024 net product revenue of $700 million to $720 million. Share Repurchase Program The remaining amount of common stock authorized for repurchases as of June 30, 2024, was $150 million. Investor Day on October 1st The company will host an investor day in New York City on October 1st. Additional event details to follow. Conference Call Today at 8:30 a.m. ET We are hosting our second quarter 2024 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 at https://ir.harmonybiosciences.com/. To participate in the live call by phone, dial (800) 225-9448 (domestic) or +1 (203) 518-9708 (international), and reference passcode HRMYQ224. Non-GAAP Financial Measures In addition to our GAAP results, we present certain Non-GAAP metrics 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 for 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) TabletsWAKIX, a first-in-class medication, is approved by the U.S. Food and Drug Administration for the treatment of excessive daytime sleepiness or cataplexy in adult patients with narcolepsy and has been commercially available in the U.S. since Q4 2019. 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 (see full prescribing information). WAKIX is not recommended in patients with end-stage renal disease (ESRD). Adverse ReactionsIn 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. 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 (see full prescribing information). 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. Therefore, reduced effectiveness of sensitive CYP3A4 substrates may occur when used concomitantly with WAKIX. The effectiveness of hormonal contraceptives may be reduced when used with WAKIX and effectiveness may be reduced for 21 days after discontinuation of therapy. Use in Specific PopulationsWAKIX may reduce the effectiveness of 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. 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 in patients less than 18 years of age. 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 moderate or severe renal impairment. 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 NarcolepsyNarcolepsy 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 HypersomniaIdiopathic 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 Prader-Willi syndromePWS is an orphan/rare, genetic neurological disorder with many of the symptoms resulting from hypothalamic dysfunction. The hypothalamus is the part of the brain that controls both sleep-wake state stability and signals that mediate the balance between hunger and satiety, resulting in two of the main symptoms in patients with PWS; EDS and hyperphagia (an intense persistent sensation of hunger accompanied by food preoccupations, an extreme drive to consume food, food-related behavior problems, and a lack of normal satiety). Other features include low muscle tone, short stature, behavioral problems, and cognitive impairment. Approximately 15,000 to 20,000 people in the U.S. live with PWS, and over half of them experience EDS and the majority of them have behavioral disturbances. About ZYN002ZYN002 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 SyndromeFragile 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 22q11.2 Deletion Syndrome22q11.2 deletion syndrome (22q) is a disorder caused by a small missing piece of the 22nd chromosome. The deletion occurs near the middle of the chromosome at a location designated q11.2. It is considered a mid-line condition, with physical symptoms including characteristic palate abnormalities, heart defects, immune dysfunction, and esophageal/ GI issues, as well as debilitating neuropsychiatric and behavioral symptoms, including anxiety, social withdrawal, ADHD, cognitive impairment and autism spectrum disorder. It is estimated that 22q occurs in one in 4,000 live births, suggesting that there are approximately 80,000 people living with 22q in the U.S. and 129,000 in the European Union and the UK. Patients with 22q deletion syndrome are managed by multidisciplinary care providers, and there are currently no FDA approved treatments for this disorder. 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.1 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 SyndromeDravet 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 SyndromeLennox-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 BiosciencesAt Harmony Biosciences, we specialize in developing and delivering treatments for rare neurological diseases that others often overlook. We believe that where empathy and innovation meet, a better life can begin for people living with neurological diseases. Established by Paragon Biosciences, LLC, in 2017 and headquartered in Plymouth Meeting, PA, our team of experts from a wide variety of disciplines and experiences is driven by our shared conviction that innovative science translates into therapeutic possibilities for our patients, who are at the heart of everything we do. For more information, please visit www.harmonybiosciences.com. Forward-Looking StatementsThis 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 2024 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; 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 the significant costs and required management time as a result of operating as a public company. 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 22, 2024, 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 SUBSIDIARIESCONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE INCOME(In thousands, except share and per share data) Three Months Ended June 30, Six Months Ended June 30, 2024 2023 2024 2023Net product revenue $172,814 $134,216 $327,429 $253,342 Cost of product sold 32,144 25,008 59,628 45,788 Gross profit 140,670 109,208 267,801 207,554 Operating expenses: Research and development 63,583 14,969 85,772 28,258 Sales and marketing 28,507 24,528 55,740 47,100 General and administrative 27,224 22,809 52,900 44,871 Total operating expenses 119,314 62,306 194,412 120,229 Operating income 21,356 46,902 73,389 87,325 Other (expense) income, net 37 (31) (104) (29)Interest expense (4,404) (6,218) (8,939) (11,949)Interest income 4,705 3,442 9,133 6,528 Income before income taxes 21,694 44,095 73,479 81,875 Income tax expense (10,103) (9,795) (23,554) (18,090)Net income $11,591 $34,300 $49,925 $63,785 Unrealized (loss) income on investments (63) (491) (236) (371)Comprehensive income $11,528 $33,809 $49,689 $63,414 EARNINGS PER SHARE: Basic $0.20 $0.57 $0.88 $1.07 Diluted $0.20 $0.56 $0.87 $1.05 Weighted average number of shares of common stock - basic 56,802,357 59,974,123 56,786,873 59,853,808 Weighted average number of shares of common stock - diluted 57,541,696 60,743,953 57,571,570 60,997,410 HARMONY BIOSCIENCES HOLDINGS, INC. AND SUBSIDIARIESCONSOLIDATED BALANCE SHEETS (In thousands except share and per share data) June 30, December 31, 2024 2023ASSETS CURRENT ASSETS: Cash and cash equivalents $317,296 $311,660 Investments, short-term 29,614 41,800 Trade receivables, net 83,157 74,140 Inventory, net 5,643 5,363 Prepaid expenses 16,127 12,570 Other current assets 6,507 5,537 Total current assets 458,344 451,070 NONCURRENT ASSETS: Property and equipment, net 754 371 Restricted cash 270 270 Investments, long-term 87,178 72,169 Intangible assets, net 125,186 137,108 Deferred tax asset 180,186 144,162 Other noncurrent assets 6,465 6,298 Total noncurrent assets 400,039 360,378 TOTAL ASSETS $858,383 $811,448 LIABILITIES AND STOCKHOLDERS’ EQUITY CURRENT LIABILITIES: Trade payables $22,683 $17,730 Accrued compensation 9,641 23,747 Accrued expenses 91,644 99,494 Current portion of long-term debt 15,000 15,000 Other current liabilities 7,614 7,810 Total current liabilities 146,582 163,781 NONCURRENT LIABILITIES: Long-term debt, net 171,422 178,566 Other noncurrent liabilities 1,796 2,109 Total noncurrent liabilities 173,218 180,675 TOTAL LIABILITIES 319,800 344,456 COMMITMENTS AND CONTINGENCIES (Note 13) STOCKHOLDERS’ EQUITY: Common stock—$0.00001 par value; 500,000,000 shares authorized at June 30, 2024 and December 31, 2023, respectively; 56,833,771 and 56,769,081 shares issued and outstanding at June 30, 2024 and December 31, 2023, respectively 1 1 Additional paid in capital 632,168 610,266 Accumulated other comprehensive (loss) income (234) 2 Accumulated deficit (93,352) (143,277)TOTAL STOCKHOLDERS’ EQUITY 538,583 466,992 TOTAL LIABILITIES AND STOCKHOLDERS’ EQUITY $858,383 $811,448 HARMONY BIOSCIENCES HOLDINGS, INC. AND SUBSIDIARIESRECONCILIATION OF GAAP TO NON-GAAP FINANCIAL RESULTS(In thousands except share and per share data) Three Months Ended Six Months Ended June 30, June 30, June 30, June 30, 2024 2023 2024 2023GAAP net income $11,591 $34,300 $49,925 $63,785 Non-GAAP Adjustments: Non-cash interest expense (1) 176 424 356 840 Depreciation 91 103 254 206 Amortization (2) 5,961 5,961 11,922 11,922 Stock-based compensation expense 10,963 7,793 21,397 14,354 Licensing fee and milestone payments (3) 25,500 - 25,500 750 Transaction related costs (4) 17,095 - 17,095 - Income tax effect related to non-GAAP adjustments (5) (10,769) (2,712) (15,119) (5,252)Non-GAAP adjusted net income $60,608 $45,869 $111,330 $86,605 GAAP reported net income per diluted share $ 0.20 $ 0.56 $0.87 $1.05 Non-GAAP adjusted net income per diluted share $1.05 $0.76 $1.93 $1.42 Weighted average number of shares of common stock used in non-GAAP diluted per share 57,541,696 60,743,953 57,571,570 60,997,410 (1) Includes amortization of deferred finance charges.(2) Includes amortization of intangible asset related to WAKIX.(3) Amount represents upfront licensing fee incurred upon closing the 2024 Bioprojet Sublicense Agreement and milestone payment related to HBS102 in March 2023.(4) Includes IPR&D charge related to the acquisition of Epygenix. (5) Calculated using the reported effective tax rate for the periods presented less impact of discrete items. Harmony Biosciences Investor Contact:Brennan Doyle484-539-9700bdoyle@harmonybiosciences.com Harmony Biosciences Media Contact:Cate McCanless202-641-6086cmccanless@harmonybiosciences.com