22q11 Deletion Syndrome

A single genetic test could potentially replace the current two-step approach to diagnosing rare developmental disorders in children. This shift could enable earlier diagnoses for families and save vital resources. A single genetic test could potentially replace the current two-step approach to diagnosing rare developmental disorders in children. This shift could enable earlier diagnoses for families and save the NHS vital resources. Researchers from the Wellcome Sanger Institute, and their collaborators at the University of Exeter and the University of Cambridge, were able to reassess genetic data from nearly 10,000 families from the Deciphering Developmental Disorders study. In a new study, recently published in Genetics in Medicine, they show for the first time that using exome sequencing -- which reads only protein-coding DNA -- is as accurate, if not better, than standard microarrays at identifying disease-causing structural genetic variations. Its adoption offers hope for faster and more accurate diagnoses of rare genetic diseases. It could also deliver substantial cost savings for the NHS, though more training is needed for specialists to generate and analyse the data, say researchers. Changes in our genetic code can range from single letter changes to the deletion or duplication of larger stretches of DNA. These bigger changes -- called copy number variations (CNVs) -- can be harder for clinical teams to detect in sequencing data and understand, which is why microarrays are used. While usually harmless, making up one of the major sources of genetic diversity in humans, these large-scale variations can sometimes cause various neurodevelopmental disorders, including Angelman syndrome, DiGeorge syndrome, and Williams-Beuren syndrome. Currently, children suspected to have genetic diseases arising from these large deletions or duplications of DNA go through a lengthy process of testing and waiting for results from multiple diagnostic approaches, starting with a microarray test before progressing to a broader genome-wide sequencing test (such as exome or genome sequencing). In this new study, scientists set out to develop a single approach to detect these structural changes, using data available from genome-wide exome sequencing assays. Using data from the Deciphering Developmental Disorders study, the team developed a single-assay approach that combined four algorithms using machine learning methods to analyse exome sequencing data. Comparison of the new single-assay approach with current standard clinical methods revealed it could reliably detect 305 large-scale pathogenic mutations, including 91 not previously detectable using standard clinical microarrays. The findings suggest it could replace the current methods. Caroline Wright, Professor of Genomic Medicine at the University of Exeter, and author of the study, said: "Using exome sequencing data to detect clinically important large-scale changes, at the same time as small genetic variants, marks a significant step forward in making genetic testing simpler, cheaper and more accessible." Helen Firth, Professor of Clinical Genomics at the University of Cambridge, lead clinician and author of the study, said: "Under the current system, children often endure a lengthy, step-wise process of different genetic tests before reaching a diagnosis. This research brings hope that, in the near future, families might only need one test." Professor Matthew Hurles, Director of the Wellcome Sanger Institute and senior author of the study, said: "We are still learning how large-scale genetic variations impact human health. This study proves that with the right computational methods, a single test can accurately detect them. Our findings support its widespread adoption in NHS clinical practice, and the adequate bioinformatics training to support this."

Qualitative interview study informs future clinical trial endpoints for evaluating ZYN002 PLYMOUTH MEETING, Pa., Dec. 5, 2023 /PRNewswire/ -- Harmony Biosciences Holdings, Inc. ("Harmony" or the "Company") (Nasdaq: HRMY), a pharmaceutical company dedicated to developing and commercializing innovative therapies for patients with rare neurological diseases, will present caregiver-reported impacts of 22q11.2 deletion syndrome (22q) and data from the Phase 2 INSPIRE trial at the American College of Neuropsychopharmacology Annual Meeting from December 3-6, 2023. The INSPIRE trial evaluated ZYN002 as a potential treatment for anxiety and other irritable behavioral symptoms associated with 22q. Qualitative behavioral analyses of patients and their caregivers, both from INSPIRE and an independent panel, as well as prospective post-hoc analyses of the INSPIRE trial, informed the creation of a conceptual framework for the selection of patient-centered assessments for future clinical trials. This framework proposes endpoint measures to assess the treatment of behavioral symptoms associated with the condition, which currently lacks FDA-approved treatments and affects approximately 80,000 individuals in the U.S. and 129,000 in the EU and UK. "Harmony is dedicated to finding effective treatments for children and their families living with 22q and other rare neuropsychiatric conditions that currently lack approved therapies," said Kumar Budur, M.D., M.S., Chief Medical Officer at Harmony Biosciences. "Through our recent acquisition of Zynerba, we are making meaningful strides toward developing new treatments for individuals with the behavioral symptoms associated with 22q and Fragile X syndrome (FXS). The development of endpoint measures for future clinical trials is an important step forward in our work for 22q patients who have high unmet medical needs." Poster: Anxious and Irritable Behaviors in Children with 22q11.2 Deletion Syndrome: A Qualitative Interview Study and Development of a Conceptual Framework Poster Session II: Tuesday, December 5, 5PM – 7PM (ET) ZYN002 is being evaluated as an investigational treatment for 22q. It is not approved for commercial distribution by government regulatory bodies, including the U.S. Food and Drug Administration (FDA). About the INSPIRE Trial The 38-week INSPIRE trial was an open-label, Phase 2 clinical trial designed to evaluate the safety, tolerability and effectiveness of ZYN002 in children and adolescents (ages four through 15) with genetically confirmed 22q11.2 deletion syndrome. Enrolled patients received weight-based doses of 250 mg or 500 mg daily of ZYN002. Patients were allowed to increase the daily dose after six weeks of treatment to 500 mg and 750 mg if the investigator felt such an increase was appropriate. At the completion of the first 14-week period of treatment, patients who demonstrated an improvement in symptoms of irritability continued ZYN002 for an additional six months, for a total of 38 weeks of treatment. 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 22q11.2 Deletion Syndrome 22q11.2 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 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, affecting 1 in 3,600 to 4,000 males and 1 in 4,000 to 6,000 females. 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. There are approximately 80,000 people in the U.S. and approximately 121,000 people in the European Union and UK living with FXS. 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 Harmony Biosciences At 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 . Forward Looking Statement This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements are based on the current beliefs and expectations of Harmony's management and are subject to significant risks and uncertainties. Actual results may differ materially from those described in the forward-looking statements. All statements contained in this press release that do not relate to matters of historical fact, including statements about our beliefs and expectations, should be considered forward-looking statements. Forward-looking statements include information concerning possible or assumed future results of operations, including descriptions of our business plans and strategies. These statements often include words such as "anticipate," "expect," "guidance," "suggest," "plan," "believe," "intend," "estimate," "target," "project," "should," "could," "would," "may," "will," "forecast," "outlook," "potential," "continues," "seeks," "predicts," or the negative of these words and other similar expressions. Factors that could cause actual results to differ materially from those described in the forward-looking statements include: risks related to the distraction of management from ongoing business operations and other opportunities due to recent acquisitions; our ability to acquire businesses, successfully secure financing for our acquisitions and timely consummate such acquisitions; the possibility that we will not successfully integrate the operations of our acquisitions, control the costs of integrating our acquisitions or realize the intended benefits of such acquisitions, including our recent Zynerba acquisition; government regulation and changes in the regulatory environment; litigation or regulatory proceedings; our ability to effectively manage our costs; our ability to retain or renew existing agreements with large or long-term customers; our ability to manage and expand our operations and keep up with rapidly changing technologies; our ability to maintain the security and integrity of our data; losses against which we do not insure; our ability to make timely payments of principal and interest on our indebtedness; our ability to satisfy covenants in the agreements governing our indebtedness; our ability to maintain our liquidity; our reliance on key management personnel; and other one-time events and other factors that can be found in our Annual Report on Form 10-K for the year ended December 31, 2022, and any subsequent Quarterly Report on Form 10-Q or Current Report on Form 8-K, which are filed with the Securities and Exchange Commission. Many of these factors are beyond our control. The forward-looking statements contained in this earnings release speak only as of the date of this earnings release. We undertake no obligation to publicly release the result of any revisions to these forward-looking statements to reflect the impact of events or circumstances that may arise after the date of this earnings release. Harmony Biosciences Media Contact: Cate McCanless 202-641-6086 cmccanless@harmonybiosciences.com Harmony Biosciences Investor Contact: Luis Sanay, CFA 445-235-8386 lsanay@harmonybiosciences.com View original content to download multimedia: SOURCE Harmony Biosciences Company Codes: NASDAQ-NMS:HRMY

Continued Strong Growth with WAKIX® (pitolisant) Net Revenue of $160.3 Million for Third Quarter 2023; Increased ~37% Year-over-Year Average Number of Patients on WAKIX Increased by ~350 Sequentially to ~5,800 for Third Quarter 2023 Remain Committed and Continue to Pursue Idiopathic Hypersomnia Indication; Next Step to Meet with FDA Informed by Review of Full Data Set Expanded and Diversified Pipeline with Acquisition of Zynerba Pharmaceuticals; Zygel™ in Pivotal Phase 3 Trial for Fragile X syndrome Repurchased ~1.4 Million Shares of Common Stock for $50 Million in Third Quarter 2023; Board of Directors Authorized New $200 Million Share Repurchase Program Conference Call and Webcast to be Held Today at 8:30 a.m. ET PLYMOUTH MEETING, Pa., Oct. 31, 2023 (GLOBE NEWSWIRE) -- Harmony Biosciences Holdings, Inc. (“Harmony” or the “Company”) (Nasdaq: HRMY), a pharmaceutical company dedicated to developing and commercializing innovative therapies for patients with rare neurological diseases, today reported financial results and business updates for the quarter ended September 30, 2023. “We continue to demonstrate very strong growth in our commercial business, with WAKIX in narcolepsy delivering the strongest revenue quarter in Harmony's history,” stated Jeffrey M. Dayno, M.D., President and Chief Executive Officer of Harmony. “In addition, we advanced our pitolisant pipeline programs, and expanded our pipeline with the addition of Zygel through the closing of the Zynerba acquisition.” “Given our continued confidence in the underlying strength of the business and our conviction in the growth potential for the company, we are announcing a new share repurchase program of $200 million.” Third Quarter 2023 Financial Results Net product revenues for the quarter ended September 30, 2023 were $160.3 million, compared to $117.2 million for the same period in 2022. The 37% growth versus the same period in 2022 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 United States). The average number of patients on WAKIX increased by approximately 350 sequentially to approximately 5,800 for the quarter ended September 30, 2023. GAAP net income for the quarter ended September 30, 2023 was $38.5 million, or $0.63 earnings per diluted share, compared to GAAP net income of $87.9 million, or $1.44 earnings per diluted share, for the same period in 2022. The decrease in GAAP net income was primarily driven by the release of the valuation allowance on our deferred tax assets, which resulted in a $74.5 million income tax benefit for the quarter ended September 30, 2022, partially offset by a $30.0 million initial licensing fee as part of the 2022 Licensing and Commercialization Agreement with Bioprojet (the “2022 LCA”). For the quarter ended September 30, 2023, we also incurred a $9.8 million loss on debt extinguishment. Non-GAAP adjusted net income was $58.8 million, or $0.97 earnings per diluted share, for the quarter ended September 30, 2023, compared to Non-GAAP adjusted net income of $58.1 million, or $0.95 per diluted share, for the same period in 2022. 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 $17.5 million in the third quarter of 2023, as compared to $40.5 million for the same quarter in 2022, representing a 57% decrease, driven by a $30.0 million licensing fee as part of the 2022 LCA incurred during the third quarter of 2022;Sales and Marketing expenses were $23.4 million in the third quarter of 2023, as compared to $20.5 million for the same quarter in 2022, representing a 14% increase;General and Administrative expenses were $22.5 million in the third quarter of 2023, as compared to $21.3 million for the same quarter in 2022, representing a 6% increase; andTotal Operating Expenses were $63.5 million in the third quarter of 2023, as compared to $82.3 million for the same quarter in 2022, representing a 23% decrease. As of September 30, 2023, Harmony had cash, cash equivalents and investment securities of $438.4 million, compared to $345.7 million as of December 31, 2022. Company Updates Reported topline results from the Phase 3 INTUNE study in adult patients with idiopathic hypersomnia (IH). While the primary endpoint did not reach statistical significance during the randomized withdrawal phase, a robust clinical effect was demonstrated in the open label phase of the study. Based on the totality of the data, the company remains committed and continues to pursue an indication for pitolisant in IH. Next step is to meet with the FDA informed by the review of the full data set. Received FDA alignment on the protocol for the Phase 3 TEMPO study in patients with Prader-Willi syndrome (PWS) which will satisfy the requirements for both the registrational trial and now pediatric exclusivity as well. We expect to initiate the study in the first quarter of 2024. On track for topline data from the Myotonic Dystrophy (DM1) Phase 2 proof-of-concept signal detection trial in the fourth quarter of 2023. On track to submit a supplemental new drug application (sNDA) for a pediatric narcolepsy indication to the FDA in the fourth quarter of 2023.Advancing new pitolisant based formulations into the clinic in the fourth quarter of 2023. Anticipate data in the first half of 2024.Expanded and diversified our pipeline with the acquisition of Zynerba Pharmaceuticals. Zygel is in a Pivotal Phase 3 trial for Fragile X syndrome (FXS).During the third quarter of 2023, the company repurchased 1,439,792 shares of common stock at an aggregate cost of $50 million, as part of the prior $125 million share repurchase program, which we closed.Our Board of Directors authorized a new $200 million share repurchase program. Conference Call Today at 8:30 a.m. ET We are hosting our third quarter 2023 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) 245-3047 (domestic) or +1 (203) 518-9765 (international), and reference passcode HRMYQ323. Non-GAAP Financial MeasuresIn 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 or cataplexy in adult patients 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 165,000 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 Zygel™ Zygel is the first and only pharmaceutically manufactured, synthetic cannabidiol, non-euphoric cannabinoid, formulated as a patent-protected permeation-enhanced gel for transdermal delivery through the skin and into the circulatory system. Zygel is manufactured through a synthetic process in a cGMP facility and is not extracted from the cannabis plant. Therefore, it is devoid of THC, which is what causes the euphoric effect of cannabis, and has the potential to be a nonscheduled product if approved. Cannabidiol, the active ingredient in Zygel, has been granted orphan drug designation by the FDA and the EMA for the treatment of FXS and for the treatment of 22q11.2 deletion syndrome (22q). Additionally, Zygel 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, affecting 1 in 3,600 to 4,000 males and 1 in 4,000 to 6,000 females. 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. There are approximately 80,000 people in the U.S. and approximately 121,000 people in the European Union and UK living with FXS. 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 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 product WAKIX and our future capabilities following the acquisition of Zynerba. 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 WAKIX, 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 development activities with Bioprojet, and plans to explore the therapeutic potential of pitolisant in additional indications; our ongoing and planned clinical trials; 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 of our product candidates, including those we are developing with Bioprojet; our failure to achieve the potential benefits of the 2022 LCA with Bioprojet; our ability to recognize the intended benefits of our acquisition of Zynerba Pharmaceuticals; our estimates regarding expenses, future revenue, capital requirements and needs for additional financing; our ability to identify 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 21, 2023, 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 CONSOLIDATEDSTATEMENTS OF OPERATIONS AND COMPREHENSIVE INCOME (In thousands, except share and per share data) Three Months Ended September 30, Nine Months Ended September 30, 2023 2022 2023 2022Net product revenues $ 160,268 $ 117,206 $ 413,610 $ 309,547Cost of product sold 32,296 22,959 78,084 56,596Gross profit 127,972 94,247 335,526 252,951Operating expenses: Research and development 17,499 40,548 45,757 60,794Sales and marketing 23,418 20,467 70,518 58,210General and administrative 22,546 21,331 67,417 61,374Total operating expenses 63,463 82,346 183,692 180,378Operating income 64,509 11,901 151,834 72,573Loss on debt extinguishment (9,766) — (9,766) —Other (expense) income, net (5) 56 (34) 96Interest expense, net (2,906) (3,990) (8,327) (12,086)Income before income taxes 51,832 7,967 133,707 60,583Income tax (expense) benefit (13,371) 79,976 (31,461) 72,376Net income $ 38,461 $ 87,943 $ 102,246 $ 132,959Unrealized income (loss) on investments 6 (149) (365) (178)Comprehensive income $ 38,467 $ 87,794 $ 101,881 $ 132,781 EARNINGS PER SHARE: Basic $ 0.64 $ 1.48 $ 1.71 $ 2.25Diluted $ 0.63 $ 1.44 $ 1.68 $ 2.18Weighted average number of shares of common stock - basic 59,863,102 59,234,720 59,856,941 59,070,063Weighted average number of shares of common stock - diluted 60,681,676 61,207,625 60,892,992 60,921,482 HARMONY BIOSCIENCES HOLDINGS, INC.CONSOLIDATED BALANCE SHEETS(In thousands except share and per share data) September 30, December 31, 2023 2022 ASSETS CURRENT ASSETS: Cash and cash equivalents $324,603 $243,784 Investments, short-term 46,071 79,331 Trade receivables, net 67,264 54,740 Inventory, net 5,087 4,297 Prepaid expenses 14,269 9,347 Other current assets 5,704 8,786 Total current assets 462,998 400,285 NONCURRENT ASSETS: Property and equipment, net 428 573 Restricted cash 250 750 Investments, long-term 67,700 22,568 Intangible assets, net 143,069 160,953 Deferred tax asset 100,485 85,943 Other noncurrent assets 2,836 2,798 Total noncurrent assets 314,768 273,585 TOTAL ASSETS $777,766 $673,870 LIABILITIES AND STOCKHOLDERS’ EQUITY CURRENT LIABILITIES: Trade payables $6,539 $3,786 Accrued compensation 10,322 11,532 Accrued expenses 72,761 59,942 Current portion of long-term debt 15,000 2,000 Other current liabilities 7,786 1,624 Total current liabilities 112,408 78,884 NONCURRENT LIABILITIES: Long-term debt, net 182,131 189,647 Other noncurrent liabilities 1,895 2,501 Total noncurrent liabilities 184,026 192,148 TOTAL LIABILITIES 296,434 271,032 COMMITMENTS AND CONTINGENCIES (Note 12) STOCKHOLDERS’ EQUITY: Common stock—$0.00001 par value; 500,000,000 shares authorized at September 30, 2023 and December 31, 2022, respectively; 58,571,944 shares and 59,615,731 issued and outstanding at September 30, 2023 and December 31, 2022, respectively 1 1 Additional paid in capital 651,731 675,118 Accumulated other comprehensive (loss) income (516) (151)Accumulated deficit (169,884) (272,130)TOTAL STOCKHOLDERS’ EQUITY 481,332 402,838 TOTAL LIABILITIES AND STOCKHOLDERS’ EQUITY $777,766 $673,870 HARMONY BIOSCIENCES HOLDINGS, INC.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, 2023 2022 2023 2022 GAAP net income $38,461 $87,943 $102,246 $132,959 Non-GAAP Adjustments: Non-cash interest expense (1) 2,221 418 3,061 1,241 Depreciation 144 101 350 312 Amortization (2) 5,962 5,962 17,884 17,005 Stock-based compensation expense 7,957 6,967 22,311 19,234 Licensing fee (3) - 30,000 - 30,000 Loss on debt extinguishment 9,766 - 9,766 - Valuation allowance release - (74,474) - (74,474)Income tax effect related to non-GAAP adjustments (4) (5,723) 1,175 (10,835) (2,341)Non-GAAP adjusted net income $58,788 $58,092 $144,783 $123,936 GAAP reported net income per diluted share $0.63 $1.44 $1.68 $2.18 Non-GAAP adjusted net income per diluted share $0.97 $0.95 $2.38 $2.03 Weighted average number of shares of common stock used in non-GAAP diluted per share 60,681,676 61,207,625 60,892,992 60,921,482 (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 2022 Licensing and Commercialization Agreement with Bioprojet.(4) Calculated using the reported effective tax rate for the periods presented less impact of discrete items Harmony Biosciences Investor Contact:Luis Sanay, CFA445-235-8386lsanay@harmonybiosciences.com Harmony Biosciences Media Contact:Cate McCanless202-641-6086cmccanless@harmonybiosciences.com