REM Sleep Parasomnias

-- LUMRYZ is the only FDA-approved once-at-bedtime oxybate treatment for cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age and older with narcolepsy— -- Granted Orphan Drug Exclusivity in pediatric narcolepsy patients 7 years and older through October 16, 2031 -- DUBLIN, Oct. 17, 2024 (GLOBE NEWSWIRE) -- Avadel Pharmaceuticals plc (Nasdaq: AVDL), a biopharmaceutical company focused on transforming medicines to transform lives, announced today that the U.S. Food and Drug Administration (FDA) has approved its supplemental new drug application (sNDA) for LUMRYZ for the treatment of cataplexy or EDS in patients 7 years of age and older with narcolepsy. “This approval represents an important milestone for the narcolepsy community, specifically for younger narcolepsy patients and their caregivers who face significant challenges associated with waking up in the middle of the night to complete treatment regimens. With this label expansion, pediatric patients 7 years and older living with narcolepsy now have the same option that adult patients with narcolepsy have – to choose a once-nightly treatment option that does not disrupt sleep for a middle of the night dose,” said Greg Divis, Chief Executive Officer of Avadel Pharmaceuticals. “In less than two years, Avadel has made great strides in establishing our commitment to the development of transformative medicines for sleep disorders. This includes successfully launching LUMRYZ for the adult narcolepsy population, initiating a Phase 3 pivotal trial evaluating LUMRYZ for the treatment of idiopathic hypersomnia, and now the expansion of LUMRYZ into the pediatric narcolepsy population.” "I have been prescribing sodium oxybate for children and adolescents with narcolepsy for years as I have seen how effective this medication is and can safely be used," said Anne Marie Morse, DO, a board-certified and fellowship-trained pediatric neurologist and sleep medicine specialist at Geisinger Health System. “And before this, although numerous families have also witnessed the transformation in their children's lives, I have also had many families turn down the medication, or discontinue after starting, because of the challenge experienced or feared to experience with a forced awakening causing a purposeful nightly disruption, many times met with an exhausting fight, to take the second dose of first-generation oxybates. The expanded FDA approval for LUMRYZ allows me to now share with my patients and their families that there is an FDA-approved treatment that offers a single bedtime dose of medication, provided in a pre-filled packet. I can now offer more options to more patients which allows me to continue my role as a partner in my patients' journeys." Narcolepsy is a chronic neurological condition that impairs the brain's ability to regulate the sleep-wake cycle. The condition affects approximately 1 in 2,000 people in the United States, where roughly 5% of patients are under the age of 18. Symptoms of narcolepsy are EDS and may also include a sudden loss of muscle tone usually triggered by strong emotion (cataplexy), disrupted nighttime sleep, sleep paralysis and hallucinations when falling asleep or waking up. LUMRYZ is a once-at-bedtime formulation extended-release sodium oxybate and was first approved by the FDA on May 1, 2023, for the treatment of cataplexy or EDS in adult patients with narcolepsy. LUMRYZ was approved by the FDA for use in the treatment of cataplexy or EDS in the pediatric narcolepsy population 7 years and older on October 16, 2024, and was granted Orphan Drug Exclusivity through October 16, 2031. LUMRYZ has a boxed warning as a central nervous system depressant, and for its potential for abuse and misuse. LUMRYZ is available only through a restricted program under a Risk Evaluation and Mitigation Strategy called the LUMRYZ REMS. Most common adverse reactions (incidence > 5% and greater than placebo) reported for all doses of LUMRYZ combined in a trial of adults with narcolepsy were nausea, dizziness, enuresis, headache, and vomiting. Similarly, in a trial of pediatric narcolepsy patients receiving immediate-release sodium oxybate, the most commonly observed adverse reactions (incidence ≥5%) were nausea, enuresis, vomiting, headache, decreased weight, decreased appetite, dizziness, and sleepwalking. About LUMRYZ™ (sodium oxybate) for extended-release oral suspensionLUMRYZ is an extended-release sodium oxybate medication approved by the FDA on May 1, 2023, as the first and only once-at-bedtime treatment for cataplexy or excessive daytime sleepiness (EDS) in adults with narcolepsy.  On October 16, 2024, LUMRYZ was additionally approved as a once-at-bedtime treatment for cataplexy or EDS in patients 7 years of age and older with narcolepsy.  The FDA approval of LUMRYZ was supported by results from REST-ON, a randomized, double-blind, placebo-controlled, pivotal Phase 3 trial in adults with narcolepsy. LUMRYZ demonstrated statistically significant and clinically meaningful improvements in the three co-primary endpoints: EDS (MWT), clinicians’ overall assessment of patients’ functioning (CGI-I), and cataplexy attacks, for all three evaluated doses when compared to placebo.   With its approval in May 2023, the FDA also granted 7 years of Orphan Drug Exclusivity to LUMRYZ for the treatment of cataplexy or EDS in adults with narcolepsy due to a finding of clinical superiority of LUMRYZ relative to currently available oxybate treatments. In particular, the FDA found that LUMRYZ makes a major contribution to patient care over currently available, twice-nightly oxybate products by providing a once-nightly dosing regimen that avoids nocturnal arousal to take a second dose. About Avadel Pharmaceuticals plc Avadel Pharmaceuticals plc (Nasdaq: AVDL) is a biopharmaceutical company focused on transforming medicines to transform lives. Our approach includes applying innovative solutions to the development of medications that address the challenges patients face with current treatment options. Avadel’s commercial product, LUMRYZ, was approved by the U.S. Food & Drug Administration (FDA) as the first and only once-at-bedtime oxybate for the treatment of cataplexy or EDS in both adults and pediatrics with narcolepsy. For more information, please visit www.avadel.com. INDICATIONSLUMRYZ (sodium oxybate) for extended-release oral suspension is a prescription medicine used to treat the following symptoms in patients 7 years of age and older with narcolepsy: sudden onset of weak or paralyzed muscles (cataplexy)excessive daytime sleepiness (EDS) IMPORTANT SAFETY INFORMATION WARNING: Taking LUMRYZ™ (sodium oxybate) with other central nervous system (CNS) depressants, such as medicines used to make you fall asleep, including opioid analgesics, benzodiazepines, sedating antidepressants, antipsychotics, sedating anti-epileptic medicines, general anesthetics, muscle relaxants, alcohol or street drugs, may cause serious medical problems, including trouble breathing (respiratory depression), low blood pressure (hypotension), changes in alertness (drowsiness), fainting (syncope) and death.The active ingredient of LUMRYZ (sodium oxybate) is a form of gamma hydroxybutyrate (GHB), a controlled substance. Abuse or misuse of illegal GHB alone or with other CNS depressants (drugs that cause changes in alertness or consciousness) have caused serious side effects. These effects include seizures, trouble breathing (respiratory depression), changes in alertness (drowsiness), coma and death. Call your doctor right away if you have any of these serious side effects.Because of these risks, LUMRYZ is available only by prescription and filled through certified pharmacies in the LUMRYZ REMS. You must be enrolled in the LUMRYZ REMS to receive LUMRYZ. Further information is available at www.LUMRYZREMS.com or by calling 1-877-453-1029. Do not take LUMRYZ if you take or your child takes other sleep medicines or sedatives (medicines that cause sleepiness), drink alcohol or have a rare problem called succinic semialdehyde dehydrogenase deficiency. Keep LUMRYZ in a safe place to prevent abuse and misuse. Selling or giving away LUMRYZ may harm others and is against the law. Tell your doctor if you or your child have ever abused or been dependent on alcohol, prescription medicines or street drugs. Anyone who takes LUMRYZ should not do anything that requires them to be fully awake or is dangerous, including driving a car, using heavy machinery or flying an airplane, for at least six (6) hours after taking LUMRYZ. Those activities should not be done until you know how LUMRYZ affects you. Falling asleep quickly, including while standing or while getting up from the bed, has led to falls with injuries that have required some people to be hospitalized. LUMRYZ can cause serious side effects, including the following: Breathing problems, including slower breathing, trouble breathing and/or short periods of not breathing while sleeping (e.g., sleep apnea). People who already have breathing or lung problems have a higher chance of having breathing problems when they take LUMRYZ.Mental health problems, including confusion, seeing or hearing things that are not real (hallucinations), unusual or disturbing thoughts (abnormal thinking), feeling anxious or upset, depression, thoughts of killing yourself or trying to kill yourself, increased tiredness, feelings of guilt or worthlessness and difficulty concentrating. Tell your doctor if you or your child have or had depression or have tried to harm yourself. Call your doctor right away if you or your child have symptoms of mental health problems or a change in weight or appetite.Sleepwalking. Sleepwalking can cause injuries. Call your doctor if you or your child start sleepwalking. Tell your doctor if you or your child are on a salt-restricted diet or have high blood pressure, heart failure or kidney problems. LUMRYZ contains a lot of sodium (salt) and may not be right for you.The most common side effects of LUMRYZ in adults include nausea, dizziness, bedwetting, headache and vomiting. Your side effects may increase when you take higher doses of LUMRYZ. The most common side effects in children include nausea, bedwetting, vomiting, headache, decreased weight, decreased appetite, dizziness, and sleepwalking. LUMRYZ can cause physical dependence and craving for the medicine when it is not taken as directed. These are not all the possible side effects of LUMRYZ. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088. Please see full Prescribing Information, including BOXED Warning. Cautionary Disclosure Regarding Forward-Looking StatementsThis press release includes “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. These forward-looking statements relate to our future expectations, beliefs, plans, strategies, objectives, results, conditions, financial performance, prospects or other events. Such forward-looking statements include, but are not limited to, expectations regarding the safety and potential therapeutic benefit of, and market and prescriber preference for, LUMRYZ in treating cataplexy and EDS in patients 7 years of age and older with narcolepsy; and the pediatric Orphan Drug Exclusivity for LUMRYZ and potential benefits resulting from such exclusivity. In some cases, forward-looking statements can be identified by the use of words such as “will,” “may,” “could,” “believe,” “expect,” “look forward,” “on track,” “guidance,” “anticipate,” “estimate,” “project,” “next steps” and similar expressions and the negatives thereof (if applicable). The Company’s forward-looking statements are based on estimates and assumptions that are made within the bounds of our knowledge of our business and operations and that we consider reasonable. However, the Company’s business and operations are subject to significant risks, and, as a result, there can be no assurance that actual results and the results of the company’s business and operations will not differ materially from the results contemplated in such forward-looking statements. Factors that could cause actual results to differ from expectations in the Company’s forward-looking statements include the risks and uncertainties described in the “Risk Factors” section of Part I, Item 1A of the Company’s Annual Report on Form 10-K for the year ended December 31, 2023, which was filed with the Securities and Exchange Commission (SEC) on February 29, 2024, and subsequent SEC filings.Forward-looking statements speak only as of the date they are made and are not guarantees of future performance. Accordingly, you should not place undue reliance on forward-looking statements. The Company does not undertake any obligation to publicly update or revise our forward-looking statements, except as required by law. Investor Contact:Courtney MogerleyPrecision AQCourtney.Mogerley@precisionaq.com(212) 698-8687 Media Contact:Lesley StanleyReal Chemistrylestanley@realchemistry.com(609) 273-3162

Cognition is advancing CT1812 in the Phase 2 ‘SHIMMER’ clinical trial for the treatment of dementia with Lewy bodies with data readout in the fourth quarter of 2024PURCHASE, N.Y., Oct. 01, 2024 (GLOBE NEWSWIRE) -- Cognition Therapeutics, Inc., (the “Company” or “Cognition”) (NASDAQ: CGTX), a clinical stage company developing drugs that treat neurodegenerative disorders, supports Lewy Body Dementia Awareness Month and the critical need for more attention, research, and treatments for people with dementia with Lewy bodies (DLB). DLB is the second most common form of progressive dementia, affecting approximately 1.4 million people in the U.S., with no approved treatments available. DLB is caused by the buildup of a protein called alpha-synuclein, which forms deposits called Lewy bodies inside neurons. Over time, these deposits interfere with normal cellular functions, causing a progressive decline in cognitive and motor skills. Symptoms of DLB vary among patients and fluctuate in intensity, making it challenging to diagnose and manage. These symptoms include impaired cognition and mental organization, visual hallucinations, REM sleep behavior disorder, and movement issues similar to Parkinson’s disease. "Lewy Body Dementia Awareness Month is an important opportunity to raise awareness of this underdiagnosed but prevalent condition that can be devastating for patients and their loved ones," said Lisa Ricciardi, CEO of Cognition Therapeutics. "At Cognition, we are committed to developing new treatments for neurodegenerative diseases like DLB, and believe our lead candidate, CT1812, has the potential to address the complex pathology driving this disease." Cognition Therapeutics partnered with experts at the Lewy Body Dementia Association (LBDA) and the University of Miami Miller School of Medicine to design the Phase 2 SHIMMER trial, which has enrolled 130 patients with mild-to-moderate DLB at centers of excellence across the United States. Topline results, which are anticipated later this year, are expected to provide insights into this patient population and the potential therapeutic impact of CT1812 on the constellation of symptoms that affect DLB patients. “The DLB community will be convening at the first Externally Led Patient-Focused Drug Development (EL-PFDD) Meeting* on October 15, 2024. During the meeting, patients and their care partners will relay their experiences directly to the FDA,” said Anthony Caggiano, M.D., Ph.D., Cognition’s CMO and head of R&D. “We look forward to hearing more about the most challenging aspects of DLB from these patient testimonials and applying those learnings to our development plan for CT1812.” For registration and more information on the EL-PFDD meeting on DLB, which is hosted by the LBDA in collaboration with the Alzheimer’s Association, visit https://www.lbda.org/el-pfdd. About CT1812 CT1812 is an experimental orally delivered small molecule oligomer antagonist that penetrates the blood-brain barrier and binds selectively to the sigma-2 receptor complex. Preclinical and clinical data demonstrate that this binding results in the displacement of toxic oligomers. The sigma-2 receptor complex is involved in the regulation of key cellular processes such as membrane trafficking and autophagy that are damaged by oligomers and other stressors. This damage to sensitive synapses can progress to a loss of synaptic function, which drives the progression of neurodegenerative diseases like Alzheimer’s disease and DLB. About the SHIMMER StudyThe SHIMMER study is a Phase 2 signal-finding clinical trial that enrolled 130 adults with mild-to-moderate DLB. Participants are evenly randomized to receive either placebo or one of two oral once-daily doses of CT1812 (100 mg or 300 mg) for six months. The SHIMMER study is supported by a grant award from the National Institute on Aging of the National Institutes of Health (NIH) totaling approximately $30 million and is being conducted in collaboration with James E. Galvin, MD, MPH, director of the Comprehensive Center for Brain Health at the University of Miami Miller School of Medicine and the Lewy Body Dementia Association (LBDA). The SHIMMER study is being conducted at over 30 sites in the United States, many of which are LBDA centers of excellence. About Cognition Therapeutics, Inc. Cognition Therapeutics, Inc., is a clinical-stage biopharmaceutical company discovering and developing innovative, small molecule therapeutics targeting age-related degenerative disorders of the central nervous system and retina. We currently are investigating our lead candidate CT1812 in clinical programs in Alzheimer’s disease, dementia with Lewy bodies (DLB) and dry age-related macular degeneration (dry AMD). We believe CT1812 and our pipeline of σ-2 receptor modulators can regulate pathways that are impaired in these diseases that are functionally distinct from other approaches for the treatment of degenerative diseases. More about Cognition Therapeutics and our pipeline can be found at https://cogrx.com. Forward-Looking Statements This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. All statements contained in this press release, other than statements of historical facts or statements that relate to present facts or current conditions, including but not limited to, statements regarding our product candidates, including CT1812, and any expected or implied benefits or results, including that initial clinical results observed with respect to CT1812 will be replicated in later trials and our clinical development plans, are forward-looking statements. These statements, including statements relating to the timing and expected results of our clinical trials 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. In some cases, you can identify forward-looking statements by terms such as “may,” “might,” “will,” “should,” “expect,” “plan,” “aim,” “seek,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “forecast,” “potential” or “continue” or the negative of these terms or other similar expressions. We have based these forward-looking statements largely on our current expectations and projections about future events and financial trends that we believe may affect our business, financial condition, and results of operations. These forward-looking statements speak only as of the date of this press release and are subject to a number of risks, uncertainties and assumptions, some of which cannot be predicted or quantified and some of which are beyond our control. Factors that may cause actual results to differ materially from current expectations include, but are not limited to: competition; our ability to secure new (and retain existing) grant funding; our ability to grow and manage growth, maintain relationships with suppliers and retain our management and key employees; our ability to successfully advance our current and future product candidates through development activities, preclinical studies and clinical trials and costs related thereto; uncertainties inherent in the results of preliminary data, pre-clinical studies and earlier-stage clinical trials being predictive of the results of early or later-stage clinical trials; the timing, scope and likelihood of regulatory filings and approvals, including regulatory approval of our product candidates; changes in applicable laws or regulations; the possibility that the we may be adversely affected by other economic, business or competitive factors, including ongoing economic uncertainty; our estimates of expenses and profitability; the evolution of the markets in which we compete; our ability to implement our strategic initiatives and continue to innovate our existing products; our ability to defend our intellectual property; impacts of ongoing global and regional conflicts on our business, supply chain and labor force; and the risks and uncertainties described more fully in the “Risk Factors” section of our annual and quarterly reports filed with the Securities Exchange Commission and are available at www.sec.gov. These risks are not exhaustive and we face both known and unknown risks. You should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected in our forward-looking statements may not be achieved or occur, and actual results could differ materially from those projected in the forward-looking statements. Moreover, we operate in a dynamic industry and economy. New risk factors and uncertainties may emerge from time to time, and it is not possible for management to predict all risk factors and uncertainties that we may face. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. Contact Information:   Cognition Therapeutics, Inc.    info@cogrx.com Casey McDonald (media)  Tiberend Strategic Advisors, Inc.     cmcdonald@tiberend.com Mike Moyer (investors) LifeSci Advisors mmoyer@lifesciadvisors.com This press release was published by a CLEAR® Verified individual.

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. 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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