REM Sleep Behavior Disorder

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.

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

PALO ALTO, Calif., July 30, 2024 (GLOBE NEWSWIRE) -- PALO ALTO, Calif., July 30, 2024 (GLOBE NEWSWIRE) -- 180 Life Sciences Corp. (NASDAQ: ATNF) (“180 Life Sciences” or the “Company”), today announced topline results from a clinical pharmacology study (the “Study”), that evaluated the uptake of cannabidiol (CBD) in a solid formulation which can be delivered as a pill orally. The clinical trial in humans, performed with Prof. Avi Domb of the Hebrew University, School of Pharmacy, and with Prof. Elyad Davidson, of Hadassah Hospital, compared two solid formulations of CBD with a U.S. Food and Drug Administration (FDA) approved drug for epilepsy, Epidiolex. The purpose of the Study was to compare the pharmokinetic (PK) profile of a generic approved CBD product, Epidiolex®, with two solid formulations. We believe this type of trial has yet to be examined in a clinical setting. For the Company’s trial, twelve volunteers received all three formulations in a crossover randomized trial. Epidiolex is a CBD dissolved in 8% ethanol and 80% sesame seed oil, plus flavoring agents, that is given as a liquid solution via syringe in the mouth. Results of the clinical trial indicate that one of the two solid forms was absorbed faster and exhibited higher maximal levels compared to Epidiolex. Both of the solid formulations were well tolerated. CBD is a purified product that is not psychoactive, which we believe has potential benefits for treatment of inflammatory processes and pain. A major problem in working with CBD is its low, unpredictable and variable uptake following the most convenient delivery form, by mouth, as a liquid CBD in oil like the approved pharmaceutical Epidiolex, given for epilepsy. To help try to solve this problem, Prof. Domb and colleagues developed “ProNanoLipospheres” (PNL), a mixture of components available over-the-counter, which form little droplets and have been shown to be absorbed from the gastrointestinal tract into blood. The results of the clinical trial performed on 12 adult males at the Hadassah Hospital, shows that capsules composed of one of the PNL formulations performed better statistically than Epidiolex in terms of the speed of absorption and achievement of maximal levels. The other PNL formulation, also given as a capsule, was statistically equivalent to Epidiolex in terms of speed of absorption and achievement of maximal levels. We believe that a solid formulation for testing in clinical trials will advance testing CBD in other indications. CBD has shown promise in studies on treatment of pain, post-traumatic stress disorder (PTSD), head trauma, and other indications, yet an oral liquid formulation is undesirable.1 The new formulations tested by 180 Life Sciences and its collaborators open a potential path for testing solid CBD given by mouth in a capsule. According to Prof. Avi Domb, “If shown via further clinical testing, 180 Life Sciences’ proprietary solid formulation for the delivery of CBD may provide medical professionals with greatly expanded options to prescribe and deliver CBD in a precisely dosed, high uptake pill format rather than the current liquid format. This may have potentially significant commercial market potential by avoiding the complexity associated with unpredictable liquid formulation delivery. Both physicians and patients may have broader acceptance of a solid oral pill format.” Full study results are not yet available. The trial results are planned to be submitted for scientific publication at a later date. We do not anticipate the outcome of this trial to have any effect on our financial results for the year ended December 31, 2024. About 180 Life Sciences Corp. 180 Life Sciences Corp. is a clinical stage biotechnology company focused on the development of therapeutics for unmet medical needs in chronic pain, inflammation and fibrosis by employing innovative research, and, where appropriate, combination therapy. Forward-Looking Statements This press release includes “forward-looking statements”, including information about management’s view of the Company’s future expectations, plans and prospects, within the safe harbor provisions provided under federal securities laws, including under The Private Securities Litigation Reform Act of 1995 (the “Act”). Words such as “expect,” “estimate,” “project,” “budget,” “forecast,” “anticipate,” “intend,” “plan,” “may,” “will,” “could,” “should,” “believes,” “predicts,” “potential,” “continue” and similar expressions are intended to identify such forward-looking statements. These forward-looking statements involve significant risks and uncertainties that could cause the actual results to differ materially from the expected results and, consequently, you should not rely on these forward-looking statements as predictions of future events. These forward-looking statements and factors that may cause such differences include, without limitation, statements expressed or implied relating to the properties or potential benefits of PNL; our ability to commercialize PNL and our other drug candidates, if proven successful for treatment in trials; risks regarding whether the administrative processes required for the issuance of patents will be completed in a timely manner or at all; the Company’s ability to meet Nasdaq’s conditions for continued listing on Nasdaq, and the timing relating thereto; the ability of the Company to maintain the continued listing of the Company’s securities on The Nasdaq Stock Market, including that the Company is not currently in compliance with Nasdaq’s continued listing standards; the review and evaluation of strategic transactions and their impact on shareholder value; the process by which the Company engages in evaluation of strategic transactions; the outcome of potential future strategic transactions and the terms thereof; the ability of the Company to raise funding, the terms of such funding, and dilution caused thereby; risks regarding the outcome of pharmaceutical studies, the timing and costs thereof, and the ability to obtain sufficient participants; the timing of, outcome of, and results of, clinical trials statements regarding the timing of marketing authorization application (MAA) submissions to the UK Medicines and Healthcare products Regulatory Agency (MHRA) and New Drug Application submissions (NDA) to the U.S. Food and Drug Administration (FDA), our ability to obtain approval and acceptance thereof, the willingness of MHRA to review such MAA and the FDA to review such NDA, and our ability to address outstanding comments and questions from the MHRA and FDA; statements about the ability of our clinical trials to demonstrate safety and efficacy of our product candidates, and other positive results; the uncertainties associated with the clinical development and regulatory approval of 180 Life Sciences’ drug candidates, including potential delays in the enrollment and completion of clinical trials, the costs thereof, closures of such trials prior to enrolling sufficient participants in connection therewith, issues raised by the FDA, the MHRA and the European Medicines Agency (EMA); the ability of the Company to persuade regulators that chosen endpoints do not require further validation; timing and costs to complete required studies and trials, and timing to obtain governmental approvals; the accuracy of simulations and the ability to reproduce the outcome of such simulations in real world trials; 180 Life Sciences’ reliance on third parties to conduct its clinical trials, enroll patients, and manufacture its preclinical and clinical drug supplies; the ability to come to mutually agreeable terms with such third parties and partners, and the terms of such agreements; estimates of patient populations for 180 Life Sciences planned products; 180 Life Sciences’ ability to fully comply with numerous federal, state and local laws and regulatory requirements, as well as rules and regulations outside the United States, that apply to its product development activities; current negative operating cash flows and a need for additional funding to finance our operating plans; the terms of any further financing, which may be highly dilutive and may include onerous terms, increases in interest rates which may make borrowing more expensive and increased inflation which may negatively affect costs, expenses and returns; statements relating to expectations regarding future agreements relating to the supply of materials and license and commercialization of products; the availability and cost of materials required for trials; the risk that initial drug trials and results are not predictive of future results or will not be able to be replicated in clinical trials or that such drugs selected for clinical development will not be successful; challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; the inherent risks in early stage drug development including demonstrating efficacy; development time/cost and the regulatory approval process; the progress of our clinical trials; our ability to find and enter into agreements with potential partners; our ability to attract and retain key personnel; changing market and economic conditions; competition, including technological advances, new products and patents attained by competitors; challenges to patents; changes to applicable laws and regulations, including global health care reforms; expectations with respect to future performance, growth and anticipated acquisitions; expectations regarding the capitalization, resources and ownership structure of the Company; the ability of the Company to execute its plans to develop and market new drug products and the timing and costs of these development programs; estimates of the size of the markets for the Company’s potential drug products; the outcome of current litigation involving the Company; potential future litigation involving the Company or the validity or enforceability of the intellectual property of the Company or lawsuits alleging that we have violated the intellectual property of others; global economic conditions; geopolitical events and regulatory changes; the expectations, development plans and anticipated timelines for the Company’s drug candidates, pipeline and programs, including collaborations with third parties; and the effect of changing interest rates and inflation, economic downturns and recessions, declines in economic activity or global conflicts. These risk factors and others are included from time to time in documents the Company files with the Securities and Exchange Commission, including, but not limited to, its Form 10-Ks, Form 10-Qs and Form 8-Ks, and including the Annual Report on Form 10-K for the year ended December 31, 2023, and Quarterly Report on Form 10-Q for the quarter ended March 31, 2024, and future SEC filings. These reports and filings are available at www.sec.gov and are available for download, free of charge, soon after such reports are filed with or furnished to the SEC, on the “Investors”, “SEC Filings”, “All SEC Filings” page of our website at www.180lifesciences.com. All subsequent written and oral forward-looking statements concerning the Company, the results of the Company’s clinical trial results and studies or other matters and attributable to the Company or any person acting on its behalf are expressly qualified in their entirety by the cautionary statements above. Readers are cautioned not to place undue reliance upon any forward-looking statements, which speak only as of the date made, including the forward-looking statements included in this press release, which are made only as of the date hereof. The Company cannot guarantee future results, levels of activity, performance or achievements. Accordingly, you should not place undue reliance on these forward-looking statements. The Company does not undertake or accept any obligation or undertaking to release publicly any updates or revisions to any forward-looking statement to reflect any change in its expectations or any change in events, conditions, or circumstances on which any such statement is based, except as otherwise provided by law. Investors: Please contact Blair Jordan, Interim CEO – bjordan@180lifesciences.com 1 See, for example: Izzo, A. A., Borrelli, F., Capasso, R., Di Marzo, V. & Mechoulam, R. 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Cannabidiol, a non-psychoactive component of cannabis and its synthetic dimethylheptyl homolog suppress nausea in an experimental model with rats. Neuroreport 13, 567–570 (2002).Ribeiro, A. et al. Cannabidiol, a non-psychotropic plant-derived cannabinoid, decreases inflammation in a murine model of acute lung injury: Role for the adenosine A2A receptor. Eur. J. Pharmacol. 678, 78–85 (2012).WHO, W. H. O. Cannabidiol (CBD): pre-review report. Expert Committee on Drug Dependence 39, (2017).