Attention Deficit and Disruptive Behavior Disorders

Children prenatally exposed to anesthesia for maternal surgery during pregnancy were significantly more likely than unexposed children to receive a diagnosis of a disruptive or internalizing behavioral disorder including attention deficit hyperactivity disorder, behavioral disorders, developmental speech or language disorders and autism, according to a new study. Children prenatally exposed to anesthesia for maternal surgery during pregnancy were significantly more likely than unexposed children to receive a diagnosis of a disruptive or internalizing behavioral disorder including attention deficit hyperactivity disorder, behavioral disorders, developmental speech or language disorders and autism, according to a new study at Columbia University Mailman School of Public Health and Columbia University Irving Medical Center (CUIMC). Until now associations between prenatal exposure to general anesthesia for maternal surgery during pregnancy and subsequent risk of behavioral disorders in children was unclear. The findings are published online in the British Journal of Anesthesia. Prenatal exposure to general anesthesia was associated with a 31 percent increased risk for a subsequent disruptive or internalizing behavioral disorder (DIBD) diagnosis in children, with higher risk when the exposure occurred in the second or third trimester of pregnancy. The probabilities of DIBD diagnosis between exposed and unexposed children were similar in the first three years of life, but diverged thereafter. "For several years there have been concerns about the long-term neurodevelopmental effects of anesthetic exposure in children, with the FDA in 2016 releasing a Drug Safety Communication warning against repeated or lengthy use of anesthesia in young children and pregnant women," said Caleb Ing, MD, MS, associate professor of Anesthesiology and Epidemiology at Columbia Public Health and CUIMC and first author. "Studies evaluating exposures in children however have been limited because children needing surgery and anesthesia may have more underlying health problems which may predispose them to neurodevelopmental disorders. Prenatal exposures are particularly relevant because general anesthetic drugs cross the placenta, and since the need for anesthesia is related to maternal medical problems, the risk of bias due to underlying health problems in children is reduced, according to the authors. "However, caution is advised, as many procedures in pregnant women may be necessary, and avoidance of necessary procedures can have detrimental effects on mothers and their children," advises Ing. The study population was drawn from Medicaid Analytic eXPrenatal eXtract for general anesthetic exposure and was identified using maternal claims with International Classification of Disease for either an appendectomy or cholecystectomy which are the two most common non-obstetric procedures performed during pregnancy. Exposures were classified as occurring in the first, second, or third trimester of pregnancy. The researchers also controlled for a variety of factors including age, race, ethnicity, state of residence, income based on zipcode, and Medicaid enrollment for disability vs. poverty. Each prenatally exposed child was matched with five unexposed children. The population consisted of 16,778,231 deliveries linked to an infant born between 1999 and 2013 with known sex. Of those, 34,271 children were exposed to general anesthesia due to maternal appendectomy or cholecystectomy during pregnancy. "This study provides compelling evidence that prenatal exposure to surgery and general anesthesia may have adverse effects on children's neurobehavioral development ," said Guohua Li, MD, DrPH, professor of Epidemiology and Anesthesiology at Columbia Mailman School and Vagelos College of Physicians and Surgeons, and senior author. "Our findings could help inform preoperative risk assessment in pregnant women, especially when the surgical procedure is elective or when viable treatment is available. Results of this study also give added impetus to research on safer anesthetic drugs and techniques." Co-authors are Jeffrey H. Silber,,Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine; Deven Lackraj, Stanford Chihuri, and Ling Guo , Columbia University Vagelos College of Physicians and Surgeons; Mark Olfson and Melanie Wall, Columbia Mailman School of Public Health and Vagelos College of Physicians and Surgeons; Caleb Miles, Columbia Mailman School of Public Health; Joseph G. Reiter and Siddharth Jain, Children's Hospital of Philadelphia; and Cynthia Gyamfi-Bannerman, University of California San Diego. The study was supported by the Agency for Healthcare Research and Quality (AHRQ), grant R01HS026493.

With the advent of rapid whole genome sequencing, children presenting with an intellectual disability or developmental delay are recommended to have their DNA sequenced to identify the underlying genetic cause. Researchers have now published the results of an analysis of data from almost 2,800 young people with rare genomic variants -- changes to their DNA -- that are associated with intellectual disability. A major study of children with intellectual disabilities has highlighted the additional challenges that they often face, including a much-increased likelihood of being diagnosed as autistic, as well as Attention Deficit Hyperactivity Disorder (ADHD) and other mental health difficulties. With the advent of rapid whole genome sequencing, children presenting with an intellectual disability or developmental delay are recommended to have their DNA sequenced to identify the underlying genetic cause. To capitalise on this recent NHS development, researchers at the University of Cambridge, University College London and Cardiff University established IMAGINE ID ( ), a national UK cohort study that aims to discover how genetic changes affect children and young people's behaviour, in order to inform better care of families and children now and in the future. Writing in The Lancet Psychiatry today, the researchers have published the results of an analysis of data from almost 2,800 young people with rare genomic variants -- changes to their DNA -- that are associated with intellectual disability. Professor Lucy Raymond from the University of Cambridge, the study's senior author, said: "Thanks to all the families that have taken part in our research, we've been able to conduct the largest study to date of the impact of rare genetic variants associated with intellectual disability. What we've found from parents is that these children are extremely likely to develop other neurodevelopmental or mental health conditions, which can present additional challenges both to the children and their families." All the participants were aged between four and 19 years. Just under three-quarters (74%) had an intellectual disability caused by a duplication or deletion of sections of DNA -- a so-called copy number variant (CNV). The remaining young people had a disability caused by a single 'spelling error' in their DNA -- a change in the A, C, G or T nucleotides -- referred to as a single nucleotide variant (SNV). Compared to the English national population, children in the study were almost 30 times as likely to have been diagnosed as autistic. In the general population, 1.2% of people are diagnosed with the condition compared to 36% of the study participants. Similarly, 22% of the study population were diagnosed with ADHD, compared to 1.6% of the general population, meaning that they were more than 13 times more likely to have the condition. Around one in eight children (12%) had been diagnosed with oppositional defiant disorder, in which children are uncooperative, defiant, and hostile toward others -- a rate 4.4 times higher than in the general population. One in ten (11%) had an anxiety disorder, a 1.5 times increased risk. Rates of childhood depression were significantly lower, at just 0.4% compared with 2.1% of the general population, but this may increase over the next few years as some mental health disorders do not start until later adolescence or early adult life. Almost all of the children (94%) were reported to have at least one significant physical health problem, including disturbed sleep (65%), motor or movement disorders (64%) or seizures (30%). Dr Jeanne Wolstencroft from Great Ormond Street Institute of Child Health, University College London, said: "Routine genomic testing now allows parents to understand the genetic cause of intellectual disabilities in an increasing number of children but, because so many of these conditions are rare, we still lack information on the impact this has on their children's future mental health. "We already know that intellectual disabilities tend to be associated with an increased likelihood of neurodevelopmental conditions, as well as emotional and behavioural difficulties, but we found that where there is an identifiable genetic cause, the likelihood is amplified considerably. This suggests that these children should be provided with early assessment and help where appropriate." The team has also shown for the first time that children with intellectual disability caused by a genetic variant inherited from a family member, are more likely to come from a more deprived socioeconomic background. This suggests that some parents or family members with the same variant may also have unrecognised difficulties that placed them at a social and educational disadvantage. These children were more likely to be diagnosed with a neuropsychiatric condition and were also more likely to exhibit behavioural difficulties. Professor David Skuse from Great Ormond Street Institute of Child Health, University College London, said: "We hope this work helps improve the targeting of assessments and interventions to support families at the earliest opportunity. We'd like to see better training for health care providers about the wider use and utility of genetic testing. We have identified its potential value in terms of prioritising children with mental health needs for child mental health services, who are currently hugely limited in the UK." The research was funded by the Medical Research Council (part of UK Research & Innovation) and the Medical Research Foundation. Additional support was provided by the NIHR Cambridge Biomedical Resource Centre and the NIHR GOSH BRC.

CAPLYTA supplemental new drug applications (sNDAs) for the treatment of bipolar depression in adults as both monotherapy and adjunctive treatment with lithium or valproate have been accepted for review by the FDA, with a PDUFA target action date of December 17, 2021. First quarter CAPLYTA total prescriptions (TRx) increased 23% versus the previous quarter. Total revenues for the first quarter were $15.9 million. CAPLYTA achieved net product revenues of $15.6 million for the first quarter. Introduced ITI-1284 ODT-SL, a deuterated form of lumateperone delivered sublingually as an orally disintegrating tablet. NEW YORK, May 10, 2021 (GLOBE NEWSWIRE) -- Intra-Cellular Therapies, Inc. . (Nasdaq: ITCI), a biopharmaceutical company focused on the development and commercialization of therapeutics for central nervous system (CNS) disorders, today announced its financial results for the first quarter ended March 31, 2021 and provided a corporate update. “The acceptance of our sNDAs by the FDA is an important step towards a potential new treatment option for patients living with bipolar depression, a condition with a limited number of approved treatments. While preparing for this significant opportunity, our team will continue to execute on our commercial objectives for CAPLYTA and advance our robust pipeline,” said Dr. Sharon Mates, Chairman and CEO of Intra-Cellular Therapies. First Quarter Financial Highlights: Total revenues were $15.9 million for the first quarter of 2021, compared to $1.1 million of total revenues for the first quarter of 2020. Net product revenues of CAPLYTA were $15.6 million for the first quarter of 2021, compared to $0.9 million in net product revenues of CAPLYTA for the same period in 2020. Cost of product sales were $1.5 million in the first quarter of 2021 compared to $0.1 million for the first quarter of 2020. Research and development (R&D) expenses for the first quarter of 2021 were $15.1 million, compared to $16.0 million for the first quarter of 2020. This decrease is due primarily to a decrease in manufacturing expense and is partially offset by an increase of lumateperone clinical and non-clinical expenses. Selling, general and administrative (SG&A) expenses were $52.6 million for the first quarter of 2021, compared to $34.1 million for the same period in 2020. This increase is primarily due to an increase in sales related labor costs and commercialization costs. Net loss for the quarter ended March 31, 2021 was $52.7 million compared to a net loss of $47.4 million for the quarter ended March 31, 2020. Cash, cash equivalents, restricted cash and investment securities totaled $613.4 million at March 31, 2021, compared to $658.8 million at December 31, 2020. COMMERCIAL HIGHLIGHTS Despite the continued impact of COVID-19 on the healthcare system during the first quarter, our commercial organization continued to effectively engage with our prescribing audience through a hybrid model of in-person and virtual interactions, enhanced by digital marketing initiatives. First quarter CAPLYTA results reflect strong commercial execution delivering continued prescription growth, increasing total prescriptions 23% versus the fourth quarter. CAPLYTA market access coverage is strong with greater than 95% of covered lives in both Medicare Part D and State Medicaid, the major payer channels in schizophrenia. Our LytaLink program continues to be highly competitive and effective in supporting prescribing physicians and eligible patients’ access to CAPLYTA. CLINICAL HIGHLIGHTS Lumateperone - Bipolar Depression Program : The U.S. Food and Drug Administration (FDA) has accepted for review the sNDAs for lumateperone for the treatment of depressive episodes associated with bipolar I or II disorder (bipolar depression) as monotherapy and as adjunctive therapy with lithium or valproate. The FDA has assigned a PDUFA target action date of December 17, 2021 for these applications. At the American Psychiatric Association (APA) Annual Meeting held from May 1-3, 2021, we had several presentations describing lumateperone study results. These included results from Study ‘402, a global Phase 3 clinical trial evaluating lumateperone as adjunctive therapy to lithium or valproate in the treatment of major depressive episodes associated with bipolar I or bipolar II disorder and analyses from Study ‘404 highlighting the efficacy results of patients with bipolar depression who exhibit mixed features. Another presentation summarized the overall safety and tolerability profile of the bipolar depression monotherapy program. Other Lumateperone Programs Mixed Features program : Study ‘403 evaluating lumateperone 42 mg in patients with major depressive disorder (MDD) and in patients with bipolar depression who exhibit mixed features is ongoing. : Study ‘403 evaluating lumateperone 42 mg in patients with major depressive disorder (MDD) and in patients with bipolar depression who exhibit mixed features is ongoing. Adjunctive MDD program : Clinical conduct in two studies, Studies ‘501 and ‘502, our Phase 3 clinical trials evaluating lumateperone 42 mg as an adjunctive therapy to antidepressants for the treatment of MDD is anticipated to begin later this year. : Clinical conduct in two studies, Studies ‘501 and ‘502, our Phase 3 clinical trials evaluating lumateperone 42 mg as an adjunctive therapy to antidepressants for the treatment of MDD is anticipated to begin later this year. Lumateperone Long Acting Injectable (LLAI) formulation : Study ITI-007-025, a Phase 1 single ascending dose study of LLAI, a formulation designed to be administered subcutaneously and to maintain therapeutic levels of lumateperone for at least one month is ongoing. Initial results from this study are anticipated in the second half of 2021. CAPLYTA- Schizophrenia Announced the publication of “Safety and tolerability of lumateperone 42 mg: An open-label antipsychotic switch study in outpatients with stable schizophrenia” (Correll et al. 2021) in the journal, Schizophrenia Research. At APA we presented analyses from Study 303, our long-term safety schizophrenia study, evaluating the antidepressant effects of CAPLYTA in patients with schizophrenia with co-morbid depression, with and without concomitant antidepressant treatments. Other Programs ITI-1284 program : We introduced ITI-1284 ODT-SL, a deuterated form of lumateperone, a new molecular entity formulated as an orally disintegrating tablet for sublingual administration. We plan to initiate studies evaluating ITI-1284 ODT-SL for the treatment of behavioral disturbances in patients with dementia, the treatment of dementia-related psychosis and the treatment of certain depressive disorders in the elderly. : We introduced ITI-1284 ODT-SL, a deuterated form of lumateperone, a new molecular entity formulated as an orally disintegrating tablet for sublingual administration. We plan to initiate studies evaluating ITI-1284 ODT-SL for the treatment of behavioral disturbances in patients with dementia, the treatment of dementia-related psychosis and the treatment of certain depressive disorders in the elderly. Phosphodiesterase type I inhibitor (PDE1) program : Our PDE1 inhibitor program is focused on diseases in which the PDE1 enzyme is over-expressed and/or abnormal immune cell function contributes to disease pathology. This suggests therapeutic potential across a variety of diseases, including neurological and cardiovascular diseases, as well as cancer. We plan to advance our lead molecule, lenrispodun (ITI-214), into a Phase 2 clinical study in Parkinson’s disease in the second half of 2021. At the American Association for Cancer Research (AACR) Virtual Annual Meeting, we presented preclinical data supporting the potential of PDE1 inhibition to enhance the anti-tumor effects of immunotherapies by altering the tumor micro-environment. Our prior studies elucidating the neuroprotective and anti-inflammatory effects of PDE1 inhibitors in the brain by regulating microglia function (brain resident macrophage-like cells) led to our exploration of similar effects outside the brain. Therefore, we hypothesized PDE1 inhibition could result in antitumor effects by controlling similar functions of macrophages in the tumor micro-environment. Our experiments indicate PDE1 inhibition prevents the migration and accumulation of monocytes and macrophages in the tumor micro-environment and could represent a novel and broadly applicable approach to the treatment of immune responsive cancers. : Our PDE1 inhibitor program is focused on diseases in which the PDE1 enzyme is over-expressed and/or abnormal immune cell function contributes to disease pathology. This suggests therapeutic potential across a variety of diseases, including neurological and cardiovascular diseases, as well as cancer. ITI-333 program in opioid use disorder : Study ITI-333-001, a Phase 1 single ascending dose study evaluating the safety, tolerability and pharmacokinetics of ITI-333 in healthy volunteers is ongoing. Results from this study are anticipated in the second half of 2021. Conference Call and Webcast Details The Company will host a live conference call and webcast today at 8:30 AM Eastern Time to discuss the Company’s financial results and provide a corporate update. The live webcast and subsequent replay may be accessed by visiting the Company’s website at . Please connect to the Company’s website at least 5-10 minutes prior to the live webcast to ensure adequate time for any necessary software download. Alternatively, please call 1-(844) 835-6563 (U.S.) or 1-(970) 315-3916 (international) to listen to the live conference call. The conference ID number for the live call is 3244409. Please dial in approximately 10 minutes prior to the call. CAPLYTA® (lumateperone) is indicated for the treatment of schizophrenia in adults. CAPLYTA is available in 42 mg capsules. Important Safety Information Boxed Warning: Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. CAPLYTA is not approved for the treatment of patients with dementia-related psychosis. Contraindications: CAPLYTA is contraindicated in patients with known hypersensitivity to lumateperone or any components of CAPLYTA. Reactions have included pruritus, rash (e.g. allergic dermatitis, papular rash, and generalized rash), and urticaria. Warnings & Precautions: Antipsychotic drugs have been reported to cause: Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis , including stroke and transient ischemic attack. See Boxed Warning above. , including stroke and transient ischemic attack. See Boxed Warning above. Neuroleptic Malignant Syndrome (NMS) , which is a potentially fatal reaction. Signs and symptoms include: high fever, stiff muscles, confusion, changes in breathing, heart rate, and blood pressure, elevated creatinine phosphokinase, myoglobinuria (and/or rhabdomyolysis), and acute renal failure. Patients who experience signs and symptoms of NMS should immediately contact their doctor or go to the emergency room. , which is a potentially fatal reaction. Signs and symptoms include: high fever, stiff muscles, confusion, changes in breathing, heart rate, and blood pressure, elevated creatinine phosphokinase, myoglobinuria (and/or rhabdomyolysis), and acute renal failure. Patients who experience signs and symptoms of NMS should immediately contact their doctor or go to the emergency room. Tardive Dyskinesia , a syndrome of uncontrolled body movements in the face, tongue, or other body parts, which may increase with duration of treatment and total cumulative dose. TD may not go away, even if CAPLYTA is discontinued. It can also occur after CAPLYTA is discontinued. , a syndrome of uncontrolled body movements in the face, tongue, or other body parts, which may increase with duration of treatment and total cumulative dose. TD may not go away, even if CAPLYTA is discontinued. It can also occur after CAPLYTA is discontinued. Metabolic Changes , including hyperglycemia, diabetes mellitus, dyslipidemia, and weight gain. Hyperglycemia, in some cases extreme and associated with ketoacidosis, hyperosmolar coma or death, has been reported in patients treated with antipsychotics. Measure weight and assess fasting plasma glucose and lipids when initiating CAPLYTA and monitor periodically during long-term treatment. , including hyperglycemia, diabetes mellitus, dyslipidemia, and weight gain. Hyperglycemia, in some cases extreme and associated with ketoacidosis, hyperosmolar coma or death, has been reported in patients treated with antipsychotics. Measure weight and assess fasting plasma glucose and lipids when initiating CAPLYTA and monitor periodically during long-term treatment. Leukopenia, Neutropenia, and Agranulocytosis (including fatal cases) . Complete blood counts should be performed in patients with pre-existing low white blood cell count (WBC) or history of leukopenia or neutropenia. CAPLYTA should be discontinued if clinically significant decline in WBC occurs in absence of other causative factors. . Complete blood counts should be performed in patients with pre-existing low white blood cell count (WBC) or history of leukopenia or neutropenia. CAPLYTA should be discontinued if clinically significant decline in WBC occurs in absence of other causative factors. Decreased Blood Pressure & Dizziness . Patients may feel lightheaded, dizzy or faint when they rise too quickly from a sitting or lying position (orthostatic hypotension). Heart rate and blood pressure should be monitored and patients should be warned with known cardiovascular or cerebrovascular disease. Orthostatic vital signs should be monitored in patients who are vulnerable to hypotension. . Patients may feel lightheaded, dizzy or faint when they rise too quickly from a sitting or lying position (orthostatic hypotension). Heart rate and blood pressure should be monitored and patients should be warned with known cardiovascular or cerebrovascular disease. Orthostatic vital signs should be monitored in patients who are vulnerable to hypotension. Falls . CAPLYTA may cause sleepiness or dizziness and can slow thinking and motor skills, which may lead to falls and, consequently, fractures and other injuries. Patients should be assessed for risk when using CAPLYTA. . CAPLYTA may cause sleepiness or dizziness and can slow thinking and motor skills, which may lead to falls and, consequently, fractures and other injuries. Patients should be assessed for risk when using CAPLYTA. Seizures . CAPLYTA should be used cautiously in patients with a history of seizures or with conditions that lower seizure threshold. . CAPLYTA should be used cautiously in patients with a history of seizures or with conditions that lower seizure threshold. Sleepiness and Trouble Concentrating . Patients should use caution when operating machinery or motor vehicles until they know how CAPLYTA affects them. . Patients should use caution when operating machinery or motor vehicles until they know how CAPLYTA affects them. Body Temperature Dysregulation . CAPLYTA should be used with caution in patients who may experience conditions that may increase core body temperature such as strenuous exercise, extreme heat, dehydration, or concomitant anticholinergics. . CAPLYTA should be used with caution in patients who may experience conditions that may increase core body temperature such as strenuous exercise, extreme heat, dehydration, or concomitant anticholinergics. Dysphagia. CAPLYTA should be used with caution in patients at risk for aspiration. Drug Interactions: CAPLYTA should not be used with CYP3A4 inducers, moderate or strong CYP3A4 inhibitors and UGT inhibitors. Special Populations: Newborn infants exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. Breastfeeding is not recommended. Use of CAPLYTA should be avoided in patients with moderate or severe liver problems. Adverse Reactions: The most common adverse reactions in clinical trials with CAPLYTA vs. placebo were somnolence/sedation (24% vs. 10%) and dry mouth (6% vs. 2%). Please click here to see full Prescribing Information including Boxed Warning . About CAPLYTA (lumateperone) CAPLYTA 42mg/day is an oral, once daily atypical antipsychotic approved for the treatment of schizophrenia of adults. While the mechanism of action of CAPLYTA in the treatment of schizophrenia is unknown, the efficacy of CAPLYTA could be mediated through a combination of antagonist activity at central serotonin 5-HT2A receptors and postsynaptic antagonist activity at central dopamine D2 receptors. Lumateperone is being investigated for the treatment of bipolar depression, depression and other neuropsychiatric and neurological disorders. CAPLYTA is not FDA approved for these disorders. About Intra-Cellular Therapies Intra-Cellular Therapies is a biopharmaceutical company founded on Nobel prize-winning research that allows us to understand how therapies affect the inner-workings of cells in the body. The company leverages this intracellular approach to develop innovative treatments for people living with complex psychiatric and neurologic diseases. For more information, please visit . Forward-Looking Statements This news release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 that involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. Such forward-looking statements include statements regarding, among other things, our expectations regarding the commercialization of CAPLYTA; our expectations regarding the sNDAs, including the adequacy of the data contained in the sNDAs to serve as the basis for approval of lumateperone for the treatment of depressive episodes associated with bipolar I or II disorder both as monotherapy and as adjunctive therapy in adults; the potential approval by the FDA of the sNDAs for lumateperone for the treatment of bipolar depression; the potential timing of review and action by the FDA with respect to the sNDAs; our plans and expected timing to initiate our lumateperone clinical studies in major depressive disorder; our plans and expected timing for results from our lumateperone long-acting injectable clinical trial; our plans and expected timing for results from our ITI-333 clinical trial; our development plans for our PDE program, including ITI-214, and the potential benefits of PDE1 inhibition; our development plans for our ITI-1284 program; our beliefs about the potential utility of our product candidates; and development efforts and plans under the caption “About Intra-Cellular Therapies.” All such forward-looking statements are based on management's present expectations and are subject to certain factors, risks and uncertainties that may cause actual results, outcome of events, timing and performance to differ materially from those expressed or implied by such statements. These risks and uncertainties include, but are not limited to, the following: whether the preclinical and clinical results of the lumateperone studies will meet the regulatory requirements for approval by the FDA for the proposed indications; whether the sNDAs will be approved by the FDA and whether the FDA will complete its review within its target timelines, including its target action date; whether the FDA will require additional information, whether we will be able to provide in a timely manner any additional information that the FDA requests, and whether such additional information will be satisfactory to the FDA; there are no guarantees that CAPLYTA will be commercially successful; we may encounter issues, delays or other challenges in commercializing CAPLYTA; the COVID-19 pandemic may negatively impact our commercial plans and sales for CAPLYTA; the COVID-19 pandemic may negatively impact the conduct of, and the timing of enrollment, completion and reporting with respect to, our clinical trials; whether CAPLYTA receives adequate reimbursement from third-party payors; the degree to which CAPLYTA receives acceptance from patients and physicians for its approved indication; challenges associated with execution of our sales activities, which in each case could limit the potential of our product; results achieved in CAPLYTA in the treatment of schizophrenia following commercial launch of the product may be different than observed in clinical trials, and may vary among patients; any other impacts on our business as a result of or related to the COVID-19 pandemic; risks associated with our current and planned clinical trials; we may encounter unexpected safety or tolerability issues with CAPLYTA following commercial launch for the treatment of schizophrenia or in ongoing or future trials and other development activities; our other product candidates may not be successful or may take longer and be more costly than anticipated; product candidates that appeared promising in earlier research and clinical trials may not demonstrate safety and/or efficacy in larger-scale or later clinical trials or in clinical trials for other indications; our proposals with respect to the regulatory path for our product candidates may not be acceptable to the FDA; our reliance on collaborative partners and other third parties for development of our product candidates; and the other risk factors detailed in our public filings with the Securities and Exchange Commission. All statements contained in this press release are made only as of the date of this press release, and we do not intend to update this information unless required by law. Contact: Intra-Cellular Therapies, Inc. Juan Sanchez, M.D. Vice President, Corporate Communications and Investor Relations 646-440-9333 Burns McClellan, Inc. Lisa Burns cradinovic@burnsmc.com 212-213-0006 MEDIA INQUIRIES: Ana Fullmer Corporate Media Relations W2Owcg afullmer@wcgworld.com 202-507-0130 INTRA-CELLULAR THERAPIES, INC. CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (1) The condensed consolidated statements of operations for the quarters ended March 31, 2021 and 2020 have been derived from the financial statements but do not include all of the information and footnotes required by accounting principles generally accepted in the United States for complete financial statements. INTRA-CELLULAR THERAPIES, INC. CONDENSED CONSOLIDATED BALANCE SHEETS (1) The condensed consolidated balance sheets at March 31, 2021 and December 31, 2020 have been derived from the financial statements but do not include all of the information and footnotes required by accounting principles generally accepted in the United States for complete financial statements.