Hyperglycemic Hyperosmolar Nonketotic Coma

UZEDY is currently approved in the US as a subcutaneous long-acting injectable (LAI) for use every one or two months for the treatment of schizophrenia in adults 1 LAI treatment options may help address unmet needs of people living with bipolar I disorder (BP-I) BP-I filing acceptance for UZEDY represents Teva’s commitment to pursuing new advances in neuroscience PARSIPPANY, N.J. and TEL AVIV, Israel and PARIS, Feb. 25, 2025 (GLOBE NEWSWIRE) -- Teva Pharmaceuticals, a U.S. affiliate of Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA), and Medincell (Euronext: MEDCL) announced today that the supplemental New Drug Application (sNDA) for UZEDY extended-release injectable suspension for the maintenance treatment of BP-I in adults has been accepted for filing by the U.S. Food and Drug Administration (FDA). The sNDA is based on leveraging the existing clinical data for UZEDY coupled with the Agency’s previous findings of safety and efficacy of past risperidone formulations approved for the treatment of BP-I. “Since the FDA approval of UZEDY almost two years ago, it has proven to be an important treatment option for people living with schizophrenia,” said Eric Hughes, MD, PhD, Executive Vice President of Global R&D and Chief Medical Officer at Teva. “Today’s filing demonstrates the potential of UZEDY’s clinical pro a long-acting treatment for bipolar-I, a complex mental health disorder that significantly affects a person’s mood, behavior, and overall state of mind. Debilitating manic and depressive symptoms and signs can also occur.” Teva will lead the regulatory process and be responsible for potential commercialization of UZEDY for BP-I, with Medincell eligible for royalties on net sales. “Long-acting injectables are key drivers of innovation in the CNS field today,” said Dr. Richard Malamut, Chief Medical Officer at Medincell. “In bipolar I disorder, as in schizophrenia, nonadherence remains a major barrier to effective care, one that UZEDY has the potential to help. We are proud to partner with Teva to deliver treatment options aimed at meeting unmet medical needs.” UZEDY was approved in the U.S. for the treatment of schizophrenia in adults in 2023. 2 The efficacy and long-term safety and tolerability of UZEDY for the treatment of schizophrenia have been evaluated in two Phase 3 pivotal studies: TV46000-CNS-30072 (the RISE Study – The Risperidone Subcutaneous Extended-Release Study) 3 and TV46000-CNS-30078 (the SHINE Study – Safety in Humans of TV-46000 sc INjection Evaluation) 2 . The safety and efficacy of UZEDY for BP-I are not established and UZEDY is not approved by any regulatory authority for this indication. About Bipolar I Disorder Bipolar Disorder I (BP-I) is a manic-depressive condition that leads to large swings in mood and actions that greatly impact quality of life and ability to complete day-to-day tasks. It is challenging to diagnose and is often accompanied by other psychiatric comorbidities. BP-I is associated with poor long-term outcomes and a substantial increase in mortality compared to the general population from both suicide and cardiovascular disease. An estimated 1% or 3,400,000+ of U.S. adults will develop BP-I in their lifetime. 4 About the RISE Study RISE, Teva’s Phase 3 study, was a multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy of risperidone extended-release injectable suspension for subcutaneous use as a treatment in patients (ages 13-65 years) with schizophrenia. 3 544 patients were randomized to receive a subcutaneous injection of UZEDY once monthly (q1M), once every two months (q2M), or placebo in a 1:1:1 ratio. The primary endpoint was time to impending relapse. 3 About the SHINE Study The second of Teva’s Phase 3 studies; designed to evaluate the long-term safety, tolerability and effectof UZEDY subcutaneously administered q1M or q2M for up to 56 weeks in 331 patients (ages 13-65 years) with schizophrenia. The primary endpoint was the frequency of all adverse events, including serious adverse events. 2 About UZEDY UZEDY (risperidone) extended-release injectable suspension for subcutaneous use is indicated for the treatment of schizophrenia in adults. In clinical trials, UZEDY significantly reduced the risk of schizophrenia relapse. 1, 2 UZEDY administers risperidone through copolymer technology under license from Medincell that allows for absorption and sustained release after subcutaneous injection. UZEDY is the only long-acting, subcutaneous formulation of risperidone available in both one- and two-month dosing intervals. 1 For full prescribing information, visit . INDICATION AND USAGE UZEDY (risperidone) extended-release injectable suspension for subcutaneous use is indicated for the treatment of schizophrenia in adults. WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. UZEDY is not approved for use in patients with dementia-related psychosis and has not been studied in this patient population. See below for additional Important Safety Information. IMPORTANT SAFETY INFORMATION CONTINUED CONTRAINDICATIONS: UZEDY is contraindicated in patients with a known hypersensitivity to risperidone, its metabolite, paliperidone, or to any of its components. Hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported in patients treated with risperidone or paliperidone. WARNINGS AND PRECAUTIONS Cerebrovascular Adverse Reactions: In trials of elderly patients with dementia-related psychosis, there was a significantly higher incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, in patients treated with oral risperidone compared to placebo. UZEDY is not approved for use in patients with dementia-related psychosis. Neuroleptic Malignant Syndrome (NMS): NMS, a potentially fatal symptom complex, has been reported in association with antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status including delirium, and autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. If NMS is suspected, immediately discontinue UZEDY and provide symptomatic treatment and monitoring. Tardive Dyskinesia (TD): TD, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements, may develop in patients treated with antipsychotic drugs. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to predict which patients will develop the syndrome. Whether antipsychotic drug products differ in their potential to cause TD is unknown. The risk of developing TD and the likelihood that it will become irreversible are believed to increase with the duration of treatment and the cumulative dose. The syndrome can develop, after relatively brief treatment periods, even at low doses. It may also occur after discontinuation. TD may remit, partially or completely, if antipsychotic treatment is discontinued. Antipsychotic treatment, itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome, possibly masking the underlying process. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown. If signs and symptoms of TD appear in a patient treated with UZEDY, drug discontinuation should be considered. However, some patients may require treatment with UZEDY despite the presence of the syndrome. In patients who do require chronic treatment, use the lowest dose and the shortest duration of treatment producing a satisfactory clinical response. Periodically reassess the need for continued treatment. Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/cerebrovascular risk. These metabolic changes include hyperglycemia, dyslipidemia, and body weight gain. While all of the drugs in the class have been shown to produce some metabolic changes, each drug has its own specific risk profile. Hyperglycemia and diabetes mellitus (DM): in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, have been reported in patients treated with atypical antipsychotics, including risperidone. Patients with an established diagnosis of DM who are started on atypical antipsychotics, including UZEDY, should be monitored regularly for worsening of glucose control. Patients with risk factors for DM (e.g., obesity, family history of diabetes) who are starting treatment with atypical antipsychotics, including UZEDY, should undergo fasting blood glucose (FBG) testing at the beginning of treatment and periodically during treatment. Any patient treated with atypical antipsychotics, including UZEDY, should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics, including UZEDY, should undergo FBG testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic, including risperidone, was discontinued; however, some patients required continuation of antidiabetic treatment despite discontinuation of risperidone. Dyslipidemia has been observed in patients treated with atypical antipsychotics. Weight gain has been observed with atypical antipsychotic use. Monitoring weight is recommended. Hyperprolactinemia: As with other drugs that antagonize dopamine D 2 receptors, risperidone elevates prolactin levels and the elevation persists during chronic administration. Risperidone is associated with higher levels of prolactin elevation than other antipsychotic agents. Orthostatic Hypotension and Syncope: UZEDY may induce orthostatic hypotension associated with dizziness, tachycardia, and in some patients, syncope. UZEDY should be used with particular caution in patients with known cardiovascular disease, cerebrovascular disease, and conditions which would predispose patients to hypotension and in the elderly and patients with renal or hepatic impairment. Monitoring of orthostatic vital signs should be considered in all such patients, and a dose reduction should be considered if hypotension occurs. Clinically significant hypotension has been observed with concomitant use of oral risperidone and antihypertensive medication. Falls: Antipsychotics, including UZEDY, may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other fall-related injuries. Somnolence, postural hypotension, motor and sensory instability have been reported with the use of risperidone. For patients, particularly the elderly, with diseases, conditions, or medications that could exacerbate these effects, assess the risk of falls when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy. Leukopenia, Neutropenia, and Agranulocytosis have been reported with antipsychotic agents, including risperidone. In patients with a pre-existing history of a clinically significant low white blood cell count (WBC) or absolute neutrophil count (ANC) or a history of drug-induced leukopenia or neutropenia, perform a complete blood count (CBC) frequently during the first few months of therapy. In such patients, consider discontinuation of UZEDY at the first sign of a clinically significant decline in WBC in the absence of other causative factors. Monitor patients with clinically significant neutropenia for fever or other symptoms or signs of infection and treat promptly if such symptoms or signs occur. Discontinue UZEDY in patients with ANC < 1000/mm 3 ) and follow their WBC until recovery. Potential for Cognitive and Motor Impairment: UZEDY, like other antipsychotics, may cause somnolence and has the potential to impair judgement, thinking, and motor skills. Somnolence was a commonly reported adverse reaction associated with oral risperidone treatment. Caution patients about operating hazardous machinery, including motor vehicles, until they are reasonably certain that treatment with UZEDY does not affect them adversely. Seizures: During premarketing studies of oral risperidone in adult patients with schizophrenia, seizures occurred in 0.3% of patients (9 out of 2,607 patients), two in association with hyponatremia. Use UZEDY cautiously in patients with a history of seizures or other conditions that potentially lower the seizure threshold. Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Antipsychotic drugs, including UZEDY, should be used cautiously in patients at risk for aspiration. Priapism has been reported during postmarketing surveillance for other risperidone products. A case of priapism was reported in premarket studies of UZEDY. Severe priapism may require surgical intervention. Body temperature regulation . Disruption of the body’s ability to reduce core body temperature has been attributed to antipsychotic agents. Both hyperthermia and hypothermia have been reported in association with oral risperidone use. Strenuous exercise, exposure to extreme heat, dehydration, and anticholinergic medications may contribute to an elevation in core body temperature; use UZEDY with caution in patients who experience these conditions. ADVERSE REACTIONS The most common adverse reactions with risperidone (≥5% and greater than placebo) were parkinsonism, akathisia, dystonia, tremor, sedation, dizziness, anxiety, blurred vision, nausea, vomiting, upper abdominal pain, stomach discomfort, dyspepsia, diarrhea, salivary hypersecretion, constipation, dry mouth, increased appetite, increased weight, fatigue, rash, nasal congestion, upper respiratory tract infection, nasopharyngitis, and pharyngolaryngeal pain. The most common injection site reactions with UZEDY (≥5% and greater than placebo) were pruritus and nodule. DRUG INTERACTIONS Carbamazepine and other strong CYP3A4 inducers decrease plasma concentrations of risperidone. Fluoxetine, paroxetine, and other strong CYP2D6 inhibitors increase risperidone plasma concentration. Due to additive pharmacologic effects, the concomitant use of centrally-acting drugs, including alcohol, may increase nervous system disorders. UZEDY may enhance the hypotensive effects of other therapeutic agents with this potential. UZEDY may antagonize the pharmacologic effects of dopamine agonists. Concomitant use with methylphenidate, when there is change in dosage of either medication, may increase the risk of extrapyramidal symptoms (EPS) USE IN SPECIFIC POPULATIONS Pregnancy: May cause EPS and/or withdrawal symptoms in neonates with third trimester exposure. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including UZEDY, during pregnancy. Healthcare providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or online at . Lactation: Infants exposed to risperidone through breastmilk should be monitored for excess sedation, failure to thrive, jitteriness, and EPS. Fertility: UZEDY may cause a reversible reduction in fertility in females. Pediatric Use: Safety and effectiveness of UZEDY have not been established in pediatric patients. Renal or Hepatic Impairment: Carefully titrate on oral risperidone up to at least 2 mg daily before initiating treatment with UZEDY. Patients with Parkinson’s disease or dementia with Lewy bodies can experience increased sensitivity to UZEDY. Manifestations and features are consistent with NMS. Please see the full Prescribing Information for UZEDY, including Boxed WARNING. About Teva Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) is a different kind of global pharmaceutical leader, one that operates across the full spectrum of innovation to reliably deliver medicines to patients worldwide. For over 120 years, Teva’s commitment to bettering health has never wavered. Today, the company’s global network of capabilities enables its 37,000 employees across 57 markets to advance health by developing medicines for the future while championing the production of generics and biologics. If patients have a need, we’re already working to address it. To learn more about how Teva is all in for better health, visit . Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, which are based on management’s current beliefs and expectations and are subject to substantial risks and uncertainties, both known and unknown, that could cause our future results, performance or achievements to differ significantly from that expressed or implied by such forward-looking statements. You can identify these forward-looking statements by the use of words such as “should,” “expect,” “anticipate,” “estimate,” “target,” “may,” “project,” “guidance,” “intend,” “plan,” “believe” and other words and terms of similar meaning and expression in connection with any discussion of future operating or financial performance. Important factors that could cause or contribute to such differences include risks relating to: our ability to successfully develop and commercialize UZEDY (risperidone) extended-release injectable suspension for the maintenance treatment of BP-I in adult patients; our ability to successfully compete in the marketplace, including our ability to develop and commercialize additional pharmaceutical products; our ability to successfully execute our Pivot to Growth strategy, including to expand our innovative and biosimilar medicines pipeline and profitably commercialize the innovative medicines and biosimilar portfolio, whether organically or through business development, and to sustain and focus our portfolio of generic medicines; and other factors discussed in our Annual Report on Form 10-K for the year ended December 31, 2024, including in the section captioned “Risk Factors and “Forward Looking Statements.” Forward-looking statements speak only as of the date on which they are made, and we assume no obligation to update or revise any forward-looking statements or other information contained herein, whether as a result of new information, future events or otherwise. You are cautioned not to put undue reliance on these forward-looking statements. UZEDY® (risperidone) extended-release injectable suspension, for subcutaneous injection Current Prescribing Information. Parsippany, NJ. Teva Neuroscience, Inc. Data on file. Parsippany, NJ: Teva Neuroscience, Inc. Clinicaltrials.gov. Study to Evaluate TV-46000 as Maintenance Treatment in Adult and Adolescent Participants With Schizophrenia (RISE). Accessed November 2024. Merikangas KR, Akiskal HS, Angst J, et al. Lifetime and 12-Month Prevalence of Bipolar Spectrum Disorder in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2007;64(5):543–552. doi:10.1001/archpsyc.64.5.543 Teva Media Inquiries: TevaCommunicationsNorthAmerica@tevapharm.com Teva Investor Relations Inquires TevaIR@Tevapharm.com About Medincell Medincell is a clinical- and commercial-stage biopharmaceutical licensing company developing long-acting injectable drugs in many therapeutic areas. Our innovative treatments aim to guarantee compliance with medical prescriptions, to improve the effectiveness and accessibility of medicines, and to reduce their environmental footprint. They combine active pharmaceutical ingredients with our proprietary BEPO® technology which controls the delivery of a drug at a therapeutic level for several days, weeks or months from the subcutaneous or local injection of a simple deposit of a few millimeters, entirely bioresorbable. The first treatment based on BEPO® technology, intended for the treatment of schizophrenia, was approved by the FDA in April 2023, and is now distributed in the United States by Teva under the name UZEDY® (BEPO® technology is licensed to Teva under the name SteadyTeq™). We collaborate with leading pharmaceutical companies and foundations to improve global health through new treatment options. Based in Montpellier, Medincell currently employs more than 140 people representing more than 25 different nationalities. Contact: communication@medincell.com

Fourth quarter 2024 CAPLYTA net product sales grew to $199.2 million , representing a 51% increase over the same period in 2023 Full year 2024 CAPLYTA net product sales were $680.5 million , representing year-over-year growth of 47% The U.S. Food and Drug Administration (FDA) accepted for review the lumateperone supplemental New Drug Application (sNDA) submission for adjunctive treatment of major depressive disorder (MDD) BEDMINSTER, N.J. , Feb. 21, 2025 (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 fourth quarter ended December 31, 2024 and provided a corporate update. Financial Highlights Net product sales of CAPLYTA were $680.5 million for the full year 2024. This represents an increase of 47% compared to 2023. Net product sales of CAPLYTA were $199.2 million for the fourth quarter of 2024, compared to $131.5 million for the same period in 2023, representing 51% growth. Selling, general and administrative (SG&A) expenses were $504.5 million for the year ended December 31, 2024 , compared to $409.9 million for the same period in 2023. This increase is primarily due to an increase in commercialization, marketing and infrastructure costs. Research and development (R&D) expenses were $236.1 million for the year ended December 31, 2024 , compared to $180.1 million for the same period in 2023. This increase is primarily due to higher lumateperone and non-lumateperone project costs, including the ITI-1284, ITI-214, and ITI-1500 programs. Cash, cash equivalents, investment securities, and restricted cash totaled $1.0 billion on December 31, 2024 , compared to $499.7 million at December 31, 2023 . Commercial and Clinical Highlights In the first quarter of 2025, we commenced a field sales force expansion in anticipation of the potential approval of CAPLYTA for the adjunctive treatment of MDD. The FDA has accepted for review the sNDA for lumateperone, an investigational agent for the treatment of MDD as adjunctive therapy. Two positive Phase 3 global placebo-controlled studies, Study 501 and Study 502, as well as the long term open-label safety Study 503, form the basis of the sNDA. Advancing our pipeline: In 2024, we initiated 10 late-stage clinical trials including six Phase 3 lumateperone clinical trials and four ITI-1284 clinical trials.Lumateperone: In our pediatric program, in the fourth quarter of 2024, we commenced patient enrollment in two Phase 3 studies in pediatric patients for the treatment of irritability associated with autism spectrum disorder. Patient enrollment is ongoing in our double-blind, placebo-controlled study in bipolar depression and in our open-label safety study in schizophrenia and bipolar disorder in pediatric patients.Patient enrollment is ongoing in our two Phase 3 studies evaluating lumateperone in adults in the acute treatment of manic or mixed episodes associated with bipolar I disorder (bipolar mania). ITI-1284-ODT-SL program: Patient enrollment is ongoing in two Phase 2 clinical studies evaluating ITI-1284 in patients with generalized anxiety disorder (GAD). Our first study evaluates ITI-1284 as an adjunctive therapy to approved GAD medications while a second study evaluates ITI-1284 as monotherapy.Patient enrollment continues in a Phase 2 clinical study evaluating ITI-1284 in patients with psychosis associated with Alzheimer’s disease (AD) and in our Phase 2 program in agitation associated with AD. Other pipeline programs:Phosphodiesterase type I inhibitor (PDE1) program: Patient enrollment in our lenrispodun (ITI-214) Phase 2 Study in Parkinson’s disease (PD) is ongoing. Our second PDE1 inhibitor, ITI-1020 being developed in oncology indications, continues its Phase 1 single ascending dose study in healthy volunteers.ITI-1500 non-hallucinogenic neuroplastogen program: ITI-1549 is advancing IND enabling studies. Important Safety Information Boxed Warnings: 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. Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adults in short-term studies. All antidepressant-treated patients should be closely monitored for clinical worsening, and for emergence of suicidal thoughts and behaviors. The safety and effectiveness of CAPLYTA have not been established in pediatric patients. 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. 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. 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. 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. 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. 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. 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. Seizures. CAPLYTA should be used cautiously in patients with a history of seizures or with conditions that lower seizure threshold. Potential for Cognitive and Motor Impairment. 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. Dysphagia. CAPLYTA should be used with caution in patients at risk for aspiration. Drug Interactions: CAPLYTA should not be used with CYP3A4 inducers. Dose reduction is recommended for concomitant use with strong CYP3A4 inhibitors or moderate CYP3A4 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. Dose reduction is recommended for patients with moderate or severe hepatic impairment. Adverse Reactions: The most common adverse reactions in clinical trials with CAPLYTA vs. placebo were somnolence/sedation, dizziness, nausea, and dry mouth. CAPLYTA is available in 10.5 mg, 21 mg, and 42 mg capsules. Please click here to see full Prescribing Information including Boxed Warning. About CAPLYTA (lumateperone) CAPLYTA 42 mg is an oral, once daily atypical antipsychotic approved in adults for the treatment of schizophrenia and the treatment of depressive episodes associated with bipolar I or II disorder (bipolar depression) as monotherapy and as adjunctive therapy with lithium or valproate. While the mechanism of action of CAPLYTA 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 studied for the treatment of major depressive disorder, and other psychiatric and neurological disorders. Lumateperone 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 www.intracellulartherapies.com. 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, the potential approval of CAPLYTA (lumateperone) for the treatment of major depressive disorder as adjunctive therapy; our financial and operating performance, including our future revenues and expenses; our expectations regarding the commercialization of CAPLYTA; our plans to expand our sales force; our plans to conduct clinical or non-clinical trials and the timing of developments with respect to those trials, including enrollment, initiation or completion of clinical conduct, or the availability or reporting of results; whether clinical trial results will be predictive of future real-world results; whether CAPLYTA will serve an unmet need; the goals of our development programs; 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: there is no guarantee we will complete the pending transaction with Johnson & Johnson within the timeframe we anticipate or at all; there are no guarantees that CAPLYTA will be commercially successful; we may encounter issues, delays or other challenges in commercializing CAPLYTA; whether CAPLYTA receives adequate reimbursement from third-party payors; the degree to which CAPLYTA receives acceptance from patients and physicians for its approved indications; 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 and bipolar depression following commercial launch of the product may be different than observed in clinical trials, and may vary among patients; challenges associated with supply and manufacturing activities, which in each case could limit our sales and the availability of our product; 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 bipolar depression or in ongoing or future trials and other development activities; there is no guarantee that a generic equivalent of CAPLYTA will not be approved and enter the market before the expiration of our patents; there is no guarantee that our sNDA for the adjunctive treatment of MDD will be approved, if at all, on the timeline that we expect; 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; impacts on our business, including on the commercialization of CAPLYTA and our clinical trials, as a result of the COVID-19 pandemic, the conflicts in Ukraine , Russia and the Middle East , global economic uncertainty, inflation, higher interest rates or market disruptions; 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 Relations646-440-9333 Burns McClellan, Inc. Cameron Radinovic cradinovic@burnsmc.com212-213-0006 (1) The condensed consolidated statements of operations for the three and twelve months ended December 31, 2024 and 2023 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. (2) Some amounts in this statement may not add due to rounding. All percentages have been calculated using unrounded amounts. The condensed consolidated balance sheets at December 31, 2024 and December 31, 2023 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. Source: Intra-Cellular Therapies, Inc.

Presentations complement topline data with new data from two pivotal studies (Studies 501 and 502) evaluating lumateperone as an adjunctive therapy for the treatment of major depressive disorder Data shows robust remission and response efficacy rates in patients taking CAPLYTA Robust improvements in anxiety symptoms were also observed in patients taking CAPLYTA as measured by the Generalized Anxiety Disorder Questionnaire (GAD-7) Pooled safety and tolerability data from Studies 501 and 502 show favorable safety and tolerability profile for CAPLYTA consistent with prior studies A post-hoc analysis from Study 403 in mixed features shows CAPLYTA significantly improved anhedonia symptoms as measured by the MADRS anhedonia factor score BEDMINSTER, N.J., Dec. 11, 2024 (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 presentations at the 63rd Annual Meeting of the American College of Neuropsychopharmacology (ACNP) which included new efficacy, safety, and tolerability analyses from its CAPLYTA adjunctive major depressive disorder (MDD) pivotal program. “We have previously shared positive results from Studies 501 and 502 demonstrating a robust clinical profile of CAPLYTA as an adjunctive treatment in MDD with strong efficacy results in the Montgomery Asberg Depression Rating Scale (MADRS) total score, the Clinical Global Impression Scale for Severity of Illness (CGI-S) and the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR-16) scale. We are excited to share new data that further characterize CAPLYTA’s robust efficacy and favorable safety and tolerability profile,” said Dr. Suresh Durgam, Executive Vice President and Chief Medical Officer of Intra-Cellular Therapies. “In addition, the improvements in anhedonia symptoms observed in Study 403 further contribute to enriching CAPLYTA’s profile in the treatment of MDD and bipolar depression.” Details of the presentations are as follows: Poster T126 “Lumateperone as Adjunctive Therapy in Patients with Major Depressive Disorder: Results from a Randomized, Double-blind, Phase 3 Trial,” Tuesday, December 10 Poster W85 “Adjunctive Lumateperone in Patients With Major Depressive Disorder: Results From an Additional Randomized, Double-Blind, Phase 3 Trial,” Wednesday, December 11 These poster presentations highlight the efficacy of lumateperone 42mg adjunctive to anti-depressant therapy (ADT) shown in two similarly designed trials (Studies 501 and 502). In these studies, lumateperone 42 mg demonstrated significant and clinically meaningful efficacy over placebo, improving depressive symptoms and disease severity. Lumateperone plus ADT improved depression as measured by both clinician-rated and patient-reported outcomes (MADRS total score, CGI-S score, and QIDS-SR-16 total score). Subject to FDA approval, we believe these results demonstrate lumateperone represents a promising new treatment option for adults with MDD with inadequate response to prior ADT. In both studies, MADRS response and remission rates were significantly greater with lumateperone compared to placebo. Specifically, in Study 501 the response rates for CAPLYTA were 45.6% vs. 24.0% for placebo (p<0.0001) and remission rates were 25.9% vs. 13.6% for placebo (p<0.001). In Study 502 the response rates for CAPLYTA were 40.1% vs. 25.3% for placebo (p<0.01) and remission rates were 25.0% vs. 13.5% for placebo (p<0.01). In Study 501 anxiety symptoms were measured using the GAD-7 scale. Lumateperone plus ADT significantly improved self-reported anxiety symptoms, as measured by the GAD-7 total score, compared with placebo from baseline to Day 43 (Cohen’s d effect size (ES): 0.43; p<0.0001). Poster W84 “Safety and Tolerability of Lumateperone 42 mg for the Treatment of Major Depressive Disorder: A Pooled Analysis of 2 Randomized Placebo-Controlled Trials,” Wednesday, December 11 A pooled analysis of Studies 501 and 502 demonstrates the safety and tolerability of lumateperone 42 mg plus ADT in patients with MDD who had inadequate response to ADT. The most common adverse reactions in the lumateperone group (defined as ≥5% of patients and at more than twice the rate of placebo) were dizziness, dry mouth, somnolence, nausea, and fatigue. In Studies 501 and 502 changes in cardiometabolic parameters, prolactin levels and body morphology with lumateperone were similar to placebo. The risk of extrapyramidal symptoms and motor symptoms with lumateperone was low. Poster W88 “Lumateperone Treatment for Major Depressive Episodes With Mixed Features in Major Depressive Disorder and Bipolar I or Bipolar II Disorder: A Post Hoc Analysis of Anhedonia,” Wednesday, December 11 The poster reports on a post-hoc analysis from Study 403 evaluating the efficacy of lumateperone 42mg monotherapy in improving the anhedonia factor score in patients with MDD or bipolar depression with mixed features. The results from this analysis support lumateperone to treat the broad range of anhedonia symptoms of a major depressive episode in these patient populations. Anhedonia, which is diminished interest or pleasure, occurs in approximately 70% of patients with MDD and approximately 50% of patients with bipolar depression. Heightened levels of anhedonia in mood disorders are associated with more severe and recurrent depressive illness, a greater risk of suicidal ideation, and poorer treatment response compared with lower levels of anhedonia. Lumateperone significantly improved the MADRS anhedonia factor score from baseline to Day 43 compared with placebo in the combined MDD/bipolar depression population with mixed features (least squares mean difference (LSMD)= -3.4; ES= 0.63; p<0.0001) as well as both individual populations of patients with MDD with mixed features (LSMD= -3.4; ES= 0.63; p<0.0001) and bipolar depression with mixed features (LSMD= -3.3; ES= 0.61; p<0.0001). CAPLYTA® (lumateperone) is indicated in adults for the treatment of schizophrenia and 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. Important Safety Information Boxed Warnings: 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.Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adults in short-term studies. All antidepressant-treated patients should be closely monitored for clinical worsening, and for emergence of suicidal thoughts and behaviors. The safety and effectiveness of CAPLYTA have not been established in pediatric patients. 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.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.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.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.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.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.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.Seizures. CAPLYTA should be used cautiously in patients with a history of seizures or with conditions that lower seizure threshold.Potential for Cognitive and Motor Impairment. 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.Dysphagia. CAPLYTA should be used with caution in patients at risk for aspiration. Drug Interactions: CAPLYTA should not be used with CYP3A4 inducers. Dose reduction is recommended for concomitant use with strong CYP3A4 inhibitors or moderate CYP3A4 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. Dose reduction is recommended for patients with moderate or severe hepatic impairment. Adverse Reactions: The most common adverse reactions in clinical trials with CAPLYTA vs. placebo were somnolence/sedation, dizziness, nausea, and dry mouth. CAPLYTA is available in 10.5 mg, 21 mg, and 42 mg capsules. Please click here to see full Prescribing Information including Boxed Warning. About CAPLYTA (lumateperone) CAPLYTA 42 mg is an oral, once daily atypical antipsychotic approved in adults for the treatment of schizophrenia and the treatment of depressive episodes associated with bipolar I or II disorder (bipolar depression) as monotherapy and as adjunctive therapy with lithium or valproate. While the mechanism of action of CAPLYTA 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 studied for the treatment of major depressive disorder, and other psychiatric and neurological disorders. Lumateperone 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 www.intracellulartherapies.com. 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, the potential approval of CAPLYTA (lumateperone) for the treatment of major depressive disorder as adjunctive therapy; our expectations regarding the commercialization of CAPLYTA; our plans to conduct clinical or non-clinical trials and the timing of developments with respect to those trials, including enrollment, initiation or completion of clinical conduct, or the availability or reporting of results; plans to make regulatory submissions to the FDA and the timing of such submissions and any product approvals; whether clinical trial results will be predictive of future real-world results; whether CAPLYTA will serve an unmet need; the goals of our development programs; 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: there are no guarantees that CAPLYTA will be commercially successful; we may encounter issues, delays or other challenges in commercializing CAPLYTA; whether CAPLYTA receives adequate reimbursement from third-party payors; the degree to which CAPLYTA receives acceptance from patients and physicians for its approved indications; 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 and bipolar depression following commercial launch of the product may be different than observed in clinical trials, and may vary among patients; challenges associated with supply and manufacturing activities, which in each case could limit our sales and the availability of our product; 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 bipolar depression or in ongoing or future trials and other development activities; there is no guarantee that a generic equivalent of CAPLYTA will not be approved and enter the market before the expiration of our patents; there is no guarantee that our supplemental New Drug Application (sNDA) for the treatment of MDD will be approved, if at all, on the timeline that we expect; 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; impacts on our business, including on the commercialization of CAPLYTA and our clinical trials, as a result of the COVID-19 pandemic, the conflicts in Ukraine, Russia and the Middle East, global economic uncertainty, inflation, higher interest rates or market disruptions; 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 Relations646-440-9333 Burns McClellan, Inc.Cameron Radinoviccradinovic@burnsmc.com646-930-4406