Fluoxetine Hydrochloride

New Analyses Related to Aficamten Expand on its Metabolism Pathways, Treatment Effect Associated with Combination Therapy with Disopyramide and Longer-Term Effect on Cardiac Structure and Function SOUTH SAN FRANCISCO, Calif., March 17, 2025 (GLOBE NEWSWIRE) -- Cytokinetics, Incorporated (Nasdaq: CYTK) today announced five presentations related to aficamten, an investigational cardiac myosin inhibitor, and hypertrophic cardiomyopathy (HCM), at the American College of Cardiology (ACC) Annual Scientific Session & Expo taking place from March 29, 2025–March 31, 2025 in Chicago, IL. “We are pleased to be sharing several new analyses relating to aficamten at the upcoming ACC Scientific Session & Expo,” said Stephen Heitner, M.D., Vice President, Head of Clinical Research. “The presentations describe the drug metabolism of aficamten, the safety of combination therapy with the standard of care medication disopyramide, and the effect of longer-term use of aficamten. Together these analyses add to the strong and growing evidence base supporting the potential for aficamten in patients with obstructive HCM and inform how it may be used in clinical practice.” Evaluation of Cytochrome P450 2C9, 2C19, and 2D6 Inhibition on the Pharmacokinetics of Aficamten in Healthy Participants (1091-139) Poster Presentation, March 29, 2025, 2:00-3:00 PM CT, South Hall. Neha Maharao, Ph.D., Senior Clinical Pharmacologist, Cytokinetics. Data from an open-label, fixed-sequence drug-drug interaction (DDI) study of aficamten in healthy participants will be presented in a poster presentation. A previous study showed that aficamten is metabolized, in part, by the cytochrome P450 (CYP) enzyme 3A41. To further characterize its metabolic pathways, aficamten was evaluated with concomitant administration of three strong inhibitors of one or more of the CYP pathways: fluconazole (inhibitor of 2C9, 2C19, and 3A4), paroxetine (inhibitor of 2D6) and fluoxetine (inhibitor of 2C19 and 2D6). The data show that aficamten was eliminated by multiple CYP pathways, primarily by CYP2C9 (fraction metabolized [fm]=50%), with contributions from CYP3A (fm=26%), CYP2D6 (fm=21%) and CYP2C19 (fm=3%). Safety and Outcomes of Concomitant Aficamten and Disopyramide Use and Withdrawal in Patients with Obstructive Hypertrophic Cardiomyopathy: An Analysis of REDWOOD-HCM Cohort 3, SEQUOIA-HCM, and FOREST-HCM Trials (411-06) Oral Presentation, March 31, 2025, 9:11-9:18 AM CT, S406b. Ahmad Masri, M.D., MS, Director of the Hypertrophic Cardiomyopathy Center at Oregon Health & Science University. Data from an analysis of concomitant treatment with aficamten and disopyramide from completed and ongoing clinical trials of aficamten in patients with obstructive HCM will be presented in an oral presentation. The analysis included 50 participants from Cohort 3 of REDWOOD-HCM (Randomized Evaluation of Dosing With CK-274 in Obstructive Outflow Disease in HCM), SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM) and FOREST-HCM (Follow-up, Open-Label, Research Evaluation of Sustained Treatment with Aficamten in HCM) who were receiving disopyramide at baseline. Participants were separated into four groups: those on disopyramide who underwent withdrawal of aficamten due to end of treatment in Cohort 3 of REDWOOD-HCM or SEQUOIA-HCM (n=29), patients on disopyramide receiving placebo in SEQUOIA-HCM (n=20), patients on aficamten who underwent disopyramide withdrawal in FOREST-HCM (n=17) and patients on aficamten who maintained treatment with disopyramide in FOREST-HCM (n=27). Combination therapy with aficamten and disopyramide was well-tolerated; the analysis suggests that combination of disopyramide with aficamten did not result in lower left ventricular outflow tract (LVOT) gradients compared to treatment with aficamten alone. The analysis suggests that withdrawal of disopyramide while receiving aficamten did not reduce the efficacy of aficamten and further that withdrawal of aficamten while on disopyramide resulted in the return of LVOT obstruction and symptoms, with an increase in NT-proBNP. There were no safety events reported with either aficamten or disopyramide withdrawal, and no episodes of atrial fibrillation after disopyramide withdrawal were reported. Effect of Aficamten Treatment for Up to 72 Weeks on Cardiac Structure and Function in Patients with Obstructive Hypertrophic Cardiomyopathy: The SEQUOIA-HCM and FOREST-HCM CMR Sub-studies (964-09) Moderated Poster Presentation, March 30, 2025, 12:06-12:13 PM CT, Theater 5. Ahmad Masri, M.D., MS, Director of the Hypertrophic Cardiomyopathy Center at Oregon Health & Science University. New data from the cardiac magnetic resonance (CMR) imaging sub-studies of FOREST-HCM and SEQUOIA-HCM will be presented in a moderated poster presentation. At the time of the current analysis, 64 patients had completed a baseline CMR, including 36 patients who had completed a follow-up CMR at 72 weeks, and 28 patients who had completed a follow-up CMR at 48 weeks. Longer-term treatment with aficamten resulted in statistically significant improvements (mean ±SD) in measures of cardiac structure and function including left ventricular mass index (-9.8 g/m2 ±18.1, p<0.0001), maximum left ventricular septal wall thickness (-2.4 mm ±2.3, p<0.0001), left atrial volume (-17.9 ml ±28.3, p<0.0001) and mitral regurgitant volume (-18.1 ml ±19.2, p<0.0001) and fraction (-14.2% ±15.6, p<0.0001). These changes were accompanied by stable replacement fibrosis (late gadolinium enhancement mass = -0.3 g ±5.0, p=0.51) and reduced interstitial fibrosis (global extracellular volume (ECV) = -1.2 % ±2.8, p = 0.002; Native T1 = -36.6 ms ±55.7, p<0.0001). Understanding the Impact of Placebo on Patient-Reported Health Status: An Analysis from SEQUOIA-HCM (1029-176) Poster Presentation, March 29, 2025, 9:30-10:30 AM CT, South Hall. Charles F. Sherrod, M.D., M.Sc., Cardiology Fellow, UMKC Healthcare Institute for Innovations in Quality, Saint Luke’s Mid America Heart Institute. A new analysis from SEQUOIA-HCM of the placebo effect on Kansas City Cardiomyopathy Questionnaire Overall Summary Scores (KCCQ-OSS) will be presented in a poster presentation. In patients randomized to placebo in SEQUOIA-HCM, the change in KCCQ-OSS was evaluated from baseline to Week 24 and following blinded treatment withdrawal from Week 24 to Week 28. Among the 140 (47%) patients on placebo, the median KCCQ-OSS at baseline was 67.2 (95% CI: 62.9, 71.5) and the median improvement at Week 24 was 5.7 points (95% CI: 3.2, 8.3; p<0.01). After withdrawal from Week 24 to Week 28, the median score decreased by only 2.1 points (95% CI: -3.5, -0.7; p<0.01). These results suggest that about one-third of the improvement observed in KCCQ-OSS in patients receiving placebo was due to a placebo effect, further suggesting that other changes in health status following treatment with placebo may be due to other factors involved in clinical trial participation, such as receiving treatment at expert centers and changes in patient behavior. Association Between Race/Ethnicity and Outcomes in Patients with Non-Obstructive Hypertrophic Cardiomyopathy (1251-173) Poster Presentation, March 31, 2025, 10:30-11:30 AM CT, South Hall. Nosheen Reza, M.D., Assistant Professor of Medicine, Division of Cardiovascular Medicine, the Hospital of the University of Pennsylvania. Data from a new health economics and outcomes research (HEOR) analysis of the association between race/ethnicity and outcomes in non-obstructive HCM patients will be presented in a poster presentation. This retrospective cohort study included adult patients diagnosed with non-obstructive HCM from January 1, 2013 to December 31, 2021. Of the 9,842 patients included, 74.2% were non-Hispanic white, 19.5% were non-Hispanic Black/African American, 4.2% were Hispanic and 2.1% were non-Hispanic Asian. White patients had greater rates of atrial fibrillation and cardiovascular hospitalization compared to Asian and Hispanic patients. Compared to white patients, Black patients had increased rates of stroke (risk ratio [RR] 1.76), heart failure (RR 1.73), ventricular tachycardia (RR 1.24), sudden cardiac arrest (RR 1.90), cardiovascular hospitalization (RR 1.42) and cardiovascular rehospitalization (RR 1.31) and a lower rate of atrial fibrillation (RR 0.74; all p<0.001). All-cause mortality was highest among Black patients (p<0.001). Compared to white patients, non-Hispanic Black patients had the highest rate of adverse cardiovascular outcomes and all-cause mortality, while Asian and Hispanic patients experienced lower rates. These results highlight an urgent need to address drivers of race/ethnicity-based disparities in patients with nHCM. About Aficamten Aficamten is an investigational selective, small molecule cardiac myosin inhibitor discovered following an extensive chemical optimization program that was conducted with careful attention to therapeutic index and pharmacokinetic properties and as may translate into next-in-class potential in clinical development. Aficamten was designed to reduce the number of active actin-myosin cross bridges during each cardiac cycle and consequently suppress the myocardial hypercontractility that is associated with HCM. In preclinical models, aficamten reduced myocardial contractility by binding directly to cardiac myosin at a distinct and selective allosteric binding site, thereby preventing myosin from entering a force producing state. The development program for aficamten is assessing its potential as a treatment that improves exercise capacity as measured by peak oxygen uptake (pVO2) and relieves symptoms in patients with HCM. Aficamten was evaluated in SEQUOIA-HCM, a positive pivotal Phase 3 clinical trial in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). Aficamten received Breakthrough Therapy Designation for the treatment of symptomatic obstructive HCM from the U.S. Food & Drug Administration (FDA) and from the National Medical Products Administration (NMPA) in China. Aficamten is currently under regulatory review in the U.S, where the FDA is reviewing a New Drug Application (NDA) for aficamten, which was assigned standard review and a Prescription Drug User Fee Act (PDUFA) target action date of September 26, 2025. Additionally, the European Medicines Agency (EMA) is reviewing a Marketing Authorization Application (MAA) for aficamten, and The Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) is reviewing an NDA for aficamten with Priority Review. Aficamten is also currently being evaluated in MAPLE-HCM, a Phase 3 clinical trial of aficamten as monotherapy compared to metoprolol as monotherapy in patients with obstructive HCM; ACACIA-HCM, a Phase 3 clinical trial of aficamten in patients with non-obstructive HCM; CEDAR-HCM, a clinical trial of aficamten in a pediatric population with obstructive HCM; and FOREST-HCM, an open-label extension clinical study of aficamten in patients with HCM. About Hypertrophic Cardiomyopathy Hypertrophic cardiomyopathy (HCM) is a disease in which the heart muscle (myocardium) becomes abnormally thick (hypertrophied). The thickening of cardiac muscle leads to the inside of the left ventricle becoming smaller and stiffer, and thus the ventricle becomes less able to relax and fill with blood. This ultimately limits the heart’s pumping function, resulting in reduced exercise capacity and symptoms including chest pain, dizziness, shortness of breath, or fainting during physical activity. HCM is the most common monogenic inherited cardiovascular disorder, with approximately 280,000 patients diagnosed, however, there are an estimated 400,000-800,000 additional patients who remain undiagnosed in the U.S.2,3,4 Two-thirds of patients with HCM have obstructive HCM (oHCM), where the thickening of the cardiac muscle leads to left ventricular outflow tract (LVOT) obstruction, while one-third have non-obstructive HCM (nHCM), where blood flow isn’t impacted, but the heart muscle is still thickened. People with HCM are at high risk of also developing cardiovascular complications including atrial fibrillation, stroke and mitral valve disease.5 People with HCM are at risk for potentially fatal ventricular arrhythmias and it is one of the leading causes of sudden cardiac death in younger people or athletes.6 A subset of patients with HCM are at high risk of progressive disease leading to dilated cardiomyopathy and heart failure necessitating cardiac transplantation. About Cytokinetics Cytokinetics is a leading muscle biology specialty biopharmaceutical company focused on discovering, developing and commercializing muscle biology-directed drug candidates as potential treatments for debilitating diseases in which muscle performance is compromised. As a pioneer in muscle and the mechanics of muscle performance, Cytokinetics is intent on meaningfully improving the lives of patients through global access to innovative medicines. Cytokinetics is readying for potential regulatory approvals and commercialization of aficamten, a potential next-in-class cardiac myosin inhibitor, following positive results from SEQUOIA-HCM, the pivotal Phase 3 clinical trial in patients with obstructive hypertrophic cardiomyopathy (HCM). Aficamten is also being evaluated in additional clinical trials enrolling patients with obstructive and non-obstructive HCM. Cytokinetics is also developing omecamtiv mecarbil, a cardiac myosin activator, in patients with heart failure with severely reduced ejection fraction (HFrEF), CK-586, a cardiac myosin inhibitor with a mechanism of action distinct from aficamten, for the potential treatment of heart failure with preserved ejection fraction (HFpEF) and CK-089, a fast skeletal muscle troponin activator with potential therapeutic application to a specific type of muscular dystrophy and other conditions of impaired skeletal muscle function. For additional information about Cytokinetics, visit www.cytokinetics.com and follow us on X, LinkedIn, Facebook and YouTube. Forward-Looking Statements This press release contains forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995 (the “Act”). Cytokinetics disclaims any intent or obligation to update these forward-looking statements and claims the protection of the Act’s Safe Harbor for forward-looking statements. Examples of such statements include, but are not limited to, statements express or implied relating to the properties, treatment effect or potential benefits of aficamten or any of our other drug candidates or our ability to obtain regulatory approval for aficamten for the treatment of obstructive hypertrophic cardiomyopathy or any other indication from FDA or any other regulatory body in the United States or abroad. Such statements are based on management’s current expectations, but actual results may differ materially due to various risks and uncertainties, including, but not limited to the risks related to Cytokinetics’ business outlines in Cytokinetics’ filings with the Securities and Exchange Commission. Forward-looking statements are not guarantees of future performance, and Cytokinetics’ actual results of operations, financial condition and liquidity, and the development of the industry in which it operates, may differ materially from the forward-looking statements contained in this press release. Any forward-looking statements that Cytokinetics makes in this press release speak only as of the date of this press release. Cytokinetics assumes no obligation to update its forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release. CYTOKINETICS® and the CYTOKINETICS and C-shaped logo are registered trademarks of Cytokinetics in the U.S. and certain other countries. Contact: Cytokinetics Diane Weiser Senior Vice President, Corporate Affairs (415) 290-7757 References: Source: Cytokinetics, Incorporated

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