Intra-Cellular Therapies Highlights Lumateperone Presentations at the 59th Annual Meeting of the American College of Neuropsychopharmacology

Presentations highlight lumateperone’s broad antidepressant effects in patients with bipolar disorder and in patients with schizophrenia with co-morbid depression

NEW YORK, Dec. 09, 2020 (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 two presentations at the 59th Annual Meeting of the American College of Neuropsychopharmacology (ACNP) being held virtually, December 6-9, 2020.

• “Lumateperone (ITI-007) in the Treatment of Bipolar Depression: Efficacy Across Symptoms” (Poster T110).

This poster presented additional data from Study 404, a Phase 3 clinical trial evaluating lumateperone as monotherapy for the treatment of patients with bipolar depression. In this Study, lumateperone 42 mg met its primary endpoint of change from baseline at day 43 on the Montgomery-Åsberg Depression Rating Scale (MADRS) total score versus placebo (p<.0001; effect size (ES) = 0.56).

A prospective analysis demonstrated lumateperone 42 mg significantly improved each of the 10 individual MADRS items versus placebo (P<.05 to P<.0001) indicating treatment with lumateperone results in reductions in all depression symptom domains.

Data presented also included the categorical shift in severity of depression symptoms as assessed by the MADRS single-item scores. Results showed a higher proportion of lumateperone patients than placebo patients had improvements in overall bipolar illness severity shifting from severe to moderate/mild or no illness. These findings are consistent with the broad antidepressant effects seen with lumateperone in our depression programs.

About the Montgomery-Åsberg Depression Rating Scale¹

The Montgomery-Åsberg Depression Rating Scale (MADRS) is a 10-item, validated rating scale used to diagnose and rate the severity of depressive episodes and is an accepted regulatory endpoint in clinical trials of depression.

The scale includes questions on the following items: 1. Apparent sadness; 2. Reported sadness; 3. Inner tension; 4. Reduced sleep; 5. Reduced appetite; 6. Concentration difficulties; 7. Lassitude; 8. Inability to feel; 9. Pessimistic thoughts; and 10. Suicidal thoughts. Each item can be scored 0 (no abnormality) to 6 (severe) with the potential overall score ranging from 0 to 60.

• “Efficacy of Lumateperone (ITI-007) in Depression Symptoms Associated with Schizophrenia” (Poster T148).

This poster presented a post-hoc analysis from the lumateperone long-term safety study (Study 303) in patients with stable schizophrenia with comorbid depression (Calgary Depression Scale for Schizophrenia or CDSS score ≥6) who were switched from prior antipsychotics.

In patients with schizophrenia, depression symptoms are highly prevalent, even in stable patients following antipsychotic treatment. Depression associated with schizophrenia is linked to poorer patient outcomes, including increased risk of relapse and suicidality, worse functioning, and decreased quality of life.

In patients with stable schizophrenia and comorbid moderate-to-severe depression (CDSS≥6; n=80), lumateperone 42 mg significantly improved a broad range of depression symptoms. The mean baseline CDSS score in these patients was 7.6. Following one year of lumateperone 42 mg treatment, the mean CDSS score was reduced by 4.8 points (p=<.0001) to 2.4 points. Significant improvement compared with baseline was observed as early as Day 75, the first on-treatment CDSS assessment.

In this one year study lumateperone 42 mg significantly reduced a broad range of depression symptoms and maintained effectiveness over the entire treatment period as assessed by the CDSS. Each of the nine individual items of the CDSS were also analyzed and demonstrated significant improvement (P<.05 to P<.0001) versus baseline at day 75 (the earliest assessment).

Clinically meaningful reduction of depression symptoms (response defined as ≥50% reduction from baseline on the CDSS) was achieved in 50% of patients with comorbid depression at baseline.

These results support the potential benefits of lumateperone 42 mg in treating depression symptoms associated with schizophrenia and advancing the development of lumateperone in a variety of depressive disorders.

About the Calgary Depression Scale for Schizophrenia²

Calgary Depression Scale for Schizophrenia (CDSS) is a 9-item, validated scale used specifically to assess depression in people with schizophrenia. The scale was developed from, and validated against, the Hamilton Depression Rating Scale (HDRS), Beck Depression Inventory (BDI), and the Brief Psychiatric Rating Scale (BPRS). The CDSS scale was also validated against the MADRS³. The scale uniquely distinguishes depressive symptoms from positive, negative, and extrapyramidal symptoms in patients with schizophrenia. The CDSS, therefore, is the most suitable measure of depression in schizophrenia when compared to other scales that do not reliably distinguish depression from other symptoms associated with schizophrenia.

The scales include questions on the following items: 1. Depression; 2. Hopelessness; 3. Self-Depreciation; 4. Guilty Ideas of Reference; 5. Pathological Guilt 6. Morning Depression; 7. Early Wakening; 8. Suicide; and 9. Observed Depression. Each item can be scored 0 to 3 (Absent, Mild, Moderate, or Severe) with the potential overall score ranging from 0 to 27.

^{¹ Montgomery SA, Asberg M. “A new depression scale designed to be sensitive to change”. British Journal of Psychiatry. 1979; 134 (4): 382–89.}

^{² Addington D, Addington J, Schissel B. “A depression rating scale for schizophrenics”. Schizophr Res. 1990;3 (4):247–251.}

^{³ Lako et al. “A systematic review of instruments to measure depressive symptoms in patients with schizophrenia”. Journal of Affective Disorders 140 (2012) 38–47.}

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.
• 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.
• Sleepiness and Trouble Concentrating. 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, 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 see click here for full Prescribing Information, including Boxed Warning.

CAPLYTA is a registered trademark of Intra-Cellular Therapies, Inc.
© 2020 Intra-Cellular Therapies, Inc. All rights reserved. 3/2020 US-CAP-2000150

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.

CAPLYTA (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.

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 potential benefits of lumateperone 42 mg in treating depression symptoms associated with schizophrenia and the potential to advance the development of lumateperone as a potential treatment for a variety of depressive disorders; 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: the COVID-19 pandemic may negatively impact the conduct of, and the timing of enrollment, completion and reporting with respect to, our clinical trials; 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
jgrimaldi@burnsmc.com
212-213-0006

MEDIA INQUIRIES:
Ana Fullmer
Corporate Media Relations W2Owcg
afullmer@wcgworld.com