Intra-Cellular Therapies Highlights Data Presentations at the American College of Neuropsychopharmacology Annual Meeting

Company presents positive results of a pre-specified patient population in Study 403 examining the effects of CAPLYTA^® (lumateperone) in patients experiencing a major depressive episode with anxious distress and mixed features.

Company presents preclinical data on ITI-1549, our lead product candidate in our non-hallucinogenic psychedelics program in mood disorders and other psychiatric disorders.

NEW YORK, Dec. 05, 2023 (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 data presentations at the American College of Neuropsychopharmacology (ACNP) 62nd Annual Meeting.

“We are pleased to present new analyses at ACNP showing the antidepressant effects of lumateperone in patients with anxious distress and mixed features which further strengthen our confidence in CAPLYTA’s potential as a broad treatment for MDD and other mood disorders,” said Dr. Suresh Durgam, Executive Vice President and Chief Medical Officer of Intra-Cellular Therapies. “In addition, we are excited to share preclinical data on our newly introduced non-hallucinogenic psychedelic development program.”

Monday, December 4:

Poster M91: “Lumateperone in the Treatment of Patients With Major Depressive Disorder and Bipolar Disorder with Anxious Distress and Mixed Features”

The poster presented at ACNP reports on an important post-hoc analysis from Study 403 evaluating the antidepressant effects of lumateperone in a pre-specified subgroup of patients with mixed features exhibiting anxious distress (commonly known as anxious depression).

Lumateperone improved change from baseline for MADRS total score at Day 43 compared with placebo in all three populations with anxious distress: combined major depressive disorder (MDD)/bipolar depression population (6.1 point reduction v. placebo; Cohen’s d effect size (ES) = 0.67), MDD individual population (6.8 point reduction v. placebo; ES= 0.79), and bipolar depression individual population (5.5 point reduction v. placebo; ES= 0.59). Greater improvements vs placebo in MADRS Total score occurred by Day 15 and persisted throughout the study. Similarly, in the Clinical Global Impression Scale-Severity (CGI-S) lumateperone was superior versus placebo in all three patient populations. Cohen-D effect sizes on the CGI-s ranged from 0.48 to 0.66.

In DSM-5 anxious distress is defined as the presence of ≥2 anxious symptoms (feeling tense, feeling restless, difficulty concentrating, fearful something awful may happen, or feeling out of control) during the majority of days during the current or most recent major depressive episode. Using this definition, anxious distress was present in 73.9% in MDD and 54.3% in bipolar depression patients enrolled in the study, highlighting its high prevalence, consistent with the literature.

Inner tension is an item within the MADRS which is often used as a surrogate marker for anxiety. With respect to the MADRS inner tension single-item score, lumateperone improved change from baseline at Day 43 compared with placebo for all three populations with anxious distress, demonstrating the consistency of the results.

The data presented in this poster represent further analyses from Study 403. Study 403 evaluated lumateperone 42mg as monotherapy in the treatment of major depressive episodes in patients with MDD with mixed features and in patients with bipolar depression with mixed features. Topline results for Study 403 are shown in Poster M88 and described below.

Both DSM-5 specifiers, mixed features and anxious distress, are common in patients with MDD and bipolar depression and their presence is associated with more pernicious forms of depressive illness (symptom severity, more comorbidities, increased suicide risk) and poor treatment response. In this analysis, lumateperone improved depression symptoms and severity score versus placebo in patients with MDD or bipolar depression with anxious distress and mixed features.

Poster M131: “Discovery and Characterization of ITI-1549, a Novel Non-hallucinogenic Psychedelic For the Treatment of Neuropsychiatric Disorders”

We are developing novel non-hallucinogenic psychedelics that allow exploration of this psychoactive drug class in neuropsychiatric conditions including mood disorders without the liabilities of known psychedelics, such as induction of hallucinations and risks for cardiac valvular pathologies. The lead molecule in this program, ITI-1549, is advancing through IND enabling studies and is expected to enter human testing in late 2024 or early 2025.

This poster describes the in-vitro and in-vivo preclinical characterization of ITI-1549. In vitro, similar to known hallucinogenic psychedelics, ITI-1549 exhibits high affinity binding to 5-HT2a receptors. Functionally, ITI-1549 acts as an agonist at 5-HT2A receptors favoring postsynaptic signaling within the beta-arrestin pathway over G-protein coupled pathways.

Activation of the 5-HT2a receptor coupled Gq signaling pathway has been linked to hallucinogenic properties of psychedelic compounds. By preferentially activating the beta-arrestin pathway, ITI-1549 and compounds in this chemical series may retain the beneficial therapeutic effects of psychedelics without hallucinogenic effects.

Importantly, unlike most psychedelics, ITI-1549 is not a 5-HT2b agonist which has been associated with heart valve pathologies.

In animal models, we have shown that ITI-1549 does not elicit head twitch behaviors in mice, which are predictive of hallucinogenic potential in humans; based on these data ITI-1549 can be classified as a non-hallucinogenic agent. ITI-1549 has also shown to increase social interaction and reduce anxiety and depressive symptoms in preclinical models. It also activates the mTOR pathway in the prefrontal cortex, which is associated with increased neuroplasticity and rapid antidepressant activity in preclinical models.

In conclusion, ITI-1549 may be a safe, non-hallucinogenic psychedelic without the liability to induce hallucinations and cardiac pathologies while retaining the potential as an acute or chronic treatment of mood, anxiety and other neuropsychiatric disorders.

Poster M88: “Lumateperone Treatment for Major Depressive Episodes with Mixed Features in Major Depressive Disorder and Bipolar I or Bipolar II Disorder”

This poster describes further data analyses from Study 403 in mixed features. In this study, lumateperone 42mg was statistically significant on the primary endpoint of symptom reduction on the MADRS for the combined mixed features patient population of MDD and bipolar depression (5.7 point reduction v. placebo; p<0.0001; Cohen’s d effect size (ES) of 0.64) and the individual patient populations of MDD with mixed features (5.9 point reduction v. placebo; p<0.0001; ES= 0.67) and bipolar depression with mixed features (5.7 point reduction v. placebo; p<0.0001; ES= 0.64). Lumateperone 42mg also met the key secondary endpoint by demonstrating a statistically significant and clinically meaningful reduction in the Clinician’s Global Impression scale or CGI compared to placebo at Week 6 in all three patient populations.

Lumateperone was generally safe and well tolerated, with a side effect profile consistent with prior lumateperone trials. The most common adverse events in the study were somnolence, dizziness and nausea.

There were no notable changes in weight, body mass index, or waist circumference and no clinically relevant changes in metabolic parameters.

CAPLYTA^® (lumateperone) is indicated in adults for the treatment of schizophrenia and 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 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 neuropsychiatric 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, our plans to conduct clinical or non-clinical trials and the timing of those trials, including enrollment, initiation or completion of clinical conduct, or the availability of results; plans to make regulatory submissions to the FDA and the timing of such submissions; 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; 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 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 Relations
646-440-9333

Burns McClellan, Inc.
Cameron Radinovic
cradinovic@burnsmc.com
212-213-0006