Intra-Cellular Therapies Announces the Initiation of Clinical Trials for ITI-LLAI, a Long-Acting Injectable Formulation of Lumateperone for the Treatment of Schizophrenia and for ITI-333, a Novel Treatment for Opioid Use Disorder

The Company continues expansion of its lumateperone programs with the advancement of a Long-Acting injectable formulation into clinical trials.

ITI-333 introduces a unique pharmacology for the treatment of opioid use disorder.

NEW YORK, NY, USA I December 29, 2020 I 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 the initiation of clinical programs for the Company’s lumateperone long-acting injectable formulation (ITI-LLAI) and for ITI-333, a novel molecule for the treatment of opioid use disorder.

“I am pleased to announce that two important proprietary programs have advanced into human clinical testing, further demonstrating our commitment to patients through the development of novel treatments for schizophrenia, mood disorders and other neuropsychiatric and neurologic disorders,” said Dr. Sharon Mates, Chairman and CEO of Intra-Cellular Therapies.

LLAI, Study ITI-007-025: A Phase 1 single ascending dose study of LLAI, a formulation designed to be administered subcutaneously and to maintain therapeutic levels of lumateperone for at least 1 month. This study will evaluate the pharmacokinetics, safety and tolerability of lumateperone LAI in patients with stable symptoms of schizophrenia. Results from this study will inform the dosing strategy for future studies.

Maintaining patients symptomatically stable and functional are the primary objectives of the treatment of schizophrenia. Long-acting injectable antipsychotics provide patients with blood concentrations of active drug that remain within a therapeutic range for an extended period. These formulations represent a treatment option for patients who prefer not to take medication daily or have history of poor adherence to oral treatments as they have the potential to improve adherence and prevent relapse. Oral lumateperone has demonstrated efficacy in treating schizophrenia symptoms with a favorable safety and tolerability profile. A long-acting formulation of lumateperone if successfully developed and approved will provide an additional option for patients.

ITI-333, Study ITI-333-001: A Phase 1 single ascending dose study evaluating the safety, tolerability and pharmacokinetics of ITI-333 in healthy volunteers. ITI333 is a novel compound that uniquely combines activity as an antagonist at serotonin 5-HT2A receptors and a partial agonist at μ-opioid receptors. These combined actions support the potential utility of ITI-333 in the treatment of opioid use disorder and associated comorbidities (e.g., depression, anxiety, sleep disorders) without opioid-like safety and tolerability concerns.

Opioid use disorder is a chronic disorder with over 10 million people in the United States having misused opioids and nearly fifty-thousand persons died from opioid drug overdoses in 2018.

About Lumateperone Long Acting Injectable (LLAI) formulation

The Company is developing a long-acting injectable formulation of lumateperone (LLAI) that is designed for once monthly administration by subcutaneous injection for the treatment of schizophrenia. Nonclinical studies in rodents and monkeys have shown the LLAI formulation is safe and well tolerated in single and once monthly multiple dose studies and sustains plasma lumateperone levels for 28 day or longer after each injection.

Pharmacodynamic studies have shown lumateperone acts as a potent serotonin 5-HT2A receptor antagonist with high binding affinity, as a postsynaptic D2 receptor antagonist with moderate binding affinity, as an inhibitor of the serotonin reuptake transporter (SERT) with moderate binding affinity. Lumateperone also has moderate binding affinity to the D1 receptor (which may contribute to the indirect activation of NMDA and AMPA neurotransmission).  These drug targets are believed to play an important role in in schizophrenia, bipolar disorder, depressive disorders and other neuropsychiatric disorders.  In vitro studies have shown lumateperone has a ~60-fold greater affinity for 5-HT2A receptors vs D2 receptors.

Lumateperone is being investigated for the treatment of bipolar depression, major depressive disorders and other neuropsychiatric and neurological disorders. Lumateperone is not FDA approved for these disorders. CAPLYTA 42 mg (lumateperone) is approved by the U.S. Food and Drug Administration for the treatment schizophrenia of adults.

About ITI-333

ITI333 is a novel compound that uniquely combines activity as an antagonist at serotonin 5-HT2A receptors and a partial agonist at μ-opioid receptors. These combined actions support the potential utility of ITI-333 in the treatment of opioid use disorder and associated comorbidities (e.g., depression, anxiety, sleep disorders) without opioid-like safety and tolerability concerns. In addition, ITI-333 exhibits analgesic efficacy in acute and chronic preclinical models of pain supporting its potential utility in the management of pain.

ITI333’s pharmacology is predominantly driven by high affinity binding to serotonin 5-HT2A (Ki = 8.3 nM) and μ-opioid (Ki = 11 nM) receptors. ITI333 shows modest affinity for dopamine D1 receptors, low affinity for κ-opioid receptors, and no binding to δ-opioid and NOP receptors.

In vivo, ITI-333 elicits potent analgesia in rodents that is blocked by the opioid antagonist, naloxone. Further, ITI-333 mitigates symptoms associated with opioid withdrawal and blocks reinstatement of opioid mediated behaviors; behaviors thought to be associated with a return to opioid use after a period of abstinence.

ITI-333 possesses low potential for abuse liability. Unlike opioid agonists, ITI-333 is not self-administered, does not develop physical tolerance/dependences and does not impair gastrointestinal and pulmonary function. This pharmacologic profile is unique and supports the study of ITI-333 in humans as a potential treatment for opioid use disorder and pain.

Intra-Cellular Therapies has received a grant from the National Institute on Drug Abuse as part of the NIH Helping to End Addiction Long-term initiative, or HEAL, to support the early clinical development of ITI-333 for the treatment of opioid use disorder.

CAPLYTA™ (lumateperone) is indicated for the treatment of schizophrenia in adults. CAPLYTA is available in 42 mg capsules.

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.

SOURCE: Intra-Cellular Therapies

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