ITI-333 / J&J - LARVOL DELTA

A PET Study Following a Single Oral Dose of ITI-333 in Healthy Subjects (clinicaltrials.gov) - P1 | N=12 | Completed | Sponsor: Intra-Cellular Therapies, Inc. | Recruiting ➔ Completed | N=24 ➔ 12

Enrollment change • Trial completion

Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of ITI 333 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=32 | Completed | Sponsor: Intra-Cellular Therapies, Inc. | Recruiting ➔ Completed

Trial completion

Discovery of ITI-333, a Novel Orally Bioavailable Molecule Targeting Multiple Receptors for the Treatment of Pain and Other Disorders. (PubMed, J Med Chem) - "ITI-333 exhibited dose-dependent analgesic effects in rodent models of acute pain. Currently, this investigational new drug is in phase I clinical development."

Journal • Addiction (Opioid and Alcohol) • Pain

Pharmacologic profile of ITI-333: a novel molecule for treatment of substance use disorders. (PubMed, Psychopharmacology (Berl)) - "ITI-333 acts as a potent 5-HT2A receptor antagonist, as well a biased MOP receptor partial agonist with low intrinsic efficacy. ITI-333 mitigates opioid withdrawal/reinstatement, supporting its potential utility as a treatment for OUD."

Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Gastrointestinal Disorder • Pain • Psychiatry • Substance Abuse

Intra-Cellular Therapies Reports Fourth Quarter and Full-Year 2022 Financial Results and Provides Corporate Update (GlobeNewswire) - “ITI-1284-ODT-SL program: In 2023, we plan to begin Phase 2 programs in agitation in patients with Alzheimer’s disease (AD), generalized anxiety disorder, and psychosis in patients with AD….Lenrispodun (ITI-214) is our lead PDE1 inhibitor compound….We expect to commence clinical conduct in a Phase 2 trial in Parkinson’s disease later this month….ITI-333 program: ITI-333, a 5-HT2A receptor antagonist and μ-opioid receptor partial agonist, provides potential utility in the treatment of opioid use disorder, pain and mood disorders. A multiple ascending dose study in healthy volunteers evaluating pharmacokinetics (PK), safety and tolerability commenced clinical conduct in the first quarter of 2023. ”

New P1 trial • New P2 trial • Alzheimer's Disease • CNS Disorders • Pain • Parkinson's Disease

Intra-Cellular Therapies Reports Fourth Quarter and Full-Year 2022 Financial Results and Provides Corporate Update (GlobeNewswire) - “Net product sales of CAPLYTA were $87.4 million for the fourth quarter of 2022, compared to $25.5 million for the same period in 2021, representing a year-over-year increase of 243% and a 22% increase over the third quarter of 2022….Research and development (R&D) expenses for the fourth quarter of 2022 were $33.9 million, compared to $29.5 million for the fourth quarter of 2021. This increase is primarily due to higher lumateperone and non-lumateperone project costs, including the ITI-1284, ITI-214, and ITI-333 programs.”

Commercial • Sales • Alzheimer's Disease • Bipolar Disorder • CNS Disorders • Depression • Major Depressive Disorder • Pain • Parkinson's Disease

Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of ITI 333 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: Intra-Cellular Therapies, Inc.

New P1 trial

A PET Study Following a Single Oral Dose of ITI-333 in Healthy Subjects (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Intra-Cellular Therapies, Inc. | Trial completion date: Dec 2022 ➔ Aug 2023 | Trial primary completion date: Dec 2022 ➔ Aug 2023

Trial completion date • Trial primary completion date

A PET Study Following a Single Oral Dose of ITI-333 in Healthy Subjects (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Intra-Cellular Therapies, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open

Mechanism of Action of ITI-333, a Novel Modulator of Mu Opioid, Serotonin, and Dopamine and for the Treatment of Opioid Use Disorder (ACNP 2022) - "Results Cell-based assays demonstrate ITI-333 is a biased MOP receptor partial agonist, acting as an antagonist to block effects of high doses of morphine in pain and motor activity models; acting alone as an analgesic in acute and inflammatory pain models...ITI-333 (0.3, 1, and 3mg/kg, SC) dose-dependently suppresses signs of opioid withdrawal precipitated by naloxone injection in oxycodone-dependent mice (i.e., oxycodone dosed for 8 days; increasing daily doses of 9-33 mg/kg, n=10/group)...ITI-333 was safe and well-tolerated in a first-in-human safety study and continues in clinical development as a treatment for OUD. Conclusions Data support a role for ITI-333 in mitigating opioid withdrawal symptoms with no significant indications of abuse liability."

Addiction (Opioid and Alcohol) • CNS Disorders • Pain • Psychiatry • Substance Abuse

Clinical Research on Novel Pharmacologic and Immunologic Approaches to Treating Cannabis Use Disorder and Opioid Use Disorder (ACNP 2022) - "Haney will present Phase 1-2a studies testing the pregnenolone analogue, AEF0117, a signaling specific inhibitor of the cannabinoid type 1 receptor...D’Souza, will describe findings from a near-completed multi-site Phase 2b trial testing the effects of PF-04457845, an orally active, longacting, potent, and selective inhibitor of fatty acid amide hydrolase (FAAH), the primary enzyme degrading the endocannabinoid, anandamide...Comer will present the safety, immunogenicity, and preliminary efficacy data from a Phase 1a/1b study to evaluate an opioid vaccine targeting oxycodone in non-treatment-seeking participants with OUD, as well as preclinical data that were used to support the clinical research. Snyder will present unpublished data describing the preclinical pharmacological profile of ITI-333 in animal models of opioid withdrawal and craving and the clinical translation of ITI-333 into Phase I SAD study."

Clinical • Addiction (Opioid and Alcohol) • Substance Abuse

A PET Study Following a Single Oral Dose of ITI-333 in Healthy Subjects (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: Intra-Cellular Therapies, Inc.

New P1 trial

Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of ITI 333 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=48 | Completed | Sponsor: Intra-Cellular Therapies, Inc. | Recruiting ➔ Completed

Trial completion

Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of ITI 333 in Healthy Volunteers (clinicaltrials.gov) - P1; N=64; Recruiting; Sponsor: Intra-Cellular Therapies, Inc.

Clinical • New P1 trial

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 (GlobeNewswire) - "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."

Trial status • Addiction (Opioid and Alcohol) • CNS Disorders

Intra-Cellular Therapies reports fourth quarter and full-year 2019 financial results and provides corporate update (Intra-Cellular Therapies) - “Intra-Cellular Therapies…today announced its financial results for the fourth quarter and year ending December 31, 2019, and provided a corporate update….We plan to develop ITI-333…for the treatment of opioid and other substance use disorders, pain, and mood disorders. The pharmacological profile has the potential…as a therapeutic to ease…for analgesia with minimal addictive potential….We expect to initiate our clinical program in 2020.”

New trial

Intra-Cellular Therapies to present data on lumateperone and ITI-333 at the 58th Annual Meeting of the American College of Neuropsychopharmacology (GlobeNewswire) - "Intra-Cellular Therapies, Inc....today announced that the Company will be presenting at the 58th Annual Meeting of the American College of Neuropsychopharmacology (ACNP) to be held in Hollywood, FL, December 8-11, 2019. Intra-Cellular Therapies will be presenting the following posters and presentations at ACNP, which will include results from Study 404, a Phase 3 clinical trial evaluating lumateperone for the treatment of bipolar depression, as well as new data from the schizophrenia clinical program including the long-term safety study....Preclinical data on ITI-333, our novel compound with high affinity at serotonin 5-HT2A, dopamine D1 and mu opioid (MOP) receptors for the potential treatment of substance use disorders and pain will also be presented."

Clinical data • P3 data • Preclinical

Intra-Cellular therapies provides corporate update and reports third quarter 2019 financial results (GlobeNewswire) - "We plan to develop ITI-333, our novel, oral modulator of serotonin, dopamine, and mu opioid receptors, for the treatment of opioid and other substance use disorders, pain, and mood disorders. We plan to present preclinical data from this program at a medical conference later this year and expect to initiate our clinical program in the first half of 2020."

Clinical • Preclinical

Responses to the Opioid Epidemic: Government, Industry and Academic Perspectives (ACNP 2019) - "As an example of industry response to the opioid crisis, Kimberly Vanover, PhD (SVP, Early Stage Clinical Development and Translational Medicine, Intra-Cellular Therapies), will describe updated results for compound, ITI-333, is a serotonin 5-HT2A antagonist, a biased partial mu opioid agonist, and has affinity for dopamine D1 receptors...For the treatment of opioid overdose, NIDA is supporting the development of a nasal spray containing nalmefene, a longer acting alternative to naloxone...From an academic perspective, Laura Bohn, PhD, will discuss development of novel mu opioid receptor biased agonists. Unique Data Unique data from NIDA, NINDS, industry and academic sources will be presented."

ITI-333: An Investigational Drug for the Treatment of Opioid Use Disorder (ACNP 2019) - "New data include, but are not limited to, results in neuropathic pain models in rodents and nonhuman primate self administration. New plans for clinical development of ITI-333 will also be discussed."

Intra-Cellular Therapies Provides Corporate Update and Reports Second Quarter 2019 Financial Results (GlobeNewswire, Intra-Cellular Therapies Inc.) - "We plan to develop ITI-333, our novel, oral modulator of serotonin, dopamine, and mu opioid receptors, for the treatment of..mood disorders. We expect to initiate our clinical program in late 2019 or early 2020."

Clinical