# Development of ITI-333, a μ-opioid Receptor Partial Agonist and 5HT2A and D1 Receptor Antagonist, for the Treatment of Opioid Use Disorders

> **NIH NIH UG3** · INTRA-CELLULAR THERAPIES, INC. · 2021 · $2,917,074

## Abstract

RFA-DA-19-002 Principal Investigator/PD: Vanover, Kimberly E.
Project Summary/Abstract
Intra-Cellular Therapies Inc (ITI), a clinical-stage biopharmaceutical company, is developing ITI-333, a novel
compound with high affinity activity at mu opiate (MOP), 5-HT2A, and D1 receptors. The nonclinical profile of
ITI-333 suggests a promising medication, lacking abuse liability, with partial agonist activity at MOP
receptors useful for treatment of opiate withdrawal in individuals with Opioid Use Disorders (OUD). ITI is
currently completing IND-enabling nonclinical safety, toxicology, pharmacokinetic and manufacturing
activities, with the goal of launching Phase 1 human clinical evaluation of ITI-333 in healthy volunteers in Q1
2019. ITI seeks to partner with NIDA in the development of this compound for a novel and safe therapeutic
for use in treating OUD, requesting support of clinical development of ITI-333, while committing significant
internal funds to a parallel program of non-clinical development and CMC activities in support of the clinical
plan. To this end, we submit this application, “Development of ITI-333, a µ-opioid Receptor Partial
Agonist and 5HT2A and D1 Receptor Antagonist, for the Treatment of Opioid Use Disorders” to NIDA
RFA-DA-19-002, Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose
(UG3/UH3). Here, we propose a 2-year UG3 program, including a First-in-Man, single ascending dose
(SAD) study (ITI-333-001) to assess the safety, tolerability and pharmacokinetics of ITI-333 in healthy
volunteers. The safety, tolerability, and pharmacokinetics of multiple, ascending doses (MAD) of ITI-333 will
then be evaluated in a single-center in-patient study (ITI-333-002) with the goal of determining a maximally-
tolerated dose (MTD). Both studies will be conducted in collaboration with Clinilabs, a NYC-based CRO. In
parallel with the MAD study, we will characterize the in vivo receptor pharmacology of ITI-333 at MOP, 5-
HT2A, and D1 receptors in human brain using PET imaging (with Dr. Dean Wong, JHU, ITI-333-003), thereby
leveraging our SAD data to clinically validate the mechanism of action of ITI-333 and to inform Phase 2
dose selection. These data will enable us to launch a 3-year UH3 program exploring the human abuse
liability (HAL) and functional pharmacology of ITI-333 in collaboration with Dr. Sandra Comer (CUMC), a
clinical expert in opioid use and abuse. The HAL study (Phase 2a, ITI-333-004) will characterize the opioid
receptor antagonist/partial agonist profile of ITI-333 in humans to explore potential abuse liability in humans.
Additional Phase 2 studies will evaluate the in vivo functional pharmacology of ITI-333 in a model of
withdrawal precipitation in non-treatment seeking heroin users (ITI-333-005) and in a model of mu-opioid
receptor blockade in treatment-seeking heroin users (ITI-333-006). Together, we believe this clinical
development plan with inform further development of ITI-333 and the selecti...

## Key facts

- **NIH application ID:** 9841388
- **Project number:** 5UG3DA047699-02
- **Recipient organization:** INTRA-CELLULAR THERAPIES, INC.
- **Principal Investigator:** SANDRA D. COMER
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,917,074
- **Award type:** 5
- **Project period:** 2019-01-01 → 2025-01-02

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9841388

## Citation

> US National Institutes of Health, RePORTER application 9841388, Development of ITI-333, a μ-opioid Receptor Partial Agonist and 5HT2A and D1 Receptor Antagonist, for the Treatment of Opioid Use Disorders (5UG3DA047699-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9841388. Licensed CC0.

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