U01DA060704

Development of the novel mu-opioid receptor antagonist methocinnamox (MCAM) for preventing relapse and overdose - project summary/abstract

In response to PAR-22-202 “Grand Opportunity in Medications Development for Substance-Use Disorders (U01 Clinical Trial Optional),” this revised application (U01DA060704) requests 3 years of support to continue developing the novel opioid receptor antagonist methocinnamox (MCAM) for preventing opioid relapse after detoxification.

MCAM will fill an unmet need for an orally bioavailable, shelf-stable, long-acting medication for preventing relapse.

MCAM prevents and reverses the effects of μ-opioid receptor (MOR) agonists, including ultra-potent agonists such as fentanyl, in several species and by multiple routes of administration with a single dose being effective for >2 weeks.

In vitro and in vivo studies have not identified any clinical adverse signs for MCAM over a >3,000-fold dose range.

IND-enabling safety pharmacology and toxicology studies in rats and dogs (Charles River Laboratories) are complete and found no adverse clinical signs.

Synthesis of MCAM (Veranova) was improved, increasing the yield, maleate was determined to be a preferred salt, two 1-kilogram batches of non-GMP MCAM were manufactured for non-clinical studies, ongoing stability studies are showing MCAM to be shelf stable for at least 9 months, and analytical methods for manufacturing GMP MCAM are being developed.

In a pre-IND meeting in November 2023 (facilitated by Allucent), the FDA agreed with our proposed non-clinical and clinical programs.

A use patent for MCAM was issued in 2019 and 3 other patents are pending.

This application includes scientists with expertise in drug discovery and development, basic scientists who have studied MCAM extensively, clinicians with expertise testing medications for substance use disorders, as well as commercial CRO partners that will manufacture GMP MCAM (Veranova), synthesize deuterated MCAM (Moravek), conduct non-clinical toxicology and safety pharmacology studies (Charles River Laboratories), and serve as the regulatory agent to the FDA as well as manage clinical trials (Allucent; including a former senior pharmacology/toxicology reviewer who served in the Division of Anesthesia, Addiction Medicine and Pain Medicine, the division that participated in the pre-IND meeting and will review the IND application).

This revised application requests 3 years of support to continue developing MCAM with the following 4 specific aims.

1) Submit an IND for preventing relapse.

2) Complete Phase 1 and Phase 1B clinical trials with MCAM.

3) Plan a Phase 2 clinical trial with MCAM.

4) Conduct additional non-clinical toxicology and other studies as recommended by the FDA.

Completing these aims, along with securing additional intellectual property protection through pending US patents, will further strengthen the feasibility of developing MCAM as a medication for preventing relapse after detoxification.

Completing these aims will also significantly increase the value of this project to potential future partners and investors who have the expertise and financial resources to commercialize MCAM into a marketable product for preventing relapse as well as other possible indications (e.g., prevention and reversal of opioid overdose, prophylaxis for opioid poisoning/weaponization).

The University Of Texas Health Science Center At San Antonio

TO SUPPORT BASIC AND CLINICAL NEUROSCIENCE, BIOMEDICAL, BEHAVIORAL AND SOCIAL SCIENCE, EPIDEMIOLOGIC, HEALTH SERVICES AND HEALTH DISPARITY RESEARCH. TO DEVELOP NEW KNOWLEDGE AND APPROACHES RELATED TO THE PREVENTION, DIAGNOSIS, TREATMENT, ETIOLOGY, AND CONSEQUENCES OF DRUG ABUSE AND ADDICTION, INCLUDING HIV/AIDS. TO SUPPORT RESEARCH TRAINING AND RESEARCH SCIENTIST DEVELOPMENT. TO SUPPORT DISSEMINATION OF RESEARCH FINDINGS. SMALL BUSINESS INNOVATION RESEARCH (SBIR) LEGISLATION IS INTENDED TO EXPAND AND IMPROVE THE SBIR PROGRAMS TO EMPHASIZE AND INCREASE PRIVATE SECTOR COMMERCIALIZATION OF TECHNOLOGY DEVELOPED THROUGH FEDERAL SBIR RESEARCH AND DEVELOPMENT, INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN THE SBIR PROGRAM. THE LEGISLATION INTENDS THAT THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.279 - Drug Abuse and Addiction Research Programs

National Institute on Drug Abuse (NIDA) [HHS - NIH]

San Antonio, Texas 782293901 United States

Single Zip Code

Grand Opportunity in Medications Development for Substance-Use Disorders (U01 Clinical Trial Optional) (PAR-22-202)

Amendment Since initial award the total obligations have increased 100% from $3,937,322 to $7,874,666.