UG3DA060053

Development of a safer and more effective ibogaine analog for the treatment of opioid use disorder - summary

Opioid use disorder (OUD) contributes to disability, loss of work, and over 100,000 overdose deaths per year in the U.S., emphasizing the critical need for novel medications for OUD treatment.

Ibogaine, a psychoactive alkaloid from the Tabernanthe iboga shrub, has shown promise in interrupting opioid dependence, reducing withdrawal symptoms, and increasing abstinence rates, even after a single treatment.

However, ibogaine's cardiotoxicity and neurotoxicity pose significant barriers to its development as a drug.

To leverage ibogaine’s potential as an OUD therapeutic and address the risks to patient safety, we have developed a new class of synthetic iboga alkaloids, named “OXA-iboga”.

These compounds show no pro-arrhythmic potential, no neurotoxic effects, and enhanced efficacy in OUD-relevant preclinical behavioral assays compared to ibogaine.

We propose to advance one of these compounds, GM-3009, into clinical studies by advancing GMP-manufacturing and formulation of GM-3009, completing IND-enabling toxicity studies, and determining the expected therapeutic exposures of GM-3009 and target engagement via translational biomarkers.

These studies will complete the UG3 portion of this grant.

If successful, the proposal will advance to the UH3 portion, which will conduct first-in-human trials, including safety and tolerability studies in healthy volunteers (a single ascending dose study, SAD) and a safety study with exploratory measures of efficacy in OUD patients undergoing opioid withdrawal.

The endpoint of the entire project is generation of clinical safety and preliminary efficacy data to support subsequent phase 2 efficacy studies in OUD.

The development of GM-3009 builds on decades of research on ibogaine and has the potential to deliver an innovative OUD therapy with rapid and long-term mitigation of acute and protracted withdrawal symptoms and cravings, which lead to non-medical opioid use.

Gilgamesh Pharmaceuticals

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]

New York, New York 100034527 United States

Single Zip Code

Development of Medications to Prevent and Treat Opioid and/or Stimulant Use Disorders and Overdose (UG3/UH3 - Clinical Trial Optional) (PAR-22-200)

Amendment Since initial award the total obligations have increased 99% from $2,731,914 to $5,439,548.