UH3DA057850

DEVELOPMENT OF A MONOCLONAL ANTIBODY TO REVERSE OVERDOSE FROM FENTANYL AND ITS ANALOGS: FROM MANUFACTURING TO CLINICAL TRIALS - ABSTRACT. THIS PROJECT SEEKS FUNDING TO COMPLETE MANUFACTURING AND IND-SUPPORTING PHARMACOKINETIC, EFFICACY, AND SAFETY/TOXICOLOGY PRECLINICAL STUDIES FOR A PHASE I CLINICAL TRIAL OF A CANDIDATE HUMANIZED MONOCLONAL ANTIBODY (MAB) TO TREAT AND REVERSE TOXICITY ASSOCIATED WITH OVERDOSE INVOLVING FENTANYL AND ITS POTENT ANALOGS. THE INCIDENCE OF FATAL DRUG OVERDOSES HAS DRAMATICALLY INCREASED DUE TO THE PROLIFERATION AND WIDESPREAD AVAILABILITY OF FENTANYL AND ITS ANALOGS, OFTEN FOUND IN STREET DRUG MIXTURES. FATAL DRUG OVERDOSES TOTALED MORE THAN 92,000 IN 2020. CURRENT MEDICATIONS ARE NOT ALWAYS SUFFICIENT TO PREVENT OR REVERSE OVERDOSE FROM FENTANYL AND ITS ANALOGS. AS A COMPLEMENTARY STRATEGY TO CURRENT MEDICATIONS, OUR TEAM HAS DEVELOPED HUMANIZED MABS AGAINST FENTANYL AND ITS ANALOGS. LEAD MABS ARE EFFECTIVE IN PREVENTING AND REVERSING DRUG-INDUCED RESPIRATORY DEPRESSION AND BRADYCARDIA IN RODENTS EXPOSED TO FENTANYL AND CARFENTANIL. ANTI-DRUG MABS SELECTIVELY SEQUESTER THE TARGET DRUG FROM CIRCULATION. DUE TO THEIR SELECTIVITY FOR THE TARGET(S), OUR MABS DO NOT INTERFERE WITH ENDOGENOUS LIGANDS, FDA-APPROVED MEDICATIONS FOR TREATING OPIOID USE DISORDERS (OUD) AND OVERDOSE, AND OTHER CRITICAL MEDICATIONS. ANTI-FENTANYL MABS CAN BE CO-ADMINISTERED WITH STANDARD OF CARE TREATMENTS FOR OUD AND/OR OVERDOSE, AND MAY OFFER LONGER-LASTING CLINICAL BENEFITS OVER OPIOID RECEPTOR ANTAGONISTS. TRANSLATION OF MABS WILL BENEFIT THOSE WITH AN OUD AND OTHER INDIVIDUALS AT HIGH-RISK OF FATAL OVERDOSES FROM ACCIDENTAL OR DELIBERATE EXPOSURE TO FENTANYL AND FENTANYL ANALOGS. THIS UG3/UH3 PROJECT PROPOSES A MILESTONE-DRIVEN ITERATIVE DEVELOPMENTAL PLAN WITH PREDETERMINED GO/NO GO CRITERIA TO ADVANCE A MAB AGAINST FENTANYL AND ITS ANALOGS TO THE CLINIC. AIM1 FOCUSES ON THE GMP MANUFACTURING OF A LEAD CANDIDATE MAB IN COLLABORATION WITH A PARTNER CDMO. AIM2 FOCUSES ON IND-ENABLING POTENCY AND EFFICACY STUDIES IN KEY ANIMAL MODELS. AIM3 FOCUSES ON THE GLP TOXICOLOGY AND SAFETY OF THE LEAD MAB. AIM4 FOCUSES ON PHASE I CLINICAL TRIALS TO FIRST TEST MAB SAFETY, PHARMACOKINETICS, AND IMMUNOGENICITY, AND THEN MAB EFFICACY AGAINST FENTANYL IN HEALTHY HUMAN SUBJECTS. COMPLETION OF THIS PROJECT WILL PROVIDE CLINICAL DATA TO SUPPORT MAB TESTING IN FUTURE PHASE II-III TRIALS.

University Of Washington

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]

Seattle, Washington 981951016 United States

Single Zip Code

Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional) (PAR-20-092)