IND-enabling studies and phase I clinical trials to advance CD74-target, DRhQ, as a treatment for stimulant use disorder

Virogenomics Biodevelopment, Inc., Tigard OR

Investigators

Abstract

PROJECT ABSTRACT Methamphetamine (MA) is a highly addictive central nervous system (CNS) psychostimulant. MA causes long- term damage to regions of the brain that regulate cognitive and psychiatric functions and promote drug-seeking behavior, consequently, recovery from MA addiction is extremely difficult. The current standard of care for stimulant use disorder (SUD) is behavioral therapy but, unfortunately, the majority of patients relapse to MA use within one year after treatment. There are currently no FDA-approved pharmacotherapeutics for MA use disorder (MUD). Emerging evidence demonstrates how immune factors can influence addictive behaviors and contribute to SUDs. We have a collection of MHC class II constructs that bind to and downregulate the expression of CD74—the primary receptor for macrophage migration inhibitory factor (MIF), a key inflammatory indicator in SUD, as well as other diseases. These constructs have therapeutic impact on drug-seeking and drug-taking behavior, and can also impact cognitive function, and inflammation-associated with exposure to MA, suggesting a more effective therapeutic profile than previously developed targets. The primary objective of this UG3/UH3 proposal is to advance our current generation molecule, DRhQ, which has been optimized for CD74 binding, through phase 1 safety trials in both healthy volunteers and in individuals with MUD who also test positive for MA. The UG3 portion of the grant includes using rat animal models to determine the dose and dosing schedule of DRhQ, in its final monomeric formulation, that reduces drug-taking behavior in a progressive-ratio schedule of self-administration and whether DRhQ reverses CNS neuropathology in an innovative compulsive MA use model. Large-scale manufacturing of DRhQ will be completed to support toxicology studies and the phase 1 clinical trials. Following the toxicology studies in both rats and dogs, an investigational new drug (IND) application will be submitted to the FDA for the proposed phase 1 clinical trials. An open IND will be the milestone for transitioning from the UG3 to the UH3. In the UH3, a single ascending dose (SAD) study and a multiple ascending dose (MAD) study will be completed in healthy volunteers. A second phase 1 safety study will be conducted in participants diagnosed with MUD who also test positive for MA to address the potential interaction between MA and DRhQ in patients. At the end of this proposed round of funding, we will have completed first- in-human (FIH) studies that will determine the safety of DRhQ. If found safe, the studies supported by this grant would enable larger phase 2 efficacy studies in individuals seeking treatment for MUD.