Advancing a non-addictive, peripherally acting opioid analgesic as a medication strategy to prevent opioid use disorder in patients undergoing treatment for pain

Dimerx, Mill Valley CA

Investigators

Abstract

In 2021, ~52 million U.S. adults experienced chronic pain. Opioids, commonly prescribed for chronic pain, can lead to opioid use disorder (OUD), with about 25% of patients using prescription opioids becoming addicted and transitioning to more dangerous substances like heroin and synthetic opioids such as fentanyl. In response, opioid prescriptions have been limited to prevent OUD, but this has often led to inadequate pain relief and a surge in illicit drug use. The optimum strategy for preventing OUD involves the development of an effective analgesic that treats chronic pain usually managed by conventional opioids without the risk of addiction. Thus, a molecule that can reduce pain by acting on peripheral opioid receptors while avoiding central nervous system (CNS) opioid receptor involvement, including addiction, is critically needed. DIMERx, Inc. has developed DMX- 101 (CAS No: 1820753-68-1), an innovative nonaddictive analgesic exclusively targeting peripheral opioid receptors while sparing CNS involvement. DMX-101 is synthesized by the covalent cross-linking of two didehydrogenated buprenorphine molecules to form a dimer. DMX-101 acts on peripheral opioid receptors and does not affect the CNS because it does not cross the blood-brain barrier. Therefore, DMX-101 can deliver the strong pain management effects of opioids while avoiding the negative side effects. Previous clinical trials of DMX-101 treatment of diarrhea-prominent irritable bowel syndrome, which involves visceral pain, showed beneficial effects of the drug without signs or symptoms of CNS opioid engagement, addiction, or withdrawal effects. We hypothesize that DMX-101 will ameliorate chronic pain without the inadvertent effects of opioid analgesia, including addiction and hyperalgesia. This UG3/UH3 project aims to rigorously evaluate DMX-101's safety and efficacy through various phases. The UG3 phase encompasses three aims that also meet FDA requirements: (1) assess the abuse liability potential of DMX-101 in rats, (2) demonstrate that DMX-101 does not bind to CNS opioid receptors in rats, and (3) evaluate toxicity in dogs. Successful completion of these aims, including no signs of abuse potential, no CNS receptor occupancy, and confirmation of safety and tolerability, will transition the project to the UH3 phase. This phase includes conducting two Phase 1 studies on the safety, pharmacokinetics, and pharmacodynamics of twice-daily dosing of DMX-101 in healthy adults and DMX-101's abuse liability in otherwise healthy, non-dependent, recreational opioid users to show the drug's safety profile, dosage parameters, and non-addictive nature. Successful completion of this project will support future large- scale Phase 2 clinical studies of the effectiveness of DMX-101 in individuals with chronic pain. The company will also support the program through private financing. The successful development and clinical approval of DMX- 101 would have a profound impact on public health, offering a viable solution to manage chronic pain without contributing to the escalating opioid crisis.