Novel Therapeutic Agents to Reverse Opioid Overdose

Project Summary/Abstract
The abuse of opioids is a serious national crisis that affects public health as well as social and economic welfare.
A 2018 report from the Centers for Disease Control and Prevention (CDC) shows that every day, 128 people in
the United States die from opioid overdose. Synthetic opioids (e.g. fentanyl) have become the leading cause
of drug-related deaths in recent years. The current standard of care for opioid overdose, naloxone, is not
sufficient in treating intoxication caused by synthetic opioids since its serum half-life is much shorter than that
for synthetic opioids. Renarcotization is known to occur after an initial dose of naloxone. Patients treated for
fentanyl overdose often remain hospitalized for extended periods of time, receiving multiple rounds of naloxone
via infusion. It is reported that high doses or repeated doses of naloxone can cause cardiovascular complications
and sudden withdrawal symptoms. A more effective therapeutic agent is needed to treat patients with
overdoses caused by synthetic opioids.
We have previously identified a small molecule drug candidate with a demonstrated safety and efficacy in
reversing fentanyl-induced respiratory depression in a rat model. Our drug candidate addresses the drawbacks
of naloxone including renarcotization and sudden withdrawal symptoms via a different mechanism of action –
sequestration and removal of opioids in the bloodstream as an effective means of reversing intoxication (similar
to an antibody). Our drug candidate binds opioid in the blood and facilitates its removal from the body. We
propose to conduct a small pilot preclinical study to evaluate the efficacy of our drug candidate in a standard
non-human primate model. The results from this study will allow us to enter an IND-enabling preclinical study
on the candidate molecule.Project Narrative
The goal of this program is to develop a new therapeutic agent to treat intoxication caused by opioids and
especially synthetic opioids. We have identified a lead candidate which reverses fentanyl-induced respiratory
depression and dysfunction of the central nerve system without the drawbacks of naloxone. We propose to
further develop this compound into an effective therapeutic agent.