Clinical Development of SBS-147: First-in-class Oral Arylepoxamide Agonist for Pain

ABSTRACT
Pain, both acute and chronic, are serious medical conditions that have and continue to
significantly drive the growing opioid epidemic in the US. Opioids can be effective analgesics
when used appropriately, but their adverse event profile and abuse potential are major contributors
to the devasting prevalence of OUD and overdose deaths. Even when used as indicated, ~6% of
opioid naïve patients who receive opioids post op becoming chronic opioid users. Chronic opioid
use is a risk factor for developing opioid use disorder (OUD) due to development of physical
dependence and psychological factors. Therefore, it is clear that any use of opioids for the
treatment of acute or chronic pain poses a risk of developing OUD and worsening the opioid
epidemic. However, strong pain relievers are critical in treating acute pain because considerable
evidence suggests that the intensity and duration of untreated acute pain independently predicts
the risk of developing long-term chronic pain, which is in itself a risk factor for developing opioid
dependence, substance use disorders, and overdose death. Novel analgesics are needed to prevent
the growing prevalence of OUD and overdose deaths.
SBS-147 is a first-in-class non-opioid oral AEAr agonist being developed for both acute
and chronic pain. Preclinically it is effective in treating moderate to severe nociceptive,
neuropathic, and inflammatory pain. Most importantly, it does not demonstrate physical
dependence, respiratory depression, or abuse liability. SBS-147 is an oral version of SBS-1000 IV
which recently completed a phase 1 clinical trial. SBS-1000 demonstrated safety and tolerability
in healthy volunteers with a signal of efficacy in the Cold Pressor Test and no pupil constriction
indicating no opioid receptor involvement. Therefore, development of SBS-147 is derisked given
the existing clinical data on SBS-1000.
This grant proposes to conduct clinical development of SBS-147 via a Phase 1 SAD/MAD
clinical trial to characterize the safety/tolerability and pharmacokinetics of the compound as well
as a Phase 2A dental pain study to generate proof of concept efficacy data. Overall, the
development of SBS-147 as a novel analgesic could curb the opioid epidemic by providing a non-
opioid alternative for a variety of pain types and preventing the utilization of opioids.

Grant Number: 1UG3DA064392-01
NIH Institute/Center: NIH
Principal Investigator: Judy Ashworth