Pharmacokinetic and toxicology studies of AYX2, a transcription factor decoy, non-opioid, disease modifying drug candidate for the long-term treatment of chronic pain - RESEARCH AND RELATED OTHER PROJECT INFORMATION - PROJECT SUMMARY / ABSTRACT
Funding Opportunity: PA-18-574 - PI Name: Mamet, Julien
As described by the HEAL Initiative Notice NOT-NS-19-014, there currently exists an urgent unmet need
for enhanced pain management in the form of safe, effective, non-opioid pain treatments. Chronic focal
neuropathic pain, which includes pain etiologies such as radiculopathy and radiculitis1-3, focal peripheral
neuropathies4, and low back pain5, affects as many as 25 million patients annually in the United States. These
conditions are commonly treated with opioid analgesics, with some patients subsequently experiencing addiction
and abuse. Chronic focal neuropathic pain is maintained by genome-wide transcription regulation in the dorsal
root ganglia (DRG) / spinal cord network. The transcription factors driving this regulation constitute a promising
class of targets with the potential to alter the course of pain with a single treatment.
DNA decoys are oligonucleotides that specifically inhibit the activity of certain transcription factors.
Following advancement of Adynxx’s lead decoy program, brivoligide (formerly AYX1) the for treatment
postoperative pain, into Phase 2 clinical studies, Adynxx began development of its second decoy AYX2 for
altering the course of chronic pain. AYX2 binds and inhibits Krüppel-like transcription factors (KLF) 6, 9 and 15
in the DRG-spinal cord. In the Spared Nerve Injury and Chronic Constriction Injury rat models of chronic pain, a
single intrathecal (IT) injection of AYX2 produces a substantial, weeks-long reduction of pain compared to
controls.6
The goal of this Phase 1 proposal is to advance AYX2 toward an IND submission, allowing for human
clinical trials. We propose in Aim 1 to characterize AYX2 pharmacokinetics in the cerebrospinal fluid and plasma
and its distribution in the DRG, spinal cord and brain following an IT injection. With this information, AYX2 will
be tested in a panel of complementary toxicology studies in Aim 2 to allow for final IND-enabling studies,
supported by Phase 2 of the grant. This research will accelerate development of AYX2 as a novel drug candidate
for the non-opioid treatment of pain.
