Pain Syndromes, whether acute, persistent, or chronic, are the result of complex overlapping, and interrelated mechanisms. Current therapies for both Post-surgical pain and chronic pain are inadequate, treating symptoms or individual mechanisms of pain rather than its molecular root causes, allowing redundancies in the system to overcome therapeutic effects.
Standard analgesic regimens for post-operative care can provide management of pain at rest, but often with troubling and dose-limiting side effects. Patient recovery is often limited by poorly controlled spikes in movement-evoked pain, which is currently not addressed by standard-of-care. These aspects of pain remain inadequately addressed by current therapies and can impede normal activity, exacerbate depression and diminish overall quality of life. Across the course of of post-surgical pain, current standard-of-care is not capable of modifying the course of pain and requires repeated administration to produce treatment effects. There exists significant unmet need for pain treatments that can reduce post-surgical pain at rest and with movement, and modify the course of post-surgical pain, potentially preventing the development of chronic pain.
Chronic pain, or pain that limits daily function and persists for three months or longer, has a significant negative impact on individual patients, the entire healthcare system, and the broader economy in general. Current treatments for multiple etiologies of chronic pain primarily ameliorate the symptoms of pain but do not address the molecular root causes of the disorder.
The AYX platform of oligonucleotide therapeutics is specifically designed to transform the treatment of pain by selectively disrupting the complex neuronal mechanisms responsible for establishing and maintaining pain over time, rather than managing pain as a symptom that can be temporarily blunted or dulled with repeated analgesic administrations.
Pain is a complex and dynamic condition resulting from the combined and overlapping activity of a wide array of proteins that establish and maintain nociception and downstream pain sensations. Transcription factors regulate the expression of multiple proteins associated with the establishment and maintenance of pain: they represent a novel class of therapeutic targets with the unique potential to address the molecular complexity underlying pain.
The Adynxx platform utilizes a proprietary technology family of oligonucleotide decoys to selectively inhibit the activity of transcription factors that control proteins responsible for establishing and maintaining nociception and related pain. As a result, AYX therapeutics have the potential to produce transformative therapeutic profiles: one time administration or short course of treatment producing robust and long-lasting pain prevention or suppression.
EGR1 is a transcription factor transiently upregulated in the spinal cord and dorsal root ganglia at the time of surgery or trauma. During this short period of upregulation, EGR1 triggers waves of gene transcription and subsequent protein expression that change neuronal properties, establishing mechanical hypersensitivity and leading to long-term movement-evoked pain arising from a single traumatic incident.
Brivoligide, Adynxx’s lead investigational drug, is a transcription factor decoy that is intended to reduce acute post-surgical pain and prevent the transition to persistent or chronic pain with a single administration at the time of surgery by specifically targeting EGR1. It acts by binding EGR1 locally in the spinal cord/dorsal root ganglia network at the time of surgery or trauma, essentially preventing EGR1 from switching on the sequence of events that lead to persistent and chronic pain after surgery.
Adynxx has successfully completed two Phase 2 studies of brivoligide for the prevention of pain following total knee replacement surgery. In 2013 brivoligide was granted Fast Track designation by the FDA for the prevention of chronic pain.
Chronic pain is the result of undesired and persistent changes to the normal function of neuronal mechanisms. These changes are sustained over time by the continued activity of transcription factors regulating pain-related genes and proteins across multiple etiologies of chronic pain. The ongoing activity of transcription factors in the spinal cord/dorsal root ganglia network serves to both sustain and define the chronic pain state.
AYX2 is specifically designed to target the transcription factors that sustain chronic pain following inflammatory and/or neuropathic insult. By switching off the neuronal mechanisms that maintain chronic pain, AYX2 administration can produce a robust and long-lasting suppression of multiple etiologies of chronic pain.