History of Innovation
Adolore Biotherapeutics, Inc. is a new biotechnology company focused on developing breakthrough opioid-free pain relieving (analgesic) treatments for chronic pain. Our founders have started numerous successful innovative therapeutic companies. Building on years of rigorous scientific discovery, continuing innovation, and operational excellence, we are working to make meaningful improvements in the lives of underserved patient populations suffering from debilitating chronic pain conditions. Our enduring efforts have led to the development of first- and best-in-class, long-acting local analgesics that represent Disease-Modifying Anti-Pain therapies (DMAPs) with the capability to alter the underlying pathophysiology of chronic pain.
Our scientific discoveries have taught us that naturally occurring carbonic anhydrase-like peptides (eg, CA proteins) regulate pain sensation and analgesic responses. When CA transgenes producing CA peptides are delivered to the peripheral nervous system using gene therapy via clinically relevant routes of administration, they act as ‘local anesthetics’ transducing pain-sensing neurons to produce profound long-lasting analgesia (estimated greater than 100mg of oral morphine in an average sized adult), without motor blockade (weakness) or clinical pathology in a variety of chronic animal pain models (e.g., nociceptive pain, inflammatory pain and neuropathic pain). Our CA-mediated viral gene therapeutic platform has the potential to be exploited using cutting-edge gene therapy to produce a DMAP pipeline to fight chronic pain as a disease.
Kv7 voltage-gated potassium channel activation can result in dramatic decreases in the frequency of sensory neuron firing while receiving continuous excitatory input from peripheral pain stimuli.
Substantial clinical experience shows Kv7 voltage-gated potassium channel openers (e.g., flupirtine, retigabine) can produce non-opioid-based analgesia in a variety of animal models and human chronic pain conditions. However, despite their great utility in treating various forms of chronic noncancer pain, all Kv7 channel openers were removed from the market several years ago due to adverse events related to their parenteral use. Nonetheless, Kv7 channels remain important analgesic targets. Consequently, our locally administered rdHSV-CA gene therapy addresses a major unmet need by providing a unique safe and effective alternative to opioids with powerful analgesic properties.
We have published and presented extensive proof-of-concept studies in animals establishing CA-mediated analgesia that is produced by decreasing pain sensory neuron excitability through Kv7 voltage-gated potassium channel activation. Adolore is leveraging the advantageous properties of proprietary replication defective type-1 herpes simplex virus (rdHSV) engineered to deliver and express CA analgesic peptides long-term in pain-sensing neurons to treat chronic pain without the limitations and toxicity inherent with most other gene therapies.
Our team has over 30 years each of experience in the progressive design, ‘recombineering’, manufacturing, and quality control of these safe, non-toxic rdHSV vectors to deliver and express therapeutic proteins long-term in the peripheral nervous system. JDNI8 represents the latest version of these rdHSV vector backbones that lacks all viral replication genes making it completely nontoxic. These recent improvements represent a milestone in the development of an ideal vector for our purposes. JDNI8 is the most advanced rdHSV vector backbone platform available, superior to all prior HSV vectors being used in approved therapies and ongoing clinical trials.
These next generation JDNI8 rdHSV vectors have been engineered through ‘recombineering’ to remove all the HSV regulatory genes including ‘ICP0’ required for replication, thereby rendering the vectors completely harmless to humans and animals. The presence of HSV LAT insulator elements in these next generation rdHSV vectors, or the inclusion of cellular insulators in the JDNI8 vector backbone has enabled the long-term expression of transgenes in targeted neurons of the peripheral nervous system.