Kannalife Sciences Inc.

Development of KLS-13019 for Neuropathic Pain - Neuropathic Pain Remains a Challenging Neurologic Disorder That Adversely Affects Quality of Life and Presents a Large Unmet Medical Need. Chemotherapy-induced Peripheral Neuropathy (CIPN) Is a Chronic, Severely Debilitating Consequence of Cancer Therapy for Which There Are No Effective Management Strategies. Upwards of 80-97% of Cipn Patients Reported Using Prescription Opioids for This Pain Management. Mitochondrial Dysfunction, Oxidative Stress, and Inflammation Have All Been Implicated in Cipn Etiology. in a Mouse Model of Paclitaxel-induced Pain Sensitivity, We Have Previously Reported That Cannabidiol (CBD) Is Effective in Preventing the Onset of This Treatment Consequence. Now a New CBD Analogue (KLS-13019) Has Been Discovered in Our Laboratory That Has Improved Drug-like Properties in Comparison to CBD, While Retaining Neuroprotective Properties. in Our Phase 1 STTR, the Previous Neuroprotective Effects of CBD to Prevent the Development of Mechanical Sensitivity in the Presence of Paclitaxel Were Confirmed and Extended to the Structural Analogue KLS- 13019. Both Compounds Were Equi-effective and Equi-potent Following Oral Administration. in the Reversal Studies, CBD Did Not Attenuate Mechanical Sensitivity When Administered After Cipn Was Induced by Paclitaxel Treatment. However, KLS-13019 Significantly and Dose-dependently Attenuated Tactile Sensitivity in the Reversal Paradigm and Was More Potent and Effective Than Treatment With Morphine. Importantly, KLS-13019 Also Attenuated the Reinforcing Properties of Morphine in a Mouse Model of Morphine Self-administration. in Vitro, We Have Shown That KLS-13019 and CBD Protect Against Paclitaxel-induced Oxidative Stress in Dorsal Root Ganglia Cultures, and That a Mechanism Underlying This Neuroprotection Is Regulation of Intracellular Calcium via the Mitochondrial Na+/ca++ EXCHANGER-1 (MNCX-1). Our Central Hypothesis Is That Administration of CBD or KLS-13019 Preserves CA2+ Homeostasis by Promoting Activity of the MNCX-1. Furthermore, Our New Data Demonstrates That the Putative Cannabinoid Receptor GPR55 Is Induced Following Paclitaxel Treatment and Contributes to Sensory Neuron Toxicity and Inflammation That Can Be Reversed by KLS-13019, But Not CBD. These Studies Support a Pro- Nociceptive, Pro-inflammatory Role for GPR55 That Mediates Pain Associated With Cipn. We Predict Bi-modal Pharmacological Effects of KLS-13019 That Can Both Increase Viability of Sensory Neurons Exposed to Paclitaxel Acutely and Decrease Inducible GPR55 That Contributes to Long-term Neuroinflammation. Evidence Has Been Obtained That KLS-13019 Is an Antagonist to GPR55 as Shown in a Ss-arrestin Assay. in Phase 2, We Will Optimize the Process to Prepare KLS-13019, Develop Analytical Methods, Optimize Formulation, and Evaluate in Pharmacokinetic Studies. a Fully Battery of Genotoxicity, Safety Pharmacology, Toxicokinetic, and Toxicology Reports Will Be Completed. KLS-13019 Will Be Evaluated in a Rat Models of Cipn, Tolerance, Impairment, and Abuse Liability. at the Conclusion of This Grant, the Data Will Be Submitted to the Fda and a Pre-ind Meeting Will Be Completed.