KLS-13019 / Neuropathix - LARVOL DELTA

KLS-13019, a novel structural analogue of cannabidiol (CBD) and GPR55 receptor antagonist, Prevents and Reverses Chemotherapy-Induced Peripheral Neuropathy (CIPN) in Rats. (PubMed, J Pharmacol Exp Ther) - "Tactile sensitivity associated with chemotherapy exposure was induced in rats with once daily 1mg/kg paclitaxel injections for 4 days or 5 mg/kg oxaliplatin every third day for one week. GPR55 antagonist KLS-13019 represents a novel class of drug for this condition that is a potent, durable inhibitor of allodynia associated with CIPN in rats in both prevention and reversal dosing paradigms. This novel therapeutic approach addresses a critical area of unmet medical need."

Journal • Preclinical • Addiction (Opioid and Alcohol) • Colorectal Cancer • Neuralgia • Oncology • Pain • GPR55

Knockdown siRNA Targeting GPR55 Reveals Significant Differences Between the Anti-inflammatory Actions of KLS-13019 and Cannabidiol. (PubMed, J Mol Neurosci) - "CBD was shown previously to be ineffective in reversing paclitaxel-induced mechanical allodynia. The present studies indicated significant differences between the anti-inflammatory properties of KLS-13019 and CBD which may play a role in their observed differences in the reversibility of mechanical allodynia in a mouse model of CIPN."

Journal • Inflammation • Pain • GPR55 • IL1B • NLRP3

Efficient Syntheses of KLS-13019 Using Palladium Mediated Cross Couplings. (PubMed, Tetrahedron Lett) - "KLS-13019 is a structural analogue of cannabidiol, that shows improved bioavailability and potency in both preventing and reversing paclitaxel-induced neurotoxicity in vitro and in vivo. Two new syntheses are reported that make use of the palladium catalyzed cross couplings to a chemically advanced intermediate 5, dramatically shortening (3-4 steps) and improving the overall yield. In addition, a convenient one pot Boc-cleavage and acetylation procedure is described to avoid impurities generated from a step-wise process."

Journal

Anti-Inflammatory Properties of KLS-13019: a Novel GPR55 Antagonist for Dorsal Root Ganglion and Hippocampal Cultures. (PubMed, J Mol Neurosci) - "Time course studies with 3 µM paclitaxel indicated > 1.9-fold increases in immunoreactive (IR) area for cell body GPR55 after 30 min as determined by high content imaging. These studies indicated that KLS-13019 has anti-inflammatory properties mediated through GPR55 antagonist actions. Together with previous studies, KLS-13019 is a potent neuroprotective, anti-inflammatory cannabinoid with therapeutic potential for high efficacy treatment of neuropathic pain."

Journal • Immunology • Inflammation • Neuralgia • Pain • Peripheral Neuropathic Pain • IL1B • NLRP3

Neuropathix, Inc. Highlights Positive Preclinical Study Results on Lead Drug Candidate KLS-13019 (Yahoo News) - "Neuropathix, Inc...today positive preclinical data published in the British Journal of Pharmacology. The publication centered on pre-clinical research for its proprietary, cannabinoid-derived analog KLS-13019 showing both the prevention and reversal of chemotherapy-induced peripheral neuropathy (CIPN)....Over the course of several weeks, nine unique experiments took place where researchers introduced mice to a pure form of CBD, morphine or KLS-13019, then observed their effects on the mechanical sensitivity of the mice. Key findings from the studies showed that while CBD and KLS-13019 were both effective in preventing the development of pain associated with CIPN, KLS-13019 was also able to reverse CIPN-related pain - while CBD proved ineffective in doing so. Even more noteworthy, results from the studies revealed that KLS-13019 did not bind to opioid receptors in the brain, meaning it holds a very low risk for chemical dependency."

Preclinical • CNS Disorders • Neuralgia • Pain • Peripheral Neuropathic Pain

Neuropathix, Inc. CEO Issues New Letter to Shareholders; Updates Market on Milestones in Research and Funding (Yahoo News) - "Neuropathix, Inc...announced today that its CEO Dean Petkanas has issued a letter to its shareholders, providing commentary on the Company's recently achieved milestones, updates on its research and financial positioning....Neuropathix continues to move forward in preparation of an IND filing for the use of KLS-13019 in CIPN. The next two major steps in 2022 will be the successful completion of the first leg of commercial scale up and a drug discrimination study in animals. Year two of the grant funding should enable the Company to move KLS-13019 into animal toxicity studies by early 2023, as the next steps towards IND submission with the US FDA."

Preclinical • CNS Disorders • Neuralgia • Pain • Peripheral Neuropathic Pain

Neuropathix, Inc. Chooses Purisys for Process Optimization and Scale Up of Its Lead Drug Candidate KLS-13019 (Yahoo News) - "Neuropathix, Inc...announced today that it has chosen to engage Purisys LLC to optimize and scale up KLS-13019 as the Company moves forward with its plans for animal toxicity studies in 2022, and a path towards human clinical trials thereafter....The Company's clinical development approach calls for, among other things, the optimization by Purisys of the current synthesis and process of producing KLS-13019. A successful bulk synthetic API process for KLS-13019 will enable animal toxicity studies and be central to the Company's clinical manufacturing plans of KLS-13019 when it files its IND with the FDA for the treatment of the prevention and reversal of chemotherapy induced peripheral neuropathy (CIPN)."

Commercial • CNS Disorders • Neuralgia • Pain • Peripheral Neuropathic Pain

Neuropathix, Inc. Wholly Owned Subsidiary Kannalife Sciences, Inc. Awarded $2.97 Million Phase 2 Study Grant from National Institute of Neurological Disorders and Stroke (NINDS) (Yahoo News) - Pharmaceutical Assets Include Company's Non-Opioid Anti-inflammatory Compound KLS-13019 to Treat Chemotherapy Induced Peripheral Neuropathy (CIPN). Company's Strategy is to Utilize the Phase 2 Study Grant Funds to Complete Preclinical Studies in CIPN and Ready the Company to Begin FDA Phase 1 Human Clinical Trials...Neuropathix...announces that its wholly owned subsidiary, Kannalife Sciences, Inc. has received a notice of award from the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NIH) for a $2.97 million Phase 2 STTR Study Grant....The Notice of Award R42NS120548 sets forth the funding allocation of $977,054 in year 1, $991,944 in year 2 and $1,001,774 in year 3."

Financing • CNS Disorders • Neuralgia

Neuropathix, Inc. Announces Publication of Validated Preclinical Studies on KLS-13019 in the British Journal of Pharmacology (GlobeNewswire) - "Neuropathix...The findings, published in the British Journal of Pharmacology, show the ability of Neuropathix’s patented compound KLS-13019 to prevent and reverse chemotherapy-induced peripheral neuropathy (CIPN) in mice...The paper, titled 'Behavioral and pharmacological effects of cannabidiol (CBD) and the CBD analogue KLS-13019 in mouse models of pain and reinforcement,' details the results found in the study...'We are excited to share these preclinical results with our communities and continue to characterize the safety and effectiveness of KLS-13019.'"

Preclinical • Neuralgia • Pain • Peripheral Neuropathic Pain

"$NPTX Neuropathix, Inc. Announces Publication of Validated Preclinical Studies on KLS-13019 in the British Journal of Pharmacology https://t.co/SGVsGmAMo9" (@otcdynamics)

Preclinical

Behavioral and pharmacological effects of cannabidiol (CBD) and the CBD analogue KLS-13019 in mouse models of pain and reinforcement. (PubMed, Br J Pharmacol) - "KLS-13019 shares CBD's ability to prevent the development of CIPN, while KLS-13019 uniquely attenuated established CIPN. Because KLS-13019 binds to fewer biological targets, these findings can bring us closer to identifying molecular mechanisms shared by the two compounds as well as those unique to KLS-13019. Lastly, KLS-13019 may possess the ability to attenuate reinforced behavior, an effect not observed in the present study with CBD."

Journal • Preclinical • Pain

Neuropathix, Inc. CEO Recaps 2020 Advances and Potential Ahead (GlobeNewswire) - "Today we believe, more than ever before, that our Company has positioned our lead therapeutic compound KLS-13019 as a very viable candidate for a future human clinical trial program for the treatment of CIPN...We are excited for the 2021 campaign and our drive to move KLS-13019 into FDA human clinical trials."

New trial • Neuralgia • Pain • Peripheral Neuropathic Pain

Neuropathix, Inc. Reveals Visual Identity to Coincide With Its Mission for Socially Responsible Pain Management (GlobeNewswire) - "Neuropathix, Inc....formerly Kannalife, Inc., is a socially responsible pain management life sciences company....Coinciding with its new brand identity and name change, the Company has updated its logo and visual identity to reflect the Company’s extensive life sciences research in cannabinoid therapeutics, drug discovery and current goal of bringing much-needed potent, non-opioid alternatives for the treatment of chronic and neuropathic pain to market."

Commercial • Alzheimer's Disease • CNS Disorders • Neuralgia • Pain • Parkinson's Disease

Kannalife, Inc. Receives Patent in the European Union (EU) for its Novel Monotherapeutic Compound to Treat CNS and PNS Disorders (GlobeNewswire, Kannalife, Inc.) - "Kannalife, Inc....announced today that the European Patent Office has issued the Company, European Patent EP3094318B1 (the 'i8l.utPatent') specific to 'Novel Functionalized 1,3-Benzene Diols and their Method of Use for the Treatment of Hepatic Encephalopathy'...Under the Patent, Kannalife will further explore the application and potential of new molecular entities (NMEs) across epilepsy, neuropathic pain...Epileptic Encephalopathy, and neurodegenerative diseases such as Parkinson's disease, Alzheimer's, Huntington's disease, and amyotrophic lateral sclerosis (ALS)....The Company recently completed a phase 1 study funded by a grant from the National Institutes of Health’s National Institute on Drug Abuse."

Patent • Trial completion • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • Cardiovascular • CNS Disorders • Complement-mediated Rare Disorders • Epilepsy • Gene Therapies • Hepatic Encephalopathy • Huntington's Disease • Movement Disorders • Neuralgia • Pain • Parkinson's Disease • Reperfusion Injury

Kannalife, Inc. Bolsters IP Portfolio with Multiple Patents Issued in 12 Key European Territories (GlobeNewswire) - "Kannalife, Inc....announced today that the Company has been issued patents in Switzerland (CH), Germany (DE), France (FR), United Kingdom (GB), Ireland (IE), Italy (IT), Spain (ES), Belgium (BE), Sweden (SE), Turkey (TR), the Netherlands (NL), and Denmark (DK) for its patent known as WO2015/106108A2....The Company recently completed a STTR phase 1 study funded by a grant from the National Institutes of Health’s National Institute on Drug Abuse. The study was performed in an animal model to evaluate the potential use of KLS-13019 as a potent, non-opioid alternative monotherapeutic in the prevention and reversal of CIPN."

Patent • Preclinical • CNS Disorders • Hepatic Encephalopathy • Pain

Kannalife, Inc. CEO Featured in OTCQB Podcast Discussing KLS-13019 and Its Potential Role as a Non-Opioid Treatment for Neuropathic Pain (GlobeNewswire, Kannalife, Inc.) - "Petkanas explained how the Company’s patented leading drug candidate, KLS-13019, may reduce the use of opioids in the treatment of neuropathic pain. While opioids are considered the standard of care to treat neuropathic pain in the U.S., he spoke of the Company’s promising research efforts and the recently published preclinical results showing that KLS-13019 may be a viable non-addictive, non-opioid option to prevent and reverse neuropathic pain....During the podcast, Mr. Petkanas also discussed...how the Company pivoted to chronic pain through a Phase 1 research grant from the National Institutes of Health – National Institute on Drug Abuse (NIH-NIDA) to study KLS-13019 as a potential treatment for Chemotherapy-Induced Peripheral Neuropathy (CIPN)."

Preclinical • Addiction (Opioid and Alcohol) • CNS Disorders • Gene Therapies • Genetic Disorders • Metabolic Disorders • Neuralgia • Pain • Peripheral Neuropathic Pain • Psychiatry

Kannalife, Inc. Receives Seventh Patent by Extending Patent Family to Australia for Its Novel Monotherapeutic Compounds to Treat CNS and PNS Disorders (GlobeNewswire, Kannalife, Inc.) - " Kannalife, Inc....announced today that the Company has been issued Australian Patent AU2015204609B2 (the 'Patent') specific to 'Novel Functionalized 1,3-Benzene Diols and their Method of Use for the Treatment of Hepatic Encephalopathy'...Under the Patent, Kannalife will further explore the application and potential of new molecular entities (NMEs) across epilepsy, neuropathic pain, traumatic head injury, stroke, Chronic Traumatic Encephalopathy (CTE), Post Cardiac Arrest Hypoxic Ischemic Encephalopathy, Epileptic Encephalopathy, and neurodegenerative diseases such as Parkinson's disease, Alzheimer's, Huntington's disease, and amyotrophic lateral sclerosis (ALS)."

Patent

Kannalife Bolsters its Global Intellectual Property Portfolio with New Chinese-Issued Patent (GlobeNewswire, Kannalife, Inc.) - "Kannalife, Inc....announced today that China has issued the Company, Chinese Patent CN106456573B (the 'Patent') specific to 'Novel Functionalized 1,3-Benzene Diols and their Method of Use for the Treatment of Hepatic Encephalopathy,' which further bolsters the Company’s global patent portfolio of cannabidiol (CBD)-like molecules. The Company anticipates receipt of patent grants from the EU and Australia sometime during the first and second quarters of 2020....Kannalife’s intellectual property estate of CBD-like molecules...KLS-13019, are capable of acting as neuroprotective agents and have the potential to treat a range of diseases, including nervous system, oxidative stress and neurodegenerative disorders."

Patent

Kannalife Bolsters its Global Intellectual Property Portfolio with New Chinese-Issued Patent (GlobeNewswire, Kannalife, Inc.) - "Kannalife, Inc....announced today that China has issued the Company, Chinese Patent CN106456573B (the 'Patent') specific to 'Novel Functionalized 1,3-Benzene Diols and their Method of Use for the Treatment of Hepatic Encephalopathy,' which further bolsters the Company’s global patent portfolio of cannabidiol (CBD)-like molecules. The Company anticipates receipt of patent grants from the EU and Australia sometime during the first and second quarters of 2020....Under the Patent, Kannalife will further explore the application and potential of new molecular entities (NMEs) across epilepsy, neuropathic pain, traumatic head injury, stroke, Chronic Traumatic Encephalopathy (CTE), Post Cardiac Arrest Hypoxic Ischemic Encephalopathy, Epileptic Encephalopathy, and neurodegenerative diseases such as Parkinson's disease, Alzheimer's, Huntington's disease, and amyotrophic lateral sclerosis (ALS)."

Patent

Kannalife, Inc. Announces Completion of NIH-NIDA Phase 1 Grant and Results from Lewis Katz School of Medicine at Temple University for the Potential Use of KLS-13019 in the Treatment of CIPN (GlobeNewswire, Kannalife, Inc.) - "Kannalife...announced today that it has completed its phase 1 study funded by a grant (1R41DA044898-01) from the National Institutes of Health’s (NIH) National Institute on Drug Abuse (NIDA). The study was performed by Kannalife and the Lewis Katz School of Medicine at Temple University (LKSOM) to assess KLS-13019, the Company’s patented cannabidiol (CBD)-like molecule as a potential treatment of neuropathic pain and drug dependence."

Grant

Kannalife, Inc. CEO Recaps 2019 Advances and Potential Ahead (GlobeNewswire, Kannalife, Inc.) - "Results from Kannalife’s study published in the Journal of Molecular Neuroscience regarding the pharmacological comparisons between cannabidiol (CBD) and leading drug candidate KLS-13019 for the potential treatment of Chemotherapy-Induced Peripheral Neuropathy (CIPN), conducted under a research grant from the National Institute of Health (NIH) - National Institute on Drug Abuse (NIDA). Clinical trials for KLS-13019 for CIPN are targeted to begin in Q3 2021."

Clinical • Trial status

Kannalife, Inc. Issues Update on Intellectual Property and Patent Estate (GlobeNewswire, Kannalife, Inc.) - “Kannalife’s intellectual property estate of the KLS Family of cannabidiol (CBD)-like molecules led by KLS-13019, as the patent states, are molecules capable of acting as neuroprotective agents and could potentially be useful for the treatment of...neurodegenerative diseases such as Parkinson's disease, Alzheimer's, Huntington's disease, and amyotrophic lateral sclerosis (ALS).”

Clinical • Commercial

Kannalife, Inc. further elucidates mechanism of action behind KLS-13019, the company’s leading drug candidate for the potential treatment of neuropathic pain (GlobeNewswire, Kannalife, Inc.) - "Kannalife...announced today that it has further elucidated the mechanism of action (MOA) of its leading investigative drug candidate KLS-13019, a CBD-like molecule for the potential treatment of neuropathic pain....KLS-13019 plays an important role in the regulation of mNCX-1, an important pharmacological target in the prevention and in-part reversal of CIPN in the pre-clinical animal model."

Preclinical

Knockdown siRNA Targeting the Mitochondrial Sodium-Calcium Exchanger-1 Inhibits the Protective Effects of Two Cannabinoids Against Acute Paclitaxel Toxicity. (PubMed, J Mol Neurosci) - "Treatment with cannabidiol (CBD) or KLS-13019 (novel CBD analog), has previously been shown to prevent paclitaxel-induced mechanical allodynia in a mouse model of chemotherapy-induced peripheral neuropathy (CIPN). These data indicate that decreases in neuritic mNCX-1 corresponded closely with decreased protection after siRNA treatment. Pharmacological blockade of mNCX-1 with CGP-37157 produced complete inhibition of cannabinoid-mediated protection from paclitaxel in DRG cultures, supporting the observed siRNA effects on mechanism."

Journal

Kannalife, Inc. to Present Breakthrough CIPN Study Findings on the Comparison of KLS-13019 to CBD at 29th Annual International Cannabinoid Research Society Conference (GlobeNewswire, Kannalife, Inc.) - "Kannalife, Inc....announced today that Douglas Brenneman, PhD, will present the Company’s recent research findings at the 29th Annual International Cannabinoid Research Society Symposium on the Cannabinoids in Bethesda, Md., on July 2. Dr. Brenneman, slated to begin his presentation at 11:15 am EST on July 2, will discuss the Company’s research findings recently published in the Journal of Molecular Neuroscience (JOMN). The research published in the JOMN describes, in detail, the siRNA knockdown and mechanism of action for both KLS-13019 and cannabidiol (CBD) in the potential treatment of chemotherapy-induced peripheral neuropathy (CIPN)."

Clinical