Cannabidiol - Kali-Extracts/PAO Group
Alternative Names: NCMB-1; RespRxLatest Information Update: 28 Feb 2024
At a glance
- Originator Kali-Extracts
- Developer Kali-Extracts; PAO Group
- Class Analgesics; Anti-inflammatories; Anti-ischaemics; Antiacnes; Antibacterials; Antiepileptic drugs; Antihyperglycaemics; Antihyperlipidaemics; Antineoplastics; Antiparkinsonians; Antipsoriatics; Antipsychotics; Antirheumatics; Antivirals; Anxiolytics; Behavioural disorder therapies; Cannabinoids; Cardiovascular therapies; Cyclohexenes; Drug withdrawal therapies; Heart failure therapies; Hepatoprotectants; Muscle relaxants; Neuroprotectants; Obesity therapies; Resorcinols; Skin disorder therapies; Small molecules
- Mechanism of Action 5-HT1 serotonin receptor modulators; Cannabinoid receptor CB1 inverse agonists; Cannabinoid receptor CB2 inverse agonists; Transient receptor potential channel modulators; Virus internalisation inhibitors
-
Orphan Drug Status
Orphan designation is assigned by a regulatory body to encourage companies to develop drugs for rare diseases.
- New Molecular Entity No
Highest Development Phases
- Preclinical Lung cancer
- No development reported Chronic obstructive pulmonary disease; COVID 2019 infections; Respiratory tract disorders
Most Recent Events
- 28 Feb 2024 No recent reports of development identified for research development in Respiratory-tract-disorders in USA (PO, Liquid)
- 28 Sep 2023 No recent reports of development identified for clinical-Phase-Unknown development in COVID-2019-infections in USA (PO, Liquid)
- 28 Aug 2022 No recent reports of development identified for phase-I development in Chronic-obstructive-pulmonary-disease in USA (PO, Liquid)
Development Overview
Introduction
A liquid formulation of cannabidiol enriched extract (also known as NCMB1) is being developed by PAO Group, for the treatment of symptoms associated with chronic obstructive pulmonary disease (COPD), coronavirus infection, other respiratory conditions and lung cancer. Specifically for COVID-2019 infections, the two compounds, CBDA and CBGA, bind to spike proteins on the virus and block the spike protein from binding to sites in human host. The drug was originally developed by Kali Extracts, and later acquired by PAO Group. Kali Extracts used a patented cannabis extraction process of NCM Biotech for extraction of cannabinoid extract. Clinical development for the treatment of chronic obstructive pulmonary disease and symptoms associated with COVID-2019 infections is underway in the US. Preclinical development for the treatment of lung cancer is underway in the US. Early research for the treatment of respiratory conditions is ongoing in the US.
In 2018, Kali-Extracts acquired NCM Biotech [1] .
As at August 2022, no recent reports of development had been identified for phase-I development in Chronic-obstructive-pulmonary-disease in USA (PO, Liquid).
As at September 2023, no recent reports of development had been identified for clinical-Phase-Unknown development in COVID-2019-infections in USA (PO, Liquid).
As at February 2024, no recent reports of development had been identified for research development in Respiratory-tract-disorders in USA (PO, Liquid).
Company Agreements
In July 2020, PAO Group Inc entered into a purchase agreement with Kali-Extracts Inc for acquiring cannabidiol (RexpRx) from the latter. PAO purchased the drug from Kali in an all stock deal for common stock. PAO is undergoing negotiations with Kali for the potential comprehensive acquisition of the underlying patent from which the cannabidiol formula was derived. [2]
Key Development Milestones
In October 2021, PAO Group reported that cannabidiol (RespRx) in non-clinical trials demonstrated efficacy in treatment of lung cancer [3] .
In August 2020, PAO Group announced that it intends to submit IND application for cannabidiol (RexpRx) to US FDA for the treatment of chronic obstructive pulmonary disease [4] .
As of August 2020, PAO Group completed a clinical trial of cannabidiol in 25 patients with symptoms associated with COVID-2019 infections. Based on positive results from this trial, the company also plans to make Coronavirus Treatment Acceleration Program (CTAP) application, in collaboration with a CRO [4] .
As at July 2019, liquid formulation of cannabidiol was in a phase I development for the treatment of chronic obstructive pulmonary disease [1] .
In in vitro studies, liquid formulation of cannabidiol down-regulated genes responsible for inflammation and demonstrated improvement in airway function in non-human primates model of with chronic pulmonary fibrosis [5] [6] [7] .
Research from a cannabidiol study indicated that cannabidiol impacted hyper-immune responses which potentially develop into a cytokine storm which in-turn impacts COVID-19 patients. Cannabidiol also positively stimulated immune responses countering bad cells. Results from a tetrahydrocannabinol-based study showcased its ability relieve pain, but also indicated immune response manipulation capabilities to include anti-inflammatory reactions, along with stimulation of immune responses to fight bad cells. Both studies were conducted to investigate and explain the therapeutic potential of RexpRx [8] .
Patent Information
As of October 2021,USPTO granted patent to PAOG associated with a patented cannabis extraction method encloses U.S. Patent No. 9 199 960 entitled methods and apparatus for processing herbaceous plant materials including the cannabis plant [9] .
In January 2020, Kali-Extracts filed a patent application for cannabidiol formulation for the treatment of symptoms associated with chronic obstructive pulmonary disease (COPD) and other respiratory conditions [10] .
In December 2015, the US PTO issued a patent number US 9 199 960 B2 entitled "Method and apparatus for processing herbaceous plant materials including the cannabis plant". The US patent provides protection to method to increase the yield of cannabinoids, particularly cannabidiol from Cannabis plant material [11] .
Drug Properties & Chemical Synopsis
- Route of administration PO
- Formulation Liquid, unspecified
- Class Analgesics, Anti-inflammatories, Anti-ischaemics, Antiacnes, Antibacterials, Antiepileptic drugs, Antihyperglycaemics, Antihyperlipidaemics, Antineoplastics, Antiparkinsonians, Antipsoriatics, Antipsychotics, Antirheumatics, Antivirals, Anxiolytics, Behavioural disorder therapies, Cannabinoids, Cardiovascular therapies, Cyclohexenes, Drug withdrawal therapies, Heart failure therapies, Hepatoprotectants, Muscle relaxants, Neuroprotectants, Obesity therapies, Resorcinols, Skin disorder therapies, Small molecules
- Target 5-HT1 serotonin receptor; Cannabinoid receptor CB1; Cannabinoid receptor CB1 inverse; Cannabinoid receptor CB2; Cannabinoid receptor CB2 inverse; Transient receptor potential channel; Virus internalisation
- Mechanism of Action 5-HT1 serotonin receptor modulators; Cannabinoid receptor CB1 inverse agonists; Cannabinoid receptor CB2 inverse agonists; Transient receptor potential channel modulators; Virus internalisation inhibitors
-
WHO ATC code
L01 (Antineoplastic Agents)
N03A-X24 (Cannabidiol)
R (Respiratory System)
R03 (Drugs for Obstructive Airway Diseases)
-
EPhMRA code
L1 (Antineoplastics)
R (Respiratory System)
R3 (Anti-Asthma and COPD Products)
V (Various)
- Chemical name 2-[(1R,6R)-3-methyl-6-prop-1-en-2-ylcyclohex-2-en-1-yl]-5-pentylbenzene-1,3-diol
- Molecular formula C21 H30 O2
- CAS Registry Number 3556-78-3
Biomarkers Sourced From Trials
Indication | Biomarker Function | Biomarker Name | Number of Trials |
---|---|---|---|
absence epilepsy |
Eligibility Criteria |
FSH |
|
adenocarcinoma |
Eligibility Criteria |
PSA |
|
adenocarcinoma |
Outcome Measure |
Testosterone PSA |
|
arthralgia |
Outcome Measure |
Estradiol-17beta 3-sulfate |
|
autistic disorder |
Outcome Measure |
N-Acetyl-L-aspartic acid L-Glutamine |
|
cardiovascular disorders |
Detailed Description |
Tumor necrosis factor alpha (TNF-alpha) Interleukin-6 (IL-6) Interleukin-10 (IL-10) Interleukin 1 Beta (IL-1β) Ferritin D-dimer Cardiac Troponin I C-reactive protein (CRP) BNP |
|
cerebral ischaemia |
Brief Summary |
carboxylesterase 1 |
|
cerebral ischaemia |
Brief Title |
carboxylesterase 1 |
|
cerebral ischaemia |
Official Title |
carboxylesterase 1 |
|
DiGeorge syndrome |
Eligibility Criteria |
MDD1 (Major depressive disorder) |
|
Dravet syndrome |
Outcome Measure |
CLYBL |
|
Dravet syndrome |
Brief Title |
carboxylesterase 1 |
|
Dravet syndrome |
Arm Group Description |
Sucralose |
|
Dravet syndrome |
Official Title |
carboxylesterase 1 |
|
Dravet syndrome |
Brief Summary |
Estradiol-17beta 3-sulfate carboxylesterase 1 |
|
drug dependence |
Outcome Measure |
Hydrocortisone |
|
dyslipidaemias |
Eligibility Criteria |
Insulin |
|
dyslipidaemias |
Outcome Measure |
Insulin Fructosamine C-peptide Apolipoprotein B (AOPB) |
|
early breast cancer |
Arm Group Label |
9-cis-Retinoic acid 13-cis-Retinoic acid |
|
early breast cancer |
Outcome Measure |
pregnancy specific beta-1-glycoprotein 2 Cytokeratin 5 CEA carcinoembryonic antigen related cell adhesion molecule 3 CA 15-3 9-cis-Retinoic acid |
|
early breast cancer |
Brief Title |
9-cis-Retinoic acid |
|
early breast cancer |
Arm Group Description |
9-cis-Retinoic acid 13-cis-Retinoic acid |
|
early breast cancer |
Detailed Description |
Cytokeratin 5 |
|
early breast cancer |
Eligibility Criteria |
pregnancy specific beta-1-glycoprotein 2 CEA carcinoembryonic antigen related cell adhesion molecule 3 |
|
early breast cancer |
Official Title |
9-cis-Retinoic acid |
|
early breast cancer |
Brief Summary |
PGR Estrogen receptor alpha (ER alpha) Cytokeratin 5 9-cis-Retinoic acid |
|
epilepsy |
Brief Summary |
Estradiol-17beta 3-sulfate carboxylesterase 1 |
|
epilepsy |
Brief Title |
Valproic acid glucuronide carboxylesterase 1 |
|
epilepsy |
Official Title |
Valproic acid glucuronide carboxylesterase 1 |
|
epilepsy |
Outcome Measure |
CLYBL |
|
fibromyalgia |
Outcome Measure |
Hydrocortisone |
|
fragile X syndrome |
Eligibility Criteria |
FRAXA FMR1 intronic transcript 1 FMR1 |
|
fragile X syndrome |
Outcome Measure |
FRAXA FMR1 intronic transcript 1 FMR1 ATP-binding cassette, sub-family A (ABC1), member 3 |
|
generalised epilepsy |
Eligibility Criteria |
FSH |
|
glioblastoma |
Eligibility Criteria |
MGMT |
|
glioblastoma |
Official Title |
MGMT |
|
Heroin-related disorders |
Brief Summary |
carboxylesterase 1 |
|
Heroin-related disorders |
Brief Title |
carboxylesterase 1 |
|
Heroin-related disorders |
Official Title |
carboxylesterase 1 |
|
infantile spasms |
Brief Summary |
carboxylesterase 1 |
|
infantile spasms |
Brief Title |
carboxylesterase 1 |
|
infantile spasms |
Official Title |
carboxylesterase 1 |
|
Lennox-Gastaut syndrome |
Brief Summary |
Estradiol-17beta 3-sulfate carboxylesterase 1 |
|
Lennox-Gastaut syndrome |
Brief Title |
carboxylesterase 1 |
|
Lennox-Gastaut syndrome |
Official Title |
carboxylesterase 1 |
|
major depressive disorder |
Detailed Description |
Thyroid stimulating hormone beta (TSH) matrilin 1, cartilage matrix protein GATA3 Cytidine monophosphate CD59 molecule, complement regulatory protein |
|
multiple sclerosis |
Arm Group Description |
Piperine |
|
myocarditis |
Detailed Description |
Cardiac Troponin I BNP |
|
myocarditis |
Eligibility Criteria |
Cardiac Troponin I |
|
myocarditis |
Outcome Measure |
Tumor necrosis factor alpha (TNF-alpha) Interleukin-6 (IL-6) Interleukin-10 (IL-10) Interleukin 1 Beta (IL-1β) Ferritin Cardiac Troponin I C-reactive protein (CRP) BNP |
|
myoclonic epilepsies |
Brief Title |
Valproic acid glucuronide |
|
myoclonic epilepsies |
Official Title |
Valproic acid glucuronide |
|
Opioid-related disorders |
Outcome Measure |
Retinoyl b-glucuronide Anandamide 2-Arachidonylglycerol |
|
Opioid-related disorders |
Brief Title |
carboxylesterase 1 |
|
Opioid-related disorders |
Detailed Description |
Anandamide 2-Arachidonylglycerol |
|
Opioid-related disorders |
Eligibility Criteria |
Thyroxine (T4) Prolactin Luteinizing hormone (LH) Estradiol-17beta 3-sulfate Bilirubin |
|
Opioid-related disorders |
Official Title |
carboxylesterase 1 |
|
Opioid-related disorders |
Brief Summary |
carboxylesterase 1 |
|
pain |
Eligibility Criteria |
CYP2C9 |
|
pain |
Outcome Measure |
Hydrocortisone |
|
Parkinson's disease |
Brief Title |
carboxylesterase 1 |
|
Parkinson's disease |
Arm Group Description |
Sucralose |
|
Parkinson's disease |
Eligibility Criteria |
protein tyrosine phosphatase, receptor type F |
|
Parkinson's disease |
Official Title |
carboxylesterase 1 |
|
Parkinson's disease |
Brief Summary |
carboxylesterase 1 |
|
pervasive child development disorders |
Outcome Measure |
N-Acetyl-L-aspartic acid L-Glutamine |
|
postoperative pain |
Outcome Measure |
Interleukin-6 (IL-6) |
|
prostate cancer |
Eligibility Criteria |
PSA |
|
prostate cancer |
Outcome Measure |
Testosterone PSA |
|
Rett syndrome |
Outcome Measure |
IGF1 |
|
Rett syndrome |
Brief Title |
carboxylesterase 1 |
|
Rett syndrome |
Eligibility Criteria |
MECP2 L-Aspartic acid ALT |
|
Rett syndrome |
Official Title |
carboxylesterase 1 |
|
Rett syndrome |
Brief Summary |
carboxylesterase 1 |
|
schizophrenia |
Arm Group Label |
Insulin E1A binding protein p300 |
|
schizophrenia |
Brief Title |
carboxylesterase 1 |
|
schizophrenia |
Arm Group Description |
Insulin fatty acid amide hydrolase E1A binding protein p300 |
|
schizophrenia |
Official Title |
carboxylesterase 1 |
|
schizophrenia |
Brief Summary |
carboxylesterase 1 |
|
seizures |
Eligibility Criteria |
FSH |
|
seizures |
Outcome Measure |
IGF1 |
|
substance-related disorders |
Eligibility Criteria |
UDP glucuronosyltransferase family 1 member A complex locus T-cell surface antigen CD4 solute carrier family 35 (UDP-galactose transporter), member A2 |
|
substance-related disorders |
Outcome Measure |
Hydrocortisone Anandamide |
|
tonic-clonic epilepsy |
Eligibility Criteria |
FSH |
|
tremor |
Arm Group Description |
Sucralose |
|
tremor |
Eligibility Criteria |
protein tyrosine phosphatase, receptor type F |
|
tuberous sclerosis |
Brief Summary |
carboxylesterase 1 |
|
tuberous sclerosis |
Brief Title |
carboxylesterase 1 |
|
tuberous sclerosis |
Official Title |
carboxylesterase 1 |
|
tuberous sclerosis |
Outcome Measure |
IGF1 |
|
type 2 diabetes mellitus |
Eligibility Criteria |
Insulin |
|
type 2 diabetes mellitus |
Outcome Measure |
Insulin Fructosamine C-peptide Apolipoprotein B (AOPB) |
|
ulcerative colitis |
Detailed Description |
Calprotectin C-reactive protein (CRP) |
|
ulcerative colitis |
Outcome Measure |
Calprotectin |
Biomarker
Drug Name | Biomarker Name | Biomarker Function |
---|---|---|
Cannabidiol - Kali-Extracts/PAO Group | Anandamide | Outcome Measure |
BDNF | Outcome Measure | |
BPI fold containing family A member 2 | Outcome Measure | |
C-reactive protein (CRP) | Outcome Measure | |
calcineurin binding protein 1 | Arm Group Description | |
microseminoprotein, beta- | Outcome Measure | |
persephin | Outcome Measure | |
phosphoserine phosphatase | Outcome Measure | |
Prolactin | Outcome Measure | |
regenerating family member 1 alpha | Outcome Measure | |
RIDA | Outcome Measure | |
syntaxin binding protein 3 | Outcome Measure | |
Valproic acid glucuronide | Arm Group Description |
Development Status
Summary Table
Indication | Qualifier | Patient Segment | Phase | Countries | Route / Formulation | Developers | Event Date |
---|---|---|---|---|---|---|---|
COVID 2019 infections | For symptoms associated with COVID-2019-infections | - | No development reported (Clinical) | USA | PO / Liquid | PAO Group | 28 Sep 2023 |
Chronic obstructive pulmonary disease | Foe symptoms associated with COPD | - | No development reported (I) | USA | PO / Liquid | Kali-Extracts | 28 Aug 2022 |
Lung cancer | - | - | Preclinical | USA | PO / unspecified | PAO Group | 15 Oct 2021 |
Respiratory tract disorders | - | - | No development reported (Research) | USA | PO / Liquid | Kali-Extracts | 28 Feb 2024 |
Commercial Information
Involved Organisations
Organisation | Involvement | Countries |
---|---|---|
Kali-Extracts | Originator | USA |
PAO Group | Owner | USA |
University of Kentucky | Collaborator | USA |
Brand Names
Brand Name | Organisations | Indications | Countries |
---|---|---|---|
RespRx | Kali-Extracts | Chronic obstructive pulmonary disease | USA |
Scientific Summary
Pharmacodynamics
Summary
In nonhuman primates with chronic pulmonary fibrosis, 5-fold dilution of liquid cannabidiol formulation increased airway flow rate by 82%, respiration rate by 55%, airway flow rate by 82%, inspiratory airway flow velocity by 149%, and tidal volume by 38% compared with own control values after two weeks treatment. Improvement in pulmonary function in these primates also accompanied with increases in resting minute ventilation. Undiluted of liquid cannabidiol formulation also increased inspiratory flow rate by 49% and tidal volume by 24% after 2 weeks of treatment. Respiration rate was unchanged from pretreatment values. 25-fold dilution of liquid cannabidiol formulation did not showed any marked improvement on airway or lung functions. The data suggest potential of cannabidiol formulation for the treatment of chronic obstructive airway diseases that restrict inspiratory air flow [6] [7] .
In in vitro studies, cannabinoids extract alone demonstrated up- or down-regulating genes responsible for inflammation and healing by as much as 200-fold in human small airway epithelial cells (HSAEpC) [5] .
Future Events
Expected Date | Event Type | Description | Updated |
---|---|---|---|
31 Dec 2021 | Regulatory Status | PAOG plans to launch cannabidiol in fourth quarter of 2021 [9] | 13 Oct 2021 |
Development History
Event Date | Update Type | Comment |
---|---|---|
28 Feb 2024 | Phase Change - No development reported | No recent reports of development identified for research development in Respiratory-tract-disorders in USA (PO, Liquid) Updated 28 Feb 2024 |
28 Sep 2023 | Phase Change - No development reported | No recent reports of development identified for clinical-Phase-Unknown development in COVID-2019-infections in USA (PO, Liquid) Updated 28 Sep 2023 |
28 Aug 2022 | Phase Change - No development reported | No recent reports of development identified for phase-I development in Chronic-obstructive-pulmonary-disease in USA (PO, Liquid) Updated 28 Aug 2022 |
15 Oct 2021 | Phase Change - Preclinical | Preclinical trials in Lung cancer in USA (PO) [3] Updated 19 Oct 2021 |
11 Oct 2021 | Patent Information | PAO Group has patent protection for Cannabidiol in USA by October 2021 [9] Updated 13 Oct 2021 |
11 Oct 2021 | Regulatory Status | PAOG plans to launch cannabidiol in fourth quarter of 2021 [9] Updated 13 Oct 2021 |
02 Jul 2021 | Biomarker Update | Biomarkers information updated Updated 02 Oct 2021 |
06 Oct 2020 | Trial Update | 9304490 - created HE missed from MR 9300394; added results of study in KDM as discussed with SME Updated 06 Oct 2020 |
11 Aug 2020 | Trial Update | PAO Group plans clinical development in Chronic obstructive pulmonary disease in USA (PO) [4] Updated 06 Oct 2020 |
11 Aug 2020 | Phase Change - Clinical | Clinical trials in COVID-2019 infections in USA (PO) before August 2020 [4] Updated 18 Aug 2020 |
11 Aug 2020 | Regulatory Status | PAO Group announces intention to submit Coronavirus Treatment Acceleration Program application to regulatory authorities for COVID-2019 infections [4] Updated 18 Aug 2020 |
11 Aug 2020 | Regulatory Status | PAO Group announces intention to submit IND to US FDA for Chronic obstructive pulmonary disease [4] Updated 18 Aug 2020 |
30 Jul 2020 | Licensing Status | PAO Group acquires Cannabidiol from Kali-Extracts [2] Updated 18 Aug 2020 |
28 Jan 2020 | Patent Information | Kali-Extracts files for patent protection for cannabidiol formulation for treatment of chronic obstructive pulmonary disease and other respiratory conditions [10] Updated 11 Feb 2020 |
28 Jan 2020 | Phase Change | Early research in COVID-2019-infections in USA (PO) [10] Updated 30 Jan 2020 |
28 Jan 2020 | Phase Change | Early research in Respiratory tract disorders in USA (PO) [10] Updated 30 Jan 2020 |
09 Jul 2019 | Phase Change - I | Phase-I clinical trials in Chronic obstructive pulmonary disease in USA before July 2019 (PO) [1] Updated 30 Jan 2020 |
01 Feb 2019 | Phase Change - Preclinical | Preclinical trials in Chronic obstructive pulmonary disease in USA (PO) before February 2019 [6] Updated 30 Jan 2020 |
01 Feb 2019 | Scientific Update | Pharmacodynamics data from preclinical studies in Chronic obstructive pulmonary disease released by Kali-Extracts [6] [7] Updated 30 Jan 2020 |
19 Dec 2018 | Scientific Update | Pharmacodynamics data from in vitro studies in Chronic obstructive pulmonary disease released by Kali-Extracts [5] Updated 30 Jan 2020 |
01 Dec 2015 | Patent Information | kali-extracts has patent protection for extraction method of cannabinoids in USA [11] Updated 30 Jan 2020 |
References
-
KALY Adds New CBD Extraction Contract Worth $10 Million in Annual Revenue.
Media Release -
PAOG Announces Acquisition of Resprx Entering 200B Biopharma Market.
Media Release -
PAOG Cites New British Medical Journal Case Report On CBD Lung Cancer And COPD Treatment As Validation Of PAOG Ongoing RespRx Drug Research.
Media Release -
PAOG Cannabis Pharma Initiative Stands to Benefit From Senator Marco Rubio and Congresswoman Jenniffer Gonzlez Coln New Bill.
Media Release -
Kali-Extracts, Inc. Releases Preclinical Research Study Results on Therapy for Respiratory Disease Driving $11 Billion Treatment Market.
Media Release -
KALY - Kali-Extracts, Inc. Announces Cannabis Extract COPD Primate Treatment Study Research Report Preview.
Media Release -
KALY - Kali-Extracts, Inc. Previews Pending Report On Cannabis Treatment For Lung Disease Study.
Media Release -
PAOG Announces New Engagement To Prepare For Investigational New Drug Application With FDA.
Media Release -
PAOG Set To Realize First CBD Nutraceutical Sales In Q4 With Rapid Revenue Growth Expected To Follow.
Media Release -
KALY-Kali-Extracts RespRx Could Offer Treatment for Coronavirus Symptoms.
Media Release -
Method and apparatus for processing herbaceous plant materials including the cannabis plant - Patent. Internet-Doc 2020;.
Available from: URL: https://patents.google.com/patent/US9199960B2/en?oq=9%2c199%2c960
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