Completion of CimetrAT Pre-clinical Trial
MGC Pharmaceuticals Ltd.
Completion of CimetrA™ bioanalytics Pre-clinical Trial
10 January 2023
ASX, LSE: MXC
Key Highlights :
· MGC Pharma has completed the full pre-clinical rodents study panel for CimetrATM.
· The latest study, which was carried out at the Smart Assays laboratory in Israel, included the development of bioanalytical methods and validations for further pharmacokinetic analysis for CimetrATM.
· A study on chronic toxicity in rodents was also completed by Science in Action, in Israel, monitoring the potential development of adverse effects from using CimetrATM.
· Histopathology demonstrated the full safety profile for CimetrATM across all study dosage groups.
· The study results are an important step ahead of the submission to the US Food and Drug Administration (FDA) for Investigational New Drug (IND) approval.
· No anomalies were observed in the biopsies, nor were any clinical or behavioural adverse events recorded.
· CimetrATM is MGC Pharma's proprietary Investigational Medicinal Product which in previous clinical trials has demonstrated anti-inflammatory and immunomodulating properties, and is MGC's most clinically advanced product.
MGC Pharmaceuticals Ltd (' MGC Pharma' or ' the Company ') a European based pharmaceutical company specialising in the production and development of plant inspired medicines, has completed the pre-clinical rodent studies on CimetrATM, which are a key step in the clinical pathway prior to the planned FDA Investigational New Drug submission. Research using rodent and mammalian models are used to delineate the pharmacokinetic profile and general safety of a drug, as well as to identify toxicity patterns over a given period for the treatment before it advances to the next stage of trials, as required by US Food and Drug Administration (FDA) criteria.
The Study was undertaken to determine toxicological effects of CimetrATM over a 14-day period in rats, and was undertaken by the Smart Assays and Science in Action Laboratories in Israel, and comprised four study groups, three separate dosage groups, and one control group, with the treatment administered over a period of fourteen days, followed by a seven day review period. Blood samples for the pharmacokinetic analysis were taken on a daily basis, and histopathology tests were conducted on all organs per FDA guidelines. No anomalies were observed in the biopsies taken, nor were any clinical or behavioural adverse events recorded.
This Study is crucially important in the regulatory approval process for Investigational New Drugs (IND) approval by the FDA, and forms a key part of the metrics for the FDA's Center for Drug Evaluation and Research (CDER), the commercial and consumer watchdog, and gatekeeper to the US pharmaceutical market. There is a strict process for FDA approval: discovery, preclinical development, and clinical trial, where the boundary between preclinical development and clinical trial is sharply defined by the IND approval. Final FDA approvals will ensure that CimetrATM meets the criteria for further clinical study and development in the US, and ultimately commercial sale, therefore opening up the largest healthcare market globally to MGC Pharma.
Roby Zomer, co-founder, Managing Director and CEO of MGC Pharmaceuticals, commented : " The successful completion of this study and the excellent results attained is an important milestone moment for the Company, as we continue to progress CimetrATM along the mandated clinical pathway. The results of this study are a critical step in advancing MGC's submission to the FDA, and for the final approval of CimetrATM as an Investigational New Drug in the US."
A summary of results from the recently completed study can be found in Annexure A below.
About CimetrATM
CimetrATM is a nanoparticle micellar formulation based on the pharmaceutical synergetic composition consisting of Curcumin and Boswellia. In pre-clinical and clinical trials CimetrATM has demonstrated anti-inflammatory and immunomodulating effects, and can be designed for multiple therapeutic applications utilising Graft Polymer IP Ltd's proprietary GraftBioTM Self-nano-emulsifying Drug Delivery System.
Preclinical and clinical results to date have demonstrated CimetrATM's mechanism of action as an anti-inflammatory and immunomodulatory agent which is effective in the prevention of severe inflammation by its control of increased Cytokine production resulting from an infection of the different variants of SARS-CoV-2 (the virus responsible for COVID-19); and which is the forerunner of a Cytokine Storm, which is believed to be the main reason for mortality in severe COVID-19 patients.
--Ends--
Authorised for release by the board, for further information please contact:
|
MGC Pharmaceuticals Ltd Roby Zomer CEO & Managing Director +61 8 6382 3390 |
MGC Pharmaceuticals Ltd David Lim Company Secretary +61 8 6382 3390 |
|
UK Financial and Corporate Advisor Hannam & Partners Rupert Fane / Nilesh Patel +44 7810 056 104 |
UK Broker Turner Pope Andy Thacker +44 203 657 0050 |
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UK PR Advisors Tavistock Charles Vivian / Tim Pearson +44 207 920 3150
|
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About MGC Pharma
MGC Pharmaceuticals Ltd (LSE: MXC, ASX: MXC) is a European based pharmaceutical company, focused on developing and supplying accessible and ethically produced plant inspired medicines, combining in-house research with innovative technologies, with the goal of finding or producing treatments to for unmet medical conditions.
The Company's founders and executives are key figures in the global pharmaceuticals industry and the core business strategy is to develop and supply high quality plant inspired medicines for the growing demand in the medical markets in Europe, North America and Australasia.
MGC Pharma has a robust development pipeline targeting two widespread medical conditions and has further products under development.
MGC Pharma has partnered with renowned institutions and academia to optimise the development of targeted plant inspired medicines, to be produced in the Company's EU-GMP Certified manufacturing facilities.
MGC Pharma has a growing patient base in Australia, the UK, Brazil and Ireland and has a global distribution footprint via an extensive network of commercial partners meaning that it is poised to supply the global market.
Follow us through our social media channels:
Twitter: @MGC_Pharma
Facebook: @mgcpharmaceuticals
LinkedIn: MGC Pharmaceuticals Ltd.
Instagram: @mgc_pharma
Annexure A
Study Results
Histopathological examination
Severity of changes were scored by a 5-point scale as follows (Schafer et al., Toxicol Pathol 2018, 46:256-265):
Grade 0 - Normal (within range of normal histological variations)
Grade 1 - Minimal
Grade 2 - Mild
Grade 3 - Moderate
Grade 4 - Severe
Findings
· No pathological nor cytotoxic changes at all were found in the organs and tissue biopsies of the test subjects, i.e. All tissues of all animals were unaffected.
· The semi-quantitative results are presented below in Table A and B.
· All tissues of all animals were normal. It was concluded that the test article at the dosage administered did not induce toxicological changes.
| Table A. Study design |
|
|||
|
Animal No. |
Group |
Number of animals |
Treatment1 |
|
|
1-5 |
VM (Control - Male) |
5 |
Saline |
|
|
11-15 |
V (Control- Female) |
5 |
Saline |
|
|
61-65 |
HM (Test Article - Male) |
5 |
16ul |
|
|
71-75 |
HF (Test Article - Female) |
5 |
16ul |
|
|
|
Total |
20 |
|
|
1. Refer annexure B "Treatment method, route, frequency, dose levels" section for treatment dosage information
|
Table B. A semi-quantitative analysis of the histological findings, using the scoring scale above. |
||||||||||
|
Group/ treatment |
Animal NO. |
Lungs |
Liver |
Kidneys R+L |
Heart |
Trachea |
Esophagus |
Brain |
Testicle/Ovary R |
Comments |
|
VM |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
2 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
|
3 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
|
4 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
|
5 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
|
VM |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
N= 5 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
VF |
11 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
12 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
|
13 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
|
14 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
|
15 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
|
VF |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
N= 5 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
HM
|
61 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
62 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
|
63 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
|
64 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
|
65 |
0 |
0 |
0 |
0 |
NA |
0 |
0 |
0 |
|
|
|
HM |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
N= 5 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
HF |
71 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
72 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
|
73 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
|
74 |
0 |
0 |
0 |
0 |
NA |
0 |
0 |
0 |
|
|
|
75 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
|
HF |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
N= 5 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
Table C. A semi-quantitative analysis of the histological findings, using a scoring scale above |
||||||||||
|
Group/ treatment |
Animal NO. |
Testicle/Ovary L |
Lymph nodes |
Thymus |
Tongue |
Stomach |
Spleen |
Large intestine |
Small intestine |
Comments |
|
VM |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
2 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
|
3 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
|
4 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
|
5 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
|
VM |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
N= 5 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
VF |
11 |
0 |
0 |
NA |
0 |
0 |
0 |
0 |
0 |
|
|
12 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
|
13 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
|
14 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
|
15 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
|
VF |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
N= 5 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
HM
|
61 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
62 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
|
63 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
|
64 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
|
65 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
|
HM |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
N= 5 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
HF |
71 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
72 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
|
73 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
|
74 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
|
75 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
|
HF |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
N= 5 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
ANNEXURE B
Study Protocols
|
Sponsor |
MGC Pharmaceuticals Limited |
||||
|
Name and any unique identifier of the trial:
|
NON-GLP 14 Day TOX/TK Study daily Oral spray dose of CimetrATM oromucosal in SD rats.
Study number: S-22-612
|
||||
|
Test Article |
CimetrATM oromucosal oral spray of varying dosages
|
||||
|
Objective |
The objective of the study is to determine toxicological effect of CimetrATM oromucosal oral spray over 14 days in rats, conducting histopathological examinations as part of a safety-toxicological evaluation of the Test Article in rats, using histological tools.
|
||||
|
Design |
Evaluation of histopathological changes in various tissue samples of rats following high dose of tested item (ointment + particles), after an oral spray administration, in a frame of toxicological study.
|
||||
|
Description of Control Group: |
The control group consisted of 10 test subjects (5 Male and 5 Female) which was administered a phosphate-buffer saline solution with no Test Article. Inclusion of each test subject in a test group was. randomised |
||||
|
Blinding status: |
N/A |
||||
|
Treatment method, route, frequency, dose levels:
|
The Test Article was administered as an oral spray. (The oral spray route is an intended route of administration in humans) The tox study included 80 animals. Animals were allocated randomly into the study groups. Group Dosage Main Study 14d Recovery 7d TK (ul/rat) (Males/Females) (Males/Females) Control 0ul 5/5 5/5 3/3 Low Dose 4ul 5/5 5/5 6/6 Mid Dose 8ul 5/5 5/5 6/6 High Dose 16ul 5/5 5/5 6/6
TK: Toxicology Dosage:
PBS: Phosphate-buffer saline Animals were randomised into 4 groups according to a group designation table and treated according to the group dosage table above. Treatment was given to all animals in all groups once a day by oral spray for 14 days. The TK/PK groups also received treatment like the rest of the main and the recovery experiment groups. On days 1 immediately after giving the first treatment, and on day 14 after the 14th treatment, blood was taken for plasma from the TK/PK groups at 1 hr., 4 hr., 6 hr., 8 hr., 12 hr. and 24 hr, (3/3 rat for each time point), and from the Vehicle Control group at 1 hr., 6 hr., 12 hr. To test the concentration of the tested substance in the blood.
|
||||
|
Analysis |
Tissues/organs collected for histopathological examination Samples of 4% formaldehyde-fixed Lung, Liver, Kidneys (L+R), Heart, Trachea , Esophagus, Brain, Testicle R+L, Ovary R+L, Cervical Glands, Thymus, Tongue, Stomach, Spleen, Colon , Duodenum, Jejunum with Peyer's Patch and Ileum were received at Patho-Logica, where they were further fixed for 48 hours. Then, the tissues were trimmed, put in embedding cassettes and processed routinely for paraffin embedding. Twelve cassettes were prepared per animal as follows (see embedding list). Paraffin-embedded tissues were sectioned at 4 µ thickness, put on histological glass slides, stained with Hematoxylin and Eosin, and examined by light microscopy.
Embedding list per rat: § Slide #1: Lung (inflated with fixative) § Slide #2: Liver (three lobes) § Slide #3: Kidneys (L+R) § Slide #4: Heart, trachea + esophagus § Slide #5: Brain (three cross sections) § Slide #6: Testicle R / Ovary R § Slide #7: Testicle L / Ovary L § Slide #8: Lymph nodes § Slide #9: Thymus, tongue § Slide #10: Stomach + Spleen § Slide #11: Colon + cecum. § Slide #12: Duodenum, Jejunum + Peyer's Patch, Ileum |
||||
|
Number of trial subjects: |
The tox study included 10 male and 10 female rats per Main and Recovery group. (5 animals of each sex is the minimal number of animals per group required for toxicity testing). |
||||
|
Trial locations: |
Science in Action, Israel Smart Assays, Israel
|
||||
|
Trial standard: |
Non-GLP. This study was performed under the approval of the national ethics committee in compliance with "The Israel Animal Welfare Act". |
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