Cannabinoids combat brain cancer cells
MCG Pharmaceuticals has reported some new data from preclinical laboratory studies done by its research collaborator, Slovenia's National Institute of Biology. The data highlights the possible use of cannabinoids in the treatment of glioblastoma multiforme (GBM), the aggressive, and most common, brain cancer. They used cancer cells cultured from biopsy samples taken from 18 patients. This makes the data more relevant for the future design of clinical studies. Note that these are not clinical trials.
The collaboration tested different combinations of cannabinoids with and without a chemotherapeutic agent (undisclosed). The experiments examined cannabidiol (CBD) and cannabigerol (CBG), a less common cannabinoid. The compounds were used individually and as a combination. CBG has no psychotropic effects but appears to activate a different set of receptors than CBD (Nachnani et al (2021)). CBD and CBG were then examined as 3:1 and 3:2 ratio combinations. More than 5,800 individual tests were performed.
The results suggest there is a marked effect on cell viability over 150μM with apoptosis (cell death) reported as being observed in both tumour cells and tumour stem cells. Tumour stem cells are more resistant to normal cancer therapies and might regenerate the tumour if they survive therapy. The most interesting observation is that while a ratio of CBD to CBG of 3:1 appears very similar to either compound alone, a 3:2 combination ratio appears to have greater inhibition of cell viability. There was no additional cytotoxic effect from an undisclosed chemotherapeutic. The lowered cancer cell viability in drug-resistant tumours would be clinically very interesting. There are few other treatments and developments, a PI3K inhibitor (paxalisib (Kazia)), shows promise in Phase 2.
We note that the findings, although both interesting and promising, are still early stage. Both CBD and CBG are very fat-soluble so hard to administer; it may be difficult to deliver high enough doses to the brain. MGC plans to use a nano-emulsifying formulation technology from Graft Polymer to improve systemic absorption. This Graft Polymer formulation will separately need preclinical development and regulatory approval for trials. CBG will also need a full data package. CBD is well known but MGC will need documentation.
Early research data shows cannabis combo hits brain cancer
MGC is developing a diverse portfolio of cannabis and plant-based medicinal and nutritional products (ArtemiC). It plans to start a Phase 2 trial with its lead product CannEpil, a 20:1 CBD:THC combination, in refractory epilepsy. MGC is in the process of commissioning a new production facility in Malta, which should come on stream later in the second half of 2022 (H222). Recent data on a cannabis formulation, Cognicann, for symptomatic relief of dementia showed promising early clinical data. We now forecast revenues of A$4.5mln in the year to end-June 2022), which includes medicinal cannabis sales of A$3mln, service sales of A$0.5mln and a single ArtemiC order of A$1.1mln. Cash at 31 March 2022 was A$4.0mln. The prospective enterprise value (EV)/sales ratio is about 10.3. The next expected clinical news is the summer start of the CannEpil Phase 2 which will run until at least mid-2023.
Cannabis and other plant based products
Year end Jun 30 · 2020 · 2021 · 2022
Revenue (A$-000's) · 2,079 · 2,962 · 4,560
Cash(AUD$, 000's) · 1,873 · 5,433 · 989
EBITDA, € - 000s · (11,436) · (11,421) · (13,022)
In vitro cell studies have indicated that both cannabidiol (CBD) and cannabigerol (CBG) can reduce glioblastoma cell viability. Data is shown for cell line NIB140 in Figure 1. Earlier results have been published (Lah et al (2021)).
The graphs indicate some effect at 100μM but concentrations over over150μM have greater effects. Both CBD and CBG reduce cell viability similarly.
This is because greater proportions of the cultured glioblastoma cells underwent apoptosis (programmed cell death, otherwise called cell suicide). Normally, cancer cells, and GBM cells especially, are resistant to apoptosis.
Figure 1 - CBD and CBG alone
Source: MGC
The combination of CBD and CBG at different ratios and concentrations was tested, Figure 2. The data is for NIB140. While the cell viability appears comparable to Figure 1 for the 3:1 ratio, the 3:2 ratio appears to give generally lower cell viability at all concentrations and especially over160μM (95:65). Note the y-axis is extended to account for wider error bars.
As we only have selected data, it is impossible to be definitive about the results or know if how consistent across all 18 patient samples, but it is a scientifically interesting observation and merits further development. It will inform MGC's further development plans.
Figure 2 - Combination
Source: MGC
Combination cancer therapies are complex to develop. We, therefore, anticipate a preclinical timeline into 2023 with a clinical phase possibly from 2024; MGC has given no timelines. The observation that a chemotherapeutic agent (possibly temozolomide — TMZ — as this is commonly used to treat GBM) was ineffective while the cannabinoid combination was effective at higher doses may indicate that cannabioids might have more general use in GBM. TMZ works in less than half of patients (Sang Y Lee (2016)), possibly about a third.
Further development