- Standardized process for the production of cannabinoids
- First production of cannabinoids by biosynthesis without the use of yeast
- Production costs drop to one-thousandth of the previous costs
In February 2019, the Frankfurt based pharmaceutical company, Farmako, filed a worldwide patent application with the European Patent Office for a novel microorganism for the production of cannabinoids from sugar by biosynthesis. To date, cannabis plants are still cultivated for medicinal purposes and natural flowers or oils are prescribed. Cannabis drugs are proportionally expensive. Recently, bottlenecks have been so great that patients have been unable to obtain their prescribed drugs. In addition, flowers are very difficult to standardize and dose. The new synthetic organism has considerable advantages over other biosynthetic production processes of cannabinoids, which are based on yeast fungi, for example.
In the future, Farmako will be able to produce the full range of different cannabinoids for standardized medicines. For patients, this promises not only security of supply, but also significantly lower prices: Current production costs are mainly driven up by breeding and cultivation. By comparison, one kilogram of THC costs around one thousandth less in production due to Farmako’s biosynthetic process. Unlike other companies and scientists, Farmako does not use yeast cells for the biosynthesis process. Instead, the bacterium Zymomonas mobilis, which is also used for the production of tequila, was genetically modified in such a way that, in addition to CBD and THC, it can also produce 180 cannabinoids as part of a continuous synthesis.
Therefore, the pharmaceutical industry and cannabis are moving closer together. “Making any cannabinoid synthetically and incredibly efficient is the breakthrough for cannabis in
medicine,” says Niklas Kouparanis, CEO and founder of Farmako. “Our patent will revolutionize the pharmaceutical industry in cannabis as much as the biosynthesis of insulin. The cannabis industry is therefore facing such rapid upheavals as, for example, the entertainment industry when Netflix became popular. ”
“With one production run, we can produce cannabinoids for 900 hours without interruption. For example, 4.5 kilograms of THC are produced per gram of bacterial mass during this time, “explains Patrick Schmitt, co-founder of Farmako and Chief Science Officer (CSO) of the company. The molecular biologist modified the bacterium Zymomonas mobilis b y introducing genes from the malaria pathogen and the cannabis plant. He also used gene scissors to remove certain genes, which are usually responsible for alcohol production, from the bacterial genome. The artificially produced bacterium called Zymomonas cannabinoidis® is now able to produce cannabinoids from glucose. Schmitt was involved in a total of 500 products available on the market as well as several patents for medicines.
“As a research-based pharmaceutical company, we ensure that the many previously unknown possibilities of cannabinoids are finally empirically explored for the benefit of patients and put into practice. This patent application puts us in a unique position worldwide,” says Niklas Kouparanis, Managing Director and founder of Farmako.
“In principle, nothing else happens during biosynthesis than during alcohol fermentation, with the difference that cannabinoids instead of alcohol are the outcome of the process. All we need as a starting point is glucose,” said Schmitt. In order to produce exactly the desired cannabinoid from more than 180 known cannabinoids, only a single gene has to be exchanged. “A prokaryotic synthetic organism such as Zymomonas cannabinoidis® is much more economical to use for the production of cannabinoids than a eukaryotic organism such as brewer’s yeast,” explains Schmitt.
“Leading position as manufacturer of cannabinoids and cannabinoid-based medicines”
Pharmaceutical cannabis has been legal in Germany since 2017. Other European countries such as Denmark, Luxembourg and Great Britain have also legalised the use of cannabis for medical purposes. In Canada, the market has grown from 170 million to 30 billion euros within three years. The management consultants at Prohibition Partners expect the
European market to be worth 58 billion euros in 2028. So far, patients have received naturally extracted cannabis flowers or oils from the cannabis plant. Recently, shortages have repeatedly occurred, with the result that many patients have been unable to obtain the prescribed drugs for their therapies. In addition, the shortage of available cannabis flowers is driving up prices for patients. Compared to natural flowers, the production of cannabinoids by biosynthesis is much more cost-efficient.
“The new synthetic organism represents an enormous competitive advantage for Farmako. The production of cannabinoids and finished medicines based on cannabinoids will be synthetic in the future. With the patent application, we have now managed to remove a big question mark from the world as to exactly what this production looks like. We are the global leader in development and research in this field,” says Kouparanis. Farmako recently announced the world’s largest import contract to date (press release) and will import up to 50 tonnes of cannabis flowers and oils from the Polish company Pharmacann over the next four years. The distribution of the natural products will eliminate current bottlenecks in the supply of European patients. The proceeds flow directly into research and development. Starting in April, the Farmako scientists team will research the new manufacturing process and patents in its own laboratory.
Cannabinoids as medicine: 80 years unexplored
Patents for the production of cannabinoids by brewer’s yeast are held by two different companies from the USA. Extracting individual cannabinoids from the plant, for example by CO2 extraction, is time-consuming and costly. “From an economic point of view, cannabinoid synthesis in yeast fungi are not very attractive. Although brewer’s yeast can be used to produce cannabinoids, the cells have to be broken up after this synthesis, which stops production. This is very difficult if the production is to be transferred to an industrial scale. Zymomonas cannabinoides®, on the other hand, releases the produced cannabinoids directly into the surrounding medium. This allows continuous production without interruption,” says Schmitt. Experts estimate the current value of the patent at 300 million euros.
The broad range of synthetically produced cannabinoids available in the future will give evidence-based empirical research a completely new perspective. Schmitt: “Cannabinoids have not been researched for more than 80 years. Neither the production, processing nor
pharmaceutical application has made significant progress. We want to lead the race to catch up and provide doctors and researchers with a construction kit containing all the cannabinoids necessary for medical progress. We already know that cannabinoids such as THC or CBD have a better effect in many cases than conventional drugs. Be it severe pain, insomnia, nervous disorders or even cancer treatments. However, it is also known that the ratio of certain cannabinoids and different terpenes to each other plays a decisive role in the treatment of different disease patterns. For this reason, research into different cannabinoid spectra will continue to be of great importance in the future.”
Farmako GmbH is a research-based pharmaceutical company based in Frankfurt. The company relies on the distribution of pharmaceutical cannabis and research in order to catch up on the research backlog in the field of pharmaceutical cannabis. Farmako plans to become a vertically integrated market leader in every European country with a legal basis in this market. Farmako already has branches in Germany, Denmark and the United Kingdom.