Overview
Manufacturing pharmaceutical grade cannabinoids remains a challenge, especially for those that are found in only trace amounts in the cannabis plant, but nevertheless may hold very important pharmacological benefits in humans. InMed recognized that having a reliable source of pure, pharmaceutical-grade starting materials for its products that are bio-identical to the compounds found in nature would be a critical success factor for our drug development strategy.
In the current and rapidly emerging cannabinoid pharmaceutical sector, InMed’s biosynthesis approach to the production of pharmaceutical grade, bio-identical cannabinoids is a potentially disruptive technology.
There are several key advantages of manufacturing cannabinoids through a biosynthetic process:
- Cost savings relative to the existing agricultural methods (plant-grow-harvest-extract-purify);
- Enhanced production, streamlined purification and quality control versus other manufacturing methods; potentially easier path for scale-up and systems optimization;
- Access to minor cannabinoids that are currently not economically feasible to extract from plant sources and develop into drug candidates; and
- Bio-identical cannabinoids to those found in nature, in comparison to those produced by other chemical manufacturing methods where isomers (structural variations) may be a problem.
Over the last several years, InMed has made material strides in our biosynthesis program. In mid-2015, InMed commenced the development of a biosynthesis process for the manufacturing of cannabinoids through a research collaboration with Dr. Vikramaditya Yadav from the Department of Biological and Chemical Engineering at the University of British Columbia. Utilizing the basis of a vector created by InMed, Dr. Yadav commenced a Research and Development Project titled “The Metabolic Engineering of yeast and bacteria for synthesis of cannabinoids and cannabis derived terpenoids” under a Collaborative Research Agreement.
How our Technology Works
InMed is developing a proprietary, robust, microbial-based biosynthesis process for manufacturing any of the 100+ cannabinoids. The products that result from our process are bio-identical to the naturally occurring cannabinoids in the cannabis plant. Our process is designed to offer superior ease, control and quality of manufacturing when compared to alternative methods.
Microorganisms do not naturally produce cannabinoids. However, utilizing genome engineering to modify their metabolism, InMed has systematically introduced the cannabis plant’s metabolic pathways into bacteria, and has developed what it believes to be the first-of-its-kind production of downstream cannabinoids in these hosts.
Briefly, InMed has identified the specific gene sequences from the cannabis plant that encode the instructions to make specific enzymes that enable cannabinoid assembly and subsequently transplanted these genes into the bacterium E. coli. This intervention converts the bacterium into a manufacturing engine that produces large quantities of the target compound on demand.
This development provides an opportunity for industrial-scale manufacturing of naturally occurring cannabinoids, and we believe that it is a significant improvement over existing manufacturing platforms such as direct extraction from cannabis plants.
Direct extraction of minor cannabinoids is quite cumbersome, time-consuming and low yielding. The use of microorganisms for manufacturing cannabinoids eliminates the process of planting, growing, harvesting, extracting and purifying. There are also economic and environmental savings such as substantially reduced resource requirements (water, electricity, manpower, etc.). Furthermore, the growing process has several hard-to-remove impurities (e.g., pesticides), potentially presenting significant safety issues. As with all crops, yield fluctuations present an additional risk. Only a few of the 100+ cannabinoids can be extracted from the plant in sufficient quantities to make that process economically viable.
Cannabinoids are prenylated polyketides that are derived from fatty acid and terpenoid precursors. The biosynthesis of these molecules involves four metabolic pathways, two of which originate from central carbon metabolism. The first pathway (“terpenoid pathway”) culminates with the synthesis of geranyl pyrophosphate (“GPP”), and neryl pyrophosphate (“NPP”). These molecules are terpenoid building blocks, or precursors.
The second cannabinoid biosynthetic pathway, the “polyketide pathway”, is a truncated version of a polyketide biosynthetic pathway and results in the second requisite precursor, either: olivetolic acid (“OA”) and/or divarinic acid (“DVA”). The polyketide precursors subsequently combine with the terpenoid precursors in the third pathway, which comprises a single, specialized gateway enzyme, to yield the gateway cannabinoids. For instance, OA combines with GPP to yield the gateway cannabinoid cannabigerolic acid (“CBGA”).
Synthesis of the gateway cannabinoid CBGA is the most prevalent pathway in the cannabis plant, leading to high levels of both THC and CBD. InMed’s technology can mimic the natural synthesis of cannabinoids using an E. coli fermentation process.
The gateway cannabinoids are subsequently modified in the fourth pathway to yield cannabinoids such as tetrahydrocannabinolic acid (“THCA”) and cannabidiolic acid (“CBDA”). We refer to the fourth pathway as the downstream pathway and it involves the transformation of the acid form of the cannabinoids into the non-acid form via enzymes called “synthases”. Other combinations of the various precursors result in different gateway cannabinoids which, in turn, leads to diversification into the 100+ cannabinoids.
Earlier research for InMed’s bioprocesses employed E. coli and S. cerevisiae as the production hosts. Our advanced investigations have identified E. coli as a superior host for production of cannabinoids.

Successes and Future Applications
We have successfully constructed the terpenoid biosynthetic pathway and the gateway pathway for synthesis of CBGA and the downstream pathways for synthesis of THCA and CBDA. Our proprietary pathway is significantly more productive than previously patented terpenoid pathways, and we have confirmed the biosynthesis of the cannabinoids using validated HPLC methodologies and 1H-NMR instrumentation.
We have constructed a series of E. coli strains that express variations and/or subsets of the entire biosynthetic pathway and have tested production in lab-scale fermentation tanks. Next steps in the biosynthesis program are to:
- continue efforts to further diversify the number of cannabinoids produced using InMed’s system;
- scale-up the biosynthesis process to larger vessels, where protocols will be developed to optimize manufacturing parameters; and
- identify external vendors to assist in the commercial scale-up of the process.
Options for InMed’s GLP and GMP product manufacturing include either (1) building a dedicated biosynthesis facility or (2) transferring our process/know-how to a contract manufacturing organization with existing infrastructure to produce for us the preclinical, clinical and commercial scale supply of our product candidates.
In addition to providing a source of raw materials (active pharmaceutical ingredients, or “API”) for InMed’s therapeutic products, our biosynthesis program may play a significant role as a source of raw materials to other pharmaceutical companies, as well as a number to a number of other industries outside of the pharmaceutical segment.
The role of THC and CBD continues to expand at an exceptional rate in the recreational, nutraceutical and ‘medical marijuana’ spaces, where biosynthesis may prove to be an economical alternative to plant-sourced products. According to an October 2016 report issued by the Hemp Business Journal, the total consumer market for CBD alone is expected to surpass $2.1 billion by 2020, up from only $90 million in 2015. Estimates for the medical use of marijuana (delivering THC and CBD from the plant via smoking) have been estimated to be $12 billion in 2016 by Visiongain Ltd. and is expected to surpass $55 billion by 2025, according to a 2017 report by Grandview Research, Inc.