Willow Biosciences: The Science of Industrial Scale Pharmaceutical Cannabinoid Production

With the very recent loosening of restrictions on cannabis research across the world, the pharmaceutical industry is playing catchup following decades prohibition. More than 100 cannabinoids, the active ingredients in the cannabis plant, have been identified. Many of these show promise as potential treatments for a wide variety of disease indications but require much more research. Currently there are around 300 clinical trials centered around cannabinoid treatments, and that number is growing in a field basically in its infancy. One major problem? How do researchers secure an adequate supply of pure cannabinoids in a constrained market?

Willow Biosciences Inc. (CSE: WLLW) believes it has the answer. Experts in the field of synthetic biology, the company is turning that experience to the synthesis of pure, pharmaceutical grade cannabinoids for the drug development market. Willow’s processes offer many advantages over extraction from plants, and even offer the possibility of improving the performance of some cannabinoids over their naturally-derived versions. This process can also be used for the CPG (consumer packaged goods) market as well. Before major beverage companies start adding cannabinoids like CBD to their drinks for mass consumption they will likely want to secure a consistent, industrial friendly, production source for their ingredients. Synthetic biology offers that clean and pure source.

Synthetic Biosynthesis

The field of synthetic biology is fairly new. In essence, researchers apply engineering principles to natural systems and materials to improve them for specific applications. They break down natural processes into component parts, see how they work, and then design improvements to those systems. As the field applies to cannabinoid production, the goal is to engineer microbes that can produce natural, pure cannabinoids more efficiently, more cleanly, and in greater volumes than the cannabis plant itself.

The general idea of synthesizing naturally-occurring active ingredients is not new. Many of our modern drugs, including aspirin and insulin, are synthesized in some way outside of the natural environment in which they are found. The most common method has been chemical synthesis, which employs chemicals to create a chain of reactions resulting in the desired compound. Biosynthesis, however, looks to copy the DNA sequences responsible for the natural processes and insert them into living things like yeast and bacteria, turning those microorganisms into active ingredient factories.

Scientists over the past few years have been working on engineering yeast to produce opiates but ran into a problem. One of the key steps in the opium poppy’s natural pathway remained a mystery, effectively limiting the ability of the engineered yeast to make the desired opiates on a practical scale. Enter Dr. Peter Facchini, Professor of Plant Biochemistry at the University of Calgary and Willow’s Chief Science Officer. Dr. Facchini discovered a critical enzyme responsible for catalyzing a crucial step in the natural process. This discovery was a huge breakthrough, leading to an immediate 24-fold increase in the production of the desired opioid, called thebaine. Thebaine is a crucial component in the production of maloxone, buprenorphine, oxycodone, and naltrexone. This is what gives Willow Biosciences the confidence to execute on their synthetic biology business plan. They have done this process before in the opium plant and will take that structure and knowledge to the cannabis plant.


Dr. Facchini and his team are now turning their attention to cannabinoid synthesis. The cannabis plant is incredibly complex, producing more than 100 cannabinoids that may offer therapeutic potential. Many of these occur naturally in such low amounts that extracting them for research purposes is prohibitive. Even for the more widely known and naturally prevalent compounds such as THC and CBD, reliance on plant production and extraction is not practical from either an economic or scientific standpoint. Problems include waiting on plants to mature while inefficiently expressing an unknown amount of active ingredients, extraction techniques that can contaminate samples and maintain impurities carried by the plant, and high costs resulting from agricultural overhead and rarity of the active compounds.

A synthetic biology approach solves all of the problems with the agricultural/extraction solution listed above. It also offers many benefits when compared to more traditional chemical synthesis. The chemical processes have yet to be discovered for many cannabinoids, and the processes currently in place can often result in impurities, high volumes of organic waste, and long production times. Synthetic biology offers the potential of decreased costs, fewer to no impurities, and minimal waste. Production cycles range from 6 to 10 days to get a finished cannabinoid.

The Willow team is deep into the research process, identifying the genetic pathways responsible for the production of a number of cannabinoids and engineering microbes to produce those compounds purely and efficiently. Once identified and developed, the processes can be patent-protected and commercialized. The end markets are not small.

A quick search of ‘cannabinoid’ on ClinicalTrials.gov yields more than 300 results. A search for ‘CBD’ gives more than 500 results. These numbers are growing. GW Pharma’s Epidiolex®, the first CBD medicine approved by the FDA, is a treatment for two fairly rare but treatment-resistant forms of childhood epilepsy, generated net sales of $33.5 million in its first quarter. Cowen & Co analysts predicted sales of $1.3 billion by 2022, according to Reuters. These are sales projections for just one drug and two rare indications. Cannabinoids are also being researched to treat a wide variety of more common conditions, including Alzheimer’s disease, chronic pain, inflammation, cancer, and arthritis.

Willow also has its eye on the exploding consumer product market for CBD. Applications include cosmetics, anti-aging skin creams, pain relievers, anti-inflammatory creams, beverages, and edibles. It’s a broad industry that is just finding traction. Cowen & Co estimates the US CBD market could reach $16 billion in annual sales by 2025, and that is only considering the currently-known product types. Willow estimates that up to half of CBD products coming to market will require pharmaceutical-grade CBD as a basis.

The Upshot

Willow Biosciences began trading on the CSE on April 15, 2019, the result of business combination/reverse takeover and a private placement totalling CAD$29 million. The company believes it is fully funded to commercialize production of CBD, leaning on the demonstrated expertise of its scientific team as well as an impressive executive team with extensive biotech, financial, and regulatory experience. Synthetic Biology is expected to disrupt the cannabinoid industry supply chain. Keep an eye out here as we discuss Willow in greater detail and more announcements come from the company itself.


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