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COWEN COLLABORATIVE INSIGHTS February 25, 2019 controls c similar to an be implemented when producing compounds with a biosynthesis method the processes in place for pharmaceutical regulation. 2 The many perceived advantages of synthetic cannabinoid creation have led to a series of companie s entering the market, as described below. Figure 10 Selected Synthetic Biology Cannabinoid Companies Company Cellibre Notes Cellibre is a next-generation cellular agriculture company. Employing an organism-agnostic approach, Cellibre turns cells into specialized, sustainable factori es for the manufacture of globally significant products at scale. Ginkgo Bioworks Ginkgo is a Boston-based company that designs custom microbes for customers across multiple markets, developing new organisms that replace technology with biology. Hyasynth Biologicals Located in Montreal, Hyasynth Bio computational analysis to develop ogicals uses the technologies from traditional and modern biology combined with organisms at the fastest possible speed. InMed Pharmaceuticals InMed Pharmaceuticals is a biopha rmaceutical company that specializes in the discovery and development of novel, cannabinoid-based therapeutics fo r the treatment of diseases with high unmet medical need. Librede Librede has developed a yeast-bas that target the endocannabinoid system. Librede’s modular technology enables large scale production of natural cannabinoids in a more economic and environmentally sustainable way ed cannabinoid production and drug discovery platform to create chemical compounds Renew Biopharma Renew Biopharma harnesses the b brain barrier and target specific receptors associated with neuroinflammation and chronic pain. iological pathway to produce natural and novel cannabinoids that cross the blood Teewinot Life Sciences Tampa-based Teewinot combines i cannabinoid analogs and prodrugs its biosynthetic processes with sophisticated chemical synthesis to produce proprietary at commercial scale. Amyris Source: Cowen and Company Amyris is an industrial biotechnology company that has used sugarcane fermentation to create hydrocarbon molecules and produces an array of specialty ingredients and consumer products. Producing Cannabinoids Using Synthetic Biology Synthetic biology methods use fermentation to produce cannabinoids with identical chemical structures to those found in plants. Biocatalytic Cannabinoid Pathways The first step of the synthetic cannabinoid production requires identification and extraction of the desired cannabinoid biosynthetic pathways from a cannabis varietal. The biosy nthesis of cannabinoid molecules in a microbe could require four or more cannabinoid metabolic pathways. When the pathways are selected, their corresponding DNA sequences need to be cloned from the cannabis varietal and spliced into the microbial DNA. Cannabinoids could be produced biocatalytically using the following mechanism: i. Inthe first pathway, glucose is converted into G3P and pyruvate via glycolysis. These two compounds are then utilized to produce the precursors geranyl pyrophosphate (GPP), and/or neryl pyrophosphate (NPP). ii. Glycolysis of glucose also produces Acetyl CoA, which can catalyze biosynthesis of the second group of precursors: olivetolic acid (OA) and divarinic acid (DVA). COWEN.COM 19 HOUSE_OVERSIGHT_024835