Abstract
Cannabinoids and compounds made from Cannabis have a diverse range of therapeutic potentials, including
novel treatments for pain, seizure disorders, neurodegenerative diseases, addiction, and cancer. The Cannabis
plant itself produces over 400 unique compounds, 100 of which are bioactive cannabinoids that can activate the
endocannabinoid system through activating the G-protein-coupled receptors CB1 and CB2. The interest in
developing effective cannabinoid-based pharmaceuticals has only grown in recent years, with four FDA-
approved drugs on the market, and 200 trials in progress for a variety of therapeutic applications. Despite their
high therapeutic promise, critical issues in cannabinoid production have strained the commercial supply
chain. Cannibis plant cultivation uses large amounts of water and energy, and the realities of agricultural
production result in variable year-to-year yields and pesticide impurities. Adding to the issue, the purification
process of a specific cannabinoid from the many compounds produced by Cannibis plants are extremely labor
and manufacturing intensive, leading to prohibitively expensive final products. To overcome these challenges,
Cellibre is developing a fermentation-based microbial engineering and biofactory platform to produce
high-quality, cost-effective cannabinoids. This method has the potential to reduce the costs of cannabinoid
manufacturing by 5-10x and establish Cellibre as cost-effective, environmentally friendly leader in cannabinoid
manufacturing. By selecting bacterial and yest strains that naturally produce high concentrations of cannabinoid
precursors, then bioengineering them to encourage cannabinoid synthesis, Cellibre has yielded fermentations
of THCVA (2.7 g/L), CBGA (3.9 g/L) and other minor cannabinoids (i.e CBCA ~1.5 g/L) of high interest to
drug development. To accelerate these breakthroughs from proof of concept to scalable commercial platforms,
this Direct to Phase II project has the following two specific aims: 1) De-bottleneck metabolic pathways to achieve
>5 g/L of CBGA and THCVA, 2) Establish a process ready for technology transfer with an overall COGS
<$500/kg. These aims will result in the development of a pipeline capable of producing therapeutically relevant
cannabinoids at commercially viable titers, paving the way for the development and effective production of
cannabinoid-based treatments for a wide range of devastating diseases.
