"This access has significantly accelerated the timelines and production yields for our partners." Renew Biopharma is a San Diego based synthetic biology company focused on creating pure, uncontaminated, and non-psychoactive cannabinoid derivatives to enable human therapeutic breakthroughs. It employs rational enzyme engineering to modify and improve enzymes to create and manufacture these novel molecules.
Visual Image of Renew Biopharma activities
The focus is to develop therapies to treat neurodegenerative diseases, traumatic brain injuries (TBI), and pain management. "TBI is the leading cause of death in the USA for people under the age of 45, and an estimated 5.3 million Americans currently live with related disabilities. This market size and economical cost in the USA are estimated at 60 billion per year. The preclinical data shows our drug leads exhibit control over effective markers for TBI and are being moved into our mouse TBI animal model," the company says.
Recent work (K. Blal et al., 2023) has shown the therapeutic value of cannabichromene (CBC). In combining CBD with CBC, they were able to show strong anti-tumoral effects on head and neck squamous cell carcinoma (HNSCC). Renew sees the value of CBCA and other minor cannabinoids as therapeutics and has an effort to create drug leads from these molecules.
Using the crystal structure of THCAS (Shoyama et al., 2008), Renew generated CBDAS, and CBCAS models and rationally designs mutants to create libraries at key amino acid positions in the enzymes. These libraries were screened for novel synthase activity like THCVA, CBDVA, and CBCVA production and ratio of production.
All three natural cannabinoid terminal synthases (THCAS, CBDAS, CBCAS) have fidelity issues and produce all three molecules, THCA, CBDA, and CBCA, in some ratio and amount. By using rational base design, structure-function relationships for key residues were established, which assisted in creating novel terminal synthases that can either express a specific cannabinoid, or very specific cannabinoid ratios.
Cannabinoid terminal synthases were also designed for specific minor cannabinoids like THCVA, CBDVA, and CBCVA. When these minor terminal synthases are matched with Renew's complimentary engineered prenyltransferases, one can create the efficiency, scale-up, and profitability of manufacturing minor cannabinoids by fermentation or plants.
Wild Type CBDAS and THCAS are not able to cyclize CBGVA at very high efficacy. Modifying the active site of both can significantly improve CBGVA utilization to create CBDVA and THCVA for both microbial and plant production systems
Several companies have now licensed Renew's enzymes. "This access has significantly accelerated the timelines and production yields for our partners as they approach full scale commercialization and monetize Renew's intellectual property."
This includes a license to Hypercann, a plant-touching cannabis company, which has successfully shown heritable expression of Renew's engineered enzymes in hemp plants, to improve and modulate major and minor cannabinoids.
Renew's patent portfolio of engineered enzymes includes a granted patent (WO2019183152) relating to the rational-based engineering of a prenyltransferase known as NphB. This novel enzyme is instrumental in producing CBGA, CBGVA, CBG, and CBGV, the precursors to most cannabinoids (including THCVA, CBDVA, and CBCVA), and is critical to produce major and rare minor cannabinoids. Renew has pending patent applications for the engineering of other enzymes in the cannabinoid pathway, including two that describe novel cannabinoid terminal synthases, CBDAS, CBDVAS, THCAS, THCVAS, CBCAS, and CBCVAS.
"World-class enzyme engineering has always been a strategic focus of Renew. As the field of microbial biosynthesis advances and our IP matures, including our most recent patents on cannabinoid terminal synthases, I can see additional licensing opportunities in the manufacturing of minor cannabinoids with different companies working in microbial fermentation," says Mike Mendez, CEO of Renew.
"I am also excited by the progress of Hypercann and the future of our IP back into plants to provide a new field of opportunity in global cannabinoid production," he adds.
For more information:
Renew Biopharma
Mike Mendez
mendez@renewbiopharma.com
www.renewbiopharma.com