On December 1, Nemus Bioscience announced that the company found a synthetic pathway to manufacture tetrahydrocannabinol-valine-hemisuccinate (THCVHS), including the ability to scale-up production. The research was done in conjunction with Albany Molecular Research Inc., Nemus’ API contract developer and manufacturer. Furthermore, the API exceeded the FDA’s purity requirements.
Catalent Pharma Solutions is set to begin formulation work for the candidate product, NB2111, which is indicated for managing chemotherapy-induced nausea and vomiting (CINV). The company’s other candidate product, NB1111, is also a cannabinoid compound but is intended for the treatment of glaucoma.
Dr. Brian Murphy, CEO of Nemus Bioscience, participated in an exclusive Q&A with Pharmaceutical Processing on the company’s recent breakthrough. His edited responses are below.
Congrats on discovering a synthetic pathway to manufacture THCVHS! Could you tell us a little bit about your research and some of the events leading up to this discovery?
Cannabinoids, when delivered through smoking marijuana, have been known for quite some time to possess qualities that can help manage or mitigate a variety of disease processes. The only issue is that the delivery of cannabinoids via smoking is not the most effective way to provide long-term, customized, delivery of the molecules. Nemus is focused on developing synthetic, proprietary cannabinoid molecules so that cannabinoids can be delivered in the most optimized way based on the type of disease being treated and the best type of cannabinoid to impact the health of the patient. There are over 100 types of cannabinoid molecules in the marijuana plant.
What led you to investigate the potential use of synthetic cannabinoids (THC/THCVHS) in a drug product?
For the majority of pharmaceutical uses, the ability to synthesize and perform scale-up manufacturing is achieved in a much more cost-effective and predictable way using synthetic means, especially in planning to meet anticipated demand. It is also valuable to use synthetic means when working to meet regulatory agency requirements of purity, batch reproducibility, and consistency.
In your initial investigations of THC/THCVHS, what were some of the findings that sparked you to do further research?
Our initial studies revealed a decline in intra-ocular pressure in a validated animal model of glaucoma. Repeated studies revealed that THCVHS lowered IOP and entered multiple chambers of the eye while standard THC did not lower IOP and very little entered the eye. With a clinical development lead like that and the urgent medical need presented by glaucoma, we decided to push forward with development.
Your candidate product, NB111, is intended to treat glaucoma and also utilizes the patented prodrug of THC as the active ingredient. What led you to utilize THCVHS as an API for this particular candidate product and indication?
Historically, THC has been associated with a decline in intra-ocular pressure when delivered by smoking marijuana. But that delivery method is inefficient, costly, and can have systemic side effects versus what Nemus is doing with localized delivery of the prodrug to the eye. The prodrug delivers THC to the eye in a sustained way but that keeps the THC localized to the eye based on data that we have collected to-date using animal models. The prodrug allows the molecule to better able traverse ocular compartments in the eye and deliver the drug to the organs of the eye that regulate IOP.
Are there other indications that you feel THCVHS might have potential to treat as well?
Oral versions of THC have been approved for the management of CINV. In addition to pursuing that indication, we are working on glaucoma and possibly a pain syndrome further down the development path. Right now the company is focused on CINV and glaucoma.
Have you experienced any (regulatory) challenges working with synthetic cannabinoids?
Synthetic cannabinoids are the preferred method of developing regulatory approved medications. Without FDA/EMA approval to develop, test, and commercialize these molecules, they cannot move forward so it is imperative to abide by the regulatory pathways mapped out by the agencies in the respective territories.
What are some of the next steps for these two candidate products?
Next steps will focus on product formulation and preparation for an FDA meeting prior to filing an IND in order to begin human testing.