March 29, 2021 PAO-02-21-CL-06
When one examines the history of Western medicine, many of the drugs used throughout history — including today — were derived from plants. In fact, greater than 50% of all drugs that have been approved by the U.S. FDA were at least initially isolated from plant species.
Initially, our goal at GB Sciences was to explore the therapeutic properties and potential of cannabis. In order to have access to the plant and money to fund our research, we obtained state licenses to grow and sell medical cannabis. We surveyed different varieties of the Cannabis plant to understand how they differed with respect to the concentrations of cannabinoids and terpenes and other secondary metabolites. Using high-throughput screening (HTS), computer modeling based on proprietary algorithms, and disease-specific cell and animal models, we generated promising data over several years.
One of the things we learned was that — when advancing a candidate from a plant extract to a therapy — mixtures of compounds performed better than single substances. However, when we tried to match up specific plant varieties with diseases, there were always compounds in the original mixture that had no or an undesired clinical effect and needed to be removed.
Ultimately, we concluded that we needed to apply rational design to optimize these therapeutic mixtures. Using computer modeling and cell and animal data, we developed initial products containing 9–12 ingredients. We have had five patents issued in the United States for these plant-inspired optimized therapeutic mixtures. We refer to them as plant-inspired because the earliest generations of the drug prototypes contained compounds isolated from plants, even as we move away from plant-based production and design therapeutically optimal mixtures of compounds.
All of our products today are comprised of synthetic homologs or exact copies of the molecules produced using traditional synthetic chemistry under pharmaceutical GMP conditions. For each of the mixtures, we have also demonstrated in our disease models that they offer therapeutic synergies compared to the sum of benefits realized when each individual compound was used alone.
Through this strategy, we have incubated a biotech company inside a cannabis company, and at this juncture we are ready to make the pivot completely. We sold our plant-touching assets, and now all of our resources, time, and energy are dedicated to expanding and advancing our pipeline of drug candidates.
Because some of the models we used to explore underlying phenomena are common to several different diseases, GB Sciences has established seven patent families containing related diseases that we are targeting. Within each patent family, we have specific formulations for the different indications that fall within that family.
For instance, our neurodegenerative patent family includes Parkinson’s, Alzheimer’s, Huntington’s disease, and Lewy body dementia, because the cell models used to identify effective optimized mixtures were shared among those particular indications. Our animal models typically are then specific for a single disease, such as Parkinson’s or Alzheimer’s disease, to help refine the original mixtures to contain compounds that are more specific for those particular indications.
One of the challenges with cannabinoids and terpenes is the lipophilicity of these compounds. In addition to identifying the optimal mixtures of these compounds for specific indications, we have had to couple these mixtures with delivery systems that enhance their in vivo solubility and bioavailability.
There is also a need to consider the most appropriate delivery solution with respect to ease of use and patient-centricity. Many Parkinson’s patients, for instance, have trouble swallowing, yet they still prefer oral medications over injections or other unpleasant means of administration. To overcome these challenges, we are working with Catalent Pharma Solutions to formulate our Parkinson’s mixture as a small, orally disintegrating tablet that is placed on or under the tongue.
For our pain formulations, we are leveraging oral nanoparticles, because many of the small molecule terpenes in these formulations will evaporate under normal conditions. The nanoparticle format, developed by our Spanish partners at the University of Seville and the University of Cadiz, ensures that the terpenes stay in solution. We are also developing a controlled-release, cannabinoid-containing nanoparticle therapy that, in a rodent model of pain, demonstrated 11 days of pain relief with a single oral dose.
In 2020, GB Sciences received its first U.S. patent for a formulation targeting Parkinson’s. We have achieved statistically significant animal data to support this formulation and are moving to get this lead candidate into the clinic as quickly as possible. Our second candidate is a neuropathic pain formulation that contains no cannabinoids. This formulation, for which we also received a patent in 2020, is currently in a preclinical animal study.
We filed a third patent application in October 2020 for a treatment for cytokine release syndrome. This application is based on results obtained using an immune cell model in which human-derived immune cells were co-cultured. This optimized mixture regulates the cytokines that have been specifically linked to adverse outcomes in COVID-19 patients without decreasing the levels of CD4+ and CD8+T cells. This treatment thus specifically targets those cytokines that seem to be causing the problems, while preserving the patient’s ability to fight the virus.
What is really exciting about this potential COVID-19 therapy is that a proof-of-concept study is being conducted at Michigan State University to validate our previous results. If we obtain positive data from this study, we may be able to get into the clinic very quickly. In addition, this cytokine release syndrome drug has potential applications beyond COVID-19; this condition occurs with other SARS viruses and many immunotherapies.
Other products in our pipeline target heart failure, mast cell activation syndrome (MCAS), and inflammatory bowel disease.
With the intent of launching clinical studies in the near future for several of our candidate formulations, GB Sciences has begun to explore partnerships with different contract research organizations (CROs). We are currently interviewing different CROs for our Parkinson’s trials and hope to announce our selection by the summer of 2021. We are also talking with potential contract development and manufacturing organizations (CDMOs) regarding larger-scale production of our oral nanoparticle pain formulations. The goal is to identify service providers with not only the right capabilities, but also a similar culture and viewpoint.
GB Sciences is a discovery company focused on the identification of plant-inspired optimized therapeutic mixtures. As a virtual biopharma company, we have partnered with nine different universities and several different development organizations to perform the initial discovery work and preclinical studies. For any candidates with positive results in phase II, our strategy is to find appropriate partners that can help shepherd them through phase III trials, commercial launch, and marketing.
Given that GB Sciences was founded on the recognition that plants have fundamental medicinal value, we have been working to develop tools beyond our initial algorithms, cell and animal data, and information in available public databases that can provide additional insights. This work is predicated on the understanding that, throughout history, people have relied on plants for healing purposes. Societies that have existed for thousands of years typically have some form of pharmacopoeia of “traditional medicines” derived from plants. The medicines developed in each society have evolved independently, through trial and error, based on the plants accessible to them.
We have developed a new program that incorporates traditional medicine data from many different cultures — Chinese, Japanese, African, Indian, indigenous Americans, and others — into a single searchable space: the PhAROSTM (Phytomedical Analytics for Research Optimization at Scale) Drug Discovery Platform. We believe that, although these traditional medicines were developed independently in different parts of the world, there will be some convergence of value.
Using data analytics and machine learning, this program is designed to help us glean indications of efficacy for different mixtures of compounds for specific conditions across different cultures by searching for convergences in these different databases. The system is searchable starting either with a specific plant or a certain disease or set of conditions. Using these new tools, we will be able to better tap into the potential of many species of plants and move beyond just cannabis, which will allow us to cost-effectively develop a much broader range of rationally designed optimized mixtures to treat different indications
To raise the funding needed to progress our top pipeline candidates into the clinic, we plan to roll out two entities. The first will comprise our pipeline candidates headed to the clinic, which will be uplisted to Nasdaq. The second will be the Pharos Institute, which will house our intellectual property for our proprietary technology platform and any new partnerships we form related to our discovery work. This approach will enable the folks involved with the pipeline to focus on getting these candidates to the clinic, while those involved in discovery can concentrate on identifying new formulations. In particular, we are excited to start mining the new traditional medicines data for combinations of compounds from many different plants, not just for our own development efforts, but to support external parties as well.
Dr. Andrea Small-Howard leverages broad biopharmaceutical industry knowledge as the President, Chief Science Officer, and member of the Board of Directors at Gb Sciences, Inc., where she brings passion for advancing clinical research on phytochemical compounds and her strategic vision for creating a novel drug discovery engine and biopharmaceutical drug development program for disease-specific phytomedicines. Dr. Small-Howard has more than 20 years of scientific research experience; as well as executive experience in the biopharmaceutical industry supervising research and development, manufacturing, and quality control departments in both US and global divisions.