This next portion of the presentation is designed to provide a brief overview of the drug development and clinical trials process in the US and give an update on COVID-19 vaccines. So where do new drugs come from? It's a long road from the research lab to the patient. In order for a compound to become a drug that will help people, a tremendous amount of money is invested in a lot of work over many years. Once there's ample evidence that a drug can and should be used to treat patients in the United States, it must be approved by the Food and Drug Administration or the FDA. The FDA regulates all drugs, including vaccines sold in the US, as stipulated in the Federal Food, Drug, and Cosmetic Act [inaudible] passed in 1938. To sell a drug in the US, a pharmaceutical company must submit scientific data to the FDA that shows the drug is both safe and effective in humans. Within the FDA, the Center for Biologics Evaluation and Research is responsible for evaluating this data for vaccines and other biological agents. Drug development is a lengthy, expensive process. It can typically takes at least 10 years and over one billion dollars to get a drug from the pre-clinical research phase to the market. During pre-clinical research and development, thousands of chemical or biological products are tested in vitro, meaning not in an animal or person, often in cells from incubators. This list is narrowed down based on how effective the test compound is, and producing a desired response, how selected it is, and its mechanism of action. Once a compound has come this far, it is tested in several animal models. Again, efficacy, selectivity, and mechanism are evaluated. Data on metabolism and side effects is also collected. When a compound has shown to be safe and effective in animals, it can move to trials in humans. The clinical trials process involves four phases, which are sometimes broken down further. Three of which must be successfully completed before a drug can be sold to the public. Data collected during clinical trials is submitted to the FDA for review. When the FDA approves the drug, it can be put on the market. However, at that point, the drug company does not stop collecting data. Valuable information, often about side effects, is gathered during this time. Occasionally, information will come out about side effects or adverse reactions after a drug is on the market. This may cause the company to change its recommendations for use or force it to withdraw the drug altogether. The vaccine adverse event reporting system is responsible for collecting post-market data on the side effects of US licensed vaccines. This information is monitored and analyzed by the FDA and the CBC. The clinical trials process is the stage which a drug is tested in humans. Clinical trials seek to determine the safety of the drug. Do benefits outweigh risks and efficacy? How good is it at what it's designed to do? Phase 1 is when the drug is given to a small group of young healthy people, around 50 or so. That determines human dosing ranges, estimated from data collected in animal studies, safety, and side effects. Phase 2 is where the drug is given to a larger group of people who are patients, several hundred, to see how well it works versus a placebo. More data on side effects is also collected. This is the point where most drugs fail the clinical trials process. They're safe, sure, but it turns out they don't really work. Phase 3 is an even larger and more varied group of patients, thousands, often at multiple sites. Now the drug is compared against the current treatment standards. Is it better than what's already available? Always, data on side effects is collected. Usually at least two successful phase 3 trials are necessary to secure FDA approval. As of the first week of April 2020, there were 115 vaccine candidates being developed worldwide. Although the vast majority are still in the exploring first stages of research and development, [inaudible] have already rocketed forward into clinical trials. On May 12th, the FDA awarded one of the vaccine candidates' Fast Track status, a designation that allows for a more streamlined approval process. The drug company's goal is to have their vaccine in phase 3 trials this summer. This is truly remarkable, considering the genetic sequence of the coronavirus was only just published in January. Many of the biological compounds being evaluated have never before been used to generate licensed vaccines. However, recent biomedical scientific advancements and the immediacy of the need has inspire scientists to push the conventional boundaries of vaccine in research and development. Not only will this hopefully speed up the development process, but it is likely that some of these novel vaccine strategies will be safer and or more effective in certain sub-populations, such as children, the elderly, and immunocompromised individuals. Although the vaccine development outlook is very positive, significant challenges lie in the way of final vaccine approval on large-scale administration. Most current research and development is being conducted by private companies that have never manufactured products on a scale that will be demanded and necessary once the vaccine is ready. Moreover, those companies are primarily located in North America, Europe, and Asia, meaning that vaccines developed in one region may not be as effective in another region due to variability and the geographic distribution of the virus. Also, despite the fact that development timelines had been accelerated at an unprecedented rate, there is uncertainty as to how fast the process can become before safety and efficacy are in danger of being compromised for the sake of remedy. Thus, it may be at least another year before a vaccine will be available for large-scale use. Even if the process is shortened, it remains expensive. Sophisticated biosafety containment measures and specific animal models are required to conduct this type of research. Finally, once the vaccine is available, profound global coordination will be required to produce, distribute, and administer the vaccine in the fastest, most efficient way possible. However, despite all these hurdles, it is not unreasonable to be optimistic that an effective vaccine is even now in the development pipeline. References and some additional resources are available for those wanting more information on the topics discussed in this presentation.