Applied Clinical Trials
Lori McDermott, VP, Clinical Development & Regulatory Affairs at Heat Biologics, discusses their company's approach towards developing a COVID therapy.
The era of COVID-19 has brought on some exciting developments with the types of biopharmaceutical enterprises that are developing therapies and vaccines to treat the disease. Specifically, immuno-oncology enterprises are delving into the area, as their immunotherapies can also coincide with mechanisms of action that can also treat COVID. In this interview, Lori McDermott, VP, Clinical Development & Regulatory Affairs at Heat Biologics, will discuss their approaches towards developing a COVID therapy.
Moe Alsumidaie: You have focused your research efforts on Oncology, and now you're moving into COVID. How is COVID study design different than oncology? What clinical trial design approaches are you taking to developing a COVID therapy?
Lori McDermott: In solid tumor oncology, our primary endpoints are a substantial reduction in tumor size as well as those time-to-event endpoints such as progression-free survival and overall survival. Our COVID trials are going to have different endpoints such as reactogenicity, immunogenicity, and serology. We're going to have to design those early study cohorts, not just on dose level, but also on factors such as age group, and whether they're pre- versus post-exposure to SARS-CoV-2.
In oncology, it takes years to conduct a trial that impacts the standard of care that you're comparing against. We have plenty of time to account for and adjust. But in COVID trials, the standard of care can change very rapidly, especially in light of the accelerated pathways that are being supported by the FDA and other regulatory bodies.
MA: How does immunotherapy connect with COVID?
LM: With our specific vaccine, we use our proprietary platform, a cell delivery system. This involves engineering a cell line that secretes gp96 with multiple antigens. gp96 is a master chaperone serving as a molecular warning system: a natural process in the body presenting antigens, whether they be cancer-derived or viral proteins, to activate B cell and T cell responses.
In our COVID-19 program, we transfect multiple viral antigens from SARS-CoV-2 into our proprietary platform. This approach is feasible for large scale manufacturing and amenable to stockpiling. It also has the potential to offer a long-term cellular immune response, which may provide a higher level of immune protection for the elderly and those at high risk for complications and fatal outcomes due to underlying comorbidity.
What's different about this approach from other traditional vaccines is, we have the advantage of no anti-vector immunity, because we're not using a virus-based vector system. We also won't have any viral activation because we don't use attenuated virus-like conventional vaccines. We activate both T cells and B cells with high immunogenicity, driving the induction of mucosal, immunity, and long-term memory response. Those are some of the advantages, and that's how we're able to apply our platform to both oncology as well as to infectious diseases because we take the antigen and cells, whether it's from the oncology or the infectious disease setting, and we transfect into an allogeneic cell line.
There was a current need for us to take our proprietary platform and utilize it to help society as a whole. We are not detracting in any way from our oncology efforts, but rather modifying our technology to be able to serve the greater good and address the situation that we are in right now with COVID
MA: What site selection strategies are you employing for your COVID study?
LM: As opposed to the oncology trials, where our patients have a medical diagnosis, the initial COVID trials will be conducted in regular healthy volunteers. Study recruitment should be relatively straightforward in that population without any significant hurdles or challenges. Once safety is established in the healthy volunteers, we intend to shift focus to specialized subgroups such as the elderly population, healthcare workers, first responders, cancer patients, and other high-risk individuals with underlying comorbidities. To do that, we would look to engage veterans’ affairs hospitals, and health systems with expansive networks to achieve our enrollment and these target subpopulations.
MA: Can you discuss your study decentralization strategies?
LM: The patients will receive two doses of vaccine that will be administered four weeks apart. We will be following those subjects for up to a year. Because the COVID study endpoints include local systemic reactogenicity, adverse events, medically attended adverse events, new-onset chronic medical conditions, and serious adverse events, we'll be able to collect a lot of the safety information through virtual methods.
We are following FDA guidance to try to do as much data collection without requiring in-person visits to the clinic. We will be tapping into technology, utilizing ePROs, and virtual telemedicine visits to collect those endpoints. However, we also need to have the patients present to the clinic because other parameters that need to be studied are changes in your baseline IgG titer, as well as seroconversion. Those are the blood tests where we're looking at the antibody response and will have to be done by in-person visits, but we will try to limit as much as possible.
Moe Alsumidaie, MBA, MSF, is a thought leader and expert in the application of business analytics toward clinical trials, and Editorial Advisory Board member for and regular contributor to Applied Clinical Trials.