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Archive - Mar 17, 2020

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Regeneron Announces Important Advances in Novel COVID-19 Antibody Program; Human Clinical Studies of Virus-Neutralizing Anti-Spike Protein Antibody Cocktail Anticipated by Summer

On March 17, 2020, Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) announced the latest progress in its efforts to discover and develop a novel multi-antibody cocktail that can be administered as prophylaxis before exposure to the SARS-CoV-2 virus or as treatment for those already infected. Regeneron scientists have now isolated hundreds of virus-neutralizing, fully human antibodies from the company's VelocImmune® mice, which have been genetically-modified to have a human immune system. Regeneron has also isolated antibodies from humans who have recovered from COVID-19, in order to maximize the pool of potentially potent antibodies. From this large pool of candidates, Regeneron will select the top two antibodies for a “cocktail” treatment based on potency and binding ability to the SARS-CoV-2 spike protein, as well as other desirable qualities. Using a multi-antibody approach allows for targeting of different parts of the virus and may help protect against multiple viral variants. Regeneron previously used these technologies to rapidly develop a successful treatment for Ebola virus infection, which is currently under review by the U.S. Food and Drug Administration. In order to meet the pressing public health need, Regeneron is applying its VelociMab® technology to prepare manufacturing-ready cell lines as lead antibodies are selected, so that clinical-scale production can begin immediately. The company is working toward the goal of producing hundreds of thousands of prophylactic doses per month by the end of summer and hopes to have smaller quantities available for initial clinical testing at the beginning of the summer. The company is working with the U.S. Health & Human Services' Biomedical Advanced Research and Defense Authority (BARDA) to increase capacity even further.

New Understanding of Flexible Structure of Interleukin-2 (IL-2) May Guide Drug Discovery

The signaling molecule interleukin-2 (IL-2) has long been known to have powerful effects on the immune system, but efforts to harness it for therapeutic purposes have been hampered by serious side effects. Now researchers have worked out the details of IL-2's complex interactions with receptor molecules on immune cells, providing a blueprint for the development of more targeted therapies for treating cancer or autoimmune diseases. IL-2 acts as a growth factor to stimulate the expansion of T cell populations during an immune response. Different types of T cells play different roles, and IL-2 can stimulate both effector T cells, which lead the immune system's attack on specific antigens, and regulatory T cells, which serve to rein in the immune system after the threat is gone. "IL-2 can act as either a throttle or a brake on the immune response in different contexts," said Nikolaos Sgourakis, PhD, Assistant Professor of Chemistry and Biochemistry at the University of California (UC), Santa Cruz. "Our investigation used detailed biophysical methods to show how it does this." Dr. Sgourakis is a corresponding author of the new study, published online on March 17, 2020 in PNAS. The article is titled “Interleukin-2 Druggability Is Modulated by Global Conformational Transitions Controlled by a Helical Capping Switch.” The first author, Viviane De Paula, PhD, a visiting scientist in his lab from the Federal University of Rio de Janeiro, used nuclear magnetic resonance spectroscopy (NMR) to observe IL-2's structural dynamics. The study was done in close collaboration with corresponding author Dr. Christopher Garcia's group at Stanford University. The researchers were able to show that IL-2 adopts two different structural forms (termed conformations) that affect how it interacts with the receptors on different types of T cells.

Melbourne Researchers Map Immune Responses from One of Australia's First Coronavirus (COVID-19) Patients, Showing the Body's Ability to Fight the Virus and Recover from the Infection

Melbourne researchers have mapped immune responses from one of Australia's first novel coronavirus (COVID-19) patients, showing the body's ability to fight the virus and recover from the infection. Researchers at the Peter Doherty Institute for Infection and Immunity (Doherty Institute) - a joint venture between the University of Melbourne and the Royal Melbourne hospital - were able to test blood samples at four different time points in an otherwise healthy woman in her 40s, who presented with COVID-19 and had mild-to-moderate symptoms requiring hospital admission. Published online on March 16, 2020 in Nature Medicine is a detailed report of how the patient's immune system responded to the virus. The open-access article is titled “Breadth of Concomitant Immune Responses Prior to Patient Recovery: A Case Report of Non-Severe COVID-19.” One of the authors on the paper, research fellow Dr. Oanh Nguyen, said this was the first time that broad immune responses to COVID-19 have been reported. "We looked at the whole breadth of the immune response in this patient using the knowledge we have built over many years of looking at immune responses in patients hospitalized with influenza," Dr. Nguyen said. "Three days after the patient was admitted, we saw large populations of several immune cells, which are often a tell-tale sign of recovery during seasonal influenza infection, so we predicted that the patient would recover in three days, which is what happened." The research team was able to do this research so rapidly thanks to the SETREP-ID (Sentinel Travelers and Research Preparedness for Emerging Infectious Disease) platform, led by Royal Melbourne Hospital Infectious Diseases Physician Dr. Irani Thevarajan at the Doherty Institute.