On Jun. 11, 2020, Regeneron announced announced that Science has accepted for publication two papers describing the creation of its novel two-antibody cocktail, REGN-COV2, and its potential to diminish risk of viral escape by effectively binding to the virus’s critical spike protein in two separate, non-overlapping locations. The publications will be available online on Monday. Regeneron also announced today that REGN-COV2 has entered human clinical trials.

Regeneron scientists evaluated thousands of fully-human antibodies produced by the company’s proprietary VelocImmune^® mice, which have been genetically-modified to have a human immune system, as well as antibodies isolated from humans who have recovered from COVID-19. They selected the two most potent, non-competing and virus-neutralizing antibodies and have scaled them up for clinical use with the company’s in-house VelociMab^® and manufacturing capabilities. The two antibodies bind non-competitively to the critical receptor binding domain (RBD) of the virus’s spike protein, which diminishes the ability of mutant viruses to escape treatment, as demonstrated in upcoming Science publications of preclinical research.

Regeneron used the same ‘rapid response’ capabilities and cocktail approach to develop REGN-EB3, a novel triple antibody treatment for Ebola that is now under regulatory review by the U.S. Food and Drug Administration (FDA). REGN-COV2’s preclinical development and preclinical/clinical manufacturing has been funded in part with federal funds from the Biomedical Advanced Research and Development Authority (BARDA), part of the office of the Assistant Secretary for Preparedness and Response at the U.S. Department of Health and Human Services, under OT number: HHSO100201700020C.

The first two adaptive Phase 1/2/3 studies are evaluating REGN-COV2 (REGN10933+REGN10987) as a treatment for hospitalized and non-hospitalized patients with COVID-19. The Phase 1 portion will focus on virologic and safety endpoints, and the Phase 2 portion will focus on virologic and clinical endpoints. Data from the Phase 1 and Phase 2 studies will be used to refine the endpoints and determine size for the Phase 3 studies.

Regeneron’s core technologies allow for rapid and efficient generation of these protective anti-viral antibodies outside of the body, derived from either genetically-humanized mice or convalescent humans. The resulting antibodies correspond to the most potent of anti-viral antibodies that could be elicited by a vaccine or through exposure to a pathogen. These antibodies can be delivered to people via injection, providing “passive immunity” and protection from the disease immediately, though they must be re-administered to remain effective over time. These antibodies can also treat an existing infection, unlike vaccines which can only be used preventatively.

The concept that drug cocktails can prevent viral escape has previously been demonstrated for traditional antiviral drugs used to treat HIV and other viruses. In the upcoming Science publications, Regeneron scientists report the fundamental realization that this can also be true for antibody-based therapies. Regeneron’s preclinical studies demonstrate that, in the setting of a single therapeutic antibody that blocks the ability of a virus to infect healthy cells, spontaneously arising mutant forms of the virus are able to ‘escape’ or evade the antibody’s blocking action. These mutants are then ‘selected’ (i.e., are able to survive and proliferate despite the single antibody treatment) and may ultimately become the dominant strain of the virus. Regeneron therefore pursues a multi-antibody cocktail approach designed to decrease the potential for the virus to escape.

Regeneron has developed additional technologies that allow for the large-scale manufacturing and purification of these anti-viral antibodies, potentially allowing many people to be granted immunity before vaccines become widely available.