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6 BioPharm International eBook October 2020 www.biopharminternational.com ne ut r a l i z i n g a nt i b o d ie s f r o m pat ie nt s who have r e cove r e d . A mgen for med a collaborat ion w ith Adaptive Biotechnolog ies, a c o m m e r c i a l - s t a g e b i o t e c h - nolog y company specializing in immune-system based therapeu- tics, to combine their respective e x p e r t i s e i n de ve lopi ng f u l ly human neutralizing antibodies to target SARS-CoV-2 for the potential prevention of infection or to treat the disease (14). Amgen obtained viral gene sequences from hun- dreds of recovered patients, and Adaptive is using its high through- put plat for m to rapid ly screen the B -cell receptors from recov- ered patients to identify naturally occurring antibodies. From there, Amgen will select, develop, and manufacture neutralizing antibod- ies against the virus. ANTIBODY COCKTAILS A ntibody cocktails are another area of development for COVID-19 therapies. These typically involve a combination of antibodies. I n J u l y 2 0 2 0 , R e g e n e r o n Ph a r m ac e ut ic a l s w a s aw a rde d a $450 -million contract by the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretar y for Preparedness and Response at the US Department of Health and Human Services (HHS), and the Department of Defense (DOD) Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense as part of Operation Warp Speed t o m a n u f a c t u r e a n d s u p p l y Regeneron's investigational double antibody cocktail, REGN-COV2. The two antibodies that comprise REGN-COV2 were shown to bind non- competitively to a cr itical receptor-binding domain of the spike protein in the SARS-CoV-2 virus. This action diminishes the ability of mutant viruses to evade treatment, which is believed to confer protection against spike variants that may have arisen in the human population (15). REGN- COV2 is in two Phase II/III clinical trials for treating COVID-19 and in a Phase III trial for preventing COVID-19 infection. In August 2020, Regeneron part- nered with Roche (16) to develop, manufacture, and distribute the therapy. Roche will have distribu- tion responsibility outside of the US while Regeneron will distrib- ute in the US, pending success- ful clinical trials and regulatory approval. Under this collaboration, supply of REGN-COV2 is expected to increase by at least three-and- a-half times the current capacity. Future supply expansion is also possible under the agreement. In Regeneron's latest update (17) announced in September, the first data collected from an ongoing Phase I/II/III trial showed that the antibody cocktail reduced viral load and quickened the time to symptom alleviation in non-hospi- talized COVID-19 patients. AstraZeneca, in parallel to its COVID -19 vaccine development efforts, is also developing an anti- body coc kta i l aga i nst COV I D - 19. The company announced in August (18) that it had started a Phase I clinical trial for its two- mAb combination, AZD7442. The t r ia l is f u nded by BA R DA a nd the Defense Advanced Research P rojec ts Agenc y ( DA R PA), pa r t of the DOD. The two mAbs that compr ise A Z D7442 a re der ived f r o m c o n v a l e s c e n t p a t i e n t s who were infec ted w it h SA R S - CoV-2 . T he m Abs were discov- e re d by Va nde rbi lt Un ive r sit y M e d ic a l C e nte r a nd l ic e n s e d to A st ra Z e ne c a i n Ju ne 2 02 0. Astra Zeneca has optimized the m Abs w it h ha l f-l i fe e xtension and reduced Fc receptor binding. According to a study published in July (19), these mAbs were shown in preclin ica l st ud ies to block SARS-CoV-2 virus from binding to host cells. They were also shown to protect against infection in cell and animal models of disease. On Oct. 9, 2020, HHS and the DOD for med a n ag reement to fund AstraZeneca with $486 mil- lion for two Phase III clinical trials and large-scale manufacturing for AZD7442 doses in the US (20). OTHER BIOMOLECULES In addition to antibody therapeu- tics, other companies are exploring different types of biomolecules for the potential to treat COVID-19. Biopha r ma compa ny A i r way Therapeutics formed a collabora- tion with CDMO Celonic Group in May to produce AT-100 (rhSP-D), an engineered version of an endoge- nous protein that has shown in pre- clinical studies that it can reduce i n f l a m m a t i o n a n d i n f e c t i o n through modulation of the immune response. Airway is advancing devel- opment of the molecule as a poten- tial treatment for patients seriously affected by COVID-19. Prior to this collaboration, the molecule was not produced for large-scale clinical trial indications, but, under the collab- oration, Celonic is responsible for Regulatory Sourcebook Pandemic Response Backed by FDA support, bio/pharma companies are exploring new ideas as well as looking at molecules already in development.