Research & Development
Abcellera Cites Published Data Supporting Bamlanivimab High Potency Against SARS-CoV-2 and Support its Use as a Foundational Antibody Therapy to Treat and Prevent COVID-19
6 April 2021 - - Canada-based AbCellera (NASDAQ: ABCL) and collaborators are highlighting the publication of research in Science Translational Medicine characterizing the high potency of bamlanivimab (LY-CoV555) to neutralize SARS-CoV-2 by uniquely binding both the up and down confirmations of the spike receptor-binding domain and inhibiting critical interactions with the angiotensin converting enzyme 2 cellular receptor necessary for viral entry, the company said.

Data generated in a preclinical model showed prophylactic treatment with bamlanivimab resulted in significant decreases in viral load and replication in the upper and lower respiratory tracts after SARS-CoV-2 exposure, indicating the potential of bamlanivimab to reduce viral shedding and transmission.

These data, which were generated prior to initiating clinical trials in June 2020 and published TODAY, support the observed substantial clinical efficacy of bamlanivimab in treating and preventing COVID-19.

Bamlanivimab has been evaluated both alone and together with other antibodies in more than 5,000 patients across multiple clinical trials and is currently authorized in more than 15 countries.

Bamlanivimab alone versus placebo has been shown to reduce hospitalization by 70% in high-risk patients with early COVID-19 infection3 and reduce the risk of contracting COVID-19 by up to 80% in nursing home residents when used as a prophylactic.

Because of its potency, bamlanivimab also provides a therapeutic foundation to be administered with other antibodies to expand the protection against viral variants. The first of these, bamlanivimab together with etesevimab, has been authorized in the US and within the European Union, and Phase 3 data show that this antibody therapy reduces COVID-19-related hospitalizations and death by 87%.

Most importantly, across all the clinical trials, all COVID-19-related deaths occurred in patients taking the placebo; no deaths occurred in patients who received an antibody therapy, either bamlanivimab alone or together with another antibody.

Data from multiple in vitro assays of the 24 lead antibodies identified by AbCellera and collaborators indicated bamlanivimab displayed greater neutralization potency despite similar RBD-binding affinities, suggesting bamlanivimab has a unique binding profile to the SARS-CoV-2 spike protein.

Structural analysis using X-ray crystallography and electron microscopy demonstrated that bamlanivimab binds to an area on the spike protein overlapping the ACE2 binding site that is predicted to be fully accessible in both the up and down conformations.

The RBD portion of the spike protein is the primary target for virus neutralization as it mediates the conserved mechanism of viral entry to infect cells.

The spike exists in an up or down position, with the up position enabling interaction with the ACE2 receptor and the down position potentially contributing to immune system evasion.

Regardless of the state of the spike protein, bamlanivimab has high binding potency to the RBD of SARS-CoV-2 spike protein.

To determine the potential of neutralizing antibodies to prevent SARS-CoV-2 infection, nonhuman primates were prophylactically treated with 1, 2.5, 15, or 50 mg/kg of bamlanivimab 24 hours prior to viral challenge. Critically, viral replication as well as viral load were significantly reduced in the upper respiratory tract on Day 1 at multiple doses.

Additionally, viral load and replication were significantly reduced or undetectable in the lower respiratory tract at several doses. At doses of 2.5 mg/kg and higher serum concentrations were associated with maximal protection in this model.

Bamlanivimab was developed from an antibody that was discovered from the blood of a recovered COVID-19 patient using AbCellera's pandemic response platform, in partnership with the Vaccine Research Center at National Institute of Allergy and Infectious Diseases (NIAID).

Within one week of receiving the sample, AbCellera screened over five m antibody-producing cells to identify and isolate approximately 500 unique antibodies that bind to SARS-CoV-2, the virus that causes COVID-19.

The binding antibodies were then tested by AbCellera, the VRC, and Eli Lilly and Company (Lilly) to find those most effective in neutralizing the virus. Bamlanivimab was selected as the lead candidate from this group of antibodies and was the first therapeutic candidate specifically developed against SARS-CoV-2 to enter human clinical trials in North America.

Bamlanivimab was the first monoclonal antibody to receive EUA from the FDA and is currently being assessed in several clinical trials alone and together with other antibodies.

AbCellera's pandemic response capabilities were developed over the past three years as part of the Defense Advanced Research Projects Agency (DARPA) Pandemic Prevention Platform program.

The goal of the P3 program is to establish a robust technology platform for pandemic response capable of developing field-ready medical countermeasures within 60 days of isolation of an unknown viral pathogen.

AbCellera's ongoing efforts to respond to the pandemic have identified more than 2,300 unique anti-SARS-CoV-2 human antibodies from multiple patient samples. These antibodies are in various stages of testing by AbCellera and its partners.

Bamlanivimab is a recombinant, neutralizing human IgG1 monoclonal antibody directed against the spike protein of SARS-CoV-2.

It is designed to block viral attachment and entry into human cells, thus neutralizing the virus. Bamlanivimab emerged from the collaboration between Lilly and AbCellera to create antibody therapies for the prevention and treatment of COVID-19.

Lilly (NYSE: LLY) scientists rapidly developed the antibody in less than three months after it was discovered by AbCellera and the scientists at NIAID VRC. It was identified from a blood sample taken from one of the first US patients who recovered from COVID-19.

Lilly has successfully completed a Phase 1 study of bamlanivimab in hospitalized patients with COVID-19 (NCT04411628). A Phase 2/3 study in people recently diagnosed with COVID-19 in the ambulatory setting (BLAZE-1, NCT04427501) is ongoing.

A Phase 3 study of bamlanivimab for the prevention of COVID-19 in residents and staff at long-term care facilities (BLAZE-2, NCT04497987) is also ongoing. In addition, bamlanivimab is being tested in the National Institutes of Health-led ACTIV-2 study in ambulatory COVID-19 patients.

Bamlanivimab alone and together with etesevimab are authorized under special/emergency pathways, in the context of the pandemic, in the US and the European Union.

In addition, bamlanivimab alone is authorized for emergency use in Canada, Panama, Kuwait, the UAE, Israel, Rwanda, Morocco and numerous other countries. Through Lilly's work with the Bill and Melinda Gates Foundation, Lilly is providing doses of bamlanivimab free of charge in Rwanda and Morocco.

AbCellera is a technology company that searches, decodes, and analyzes natural immune systems to find antibodies that its partners can develop into drugs to prevent and treat disease.

AbCellera partners with drug developers of all sizes, from large pharmaceutical to small biotechnology companies, empowering them to move quickly, reduce cost, and tackle the toughest problems in drug development.