From a patient sample to millions of people treated during the COVID-19 pandemic
AbCellera discovered bamlanivimab, the first monoclonal antibody medicine for COVID-19 to receive U.S. FDA Emergency Use Authorization (EUA), and bebtelovimab, a second authorized antibody medicine effective against a wide range of SARS-CoV-2 variants. Together, these medicines have been used to treat millions of patients over the course of the pandemic, preventing hospitalizations and saving lives.
From sample to lead in just 3 weeks: the discovery of bamlanivimab
The Challenge
As the pandemic escalated in early 2020, millions were infected and clinical solutions to help people with COVID-19 were limited.
The Goal
Quickly find antibodies from the human immune response that:
- potently neutralize SARS-CoV-2
- can be developed into antibody treatments for COVID-19
Our Approach
We deployed our Pandemic Prevention Platform (P3) to search, analyze, and decode the human COVID-19 immune response to find antibodies with therapeutic potential, fast.
SOURCE
We received a sample from one of the first patients in the U.S. to recover from COVID-19.
SEARCH
We screened 5.8 million single antibody-producing cells using a multiplexed live cell-binding assay and identified 2,238 antibodies that bind to the SARS-CoV-2 spike protein.
DECODE
We used single-cell sequencing to decode more than 2,000 antibody-producing cells and identified more than 500 unique antibody sequences from 394 different clonal families in three days.
Bioinformatic analyses demonstrated that the antibodies were derived from robust immune responses with somatic hypermutation observed. The antibody sequences had a high degree of sequence diversity with 39 different VH genes used.
ANALYZE
Each unique antibody sequence was evaluated computationally and experimentally to identify approximately 500 different properties per antibody, yielding 220,000 data points. We used this dataset to filter down to a smaller group of lead antibodies.
The Outcome
Within 23 days of receiving the sample, we identified 24 lead antibodies for further development and clinical testing together with our partner.
Of these, bamlanivimab went from patient sample to the first monoclonal antibody treatment for COVID-19 to enter human testing in just 90 days.
Bamlanivimab was also the first monoclonal antibody treatment to receive EUA from the U.S. FDA for the treatment of mild-to-moderate COVID-19 in high-risk patients.
Bebtelovimab: a broadly effective treatment for an evolving pandemic
The Challenge
Emerging variants of SARS-CoV-2 pushed back progress by spreading more easily and threatening the effectiveness of COVID-19 treatments and vaccines.
The Goal
Find a next-generation antibody solution for COVID-19 with:
- Optimal potency
- Efficacy against a breadth SARS-CoV-2 variants
Our Approach
We expanded the search scope to identify human antibodies against SARS-CoV-2 and its variants.
SOURCE
We received a sample from a patient who had recovered from COVID-19.
SEARCH
We screened 740,000 single antibody-producing cells from the patient using a combination of multiplexed live cell-binding assays and bead-based assays. We identified 1,692 antibodies that bound to the SARS-CoV-2 spike protein.
DECODE
We sequenced 1,692 and identified 290 unique antibody sequences from 263 different clonal families.
ANALYZE
We used epitope binning with a search space focused on antibodies with different epitope specificities than existing, clinically relevant COVID-19 antibodies.
We identified an antibody that blocked SARS-CoV-2 from infecting human cells and bound an epitope that remained relatively unchanged during the pandemic.
The Outcome
We discovered bebtelovimab, a potent, neutralizing antibody effective against a wide breadth of SARS-CoV-2 variants. It helped address the challenge of treating patients during an evolving pandemic.
