Candidate: Antibodies targeting SARS-CoV-2
Type: Therapeutic antibody candidates from Twist that bind with high affinity to either SARS-CoV-2 S1 spike protein or the human ACE2 cellular receptor, using Serimmune’s Serum Epitope Repertoire Analysis (SERA) platform, designed to map the antigenic targets of antibody repertoires. Twist has studied both Immunoglobulin G (IgG) antibodies and substantially smaller single domain (VHH) “nanobodies,” the antigen binding fragment of heavy chain only antibodies.
Status: Twist Bioscience on September 9 announced positive data showing potent neutralizing effects of multiple potential therapeutic antibodies that were comparable to or better than those seen with antibody candidates derived from patients who had recovered from COVID-19.
“Importantly, the neutralizing effects seen in these in vitro studies suggest that infections in humans could be blocked. We are now evaluating the best path forward for these neutralizing antibodies to support the fight against COVID-19,” stated Emily M. Leproust, PhD, CEO and cofounder of Twist.
The in vitro studies involved testing more than 200 well characterized monoclonal antibody and VHH nanobody candidates against live virus and pseudovirus cells. Each antibody was chosen for its high and unbiased binding affinity to either the receptor binding domain of the S1 protein of SARS-CoV-2 or the extracellular domain of ACE2 in human cells.
The candidates were identified by Twist Biopharma, a division of Twist Bioscience, in six weeks by screening its proprietary synthetic antibody discovery libraries, each containing more than 10 billion antibody sequences. Within months, Twist said, it produced robust neutralization data in live virus cells.
According to Twist, the small size of VHH antibodies enables them to squeeze into spaces and bind to or block parts of molecules otherwise inaccessible to human IgG antibodies—and simplifies manufacturing of antibodies. VHH antibodies are also more thermally- and chemically-stable making them good candidates to address respiratory infections, administered by inhaler directly to the respiratory tract where the infection is concentrated, the company added.
Data was collected from studies conducted by Saint Louis University and independently verified by scientists at Colorado State University. “The results from both the IgG and VHH antibodies generated by Twist Biopharma warrant advancement of several of these compounds into animal studies and potentially into human clinical trials,” said Richard Bowen, DVM, PhD, of Colorado State.
In June, Twist Bioscience and Serimmune said they will partner to identify and evaluate SARS-CoV-2 therapeutic antibody candidates from Twist libraries using Serimmune’s SERA platform. “Serimmune’s platform will allow us to accelerate our efforts in a targeted and methodical manner to further increase the specificity of our antibodies, continuing our sprint in delivering new therapeutics to treat COVID-19,” Twist CEO and co-founder Emily Leproust, PhD, said in a statement.
Epitopes identified in the first phase will be used to re-screen Twist’s proprietary synthetic antibody discovery libraries to identify and evaluate new candidates—and to further increase the specificity of antibody candidates. Twist agreed to oversee advancement of all antibodies resulting from the collaboration.
COVID-19: 200 Candidates and Counting
To navigate through the >200 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:
● FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.
● DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data.
● KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.
● TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.
GEN has also tagged the most common treatment types: