COVID-19 mAb menagerie

A taxonomy of mAb programs against COVID-19

The COVID-19 crisis is mobilizing researchers to crank out therapeutic mAbs from a wide array of patient- and animal-based platforms, with the virus’ spike protein emerging as the consensus target antigen. But the hold-up for access to COVID-19 patient samples means some players’ most promising programs are waiting in the wings.

The speedy publication by Chinese scientists of the genomic sequence of SARS-CoV-2, the virus behind COVID-19, made it possible for companies to get a running start developing vaccines and therapeutics against the disease (see “The Race is On”).

For mAb developers, the sequence made it possible to simulate the new pathogen via recombinant proteins or pseudo-viruses, which are serving as immunization and screening tools until samples of SARS-CoV-2 from patients become more widely available.

Materials and information on the related virus SARS-CoV, which causes severe acute respiratory syndrome (SARS), is also jumpstarting mAb programs. However, a structural paper published in Science on Wednesday sheds light on the limits of extrapolating between SARS-CoV and SARS-CoV-2 (see “Insights on COVID-19 Vax, mAb Development from Spike Structure”).

COVID-19’s ark

At least five company and academic teams have disclosed use of specific mAb discovery platforms to take on COVID-19. Collectively, the platforms span at least four species (see Figure: “mAbs on the march against COVID-19”).


Figure: mAbs on the march against COVID-19

Vir Biotechnology Inc. (NASDAQ:VIR) and AbCellera Biologics Inc. are looking for mAbs in recovered patients. However, due to the current lack of access to SARS-CoV-2 samples, both are starting with mAbs from recovered SARS patients that cross-react with SARS-CoV-2.

Vir is deploying the technology it gained through its 2017 acquisition of Humabs Biomed S.A., while AbCellera is tapping its Pandemic Prevention Platform under contract with the Defense Advanced Research Projects Agency (DARPA), in collaboration with the Vaccine Research Center at NIH’s National Institute of Allergy and Infectious Diseases (NIAID) (see “COVID-19 Update”).

Vir has identified two mAbs that bind a region of the SARS-CoV-2 spike protein that the virus uses to infect cells, and is using a pseudovirus expressing the SARS-CoV-2 spike protein to assess whether these and other mAbs can neutralize viral entry.

AbCellera is using a microfluidics-based platform to screen antibodies from individual B cells. The company plans to release an update on its SARS-CoV-2 discovery work in mid-March.

Regeneron Pharmaceuticals Inc. (NASDAQ:REGN) is generating candidate mAbs by immunizing its transgenic VelocImmune mice, which produce human antibody repertoires, with a pseudovirus expressing the SARS-CoV-2 spike protein. The company is also investigating whether candidates it previously generated against MERS could cross-react with SARS-CoV-2.

The New York-based mAb company expanded its preexisting collaboration with the Biomedical Advanced Research and Development Authority (BARDA) to include therapies to treat COVID-19.

A Belgian team led by Flanders Institute for Biotechnology (VIB) and Ghent University professor Xavier Saelens has generated a single domain heavy chain antibody (VHH) candidate by immunizing llamas with a stabilized prefusion conformation of a spike protein domain that’s conserved between SARS-CoV and SARS-CoV-2.

Tim Van Acker, who is BD manager at VIB Innovation & Business, told BioCentury the team’s lead VHH candidate had an IC50 of 0.14 μg/ml in neutralization assays with SARS-CoV, and similar tests with SARS-CoV-2 are ongoing. The group is in the process of humanizing the lead construct and incorporating it into alternative formats such as fusion proteins. It also plans to immunize its llamas with SARS-CoV-2.

“The published sequence made it possible to simulate the new pathogen via recombinant proteins or pseudo-viruses”

Tool companies and CDMOs are jumping into the race.

Ligand Pharmaceuticals Inc. (NASDAQ:LGND) announced interest from undisclosed companies in using its OmniChicken platform -- one of the five transgenic animal technologies in its OmniMab portfolio -- to develop mAbs against SARS-CoV-2. The company declined to disclose details on specific programs and their targets.

Other service companies have reported they are developing mAbs against the virus but have not disclosed a specific platform technology or target.

One of Ligand’s partners, antibody discovery service company ImmunoPrecise Antibodies Ltd. (TSX-V:IPA; Pink:IPATF), said Thursday it will combine its B Cell Select and DeepDisplay mAb discovery technologies with the OmniMab platform.

ImmunoPrecise CEO Jennifer Bath declined to disclose whether the company would use Ligand’s chicken, mouse or rat technologies, but said the company will target both viral antigens and the human receptor that mediates SARS-CoV-2 entry, ACE2.

WuXi Biologics Inc. (HKEX:2269) said on Jan. 28 it had “stepped up its efforts in enabling the development of multiple neutralizing antibodies” against SARS-CoV-2 via its “integrated technology platforms.” The CDMO, which did not return requests for comment, said its first batch of mAbs targeting the virus would be ready for preclinical tox testing and first-in-human studies within two months.

Targets

ACE2 - Angiotensin-converting enzyme 2

Further analysis of the coronavirus crisis can be found at https://www.biocentury.com/coronavirus. The COVID-19 content is free to all who visit the site.

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