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Vir backs cross-reactive mAb strategy with preclinical potency data

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Vir has reported preclinical potency for a mAb against SARS-CoV-2 that beats the potencies other anti-SARS-CoV-2 mAbs recently reported and is on par with the company’s clinically validated Ebola therapy.

The mAb, dubbed S309, was isolated from a SARS patient and cross-neutralizes SARS-CoV and SARS-CoV-2. Vir’s first two clinical candidates for COVID-19, VIR-7831 and VIR-7832, are based on S309.

Vir Biotechnology Inc. (NASDAQ:VIR) has approached COVID-19 mAb discovery with a cross-reactive strategy. CEO George Scangos previously told BioCentury that because such mAbs bind epitopes conserved between the two viruses, the targeted sites are “likely to be very important for the virus in some functional sense” and unlikely to change when the virus mutates (see “Vir Scientific Path to COVID-19 Antibody Therapies”).

It also means they may be able to treat more than one type of coronavirus infection.

Reported in a Nature paper Monday, S309 neutralized SARS-CoV-2 in cell culture with an IC50 value of 79 ng/mL. In a SARS pseudovirus neutralization assay, the mAb had IC50 values of 120-180 ng/mL.

S309 is more potent than two academic mAbs reported in Science last week to reduce SARS-CoV-2 RNA levels and disease markers in the lungs of infected mice (see “COVID-19 Neutralizing mAbs Protect Mice”).

Moreover, S309’s IC50 values are comparable to that of mAb114, Vir’s anti-Ebola antibody. In cell culture, mAb114 neutralized Ebola infection with an IC50 of 90 ng/mL. The Ebola mAb has since demonstrated therapeutic efficacy in a clinical trial conducted in the Democratic Republic of the Congo, where it led to a 34% reduction in mortality. mAb114 is now being offered to patients in the country (see “Stalking Ebola” and “Two Ebola Therapies Best ZMapp in Congo Trial”).

Vir plans to begin a Phase II trial of VIR-7831 and VIR-7832 this summer, skipping Phase I.

The two mAbs have an Fc mutation that extends their half-life, increasing the time that they could provide immunity. VIR-7832 has a second Fc mutation designed to enhance binding to activating receptors on immune cells and virtually eliminate binding to inhibitory receptors. The goal is to increase near-term antiviral activity, while inducing T cell responses that could produce vaccine-like longer-term protection.

In April, Vir received a $250 million investment from GlaxoSmithKline plc (LSE:GSK; NYSE:GSK) when the two joined to accelerate the mAbs’ development (see “Vir Speeding COVID-19 mAbs into Phase II with $250M GSK Investment”).

At least three other groups have announced plans to start human testing of anti-SARS-CoV-2 mAbs this summer: Shanghai Junshi Biosciences Co. Ltd. (HKEX:1877) and partner Eli Lilly and Co. (NYSE:LLY); Regeneron Pharmaceuticals Inc. (NASDAQ:REGN); and AbCellera Biologics Inc., which is also partnered with Lilly.

After gaining 32% to $40.10 Monday, Vir shares gave back $6.12 (15%) to close at $33.98 on Tuesday.

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