Vir speeding COVID-19 mAbs into Phase II with $250M GSK investment
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A $250 million investment by GlaxoSmithKline will put the clinical trial expertise and regulatory acumen of one of the leading anti-infective drug companies behind Vir’s effort to bring an antibody therapy to fight against COVID-19, Vir CEO George Scangos told BioCentury Monday.
Vir Biotechnology Inc. (NASDAQ:VIR) expects to start a Phase II trial within three to five months of two versions of an antibody product, VIR-7831 and VIR-7832, which target the spike protein of SARS-CoV-2, and are administered via intramuscular injection.
In the deal announced Monday, GlaxoSmithKline plc (LSE:GSK; NYSE:GSK) and Vir said they would combine GSK’s functional genomics and vaccines expertise with Vir’s capabilities in CRISPR screening, artificial intelligence and epitope identification to discover new mAbs and vaccines for coronavirus infections, including but not limited to SARS-CoV-2.
In the immediate term, GSK will accelerate the enrollment and completion of trials of Vir’s two COVID-19 mAbs, handle global regulatory filings, and provide some manufacturing capacity, Scangos said.
“They had B cells in their freezers from SARS patients.”
VIR-7831 and VIR-7832 were discovered by a team at Vir subsidiary Humabs BioMed in Bellinzona, Switzerland, based on research they had conducted on SARS-CoV-1, the coronavirus behind SARS. “They had B cells in their freezers from SARS patients,” which they found contained potent neutralizers of SARS-CoV-2 as well SARS-CoV-1, said Scangos.
While Vir has subsequently discovered neutralizing antibodies in samples from recovered COVID-19 patients, the company believes there is an advantage to using those from SARS patients, Scangos said. This approach yields antibodies that recognize epitopes that are conserved between SARS-CoV-2 and SARS-CoV-1, which could provide broader protection, including against mutated versions of SARS-CoV-2, he said.
Both VIR-7831 and VIR-7832 have an Fc mutation that extends their half-life, increasing the time that they could provide immunity.
In addition, Scangos said Vir plans to add a second Fc mutation to VIR 7832 designed to enhance binding to activating receptors and virtually eliminate binding to inhibitory receptors on immune cells. The goal is to increase near-term antiviral activity while also inducing T cell responses that could produce vaccine-like longer-term protection.
Three Phase II trials
Vir plans three Phase II trials of its COVID-19 antibody products.
One of the trials will test VIR-7831 and VIR-7832 as prophylactics.
A second trial will test them in early-stage patients who have a positive diagnosis but have not experienced respiratory distress. The goal will be to determine the extent to which the investigational therapies can prevent patients from advancing to respiratory distress.
The third trial will test the ability of the antibodies to help patients who are in respiratory distress.
Vir has not released the trial sizes. Scangos said he expects each to enroll hundreds of patients.
Trials will take about 30 days and will be conducted wherever is appropriate based on the shape of the epidemic curve, Scangos said. He added that the time to completion of the trials will be determined primarily by the speed of enrollment.
GSK’s global network of clinical sites and access to key opinion leaders will dramatically speed enrollment, according to Scangos.
Beyond clinical trials, Vir and other COVID-19 antibody developers face challenges in securing manufacturing capacity.
GSK will provide some manufacturing capacity, Scangos said. In addition, Vir has a deal with WuXi Biologics Inc. (HKEX:2269) and a letter of intent with Biogen Inc. (NASDAQ:BIIB) for mAb manufacturing capacity; in the case of WuXi, the deal pairs the companies’ co-development expertise. The biotech is also working with NIH’s National Institute of Allergy and Infectious Diseases (NIAID) Vaccine Research Center to characterize its mAbs and with Xencor Inc. (NASDAQ:XNCR) to increase the mAbs’ half-lives.
Vir is in negotiation with other companies to secure manufacturing capacity, Scangos said.
These efforts may fall short unless large-scale investments in new manufacturing capacity are made quickly and construction is fast-tracked.
“It could be that unfortunately the world will need a lot of antibody” to prevent and treat COVID-19, Scangos said.
“If the vaccine works, then the antibodies would provide better protection to people in high-risk groups.”
He noted that “vaccines typically work less well in the patients who need them the most -- the elderly, and those with cardiac or other co-morbidities. If the vaccine works, then the antibodies would provide better protection to people in high-risk groups.” Scangos estimated that there are tens of millions of high-risk people in the developed world and hundreds of millions worldwide.
He pointed to another scenario in which demand for antibodies could outstrip supply.
“If the first generation of vaccines don’t work, or don’t work well enough, and the antibodies need to protect the general population, it will be very difficult to generate enough supply.”
It usually takes three years to build an antibody manufacturing plant. Scangos estimates this could be cut to 18 months.
GSK will purchase about 6.6 million shares of Vir stock at $37.73, a 30% premium over Vir’s closing price Friday of $29. Vir jumped $7.70 (27%) to $36.70 Monday, adding about $625 million to the company’s market cap.
The partnership is one of several COVID-19-related deals Vir has struck over the past few weeks (see “Dealmaking in a Pandemic”).
In parallel, Vir has partnered with Generation Bio Co. to encode its mAbs in gene therapies, and it has expanded an existing deal with Alnylam Pharmaceuticals Inc. (NASDAQ:ALNY) to add siRNAs as a therapeutic option.
The post-IPO lock-up period on Vir’s shares ends Wednesday. The lock-up, which affects more than 93% of Vir’s shares, prevents its pre-IPO shareholders from trading their holdings.
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