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Learn about ImmunoPrecise Antibodies’ efforts to stay ahead of the virus on June 17!

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Join us on Thursday June 17, 8am PT/ 11am ET / 5pm CET for

 

 

Staying ahead of the virus: From a multispecies discovery strategy to highly efficacious, clinically suitable multi-antibody cocktails targeting SARS-CoV-2.

featuring:

Ilse Roodink, PhD, Scientific Director, ImmunoPrecise Antibodies Europe and
Debby Kruijsen, PhD, General Manager, ImmunoPrecise Antibodies Europe

Whereas vaccines significantly contribute to halting transmission of SARS-CoV-2, they are not universally effective. Therapeutic antibodies can fill this gap to efficiently combat SARS-CoV-2. Obviously, long-lasting efficacy of anti-viral approaches heavily depends on the ability to protect against virus variants. As a multi-targeting strategy reduces the risk of mutagenic escape, we have isolated a diversified pool of anti-spike protein antibodies by leveraging our expertise to generate antibody libraries across multiple discovery platforms in different species, to eventually formulate a sensible therapeutic cocktail. A broad range of in vitro characterizations was applied to gain early insight into the epitope landscape and functional characteristics as well as developability profiles. This comprehensive, high-throughput characterization of the obtained lead candidate pool guided the rational combination of high value antibodies into multi-membered cocktails that unlock synergistic effects, significantly boosting neutralization potency in vitro.

To accelerate further clinical development of our prioritized antibody cocktails, 2 individual components were subjected to in silico modeling-guided light molecular optimization to minimize liabilities, while in parallel, in vivo efficacy evaluation in a hamster challenge model validated efficient prevention and treatment of SARS-CoV-2 infection following administration of our prioritized antibody cocktails. Although we anticipate that a multi-targeting strategy is the best solution to reduce mutagenic risk escape, we continuously analyze binding of the antibodies of our lead pool for reactivity towards emerging SARS-CoV-2 variants empirically. To date, we screened our prioritized antibody cocktails towards spike protein of the S. African (B.1.351 lineage), Brazilian (P.1 lineage), UK (B.1.1.7 lineage), New York (B.1.526 lineage) and Californian (B.1.429 lineage) strains and confirmed retained binding. Our pandemic preparedness is further strengthened by the readily accessible, diverse pool of antibodies that we generated, which provides enormous possibilities for plug-and-play cocktails to address future SARS-CoV-2 variants.

Click here to register for this free event!

EUA issued for anti-SARS-CoV-2 sotrovimab

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On March 27, 2021, the U.S. Food and Drug Administration issued an emergency use authorization (EUA) for sotrovimab (VIR-7831; GSK4182136) for the treatment of mild-to-moderate COVID-19 in adults and pediatric patients with positive results of direct SARS-CoV-2 viral testing and who are at high risk for progression to severe COVID-19, including hospitalization or death. The EUA was issued to GlaxoSmithKline.

Sotrovimab, a human anti-SARS-CoV2 antibody, is being evaluated in a Phase 1/2/3 randomized, double-blind, placebo-controlled clinical trial in non-hospitalized adults with mild-to-moderate COVID-19 symptoms and a positive SARS-CoV-2 test result. The EUA is based on an interim analysis of results for 583  patients in the study, 291 and 292  of whom received sotrovimab or placebo, respectively, within five days of onset of COVID-19 symptoms. The primary endpoint was progression of COVID-19 (defined as hospitalization for greater than 24 hours for acute management of any illness or death from any cause) through day 29. Hospitalization or death occurred in 21 (7%) patients who received placebo compared to 3 (1%) patients treated with sotrovimab.

Sotrovimab is administered as a 500 milligram single dose given intravenously over 30 minutes by health care providers.

Prior to the authorization of sotrovimab, FDA issued EUAs for the treatment of mild-to-moderate COVID-19 for two combinations of anti-SARS-CoV-2 monoclonal antibodies. The combination of casirivimab and imdevimab was authorized in November 2020 and the combination of bamlanivimab and etesevimab was authorized in February 2021. In addition, Celltrion’s anti-SARS-CoV-2 antibody regdanvimab (CT-P59; Regkirona) received authorization in South Korea in February 2021.

More than 20 additional anti-SARS-CoV-2 monoclonal antibodies are undergoing evaluation in clinical studies. Of these, 7 monotherapies or combinations are in late-stage clinical studies, including ADG20 (Adagio Therapeutics) and AZD7442 (AstraZeneca). The Antibody Society will continue to track these investigational antibodies and report progress in the future.

AIRR Community and Tsinghua University discuss Chinese research using AIRR-seq data to study adaptive immune response in COVID-19 patients

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A meeting focusing on Chinese researchers’ use of AIRR-seq data to study the adaptive immune response – especially in COVID-19 patients – was held recently by the AIRR Community and Tsinghua University.

The purpose of this co-organized meeting was to expose AIRR-seq researchers in China to the philosophy and tools developed by the AIRR Community and help integrate researchers from all over the world through the AIRR Community.

Although collaboration and sharing data internationally is complicated and difficult, this successful meeting was an important step in forming the relationships necessary for overcoming many of these challenges.

Tsinghua University is a major research university in Beijing and a member of the C9 League of Chinese universities. Since its establishment exactly 110 years ago, it has produced many notable leaders in science, engineering, politics, business, academia, and culture. The university is ranked as the 15th best university in the world in the QS World University Rankings and No.1 in Asia by the Asia University Rankings and the U.S. News and World Report.

The meeting followed a hybrid format, combining online lectures by AIRR Community members in the US and Europe in conjunction with an in-person meeting in Shenzhen, China that was organized by Professor Xiao Liu of Tsinghua University’s Shenzhen campus.

The in-person, all-day meeting was held on December 6, 2020 in Shenzhen, which corresponded to Saturday evening December 5 in North America.

The full meeting agenda can be found on the meeting web page and the meeting recording has been posted on the AIRR-C YouTube Channel.

 

Preventing severe disease in Covid-19 patients

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Written by Raquel Barroso Ferro, University of Aberdeen

In April 2020, Vir Biotechnology and GlaxoSmithKline (GSK) began a partnership that has proven fruitful. As announced on March 10, 2021, patients with mild or moderate Covid-19 at high risk of progression to severe disease who were treated with the human monoclonal antibody VIR-7831 (sotrovimab) in the COMET-ICE study (NCT04545060) had a reduction of 85% in hospitalization or death compared to those who received placebo. Although complete details of the ongoing trial are not yet available, this “artificial immunity” offers hope for patients. In particular, such treatment may be beneficial to those who are unable to receive a vaccine or whose immune system is weakened.

Vir and GSK plan to submit an emergency use authorization application in the US and seek authorizations in other countries.

Originally derived from a patient who survived severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003, (1) the antibody binds to a highly conserved epitope on the spike glycoprotein shared by both SARS-CoV and the virus causing the current pandemic, SARS-CoV-2. This shared epitope suggests high conservation and its likely importance for viral infection. Binding this epitope may reduce the likelihood of mutational escape, and allow the antibody to neutralize multiple variants that emerge. In fact, according to a pre-print posted March 10, 2021 on BioRxiv, the epitope of VIR-7831 does not overlap with the mutational sites observed in the circulating variants. (1)

In preclinical studies, VIR-7831 achieved high concentration in the lungs, (1) the principal site of Covid-19 infection, (2) neutralized live virus, and was shown to engage effector functions, such as antibody-dependent cytotoxicity and phagocytosis, to mediate clearance of infected cells. (1)

The announcement of positive results from the COMET-ICE study follows a March 3, 2021, announcement by Vir and GSK that the Data and Safety Monitoring Board for the ACTIV-3 trial (NCT04501978) evaluating VIR-7831 in hospitalized adults with COVID-19 has recommended that the VIR-7831 arm of the trial be closed to enrolment while the data mature. No safety signals were reported, but the sensitivity analysis called into question the magnitude of the potential benefit of VIR-7831 administration to hospitalized patients. The National Institutes of Health is sponsoring the ACTIV-3 master protocol, which is examining the clinical safety and efficacy of numerous investigational agents relative to current standard of care therapy in hospitalized patients with more severe COVID-19.

Overall, the findings from the two clinical studies suggest that VIR-7831 could be of most benefit to patients during early onset of the disease, shortly after a positive test. This treatment has great potential to reduce both the severity of the disease in individuals and the substantial burden COVID-19 has placed on hospital staff and resources.

Another challenge, however, will be instilling confidence in doctors to prescribe anti-SARS-CoV-2 monoclonal therapies to patients. According to Dr. Derek Angus, an intensive-care physician at the University of Pittsburgh who spoke to Nature, (3) the absence of data published in peer-reviewed journals has left doctors wary. Moreover, high costs and more specialized requirements for administering infusion-based therapies will make what seems to be a working therapy and hope for patients a more complicated task. Intramuscular (IM) injection, which may substantially increase patient convenience, is possible. Clinical studies for anti-SARS-CoV-2 antibodies administered via intramuscular (IM) injection, including VIR-7831 (COMET-PEAK) and AZD7442 (PROVENT, STORM CHASER), are ongoing and clinical study results have not yet been announced.

1.       Cathcart et al. The dual function monoclonal antibodies VIR-7831 and VIR-7832 demonstrate potent in vitro and in vivo activity against SARS-CoV-2. 2021. 
2.       Cevik et al. Virology, transmission, and pathogenesis of SARS-CoV-2. BMJ 2020; 371. BMJ. 2020. 
3.       Ledford H. COVID antibody treatments show promise for preventing severe disease. Nature 2021. 

FDA issues Emergency Use Authorization for bamlanivimab/etesevimab combination

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On February 9, 2021, the U.S. Food and Drug Administration issued an emergency use authorization (EUA) for bamlanivimab and etesevimab administered together for the treatment of mild to moderate COVID-19 in adults and pediatric who test positive for SARS-CoV-2 and who are at high risk for progressing to severe COVID-19. Developed by Eli Lilly and Company, bamlanivimab and etesevimab are monoclonal antibodies (mAbs) that target overlapping regions of the SARS-CoV-2 spike protein.

The EUA was based on a randomized, double-blind, placebo-controlled clinical trial in 1,035 non-hospitalized adults with mild to moderate COVID-19 symptoms who were at high risk for progressing to severe COVID-19. Of these patients, 518 received a single infusion of bamlanivimab (2.8 g) and etesevimab (2.8 g) together, and 517 received placebo. The primary endpoint was COVID-19 related hospitalizations or death by any cause during 29 days of follow-up.  Hospitalization or death occurred in 11 (2%) patients treated the mAb combination vs. 36 (7%) patients who received placebo. All 10 deaths (2%) occurred in the placebo group.

The authorized dosage of 700 milligrams bamlanivimab and 1400 milligrams etesevimab administered together is based on analyses of available preclinical, clinical, and virologic data, as well as pharmacokinetic and pharmacodynamic modeling, which, in totality, support that the authorized dosage is expected to have a similar clinical and virologic effect to the dose evaluated in the clinical trial. Use of the mAb combination is not authorized for patients who are hospitalized due to COVID-19 or require oxygen therapy due to COVID-19.

In November 2020, FDA issued an EUA for a single infusion of 700 mg bamlanivimab for the treatment of mild-to-moderate COVID-19 in adult and certain pediatric patients. Since the monotherapy and the combination treatment are expected to benefit patients at high risk of disease progression, both 700 milligrams bamlanivimab alone and the combination of 700 milligrams bamlanivimab and 1,400 milligrams etesevimab administered together will be available under an EUA.