Vaccine Info

Bebtelovimab (LY-CoV1404) Monoclonal Antibody

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Last reviewed
January 17, 2022

Bebtelovimab (LY-CoV1404, LY3853113) Monoclonal Antibody Description

Eli Lilly and Company Bebtelovimab (LY-CoV1404, LY3853113) is a potent, neutralizing SARS-CoV-2 spike glycoprotein receptor-binding domain (RBD)-specific antibody identified from a convalescent COVID-19 patient sample, obtained approximately 60 days after symptom onset. This monoclonal antibody (mAb) is directed against the spike protein of SARS-CoV-2 that maintains binding and neutralizing activity across currently known and reported variants of concern.

LY-CoV1404 is highly potent, which could have implications for reducing the amount of antibody necessary for clinical dosing, and potentially enabling a subcutaneous route of administration for either treatment or prevention of COVID-19. Pathway: SARS-CoV-2 spike glycoprotein [KO: K24152], ko03230  Viral genome structure, ko05171 COVID-19

An in-depth assessment of mutations that could inhibit neutralization of LY-CoV1404 identified two specific amino acid positions that are very rarely mutated in the general population (0.027%), as reported in the GISAID database as of April 2021. In addition, the potent activity of LY-CoV1404 against the currently known variants of concern and pseudoviruses carrying various single amino acid mutations suggests that LY-CoV1404 binds to an epitope that is highly conserved across all SARS-CoV-2 isolates that have been collected worldwide.

AbCellera (Nasdaq: ABCL) announced on May 4, 2021, LY-CoV1404 had entered clinical trials. AbCellera also released preclinical data showing LY-CoV1404 binds to a rarely mutated region of the SARS-CoV-2 spike protein and neutralizes all currently known variants of concern, including those first identified in the UK (B.1.1.7), South Africa (B.1.351), Brazil (P.1), California (B.1.426 and B.1.429), and New York (B.1.526).

Eli Lilly and Company (NYSE: LLY), Based in Indianapolis, Indian, was founded in 1876 and continues to monitor the COVID-19 pandemic and its global impact closely.

Bebtelovimab (LY-CoV1404, LY3853113) Monoclonal Antibody Indication

Bebtelovimab (LY-CoV1404) is being studied to treat mild to moderate COVID-19 both as a monotherapy and with other mAbs. On December 16, 2021, the U.S. HHS published 'Outpatient administration guide for healthcare providers.'

Bebtelovimab (LY-CoV1404, LY3853113) Monoclonal Antibody Effectiveness Against Coronavirus Variants (Omicron)

A study published on September 9, 2021, stated some of the existing therapeutic antibodies are less effective or ineffective against specific variants, and the impact of the variants on vaccine efficacy is still poorly understood. In addition, the breadth of variant binding, potent neutralizing activity, and the relatively conserved epitope suggest that LY-CoV1404 is one in a panel of well-characterized, clinically developable antibodies that could be deployed as potential long-term solutions to address current and emerging variants.

On January 7, 2022, a non-peer-reviewed study found LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants, including Omicron. In addition, no loss of potency against currently circulating variants; binding epitope on RBD of SARS-CoV-2 is rarely mutated in the GISAID database; breadth of neutralizing activity and potency supports clinical development. The structural analysis demonstrates that RBD residues comprising the LY-CoV1404 epitope are highly conserved with the exception of N439 and N501. Notably, the binding and neutralizing activity of LY-CoV1404 is unaffected by the most common mutations at these positions (N439K and N501Y). The breadth of reactivity to amino acid substitutions present among current VOC together with broad and potent neutralizing activity and the relatively conserved epitope suggests that LY-CoV1404 has the potential to be an effective therapeutic agent to treat all known variants causing COVID-19.

As of January 15, 2022, the U.S. NIH OpenData Portal reported positive in vitro Therapeutic Activity against the Omicron virus variant. And Stanford's HIVDB team website displays updated mAbs effectiveness. 

Bebtelovimab (LY-CoV1404, LY3853113) Monoclonal Antibody Availability

As of January 15, 2022, the U.S. government had not distributed Bebtelovimab in the U.S. and the U.S. FDA had not issued a EUA.

Bebtelovimab (LY-CoV1404, LY3853113) Monoclonal Antibody News

January 9, 2022 - AbCellera and its collaborators released new preclinical data showing the pseudovirus neutralization status of its two monoclonal antibodies, bamlanivimab and bebtelovimab (also known as LY-CoV1404), against the Omicron variant. The data confirmed that the investigational antibody bebtelovimab, which is currently in Phase 2 clinical trials with Eli Lilly and Company, maintains both full and potent neutralization activity against the Omicron variant and all other known SARS-CoV-2 variants of concern.

January 5, 2022 - The journal Nature published a Letter: SARS-CoV-2 Omicron RBD shows weaker binding affinity than the currently dominant Delta variant to human ACE2. In conclusion, both MD simulation and ELISA bioassay results suggest that the Omicron variant possesses comparable binding affinity to human ACE2 in comparison with the wild-type SARS-CoV-2, but much weaker binding affinity than the Delta variant. Accordingly, the Omicron variant might have similar infection capability to that of WT virus but milder than Delta if the capability depends mainly on the binding affinity. In addition, the MD simulations indicate that the new variant Omicron has a high risk of immune evasion. Accordingly, close attention should be paid intensively to Omicron as its high immune evasion risk may possibly enable its easy transmission.

September 9, 2021 - The U.S. NIH highlighted a non-peer-reviewed study: LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants. The RBD positions comprising the LY-CoV1404 epitope are highly conserved, except for N439 and N501; notably, the binding and neutralizing activity of LY-CoV1404 is unaffected by the most common mutations at these positions (N439K and N501Y).

May 4, 2021 - AbCellera today announced that a second antibody from its collaboration with Eli Lilly and Company, LY-CoV1404, has entered clinical trials in patients with mild-to-moderate COVID-19. Lilly has expanded its ongoing BLAZE-4 trials to evaluate LY-CoV1404 alone and together with other monoclonal antibodies.

Bebtelovimab (LY-CoV1404, LY3853113) Monoclonal Antibody Clinical Trials

A Randomized, Double-blind, Placebo-Controlled, Phase 2 Study to Evaluate the Efficacy and Safety of Mono and Combination Therapy With Monoclonal Antibodies in Participants With Mild to Moderate COVID-19 Illness (BLAZE-4).

AbCellera released preclinical data showing LY-CoV1404 binds to a rarely mutated region of the SARS-CoV-2 spike protein and neutralizes all currently known variants of concern.

Clinical Trials

No clinical trials found