Bristol Myers makes late play for COVID-19 antibody space, picking up 2 early-phase molecules from Rockefeller

Bristol Myers Squibb
Rockefeller used Xencor’s Fc engineering technology to extend the half-life of the antibodies. (Bristol Myers Squibb)

Bristol Myers Squibb has secured global rights to a pair of anti-SARS-CoV-2 antibodies discovered by The Rockefeller University. The antibodies entered phase 1 development last month, putting them well behind similar therapies from companies including Eli Lilly and Regeneron. 

Lilly and Regeneron have already received emergency use authorizations for their anti-SARS-CoV-2 antibodies. Bamlanivimab, Lilly’s authorized antibody, generated sales of $871 million in the fourth quarter and is under a contract with the U.S. government that will provide further revenues. Lilly and Regeneron are set to face competition from companies such as AstraZeneca and potentially declining utility in a world of mass vaccination.

Bristol Myers has weighed up that tough environment and decided to make a play for the COVID-19 antibody market. The deal will see Bristol Myers secure global rights to two antibodies in return for an undisclosed financial package. Rockefeller is in line to receive royalties on sales. 

A lot of clinical development stands between the partners and those product sales. Rockefeller began a 15-subject phase 1 clinical trial in healthy volunteers last month. The study is assessing the effects of subcutaneous and intravenous delivery of several doses of the two antibodies. Bristol Myers is now plotting a route to the rapid initiation of a registrational program after the completion of the phase 1 study. Bristol Myers has already been manufacturing clinical supplies for the phase 1 trial.

If the registrational program is successful, Bristol Myers plans to try to make the antibodies available in low- and middle-income countries. The cost of manufacturing antibodies and the challenges of administering intravenous formulations has largely limited use of existing treatments to the U.S. so far. Bristol Myers wants to change that by ensuring the “availability and affordability” of its therapy. 

If, as preclinical data suggest, a low-dose subcutaneous formulation of the two antibodies is effective, Bristol Myers may be able to deliver relatively large volumes of the product at a relatively low cost and in a format that is quick and easy to administer. 

Those benefits will count for little if the antibodies, code-named C144-LS and C-135-LS, are ineffective against the SARS-CoV-2 variants that may account for most cases in many markets by the time Bristol Myers completes development. 

A recent preprint paper (PDF) found the B.1.351 variant first found in South Africa “is not only refractory to neutralization by most [N-terminal domain] mAbs but also by multiple individual mAbs to the receptor-binding motif on [receptor-binding domain], largely due to an E484K mutation.” The B.1.1.7 variant found in the U.K. has now also acquired the E484K mutation, although the form without that alteration remains predominant.

The two antibodies licensed by Bristol Myers both target the receptor-binding domain. C144-LS targets the hACE2 interaction surface of the domain, and C-135-LS targets a separate non-overlapping epitope. Rockefeller researchers hailed C144-LS as belonging “to a particularly potent class whose mechanism of action involves blocking RBD-ACE-2 interaction and additionally locking the RBD in a closed configuration making it inaccessible to ACE2.”

Rockefeller used Xencor’s Fc engineering technology to extend the half-life of the antibodies.