ImmunoPrecise Identifies a Unique Antibody, 23-H7, That Demonstrates In Vivo Efficacy, an Alternative Mechanism of Action and Binds all Tested SARS-CoV-2 Variants of Concern
IMMUNOPRECISE ANTIBODIES LTD. (the "Company" or "IPA") (NASDAQ: IPA) (TSX VENTURE: IPA) a leader in full-service, therapeutic antibody discovery and development, today announced the identification of antibody 23-H7, which preclinical data obtained to date indicates provides strong, protective anti-viral effects in SARS-CoV-2 (COVID-19) infected Syrian hamsters via an uncommon mechanism of action.
While 23-H7 is able to perturb the interaction between the Receptor Binding Domain (RBD) and the host receptor ACE2, its epitope is not located on the mutation prone RBD/ACE2 interface, unlike the spike protein regions targeted by current, commercial SARS-CoV-2 therapies. As a result, 23-H7 is anticipated to be less vulnerable to escape mutations within the spike protein/ACE2 binding interface, like escape mutation of concern E484K. In line with this, IPA demonstrated that 23-H7 maintained binding to the full (cell-associated) spike trimer of emerging SARS-CoV-2 variants of concern B.1.1.7 (UK), B.1.351 (S. African), and P.1 (Brazilian), despite published data stating that many highly neutralizing antibody therapies against SARS-CoV-2, as well as most convalescent sera and vaccine-induced immune sera, show reduced activity against viral variants.
Preclinical efficacy study
Notably, in vivo efficacy evaluation of antibody 23-H7 when administered as a passive vaccine, twenty-four hours prior to infecting Syrian hamsters with the SARS-CoV-2-D614G, resulted in undetectable replication competent virus titer in the lungs of four of the five animals 4 days post infection, with the remaining animal showing a replication competent viral titer barely above the lowest level of detection. As binding of this antibody to multi- and single-mutated spike protein trimers and fragments, respectively, appears to be unaffected, IPA anticipates that this antibody has the potential to maintain similar in vivo protective efficacy against corresponding viral variants.
In vitro analyses of studies conducted by IPA revealed that antibody 23-H7 can co-exist on the SARS-CoV-2 spike protein with antibodies from several other epitope families, as well as antibodies directly blocking the RBD/ACE2 interface, and is able to work synergistically when combined with antibodies from other epitope families in (pseudo)virus neutralization assays. Therefore, IPA believes that this unique lead is a very promising component for a combination therapy. Apart from increasing blockade of host cell infection, applying multiple antibodies targeting different regions of the spike protein simultaneously is expected to enhance viral clearance by the host’s immune system in a coordinated effort. Next to the benefit of capturing multiple mechanisms of action in one therapy, IPA’s PolyTope antibody cocktail approach is also believed to reduce the risk of mutagenic escape, and thereby expectedly increases its sustainability.
“The identification of IPA’s genetically diverse set of therapeutic antibodies with multiple mechanisms of action and broad epitope coverage is a reflection of our proprietary technology’s ability to deeply mine diverse human antibody repertoires, which ultimately enabled the discovery of this exciting, unique antibody, 23-H7,” stated Ilse Roodink, IPA’s Global COVID-19 Program Director. “This finding is also a reflection of our overall commitment to quality science and meaningful, translational outcomes.”
About IPA’s PolyTope Platform.
IPA’s SARS-CoV-2 PolyTope monoclonal therapies are designed to protect against mutagenic escape with an emphasis on efficacy for every patient, variant, and strain of SARS-CoV-2. They are created with the goal of sustainable efficacy in the face of an evolving virus, combining extensively characterized, potently neutralizing, synergistic antibodies exhibiting richly diverse epitope coverage.
About ImmunoPrecise Antibodies Ltd.
IPA is an innovation-driven, technology platform company that supports its pharmaceutical and biotechnology company partners in their quest to discover and develop novel, therapeutic antibodies against all classes of disease
