CHEYNEY, PA — Navrogen, Inc. announced a publication describing new criteria for antibody-drug conjugate (ADC) development and preclinical efficacy of NAV-001 ADC against mesothelin-expressing tumor types. The publication is presented in the international peer-reviewed PLOS ONE journal and can be accessed at https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0285161.
NAV-001 ADC targets the cell surface mesothelin protein that is over-expressed by a number of cancers including triple negative breast, metastatic colorectal, non-small cell lung, pancreatic, ovarian and mesothelioma cancers. The publication highlights the negative impact on ADC efficacy caused by direct binding of tumor-produced Humoral Immuno-Oncology (HIO) factors to the ADC antibody component that in turn suppresses its ability to effectively internalize into antigen-expressing target cells thereby lowering its therapeutic efficacy. HIO factor binding to antibody is dependent on its three dimensional structure dictated by amino acids located in the antibody variable domain. Navrogen’s proprietary HIO factor screening platform enables the identification of antibodies that are naturally non-bound by HIO factors while its block-removed immunoglobulin technology (BRITE) platform enables engineering of HIO-refractory ADCs via replacement of amino acids responsible for HIO factor binding. NAV-001 was identified via HIO screening and contains a potent anti-cancer payload with topoisomerase II inhibitory activity. Preclinical studies using patient-derived xenograft (PDX) models have demonstrated NAV-001 single-dose efficacy across a wide array of mesothelin-positive cancers. Based on these data, NAV-001 is advancing towards clinical development as a single agent therapeutic against mesothelin-expressing cancers along with a mesothelin diagnostic for patient pre-screening.
“NAV-001 is one of several assets that we have generated overcoming the negative impact that HIO factors can have on antibody-based therapeutics, including ADCs”, said Dr. Nicholas Nicolaides, senior author. Implementing HIO screening into ADC development is another feature that may further improve the efficacy of this class of anti-cancer therapeutics”.
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