New firm claims RabMab technology generates antibodies with increased diversity, specificity, and affinity.

Centocor Research and Development is tapping into Apexigen’s expertise for the development of monoclonal antibody drugs. Under terms of the deal Apexigen will generate and screen antibodies to a number of Centocor targets. Centocor will be responsible for the development and commercialization of any resulting products and pay Apexigen an up-front license fee and potentially future developmental and regulatory milestones and sales royalties.

Apexigen was spun out of monoclonal antibody products and services firm Epitomics in June. The new firm has rights to use Epitomics’ RabMAb® (rabbit monoclonal antibody) technology and Mutational Lineage Guided (MLG) humanization technology, for applications in therapeutic antibody discovery and development. Epitomics will use the platforms to develop monoclonal antibody technologies for research and diagnostic applications.

The RabMAb technology exploits the diversity of antibody specificity generated by the rabbit’s immune system. Apexigen claims antibodies made by the rabbit immune system often have higher affinity for their targets than human or mouse antibodies. Moreover, it says, the rabbit immune system generates a greater variety of antibodies, so rabbit antibodies can potentially recognize a wider variety of epitopes than human or mouse antibodies.

The RabMAb approach essentially captures the rabbit’s innate antibody-making capability into stable, efficient hybridomas, Apexigen explains. These stable hybridomas can then be used to screen millions of individual antibodies and select those displaying optimal characteristics for drug development. The MLG humanization technology is then used to replace components of the rabbit monoclonal antibody with human antibody amino acid sequences.

RabMAb-derived antibodies have a number of advantages over mouse or human monoclonal antibodies, Apexigen suggests. These include a 10-100 fold greater affinity to their targets, along with higher target specificity. The platform is also expected to generate antibodies against a wider variety of epitopes. Moreover, because the RabMAb antibodies crossreact with both human and rodent targets, they can be evaluated in mouse-based in vivo pharmacology models, potentially removing the need for a surrogate antibody or transgenic animal models during preclinical and animal toxicity studies.

The MLG humanization procedure is both conceptually and technically different from the CDR-grafting method used in humanizing murine-derived antibodies, Apexigen adds. MLG humanization is guided by both the biological and sequence information of a panel of functional antibodies and humanizes residues in the antibody framework and also those in CDR regions. This results in humanized molecules that display full antibody activity and functionality

Apexigen aims to exploit its technologies through the development of a pipeline of products in house and through collaborations with partners. The firm’s internal pipeline includes early and late preclinical candidates against cancer, autoimmune, and bone-related diseases including solid tumors, lymphomas and myelomas, rheumatoid arthritis, diabetes, gout, osteoporosis, and bone metastases. Collaborations are ongoing with Simcere Pharmaceutical, 3SBio, and Jiangsu T-mab Biotechnology.

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