Once a human antibody is identified as effective against a particular target, it can be converted into a variety of formats such as a full-length antibody, a Fab fragment, a diabody, a TandAb™, or a Flexibody™.
Affimed scientists designed the TandAb and Flexibody formats to bind multiple targets. TandAbs and Flexibodies are tetravalent. They have two binding sites for activating immune effector cells like cytotoxic T cells or natural killer cells as well as two binding sites for a target molecule on the surface of tumor cells.
TandAbs are twice as large as bivalent diabodies and remain in the body longer. Affimed’s lead products AFM13 for Hodgkin’s disease as well as AFM11 and AFM12 for non-Hodgkin’s lymphoma are all TandAbs.
Flexibodies are multivalent antibodies with a high degree of flexibility that can more easily join molecules that are distant from each other on the cell surface.
“The selection of a particular antibody format depends on the desired target product profile and indication,” says Dr. Günther. The different antibody formats also affect the physical and chemical properties of antibodies.
Smaller recombinant antibodies or antibody fragments like diabodies have the advantage of better tissue penetration but the disadvantage of clearing from the body rapidly. Some diseases like cancer or chronic inflammation require more persistent therapies. Processes like pegylation may extend the half-life of antibodies but also add to development time and costs.
“TandAbs,” on the other hand, points out Gavin Clark, vp of business development, “have a molecular weight that is significantly higher than the threshold for first-pass renal clearance.” This could allow patients to be treated once-a-week rather than daily.
By combining three antibody libraries with the format technology, Affimed states that it can design customized antibodies for any disease target. In addition, antibodies that are already clinically validated can be improved through the format technology.
This ability to readily create different formats for second-generation antibodies, Clark says, “Greatly appeals to potential partners when I talk to them.” A strong patent portfolio protects Affimed’s antibody libraries, phage display technology, and novel format technologies.