Our FIT-Ig (Fabs-In-Tandem) technology is based on the scientific rationale to combine the functions of two parental antibodies into one single molecule. This is achieved by re-arranging the DNA sequences of two monoclonal antibodies into three constructs and co-expressing them in mammalian cells. Our unique approach requires no Fc mutation; no scFv elements; and no linker or peptide connector. The Fab-domains in each arm work “in tandem” forming a tetravalent bi-specific antibody with four active and independent antigen binding sites that fully retain the biological function of their parental antibodies. By increasing the variety of FIT-Ig molecules further, EpimAb plans to build up technical know-how and generate additional scientific insights to explore the unique features and overall capabilities of this new drug format.
EpimAb’s lead candidate, EMB-01 has shown that the FIT-Ig format can also achieve significant efficacy superior to separate antibodies as well as their open combination. Read more here.
Key advantages are:
• expression in good quantities and easy one-step purification;
• binding to their antigens with the affinity of their parental antibodies;
• demonstrating comparable stability and solubility to monoclonal antibodies in
standard buffer systems; and
• a pharmacokinetic profile evaluated in vivo that is comparable to monoclonal antibodies after intravenous or subcutaneous administration.
Antibodies were designed by nature to bind particles they recognize as potentially harmful, thereby flagging them for the immune system. Antibodies share a common general Y-shaped structure. While the stem of the Y, the Fc-domain, remains constant among antibodies of a given species, the two arms, the Fab-domains, constitute the antigen binding part that varies from antibody to antibody. The Fab-domains of a given antibody molecule are identical and are directed against one defined target molecule called an antigen.
Bi-specific antibodies are engineered from two different monoclonal antibodies combining their key features into one molecule. They provide new options for the treatment of many fatal diseases such as cancer. However, even minor modifications to an antibody can significantly alter its binding properties, pharmacokinetics, stability, solubility or the ability to manufacture the molecule in sufficient amounts. Most commercially available bi-specific technologies rely on significant modifications of the basic structural elements of an antibody. The vast majority of them insert mutations to the Fc-domain or omit it entirely, many of them add fragments such as less stable single chain fragments (scFv’s) or linkers that can completely change the overall stability or enhance immunogenicity.
Monoclonal antibodies have transformed the treatment of human diseases, including inflammatory and autoimmune diseases, cancer, severe infections and many rare conditions over the course of the past two decades. Bispecific antibodies are engineered from two different monoclonal antibodies and combine their key features into one molecule. As a novel drug class, bispecifics provide additional options for the treatment of many life-threatening diseases such as cancer. However, even minor modifications to any pharmaceutically active biologic, such as an antibody, can significantly change the properties critical to its development, such as its binding properties, the pharmacokinetics, its stability, solubility and the ability to produce it in sufficient quantities at reasonable costs. This challenge has prevented a majority of bi-specific antibodies of potential interest to scientists and clinicians from advancing into clinical development because their drug-like features were compromised. Thus, the need for a new generation of bispecific antibody therapeutics in the pharmaceutical industry remains high.