True Human™

A principle concern with the development of therapeutic antibodies is the problem of tolerability, safety and long-term efficacy. This problem results from immune responses in patients against the therapeutic antibody drug. XBiotech anticipated that difficulties in the development of safe and effective antibodies would not be completely solved using current humanization or other strategies.

XBiotech has sought to avoid the use of antibodies derived from mice, genetically modified animals, or from antibodies engineered using modifications to change binding characteristics. In each of these situations, antibodies may be detected by the human body as foreign and cause unwanted reactions.

With the knowledge that clinically relevant antibodies were present in humans, XBiotech set out to use only True Human™ antibodies in the development of therapeutics. The fundamental objective: to use True Human™ antibodies as therapeutics in order to avoid reactions in patients that diminish usefulness, tolerability and safety.

Patient immune reactions against monoclonal antibody drugs reduce efficacy and increase the risk of serious side effects. The ability of a substance to induce or provoke an immune response is termed “immunogenicity.” A substance that potently causes an immune reaction is highly “immunogenic,” whereas a substance that only weakly stimulates an immune response is said to have little immunogenicity.

It is highly unfavorable for therapeutic antibodies (or other drugs) to exhibit any significant degree of immunogenicity. Nonetheless, immunogenicity is a pervasive problem in the development of safe and effective therapeutic antibodies.

The problem of immunogenic therapeutic antibodies has had a significant impact on the development and success of therapeutic antibodies for the industry as a whole. It is anticipated that future growth of the industry will be constrained by failure to reduce the problem of immunogenicity.

Reducing immunogenicity of therapeutic antibodies would, in itself, represent a significant advance for antibody therapeutics. XBiotech’s True Human™ antibody, MABp1, is expected to have the smallest immunogenic footprint possible for a biological drug.

The anti-IL-1α therapeutic antibody product MABp1 is expected to be used in many different disease indications. Some of these indications have not been well penetrated by therapeutic antibodies, largely because of safety or efficacy concerns. Thus we believe the True Human™ therapeutic antibody platform has tremendous potential in our lead product candidate MABp1.