Unlike previous generations of antibody therapies, XBiotech’s True Human™ antibodies are 100 percent human, derived from individuals who possess natural immunity to certain diseases.
Natural immunity is harnessed by directly cloning antibody sequences from individual donors.
Harness natural immunity - human antibody cloned directly from individual donors
Unmatched safety and efficacy - antibodies retain natural physiology and tolerance; having passed rigors of immune selection in the body
Enables extraordinarily rapid transition from initial discovery/validation to scalable product manufacturing
Disruptive Technology Offers Potential to Deliver Unmatched Safety and Efficacy Compared to Engineered Antibody Technologies
- Thousands of human donors potentially screened to find an individual who possesses natural immunity against target disease
- White blood cells are obtained and the unique gene that produced the antibody is cloned
- An exact replica of the antibody sequence is produced using genetic information
- Large quantities of natural antibody are produced using innovative scalable technologies
First Generation: Murine
Therapeutic antibodies for treatment of human disease were first developed from mice (murine) about twenty years ago. Although still available as drugs, murine antibodies have limited therapeutic value, because when injected they are recognized by the human body as foreign substances. The ensuing human immune response neutralizes the foreign antibody, thus limiting its effectiveness and even resulting in dangerous side effects such as anaphylaxis.
Second Generation: Chimeric
Soon after the arrival of murine antibodies for treating human disease, therapeutic antibodies were introduced that were fusion molecules, combining murine and human antibody segments. These so-called chimeric antibodies have achieved great commercial success, and include the blockbuster product Rituxan®, used to treat certain kinds of cancer.
Third Generation: Humanized
While chimeric antibodies were finding their way into human therapies, other sophisticated approaches to further reduce murine content of antibodies were well underway. In addition to the fusion of murine and human segments that comprised the chimeric antibodies, humanized antibodies further interspersed human sequences into the murine segments. From 2003-2006, sales growth for therapeutic antibodies was primarily driven by the humanized products, although chimeric antibodies continued to hold strong market positions.
Fourth Generation: "Fully Human"
More recently, R&D efforts in the industry have centered on the production of so-called "fully human" antibodies. Despite the reassuring title, these antibodies have actually not been selected in a human. Rather, they are engineered in mice that have been genetically modified with human antibody gene sequences. Extensive clinical experience with these antibodies now indicates that fully human antibodies are indeed immunogenic. However, these antibodies can cause reaction in the human body and typically require pre-treatment with corticosteroids. In addition, they can get neutralized over time due to being labeled as foreign and cleared over time by human antibodies.
Next Generation: True Human™
True Human™ antibodies are 100 percent human, derived from individuals who possess natural immunity to certain diseases. The True Human™ antibody gene is derived directly from a human gene, using proprietary methods and technology to ensure faithful reproduction of the original human gene.
True Human™ antibodies faithfully derived from a human will naturally not be detected by the human immune system as a foreign substance. True Human™ antibodies will be "invisible" to the body's immune system, and will thus exhibit better safety, efficacy and commercial value compared to earlier generation antibody therapeutics. XBiotech believes that its True Human™ antibodies represent the first of a next generation of antibody therapy.
Shortcomings of past technology (i.e. "Fully Human" antibodies):
- "Fully Human" misnomer - all existing products are engineered through gene sequence modification
- Laboratory-engineered antibodies are not from sequences that have gone through the selection process
- Prone to problems including anaphylactic reactions and risk of infusion
- Marketplace's incorrect assumption that fully human antibodies are the same as real human antibodies which is potentially misleading in safety and risk factors