INFECTIOUS DISEASES
We believe True Human™ antibody therapies have a very important application in the case of potent viruses; for example, influenza or SARS-COV-2, where the aggressive nature of the virus challenges the limits of even strong immune systems. Here again, in the elderly, the young, or individuals with weakened immune conditions, an aggressive virus can have a significant degree of morbidity and mortality. XBiotech is able to capture the genetic information for anti-virus neutralizing antibodies from robust healthy immune responses that have successfully cleared the infection, and safely give them to other humans whose immune systems need help. Consequently, we believe there is an opportunity for an array of True Human™ products to treat viral and bacterial infectious diseases.
XBiotech continued to achieve significant milestones with its infectious disease pipeline in 2019. The Company has identified several major areas of urgent unmet medical need for True Human™ anti-infective antibody therapies, including targeting both bacterial and viral diseases. True Human™ antibodies may be used therapeutically or prophylactically to supplement immunity in various patient populations. True Human™ antibodies derived from healthy individuals with strong natural immunity to specific diseases are the source of our product candidates that can be used to supplement weakened immune systems.
TRUE HUMAN™ TECHNOLOGY AND INFECTIOUS DISEASE PIPELINE
XBiotech has unique capabilities to expeditiously develop testing technologies and therapies for viral or bacterial infectious disease outbreaks. Our core discovery technology enables rapid identification of neutralizing antibodies directly from human blood samples. High stringency screening enables us to reliably find bloods with true neutralizing antibodies; and our proprietary cloning technology interrogates the most diverse repertoire and captures all superior product candidates. The result is the rapid generation of monoclonal human antibody product candidates from immune human blood samples that are very likely to recapitulate the natural immunity of the blood donor. We combine this discovery program with a novel manufacturing platform to enable rapid scale-up for commercial production. We believe XBiotech’s technology and capabilities are unparalleled for creating novel, effective treatments for infectious disease, and moreover for rapidly addressing infectious disease outbreaks. XBiotech is currently advancing product candidates for various infectious diseases.
VARICELLA
Natural human immunity is very effective at neutralizing varicella for most of our lives, when we might have billions of different antibodies. Later in life, as we age, the quantity and diversity of our antibody repertoires diminishes. We produce less antibodies against fewer targets. Even though we may have had decades of antibodies protecting us against varicella, as we age a “hole” can develop in the antibody repertoire that was responsible for controlling varicella. When this happens, varicella virus that has been “hiding” in cells of our body can resurge, spread about the body and cause debilitating disease. XBiotech has isolated potent True Human™ antibodies from healthy donors with potent neutralizing antibodies against varicella. We believe that patients suffering from resurgent varicella due to aging immune systems can be effectively treated. There is a substantial unmet medical need for shingles therapy. There are also other indications where uncontrolled varicella infections, such in infants whose immune systems are not yet adequately developed, would be treatable with such a product.
C. DIFFICILE
Along with other infectious disease targets in the Company’s pipeline, the ABSL2 laboratory has been testing True Human™ product candidates against C. difficile bacteria, the cause of debilitating and deadly intestinal infections. Healthy individuals with no history of C. difficile have potent antibodies against the potentially deadly bacteria. We believe this indicates that these natural antibodies are capable of providing protection against the disease and could be useful medically. The Company’s C. difficile program has resulted in the discovery of novel True Human™ antibodies that are able to block both the motility and prevent adhesion of C. difficile bacteria, two features of the bacteria essential to its maneuvering and adhering to the lining of the intestine, respectively. The Company has been developing a first-of-its-kind oral therapy, which would allow a True Human™ antibody to be delivered in pill form to the intestine, where the drug could neutralize the bacteria such that it is carried away harmlessly and lost with fecal matter. A manufacturing process is in development to further reduce the cost of production for this oral product by more than 75% compared to injectable antibody preparations (all marketed monoclonal antibody products are currently delivered by injection).
INFLUENZA
The Company is also working on a number of other infectious disease products. With analyses of genetic information from over one century of influenza virus, which kills tens of thousands of individuals each year, the Company identified common genetic variants that allowed them to search healthy humans for True Human™ antibodies that could potentially provide immunity to a range of pathogenic influenza strains. XBiotech’s scientists found True Human™ antibodies from healthy individuals capable of specifically blocking the influenza neuraminidase across multiple, potentially lethal, strains of the virus. The antibody blocks the enzymatic activity of the virus neuraminidase (like other current antiviral drugs on the market), stopping the action of the enzyme involved in releasing the virus from infected cells. This is a necessary step for spread of the virus in the body. As an antibody therapy, however, there is an additional benefit over current antiviral drugs, as it can bind virus particles at their surface and facilitate clearance of the virus by white blood cells, enhancing the immune system’s ability to fight the infection.
STAPHYLOCOCCUS AUREUS (S. AUREUS)
XBiotech previously launched a therapy for S. aureus infections and completed Phase I/II double blinded placebo controlled clinical study. The study was performed in patients with so called bacteremia, where the S. aureus had sufficiently overwhelmed the patients’ immune systems such that the bacteria could be observed and cultured from the blood of the infected individual. Once S. aureus gains access into the body, it has an immune evasion mechanism that can allow it to overwhelm defense and establish uncontrolled and lethal infections. Prognosis is very poor in individuals with bacteremia. The study showed a 52% reduction in the incidence of S. aureus related serious adverse events and a 30% reduction in the duration of hospital stays of those receiving True Human™ antibody therapy compared with placebo controls. With the opioid epidemic, S. aureus infections in the blood, and consequent infections of the heart as a result of needle use, are having a devastating impact. S. aureus infections are also the second leading cause of death for end-stage renal disease patients undergoing hemodialysis. We plan to continue clinical development of our S. aureus True Human™ antibody therapy that can be effective in areas of serious unmet medical need.
