Chronic or sterile inflammation has been long associated with disease. XBiotech is using True Human™ antibody technology to block a master regulator of inflammation—IL-1α. The Company believes that there is a tremendous unmet medical need—in multiple diseases—that may be addressed by interrupting chronic (sterile) inflammation.
Tissue injury and cell death (necrosis) leads to inflammation. Tissue injury and necrosis do not necessarily involve infectious agents (i.e. blunt trauma, blood clot, etc.), yet they are able to potently induce inflammatory responses. This non-infectious activation of an inflammatory response can be termed sterile inflammation. When we refer to chronic inflammation we are often speaking of sterile inflammation, since in many chronic diseases there is no known infectious cause. Chronic inflammation is thus a culprit in tissue destruction and disease progression in most non-infectious, chronic diseases.
Indeed, wherever there is ongoing disease, there is an underlying process of chronic inflammation. For many diseases, in fact, the unwanted effects of chronic inflammation may explain some or all of the disease process. For many conditions, the effect of chronic inflammation is virtually all that is known of the disease process.
For example, in rheumatoid arthritis the underlying cause is not known. However, inflammation in an affected joint is quite obviously a source of pain and joint destruction. Curing joint inflammation would effectively “cure” the disease, even though whatever underlying problem caused the inflammation may be unknown.
As another example, different situations can predispose to atherosclerosis, such as smoking or obesity. Although there are different causes, the pathological process that results in atherosclerosis appears to be the same: white blood cell infiltrate (e.g. inflammation) into the lining of the artery, eventually forming plaques and blockage. If the process of white blood cell infiltration into the artery wall could be stopped, disease progression would be effectively treated, regardless of the cause. While chronic inflammation may not be the cause of atherosclerosis, blocking this inflammation could represent an effective treatment or cure.
Another example is a skin disease such as psoriasis, where the underlying cause is not well understood. It is clear, however, that white blood cell infiltration into skin results in the formation of lesions, often appearing over much of the body surface. If white blood cells could be stopped from entering the skin, there would be no evidence of disease, regardless of the underlying process that normally causes this problem.
In the broadest sense, therefore, disease may be thought of as inflammation in a given tissue: the joint in arthritis; the artery in atherosclerosis; and the skin, in the case of psoriasis.
In other situations, the relationship between chronic inflammation and disease progression is more dynamic. In cancer, the tumor exploits inflammation, using the healing properties of white blood cells to help stimulate the growth of blood supply to the tumor, or even piggybacking on white blood cells to facilitate tumor cell transit through the blood.
IL-1α is a master regulator of chronic inflammation. IL-1α is present on and in the white blood cells—and other cells, including tumors—that mediate inflammation, where it plays a pivotal role in triggering and sustaining the inflammatory process. Targeting IL-1α with a neutralizing monoclonal antibody thus holds promise to treat many important disease processes. XBiotech believes that IL-1α represents a novel and unprecedented target to control chronic and sterile inflammatory processes. We thus believe that our product candidate holds promise as a breakthrough in the management of a significant portion of human disease.
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