clinical timelines

XBiotech plans to launch its human Phase I/II clinical trial program for its lead product candidate during the 4th quarter, 2009. The Company is currently undertaking its formal toxicology studies. After completion of these studies, the Company will announce its launch indication. The three areas of medicine under consideration for launch of its lead product candidate are in the areas on oncology, cardiovascular medicine and rheumatoid arthritis.

 

 

Markets:
Therapeutic Antibody for Cardiovascular Disease

Currently about 88% of all revenues from therapeutic antibodies are generated from product sales in the areas of oncology and inflammatory diseases. XBiotech’s human therapeutic antibody program for cardiovascular disease is thus notably important. To date, there has been very little development for therapeutic antibodies in this sector, and the market remains virtually wide open. At the same time, cardiovascular disease is by far the largest unmet medical need in the industrialized world, with annual global expenditures in this area of medicine at around $1,000 billion (US$).

 

Antibody Therapeutics Targeting Autoimmune Diseases

Sales of drugs to treat autoimmune disease reached about $32 billion in 2007 and is forecast to grow to a total global value of over $50 billion in 2013. Since 2000, sales of drugs to treat autoimmune disorders have in fact been one of the most significant growth areas in the pharma industry. Expanding patient populations, continued unmet need are key drivers in this segment; however, the dramatic success of therapeutic antibodies in some areas, such as against TNF (Tumor Necrosis Factor), have provided new hope to patients and physicians, and this too has been a key aspect of growth.

The disease targets for various NATHMAB™ in our pipeline are indicated in figure above. Each of these NATHMAB™ candidates are in early discovery stages and require further key technical development and validation before being considered as becoming clinical trial candidates. Nonetheless, the breadth of potential medical value from these true human antibodies is impressive. Several of these potential NATMAB™ antibodies would represent blockbuster drugs (over $1Billion annual revenue) upon successful commercialization. Each of these development initiatives target inflammation-related substances produced by the body, each involved in one or more autoimmune diseases.

 

Background for Anti-Inflammatory Therapeutic Antibody Treatments

Uncontrolled inflammation is involved in progression of many diseases, including arthritis, inflammatory bowel disease, systemic lupus erythematosus, multiple sclerosis, cancer and even heart disease. In healthy individuals inflammation is properly balanced and under control. Healthy control of inflammation requires a precise orchestration of many cell types and tissues involved in initiation and termination of the immune response. When not properly orchestrated (when the checks and balances go awry), instead of healing wounds and eliminating pathogens, inflammation can result in tissue injury and progressive disease.

“When inflammation cannot accomplish that salutary purpose, it does mischief.” British surgeon John Hunter (1740-1794)

Maintaining control of the body’s immune system starts with the body’s production of myriad different proteins called cytokines. To regulate the immune system, a complex network of cytokines enhance, suppress or direct immune responses. Cytokines may be produced by virtually any cell in the body, but white blood cells are an especially important source. The concerted orchestration of cytokines allows subtle control of white blood cell activity, regulating important immune system responses such as clearance of infectious agents, angiogenesis, tissue remodeling and wound healing.

Considerable scientific attention has been given to the role of cytokines and their ability to activate or down-regulate the inflammatory action of white blood cells. During chronic diseases, including many autoimmune diseases, cytokine production appears to be de-regulated, perhaps as a result or even the cause of the disease. A major advance in the therapy of inflammatory disease has been the introduction of anti-cytokine therapy, using therapeutic antibodies. This is one of the most successful areas for therapeutic antibody products.

The first anti-cytokine product approved was in 1998, a mouse-derived therapeutic antibody for the treatment of rheumatoid arthritis. The antibody neutralizes the inflammatory cytokine known as tumor necrosis factor alpha (TNFα). Use of this antibody strongly confirmed the ability to treat inflammatory disease using an antibody by targeting a single cytokine. The antibody, marketed under the name Remicade™, has been a blockbuster success with global markets and multi-billion dollar annual revenues.

More recently, a number of antibodies that target (neutralize) cytokines have been tested in human clinical trials and approved as drugs. Many ongoing human clinical trials for new products show promising results.

 

XBiotech’s Lead Therapeutic Antibody: Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a debilitating disease with serious disease-related complications. RA is associated with progressive joint damage; significant functional disability; and shortened life span. The long and extensive research to understand the cause for RA has to date not resulted in new means for treatment. The greatest progress in treatment has been made in the development of agents that block inflammatory cytokines produced by white blood cells (especially monocytes and macrophages) that infiltrate the rheumatoid joints. These treatments were developed as a result of numerous scientific studies that showed high levels of pro-inflammatory cytokines present in rheumatoid joints. These cytokines, include TNF-α, IL-1 and IL-6, which appear to be produced from monocytes, macrophages and other cells involved in a vicious cycle of inflammation and further recruitment of inflammatory cells.

What drives the initial process of cell recruitment into the rheumatoid joint is not known. However, it is clear from the use of present antibody therapeutics that block these key inflammatory cytokines, the cycle of joint inflammation can be broken. XBiotech’s lead product candidate will target a crucial pro-inflammatory cytokine that is known to be involved in the inflamed joints of rheumatoid arthritis.

Thus far, the use of therapeutic antibodies such as Remicade™ have suggested that long term treatment is required, since cessation of therapy often results in relapse of the symptoms. The costs for extended treatment have remained high; however, immunogenicity of drugs like Remicade™ may limit the efficacy of the product for long term use in some patients. Our true human NATMAB™ product candidate is expected to have minimal immunogenicity and thus will be ideally suited for use in the treatment of rheumatoid arthritis, where repeated anti-cytokine therapy is required over an extended period of time.