XOMA 052

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XOMA 052
Xoma Ltd.

Description
Engineered as a broad anti-inflammatory agent, XOMA 052 has potential as a treatment for many diseases, including diabetes, rheumatoid arthritis, acute gout, and systemic juvenile idiopathic arthritis (sJIA). This multi-indication potential makes it the most versatile and exciting product in our pipeline.

In the last decade of medical research, inflammation has emerged as a major contributor to countless conditions including rheumatoid, neurological and cardiovascular diseases. In a recent proof of concept study, inflammation via the Interleukin-1 (IL-1) pathway was established as a major factor in the progression of diabetes. Treatment with an approved IL-1 blocker led to improved glycemic control of blood sugar and a sustained increase in insulin production among a group of Type 2 diabetes patients.

XOMA used its antibody expertise and technologies to develop XOMA 052, a highly potent and highly specific antibody IL-1 inhibitor that is the first in a new generation of anti-inflammatory IL-1 blocking agents.

XOMA 052 binds strongly to Interleukin-1 beta (IL-1β), a pro-inflammatory signaling protein, called a cytokine, that is believed to be a primary cause of inflammation. By binding IL-1β, the drug blocks the activation of the IL-1 receptor, thereby preventing the cellular signaling events that produce inflammation. XOMA 052 is a Human Engineered™ IgG2 antibody with a half-life of 22 days. It has an ultra high binding affinity for IL-1β of 300 femtomolar. Based on its combined pharmacokinetic and binding properties, XOMA 052 may provide convenient dosing of once per one month or longer.

Clinical Development
XOMA 052 is currently in two Phase 1 clinical studies in Type 2 diabetes patients. XOMA 052 could prove to be a disease-modifying therapy for diabetes by addressing inflammation as an underlying cause of this epidemic disease, whereas current therapies focus almost exclusively on improving the body’s ability to produce and process insulin.

XOMA plans to continue studies in Type 2 diabetes and initiate clinical studies of XOMA 052 in rheumatoid arthritis, acute gout, and systemic juvenile idiopathic arthritis (sJIA).

Preclinical Development
XOMA is evaluating the effectiveness of XOMA 052 in a number of animal disease models, including diabetes, rheumatoid arthritis and gout.

In animal models of diet-induced obesity, XOMA 052 preserved beta cell function, reduced hyperglycemia and showed positive effects on levels of cholesterol.

In models of collagen-induced arthritis, XOMA 052 showed maintenance of bone and cartilage structure in histology studies and suppression of disease using an arthritis index of swelling and inflammation.

Additionally, in a mouse model of acute gout, monosodium urate crystals, similar to the crystals found in gout patients, were used to induce inflammation. XOMA 052 effectively reduced infiltration of neutrophils and subsequent inflammatory sequelae.

Studies in additional animal models of human disease are ongoing.

References
[1] Larsen, C. M., M. Faulenbach, A. Vaag, A. Vølund, J. A. Ehses, B. Seifert, Mandrup-Poulsen, and M. Y. Donath. 2007. Interleukin-1–Receptor Antagonist in Type 2 Diabetes Mellitus. New Engl J Med 356:1517.
[2] Ibid.

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