Mice treated with XOMA 052 experiences improvement in measures associated with diabetes: Endocrinology

XOMA Ltd. (Nasdaq:XOMA), a leader in the discovery and development of therapeutic antibodies, announced the publication of data from a mouse model of diet-induced obesity in the June, 2010 edition of the journal Endocrinology. The data showed that mice treated with XOMA 052 both prophylactically and therapeutically experienced improvement in measures associated with diabetes and cardiovascular disease including reduction in glycosylated hemoglobin (HbA1c) levels, improvement in glucose control, improved beta-cell survival and function, and a reduction in total cholesterol without reduction in high density lipoprotein. Each of these parameters is an important goal for the management of Type 2 diabetes, and well-controlled blood glucose levels and reductions in lipid levels can help minimize the risk of long-term consequences associated with diabetes. Much of the data were presented at the American Diabetes Association's 2009 Scientific Sessions.

"Rarely do results from animal models mirror what we see in humans. So far, what we've seen when we compare mouse data to the Phase 1 human data is very encouraging, and while there are limitations to this comparison, we are hopeful that the similarities will carry through to our Phase 2a and Phase 2b data," said Patrick J. Scannon, M.D., Ph.D., Executive Vice President and Chief Medical Officer of XOMA. "With results demonstrating reduction in total cholesterol without decreasing high density lipoprotein, also referred to as 'good cholesterol', the data also highlight the potential application of IL-1 beta inhibition in the treatment of cardiovascular diseases."

In the experiments detailed in the paper, groups of mice received a high fat diet. Without treatment, the mice exhibited signs of Type 2 diabetes such as elevated blood glucose and HbA1c levels, impaired glucose tolerance and impaired insulin secretion. Treatment with XOMA 052 prevented these abnormalities as compared to treatment with an inactive control antibody. Treatment with XOMA 052 also reduced beta-cell apoptosis and increased beta-cell proliferation in the mice fed the high fat diet, and mice treated with XOMA 052 demonstrated improvements in insulin resistance induced by the high fat diet compared to control. The data provide evidence that targeting IL-1 beta in vivo could improve insulin sensitivity.

In addition, the study examined lipid levels in mice fed the high fat diet and either treated with XOMA 052 or the control. Without treatment, mice eating the high fat diet showed increases in the blood levels of lipids like total cholesterol, triglycerides and free fatty acids. The mice treated with XOMA 052 demonstrated reduced levels of lipids compared to the control.

XOMA also announced that two posters on XOMA 052 in the treatment of Type 2 diabetes will be presented at the American Diabetes Association 70^th Scientific Sessions, occurring June 25 through June 29, 2010. A third abstract from XOMA was accepted on a published-only basis. The two posters will be presented on June 28 between 12 noon and 2:00 PM Eastern time. They are entitled:

• Combination Studies of the Anti-Interleukin-1beta Monoclonal Antibody XOMA 052 with Exendin-4 or Sitagliptin in a Diet-Induced Obesity Mouse Model of Type 2 Diabetes Mellitus
• Inhibition of Interleukin-1beta with the Monoclonal Antibody XOMA 052 Reveals the Differential Sensitivities of Glycemic and Pancreatic Function Parameters to Chronic Inflammation

The published-only abstract is entitled:

• The Role of Interleukin-1beta in Insulin Resistance