Xoma recently presented new results from a phase I clinical trial of XOMA-052, a novel antiinflammatory approach for the treatment of type 2 diabetes. XOMA-052 is a humanized monoclonal antibody (MAb) against interleukin-1beta (IL-1beta), the elevated expression of which has been correlated with damage to insulin-producing beta cells in patients with type 2 diabetes. In this trial, a single intravenous infusion of XOMA-052 (0.01, 0.03 or 0.1 mg/kg) or placebo was administered to individuals with inadequately controlled type 2 diabetes who were subsequently assessed for safety, pharmacokinetics and various diabetes and inflammation-related parameters for up to a period of 3 months. Treatment with XOMA-052 was well tolerated without the incidence of any serious adverse events. A reduction in glycated hemoglobin A1c (HbA1c) was seen at 3 months following a single dose of XOMA-052 (median 1.1%, maximum 2.2%), whereas placebo-treated patients exhibited an increase of 0.1% in HbA1c. Intravenous stimulation tests revealed a continuous increase in insulin production at 1 and 3 months following XOMA-052, but not placebo, administration. Future studies with monthly or less frequent dosing are planned (Donath, M.Y. et al. 69th Annu Meet Sci Sess Am Diabetes Assoc (ADA) (June 5-9, New Orleans) 2009, Abst 113-OR). XOMA-052 clinical data also correlate with results obtained from studies in the diet-induced obesity (DIO) mouse model, where administration of twice weekly intraperitoneal doses of XOMA-052 (0.1 to 0.5 mg/kg) for up to 19 weeks led to significant reductions in fasting serum glucose, HbA1c, insulin resistance, fasting cholesterol, triglycerides and free fatty acid levels. The treatment was also found to improve glucose tolerance and beta-cell function (Owyang, A.M. et al. 69th Annu Meet Sci Sess Am Diabetes Assoc (ADA) (June 5-9, New Orleans) 2009, Abst 310-OR). Taken together, these data support the promising potential of XOMA-052 for the treatment of type 2 diabetes.

In addition to type 2 diabetes, Xoma is developing XOMA-052 for the indications of rheumatoid arthritis, acute gout and systemic juvenile idiopathic arthritis. In March 2009, Xoma commenced a phase IIa clinical study evaluating XOMA-052 for the treatment of rheumatoid arthritis (RA). The U.S.-based clinical study is a randomized, placebo-controlled study designed to enroll up to 18 patients with moderate to severe RA and evaluate the safety, pharmacokinetics and disease-specific outcomes of XOMA-052. Standard rheumatoid arthritis clinical assessment scores will be calculated using the American College of Rheumatology (ACR) core criteria, which assess inflammatory status, joint physical exam and general patient functional status. Patients will be enrolled into one of three groups. Each group will include one patient who will receive standard-of-care-treatment plus placebo and five who will receive standard-of-care treatment plus a single dose of XOMA-052 at 0.3 mg/kg. In one group, XOMA-052 will be administered by s.c. injection and in the other two groups by i.v. infusion. Patients will be followed for eight weeks.