Efficacy of SMIP-016, a novel CD37-directed biologic therapy, in human NHL tumor xenograft models

Abstract

2565 Background: Small Modular Immuno-Pharmaceuticals (SMIP) biopharmaceuticals belong to a novel proprietary biologic compound class that retain Fc mediated effector functions and are smaller than monoclonal antibodies. SMIP-016 is a SMIP product candidate that binds to CD37 on human B cells and has potent ADCC and apoptotic activity in vitro. CD-37 is known to be over-expressed in non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic leukemia (CLL). We have evaluated the activity of SMIP-016 in established human tumor xenograft models in nude mice. Methods: Nude mice were injected subcutaneously with either Ramos or Daudi tumor cells. At approximately 7 days post tumor inoculation the mice were randomized to groups with roughly equivalent mean tumor volumes (>200mm3) and were treated with SMIP-016 or rituximab as a comparator. Groups were evaluated for median survival time (MST), tumor volume and percentage of tumor-free animals. Results: In nude mice bearing Daudi tumors, SMIP-016 treated mice showed a significant improvement in MST compared to control mice (p < 0.0001). Nude mice bearing Ramos tumors treated with SMIP-016 also demonstrated a significant enhancement in their median survival time (MST) in comparison to control mice (p < 0.0001). In addition, mice receiving SMIP-016 administered in combination with rituximab in this model demonstrated improvements in survival time over either single agent therapy alone. Conclusions: SMIP-016 is effective in treating established tumors in these human tumor xenograft models. Addition of SMIP-016 to rituximab therapy resulted in enhanced survival times compared to animals treated with rituximab alone. [Table: see text]