Hematology
Nonclinical studies have indicated opportunities for use of ZT-031 [Ostabolin-C, cyclic PTH-(1-31)] and other proprietary PTH analogs in hematology indications. Zelos is conducting preclinical validation studies with collaborators at Massachusetts General Hospital and other research institutions using ZT-031; however, the Company intends to utilize another one of its proprietary PTH analogs in stem cell transplantation, once the program reaches IND stage. We believe that these hematologic indications can be commercialized successfully by establishing individualized high dose therapy administered subcutaneously.
Bone marrow/stem cell transplant
Hematopoietic stem cells, the precursors of all differentiated blood cells, occupy a physical space close to the inner surface of bone, also known as the hematopoietic stem cell niche. In this microenvironment, preclinical studies suggest that PTH appears to play an important role in the maturation and differentiation of such cells. Initial preclinical studies suggest that PTH analogs may have a role in bone-marrow transplant, including improving the success of stem-cell harvest and/or engraft1. This indication represents a significant market opportunity as 65% of patients whose bone marrow transplant fails to engraft die within one-year of transplant2.
1Adams, G., et. al; Massachusetts General Hospital
2Bone Marrow Registry, 2005
Multiple myeloma
PTH analogs such as ZT-031 may also play a therapeutic role in the treatment of certain tumors including multiple myeloma. Multiple myeloma is the second most common hematologic malignancy in the United States. At present, myeloma is treatable but almost inevitably relapses. It is a disease of plasma cells characterized by lytic bone lesions, marked reduction in bone formation, profound osteoporosis and severe bone pain.
Osteoporosis and bone lesions are a well known and common occurrence in patients with multiple myeloma. Large increases in bone resorption stimulated by factors released by myeloma cells are an important cause of myeloma bone disease. Therefore, intravenous bisphosphonate treatment has become established in standard treatment regimens for multiple myeloma. A profound reduction in bone formation is also usually present in myeloma patients and may contribute to the pathogenesis of myeloma bone disease. PTH analogs with increased anabolic potential may be useful to treat reduced bone formation in these patients without exacerbating hypercalcemia, which is a common clinical occurrence in multiple myeloma.
In addition to the effect on myeloma bone disease, PTH analogs may also be effective in the treatment of multiple myeloma itself. Observations in patients treated with Velcade® (bortezomib) have noted that an increase in PTH levels precedes the onset of clinical response. Further studies have indicated that Velcade also increases bone formation in these patients. Further study in animal models of multiple myeloma has shown that PTH analogs can reduce the survival of myeloma cells in vivo even when bortezomib is not present. Zelos has initiated studies in mouse models to assess the positive effects of ZT-031 both in terms of effect on bone formation and also on the growth of tumor cells1.
Velcade® is a registered trademark of Millennium Pharmaceuticals, Inc.
1Zangari, M. et al; Response to bortezomib and activation of osteoblasts in multiple myeloma; Clin Lymphoma Myeloma. 2006 Sep;7(2):109-14
