SBIR-STTR Award

A peptide receptor radionuclide therapy PRRT using Lu Y labeled somatostatin analogs have been proven to induce objective response in of patients with advanced progressive neuroendocrine tumors The complete response to beta emitter PRRT is rare This is due to the fact that NETs are diagnosed at late stage of disease the NETs patients with remissions could develop resistance to beta radiation therapy that could be overcome by alphaemitter targeted therapy TAT The commercial potential of TAT has been confirmed by recent introduction ofXofigo for therapy of bone metastasis in prostate cancer and remissions of NETs in patients undergoing therapy with Bi DOTATOC and Ac DOTATATOC The TAT has a potential to revolutionize treatment of NETs whether applied alone or supported by beta emitter PRRT It can significantly enhance therapeutic efficacy of PRRT without side effects on non targeted normal tissues In the proposed research we will determine the commercial feasibility of Pb octreotate The objective of this Phase I SBIR is to Determine the feasibility of radiosynthesis of Pb octreotate produced using AREVA Med high purity Pb generator Evaluate the pharmacokinetic efficacy and toxicity of Pb octreotate therapy in AR J xenographs With success in these aims we expect to advance our compound toward initiation of clinical studies and submission of NDA

A peptide receptor radionuclide therapy (PRRT) using [177Lu]/[90Y]-labeled somatostatin analogs has been proven to induce objective response in 30-45% of patients with advanced/progressive neuroendocrine tumors (NETs). The complete response to beta-emitter PRRT is rare. This is due to the fact that NETs are diagnosed at late stage of disease; the NETs patients with remissions could develop resistance to beta-radiation therapy that could be overcome by alpha-emitter-targeted-therapy (TAT). The commercial potential of TAT has been confirmed by recent introduction of Xofigo for therapy of bone metastasis in prostate cancer; and remissions of NETs in patients undergoing therapy with [213Bi]DOTATOC and [225Ac]DOTA-TATOC. The TAT has a potential to revolutionize treatment of NETs whether applied alone or supported by beta-emitter PRRT. It can significantly enhance therapeutic efficacy of PRRT without side effects on non-targeted normal tissues. Our Phase I Contract produced favorable results of the pre-clinical efficacy, long term-toxicity and dosimetry studies [212Pb]-octreotate. These results together with the safety, and dosimetry of 203Pb-octreotate in human allow us to propose the following objectives for the Phase II Contract: 1) Manufacturing of the clinical doses of [212Pb]-octreotate; (2) Initiation of Phase I dose escalation clinical studies of [212Pb]-octreotate in NETs patients. With success in these aims, we expect to a) evaluate our bussiness model of centralized production of clinical doses of [212Pb]-octreotate; b) assess the safety, and dose limiting toxicity of ascending doses of agent used for TAT of subjects with somatostatin receptor expressing NETs; c) determine the PK and the preliminary effectiveness of ascending doses of this drug.