Threshold Pharmaceuticals Making Good Clinical Progress on Several Fronts

Threshold Pharmaceuticals, Inc. THLD today announced clinical trial results of the Phase 1 study of TH-302 in patients with advanced leukemias conducted at MD Anderson's Cancer Center in Houston, Texas.

Thirty-two patients with either acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL) have been enrolled in the trial to date. At the current dosing two patients developed dose limiting mucosal toxicity. The maximum tolerated daily dose (MTD) of TH-302 was established at 460 mg/m2. Efficacy assessments have demonstrated TH-302 activity in multiple subjects with relapsed/refractory AML and ALL as evidenced by stabilization or reduction of bone marrow and peripheral blast counts. One patient had a complete response with incomplete platelet recovery (CRp) with resolution of leukemia cutis.

"With the establishment of the MTD, we look forward to better defining the safety and efficacy of single agent TH-302 in patients with advanced leukemias," said Dr. Marina Konopleva, M.D., Associate Professor in the Department of Leukemia at MD Anderson Cancer Center. "The accumulating evidence of the importance of hypoxia in advanced leukemias and our initial findings that TH-302 can reduce blasts in patients with refractory advanced leukemias are promising. Ongoing preclinical investigations have demonstrated that TH-302 is active as a monotherapy and demonstrate synergistic activity in combination with multiple chemotherapies. We are excited to continue further clinical investigations."

Threshold Pharmaceuticals has built a pipeline of drugs by selectively targeting tumor cells that are more effective and less toxic to healthy tissues than conventional drugs. The company's product candidates are focused on treating patients with significant unmet medical needs. Its product pipeline includes: TH-302, a hypoxia-activated prodrug (HAP) indicated for the treatment of solid tumors; Glufosfamide, a small molecule indicated for the treatment of pancreatic cancer, small cell lung cancer, platinum-resistant ovarian cancer and advanced soft tissue sarcoma; and 2-Deoxyglucose or 2DG in combination with Taxotere indicated for the treatment of solid tumors. Its other products include: TH-CR-402, TH-CR-403, TH-CR-401, etc indicated for the treatment of various cancers.

A look at the BioMedReports FDA calendar which tracks thousands of regulatory and clinical trial catalysts shows that a March 10-K filing with the SEC by the firm disclosed that Threshold also expects to report top line efficacy results from the randomized Phase II trial for TH302 with Gemcitabine as a First Line Pancreatic Cancer treatment at the end of 2011. That is one of several milestones listed for the firm.

In October, Threshold Pharmaceuticals announced the results from Phase II clinical trial of TH-302. This single arm study investigated TH-302 in combination with doxorubicin in patients with advanced soft tissue sarcoma. Best responses were: 2 complete responses, 30 partial responses and 43 patients with stable disease for an overall response rate of 36% and a stable disease or better rate of 84%.

Prior to that, in late September, the firm announced that Threshold, in collaboration with Sarcoma Alliance for Research through Collaboration (SARC), had initiated a Phase III randomized clinical trial of TH-302 in patients with soft tissue sarcoma. That Phase III trial will be a 450 patient, randomized, open-label, multi-center trial comparing two treatment regimens for patients with metastatic and/or advanced unresectable soft tissue sarcoma who have not received prior systemic therapy. This trial is designed to demonstrate the clinical benefit of TH-302 in combination with doxorubicin compared to doxorubicin alone based on a primary efficacy endpoint of overall survival. The trial includes an interim futility analysis based on progression-free survival expected to occur about half-way into enrollment and an interim analysis based on overall survival expected to occur at the end of enrollment.

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TH302 is a hypoxically activated prodrug (HAP) designed to exploit low oxygen levels in tumors. It combines a 2-nitroimidazole oxygen-sensing trigger with a masked DNA crosslinker.



Disclosure: none