Key Developments: Threshold Pharmaceuticals Inc (THLD.OQ)
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Latest Key Developments (Source: Significant Developments)
Threshold Pharmaceuticals Inc Announces Data From Two Ongoing Phase 1/2 Trials of TH-302
Threshold Pharmaceuticals Inc announced data from two ongoing Phase 1/2 trials evaluating TH-302, an investigational hypoxia-targeted drug, at the 49th Annual Meeting of the American Society of Clinical Oncology (ASCO), which is being held in Chicago, Ill., May 31 through June 4. Updated results from a Phase 1/2 study of TH-302 plus dexamethasone in patients with relapsed/refractory multiple myeloma were presented supplementing the data published in the meeting abstract (Abstract #8602). Of 12 evaluable patients, 2 achieved partial responses (PRs) and 2 minimal responses (MRs) for a clinical benefit rate (MR or better) of 33%. In a Phase 1/2 clinical trial of TH-302 administered in combination with the antiangiogenic therapy sunitinib, one of 4 patients with gastrointestinal stromal tumors (GIST) achieved a confirmed PR, and 3 of 4 patients with renal cell carcinoma (RCC) achieved PRs. A total of 13 patients with relapsed/refractory multiple myeloma and a median number of 6 prior therapies initiated treatment with TH-302 plus dexamethasone in an ongoing Phase 1/2 trial. All patients had received prior therapy with regimens containing a proteasome inhibitor, an immunomodulatory drug (IMiD), and an alkylating agent. TH-302 was dosed at 240 mg/m2 (n=5), 340 mg/m2 (n=6), and 480 mg/m2 (n=2) for a median of 5 cycles. TH-302 was administered with dexamethasone (fixed oral 40 mg dose) on days 1, 4, 8, and 11 of a 21-day cycle. Full Article
Levi & Korsinsky, LLP Launches Investigation into Possible Breaches of Fiduciary Duty by Board of Directors of Threshold Pharmaceuticals Inc
Levi & Korsinsky, LLP announced that it is investigating Threshold Pharmaceuticals Inc, and its Board of Directors, in connection with possible claims of breaches of fiduciary duty. Full Article
Threshold Pharmaceuticals Inc And Merck KGaA's Merck Serono Announce Initiation Of TH-302 Phase 3 MAESTRO Study In Patients With Locally Advanced Or Metastatic Pancreatic Adenocarcinoma
Threshold Pharmaceuticals Inc announced that Threshold's partner Merck KGaA, Darmstadt, Germany, through its division Merck Serono, initiated the global Phase 3 MAESTRO study assessing the efficacy and safety of investigational hypoxia-targeted drug TH-302 in combination with gemcitabine in patients with previously untreated, locally advanced unresectable or metastatic pancreatic adenocarcinoma. The initiation of the Phase 3 MAESTRO study resulted in Threshold earning a $30 million payment from Merck KGaA pursuant to the terms of Threshold's license and co-development agreement with Merck KGaA, which includes an option for Threshold to co-commercialize in the U.S. MAESTRO stands for TH-302 in the treatment of MetastAtic or unrESectable pancreaTic adenocaRcinOma. MAESTRO is a randomized, placebo-controlled, international, multi-center, double-blind Phase 3 trial of TH-302 plus gemcitabine compared with placebo plus gemcitabine and is expected to enroll 660 patients. The primary efficacy endpoint is overall survival; the secondary endpoints include efficacy measured by progression-free survival (PFS), overall response rate and disease control rate, as well as assessments of safety and tolerability, pharmacokinetics and biomarkers. The study is being conducted under a Special Protocol Assessment (SPA) with the U.S. Food and Drug Administration (FDA). Full Article
Threshold Pharmaceuticals Inc Reports Updated Phase 2 Results Including Analyses of Maintenance Therapy With TH-302 Following Induction Therapy With TH-302 Plus Doxorubicin In Soft Tissue Sarcoma
Threshold Pharmaceuticals Inc announced updated results from a Phase 2 study of TH-302, the Company's investigational hypoxia-targeted drug, in patients with soft tissue sarcoma, including additional results from patients who were administered TH-302 as single agent maintenance therapy following induction with TH-302 in combination with doxorubicin. In the single-arm Phase 2 component of the study (403 trial), previously untreated patients with metastatic or locally advanced unresectable soft tissue sarcomas were treated with TH-302 (300 mg/m2 on days 1 and 8 of a 21-day cycle) and doxorubicin (75 mg/m2 on day 1) for a maximum of six cycles. After six cycles, patients with stable disease, partial or complete responses, and with acceptable toxicity, were eligible to receive TH-302 maintenance therapy (300 mg/m2 on days 1 and 8 of a 21-day cycle). Response was assessed using RECIST criteria. Results for Overall Study Population (N=91) Updated results for the 91 patients in the Phase 2 component of the study include: Median progression free survival (PFS) of 6.7 months (95% CI: 6.2 to 8.1 months). Median overall survival of 21.5 months (95% CI 16.0 to 27.6 months). One-year survival of 73% (95% CI: 63% to 82%), and two-year survival of 44% (95% CI: 32% to 55%). Overall best response (partial and complete responses, unconfirmed) of36%. Full Article
Threshold Pharmaceuticals Inc Announces Preliminary Data From Phase 1/2 Study of TH-302 in Combination With Bevacizumab in Patients With Recurrent Glioblastoma
Threshold Pharmaceuticals Inc announced preliminary data from an ongoing dose-escalation Phase 1/2 clinical trial of its investigational hypoxia-targeted drug TH-302 in combination with bevacizumab in patients with recurrent glioblastoma. No dose-limiting toxicity has been reported to date in the first two dose cohorts (240 mg/m2 TH-302 plus bevacizumab and 340 mg/m2 TH-302 plus bevacizumab); dose escalation is ongoing. Preliminary results in six patients show a median time to progression (worsening of disease) of 128 days compared with a median time to progression of 89.5 days these same patients experienced while taking single-agent bevacizumab prior to study enrollment. Glioblastoma remains an incurable malignancy with poor survival despite aggressive surgery and chemoradiation therapy. When glioblastoma recurs, a standard salvage therapy is bevacizumab, a biologic antibody designed to interfere with the tumor blood supply by directly binding to a protein called VEGF. Preclinical data suggest that antiangiogenic agents, such as bevacizumab, may increase tumor hypoxia, which supports the rationale for combining TH-302 -- a drug designed to target and kill cells in hypoxic regions of the tumor -- with bevacizumab in treating glioblastoma. The study is enrolling patients with recurrent glioblastoma whose disease has progressed following initial treatment with bevacizumab and who are scheduled for debulking craniotomy (brain surgery to remove tumor tissue). Full Article
Threshold Pharmaceuticals Inc Announces Data From Phase 2b Clinical Trial Of TH-302 In Combination With Gemcitabine In Advanced Pancreatic Cancer
Threshold Pharmaceuticals Inc announced that data from a randomized open-label Phase 2b clinical trial of investigational hypoxia-targeted drug TH-302 in patients with advanced pancreatic cancer. The Company announced in February 2012 that study met primary endpoint demonstrating a statistically 63% improvement (p=0.005) in progression free survival (PFS) for patients treated with TH-302 and gemcitabine versus gemcitabine alone. This represented a 2-month increase in PFS for patients treated with TH-302. New findings on overall survival, which was a secondary endpoint of the study, indicate that patients treated with gemcitabine alone had a median overall survival of 6.9 months compared with 9.2 months for patients treated with 340 mg/m2 TH-302 plus gemcitabine (HR: 0.955, 95% CI: 0.67-1.37, p=0.800) and 8.7 months for patients treated with 240 mg/m2 TH-302 plus gemcitabine (HR: 0.960, 95% CI: 0.67-1.38, p=0.827). While not statistically, improvement in median overall survival is consistent with improvement in median PFS reported previously. The trial was not designed to detect a statistically improvement in overall survival and included a cross-over component. Patients receiving gemcitabine alone who crossed over to receive gemcitabine plus TH-302 upon disease progression did contribute to an increase in survival of the control arm. Full Article
Threshold Pharmaceuticals, Inc. Receives US Orphan Drug Designation For TH-302 For Treatment Of Soft Tissue Sarcoma
Threshold Pharmaceuticals, Inc. announced the US Food and Drug Administration (FDA) has granted Orphan Drug Designation for TH-302, a hypoxia-targeted drug, for the treatment of soft tissue sarcoma. Threshold Pharmaceuticals is conducting a pivotal Phase 3 study (TH-CR-406) in soft tissue sarcoma comparing TH-302 in combination with doxorubicin against single agent doxorubicin. The same combination regimen of TH-302 with doxorubicin was investigated in the single-arm Phase 2 (TH-CR-403) study. Data from this Phase 2 study were most recently presented at the Connective Tissue Oncology Society (CTOS) meeting in October of 2011. In February 2011, Threshold Pharmaceuticals announced that it had reached agreement with the FDA on a Special Protocol Assessment for the Phase 3 study which includes a primary efficacy endpoint of overall survival. The international, randomized, controlled Phase 3 clinical trial was initiated in September 2011, and is being conducted in partnership with the Sarcoma Alliance for Research through Collaboration (SARC). The trial is designed to enroll 450 patients with metastatic or locally advanced unresectable soft tissue sarcoma. Full Article
Threshold Pharmaceuticals, Inc.' TH-302 Receives Orphan Drug Designation In The European Union for the Treatment of Soft Tissue Sarcoma
Threshold Pharmaceuticals, Inc. announced the European Commission has granted Orphan Drug Designation for TH-302, a hypoxia-targeted drug, for the treatment of soft tissue sarcoma. Threshold Pharmaceuticals is currently conducting a pivotal Phase 3 study in soft tissue sarcoma comparing TH-302 in combination with doxorubicin against single agent doxorubicin. The same combination regimen of TH-302 with doxorubicin was investigated in the single-arm Phase 2 (TH-CR-403) study. Full Article
Threshold Pharmaceuticals, Inc. Announces Positive Phase 2b Clinical Trial Results Of TH-302 In Patients With Pancreatic
Threshold Pharmaceuticals, Inc. announced that its 214 patient randomized controlled Phase 2b clinical trial evaluating the efficacy and safety of two doses of the investigational agent TH-302 in combination with gemcitabine compared to gemcitabine alone in patients with first-line advanced pancreatic cancer achieved its primary endpoint, with a 63% improvement in progression free survival and a safety profile consistent with previous studies. The median progression-free survival (PFS) was 5.6 months for patients treated with gemcitabine in combination with TH-302 at 240 mg/m2 and 340 mg/m2 compared to 3.6 months for patients treated with gemcitabine alone. The PFS hazard ratio comparing the TH-302 combination to gemcitabine alone was 0.61 (95% confidence interval: 0.43 - 0.87) which was statistically significant (p = 0.005). The response rate in the combination arms was 22% compared to 12% in the gemcitabine alone group. Results also demonstrated greater efficacy in the higher TH-302 dose group compared to the lower dose group. Full Article
Threshold Pharmaceuticals, Inc. And Merck KGaA Announce Global Agreement To Co-Develop And Commercialize Phase 3 Hypoxia-Targeted Drug TH-302
Threshold Pharmaceuticals, Inc. announced that a global agreement was signed with Merck KGaA, Darmstadt, Germany, to co-develop and commercialize TH-302, Threshold's small molecule hypoxia-targeted drug. TH-302 is currently being investigated in a global Phase 3 clinical trial in patients with soft tissue sarcoma, a randomized Phase 2 trial in patients with advanced pancreatic cancer from which top-line results are expected in February, as well as additional clinical studies in other solid tumors and hematological malignancies. Under the terms of the agreement, Merck will receive co-development rights, exclusive global commercialization rights and will provide Threshold an option to co-commercialize the therapeutic in the United States. In exchange, Threshold will receive an upfront payment of $25 million and could receive up to $35 million in additional development milestones during 2012. Threshold is also eligible to receive a $20 million payment based on positive results from its randomized Phase 2 trial in pancreatic cancer. Total potential payments are $525 million, comprised of $280 million in regulatory and development milestones and $245 million in sales-based milestones. In the United States, Threshold will have primary responsibility for development of TH-302 in the soft tissue sarcoma indication. Threshold and Merck KGaA will jointly develop TH-302 in all other cancer indications being pursued. Merck KGaA will pay 70% of worldwide development costs for TH-302. Full Article

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