Threshold Pharma Reports Early Clinical Data for Combining TH-302, Says Trial Achieved Partial Response Rate 12%, Stable Disease Rate 64%

ThresholdPharmaceuticals, Inc. (NASDAQ: THLD) today announced early clinicaldata from two single-arm, open-label Phase 1 trials evaluatingTH-302, an investigational, hypoxia-targeted drug, in combinationwith antiangiogenic agents for the treatment of advanced solidtumors. New data from an investigator-sponsored trial (Study 4001) inpatients with advanced solid tumors showed that combination treatmentwith TH-302 plus Votrient(R) (pazopanib) achieved a clinical benefitrate of 76% (partial response rate of 12% plus stable disease rate of64%). Updated data from a company-sponsored trial (Study 410) inpatients with renal cell carcinoma (RCC) and gastrointestinal stromaltumors (GIST) showed partial responses to treatment with TH-302 plusSutent(R) (sunitinib). Detailed results for Studies 410 and 4001 willbe presented this Monday and Tuesday, respectively, at the 2013AACR-NCI-EORTC International Conference on Molecular Targets andCancer Therapeutics in Boston, Massachusetts (Abstracts #B77 and#C61, respectively)."While antiangiogenics have proven to be an important new class oftargeted cancer therapy, essentially all tumors eventually becomeresistant to these treatments. Novel therapeutic approaches thataddress treatment resistance are greatly needed," said Herbert I.Hurwitz, MD, Professor of Medicine at Duke Cancer Institute andprincipal investigator of Study 4001. "Co-targeting tumorangiogenesis and tumor hypoxia, which is believed to be a key driverof treatment resistance, is one approach to potentially prevent orreverse this mechanism of resistance. These early clinical datacombining pazopanib and TH-302 in refractory cancers demonstratepreliminary signals of activity that warrant further investigation."The combination study with TH-302 plus pazopanib was conducted in 30patients with a variety of solid tumors for whom standard therapy orpalliative measures were nonexistent or no longer effective. Theclinical benefit rate was 76% (n=25 evaluable patients) with threepatients with partial responses (12%) and 16 patients with stabledisease (64%). The partial responses were observed in patients withneuroendocrine cancer, ovarian cancer, and chondrosarcoma.Treatment-related grade 3 hematological adverse events were reportedfor neutropenia (7%), thrombocytopenia (7%), and anemia (13%).Treatment-related, grade e 2 nonhematologic adverse eventsincluded vomiting/nausea/diarrhea (7% grade 3), mucositis (7% grade3), hand foot syndrome (all grade 2), and hypertension (all grade 2).No grade 4 adverse events have been reported. The study has completedenrollment and treatment is ongoing.In addition, updated preliminary results from the combination studywith TH-302 plus sunitinib (n=12) showed that partial responses wereachieved by one of four (25%) evaluable GIST patients (confirmed) andthree of six (50%) evaluable RCC patients (two confirmed). All fourpatients with partial responses had received prior sunitinib. Grade 3thrombocytopenia and neutropenia were reported in 3 (25%) and 4 (33%)patients, respectively; grade 4 neutropenia was reported in onepatient (8%). Fatigue, nausea, and vomiting were the most commonnonhematologic adverse events occurring in 83%, 75%, and 67% ofpatients, respectively. All cases were grade 1 or 2 except for onereport of grade 3 nausea.Preclinical Data on TH-302 in Pancreatic Cancer Also to be Presentedat Meeting Preclinical data on the combination of TH-302 withGemzar(R) (gemcitabine) and Abraxane(R) (nab-paclitaxel) in models ofpancreatic cancer will be presented at the meeting on Tuesday October22 (Abstract #C287) showing in xenograft models greater anti-tumoractivity associated with the "triplet" (TH-302 plus gemcitabine plusnab-paclitaxel) compared with that of the doublet (gemcitabine plusnab-paclitaxel), and without additive hematological toxicity orperipheral neuropathy.