The following data were presented at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Geneva.

• Ariad Pharmaceuticals Inc., of Cambridge, Mass., reported preclinical data showing that its mTOR inhibitor, deforolimus, when given alone or in combination with anti-androgen agent bicalutamide in models of prostate cancer, demonstrated an ability to inhibit the growth of prostate cancer cell lines in various model systems. Ariad is testing deforolimus in an ongoing Phase II trial in advanced prostate cancer patients.

• Cougar Biotechnology Inc., of Los Angeles, reported results from its ongoing Phase II trial of CB7630 (abiraterone acetate) in combination with prednisone and administered once daily to chemotherapy-naive, ketoconazole-naive patients with castration-resistant prostate cancer who had progressive disease despite treatment with hormonal therapies. Data from the 12 evaluable patients enrolled showed a decline in prostate-specific antigen (PSA) of greater than 30 percent in 11 patients (92 percent), including six patients (50 percent) with a PSA decline greater than 90 percent. Ten patients (83 percent) have been treated with CB7630 for more than six months.

• Curis Inc., of Cambridge, Mass., presented preclinical data demonstrating the efficacy of heat-shock protein 90 inhibitor CUDC-305 in both solid tumors and hematological cancers. In xenograft mouse models, the compound exhibited high oral bioavailability and a prolonged terminal half-life of 20.5 hours in tumors. And brain pharmacokinetic data demonstrated that CUDC-305 is highly brain penetrable, which suggests that the drug might have advantages in primary or metastatic brain cancers.

• Cytokinetics Inc., of South San Francisco, reported data related to GSK-923295, a small-molecule inhibitor of centromere-associated protein E, in a London-based GlaxoSmithKline plc-sponsored Phase I trial in patients with solid tumors, which showed that plasma pharmacokinetics of GSK-923295 were dose proportional and exhibited low intrapatient and modest interpatient variability. In addition, Cytokinetics reported that its kinesin spindle protein inhibitor, SB-743921, demonstrated potent activity in preclinical models of diffuse large B-cell lymphoma both in vitro and in vivo.

• Dendreon Corp., of Seattle, said preclinical data on its lead small-molecule candidate, D-3263, showed that in vitro, the compound selectively increased the influx of calcium into Trp-p8 expressing cells leading to cell death. In animal models, D-3263 significantly inhibited the growth of Trp-p8 expressing tumors. Trp-p8, a transmembrane ion channel also known as Trp-M8, is triggered by cold temperatures and small-molecule agonists.

• EntreMed Inc., of Rockville, Md., said preclinical data showed that its Aurora A/angiogenesis kinase inhibitor, ENMD-2076, demonstrated strong antitumor effects in a xenograft model of human colon cancer. Tumor stasis was seen at dose levels of 100 mg/kg/day, and tumor regression was observed at doses of 200 mg/kg/day. Further analysis using positron emission tomography demonstrated a substantial decrease in tumor metabolic activity in animals treated with ENMD-2076.

• Exelixis Inc., of South San Francisco, reported data from an ongoing Phase I trial of XL184, a small-molecule inhibitor of MET, VEGFR2 and RET, in patients with advanced malignancies, which showed a disease control rate of 84 percent and a response rate of 55 percent in evaluable patients with medullary thyroid cancer. In a separate presentation, the company said preliminary Phase I data from a dose-escalation trial of LX228 in patients with advanced malignancies showed that seven of 16 evaluable patients have experienced prolonged stable disease, with one metastatic non-small-cell lung cancer patient experiencing a 27 percent reduction in all target lesions as measured by RECIST criteria. XL228 is a small-molecule inhibitor of insulin-like growth factor Type I receptor and SRC. In a third presentation, Exelixis reported preliminary Phase I data from a dose-escalation trial of XL281, a selective small-molecule inhibitor of wild-type and mutant RAF kinases, in patients with advanced solid malignancies. Those data showed that, of the 29 patients enrolled in seven cohorts, one patient with ocular melanoma has experienced a partial response and 12 patients with solid cancers have shown stable disease.

• Nektar Therapeutics Inc., of San Carlos, Calif., reported positive preclinical data showing that NKTR-105 (peg-docetaxel) produced significantly greater antitumor activity compared to docetaxel in colorectal (LoVo and LS174T) and non-small-cell lung (H460) mouse xenograft models of human tumors. Partial regressions were observed in two of the cell lines for NKTR-105, while no regressions were observed for docetaxel. At maximum tolerated doses, the percent of tumor growth delay for NKTR-105 was 2.5-, two- and 1.6-fold greater than docetaxel in the H640, LoVo and LS174T xenograft models, respectively.

• Oncolytics Biotech Inc., of Calgary, Alberta, presented in vitro and in vivo data showing oncolytic activity of its reovirus in combination with cisplatin in a mouse melanoma cell line. Results demonstrated that the combined therapy resulted in significantly increased cell death in vitro compared to either agent alone. In the mouse model, combination treatment suppressed tumor growth and significantly prolonged median survival time. The company is testing its Reolysin in combination with carboplatin and paclitaxel in an ongoing clinical trial in advanced cancer patients.

• Poniard Pharmaceuticals Inc., of South San Francisco, reported positive incremental data from its Phase II trial of picoplatin in patients with metastatic colorectal cancer (CRC). Expanded and updated results continue to indicate that the drug, given once every four weeks in combination with 5-fluorouracil and leucovorin, is associated with less frequent and severe neurotoxicity than oxaliplatin given in combination with 5-FU and leucovorin in the modified FOLFOX-6 regimen. Interim results from 37 evaluable FOLFOX-treated patients showed that 65 percent showed evidence of neurotoxicity, with 5 percent exhibiting severe Grade 3 or 4 neurotoxicities. Of the 34 evaluable patients in the picoplatin, 5-FU and leucovorin group, none showed any severe Grade 3 or 4 neurotoxicities and only 18 percent exhibited resolvable low-grade (Grade 2 or lower) neurotoxicities.

• Proteolix Inc., of South San Francisco, reported positive data from a Phase I trial of carfilzomib (PR-171) in patients with advanced solid tumors who previously failed at least two rounds of prior treatment with approved chemotherapies. Of the 14 patients enrolled, one renal cancer patient who had previously failed three prior rounds of treatment achieved a partial response and remains in the study after eight months of treatment. One small-cell lung cancer patient achieved stable disease and is continuing in the study after six months, and a mesothelioma patient achieved stable disease for five months.

• SuperGen Inc., of Dublin, Calif., said its lead candidate, MP-470, an orally bioavailable multitargeted tyrosine kinase inhibitor, showed encouraging tumor regression results in the first two arms (paclitaxel/carboplatin and carboplatin/etoposide) of its current Phase Ib trial in combination with five standard-of-care (SOC) cancer treatments. Data indicated that MP-470 may sensitize/re-sensitize tumors to the anticancer effects of SOC regimens of DNA-damaging agents. However, a primary endpoint of the trial, which is to determine the maximum tolerated dose of MP-470 co-administered with SOC regimens, has not been reached and dose escalation continues.

• Threshold Pharmaceuticals Inc., of Redwood City, Calif., presented preliminary results from 22 patients in an ongoing Phase I trial of its hypoxia-activated prodrug, TH-302, in patients with advanced solid tumors. Preliminary efficacy signals have been observed in two patients. One with refractory small-cell lung cancer metastatic to the liver had a partial response, as judged by RECIST criteria at their initial response assessment, but after receiving two cycles of TH-302 at 480 mg/m2, the patient was discontinued from the study after treatment delay unrelated to therapy and disease progression. One patient with melanoma metastatic to the lung and liver had a RECIST criteria partial response after two cycles of TH-302 at 670 mg/m2 and is continuing treatment.

• Ziopharm Oncology Inc., of New York, said its darinaparsin (ZIO-101) was shown to be highly active in a series of cell lines, including those resistant to inorganic arsenic, or arsenic trioxide (ATO). The compound was found to trigger apoptosis through pathways that do not completely overlap with ATO. Preliminary results from 17 evaluable patients in Phase I studies showed that 10 (59 percent) had stable disease for at least two months of treatment. The serum level obtained by oral administration compared to intravenous administration showed a very favorable bioavailability and very similar pharmacokinetics.