In other news from AACR (Bioworld):
• Alfacell Corp., of Bloomfield, N.J., presented data supporting earlier research that showed its lead drug candidate, Onconase, to be a possible treatment for non-small-cell lung cancer. Studies showed that when Onconase was combined with either cisplatin or carboplatin, the chemosensitivity was significantly enhanced. Alfacell also reported that, in large tumors, Onconase showed inhibition of tumor growth. The company initiated a Phase I/II trial in February to evaluate Onconase in patients with refractory NSCLC.
• AVI BioPharma Inc., of Portland, Ore., said preclinical data indicate that AVI-4126, a Neugene antisense oligomer inhibiting c-myc, decreases the formation of lung metastasis in an aggressive lung tumor model. In a second study, inhibition of WT1 was achieved using an antisense oligomer, leading to reduced tumor volume in a prostate cancer model. Another study suggests that Neugene produces a decrease in cell viability and in XIAP levels.
• Cerus Corp., of Concord, Calif., said preclinical data indicate that the company's Listeria-based vaccines can generate antitumor responses while maintaining safety, and can be administered repeatedly as part of a chronic treatment regimen. The company has three cancer immunotherapy products in preclinical development, including CRS-100, CRS-207 and MEDI EphA2. The company expects to file its first Listeria investigational new drug application this year.
• CuraGen Corp., of New Haven, Conn., and TopoTarget A/S, of Copenhagen, Denmark, said new preclinical data on PXD101 suggest tumor growth inhibition and prolonged survival when the drug is used in combination with 5-fluorouracil against certain types of solid tumors. The company plans to start a Phase Ib trial this year. PXD101 is an HDAC inhibitor being investigated in Phase II to treat advanced multiple myeloma.
• Ecopia BioSciences Inc., of Montreal, presented data on ECO-4601, its drug candidate for brain cancer, describing one of the possible mechanisms of action that suggest the compound is involved in the initiation and regulation of apoptosis. That data revealed that ECO-4601 has an affinity for mitochondrial peripheral benzodiazepine receptor, a component of the mitochondrial permeability transition pore, which is involved in apoptosis.
• EntreMed Inc., of Rockville, Md., said results of multiple in vitro and in vivo studies confirmed the mechanism of action for 2-methoxyestradiol (2ME2, or Panzem) in treating various types of cancer. The company reported data that indicated 2ME2 disrupts interphase microtubules, down-regulates HIF-1alpha, inhibits de novo synthesis of HIF-1alpha and induces apoptosis. Additional data further demonstrated that the product inhibits HIF-1alpha translation by preventing localization of HIF-1alpha mRNA complexes with depolymerized microtubules.
• GenVec Inc., of Gaithersburg, Md., presented data showing that TNFerade plus radiation significantly reduced the spread of cancer to lymph nodes in a mouse model of melanoma. Researchers from GenVec and partner, Fuso Pharmaceutical Industries Ltd., of Japan, also presented data demonstrating TNFerade's ability to target and treat ovarian cancer in a mouse model, using a next-generation targeted vector to deliver the tumor necrosis factor-alpha gene. TNFerade is an adenovector that contains the gene TNF-alpha and is designed to stimulate the production of TNF-alpha locally within a tumor.
• Geron Corp., of Menlo Park, Calif., said preclinical data of its telomerase inhibitor drug, GRN163L, and Velcade (Millennium Pharmaceuticals Inc.) showed the combination therapy reduced tumor growth in an animal model of human multiple myeloma by 68 percent. When GRN163L was used alone, tumor growth was reduced by 30 percent, and Velcade alone had no efficacy in the model at the dose used. Another study in human ovarian cancer showed a 90 percent reduction in tumor mass by GRN163L alone, 80 percent reduction with Taxol alone, and 96 percent reduction from the combination of the two.
• ImmunoGen Inc., of Cambridge, Mass., presented preclinical data on the tumor-activated product compound AVE9633. The company developed the CD33-targeting compound to treat acute myeloid leukemia, and licensed it to the Sanofi-Aventis Group, of Paris, as part of a broad collaboration. In vivo, the product was able to eradicate tumors consisting of human leukemia cells in xenograft models, and it achieved complete responses and cures at doses that caused little or no toxicity.
• Infinity Pharmaceuticals Inc., of Cambridge, Mass., said preclinical data of its investigational compound IPI-504, an inhibitor of heat-shock protein 90, demonstrated that it reduces tumor burden in several animal models of cancer, including multiple myeloma, breast, lung and prostate cancer. Infinity also reported a clinical benefit relative to other Hsp90 inhibitors in its proposed administration to patients using a water-based formulation.
• Insert Therapeutics Inc., of Pasadena, Calif., presented data demonstrating the improved biodistribution and preclinical efficacy in vivo of IT-101. The company is moving toward a Phase I trial of the compound, which combines Insert's polymer technology, Cyclosert, and camptothecin. The in vivo efficacy data of IT-101 were found in rodent models of colon cancer, breast cancer, lung cancer, pancreatic cancer and Ewing's sarcoma.
• Medarex Inc., of Princeton, N.J., and New York-based Bristol-Myers Squibb Co. said complete or partial responses in seven of 56 patients with metastatic melanoma showed durability ranging from four months to the longest still ongoing at more than 34 months, with five of the seven responses ongoing for more than two years. Those patients were treated in a Phase II study with the investigational fully human anti-CTLA-4 antibody, MDX-010, in combination with MDX-1379, a gp100 melanoma vaccine. The trial evaluated two dose regimens of MDX-010 in combination with MDX-1379 in patients with Stage IV disease.
• Morphogenesis Inc., of Tampa, Fla., said its cancer therapy, ImmuneFx, was able to induce tumor regression in mice with an aggressive form of cancer. The product was tested against neuroblastoma in preclinical models and was found to stimulate complete tumor regression in 81 percent of animals tested, with a survival rate of better than 88 percent at the highest dose. The company anticipates that ImmuneFx will enter human trials sometime this year.
• NeoPharm Inc., of Lake Forest, Ill., presented preclinical data on the antitumor activity for its new candidate, gemcitabine-cardiolipin conjugate. The data provided evidence that the product, also called NEO6002, might reduce the toxicity and improve the efficacy of Gemzar. Results showed a greater weight loss and significant decrease in white blood cell counts and only a 32 percent tumor inhibition in Gemzar-treated mice, while NEO6002-treated mice had less weight loss and white blood cell decrease, as well as a 52 percent tumor inhibition.
• OSI Pharmaceuticals Inc., of Melville, N.Y., presented data showing that smoking results in a reduction in the blood levels of Tarceva following oral dosing of the drug in healthy volunteers. The company plans to further explore whether an increase in the Tarceva dose in smokers will result in an enhanced clinical benefit. Tarceva was FDA approved in November to treat locally advanced or metastatic non-small-cell lung cancer after failure of at least one prior chemotherapy regimen.
• OxiGene Inc., of Waltham, Mass., presented data on Combretastatin A-4 phosphate with paclitaxel and manumycin A in a mouse xenograft model of anaplastic thyroid cancer. The triple combination had a significant effect in slowing the growth of the xenografts and researchers have observed complete remissions and stable disease in several subject animals. Another study showed that neither CA4P nor its metabolites caused any increase in the number of structural chromosomal aberrations.
• Peregrine Pharmaceuticals Inc., of Tustin, Calif., reported data showing the potential use of Tarvacin, its lead anti-phospholipid therapy agent, for imaging solid tumors. Data showed that Tarvacin could be used to deliver a radioactive arsenic compound to prostate cancer blood vessels for tumor imaging.
• Pharmacyclics Inc., of Sunnyvale, Calif., said studies suggest that human lymphoma cells undergo apoptosis when treated with Xcytrin in vitro, and preclinical results support the evaluation of Xcytrin in ongoing chronic lymphocytic leukemia trials. Further data indicate that Xcytrin inhibits the enzyme thioredoxin reductase, demonstrates an additive effect on tumor suppression when used with celecoxib, and enhances the activity of radiation in hypoxic tumors. Other preclinical data showed that a new class of compounds, called Sapphyrins, induced apoptosis in vitro in several hematologic cancer cell lines.
• Spectrum Pharmaceuticals Inc., of Irvine, Calif., said administration of SPI-1620 resulted in a 150 percent and 318 percent increase in tumor perfusion in breast and melanoma tumor-bearing animals, respectively. The preclinical studies indicated that the product could be used to increase the delivery of chemotherapy drugs to tumors and enhance their efficacy. SPI-1620, an endothelinB agonist, is designed to stimulate receptors on endothelial cells to selectively dilate blood vessels in the tumor, resulting in an increase in delivery of cancer drugs to the tumor.
• Vical Inc., of San Diego, presented preclinical data supporting the company's decision to advance into Phase I testing with its method of delivering interleukin-2 for patients with recurrent metastatic melanoma. The approach involves direct injection into a tumor lesion of plasmid DNA encoding IL-2, followed by electroporation. Preclinical results indicated that mice receiving the injections followed by electroporation had two- to threefold higher levels of IL-2 in the injected tumor and reduced tumor growth, compared with mice that did not receive the electroporation.
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