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AACR Roundup(BioWorld Today Via Thomson Dialog NewsEdge) The following items were presented at the American Association for Cancer Research meeting in San Diego. The conference ends Wednesday. (Also see, pp. 7-9.) ? Abraxis BioScience Inc., of Los Angeles, reported preclinical data demonstrating the effect of Abraxane (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) in combination with Avastin (bevacizumab, Genentech Inc.) to eradicate large-sized orthotopic breast tumors and lymphatic and systematic metastases. After treatment with two cycles of Abraxane and Avastin given concurrently, 100 percent of the preclinical models were free of metastases in lymph nodes and lungs. ? Access Pharmaceuticals Inc., of Dallas, presented data showing that ProLindac displays a cytotoxic profile in vitro that is similar to oxaliplatin in most human cancer cell lines at similar platinum concentrations. ProLindac demonstrated cell cycle arrest, apoptosis induction and gene expression, particularly increases in p21 and decreases in Ki67 and NEK2 mRNA levels. ? Active Biotech AB, of Lund, Sweden, presented results from preclinical studies showing that combining its Tumor Targeted Superantigens and Taxotere (docetaxel) significantly improved antitumor activity compared to the respective monotherapy. The combination also prolonged long-term survival in tumor-bearing mice. The company concluded that the results demonstrated that TTS therapy is suitable for combination treatment agents such as Taxotere, and suggested a significant potential for such a combination in human cancer therapy. ? Adventrx Pharmaceuticals Inc., of San Diego, said its registrational bioequivalence clinical study of ANX-530 (vinorelbine emulsion) met its primary endpoint and a new drug application will be submitted by the end of the year. The study was a crossover comparison of ANX-530 and Navelbine with a primary objective of demonstrating the pharmacokinetic equivalence of ANX-530 and Navelbine. In post hoc analyses, relative to Navelbine, ANX-530 demonstrated a statistically significant reduction in injection-site reactions. Notably, the incidence of injection-site reactions attributed to Navelbine was consistent with its product label, the company said. ANX-530 was determined to be safe and well-tolerated. Safety data will be published in the 2008 Proceedings of the American Society of Clinical Oncology. ? Amgen Inc., of Thousand Oaks, Calif., reported data showing that AMG 655, when combined with gemcitabine, enhanced apoptosis in both in vitro and in vivo pancreatic cancer models. In another study, the drug, in combination with irinotecan or 5-fluorouracil, enhanced apoptosis relative to either agent alone in colon cancer cell models. A third study indicated the use of positron emission tomography as a noninvasive method of measuring receptor occupancy of DR5, the target of AMG 655. Amgen also reported preclinical data from its AMG 479 program, showing that the drug inhibited more than 80 percent of IGF-1-induced growth activation in certain sarcoma cell lines. ? Ariad Pharmaceuticals Inc., of Cambridge, Mass., said preclinical results showed that its mTOR inhibitor deforolimus, in combination with various cancer agents, demonstrated the drug's potential in sarcomas and endometrial cancer. In vitro and in vivo studies of deforolimus as a single agent also suggested a potential option for both cancer types and also indicated potential molecular markers of drug responsiveness. ? AVEO Pharmaceuticals Inc., of Cambridge, Mass., said its oral triple VEGF receptor inhibitor AV-951 showed clinical activity in multiple advanced solid tumor types including renal, colon and lung cancers and is well tolerated according to new data from the expanded Phase I clinical trial. Partial response or stable disease was observed across all patients with renal cell carcinoma, and overall, one-third of patients across all tumor types achieved tumor shrinkage during treatment with AV-951. ? Bionovo Inc., of Emeryville, Calif., presented findings on the mechanism of action of two of its anticancer agents, BN107 and BN108. BN107 induces apoptosis through the mitochondrial pathway and induces death only in estrogen-receptor-negative breast cancer cells. BN108 induces cancer cell death by rapid inactivation of both AKT and mTOR pathways in breast cancer cells, but not in normal cells. ? Cell Genesys Inc., of South San Francisco, presented data from a preclinical study demonstrating that multiantigen immunotherapies provided superior anti-tumor protection, including improved infiltration of immune T-cells into tumors and improved tumor-specific immunologic memory, compared to single-antigen immunotherapies. Researchers observed that mice injected with the B16-specific, multiantigen immunotherapy experienced significantly stronger antitumor protection compared to mice injected with either of the B16-specific, single-antigen products. Moreover, higher numbers of tumor-infiltrating T-lymphocytes were found in tumors of animals treated with the multiantigen immunotherapy than in the single-antigen products. In a separate poster, the company reported data from an ongoing Phase I trial of GVAX immunotherapy in combination with ipilimumab (MDX-010, Medarex Inc.) in prostate cancer, which suggested an association between an increase in T-cell immunity and antitumor activity, as measured by a decrease in prostate-specific antigen serum levels. ChemGenex Pharmaceuticals Ltd., of Melbourne, Australia, presented preclinical data characterizing the bioavailability and mechanism of action of omacetaxine mepesuccinate (formerly known as Ceflatonin), saying it showed that it can be delivered orally in animals with oral bioavailability of approximately 75 percent compared with subcutaneous administration. Another presentation showed omacetaxine reduced the number of leukemic stem cells in bone marrow by more than 80 percent in an animal model of chronic myeloid leukemia. Another presentation showed that the tyrosine kinase inhibitor imatinib mesylate did not reduce leukemic stem cell number, and it caused a rapid and dose-dependent reduction in the level of the key regulatory protein Mcl-1 in a cell model of CML. Mcl-1 levels were not reduced in the short term by imatinib mesylate. ? DermTech, of La Jolla, Calif., presented data on its noninvasive assay that distinguishes melanoma from benign moles showing the assay has 100 percent sensitivity and 90.6 percent specificity. The biomarker based on 20 target genes is being developed as part of the company's molecular-based approach that uses its Epidermal Genetic Information Retrieval technology to identify melanoma at the earliest stages of disease. ? Epigenomics AG, of Berlin, said it had confirmed previous data that DNA methylation biomarkers can be measured in urine samples to distinguish prostate cancer patients from healthy individuals using its differential methylation hybridization technology. A total of 26 biomarkers were validated successfully, a number of which specifically discriminate prostate cancer from benign prostate conditions such as benign prostatic hyperplasia, the company said. ? GenVec Inc., of Gaithersburg, Md., reported preclinical data showing that TNFerade, in combination with gemcitabine, resulted in superior antitumor activity compared to chemotherapy alone in pancreatic cancer models. ? Halozyme Therapeutics Inc., of San Diego, reported preclinical findings showing that its Pegylated-rHuPH20 enzyme in animal pharmacokinetic models demonstrated a more than 2,000-fold increase in plasma half-life compared to the unmodified enzyme. Among the data presented, PEGrHuPH20 significantly reduced tumor interstitial fluid pressure (IFP) in a dose-dependent fashion, achieving more than 85 percent reduction in IFP following intravenous administration. ? Infinity Pharmaceuticals Inc., of Cambridge, Mass., said preclinical data from a model of small-cell lung cancer showed that following treatment with chemotherapy, once-daily oral administration of IPI-926 leads to a statistically significant delay in tumor regrowth compared to vehicle control. Additional in vitro data showed that IPI-926 inhibits the growth of acute lymphocytic leukemia by targeting a rare progenitor cell population believed to have greater self-renewal than most tumor cells and thought to be a likely contributor to drug resistance in ALL patients. Another poster showed that IPI-926 inhibited Hedgehog target gene expression in the skin of adult mice, demonstrating the feasibility of using skin for pharmacodynamic assessment of activity. ? InNexus Biotechnology Inc., of Vancouver, British Columbia, presented new in vivo data that it said showed DXL625 is superior to a competing commercial anti-CD20 in reducing numbers of circulating B-cells. The animal model revealed no increased immunogenicity or toxicity associated with administration of DXL625 vs. the commercial anti-CD20. The company said it is preparing for a pre-investigational new drug meeting with the FDA and expects to begin a primate study later this year. ? Medivation Inc., of San Francisco, presented data from an ongoing Phase I/II clinical trial showing that the company's androgen receptor antagonist, MDV3100, continued to reduce serum levels of prostate-specific antigen in the lowest expanded dose group tested after three months of treatment. Overexpression of the androgen receptor is believed to contribute to the progression of castration-resistant prostate cancer. The declines were consistent with the inhibition of androgen receptor signaling. MDV3100 continued to be well tolerated in all dose groups. Medivation expects to report final top-line results this year, and if positive, it expects to seek FDA approval for a pivotal Phase III registration study in castration-resistant prostate cancer. In a separate presentation, Medivation reported clinical results of its Alzheimer's drug Dimebon, showing that it led to significant improvement in patients' ability to perform daily tasks over a one-year period compared to placebo. Those data stem from a pivotal study. ? Micromet Inc., of Bethesda, Md., presented data showing good bioavailability and predictable serum levels of subcutaneously administered BiTE antibodies, which are designed to direct the body's cytotoxic, or cell-destroying, T cells against tumor cells. The company also presented data showing that anticancer antibodies trastuzumab (Herceptin), cetuximab (Erbitux) and panitumumab (Vectibix) can be converted to BiTE antibodies. Also, a presentation of preclinical data of two new human BiTE antibodies targeting CD33 and MCSP showed they were equally potent in eliminating tumor cells expressing the respective target antigens. ? Oncolin Therapeutics Inc., of Houston, presented preclinical findings showing that 2-deoxy-2-fluoro-D-mannose induces Type II cell death in gliomas. Those data on sugar analogues showed positive activity against energy-starved tumors, in particular glioma cells lines, which the company described as additional proof that targeting energetic metabolism of cancer cells using glycolysis inhibitors is a promising treatment approach. ? Oncolytics Biotech Inc., of Calgary, Alberta, reported preclinical data showing that Reolysin in combination with radiation significantly enhanced efficacy compared to either treatment alone in terms of tumor regression and event-free survival in mice implanted with pediatric rhabdomyosarcoma and Ewing's sarcoma tumors. ? Oncothyreon Inc., of Bellevue, Wash., said data from preclinical studies of PX-478, an investigational small-molecule cancer therapy, demonstrated that PX-478 enhances the effect of radiation therapy in xenograft models of both glioma, a form of brain cancer, and pancreatic cancer. Oncothyreon currently is conducting a Phase 1 clinical trial of PX-478 in patients with advanced metastatic cancer. ? Paloma Pharmaceuticals Inc., of Jamaica Plain, Mass., reported data showing that Palomid 529 enhances antitumor activity caused by radiation therapy in prostate cancer models. Additional data showed that P529 inhibited tumor angiogenesis and selectively inhibited the Akt signaling pathway. ? Peregrine Pharmaceuticals Inc., of Tustin, Calif., said preclinical data showed that a mouse equivalent of the company's antiphosphatidylserine vascular targeting antibody, bavituximab, given in combination with chemotherapy demonstrated excellent signs of efficacy in a preclinical model of hormone-refractory prostate cancer. Specifically, the combination reduced primary tumor burden by 95 percent, and also reduced the metastatic spread of tumor cells. A separate poster described the mechanism of bavituximab and PGN635 (a fully human version of the bavituximab antibody), both of which affect the tumor microenvironment by enhancing production of the pro-inflammatory cytokines TNF-alpha and GM-SCF, while decreasing anti-inflammatory cytokines. In another presentation, Peregrine reported preclinical data showing that the vaccine-like ability of immunocytokine proteins combining its anti-PS antibodies and cytokines such as IL-2 to generate protective immune responses in a highly aggressive cancer model. ? Pharmacyclics Inc., of Sunnyvale, Calif., reported preclinical data showing that its histone deacetylase (HDAC)-8 inhibitor, PCI-24781, inhibited all forms of HDAC enzymes to target a broad range of cancers. Laboratory studies showed the drug inhibited NFkB, a transcription factor known to drive tumor growth, and was active in transgenic animal models of gallbladder cancer and other solid tumors. Treatment of animals with resistant gallbladder tumors that overexpress the ErbB2 protein, or HER2, led to control of tumors in 80 percent of the animals. ? Sangamo BioSciences Inc., of Richmond, Calif., presented positive data in a mouse tumor model from its ZFP Therapeutic program for the treatment of glioblastoma multiforme, a progressive and usually fatal brain cancer. The aim of a collaboration with the City of Hope is to use Sangamo's zinc finger DNA-binding protein nuclease gene modification technology to delete the GR in T-cells engineered to express zetakine. The specific deletion of GR in the zetakine-expressing, anti-glioma T-cells allows them to be used in the presence of glucocorticoids and to be developed as an allogeneic cell product immediately available to GBM patients. The data presented suggested the strategy is effective in animal models of the disease, and Sangamo expects to file an investigative new drug application for the cell therapy in 2008. ? Seattle Genetics Inc., of Bothell, Wash., presented preclinical data showing that SGN-75 is effective in targeting and delivering its auristatin drug payload into CD70-expressing tumors, where it is selectively retained as compared to normal tissues. Additional data demonstrated that the drug had potent antitumor activity in multiple solid tumor models, including renal-cell cancer. Data also were presented showing that SGN-33 is capable of increasing survival in multidrug-resistant-positive preclinical models of acute myelogenous leukemia that characteristically are resistant to chemotherapy. ? Spectrum Pharmaceuticals Inc., of Irvine, Calif., said data on a field study with SPI-1620 in dogs with spontaneously occurring tumors demonstrated evidence of selectively and transiently increasing blood flow. The company said the dog study is more predictive than transplanted tumors in rodents. In previous rodent model studies, Spectrum said it demonstrated that SPI-1620 enhances the efficacy of a wide variety of chemotherapeutics in different tumor models. SPI-1620 is currently in a Phase I clinical trial, and could have a range of applications for use in conjunction with radiation and chemotherapy in the treatment of cancer, the company said. ? Sunesis Pharmaceuticals Inc., of South San Francisco, presented nonclinical data on SNS-595's unique mechanism of action and its anticancer activity, showing it avoids common drug-resistance pathways and may have advantages over other topoisomerase poisons, the company said. The company said the data supported ongoing clinical trials of SNS-595 in platinum-resistant ovarian cancer and acute myeloid leukemia, and provided evidence for future studies of SNS-595 in indications such as breast cancer where topoisomerase II poisons. ? SuperGen Inc., of Dublin, Ireland, said S-110, its DNA methyltransferase inhibitor, improved in vivo efficacy of decitabine. The poster abstract highlights data indicating that S-110 showed robust antitumor activity in prostate and cisplatin-resistant ovarian carcinoma xenograft models. Additionally, S-110 restored sensitivity to cisplatin in the ovarian cancer model. Importantly, reduced toxicity was observed along with an increased half-life compared to decitabine. ? Trion Pharma GmbH, of Munich, Germany, presented data showing that its trifunctional antibody ertumaxomab had comparable efficacy to trastuzumab (Herceptin, Genentech Inc.) in the elimination of HER2-high-expressing target cells, but only ertumaxomab was able to kill HER2-low-expressing tumor cells. It also was able to sustain its killing activity at low effector-to-target cell ratios. ? ? Copyright ? 2008 Thomson BioWorld, All Rights Reserved. |