Alfacell Corp. presented in vivo and in vitro data showing Onconase inhibits tumor growth of non-small-cell lung cancer and breast cancer cells.
A poster presentation at the annual meeting of the American Association for Cancer Research in Los Angeles demonstrated Onconase significantly inhibited tumor growth by inducing apoptosis in A549 and NCI-H1975 human NSCLC cells, and MDA-MB-231 and MCF-7 human breast cancer cells, without damaging noncancerous cells such as HLF-1 human lung fibroblast and NCI/3T3 fibroblast. Data also indicated twice weekly injections were more effective than an equivalent single-dose injection in those tumor types.
Onconase (ranpirnase) is a drug candidate developed with Bloomfield, N.J.-based Alfacell's riboruclease technology. It is a natural protein isolated from the leopard frog. Trials of Onconase are ongoing in the lead indication, malignant mesothelioma, and other cancer types.
Alfacell's stock (NASDAQ:ACEL) gained 38 cents Monday, or 15.3 percent, to close at $2.87.
In other news from the AACR meeting, which ends Wednesday:
• Access Pharmaceuticals Inc., of Dallas, presented preclinical data on the activity of ProLindac, a DACH-platinum linked polymer compound. Certain data showed ProLindac effectively could substitute for oxaliplatin in combination therapies. In vivo studies reported elsewhere also demonstrated that much higher doses of ProLindac vs. oxaliplatin could be administered. Access currently is studying ProLindac in a Phase II monotherapy trial in patients with relapsed ovarian cancer.
• AEterna Zentaris Inc., of Quebec City, presented an abstract outlining the first in vitro data on its pyridopyrazine derivatives with high selectivity for PI3K inhibition. Data clearly showed that the compounds selectively inhibit PI3K, it said. Several derivatives from a second-generation series are undergoing initial pharmacokinetic in vivo studies.
• Amgen Inc., of Thousand Oaks, Calif., said results from a Phase III study of Aranesp (darbepoetin alfa) for treating anemia in patients with active cancer not receiving chemotherapy or radiotherapy showed that transfusion occurrences from weeks five to 17 favored Aranesp but were not statistically significant between the groups. The company reported in January that the trial had missed its primary endpoint of reducing red blood cell transfusions. Data showed that, among those receiving Aranesp, there was a significantly higher proportion of patients with a hemoglobin response, hemoglobin correction and hematopoietic response compared to placebo. The adverse event rate was similar between the groups, though the overall number of deaths was greater in the Aranesp group (48.5 percent vs. 46 percent in placebo.) (See BioWorld Today, Jan. 29, 2007.)
• Antisoma plc, of London, presented preclinical data supporting certain drug candidates. An evaluation showed synergy when Antisoma's vascular disrupting agent AS1404 was used with Avastin and paclitaxel in a lung cancer model. It also showed synergistic effect with Erbitux in a lung cancer model. It also said the aptamer drug AS1411 kills cells from a variety of cancer cell lines, and said it has potential for use with other treatments. AS1411 has completed Phase I development.
• AVAX Technologies Inc., of Philadelphia, presented initial results of its Phase I/II bridging trial of the autologous vaccine product M-Vax for patients with metastatic melanoma. The trial was to confirm that immunological responses induced by M-Vax were similar to those observed with an earlier version of the product. AVAX said it plans to initiate soon a Phase III registrational trial of M-Vax for treating metastatic melanoma.
• Biomira Inc., of Edmonton, Alberta, said it selected PX-866 as its next clinical development candidate. PX-866 is an inhibitor of the phosphatidylinositol-3-kinase (PI3 kinase)/PTEN/AKT pathway, a survival-signaling pathway activated in many types of human cancers. Biomira presented preclinical data demonstrating PX-866 has activity in an intracranial model of glioma. Treatment resulted in growth inhibition in three different glioma cell lines, with the magnitude dependent on the status of PTEN in the lines. An investigational new drug application filing for PX-866 is expected later this year.
• Bioniche Life Sciences Inc., of Belleville, Ontario, presented data showing that intraperitoneal administration of its Mycobacterial Cell Wall-DNA Complex results in significant anticancer activity against both micrometastases and macrometastases present in the peritoneal cavity of rats with colon cancer peritoneal carcinomatosis. The study evaluated the in vivo activity of MCC against microscopic and macroscopic peritoneal nodes after administration of rat PROb colon cancer cells in animals.
• Calando Pharmaceuticals Inc., of Pasadena, Calif., a majority-owned subsidiary of Arrowhead Research Corp., presented positive results from preclinical efficacy testing in mice with the siRNA therapeutic candidate CALAA-01. The product is a nanoparticle containing nonchemically modified siRNA and a transferrin protein-targeting agent. The product targets the M2 subunit of ribonucleotide reductase. An investigational new drug application filing is expected later this year, it said.
• Ciphergen Biosystems Inc., of Fremont, Calif., presented data on the discovery of several protein biomarkers that may be potential diagnostic markers in detection of early-stage ovarian cancer. The discovery involves four proteins in urine that separate women with early cancer from healthy women with a sensitivity of 56 percent and a specificity of 95 percent. Study participants included 288 women with epithelial ovarian cancer, 52 with early stage disease, 176 with late-stage disease, 74 with benign ovarian disease and 98 normal healthy controls. The findings suggest the possibility that those proteins, in combination with other biomarkers, could help in the diagnosis of early stage ovarian cancer, the company said. Ciphergen employed protein expression profiling methods to analyze the urine samples.
• EntreMed Inc., of Rockville, Md., presented preclinical data on its tubulin-inhibitor compounds. Results demonstrated a dose-dependent inhibition of tumor growth following the administration of ENMD-1420 (previously CC-5079) in two distinct preclinical models of metastatic lung and colorectal carcinoma. Data showed the compound had both anti-angiogenic and antiproliferative activity.
• ImClone Systems Inc., of New York, and Bristol-Myers Squibb Co., also of New York, reported detailed results from an open-label Phase III study comparing Erbitux (cetuximab) plus irinotecan to irinotecan alone in patients with metastatic colorectal cancer who failed first-line therapy. As previously announced, the primary endpoint was not met, but data from the secondary endpoints of progression-free survival and response rate were significantly higher in the Erbitux-treated group. The median time of survival without disease progression was improved by 54 percent in patients who received both Erbitux and irinotecan, which produced a 31 percent reduction in the risk of disease progression. Also, patients in the Erbitux arm were four times more likely to experience a 50 percent reduction in tumor size over patients treated with irinotecan alone.
• Innovive Pharmaceuticals Inc., of New York, said additional data from its clinical evaluation of INNO-406, an oral dual Bcr-Abl and Lyn-kinase inhibitor for Gleevec-resistant or intolerant chronic myelogenous leukemia, showed that the drug was well tolerated at doses up to 240 mg twice-daily in an ongoing Phase I study, and pharmacokinetic data indicated that the 240 mg dose achieves peak blood levels that are within the therapeutic window of activity. In heavily pre-treated patients, evidence of clinical efficacy was seen at doses of 120 mg twice-daily or less. Innovive also reported preclinical data showing that INNO-406 induces tumor cell death via variable pathways in Bcr-Abl-positive leukemic cells.
• Insert Therapeutics Inc., a Pasadena, Calif.-based majority-owned subsidiary of Arrowhead Research Corp., presented data on its Cyclosert delivery system, a nanoparticle drug transport platform. In vitro studies showed a tubulysin-Cyclosert conjugate to be effective against multiple human cancer cell lines. The conjugate was found to be stable and 100 times more water soluble than the free drug.
• Introgen Therapeutics Inc., of Austin, Texas, reported updated Advexin biomarker data showing that abnormal p53 was shown to correlate with increased survival and tumor responses following Advexin treatment. Those data came from Phase II trials and involved 28 patients with recurrent head and neck cancer. Data showed that the median survival of patients with tumors expressing the abnormal p53 biomarker was 11.6 months compared to 3.5 months in patients whose tumors has normal p53. The abnormal biomarker also was associated with a statistically significant increase in tumor responses to Advexin therapy.
• Kosan Biosciences Inc., of Hayward, Calif., presented safety data from preclinical and clinical studies of its lead Hsp90 inhibitor, tanespimycin (KOS-953). Serial electrocardiogram monitoring from more than 85 patients in Phase I trials showed no effect on QTc interval in those patients. The company concluded two previously reported incidents of possible QTc interval effects were not drug related. The heat shock protein 90 inhibitor is being taken into a registrational program in multiple myeloma patients. Kosan separately said preclinical data on KOS-1803, a next-generation epothilone, showed a high level of antitumor activity and a favorable pharmacokinetic and safety profile in a range of in vitro tests and in vivo cancer models.
• Onconova Therapeutics Inc., of Lawrenceville, N.J., presented preclinical data showing that ON 01910 Na, a targeted, small-molecule, cancer compound, had broad spectrum antitumor activity against both solid tumors and hematological malignancy. One study using a nude mouse model system and human liver, hormone-refractory prostate, melanoma, pancreatic and colon tumors, showed single-agent activity for ON 01910 Na, with the drug's effect enhanced in combination with oxaliplatin. Results from a Phase I study of the drug demonstrated preliminary signs of clinical activity. Onconova is planning multiple Phase II trials and combination Phase I trials with ON 01910 Na.
• Peregrine Pharmaceuticals Inc., of Tustin, Calif., reported preclinical data showing that its monoclonal antibody, 2C3, which is designed to selectively block vascular endothelial growth factor (VEGF) from binding to the second of two VEGF receptors, demonstrates anticancer efficacy in an orthotopic model of pancreatic cancer. Data indicated that treatment with 2C3 reduced the growth of pancreatic tumors by 90 percent, and researchers said data from the compound, which blocks only VEGF receptor 2 compared favorably to that of Avastin (Genentech Inc.), which blocks VEGF binding to both receptors 1 and 2. Peregrine intends to begin clinical testing of 2C3 as soon as next year.
• Rigel Pharmaceuticals Inc., of South San Francisco, presented four research projects aimed at identifying small-molecule inhibitors of select kinases as potential therapeutics for certain cancers and other disorders. One poster focused on inhibitors of the Axl receptor tyrosine kinase. Others targeted Janus tyrosine kinase 2 (JAK 2), polo-like kinase 1 (PLK 1) and protein kinase C-related kinase 1 (PRK-1). Rigel anticipates that small-molecule candidates inhibiting those targets, and others, will form a sequential series of investigational new drug candidates in oncology.
• Sunesis Pharmaceuticals Inc., of South San Francisco, said nonclinical data demonstrated apoptotic activity of SNS-032 in a multiple myeloma model, and reported that the drug acted through inhibition of cyclin-dependent kinases (CDKs) 2, 7 and 9 to block both the cell cycle and transcription to drive apoptosis in multiple myeloma cells upon exposure for six hours. Researchers also noted that exposure to SNS-032 induced down-regulation of anti-apoptotic factors, cell survival proteins and growth factors that drive the disease. SNS-032, a selective inhibitor of CDKs 2, 7 and 9, is in Phase I testing in B-cell malignancies.
• Tapestry Pharmaceuticals Inc., of Boulder, Colo., said preclinical studies of TPI 287 demonstrated that the orally available, next-generation taxane crosses the blood-brain barrier in rodents. It also demonstrated single-agent activity and additive activity with temozolomide in an orthotopic model of glioblastoma. In addition, the drug demonstrated significant cytotoxic activity when administered either orally or intravenously. Tapestry plans to initiate multiple Phase II trials of TPI 287 this year.
• Tristar Technology Group LLC, of Rockville, Md., said its collaborator, the University Medical Center Hamburg-Eppendorf in Germany, discovered that 20 percent of women with breast cancer carry extra copies of a particular gene, ESR1, or estrogen receptor alpha. It also said those patients are more likely to respond positively to the estrogen-blocking drug tamoxifen than patients who do not carry extra copies of the gene. Research was carried out using Tristar's high-throughput tissue analysis platform.
• Ziopharm Oncology Inc., of New York, presented preclinical data on indibulin (ZIO-301) demonstrating it has distinct biologic and molecular properties from other tubulin-binding agents, and suggesting a very different toxicity profile, particularly with regard to peripheral neuropathy. While indibulin binds to tubulin in general, it does not bind to neuronal-specific tubulin and does not disrupt normal axonal microtubules in vitro, likely accounting for the difference with regard to neurotoxicity, it said. In separate news, Ziopharm reported preclinical data for an orally active form of ZIO-201 (isophosphoramide mustard) demonstrating the drug's oral bioavailability and activity in a variety of cancer models, including those with ifosfamide- and cyclophosphamide-resistant tumors.