Peregrine Pharmaceuticals Inc. reported a slew of news at the American Association of Cancer Research meeting.
Preclinical data showed that the Tustin, Calif.-based company's 2C3 antibody significantly inhibited the growth of blood vessels in a metastatic breast cancer tumor model. The product, an inhibitor of vascular endothelial growth factor, suppressed the formation of blood-transporting vessels and lymphatic vessels by 70 percent and 85 percent, respectively.
Other data showed that a fusion protein that includes interleukin-2 and NHS76, a human monoclonal antibody produced through Peregrine's Tumor Necrosis Therapy (TNT) technology platform, retained functional activity of IL-2 and had a very low toxicity profile in animal studies. TNT-directed cytokines are under development by Merck KGaA, of Darmstadt, Germany, through a licensing agreement with Peregrine.
Additional findings demonstrated that a fusion protein comprised of VEGF and the toxin gelonin inhibited blood vessel tube formation and the growth of breast cancer metastatic tumors. The VEGF construct is part of a vascular targeting agent compound family that Peregrine has licensed to SuperGen Inc., of Dublin, Calif.
The 95th AACR conference, which began Saturday in Orlando, Fla., continues through today.
In other news from the meeting:
• Agennix Inc., of Houston, said preclinical studies demonstrated the anticancer activity of recombinant human lactoferrin (rhLF). Monotherapy of a squamous-cell carcinoma in a syngeneic murine model caused a 66 percent tumor growth inhibition that was statistically significant compared to placebo (p<0.01) and comparable to that obtained by therapy with Cis-platinum, docetaxel or radiotherapy. Mice receiving both rhLF and Cis-platinum showed a statistically significant improvement over either drug alone. Tumor growth inhibition with oral rhLF also was observed in a murine renal-cell carcinoma model (p<0.01). In a mammary adenocarcinoma model, oral rhLF also induced tumor shrinkage including complete rejection of established tumors.
• Ariad Pharmaceuticals Inc., of Cambridge, Mass., reported preclinical results showing that its lead mTOR inhibitor, AP23573, augments the anticancer activity of widely used cytotoxic and new anticancer agents when given in combination. Included in the studies are imatinib (Gleevec), trastuzumab (Herceptin) and an EGFR inhibitor, as well as other chemotherapy drugs. Phase I trials of AP23573 in patients with advanced cancers are under way, with Phase II studies expected to begin this quarter.
• Can-Fite BioPharma Ltd., of Petach-Tikvah, Israel, said interim Phase II results showed that treatment with CF101 in 56 colorectal cancer patients resulted in stable disease in 20 who continued after eight weeks. Of them, six were stable after 16 weeks and two remained stable and continued after 24 weeks. In addition, confirming data showed CF101 to be safe and without side effects in therapeutic doses.
• Cell Genesys Inc., of South San Francisco, said preclinical results showed that CG5757, a virus designed to replicate preferentially in and kill cancer cells, demonstrated statistically significant antitumor efficacy in mouse tumor models of lung and bladder cancer, reducing tumor growth rates by 81 and 88 percent, respectively. The virus, derived from adenovirus, is controlled by two gene switches that enable it to grow selectively in and destroy cancer cells. The data showed that about 1,000 to 100,000 cancer cells were killed for every normal cell.
• CuraGen Corp., of New Haven, Conn., reported preclinical data demonstrating that a single dose of CG53135 was able to confer a significant benefit to in vivo models receiving total body irradiation. The product is in Phase I to investigate its use in protecting and repairing oral mucosa from injury caused by chemotherapy and radiation therapy. The company also plans to move the compound into Phase I studies for inflammatory bowel disease.
• Hybridon Inc., of Cambridge, Mass., said preclinical data showed its immunomodulatory oligonucleotide (IMO) compounds inhibited tumor growth in mouse models of cancer. In one study, IMO monotherapy was shown to inhibit tumor growth in a syngeneic mouse melanoma model. Separately, when combined with Herceptin in a mouse model of human breast cancer or Rituxan in mouse models of non-Hodgkin's lymphoma, the IMO potentiated the effectiveness of both monoclonal antibodies.
• Geron Corp., of Menlo Park, Calif., said preclinical data confirmed and extended the efficacy of GRN163L in solid tumors, specifically liver and ovarian cancer. In tissue culture, the compound inhibited telomerase in all four ovarian tumor cell lines, and caused telomere loss and cell death in three of the four. In addition, in a mouse model of human ovarian cancer, it was demonstrated that GRN163L inhibited growth in a dose-dependent manner. Separately, GRN163L was on average about 10 times more potent than GRN163 in inhibiting telomerase activity in cultured tumor cells. For two hepatoma lines in the panel, GRN163L was seven and 18 times more potent.
• Introgen Therapeutics Inc., of Houston, reported combined safety and efficacy results based on three multicenter, multinational Phase II trials of Advexin p53 gene therapy in 217 patients with recurrent squamous-cell carcinoma of the head and neck. The objective overall response rate of Advexin monotherapy was 10 percent (complete and partial response with greater than 50 percent reduction in tumor size). Tumor growth control (stable disease or better) was achieved in 59 percent of treated lesions. The product remains in two Phase III head and neck cancer trials.
• Lorus Therapeutics Inc., of Toronto, said an analysis of tumor samples from Virulizin-treated mice showed an increase in the presence of both macrophages and NK cells within the tumor tissue, as compared to tumor tissue from saline-treated mice. The response appeared to occur early in the treatment cycle and correlated with increased markers for programmed cell death within the tumors. Removal of macrophages from mice resulted in decreased numbers of NK cells in tumor samples, and NK-deficient mice did not respond to Virulizin treatment. The product is in a pivotal Phase III trial for pancreatic cancer, in combination with gemcitabine.
• MaxCyte Inc., of Rockville, Md., said it reported the results of a study that focused on its generation of a dendritic cell-based cancer vaccine using whole tumor lysate.
• Maxim Pharmaceuticals Inc., of San Diego, reported preclinical results demonstrating that treatment with MX116407 as a single agent produced tumor regression in lung cancer animal models. The compound also produced a statistically significant enhancement of antitumor activity when combined with existing cytotoxics that it said was superior to the activity of other vascular targeting agents in development. MX116407 has been shown to induce apoptosis in cancer cells and in several animal efficacy xenograph models, including models of breast, lung and colorectal cancer.
• MethylGene Inc., of Montreal, presented a poster describing the role of histone deacetylase 1 (HDAC1) in oncology, describing how specific inhibition of HDAC1 leads to growth arrest and apoptosis in human cancer cells but not in normal cells. Using functional genomics and isotypic pharmacology, the company has identified cancer-causing HDAC isoforms. MethylGene described its research in understanding the biological role of HDACs in cancer and in designing small-molecule isotype-selective HDAC inhibitors.
• NeoPharm Inc., of Lake Forest, Ill., launched NeoPhectin-AT, an in vivo agent for use in animal testing and target validation of drug product candidates. Designed for in vivo transfection, target validation and drug development, it uses the company's cationic cardiolipin.
• Point Therapeutics Inc., of Boston, said data on its lead product candidate PT-100 demonstrated preclinical tumor growth suppression and enhancement of antitumor activity when combined with the chemotherapy agents gemcitabine or docetaxel. Every dose of gemcitabine in the study (30mg/kg, 60 mg/kg and 120 mg/kg) showed significantly (p<0.05) greater antitumor effect when combined with PT-100 than either agent alone. Combination treatment caused rejection in 40 percent to 50 percent of mice by day 25 after tumor inoculation. Treatment with PT-100 and docetaxel in mice bearing human non-small-cell lung carcinoma xenografts resulted in an 88 percent reduction in tumor size by day 50 after tumor inoculation, compared to reductions of 66 percent and 50 percent, respectively, in mice treated with PT-100 and docetaxel as single agents.
• Telik Inc., of Palo Alto, Calif., said preclinical results support the advancement of Telcyta's (TLK286) clinical development to the front-line and second-line treatment settings. The addition of the drug to various chemotherapeutics resulted in synergy or enhanced inhibition of cancer cell growth, compared to either Telcyta or the other drugs alone. Other data demonstrated the drug is not cross resistant with paclitaxel, and that Telcyta treatment restored sensitivity to paclitaxel in resistant cancer cells. The product is in Phase III for resistant ovarian cancer and non-small-cell lung cancer.
• Zonagen Inc., of The Woodlands, Texas, reported data indicating Progenta's potential in treating breast cancer. Use of the drug reduced the size of established tumors significantly in mice and prevented the appearance of new tumors over the treatment period. The antitumor effects seen with Progenta correlated with suppression of growth and increased apoptosis by immunohistochemistry. The company is preparing documentation to seek approval to begin a European-based Phase I/II study of Progenta for uterine fibroids.