Investors took to news released by OxiGene Inc. at the 95th American Association for Cancer Research meeting in Orlando, Fla.
Shares in the Waltham, Mass.-based company gained 15.5 percent Monday on preclinical findings that pointed to the efficacy of its lead second-generation vascular targeting agent (VTA), OXi4503, in several human cancer models.
In research conducted at Lund University in Sweden - evaluating OXi4503 with standard-of-care chemotherapy drugs carboplatin and paclitaxel in the MDA-MB-231 human breast adenocarcinoma and the ES-2 ovarian carcinoma models grown in mice - OXi4503 doses ranging from 10 mg/kg to 50 mg/kg significantly enhanced the antitumor effects of the chemotherapeutic agents. At doses higher than 10 mg/kg, tumor growth was completely repressed, while doses above 25 mg/kg triggered tumor regression.
In another study, conducted at the University of South Florida in Tampa and the University of Florida in Gainesville, researchers concluded that OXi4503 not only shuts down blood flow to tumors, but also might play a direct role in killing tumor cells, suggesting that the VTA could be used as a single-agent therapy. Their study measured OXi4503's efficacy and histopathologic effects in rodent KHT and human KSY sarcoma models as well as in a Caki-1 model of human renal-cell carcinoma. They determined that, 24 hours after treatment with a 25-mg/kg dose of OXi4503, fewer than 6 percent of the KHT tumor cells remained viable. While cell death was evident in skeletal muscle infiltrated by the tumor, the researchers said adjacent uninvolved muscle and soft-tissue remained viable. The compound also caused significant delays in tumor growth.
OxiGene's stock (NASDAQ:OXGN) gained $1.28 to close at $9.54.
The AACR conference, which began Saturday, continues through Wednesday. In other news from the meeting:
• Altor BioScience Corp., of Miramar, Fla., said findings published in next month's issue of Cancer Immunology, Immunotherapy reveal significant advances in its soluble T-cell antigen receptor (STAR) technology program. The company found that a tumor antigen-specific T-cell receptor linked to interleukin-2 exhibited favorable pharmacokinetics and provided a substantially increased half-life for the IL-2 portion of the molecule. Collaborators at the Florida Hospital Cancer Institute in Orlando showed that the fusion protein was capable of reducing lung metastases in an experimental tumor model. Separately, Altor was awarded a Small Business Innovation Research grant to support development of STAR reagents for tumor diagnostic applications.
• Ariad Pharmaceuticals Inc., of Cambridge, Mass., said AP23464 was effective in blocking the growth of leukemia cells that harbor any of 30 different mutations in the Abl protein that confer resistance to Gleevec (imatinib), a standard treatment for chronic myelogenous leukemia. Data show that AP23464 effectively suppressed even those leukemia cells containing robust and common Gleevec-resistant mutants and provided further support for the clinical development of AP23464 in patients failing Gleevec therapy. The research was conducted at Harvard Medical School.
• Array BioPharma Inc., of Boulder, Colo., reported preclinical results showing that ARRY-142886 (AZD6244) has nanomolar activity against isolated MEK enzyme and numerous cancer cell lines. The product has demonstrated oral efficacy in several tumor xenograft models of human cancer. The MEK inhibitor is in clinical development. AstraZeneca plc, of London, has exclusive, worldwide rights to ARRY-142886 and related intellectual property for oncology indications.
• Attenuon LLC, of San Diego, said preclinical data demonstrated that treatment with ATN-161 significantly slowed the progression of primary tumors and completely inhibited the growth of well-established bone metastases. Researchers from McGill University found that in animals infused intravenously with placebo or ATN-161 for six weeks, tumors in animals receiving ATN-161 grew significantly more slowly than tumors in animals receiving placebo. The product is in Phase I trials at the Fox Chase Cancer Center in Philadelphia.
• Avanir Pharmaceuticals Inc., of San Diego, reported in vitro data showing that AVP-893 and four related analogues possess potent anti-proliferative activity and are most potent against melanoma, leukemia, breast, prostate, kidney and central nervous system tumor types. The compounds appear to work through the Golgi apparatus to inhibit tumor growth, the company said, adding that they are active alone or in combination with established chemotherapy in several in vivo tumor models.
• Cell Genesys Inc., of South San Francisco, reported that GVAX cancer vaccine and docetaxel chemotherapy exhibited synergistic antitumor activity when tested in a mouse tumor model. Those treated with GVAX and intravenous docetaxel chemotherapy demonstrated a statistically significant, 68 percent improvement in duration of survival (52 days; p=0.014), compared to mice that received subtherapeutic doses of the vaccine alone (31 days). The median survival for mice treated with docetaxel alone or mice treated with a saline control was in both cases 24 days. The product is in a Phase III development program.
• Coley Pharmaceutical Group Inc., of Wellesley, Mass., said preclinical data revealed that one of its TLR9 agonist investigational drugs strongly enhanced the response of tumors to radiation therapy. The combination of an investigational CpG TLR9 agonist with local tumor irradiation dramatically reduced tumor growth, and three of seven mice achieved complete cure and survival; neither radiation therapy nor CpG alone is highly effective in the model. The CpG enhancement of tumor radioresponse was greatly reduced when tested in immune-compromised mice, indicating that the radiation enhancement was mediated by immune activation. The animal studies were conducted at the University of Texas M.D. Anderson Cancer Center.
• CombinatoRx Inc., of Boston, said CRx-026 demonstrated anti-proliferative and cytotoxic effects across a spectrum of human cancer cell lines. The syncretic anti-mitotic agent achieved a synergistic anticancer effect through a coordinated inhibition of the mitotic kinesin, hsEg5/KSP, and the PRL phosphatases. The company has integrated the components of CRx-026 into a compound that has advanced into clinical studies.
• Dendreon Corp., of Seattle, reported updated Phase I trial results showing that APC8024 continued to demonstrate clinical benefit and statistically significant T-cell immune responses in patients with advanced, metastatic, HER-2/neu-positive breast cancer. Results from 18 patients were presented. Clinical benefit was demonstrated in 22 percent of patients treated with APC8024, including three patients with prolonged stabilization of disease. Dendreon said long-term follow-up on the patients indicated they experienced stabilization of their disease for 15, 20 and 22 months following treatment with APC8024, without requiring additional chemotherapy.
• Ecopia BioSciences Inc., of Montreal, reported preclinical data that revealed the chemical structure of ECO-04601, as well as findings that further support previously reported results showing tumor growth inhibition in a mouse model of glioma. In addition, the data revealed that the compound was well tolerated following oral and parenteral administration, even in chronic treatment regimens.
• EntreMed Inc., of Rockville, Md., reported that three months following administration with ENMD 0996, preclinical animal models showed inhibition of metastases. Data demonstrated that ENMD 0996 specifically blocks the activity of basic fibroblast growth factor (FGF-2), a naturally occurring protein that stimulates angiogenesis, but had no effect on other angiogenesis stimulators. Additionally, ENMD 0996 caused an activation of specific immune cells in response to FGF-2. Those activities might contribute to the compound's antitumor effects. To date, ENMD 0996 has not shown evidence of toxicity in preclinical models or an effect upon normal physiology specifically related to wound healing and reproduction.
• Exelixis Inc., of South San Francisco, described the identification of two enzyme targets that play a functional role in key signaling pathways involved in cancer. The company also showed how one of the targets lies at the intersection of the PTEN and beta-catenin signaling pathways, which has implications on which patient populations to target with drugs designed to inhibit those kinases. Exelixis is generating small-molecule inhibitors against the targets as potential cancer agents.
• GPC Biotech AG, of Martinsried, Germany, said treatment with RGB-286199 resulted in cell-cycle arrest and apoptosis in a range of tumor cells in culture. The compound also was shown to be efficacious in human xenograft tumor models. RGB-286199 has been shown to inhibit several cyclin-dependent kinases, and impacts several signal transduction pathways by inhibiting a number of non-cyclin-dependent kinases. Preclinical data demonstrated the efficacy of a monoclonal antibody called 1D09C3 against hematological malignancies, including non-Hodgkin's, Hodgkin's and Burkitt lymphomas, multiple myeloma, chronic lymphoid leukemia and hairy-cell leukemia. In addition, 1D09C3 was shown to induce death in certain melanoma cells. Findings from other studies showed that satraplatin kills prostate cancer cells in several human prostate cancer cell lines. The product is partnered with Spectrum Pharmaceuticals Inc., of Irvine, Calif.
• Immunomedics Inc., of Morris Plains, N.J., and its IBC Pharmaceuticals Inc. subsidiary reported an advance in pretargeting technology involving radioimmunotherapy, whereby the selective targeting of a tumor with a bispecific antibody is separated from the second step of delivering a therapeutic isotope. They reported on the construction of a trivalent fusion protein in which two binding sites attach to carcinoembryonic antigen and the third binding site attaches to a specific peptide that can be labeled with a variety of isotopes or drugs. In an animal model of transplanted human colon cancer, the pretargeting procedure with those agents resulted in a tumor-blood ratio of 33.5 at three hours following injection of the radiolabeled peptide, increasing to 110.7 at 24 hours.
• Kosan Biosciences Inc., of Hayward, Calif., said in vitro data on 17-AAG pointed to the Hsp90 inhibitor's cytotoxic and anti-proliferative effects when used in combination with 20 different standard and new chemotherapeutics. Findings demonstrated synergistic activity consistent with the mechanism of action of Hsp90 inhibition. Clinical investigation of several of those combinations is ongoing.
• Ligand Pharmaceuticals Inc., of San Diego, said findings support enhanced activity of chemotherapeutic agents in combination with Targretin (bexarotene) in non-small-cell lung cancer. A combination of Targretin and different therapeutic agents produced a combined arrest of NSCLC cell tumor growth larger than each single agent alone. Separately, Targretin was shown to prevent or reverse acquired tumor cell resistance to Taxol (paclitaxel) in NSCLC and advanced human breast cancer cell lines. Different regimens of sequential and/or continuous combined treatment of Taxol with Targretin resulted in the prevention and/or reversal of acquired resistance to Taxol.
• MedImmune Inc., of Gaithersburg, Md., and Cerus Corp., of Concord, Calif., said preclinical results demonstrated the effectiveness of a new therapeutic vaccine technology in suppressing the growth of certain tumors. The conclusion stems from a study in which company researchers implanted mice with tumors and then treated them with Listeria strains that had been genetically engineered to trigger an immune response directed at the EphA2 protein. Protective immunization with Listeria-huEphA2 significantly suppressed tumor growth in the study and prolonged survival for treated mice. Also, 80 percent of the Listeria-huEphA2-treated mice survived more than 43 days following tumor implantation, whereas untreated controls had a median survival time of about 20 days.
• MethylGene Inc., of Montreal, said that specific inhibition of DNMT1 by MG98 resulted in significant cancer-growth inhibition in a variety of human gastric cancer cell lines. Associated with growth impairment was concomitant re-expression of multiple methylation-silenced tumor suppressor genes including p16ink4a and RUNX3. In addition, MG98 inhibited growth of malignant tissue in mice previously implanted with human gastric cancer tumors. Separately, researchers from the Cleveland Clinic and MethylGene reported that in interferon-resistant renal cancer cells, MG98 treatment reactivated a methylation-silenced tumor-suppressor gene called RASSF1A and sensitized the cancer cells to apoptosis in response to subsequent interferon challenge. Human genome array analyses also demonstrated that three genes that were upregulated in the renal cancer cells by MG98 treatment are implicated in apoptosis.
• NeoPharm Inc., of Lake Forest, Ill., said data detailed its new Tandem Technology for entrapping two drugs in a single liposome for combination therapy. In a poster describing the combination of liposomal paclitaxel and either doxorubicin or mitoxantrone into a single liposomal delivery system using NeoPharm's NeoLipid technology, the company showed that two cancer drugs can be co-entrapped without any compromise in the stability or entrapment efficiencies of the loaded drugs. Preliminary studies of liposomal paclitaxel and doxorubicin on tumor-bearing mice showed promising results in overcoming resistant cancers. Separate preclinical data on a new formulation of LErafAON (liposome entrapped c-raf antisense oligonucleotide) pointed to its anticancer effects against several mouse tumor models.
• Nereus Pharmaceuticals Inc., of San Diego, said preclinical data demonstrated that NPI-2358 induces tubulin depolymerization in vitro and tumor vascular collapse in vivo. The company expects to file an investigational new drug application for its lead product with the FDA later this year. Separate findings from its NPI-0052 program demonstrated the compound's potential use in treating cancer and inflammation.
• Peregrine Pharmaceuticals Inc., of Tustin, Calif., said preclinical data demonstrated that its anti-phospholipid antibody 3G4 significantly enhanced the efficacy of chemotherapy. Data showed that treatment with a combination of 3G4 and docetaxel resulted in a 93 percent inhibition of human breast cancer growth in such models. Peregrine has developed a chimeric 3G4 analogue that it is developing under the trade name Tarvacin, which is expected to enter human studies later this year. The preclinical research was conducted at the University of Texas Southwestern Medical Center in Dallas.
• Pharmacyclics Inc., of Sunnyvale, Calif., said findings from several preclinical studies demonstrated the mechanism of action and rationale for ongoing clinical trials with its lead investigational drug Xcytrin (motexafin gadolinium) in hematologic and other cancers. Three studies showed that the product is cytotoxic to various lymphoma and myeloma cell lines in vitro. Also, Xcytrin was found to be synergistic with several other commonly used agents for those types of cancers, such as Rituxan and Velcade.
• Transgenomic Inc., of Omaha, Neb., said several of its customers from worldwide research institutes reported findings in which the company's WAVE System played a role. Specific scientific applications include mutation detection, analysis of DNA methylation, microsatellite instability and loss of heterozygosity.