Titan Pharmaceuticals Inc. presented preclinical study results on its cancer drug Pivanex at the 94th annual meeting of the American Association for Cancer Research held in Washington.
Results showed the drug, which is designed to act by inhibiting histone deacetylases, in combination with docetaxel increased antitumor activity in non-small-cell lung cancer. Two non-small-cell lung cancer cell lines were treated with Pivanex alone, docetaxel alone and Pivanex plus docetaxel. The results showed the combination resulted in enhanced tumor cell death in comparison to either single treatment.
A previous Phase II open-label study in non-small-cell lung cancer using Pivanex as a single agent showed "encouraging" tumor response and survival data, Titan said. Based on earlier studies and in vitro and in vivo research that showed the positive effects of combining Pivanex and docetaxel, Titan, of South San Francisco, began a Phase IIb combination study in second-line treatment. The ongoing study is expected to enroll 225 patients at more than 50 sites.
Titan's stock (AMX:TTP) rose 15 cents Monday to close at $2.51.
In other news from the meeting:
Ariad Pharmaceuticals Inc., of Cambridge, Mass., presented results of preclinical studies demonstrating the potential benefits AP23841 to treat cancer that has spread to bone. It is designed to block both tumor growth and bone destruction through the inhibition of the activity of mTOR, it said.
Avanir Pharmaceuticals Inc., of San Diego, said AVP-893 showed selective growth inhibition against a variety of cancer cell lines in preclinical testing and early compound screening performed by the National Cancer Institute in Bethesda, Md. The data demonstrated that animal tumor models responded to AVP-893 or an analogue with effects ranging from inhibition of growth to ablation of the tumor. In addition to its effect on the growth of the primary tumor, AVP-893 appears to inhibit metastatic spread of certain tumors, it said.
Cell Therapeutics Inc., of Seattle, presented data on a cancer target, LPAAT-beta. LPAAT-beta produces phosphatidic acid, a cofactor for molecules in the Raf and mTOR pathways. CTI scientists found that although LPAAT-beta is minimally expressed in most normal tissue, it is highly expressed in most solid tumors, including lung, ovarian, prostate, bladder and cervical, as well as in leukemias and lymphomas. Preclinical research has indicated that the inhibition of LPAAT-beta by genetic knockdown with RNAi leads to tumor cell death through apoptosis, it said.
Cyclacel Ltd., of Dundee, UK, reported that CYC202 (R-roscovitine), its lead CDK inhibitor drug candidate, appears to induce cancer cell apoptosis in patients receiving the drug. Biomarker analysis of blood samples from cancer patients treated with CYC202 demonstrated that 14 of 26 analyzed tested positive for apoptosis following single-agent treatment with the drug. Also, seven CYC202 Phase I patients with various tumors, including pancreatic and lung cancer, experienced tumor stabilization.
Dendreon Corp., of Seattle, presented updated results from its ongoing Phase I trial of APC8024, its immunotherapy for breast, colon and ovarian cancer. Results indicated APC8024 is showing continued clinical benefit and targeted T-cell immune responses in patients with advanced metastatic Her-2-positive breast cancer. Also, results were presented for the first time that demonstrated a durable immune response could be boosted by retreatment with APC8024.
EntreMed Inc., of Rockville, Md., presented preclinical data from three studies of Panzem (2-methoxyestradiol, or 2ME2), its lead clinical drug candidate, demonstrating anticancer activity and lack of toxicity. In the first study, investigators concluded that at the molecular level Panzem inhibits microtubules and HIF (hypoxia inducible factor 1 alpha) without associated toxicity. Data from the second study showed that Panzem inhibited tumor growth in an animal model of breast cancer. Resistant cell line data produced from a third Panzem study will be used for the elucidation of the mechanisms of actions and selection of lead drug candidates from new chemical entities based on 2ME2-related structures, it said.
Exact Sciences Corp., of Marlborough, Mass., presented data suggesting that the incorporation of Effipure technology into its PreGen-Plus assay would likely result in an increase in sensitivity of the assay, although it said further studies need to be performed to confirm the results. Effipure will be incorporated into the version of PreGen-Plus that Exact and Laboratory Corp. of America Holdings expect to make commercially available in the third quarter.
Geron Corp., of Menlo Park, Calif., presented preclinical data on both the safety and stability of its telomerase inhibitor cancer drug, GRN163. The results demonstrated safety and tolerability of daily intravenous dosing in rats for four weeks and, in a separate study, in dogs for seven days, as well as good tolerability of continuous intracranial delivery for the same time periods in both species. Also, a series of stability studies demonstrated that GRN163 has appropriate stability in both liquid and powder formulations.
Hybridon Inc., of Cambridge, Mass., presented data from the Phase I trial of GEM231, its second-generation antisense compound. The study was designed to evaluate safety and effects on extracellular protein kinase A as a potential biomarker of GEM231 activity and had "promising" results, the company said. Also, Hybridon and Aegera Therapeutics Inc., of Montreal, selected a XIAP antisense oligonucleotide, AEG35156/GEM640, as a development candidate. The drug showed antitumor activity in cell-based assays and human tumor xenograft models of lung, breast, ovarian, prostate and colorectal cancer, they said. In September, Hybridon and Aegera entered an agreement that combined Hybridon's antisense technology with Aegera's target, the X-linked Inhibitor of Apoptosis Protein.
Igeneon AG, of Vienna, Austria, presented data on IGN311, which showed its mechanism of action might be broader than originally thought, and that it includes features similar to growth factor receptor-specific antibodies. It also presented results of a multiarray analysis showing the co-expression of Igeneon's target antigens Lewis Y and EpCAM in breast cancer correlates with poor prognosis, thus supporting the selection of the targets, it said.
ImClone Systems Inc., of New York, presented preclinical data highlighting progress in several pipeline programs. It presented a number of abstracts at the conference, including presentations on monoclonal antibody therapeutics being developed as angiogenesis and growth factor inhibitors, such as its VEGF receptor-1 program, IGF-1 receptor research, VE-cadherin research and its VEGF receptor-2 program.
Insmed Inc., of Richmond, Calif., reported data from recent studies of its recombinant human insulin-like growth factor binding protein-3. The study was designed to examine the effect of rhIGFBP-3 in three solid tumor models: lung, breast and colon, with the objective of determining the therapeutic capability of rhIGFBP-3 in human trials. In summary, rhIGFBP-3 exhibited single-agent and/or combinatorial antitumor effects in all three solid tumor models, it said. No signs of rhIGFBP-3 toxicity were noted in any of the animal studies.
Introgen Therapeutics Inc., of Austin, Texas, presented preclinical data that had previously been published in the first edition of the 2003 Proceedings of the AACR. Introgen researchers and scientists from the M.D. Anderson Cancer Center looked at the antitumor activity of INGN 241 and the methods in which ovarian cancer cells were killed. INGN 241-treated cells express high levels of MDA-7 protein, which suppressed the growth of the ovarian cancer cells as well as induced the death of the cells, Introgen said. Ad-mda7 treatment induced high levels of apoptosis in ovarian cancer cells, but not normal cells. Also, molecules involved in cell death pathways were induced by the drug in tumor cells but not normal cells.
Kosan Biosciences Inc., of Hayward, Calif., presented results of a preclinical study of 17-allylamino-17-demethoxygeldanamycin (17-AAG). Study findings demonstrated that 17-AAG and 5-fluorouracil (5-FU), administered in combination against human colon cancer cell lines, results in a synergistic growth-inhibiting effect. It also presented results of two preclinical studies of KOS-862 (Epothilone D). The studies assessed the oral bioavailability of KOS-862 and the synergistic antitumor effects of KOS-862 in combination with 5-FU. KOS-862 is in three Phase I studies, and initiation of Phase II trials is planned in the second half of 2003, it said.
Oxford BioMedica plc, of Oxford, UK, presented clinical data on TroVax. Following an earlier Phase I/II trial in colorectal cancer patients using intramuscular delivery, the company conducted a five-patient Phase I/II study to evaluate intradermal delivery of TroVax as an alternative method of administration. All primary endpoints of the intradermal study were achieved, Oxford said.
Peregrine Pharmaceuticals Inc., of Tustin, Calif., said researchers at the University of Texas Southwestern Medical Center at Dallas presented six poster sessions on vascular targeting agents (VTA). The presentations covered various aspects of Peregrine's VTA technology platform and highlighted the potential of the approach to treating solid tumors. More specifically, researchers at the university and at the University of Texas M.D. Anderson Cancer Center demonstrated in animal models that a fusion protein comprised of vascular endothelial growth factor with a toxin (gelonin) inhibited the growth of breast cancer metastatic tumors by 50 percent.
Pharmacyclics Inc., of Sunnyvale, Calif., presented data demonstrating the potential application of Xcytrin (motexafin gadolinium) injection for the treatment of multiple myeloma. Company researchers and collaborators at Northwestern University described preclinical findings that provided an indication of the potential therapeutic effect of Xcytrin in cells derived from hematopoietic malignancies, including multiple myeloma.
Sonus Pharmaceuticals Inc., of Bothell, Wash., said Tocosol paclitaxel is showing favorable antitumor activity, including complete and partial responses, in cancer patients who have failed prior chemotherapeutic regimens. Tocosol also is demonstrating tolerability over multiple treatment cycles. Data from three ongoing Phase II studies were presented.
SuperGen Inc., of Dublin, Calif., reported limited Phase I data supporting the theory behind the combination trial with Dacogen (decitabine) injection and carboplatin in cancer patients with advanced solid tumors. The abstract concluded that, although at a preliminary stage in the clinical trial, the data showed Dacogen can induce consistent changes in biological markers in advanced cancer patients that mimic those reported in mouse models and that the changes in mice resulted in the chemosensitization of drug-resistant human tumor xenografts.
Targeted Genetics Corp., of Seattle, presented data from studies using a targeted formulation of its synthetic, lipid-based gene delivery system called LPD-PEG. Data demonstrated LPD-PEG, along with an additional targeting molecule, delivered systemically resulted in a reduction in tumor size and an increase in survival time when compared to nontargeted LPD-PEG in animal models of breast cancer. Targeted Genetics also presented results suggesting that after systemic administration, LPD-PEG can effectively deliver the human interferon-B gene to tumors, resulting in a decrease in tumor size in animal models after 75 days.
Vion Pharmaceuticals Inc., of New Haven, Conn., presented preclinical data on Triapine in combination with Ara-C. The experiments were performed in cancer cell lines and demonstrated that Triapine increases uptake of Ara-C in cancer cells while increasing incorporation of Ara-C into cellular DNA, producing cell death. The combination of low doses of Triapine followed by exposure to Ara-C resulted in either synergistic or additive cytotoxicity to cancer cell lines in vitro. Triapine is designed to be a potent inhibitor of ribonucleotide reductase. Vion's stock (NASDAQ:VION) rose 32 cents Monday, or 17.6 percent, to close at $2.14.
ZymoGenetics Inc., of Seattle, said interleukin-21 treatment suppressed the growth of tumors in mice without the toxic effects commonly seen with other cytokine therapies. In a mouse model of melanoma, IL-21 was able to decrease the number of metastases that formed in the lungs. IL-21 is designed to stimulate the proliferation and activation of natural killer cells and cytotoxic T cells.