Awaiting word from partner GlaxoSmithKline plc on whether it will license cancer drug candidate XL880 for further development, Exelixis reported encouraging data from an ongoing Phase II study of the compound in kidney cancer patients at the American Association for Cancer Research, National Cancer Institute and European Organization for Research and Treatment of Cancer (AACR-NCI-EORTC) conference in San Francisco.

Of 19 evaluable patients with papillary renal-cell carcinoma treated with XL880, an inhibitor of MET and vascular endothelial growth factor receptor 2 (VEGFR2) kinases, 15 (79 percent) have had a decrease in tumor size (4-33 percent), including one patient with a partial response. All 19 patients with at least one post-baseline tumor assessment have shown stable disease for at least three months, and of those, 12 have had stable disease for six months to more than 15 months. Analyst Joel Sendek, of New York-based Lazard Capital Markets LLC, said that data showed "impressive 100 [percent] disease control," and he anticipates "a GSK opt-in decision this December."

XL880 is one of the compounds included in Exelixis' 2002 collaboration with London-based GSK. Terms of that deal involves the development of up to 10 compounds at Exelixis, from which GSK is permitted to select two or three for further development. Exelixis submits a data package to the pharma firm at the conclusion of Phase IIa proof-of-concept studies. The data package for XL880 was submitted in September, giving GSK 90 days to make a decision. If GSK licenses the program, the big pharma firm would pay Exelixis milestones and royalties. Meanwhile, any programs in the collaboration that GSK declines to take forward will remain in the hands of Exelixis to develop on its own or with a partner, though it would pay GSK a 3 percent royalty rate on net product sales.

In July, GSK passed on the first compound submitted by Exelixis, XL647, a receptor tyrosine kinase inhibitor aimed at inhibiting epidermal growth factor receptor (EGFR), HER2 and VEGFR. At that time, executives from South San Francisco-based Exelixis said the drug continued to show promise, and the company planned to pursue development on its own. At the conference this week, investigators presented updated Phase II data from LX647 in previously untreated, clinically selected non-small-cell lung cancer patients, which show antitumor activity when administered on an intermittent schedule. Sixty-eight percent of the 34 evaluable patients had clinical benefit, including 10 patients with partial responses and 13 patients with stable disease.

All seven patients with activating EGFR mutations experienced tumor shrinkage, and three patients with wild-type EGFR achieved partial responses. (See BioWorld Today, July 27, 2007.)

A pivotal program of XL647 in NSCLC is anticipated to begin next year.

Additional data from a Phase I dose-escalation study of XL647 in solid tumors showed that 11 of the 21 patients assessable for tumor response receiving doses ranging from 75 mg to 300 mg achieved stable disease for at least three months.

Exelixis' stock (NASDAQ:EXEL) closed at $10.97 Thursday, down 27 cents.

In other AACR-NCI-EORTC news:

• Adventrx Pharmaceuticals Inc., of San Diego, presented preclinical results demonstrating that ANX-514, its docetaxel emulsion product candidate, reduced hypersensitivity reactions without affecting pharmacokinetics or antitumor activity when compared to Taxotere (docetaxel). In an animal model, anaphylactoid clinical reactions were observed following Taxotere administration, including decreased respiration, swelling and tremors, whereas hypersensitivity reactions were not seen after ANX-514 administration. Adventrx's drug resulted in no treatment-related change in blood pressure and no increase in histamine levels. And in an in vivo model, ANX-514 demonstrated dose-dependent inhibition of tumor growth with equivalent antitumor activity vs. Taxotere.

• Antigenics Inc., of New York, said follow-up data from a Phase I/II trial of its Oncophage (vitespen) cancer vaccine showed that 11 out of 12 high-grade glioma patients exceeded the historical median benchmark of 6.5 months survival from time of recurrence. The study showed that all 12 treated patients demonstrated a significant immune response after vaccination with Oncophage and that patients with minimal disease at the time of first vaccination were more likely to survive beyond nine months compared to patients with significant residual disease.

• Arius Research Inc., of Toronto, presented preclinical findings from its Trop-2 antibody program demonstrating significant antitumor effects in animal models of human pancreatic cancer by inhibiting tumor growth by up to 100 percent. Subsequent testing showed efficacy in animal models of breast, colon and prostate cancers, as well, and the antibody compared favorably to Taxotere in a prostate cancer model. Findings from the company's CD59 program showed that an antibody targeting CD59 activates complement any activity against cancer cells and inhibits tumor growth in animal models of breast, colon, lung and prostate. In animal models of breast cancer, tumor growth was inhibited by up to 100 percent.

• ArQule Inc., of Woburn, Mass., presented Phase I data showing early clinical signs of potential antimetastatic activity with ARQ 197, a selective, small-molecule inhibitor of the c-Met receptor tyrosine kinase. Of the 49 evaluable patients to complete at least one cycle of treatment, three (6.1 percent) had partial responses, 31 (63.2 percent) had stable disease for more than eight weeks and 18 (36.7 percent) had prolonged stable disease for periods ranging from 16 to 74 weeks. Eighteen of 19 patients (94.7 percent) treated with ARQ 197 for 12 weeks or longer did not develop detectable new metastatic lesions, whereas, in contrast, 11 of 19 patients (57.9 percent) treated for six weeks or less developed new metastatic lesions. ArQule also presented preclinical findings showing that 20 percent of mice, which were implanted with human bone grafts and injected with breast cancer cells then treated with ARQ 197, showed metastases of those cells to the bone grafts, compared to 50 percent of mice in the paclitaxel and control groups that showed mestastases.

• Array BioPharma Inc., of Boulder, Colo., said Phase I data showed that its ARRY-543, an ErbB-2/EGFR inhibitor, produced stable disease in refractory patients with advanced solid tumors. In completed cohorts, 60 percent of patients receiving doses of 200 mg BID and higher had prolonged stable disease.

• Avalon Pharmaceuticals Inc., of Germantown, Md., said compounds from its beta-catenin pathway inhibitor program demonstrated significant tumor growth inhibition in multiple animal models. Data showed that compounds selected and optimized from a biomarker-based beta-catenin pathway screen decreased beta-catenin protein levels in xenograft tumors, while inducing a gene expression signature consistent with beta-catenin inhibition and exhibiting antitumor growth properties.

• Bionovo Inc., of Emeryville, Calif., presented the mechanism of action behind its cancer drug, BZL101, showing that the compound elicits a cytotoxic activity on cancer cells while avoiding normal cells. The drug leads to the inhibition of glycolysis, which tumor cells rely on for energy production. BZL10 is in a Phase I/II trial in late-stage breast cancer.

• BiPar Sciences Inc., of Brisbane, Calif., reported molecular biomarker data demonstrating the overexpression of the PARP (poly-ADP-ribose polymerase) protein in multiple cancers. Researchers used Gene Logic Inc.'s BioExpress System database to analyze PARP-1 gene expression and compared those results to normal counterpart tissue. PARP expression was found to be above the 95 percent upper confidence limit for normal tissue in ovarian cancer, intraductal breast cancer, lung cancer and uterine cancer. BiPar anticipates initiating Phase Ib and Phase II trials of its PARP-targeting drug, BSI-201, in tumor types, as guided by gene expression data.

• Cell Therapeutics Inc., of Seattle, and its wholly owned subsidiary, Systems Medicine LLC, reported preclinical data showing that an antibody to IGF-II might solve the problems of low blood sugar associated with drug candidates working through insulin receptor-linked pathways. Data showed that the hmAb m610, designed to recognize the mature and premature forms of IGF-II, evaluated in an in vivo MCF-7 cell-based mouse xenograft model, showed that levels of soluble ligand-specific antibody in the blood could result in a decrease of ligand concentration in the tumor.

• Cougar Biotechnology Inc., of Los Angeles, reported positive Phase I data on CB7630 (abiraterone acetate), its prostate cancer drug, showing that 16 of 27 patients (59 percent) experienced a greater than 50 percent decline in prostate-specific antigen levels. Those results include 18 patients who fasted before treatment, of which 11 (61 percent) experienced a greater than 50 percent PSA decline, and nine patients who were treated on a full stomach, of which five (56 percent) achieved that PSA decline. The trial involved chemotherapy-naïve patients with castration refractory prostate cancer who had progressive disease despite treatment with luteinizing hormone-releasing hormone analogues and other hormonal therapies.

• CuraGen Corp., of Branford, Conn., reported Phase I results of CR011-vcMMAE, an antibody-drug conjugate for metastatic melanoma, which suggested that the drug is well tolerated at doses up through 1.88 mg/kg with no dose-limiting toxicities noted. Of the 25 patients treated with doses ranging from 0.03 mg/kg to 1.88 mg/kg, six have achieved stable disease lasting up to 11 cycles and four of those patients demonstrated tumor shrinkage of up to 20 percent. Reversible neutropenia was the only drug-related Grade 3 or Grade 4 adverse event and appears to be dose-dependent.

• Curis Inc., of Cambridge, Mass., reported that CUDC-101, a synthetic inhibitor of histone deacetylase (HDAC), endothelia growth factor receptor and HER2, inhibited proliferation of cancer cell lines. The compound demonstrated improved potency compared to existing treatments in 27 cell lines of cancer types, including lung, breast, prostate, colon, liver and pancreas, and it has shown efficacy in mouse xenograft models of human cancer.

• EntreMed Inc., of Rockville, Md., presented interim Phase I results showing that ENMD-1198, is antimitotic agent, and has good pharmacokinetic parameters in advanced cancer patients. In the first four cohorts, the drug demonstrated dose proportional PK exposures across a range of 5 mg/m2 to 30 mg/m2. ENMD-1198 is based on a modified chemical structure of 2-methoxyestradiol and is designed to decrease metabolism while retaining 2ME2's mechanisms of action. The drug also was evaluated in a preclinical model of non-small-cell lung cancer, where it demonstrated a threefold increase in survival compared to cisplatin. In a separate presentation, EntreMed reported preclinical results of MKC-1, its cell-cycle inhibitor, in renal-cell carcinoma models, showing that the drug inhibited both Akt and mTOR pathway activation in vitro. That drug was further evaluated in a model consisting of a xenograft of the human RCC cell line, Caki-1, where it significantly increased survival of tumor-bearing animals.

• GlobeImmune Inc., of Louisville, Colo., said preclinical results showed that its GI-10001 Tarmogen, in development for drug-resistant chronic myelogenous leukemia, triggers the immune system in mice to selectively eliminate leukemic cells with the Bcr-Abl T3151 mutation. The Tarmogen drug, which is designed to express that mutation, also significantly extended survival in mice after lethal challenge with cells driven by the T3151-mutated Bcr-Abl. Tarmogens, or Targeted Molecular Immunogens, are GlobeImmune's immunotherapeutic platform, uses whole, heat-killed recombinant Saccharomyces cerevisiae yeast that is genetically modified to express disease-specific protein targets.

• Hana Biosciences Inc., of South San Francisco, said preclinical results showed that Marqibo (vincristine sulfate injection) using the company's Optisome platform concentrates vincristine in the tumor tissue and bone marrow of tumor-bearing mice. The company reported similar results with Optisome-based Alocrest (vinorelbine tartrate injection) and Brakiva (topotecan hydrochloride injection), suggesting that the platform might offer advantages to cell-cycle-specific chemotherapeutics by transforming them into targeted medicines and enhancing their activity. When studied in tumor-bearing animals, Hana's Optisome-encapsulated drugs preferentially accumulated in implanted tumors and other target tissues.

• ImmunoGen Inc., of Cambridge, Mass., said Phase I findings of huC242-DM4 in patients with CanAg-expressing cancers that had not responded to approved therapies demonstrated that tumor shrinkage was observed in six of the 26 evaluable patients who received the drug at any dose level. The trial also established a maximum tolerated dose of 168 mg/m2. The company also reported preclinical data showing that juC242-DM4 is highly effective in tumor xenograft models of CanAg-positive human gastric cancer and huC242-DM4, an antibody-cytotoxic agent conjugate, demonstrated synergistic activity when used in combination with antineoplastic agents in gastric cancer cells in culture.

• Intradigm Corp., of Palo Alto, Calif., presented preclinical results demonstrating that its TargeTran delivery system is capable of delivering vascular endothelial growth factor (VEGF)-targeted small interfering RNAs to suppress tumor-induced angiogenesis by silencing target gene expression in mice. Intradigm is developing ICS-283, a nanoparticle-based compound comprised of siRNAs that target both VEGF and its main receptor.

• Molecular Insight Pharmaceuticals Inc., of Cambridge, Mass., reported preclinical data from its Trofex development program, which suggested that two molecular imaging candidates, MIP-1072 and MIP-1095, have potential use in detection and monitoring prostate cancer. Both compounds are radiolabeled small molecules that target prostate-specific membrane antigen, and in xenograft models, MIP-1072 and MIP-1095 achieved peak uptake of 17 percent and 34 percent of the injected dose/gram tumor, respectively, resulting in tumor-to-blood ratio of >30 to 1 and a tumor-to-muscle ration of >60 to 1.

• Nektar Therapeutics Inc., of San Carlos, Calif., presented preclinical data on NKTR-102 (PEG-irinotecan), showing the drug inhibited tumor growth by greater than 90 percent in mouse xenograft models of colorectal, lung and breast cancers, compared to controls. The studies also demonstrated that Nektar's small-molecule PEGylation technology improves the pharmacokinetics of irinotecan by increasing the effective half-life of the drug's active metabolite in tumor tissues.

• OxiGene Inc., of Waltham, Mass., said interim results from an ongoing Phase I study of OXi4503 showed the drug to be well tolerated, while reporting observations of tumor blood flow shutdown and metabolic inactivation. Disease stabilization has been achieved in several subjects. OXi4503 (combrestatin A1 diphosphate/CA1P) is a dual-mechanism vascular-disrupting agent in development for solid tumors.

• Pharmion Corp., of Boulder, Colo., and MethylGene Inc., of Montreal, reported preliminary data from their Phase I/II trial of MGCD1013 in combination with Gemzar, which showed that the two drugs can be safety administered together at their recommended doses. Of the 13 evaluable patients, there was one partial response and eight stable diseases. In addition, five of the 13 patients experienced tumor shrinkage. The partial response and near partial response were observed in pancreatic cancer patients, and the companies have initiated the Phase II portion of the trial in that cancer indication.

• Reata Pharmaceuticals Inc., of Irving, Texas, reported Phase I results showing that its lead antioxidant inflammation modulator, RTA 402, was well tolerated when given orally once daily and it provided a high degree of disease control in patients with advanced cancers. Extended periods of stable disease (six months to 12 months) have been achieved in a number of patients with metastatic melanoma, renal-cell carcinoma and thyroid cancer, and treatment with RTA 402 inhibited the formation of new metastases in a high percentage of patients. RTA 402 is designed to inhibit the activity of the transcription factors NF-kappa B and STAT3.

• Seattle Genetics Inc., of Bothell, Wash., reported preclinical data on SGN-40, a humanized monoclonal antibody, showing that the drug signals apoptosis in models of non-Hodgkin's' lymphoma by causing depletion of the BCL-6 survival signal and also increasing the level of Tap63a, a protein believed to enhance the susceptibility of tumor cells to chemotherapy. That compound is in development for both NHL and multiple myeloma in collaboration with South San Francisco-based Genentech Inc. Seattle Genetics also presented data from its anti-CD19 antibody-drug conjugate program in hematologic malignancies showing that those compounds effectively could bind to target cells with high affinity and internalize and induce apoptotic activity.

• SuperGen Inc., of Dublin, Calif., reported preclinical findings showing that MP470, its multitargeted tyrosine kinase inhibitor, demonstrated synergy with DNA-damaging agents, including platinum-based treatments, topoisomerase inhibitors, nucleoside analogues and erlotinib (Tarceva). Data also suggested that MP470 inhibits DNA damage repair through suppression of Rad51, a DNA repair protein. In a separate presentation, SuperGen reported that S110, its decitabine-derived DNA demethylating agent, showed improved preclinical activity due to increased drug delivery and stability.

• Synta Pharmaceuticals Corp., of Lexington, Mass., presented preclinical data confirming that the primary mechanism of action for elesclomol (formerly STA-4783) is through the induction of reactive oxygen species. Results also provided evidence that elesclomol enhances the efficacy of several first-line cancer agents, including Rituxan (rituximab, Biogen Idec Inc. and Genentech Inc.), Gemzar and Taxotere, with minimal additional toxicity and showed that the drug has single-agent antitumor activity.

• Ziopharm Oncology Inc., of New York, said early Phase I findings showing that two of the first three patients to receive indibulin (ZIO-301) at 400 mg twice daily on a continuous dosing schedule have shown activity. An elderly patient with metastatic papillary thyroid cancer evidenced stable disease with 11 percent tumor shrinkage and a 34 percent decrease in thyroglobulin levels, and a patient with ovarian cancer and brain metastases showed an 11 percent reduction of CA125 levels from baseline. Ziopharm also presented preclinical data showing that indibulin has targeted antitumor activity as a single agent and has synergistic activity in combination with several approved cancer drugs, particularly Tarceva (erlotinib, OSI Pharmaceuticals Inc. and Genentech Inc.) in a non-small-cell lung cancer cell line.