Staff Writer

While both the investment and clinical communities eagerly await detailed data expected next week from Dendreon Corp.'s confirmatory Phase III trial of cancer vaccine Provenge (sipuleucel-T) in late-stage prostate cancer, the company presented data from an ongoing Phase III trial in earlier-stage patients.

The randomized, double-blind, placebo-controlled Phase III trial known as PROTECT (PROvenge Treatment and Early Cancer Treatment, or P-11) included 176 men with nonmetastatic, androgen-dependent prostate cancer. All patients had rising levels of prostate-specific antigen (PSA) following surgical removal of the prostate and were randomized to receive Provenge or placebo following three months of hormone therapy.

Treatment was administered at weeks zero, two and four. Data presented at the 100th Annual Meeting of the Association for Cancer Research showed an increased cellular immune response at week four (p < 0.001) as well as corresponding upregulation of CD54 expression on antigen presenting cells, an indicator of potency.

Patients in the trial also were offered a booster shot once their PSA levels reached at least 3 ng/mL, which occurred an average of 1.1 years after the initial treatment, although the range spread from 0.2 years to 5.5 years.

The increased CD54 upregulation persisted through the booster, with cellular immune responses continuing 13 weeks after the booster (p < 0.001). In a news release, Dendreon Chief Scientific Officer David Urdal said the data "suggest that the immune response generated by Provenge is durable for a year or more after initial treatment and that it can be maintained following boosting."

Joseph Pantginis, analyst with Merriman Curhan Ford and Co., wrote in a research note that the data could be "critical" in potentially growing the Provenge approval label.

Provenge's pivotal program thus far has centered on late-stage patients with metastatic, androgen-independent prostate cancer. Pantginis estimated that there are about 30,000 such late-stage patients, while the overall incidence of prostate cancer is significantly larger - about 200,000 new cases per year.

Additionally, earlier-stage cancer patients are expected to derive a greater benefit from immunotherapies such as Provenge because their immune systems are healthier and better able to respond, Pantginis explained.

Shares of Dendreon (NASDAQ:DNDN) rose $1.53, or 8.5 percent, to close at $19.52 on Monday.

The stock may move again next week, when detailed data from the confirmatory Phase III IMPACT trial are presented at the American Urological Association's annual meeting.

Dendreon revealed last week that the trial met its primary endpoint of improving overall survival, but no actual data were provided because of the AUA's embargo policy. Even so, investors hopeful that the data will be strong enough to gain the first FDA approval of a therapeutic cancer vaccine and end Dendreon's two-year regulatory roller coaster ride pushed the stock up 133 percent. (See BioWorld Today, April 15, 2009.)

Dendreon's two previous Phase III Provenge trials missed their primary endpoint of time to progression but showed a survival benefit in post-hoc analyses. Dendreon filed a biologics license application, but the FDA handed back a complete response letter despite an endorsement from its Cellular, Tissue and Gene Therapies Advisory Committee. (See BioWorld Today, July 22, 2005, March 30, 2007, and May 10, 2007.)

In a conference call last week, Dendreon President and CEO Mitchell Gold said the IMPACT data were "unambiguous in nature" and a "clear hit" on the primary endpoint. He added that Dendreon plans to submit an amendment to its existing biologics license application in the fourth quarter.

A decision from the FDA should come approximately six months after the filing.

In other AACR news:

• Allos Therapeutics Inc., of Westminster, Colo., presented data showing that its pralatrexate has antitumor activity in nine of 15 human cell lines tested, including colon, ovarian, lung, prostate and head and neck cancer cell lines. Pralatrexate appears to cause apoptosis rapidly, within 24-72 hours of administration.

• Antisoma plc, of London, offered two presentations reporting positive data from animal tumor studies where ASA404 was given in combination with targeted therapies from the pipeline of Basel, Switzerland-based Novartis AG, Antisoma's partner for ASA404. The therapies included RAD001, an mTOR inhibitor recently approved by the FDA for patients with advanced renal cell carcinoma after failure of treatment with sunitinib or sorafenib; and patupilone, a novel nontaxane microtubule stabilizing agent in Phase III trials for ovarian cancer and in earlier-stage trials in other settings. Three other presentations reported new data on the mechanisms by which ASA404, AS1413 and AS1411 exert their anticancer effects.

• ArQule Inc., of Woburn, Mass., presented preclinical data on c-Met inhibitor ARQ 197, showing that the compound was synergistic with Nexavar (sorafenib, Onyx Pharmaceuticals Inc. and Bayer Pharmaceuticals Corp.) and with Sutent (sunitinib, Pfizer Inc.). Another study showed that ARQ 621, which inhibits Eg5 kinesin motor protein, inhibits human Eg5 in multiple cell lines without hematological changes in animal studies.

• Array BioPharma Inc., of Boulder, Colo., reported that its small-molecule p38/Tie2 inhibitor, ARRY-614, effectively inhibited angiogenesis in vivo and inhibited tumor growth in preclinical models of multiple myeloma when administered as a single agent. Additionally, administering p38 inhibitors in combination with Revlimid (lenalidomide, Celgene Corp.) led to better inhibition of proinflammatory cytokines, while combining ARRY-614 with standard-of-care agents lenalidomide and the steroid dexamethasone in multiple myeloma provided additional antitumor effects.

• Bionovo Inc., of Emeryville, Calif., presented preclinical data showing that BN108, an aqueous extract of Anemarrhena asphodeloides, selectively induced cell death in breast cancer and other tumor cells without a toxic effect on normal cells. Bionovo also said Timosaponin AIII was identified as an active compound in BN108. Shares of Bionovo (NASDAQ:BNVI) rose 16 cents, or 42 percent, to close at 54 cents on Monday.

• Caris Diagnostics Inc., of Irving, Texas, said a study conducted with the Scottsdale Healthcare Foundation using Caris' Target Now molecular profiling technology demonstrated that treatment selection based on genetic profiling could improve outcomes for patients who had failed several prior cancer treatments.

• Endocyte Inc., of West Lafayette, Ind., presented four preclinical studies. Data included evaluation of a spacer-optimized folate-targeted Vinca alkaloid EC0489, the antitumor effects of compound EC145 in combination with doxorubicin, mTOR pathway inhibition via folate receptor EC0565, and releasable dual-drug conjugates of folic acid.

• Epistem plc, of Manchester, UK, presented results from the latest plucked hair biomarker study to determine the specific response to oral administration of Erlotinib, the EGFR inhibitor, in a plucked hair preclinical model. In addition to tracking the gene expression and molecular pathway change through the preclinical and clinical development of a drug, the Erlotinib results open up the possibility for clinicians to monitor patient-specific gene responses to treatment, the company said.

• Halozyme Therapeutics Inc., of San Diego, reported that treatment with PEGPH20 significantly delayed tumor growth in preclinical breast and prostate cancer models. In a brain metastasis model, PEGPH20 combined with chemotherapy showed increased efficacy, and PEGPH20 combined with radiation prolonged survival. PEGPH20 targets and degrades the hyaluronan coating that surrounds certain solid tumor cells, which may improve response to therapeutics by selective reduction of tumor interstitial fluid pressure and facilitate tumor drug penetration.

• Immunomedics Inc., of Morris Plains, N.J., presented preclinical data showing that IMMU-114, a humanized monoclonal antibody against human leukocyte antigen-DR, exhibited cytotoxicity in vitro against multiple hematologic cancers. The company also plans to evaluate it against solid tumors and autoimmune diseases.

• InNexus Biotechnology Inc., of Vancouver, British Columbia, presented preclinical data on DXL625, a modified anti-CD20 human-mouse chimeric antibody poised to begin clinical trials in non-Hodgkin's lymphoma and chronic lymphocytic leukemia. One study showed that the safety of DXL625 was not impacted by its enhanced cytotoxicity, while another described self-binding interactions to increase binding strength.

• Lorus Therapeutics Inc., of Toronto, presented preclinical data showing that LOR-253, a small-molecule inhibitor of Metal Responsive Transcription Factor-1, activated tumor growth inhibitors and repressed tumor promoters in animal studies. The compound also inhibits angiogenesis. Lorus plans to file an investigational new drug application this quarter.

• Lpath Inc., of San Diego, presented in vivo and in vitro data showing that Lpathomab significantly reduced IL-8 and IL-6 cytokine release and inhibited tumor progression in ovarian cancer models. The drug also reduced neovascularization and showed preliminary antimetastatic activity. Lpathomab is a monoclonal antibody that binds to the bioactive lipid lysophosphatidic acid.

• Medarex Inc., of Princeton, N.J., announced preliminary data from an ongoing Phase I trial of MDX-1401 in patients with relapsed or refractory Hodgkin's lymphoma (HL) that demonstrated both clinical and immunological activity signals. MDX-1401 is a fully human, nonfucosylated antibody that targets CD30, a marker for activated lymphocytes that is present on malignant cells of HL as well as other CD30-expressing cancers.

• Mersana Inc., of Cambridge, Mass., presented data showing that its experimental anti-angiogenic drug, XMT-1107, had superior antitumor activity in tumor xenograft models in comparison to other anti-angiogenic agents and extended exposure when conjugated to the company's Fleximer, a biodegradable, bio-inert material that is meant to enhance the pharmacokinetics and safety of drugs.

• Momenta Pharmaceuticals Inc., of Cambridge, Mass., presented positive results from a preclinical study of M402 showing that it, in combination with chemotherapeutic agents, inhibited spontaneous tumor metastasis in a murine metastatic breast carcinoma model. M402 is an HSGAG mimetic engineered from low molecular weight heparin to have potent antimetastatic properties and low anticoagulant activity.

• Novelos Therapeutics Inc., of Newton, Mass., presented four preclinical posters about NOV-002, its chemoprotectant/chemopotentiator in Phase III for non-small-cell lung cancer. The posters showed that NOV-002, a glutathione disulfide-mimetic, inhibited the ability of multiple tumors to invade the extracellular matrix, triggered redox-regulated biochemical cascades, involves mechanisms upregulated in cancer, and induced changes in calcium influx and nitric oxide generation.

• Novogen Ltd., of Sydney, Australia, presented data showing that NV-128, a synthetic isoflavonoid compound, induces cell death in ovarian cancer stem cells and also blocks their differentiation into structures, which are required to support tumor growth. The antiproliferative effects were demonstrated to be achieved as a result of NV-128 inhibiting phosphorylation of the prosurvival mTOR pathway resulting in mitochondrial depolarization and cell death.

• Progen Pharmaceuticals Ltd., of Brisbane, Australia, presented preclinical data showing that PG11144, developed using Progen's epigenetic technology, inhibits lysine specific demethylase 1, an enzyme known to silence tumor-suppressing genes. Inhibiting LSD1 reactivated the silenced genes and inhibited tumor growth in animal models. Progen also presented preclinical data showing that its Phase I cell proliferation product, PG11047, demonstrated a significant additive anticancer effect when combined with chemotherapy drug cisplatin or Avastin (bevacizumab, Genentech Inc.).

• Santaris Pharma A/S, of Copenhagen, Denmark, presented in vitro and in vivo data showing that its Locked Nucleic Acid (LNA)-antimiRs recognized and inhibited disease-associated microRNAs. LNA-antimiRs are small, synthetic single-stranded oligonucleotides.

• Threshold Pharmaceuticals Inc., of Redwood City, Calif., reported preclinical results on its hypoxia-activated prodrug TH-302, which is in a Phase I/II dose escalation trial. One poster reported new results on dosing regimens, while another presented data showing that TH-302 had superior efficacy and less toxicity than the chemotherapy agent ifosfamide in metastatic and ectopic human lung carcinoma models. Shares of Threshold (NASDAQ:THLD) fell 25 cents, or 14.8 percent, to close at $1.44 on Monday.