BioWorld Today Contributing Writer

Exelixis Inc. led a large pack of biotechs presenting results at the European Organisation for Research and Treatment of Cancer (EORTC)-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Berlin.

Exelixis reported interim data for patients with metastatic castration-resistant prostate cancer (CRPC) who had been treated with its XL184. At 12 weeks, 19 of 20 patients with CRPC achieved complete or partial resolution of metastatic lesions on bone scan by independent review, with most resolving at the first post-baseline assessment at six weeks.

Shares of the South San Francisco-based company's stock (NASDAQ:EXEL) closed at $6.23, up 32 percent, or $1.51, in heavy trading on the news Thursday.

Following the EORTC presentation, Piper Jaffray analyst Edward Tenthoff issued a research note reiterating its "overweight" rating and $9 price target based on projected enterprise value of $922 million and year-end net cash of $93 million.

"We are very impressed by the activity seen in prostate cancer with 12-week disease control rate of 71 percent and 95 percent [19/20] complete or partial remission on bone scan," Tenthoff wrote. "We see XL184 as the path forward for Exelixis."

XL184 is an inhibitor of tumor growth, metastasis and angiogenesis that simultaneously targets MET and VEGFR2 – key kinases involved in the development and progression of many cancers.

In a conference call with investors following the EORTC presentation, Matthew R. Smith, program director for genitourinary oncology at Massachusetts General Hospital and a clinical investigator in the XL184 program, explained that a strong preclinical rationale exists for dual inhibition of MET and VEGFR in prostate cancer.

"MET expression is regulated by the androgen receptor, and androgen deprivation therapy increases MET expression in tumor cells," Smith said. "Increases in expression of MET and its ligand HGF may contribute to disease progression following androgen deprivation therapy. Notably, MET is more frequently expressed in poorly differentiated prostate cancer and at sites of bone metastases."

Bone metastases are the primary cause of morbidity and mortality in prostate cancer, Smith added, noting that effective therapies for CRPC represent an important unmet medical need.

"Chemotherapy, for example, modestly improves survival in metastatic CRPC, but has little impact on the metastatic bone disease," he said.

"In contrast, bone-targeted therapies may reduce skeletal morbidity, but have no documented impact on cancer progression." Improvements in bone scans are unusual following existing therapies, Smith added, noting, "In 13 years of practice in prostate cancer, I've had only one or two patients with complete resolution of bone disease on bone scans following treatment for metastatic CRPC."

The early results of XL184 in prostate cancer suggested "unprecedented activity, particularly in men with bone metastases," Smith said. Improvements were observed not only in bone scans, but also in pain relief among men who previously were treated with chemotherapy as well as those who were not.

Exelixis' Phase II adaptive randomized discontinuation trial (RDT) has enrolled patients with nine tumor types. Of these, CRPC is the only cancer type predominantly involving bone rather than soft tissue. The company also presented interim data at EORTC for patients with advanced epithelial ovarian cancer, primary peritoneal, or fallopian tube carcinoma who had been treated with XL184 during an ongoing Phase II adaptive RDT. Tumor shrinkage was observed in 30 of the 37 ovarian cancer patients with measurable metastatic lesions.

With CRPC the leading cause of cancer-related death among men in the U.S. and Europe, "the prostate cancer space is currently very active, and the opportunities for XL184 are significant," Michael M. Morrissey, the company's president and CEO, told investors during the conference call.

"If XL184 can have a durable impact on soft tissue and bone lesions, we believe it could be a major step forward in [treating] CRPC in both the metastatic and, potentially, earlier settings," he said.

Exelixis has numerous partnership deals, including two recent agreements with long-time collaborator Bristol-Myers Squibb Co., of New York, potentially worth $565 million. (See BioWorld Today, Oct. 12, 2010.)

In other EORTC presentations:

• Aeterna Zentaris Inc., of Quebec City, presented positive Phase II efficacy and safety data for AEZS-108, a targeted cytotoxic drug in which doxorubicin is linked to D-Lys(6)-luteinizing hormone releasing hormone (LHRH) in women with LHRH-R positive advanced or recurrent endometrial cancer. Of 39 patients evaluated in the study, two showed complete response, 10 showed partial response and 17 showed stable disease, with the drug well tolerated in the trial population.

• AVEO Pharmaceuticals Inc., presented findings from a Phase Ib clinical trial of the company's lead candidate, tivozanib, an inhibitor of VEGF receptors 1, 2 and 3, in combination with FOLFOX6, a standard chemotherapy regimen, in patients with advanced gastrointestinal cancers. Six of 17 patients evaluated showed partial response, and stable disease was observed in another eight patients, according to the Cambridge, Mass.-based company.

Privately held Cerulean Pharma Inc., reported findings from a dose-finding, safety and tolerability Phase I clinical study of CRLX101, indicating that five advanced cancer patients who had previously relapsed and progressed on multiple therapies were stable for more than six months on the nanopharmaceutical compound. The Cambridge, Mass.-based company will use the findings to establish the maximum tolerated dose and schedule for a planned Phase II study.

• Curis Inc., of Cambridge, Mass., presented Phase I data on CUDC-101, a multitargeted inhibitor of HDAC, EGFR and HER2, in patients with advanced cancer. Results of the open-label, dose-escalation study showed that the first development candidate in Curis' network-targeted cancer drug development platform was well tolerated at "pharmacologically meaningful concentrations" and showed evidence of biological activity, the company said.

• MethylGene Inc., of Montreal, disclosed safety and efficacy data for MGCD265, an oral multi-targeted receptor tyrosine kinase inhibitor, in a two-arm trial in which the compound is administered in combination with either docetaxel or erlotinib in solid tumor patients. In the docetaxel arm, five of 18 patients were enrolled in the study for more than four months. Of these, four non-small-cell lung cancer patients experienced stable disease for eight to 13 months, another achieved a confirmed partial response and the other three showed tumor shrinkage accompanying stable disease. In the erlotinib arm, with 12 of 27 patients enrolled for more than four months, one gastric cancer (linitis plastica) patient is currently stable for 11 cycles.

• Oncothyreon Inc., reported positive Phase I data for its PX-866, an irreversible small-molecule phosphatidylinositol-3-kinase (PI-3K) inhibitor, in patients with advanced solid tumors. The Seattle-based company presented data from the continuous dosing arm of the single-agent, open-label, dose escalation study in patients who had failed or could not tolerate standard therapy, reporting that eight of 19 evaluable patients stabilized as their best response, with good tolerability of the compound.

• Pfizer Inc., of New York, presented additional results of a Phase I study of ALK-positive advanced non-small-cell lung cancer patients treated with crizotinib (PF-02341066), an investigational oral anaplastic lymphoma kinase inhibitor, indicating that most patients respond to treatment by 12 weeks. (See BioWorld Today, Oct. 28, 2010.)

• Threshold Pharmaceuticals Inc., reported results from two trials of its clinical stage hypoxia-activated prodrug, TH-302. A Phase I/II three-arm, multicenter, dose-escalation and dose expansion trial to determine safety, efficacy and pharmacokinetics of TH-302 in combination with gemcitabine, docetaxel or pemetrexed in patients with advanced solid tumors showed partial response or stable disease in 18 patients with advanced pancreatic cancer, 17 with castrate-resistant prostate cancer and 17 with relapsed or refractory non-small-cell lung cancer. A second trial by the Redwood City, Calif.-based company showed partial response or stable disease in combination with doxorubicin in patients with advanced soft tissue sarcoma.

• Zalicus Inc., demonstrated that systematic combination studies using the company's combination high-throughput screening (cHTS) technology can reveal patterns of chemotherapeutic sensitivity and resistance, potentially leading to the development of more selective and effective combination therapies for a wide variety of cancers. The Cambridge, Mass.-based company evaluated signaling pathways containing a number of anticancer therapeutic targets, such as P13K and RAS, across a panel of cancer cell lines.