The Industry Insider: April 2007

THE INDUSTRY INSIDER

%u25BA AVAX and CTCA Collaborating for Cancer Therapies

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VAX Technologies, Inc., a developer of therapeutic cancer vaccines located in Philadelphia, PA, and Cancer Treatment Centers of America, Inc. (CTCA), a network of cancer treatment hospitals and facilities, are collaborating for the benefit of both parties’ cancer therapeutic products. The agreement will advance AVAX’s OVax ovarian cancer vaccine by facilitating a study at CTCA’s centers. At the same time, AVAX will produce CTCA’s activated natural killer cell technology for the treatment of various cancers.

The terms of the collaboration are for a three-year period, during which CTCA will provide AVAX with a funding of $1.15 billion for research and development. CTCA will fund the initial production of vaccines, and for AVAX’s clean room facility, where the company will produce its vaccines as well as CTCA’s natural killer cell preparations.

AVAX plans to activate a phase I/II IND for the treatment of stage III and IV ovarian cancer patients who have relapsed after chemotherapy. The study will evaluate patients for safety and immunological responses. It will be based at CTCA’s hospital in Zion, IL, where CTCA expects to start treating patients this summer.

The new O-Vax vaccine looks promising because it is based on the same technology as AVAX’s metastatic melanoma vaccine M-Vax, which has already been launched commercially in Switzerland and has the US FDA’s orphan drug designation. The technology, called haptenization, works by attaching a chemical hapten to tumor antigens, making it easier for the immune system to recognize the tumors. The safety and efficacy of M-Vax has been evaluated in more than 400 patients with stage III and IV melanoma, and the vaccine has been shown to increase five-year overall survival in patients with stage III melanoma. The newer O-Vax product has also seen good news recently—two phase I/II trials for the O-Vax product have provided encouraging results showing that the vaccine may prove effective in chemotherapy-resistant ovarian cancer.

“To win the fight against cancer, it is absolutely vital we do everything we can to make innovative new treatments like this available to patients as soon as possible,” said Edgar Staren, chief medical officer of CTCA. “It’s inconceivable that treatments like these that give hope to patients are often lefton the laboratory bench, while cancer patients are told there is nothing more that can be done for them.”

—Prachi Petal-Predd

%u25BA Full Speed Ahead for GPC Biotech's Satraplatin

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fter recently announcing positive results from a phase III registrational trial evaluating satraplatin against hormone refractory prostate cancer, biopharmaceutical company GPC Biotech AG has launched an expanded access program for the drug. The results of the trial showed that satraplatin significantly reduces the risk of disease progression in patients.

GPC Biotech, which is headquartered in Frankfurt, Germany, is expecting overall survival data later this year, but the company is moving forward with marketing approval applications. It has already filed the New Drug Application for satraplatin with the US FDA and expects to file an application in the EU by the end of the second quarter.

“Moving forward, we plan to work closely with the FDA regarding our application for marketing approval of satraplatin in the US,” said Bernd R. Seizinger, MD, PhD, chief executive officer of GPC Biotech. “We also are continuing to aggressively build our marketing and sales organization in the US to prepare for a potential launch of satraplatin later this year.”

The company announced the results of the Satraplatin and Prednisone Against Refractory Cancer (SPARC) trial at the American Society of Clinical Oncology Prostate Cancer Symposium in September 2006. The trial compared the effectiveness of satraplatin plus prednisone and placebo plus prednisone in 950 patients with refractory cancer who have failed chemotherapy treatment. Final progression-free survival (PFS) results for the SPARC results were presented by Daniel Petrylak, MD, associate professor of medicine at Columbia University College of Physicians & Surgeons, director of the Genitourinary Oncology Program at New York-Presbyterian Hospital/Columbia, and a principal investigator in the SPARC Study on February 24 at the American Society of Clinical Oncology (ASCO) Prostate Cancer Symposium in Orlando, Florida. Two different designs of the study showed a relative risk reduction in disease progression of 40% and 33% respectively. These results were consistent irrespective of the chemotherapy that the patients had already received.

According to Dr. Petrylak: “As there are currently no approved therapies for patients with hormone-refractory prostate cancer whose disease has already failed on one chemotherapy regimen, satraplatin has the potential to address a mounting area of unmet medical need. The data I am presenting show statistically significant results in progression-free survival in favor of those patients treated with satraplatin. These results are consistent no matter what the prior chemotherapy treatment, including Taxotere® [docetaxel, Sanofi-Aventis].”

Under GPC Biotech’s newly launched expanded access program, patients whose first-line chemotherapy has failed will have access to satraplatin free of charge from clinicians’ offices. Unlike other platinum compounds, which need to be administered intravenously, satraplatin comes in the form of capsules that patients can take at home.

— Parts of this story were contributed by John D. Zoidis, MD

%u25BA Collaboration for New Oncology Compounds

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ristol-Myers Squibb Company and Adnexus Therapeutics have announced a partnership to discover and develop Adnectin-based biological compounds for oncology-related targets. Waltham, MA-based Adnexus is the sole developer of Adnectins, a class of therapeutic proteins derived from human fibronectin that are designed and optimized using the company’s PROfusion protein design engine.

Under the agreement terms, Adnexus will identify and deliver pre-clinical Adnectin candidates to Bristol-Myers Squibb, which will then focus on global development and commercialization. Adnexus will retain a limited co-promotion right to the first product that is approved in the US.

Bristol-Myers Squibb will provide approximately $30 million over the next three years to Adnexus. These funds will consist of upfront and guaranteed research payments.

In addition, Adnexus is eligible to receive regulatory milestone payments of up to $210 million per product, as well as royalties on product sales and sales-based milestone payments.

—Prachi Petal-Predd

%u25BA Graffinity and Amgen in Drug Discovery Ageement

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raffinity Pharmaceuticals GmbH, a developer of fragment-based drug discovery technology headquartered in Heidelberg, Germany, announced a drug discovery research agreement with Amgen on February 25. As per the agreement, Graffinity will get technology access fees and success payments for generating small molecule hits against a broad range of drug targets. According to the company, it offers one of the largest fragment libraries commercially available today—about 20,000 fragments and 90,000 lead-like structures.

Thousand Oaks, CA-based Amgen will gain access to Graffinity’s fragment-based drug discovery technology. The technology uses microarrays to screen for molecule fragments that bind to a variety of drug targets that are already available or about to be discovered by genomics, which would help in fighting many major human diseases, including cancer.

The major focus of the collaboration is chemistry research and the identification of novel modes of action. The companies did not disclose the financial details of the transaction.

—Prachi Petal-Predd

%u25BA Roche Suspends Enrollment in CERA Phase II Oncology Trial

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n February 23, Roche announced that it is temporarily suspending recruitment into its phase II dose-finding study (NH19960) with the investigational drug CERA (Continuous Erythropoiesis Receptor Activator) in anemic patients with advanced (stage IIIB or IV) non—small-cell lung cancer who are receiving chemotherapy. An independent drug safety monitoring board involved in the study recommended this course of action, which Roche’s drug safety committee endorsed, according to Roche.

In this trial, enrolled patients were randomized to receive CERA 6.3μg/kg, 9μg/kg, or 12μg/kg subcutaneously every 3 weeks, or darbepoetin alfa according to the approved local label (either 6.75 μg/kg subcutaneously every 3 weeks, or 2.25 μg/kg every week).

Roche halted enrollment because of “a numerical imbalance in the number of deaths across the four arms of the study (three arms with CERA and one arm with darbepoetin alfa).” The investigators reported all deaths among study enrollees were unrelated to the study drugs.

Roche representatives said in a written statement that there “appears to be no association of these events to excessive hemoglobin levels or the administered doses based on the current review of the data.” They said they have not observed similar types of imbalance in previously completed studies with CERA in cancer patients receiving chemotherapy.

A review of patient data showed that there were imbalances in baseline disease characteristics—including extent of metastatic spread, presence of liver metastases, and incidence of chronic obstructive pulmonary disease—among enrollees in the different arms of the trial.

To date, 153 patients have been enrolled and randomized. Patients who are already enrolled will continue with the study as planned. The safety data from the patients continuing in the study will be closely monitored by Roche working with the Drug Safety Monitoring Board. Roche is further investigating the potential causes for the imbalances in the study arms.

The temporary suspension of recruitment and the decision to allow currently enrolled patients to complete the 12-week study period will permit an in-depth analysis of the data to determine potential confounding factors and potentially allow recruitment to be restarted.

Roche has informed all investigators involved in the study of its decision and is working closely with them. The company has also informed health authorities in the countries where the study is taking place.

— John D. Zoidis, MD