Seattle Genetics Announces Data from ASG-5ME Phase I Clinical Trial for Pancreatic Cancer

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American Society of Clinical Oncology 2013 Gastrointestinal Cancers Symposium

BOTHELL, Wash.--(BUSINESS WIRE)--Seattle Genetics, Inc. (Nasdaq: SGEN) today presented interim results from a phase I clinical trial evaluating ASG-5ME for the treatment of metastatic pancreatic ductal adenocarcinoma (PDA) at the American Society of Clinical Oncology (ASCO) 2013 Gastrointestinal Cancers Symposium being held January 24-26, 2013 in San Francisco, CA. ASG-5ME is an antibody-drug conjugate (ADC) targeting the SLC44A4 antigen and is being co-developed by Seattle Genetics and Agensys, Inc., an affiliate of Tokyo-based Astellas Pharma Inc., for the treatment of solid tumors. The phase I data from the ASG-5ME clinical trial in advanced pancreatic cancer identified the maximum tolerated dose (MTD) for weekly administration, demonstrated tolerability and provided preliminary evidence for antitumor activity.

"Pancreatic cancer is a terrible disease, with a median survival of only six months for metastatic disease and a five-year survival rate of less than six percent," said Jonathan Drachman, M.D., Senior Vice President, Research and Translational Medicine of Seattle Genetics. "There is an urgent need to identify more effective therapeutic options for these patients, and we are encouraged by the tolerability and evidence of antitumor activity observed in this phase I trial. We look forward to further results from ongoing trials of ASG-5ME in prostate and gastric cancer."

ADCs are monoclonal antibodies that are designed to deliver cytotoxic agents selectively to tumor cells. This approach is designed to spare non-targeted cells and thus reduce many of the toxic effects of traditional chemotherapy while enhancing antitumor activity. With over a decade of experience and knowledge in ADC innovation, Seattle Genetics has developed proprietary technology employing synthetic cytotoxic agents, such as monomethyl auristatin E (MMAE), and stable linker systems that attach these cytotoxic agents to the antibody. Seattle Genetics' linker systems are designed to be stable in the bloodstream and release the cell-killing agent once inside targeted cancer cells. ADCETRIS® (brentuximab vedotin) is the first drug approved utilizing Seattle Genetics' ADC technology.

A Phase I Study of ASG-5ME, a Novel Antibody-Drug Conjugate, in Pancreatic Ductal Adenocarcinoma (Abstract #176)

A phase I clinical trial was conducted to evaluate the safety and activity and to identify the MTD of ASG-5ME in patients with metastatic PDA. At the time of data analysis, 35 patients with metastatic PDA were enrolled in the trial. These patients had a median age of 63 and were heavily pretreated with a median of three prior therapies. The median time since initial PDA diagnosis and time since identification of metastatic disease was 1.4 years and 0.59 years, respectively. Patients received doses ranging from 0.3 milligrams per kilogram (mg/kg) to 1.5 mg/kg administered weekly for three out of every four weeks.

Key findings included:

  • The MTD was identified as 1.2 mg/kg weekly. Of the 35 patients who participated in the trial at the time of analysis, 18 were treated at the MTD.
  • Best response for the 18 patients treated at 1.2 mg/kg weekly included one patient (six percent) who achieved a partial response, six patients (33 percent) with stable disease and four patients (22 percent) who had progressive disease. Seven patients (39 percent) were not evaluable for response.
  • The most common adverse events occurring in patients at the MTD included fatigue (50.0 percent), vomiting (44.4 percent), decreased appetite (38.9 percent), abdominal pain (33.3 percent) and nausea (33.3 percent).
  • The most common Grade 3 or 4 adverse events occurring in patients at the MTD included fatigue (27.8 percent), abdominal pain (22.2 percent), vomiting (16.7 percent) and neutropenia (16.7 percent).

Enrollment of PDA patients to this ASG-5ME phase I trial is complete. Enrollment of patients with relapsed or refractory gastric adenocarcinoma is ongoing. In addition, Seattle Genetics and Agensys are evaluating ASG-5ME in a phase I study for castration-resistant prostate cancer (CRPC). For more information about the trials, visit www.clinicaltrials.gov.

About Pancreatic Cancer

Pancreatic cancer occurs when malignant (cancerous) cells grow, divide and spread in the tissues of the pancreas. The most common type of pancreatic cancer, accounting for 95 percent of tumors, is adenocarcinoma arising within the exocrine component of the pancreas. Pancreatic cancer is the fourth leading cause of cancer-related death in the United States and for all stages of the disease combined, the one- and five-year relative survival rates are 25 percent and six percent, respectively.

About ASG-5ME

ASG-5ME is an ADC composed of a fully human antibody directed to SLC44A4, a solute carrier antigen family member identified by Agensys to be overexpressed in epithelial cancers, including more than 80 percent of samples derived from patients with prostate, pancreatic and gastric cancers. The antibody is attached to monomethyl auristatin E (MMAE) via an enzyme-cleavable linker using Seattle Genetics' proprietary technology. The ADC is designed to be stable in the bloodstream, but to release MMAE upon internalization into SLC44A4-expressing tumor cells, resulting in targeted cell-killing.

Seattle Genetics and Agensys are co-developing and will globally co-commercialize and share profits on a 50:50 basis for ASG-5ME, as well as ASG-22ME, an ADC targeted to Nectin-4. Seattle Genetics also has an option for 50:50 cost and profit-sharing of a third ADC program at the time of investigational new drug submission.

About Seattle Genetics

Seattle Genetics is a biotechnology company focused on the development and commercialization of monoclonal antibody-based therapies for the treatment of cancer. The company's lead program, ADCETRIS, received accelerated approval from the U.S. Food and Drug Administration in August 2011 for two indications. In addition, under a collaboration with Millennium: The Takeda Oncology Company, ADCETRIS received conditional approval from the European Commission in October 2012. Seattle Genetics also has three other clinical-stage antibody-drug conjugate (ADC) programs: SGN-75, ASG-5ME and ASG-22ME. Seattle Genetics has collaborations for its ADC technology with a number of leading biotechnology and pharmaceutical companies, including Abbott, Agensys (an affiliate of Astellas), Bayer, Celldex Therapeutics, Daiichi Sankyo, Genentech, GlaxoSmithKline, Millennium, Pfizer and Progenics, as well as ADC co-development agreements with Agensys and Genmab. More information can be found at www.seattlegenetics.com.

Certain of the statements made in this press release are forward-looking, such as those, among others, relating to the therapeutic potential of ASG-5ME in the featured indication and initiation of future clinical trials. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the inability to show sufficient activity in subsequent trials and the risk of adverse events as ASG-5ME advances in clinical trials. More information about the risks and uncertainties faced by Seattle Genetics is contained in the company's 10-Q for the quarter ended September 30, 2012 filed with the Securities and Exchange Commission. Seattle Genetics disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.