Seattle Genetics, Inc. (NASDAQ:SGEN) today announced initiation of a phase 1 clinical trial of SGN-CD33A for patients with acute myeloid leukemia (AML). SGN-CD33A is a novel antibody-drug conjugate (ADC) utilizing Seattle Genetics’ newest ADC technology targeted to CD33, which is expressed on most AML cells. The CD33 antibody is attached to a highly potent cytotoxic DNA-crosslinking agent, a pyrrolobenzodiazepine (PBD) dimer, via a proprietary site-specific conjugation technology to a monoclonal antibody with engineered cysteines (EC-mAb). The trial is designed to assess the safety and anti-leukemia activity of SGN-CD33A. “AML is a devastating disease with poor prognostic factors and few compelling treatment options, especially in the relapsed disease setting and in patients over the age of 60,” said Jonathan Drachman, M.D., Senior Vice President, Research and Translational Medicine, at Seattle Genetics. “SGN-CD33A is an innovative ADC that utilizes our latest technology, combining a highly potent cell-killing agent with our new engineered antibody (EC-mAb) technology that results in uniform drug-loading. It is designed to be a highly potent ADC directed to the CD33 antigen, which is found on AML cells. We look forward to evaluating its use as a potential treatment option for AML patients.” The study is a phase 1, open-label, multi-center, dose-escalation clinical trial. The primary endpoints are the estimation of the maximum tolerated dose and evaluation of the safety of SGN-CD33A. In addition, the trial will evaluate anti-leukemia activity, pharmacokinetics, progression-free survival and overall survival in patients with CD33-positive AML. The dose escalation portion of the study is designed to evaluate SGN-CD33A administered every three weeks and will enroll up to approximately 90 patients at multiple centers in the United States. Patients who achieve a complete remission are eligible to continue to receive SGN-CD33A at a lower, maintenance dose given every three weeks. Dose escalation cohorts that show evidence of anti-leukemia activity may be expanded to allow for a more comprehensive evaluation of safety and clinical activity.
Preclinical data presented at the 2012 American Society of Hematology (ASH) Annual Meeting demonstrated that SGN-CD33A induced CD33-specific cytotoxic activity at low doses in a broad panel of AML cell lines and in primary AML patient samples, including those resistant to multiple other anti-leukemic agents. In addition, SGN-CD33A yielded antitumor activity and improved survival in multiple preclinical AML models.ADCs are monoclonal antibodies that are designed to selectively deliver cytotoxic agents to tumor cells. This approach is intended to spare non-targeted cells and thus reduce many of the toxic effects of traditional chemotherapy while enhancing antitumor activity. SGN-CD33A is an ADC utilizing PBD dimers, a class of DNA-crosslinking agents that are significantly more potent than systemic chemotherapeutic drugs. Seattle Genetics has been working with PBDs since 2009 under an exclusive research and licensing arrangement with Spirogen Ltd. Over the past four years, Seattle Genetics has selected and optimized specific PBD molecules for its proprietary use in ADCs. In addition, SGN-CD33A employs a novel linker system and proprietary, site-specific conjugation technology (EC-mAb) that allows uniform drug-loading of the cell-killing PBD agent to the anti-CD33 antibody. The ADC is designed to be stable in the bloodstream and to release its cytotoxic agent upon internalization into CD33-expressing cells. For more information about the trial, including enrolling centers, please visit www.clinicaltrials.gov. About Acute Myeloid Leukemia Acute myeloid leukemia, also called acute myelocytic leukemia or AML, is an aggressive type of cancer of the bone marrow and blood that progresses rapidly without treatment. AML is a cancer that starts in the cells that are supposed to mature into different types of blood cells. AML starts in the bone marrow (the soft inner part of the bones, where new blood cells are made) and quickly moves into the blood. According to the American Cancer Society, in 2013 approximately 14,590 new cases of AML (mostly in adults) will be diagnosed and about 10,370 deaths will occur from AML (almost all will be in adults).
About Seattle GeneticsSeattle 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 ® (brentuximab vedotin), received accelerated approval from the U.S. Food and Drug Administration in August 2011 and approval with conditions from Health Canada in February 2013 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 five other clinical-stage ADC programs: SGN-75, ASG-5ME, ASG-22ME, SGN-CD19A and SGN-CD33A. Seattle Genetics has collaborations for its ADC technology with a number of leading biotechnology and pharmaceutical companies, including AbbVie, Agensys (an affiliate of Astellas), Bayer, Celldex, 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 SGN-CD33A. 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 this recently initiated clinical trial and the risk of adverse events as SGN-CD33A 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 March 31, 2013, 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.