Seattle Genetics Reports Multiple Complete Remissions With SGN-33 in Acute Myeloid Leukemia at ASH

Seattle Genetics, Inc. (Nasdaq:SGEN) today announced positive data from a phase Ia clinical trial of SGN-33 (lintuzumab) demonstrating multiple complete remissions at well-tolerated doses in patients with acute myeloid leukemia (AML). Preclinical data were also presented indicating the anti-leukemic activity of SGN-33 both as a single agent and when used in combination with lenalidomide (Revlimid®) in AML, and the enhanced activity of SGN-40 when used in combination with chemotherapy regimens in non-Hodgkin’s lymphoma. The data were reported during the American Society of Hematology (ASH) 49th Annual Meeting and Exposition in Atlanta, Georgia. SGN-33, or lintuzumab, is a humanized monoclonal antibody that targets the CD33 antigen, which is expressed on a number of hematologic malignancies, including AML, MDS and several myeloproliferative diseases. "These clinical data demonstrate that SGN-33 has potent antitumor activity combined with a favorable tolerability profile that is particularly important for AML patients, many of whom are older and cannot tolerate the toxic side effects of intensive chemotherapy regimens yet are in dire need of therapies that can extend survival,” said Thomas C. Reynolds, M.D., Ph.D., Chief Medical Officer of Seattle Genetics. "We are also presenting new preclinical data for both SGN-40 and SGN-33, demonstrating the promising therapeutic potential of these product candidates when administered in combination with standard regimens.” Based on the positive SGN-33 phase Ia results, Seattle Genetics has expanded into a phase Ib clinical trial that will accrue a total of 50 additional AML and MDS patients to further estimate the single-agent response rate of SGN-33. In addition, the company recently initiated a phase IIb clinical trial of SGN-33 in combination with a low-dose regimen of the chemotherapeutic agent cytarabine for previously untreated AML patients 60 years of age and older who decline or are ineligible for intensive chemotherapy. This randomized, double-blind, placebo-controlled study is designed to assess whether this combination regimen extends survival compared to cytarabine alone. The study will accrue approximately 210 patients at multiple cancer centers around the world. SGN-33 Phase Ia Study Design and Results Data were reported from the single-arm, dose-escalation study of SGN-33 in 31 patients with AML, MDS or other myeloproliferative diseases (Abstract #159). Cohorts of patients received weekly doses of SGN-33 escalating from 1.5 milligrams per kilogram (mg/kg) to 8.0 mg/kg. The median age of enrolled patients was 75 and median time from diagnosis was 1.3 years. More than 50 percent of patients received more than one cycle of SGN-33 therapy. Out of 17 evaluable AML patients treated with SGN-33, there were four complete remissions, one complete remission with incomplete platelet recovery and two partial remissions. Stable disease was observed in six out of ten patients with MDS and in two out of four patients with other myeloproliferative diseases. SGN-33 was well-tolerated with no dose-limiting toxicities or immunogenicity identified. Adverse events were consistent with antibody administration. There was no apparent relationship between dose and related adverse events. SGN-33 Preclinical Data Seattle Genetics reported data from preclinical studies demonstrating that SGN-33 exhibits antitumor activity against both multi-drug resistant (MDR)-positive and MDR-negative AML cell lines (Abstract #919). Preclinical data also indicate that the combination of SGN-33 plus lenalidomide (Revlimid®) enhances the antitumor activity of SGN-33 by increasing the antibody-dependent cellular cytotoxicity (ADCC) effector function of the antibody, providing a rationale for combining these two agents in a clinical setting. Seattle Genetics plans to initiate a phase I combination study of SGN-33 and Revlimid to assess the safety profile and antitumor activity of the combination therapy in patients with intermediate and high risk MDS. SGN-40 Preclinical Data Seattle Genetics reported preclinical data demonstrating that SGN-40 improves the efficacy of standard therapies used for the treatment of non-Hodgkin’s lymphoma, including rituximab (Rituxan®), Rituxan plus CHOP chemotherapy and Rituxan plus ICE chemotherapy (Abstract #2342). Preclinical studies also indicate that SGN-40 downregulates the oncoprotein BCL-6, an important survival signal for tumor cells, and upregulates the proapoptotic family member Tap63alpha, a potential chemosensitizing mechanism. This is the first report of a therapeutic antibody modulating both of these pathways, and provides further support for the ongoing and planned studies of SGN-40 in combination with standard therapies for non-Hodgkin’s lymphoma. SGN-40 is a humanized monoclonal antibody that targets the CD40 antigen, which is expressed on most B lineage hematologic malignancies including non-Hodgkin's lymphoma, multiple myeloma and chronic lymphocytic leukemia. CD40 is also found on many types of solid tumors, including bladder, renal and ovarian cancer. Seattle Genetics is pursuing a broad development plan for SGN-40 under a worldwide collaboration with Genentech, Inc. About Seattle Genetics Seattle Genetics is a biotechnology company developing monoclonal antibody-based therapies for the treatment of multiple types of cancer, including lymphoma, multiple myeloma, leukemia and solid tumors. The company has an exclusive worldwide collaboration agreement with Genentech to develop and commercialize SGN-40. Seattle Genetics also has three other proprietary programs in ongoing clinical trials: SGN-33, SGN-35 and SGN-30. In addition, the company has developed proprietary antibody-drug conjugate (ADC) technology comprised of highly potent synthetic drugs and stable linkers for attaching the drugs to monoclonal antibodies. Seattle Genetics has collaborations for its ADC technology with a number of leading biotechnology and pharmaceutical companies, including Genentech, Bayer, CuraGen, Progenics and MedImmune, as well as an ADC co-development agreement with Agensys. 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 benefit of SGN-33 and SGN-40. 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 risks related to adverse clinical results as SGN-33 and SGN-40 advance in clinical trials, such as patients exhibiting progressive disease or severe adverse events. More information about the risks and uncertainties faced by Seattle Genetics is contained in the company’s filings 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.