Seattle Genetics, Inc. has announced that data from its antibody-drug conjugate (ADC) programs, SGN-35 and SGN-75, were presented at the 2009 Annual Meeting of the American Association for Cancer Research (AACR) being held in Denver, CO. Preclinical data with SGN-35 further elucidate its mechanism of action and demonstrate its superior antitumor activity in lymphoma compared with non-targeted agents. In addition, data with SGN-75 indicate its therapeutic potential in multiple types of solid tumors.
“Our increasing body of preclinical research further demonstrates the power of our ADC technology to effectively target tumor cells, deliver potent drug payloads and induce antitumor activity at well-tolerated doses,” said Clay B. Siegall, Ph.D., President and Chief Executive Officer at Seattle Genetics. “SGN-35 is in late-stage clinical trials, including an ongoing pivotal trial for Hodgkin lymphoma. We are positioning our next ADC product candidate, SGN-75, for an investigational new drug submission in the second half of 2009 for the treatment of both hematologic malignancies and solid tumors.”
SGN-35 is an ADC utilizing Seattle Genetics' proprietary technology comprising an anti-CD30 monoclonal antibody attached to the synthetic, highly potent drug monomethyl auristatin E (MMAE) through an enzyme-cleavable linker system. The linker is designed to be stable in the bloodstream but to release the drug payload under specific conditions once inside target cells, thereby sparing non-target cells many of the toxic effects of traditional chemotherapy.
Preclinical data were presented at AACR showing superior antitumor activity of SGN-35 in Hodgkin lymphoma compared to administration of several non-targeted drugs, including vinorelbine, vinblastine and unconjugated MMAE. Due to the targeting ability of SGN-35, concentrations of MMAE within tumors were up to 30-fold higher than the non-targeted drugs. Further, MMAE tumor concentrations were 1000 fold greater than MMAE blood concentrations following dosing with SGN-35. These data demonstrate that SGN-35 effectively targets and releases its cell-killing payload, MMAE, within CD30-positive tumors. The results provide a basis for understanding the profound antitumor activity of SGN-35 at well tolerated doses in clinical trials (Abstract #3234).
SGN-35 is in an ongoing pivotal clinical trial for relapsed or refractory Hodgkin lymphoma and a planned phase II trial for systemic anaplastic large cell lymphoma. The company intends to report additional phase I clinical data with SGN-35 during an oral presentation at the American Society of Clinical Oncology annual meeting to be held May 29 to June 2, 2009.
SGN-75 is an ADC comprising an anti-CD70 monoclonal antibody attached to the synthetic, highly potent drug monomethyl auristatin F (MMAF). Data presented at AACR demonstrate CD70 expression on a variety of solid tumors, including pancreatic, larynx/pharynx, ovarian, skin, lung and colon cancer. This presentation adds to data previously reported by Seattle Genetics on CD70 expression in multiple hematologic malignancies, renal cancer and glioblastoma. SGN-75 was also shown to induce potent antitumor activity in models of pancreatic and ovarian cancer, underscoring its therapeutic potential in a range of carcinomas (Abstract #4652).