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Press Release

Seattle Genetics Demonstrates Continued Leadership in Antibody-Drug Conjugates at AACR

Seattle Genetics Inc.
Posted on: 04 Apr 12

Seattle Genetics, Inc. (Nasdaq: SGEN) today announced that research related to its antibody-drug conjugate (ADC) technology was presented at the 103rd Annual Meeting of the American Association for Cancer Research (AACR) being held in Chicago, IL. The presentations highlighted data from an ADC using a potent new cytotoxic agent that can be linked to antibodies, a method to produce uniform drug-loading on antibodies with enhanced stability and a novel preclinical ADC targeted to solid tumors. In addition, data were presented showing the antitumor activity of a novel fucose inhibitor that can be administered orally.

“Our presentations at AACR highlight several significant discoveries that could augment or complement our auristatin-based ADC platform, including the introduction of a novel DNA-crosslinking agent and an engineered cysteine antibody that increases linker stability and uniformity of drug-loading,” said Jonathan Drachman, M.D., Senior Vice President, Research and Translational Medicine at Seattle Genetics. “In parallel, we are working to advance a growing pipeline of preclinical programs, which includes an integrin expressed on multiple solid tumors. We are committed to advancing the field of ADCs in order to improve the lives of people with cancer, and we believe our research moves us closer to achieving this goal.”

ADCs are monoclonal antibodies that selectively deliver potent cell-killing agents to tumor cells. With over a decade of experience and knowledge in ADC innovation, Seattle Genetics has developed proprietary technology employing synthetic cell-killing agents called auristatins (such as monomethyl auristatin E [MMAE] and monomethyl auristatin F [MMAF]) and stable linker systems that attach auristatins 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. This approach is intended to spare non-malignant cells and reduce many of the toxic effects of traditional chemotherapy while enhancing antitumor activity. ADCETRIS™ (brentuximab vedotin) is the first drug approved utilizing Seattle Genetics’ auristatin-based ADC technology.

Seattle Genetics’ presentations at AACR highlighted the following ADC findings:

  • Engineered cysteine monoclonal antibody (EC-mAb) technology enables site-specific conjugation of two cell-killing agents per antibody, resulting in uniform drug-loading. The EC-mAb technology facilitates conjugation with a broad range of chemotypes, including pyrrolobenzodiazepine dimers (PBDs). In preclinical studies, two-loaded EC-mAb ADCs demonstrated improved stability and antitumor activity comparable to traditional four-loaded ADCs in multiple tumor models. (Abstract 4634)
  • PBDs are a class of highly potent DNA-crosslinking agents, which kill cells using a mechanism of action distinct from auristatins. Under an agreement with Spirogen, Seattle Genetics has developed a single PBD molecule that is being evaluated for future clinical-candidate ADCs. Data reported at AACR demonstrate that when this PBD molecule is conjugated to an anti-CD70 antibody using Seattle Genetics’ EC-mAb technology, the resulting ADC possesses potent antitumor activity at tolerated doses in models of renal cell carcinoma. (Abstract 4631)
  • Integrin alpha-v-beta6 (“avß6”) is a promising new target antigen expressed at high levels on multiple solid tumors, including cancers of the lung, pancreas and head and neck. An anti-avß6 ADC demonstrated antitumor activity in multiple preclinical models. (Abstract 4630)

Seattle Genetics has previously reported that small molecule inhibitors of fucosylation can be used in vitro to produce defucosylated antibodies with enhanced antibody-dependent cellular cytotoxicity (ADCC) activity (SEA technology). In an oral presentation on Monday at AACR, the company reported new data that oral administration of one of these small molecules results in dose-dependent defucosylation of endogenous proteins, including antibodies. Data demonstrate antitumor activity at well-tolerated doses of the inhibitor of fucosylation in several in vivo tumor models, including a syngeneic tumor vaccine model. These early data suggest that systemic administration of the fucose inhibitor may have potential as an anti-cancer therapy. (Abstract 2945)

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 U.S. Food and Drug Administration granted accelerated approval of ADCETRIS in August 2011 for two indications. ADCETRIS is being developed in collaboration with Millennium: The Takeda Oncology Company. In addition, Seattle Genetics has three other clinical-stage 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, Bayer, Celldex Therapeutics, Daiichi Sankyo, Genentech, GlaxoSmithKline, Millennium, Pfizer and Progenics, as well as ADC co-development agreements with Agensys, an affiliate of Astellas, 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 Seattle Genetics’ product candidates and its ADC technology. 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 failure of our or our collaborators’ product candidates incorporating ADC technologies to show sufficient safety and efficacy to advance in clinical trials or obtain regulatory approval. More information about the risks and uncertainties faced by Seattle Genetics is contained in the company’s 10-K for the year ended December 31, 2011 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.

Business Wire
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Last updated on: 04/04/2012

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