Seattle Genetics and Collaborators Highlight Multiple Antibody-Drug Conjugate (ADC) Programs and Tec
Apr 9th 2013 1:20PM
Updated Apr 9th 2013 1:24PM
Seattle Genetics and Collaborators Highlight Multiple Antibody-Drug Conjugate (ADC) Programs and Technology Advances at AACR
- Presentations Highlight Preclinical Data for Novel SGN-CD33A and SGN-LIV1A Programs and Breakthroughs in Research to Develop Highly Stable Linkers and More Potent Chemotypes -
- AACR Highlights Phase 1 Data for Genentech's DMUC5754A, an ADC for Ovarian Cancer Utilizing Seattle Genetics' Technology -
BOTHELL, Wash.--(BUSINESS WIRE)-- Seattle Genetics, Inc. (NAS: SGEN) today announced that research related to its antibody-drug conjugate (ADC) technology was presented in multiple sessions at the 104th Annual Meeting of the American Association for Cancer Research (AACR) being held in Washington, D.C. Three data presentations highlight the rapid progress being made in ADC technology and testing. This includes preclinical data evaluating ADCs using a potent and newly developed cytotoxic agent, pyrrolobenzodiazepine (PBD) dimer, against two targets, CD33 and CD70. The former, SGN-CD33A, is expected to be advanced into a phase 1 clinical trial in 2013 for patients with acute myeloid leukemia (AML). In addition, preclinical data demonstrate activity of a new ADC for metastatic breast cancer, SGN-LIV1A, utilizing the same proprietary ADC technology as ADCETRIS® (brentuximab vedotin). The company also presented research on a novel method for making highly stable linkers, an advance that is being evaluated for potential future ADCs. In addition, many of the company's collaborators, including Genentech, Pfizer, Progenics and Genmab, are reporting preclinical and clinical data from multiple ADC programs utilizing Seattle Genetics' proprietary ADC technology.
"As the leader in developing ADCs for the treatment of cancer, we are focused on both the current and future technology of this important class of therapeutics. More than half of the ADCs currently in clinical development utilize our technology, and we continue to advance additional candidates, such as SGN-CD33A and SGN-LIV1A, at a rapid pace. We are also looking at ways to enhance the next generation of ADCs, and believe that new potent cytotoxic agents such as PBD dimers, advances in antibody technology such as engineered cysteine antibodies (EC-mAbs), and highly stable linkers are part of that future," said Jonathan Drachman, M.D., Senior Vice President, Research and Translational Medicine at Seattle Genetics. "We are driven to test these ADC advances quickly because cancer patients need new options to fight this relentless disease."
ADCs are designed to harness the targeting ability of antibodies to deliver cell-killing agents directly to cancer 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. Seattle Genetics and its collaborators have ten data presentations at AACR that highlight the widespread evaluation of its ADC technology to potentially impact the way cancer is treated in a meaningful way.
Seattle Genetics' presentations at AACR highlight the following ADC findings:
- PBDs are a class of highly potent, synthetic DNA-crosslinking agents. Data were presented on ADCs utilizing the company's proprietary site-specific conjugation technology (EC-mAbs) to link PBDs to monoclonal antibodies targeted to CD33, an ADC known as SGN-CD33A, and to CD70. Preclinical data demonstrated that SGN-CD33A induced significant antitumor activity in models of AML, including superior activity and potency compared to gemtuzumab ozogamicin (Mylotarg®). The anti-CD70 PBD ADC was broadly active, highly potent and immunologically specific in models of CD70-positive renal cell carcinoma and non-Hodgkin lymphoma. Seattle Genetics plans to submit an investigational new drug (IND) application and initiate a phase 1 clinical trial of SGN-CD33A for AML in 2013. The CD70 PBD ADC is a future potential IND candidate. (Abstract 4321)
- SGN-LIV1A is an ADC that targets LIV-1, which is expressed in most subtypes of metastatic breast cancer. Preclinical data demonstrated that up to 92 percent of breast tumors analyzed expressed LIV-1, while expression was limited in normal tissue. SGN-LIV1A is comprised of an anti-LIV-1 monoclonal antibody linked to a synthetic cell-killing agent called monomethyl auristatin E (MMAE). SGN-LIV1A demonstrated significant antitumor activity in multiple preclinical models at well-tolerated doses. Seattle Genetics plans to submit an IND and initiate a phase 1clinical trial of SGN-LIV1A for breast cancer in 2013. (Abstract 3962)
- Traditional drug-linkers are attached to antibodies to form ADCs in a stable but slowly reversible method. This can allow for some percentage of drug-linker to release from the antibody over the course of several days while circulating through the bloodstream, prior to reaching the designated cancer target. Data presented at AACR describe a novel method to create self-stabilizing maleimido-DPR linkers. Preclinical data demonstrate that minimal drug loss occurs, resulting in ADCs with enhanced antitumor activity and reduced toxicity in some preclinical models. The findings support potential application of the novel self-stabilizing linker technology to future IND candidates. (Abstract 4333)
Multiple presentations by Seattle Genetics' ADC collaborators highlight strong preclinical and clinical progress.
- DMUC5754A is an ADC being developed by Genentech consisting of an anti-MUC16 monoclonal antibody conjugated to the cytotoxic agent MMAE using Seattle Genetics' ADC technology. Data were reported from a phase 1 clinical trial evaluating the safety and activity of DMUC5754A in patients with advanced recurrent platinum-resistant ovarian cancer. DMUC5754A demonstrated antitumor activity with an encouraging safety profile. The phase 1 trial is currently ongoing and further studies are planned. (Abstract LB-290)
- Preclinical data on ADCs utilizing Seattle Genetics' technology from collaborators including Genentech, Pfizer, Genmab and Progenics were presented demonstrating antitumor activity in a range of cancer types. (Abstracts 5619, 4752, 1234, and 2133)
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 (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 four other clinical-stage ADC programs: SGN-75, ASG-5ME, ASG-22ME and SGN-CD19A. Seattle Genetics has collaborations for its ADC technology with a number of leading biotechnology and pharmaceutical companies, including AbbVie (formerly 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 our preclinical product candidates and collaborator ADCs. Factors that may cause such a difference include the risk of adverse events as these ADCs advance in clinical trials. More information about the risks and uncertainties faced by Seattle Genetics is contained in the company's Annual Report on Form 10-K for the year ended December 31, 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.
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