BOTHELL, Wash.--(BUSINESS WIRE)--
Seattle Genetics, Inc. (SGEN) today highlighted research related to its antibody-drug conjugate (ADC) programs and technology in more than 15 presentations at the 105th Annual Meeting of the American Association for Cancer Research (AACR) being held April 5 to 9, 2014 in San Diego, CA. The presentations describe promising advances that further enhance its ADC technology platform and review preclinical data from its proprietary SGN-CD19A and SGN-CD70A programs that support ongoing clinical development activities. In addition, presentations feature preclinical and clinical data from several collaborator ADC programs, including Genentech (a member of the Roche Group), GlaxoSmithKline, Takeda, Celldex, Agensys and Bayer. Of the collaborator presentations, AACR highlighted in a press program encouraging data from an ongoing phase 1 clinical trial of an anti-endothelian B receptor (ETBR) ADC in patients with metastatic or unresectable melanoma in development by Genentech utilizing Seattle Genetics’ technology.
“With 16 years of experience in the field of ADCs, the technology we are utilizing in our ADCETRIS, pipeline and collaborator programs represents a remarkable platform comprised of novel antibody, linker and cytotoxic payload components. Collectively, these components have been successfully combined by Seattle Genetics and our collaborators to develop a growing number of ADCs that may offer treatment options to patients with solid tumors and hematological malignancies,” said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. “The data being presented at the 2014 AACR annual meeting demonstrate our commitment to lead the ADC field today and in the future, using both our proven ADC technology that empowers our FDA approved product, ADCETRIS, and also introducing novel ADC technologies, including new linker and drug designs.”
ADCs contain monoclonal antibodies that are designed to selectively deliver cytotoxic agents to tumor cells. With over sixteen years of experience and knowledge in ADC innovation, Seattle Genetics has developed proprietary technology employing synthetic cytotoxic agents and stable linker systems that attach these cytotoxic agents to the antibody. Seattle Genetics’ linker systems are designed to be stable in the bloodstream and release the potent cell-killing agent once inside targeted 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.
Multiple corporate, investigator and collaborator presentations are being featured at AACR. Abstracts can be found at www.aacr.org and include the following:
Advances with ADC Pipeline and Research Programs
Preclinical data presentations from Seattle Genetics’ proprietary ADC programs SGN-CD70A and SGN-CD19A, in addition to a research program, support program advancement or further evaluation (Abstracts #4642, #DDT01-04, #2647 and #2890):
- SGN-CD19A is an ADC comprised of an anti-CD19 monoclonal antibody linked to a synthetic cytotoxic cell-killing agent, monomethyl auristatin F (MMAF). Data describe modeling methodology for predicting pharmacokinetic and pharmacodynamic behavior of the ADC, which may help refine dosing in future clinical trials. On Sunday, SGN-CD19A was highlighted during a special session “New Drugs on the Horizon.” Seattle Genetics plans to present additional SGN-CD19A clinical data in ALL and NHL during 2014.
- SGN-CD70A is an ADC comprised of an antibody targeted to CD70 attached to a highly potent cytotoxic agent called a pyrrolobenzodiazepine (PBD) dimer via a proprietary engineered cysteine antibody (EC-mAb). The data demonstrate SGN-CD70A induces targeted cell killing via DNA damage of treated tumors in RCC and NHL models. The company plans to advance SGN-CD70A into phase 1 clinical trials in the second half of 2014.
- A novel small molecule, 2-fluorofucose (2FF), that blocks cellular incorporation of a sugar (fucose) was shown to have antitumor activity by two distinct mechanisms. The data demonstrate 2FF as a single agent delays the growth of solid tumors in multiple xenograft models; and 2FF also enhances the antibody-mediated immune response to cancers using a tumor vaccine model.
Innovations in ADC Technology
Three presentations highlight preclinical data with innovative ADC linker systems that increased stability and enhanced the potency of ADCs (Abstracts #1786, #4465 and #4470):
- A novel linker design containing polyethylene glycol (PEG) polymer attached to the cleavable β-glucuronide- monomethyl auristatin E (MMAE) linker system delivered a greater MMAE concentration to the targeted cells and provided improved pharmacokinetics when ADCs were loaded with a higher number of drugs per antibody, enabling increased potency;
- Glucuronide-linked ADCs demonstrate enhanced cytotoxic delivery and potency in preclinical models; and
- The intrinsic hydrophobicity of drug-linkers is responsible for accelerated clearance of ADCs with eight drugs per antibody. A novel hydrophilic auristatin drug-linker was developed to increase potency and tolerability in preclinical models.
Preclinical Evaluations of ADCETRIS (Brentuximab Vedotin)
Three data presentations highlight preclinical research related to brentuximab vedotin that further characterize the targeting of CD30-positive cells, drug potency and mechanisms of resistance (SGN-35) (Abstracts #104, #688 and #3694):
- Preclinical imaging studies demonstrate that a radiolabeled SGN-35 ADC specifically targets CD30-expressing cells;
- Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) cell lines with acquired resistance to brentuximab vedotin were characterized; resistance to the payload can be overcome using novel anti-CD30 ADCs; and
- A preclinical analysis of antitumor activity of brentuximab vedotin demonstrating that efficient cell killing is related to the concentration of released payload and that brentuximab vedotin can kill CD30-negative adjacent cells via a localized bystander effect.
ADC Collaborator Presentations
Several presentations by Seattle Genetics’ ADC collaborators highlight strong preclinical and clinical progress in many disease areas, including:
- An anti-ETBR ADC that is in an ongoing phase 1 clinical trial for patients with metastatic or unresectable melanoma, and preclinical data evaluating interactions between BRAF or MEK inhibition on ETBR expression and activity (Genentech, Abstracts #CT233, #2924);
- An anti-mesothelin ADC being evaluated in mesothelin-expressing cancers (Genentech, Abstracts #4494, #4502);
- An anti-B cell maturation antigen-monomethyl auristatin F ADC being evaluated in multiple myeloma (GlaxoSmithKline, Abstract #644);
- Pharmacokinetic and efficacy model for an anti-guanylyl cyclase C (GCC) ADC (Takeda, Abstract #4649);
- An anti-GPNMB ADC (CDX-011) in evaluation for osteosarcoma (Celldex, Abstract #3984);
- A TIM-1 targeting ADC for the treatment of ovarian and renal cell carcinoma (Celldex, Abstract #2649);
- An anti-CD37 ADC being evaluated in NHL, chronic lymphocytic leukemia and acute myeloid leukemia (Agensys, Abstract #2650); and
- An anti-C4.4a (LYPD3) ADC for the treatment of lung squamous cell carcinoma (Bayer, Abstract #5445).
About Seattle Genetics
Seattle Genetics is a biotechnology company focused on the development and commercialization of innovative antibody-based therapies for the treatment of cancer. Seattle Genetics is leading the field in developing antibody-drug conjugates (ADCs), a technology designed to harness the targeting ability of antibodies to deliver cell-killing agents directly to cancer cells. The company’s lead product, ADCETRIS® (brentuximab vedotin) is an ADC that, in collaboration with Takeda Pharmaceutical Company Limited, has been approved for two indications in more than 35 countries, including the U.S., Canada, Japan and members of the European Union. Additionally, ADCETRIS is being evaluated broadly in more than 30 ongoing clinical trials. Seattle Genetics is also advancing a robust pipeline of clinical-stage ADC programs, including SGN-CD19A, SGN-CD33A, SGN-LIV1A, ASG-22ME and ASG-15ME. 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, Genentech, GlaxoSmithKline and Pfizer. 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 preclinical product candidates and collaborator ADCs. 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 risk of adverse events as these ADCs advance in other 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, 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.
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