The key components of our ADC technology are the stable, enzyme-cleavable linkers and the highly potent, synthetic
cytotoxic drugs. Our novel linkers have been shown in preclinical models to be up to 10 times more stable in blood
than conventional means of attaching drugs to antibodies. We have also developed a highly potent class of
antitubulin drugs
called auristatins, including monomethyl auristatin E (MMAE) and monomethyl auristatin F (MMAF). These auristatins
are 100 to 1000 fold more potent than traditional chemotherapy drugs. Importantly, since both the linker and drug
components are synthetic, our ADC technology is readily scalable, representing an improvement over natural product
drug systems that are typically more challenging and expensive to produce.
Our lead ADC, brentuximab vedotin (SGN-35), comprises an anti-CD30 monoclonal antibody attached to MMAE through an enzyme-cleavable
linker system. CD30 is expressed on Hodgkin lymphoma, various types of T-cell non-Hodgkin
lymphomas and other hematologic malignancies. In a phase I dose-escalation clinical trial of brentuximab vedotin for CD30-positive malignancies, primarily Hodgkin
lymphoma, at doses of 1.2 milligrams per kilogram and higher administered every
three weeks, 54% of patients achieved an objective response
(complete and partial responses), of which 39% were complete responses.
Brentuximab vedotin was generally well tolerated with the majority of adverse
events being Grade 1 and 2. These promising findings are in contrast to
clinical data with the unconjugated antibody, which did not induce objective
responses in a similar population of Hodgkin lymphoma patients.
We have also reported substantial preclinical data with brentuximab vedotin, including data demonstrating that the targeting ability
of brentuximab vedotin results in concentrations of MMAE within tumors up to 30-fold higher than non-targeted drugs. Further,
MMAE tumor concentrations were 1000 fold greater than MMAE blood concentrations following dosing with
brentuximab vedotin.
These preclinical data demonstrate that brentuximab vedotin effectively targets and releases its cell-killing payload, MMAE, within CD30-
positive tumors.
Visit our Scientific Publications page for published research on our ADC technology and programs.
ADC Product Candidates and Collaborations
Brentuximab vedotin is in multiple clinical trials for Hodgkin lymphoma and
other CD30-positive hematologic malignancies, including a pivotal trial for
relapsed and refractory Hodgkin lymphoma.
We are also advancing a second ADC program, SGN-75, which is comprised of an anti-CD70 monoclonal antibody
attached to MMAF. We have reported preclinical data on CD70 expression on a variety of solid tumors, including renal
cell carcinoma, pancreatic, ovarian and lung cancer, as well as in multiple
myeloma and non-Hodgkin lymphoma. SGN-75 has shown potent antitumor
activity in several tumor models, underscoring its therapeutic potential in a range of cancer types. We initiated a phase I clinical trial with SGN-75 in
November 2009.
Under our collaboration with Agensys, a subsidiary of Astellas Pharma, we are
also advancing ASG-5ME towards planned clinical trials in 2010. This ADC
has potential in several types of solid tumors.
Seattle Genetics has also licensed its ADC technology to multiple leading biotechnology and pharmaceutical
companies in exchange for upfront payments, fees, milestones and royalties on net sales of products incorporating our
technology.
For more information about ADC technology collaboration opportunities, please email
businessdevelopment@seagen.com.
