Seattle Genetics is another player in the ADC field, with 27 compounds in development. It developed the first new drug since 1977 to treat Hodgkin lymphoma (HL). Called Adcetris™ (brentuximab vedotin), it was approved August 2011 for both HL and a rare lymphoma known as systemic anaplastic large cell lymphoma (ALCL). Further trials for related indications are under way in collaboration with Millennium: The Takeda Oncology Company.
The company also is engaged with collaborations with 10 other companies: Abbott, Agensys—a division of Astellas, Bayer Healthcare Pharmaceuticals, Celldex Therapeutics, Daiichi-Sankyo, Genentech, Genmab, GSK, Pfizer, and Progenics Pharmaceuticals.
In June, Seattle Genetics expanded its Phase I trials of ASG-5ME, a fully humanized mAb that targets SLC44A4 (AGS-5), which is upregulated in many epithelial tumors. Trials for prostate, pancreatic, and gastric cancers are under way. Two months later, in August, it launched SGN-75, a Phase Ib study for renal cell carcinoma using its anti-CD70MAb and a monomethyl auristatin F payload, in combination with the mTOR inhibitor everolimus. Another trial also is under way, dubbed ASG-22ME. This ADC targets Nectin-4, which is expressed on cancers of the bladder, breast, lung, and pancreas.
Its R&D work focuses upon developing mAbs and ADCs with novel specificities and activities against proteins that are highly expressed on tumor cells. Antibody engineering work is ongoing, both in antibody humanization and defucosylation. Early data from an ADC based upon using small molecule inhibitors of fucosylation shows antitumor activity and good dose tolerance. Seattle Genetics says this indicates the therapeutic may have promise as a syngeneic tumor vaccine.
The company’s pipeline supports its early-stage auristatin-based ADC platform with PBDs—a class of DNA-crosslinking agents licensed from Spirogen—and an engineered systeine mAb that increases linker stability and the uniformity of drug loading. The latter enables site-specific conjugation of two cytotoxic compounds per antibody. Preclinical programs include an integrin expressed on multiple solid tumors, including cancers of the lung, pancreas, head, and neck.