Seattle Genetics has exercised an option to co-develop a second tumor-targeting antibody-drug conjugate (ADC) under its existing collaboration with Agensys, an affiliate of Tokyo-based Astellas Pharma. The new agreement covers development of ASG-22ME (formerly ASG-22M6E), an ADC targeting the nectin-4 antigen expressed on multiple solid tumors. Seattle and Agensys are already co-developing another ADC, ASG-5ME, which is in Phase I trials as a potential treatment for pancreatic and prostate cancers.
ASG-22ME comprises a fully human nectin-4 antibody linked to the cytotoxic agent monomethyl auristatin (MMAE) using Seattle’s enzyme-cleavable linker technology. The construct is designed to be stable in the bloodstream, and only release MMAE on internalization into nectin-4-expressing tumor cells. Agensys recently submitted an IND application to FDA for approval to start a Phase I study with ASG-22ME. The trial will evaluate the safety, tolerability, pharmacokinetic profile, and antitumor activity of increasing doses of the drug in up to 50 patients.
Agensys is developing a pipeline of therapeutic fully human mAbs for cancer therapy based on the firm’s portfolio of cancer targets. Its pipeline comprises both naked and ADC candidates against cancers including prostate, kidney, pancreas, ovary, bladder, lung, colon, breast, and skin.
Seattle is focused on the development of mAb-based treatments for cancer and autoimmune diseases. The Agensys-partnered ADC products ASG-5ME and ASG-22ME both utilize Seattle’s cytotoxic agent and linker technologies. The firm claims preclinical studies have shown its linkers are up to 10 times more stable in blood than conventional means of attaching drugs to antibodies, while the synthetic auristatin antimicrotubule agents attached to the antibodies are 100–1,000 times more potent than traditional chemotherapy drugs.
Seattle’s lead in-house ADC candidate, brentuximab vedotin, is partnered with Millennium. Separate BLA filings have been accepted by FDA for approval of the drug in the treatment of relapsed or refractory Hodgkin lymphoma (HL), and relapsed or refractory systemic anaplastic large cell lymphoma (ALCL). Both applications have been given an August 30, 2011 PDUFA date. Phase III brentuximab trials are also ongoing in patients at high risk of residual Hodgkin lymphoma following autologous stem cell transplant, along with Phase I or II combination studies in HL and systemic ALCL. Additional ADC candidates are in earlier clinical development by Seattle for the treatment of a range of solid and hematologic cancers as well as autoimmune diseases.
The firm has in addition licensed its ADC technology to pharma and biotech companies including Celldex, Genentech, GenMab, Bayer, Abbott, GSK, Pfizer, and Daiichi-Sankyo. Eleven collaborator ADC programs utilizing Seattle's technology are in clinical development, and the partnerships with Agensys and Genmab include opportunities for Seattle to co-develop specific ADC products.