CD70 is a receptor expressed on many types of blood cancers as well as the majority of renal cancer cases. The expression profile of this target is highly restricted to cancer cells, which, combined with its ability to internalize antibodies, makes it a desirable target for ADCs. Seattle Genetics is evaluating a naked antibody as well as an ADC that target CD70, both candidates are based on the same antibody, which was licensed from CLB-Research and Development. The naked antibody, SGN-70, is evaluated for certain blood cancers and is expected to enter phase I during 2008. Another possible use for SGN-70 is for autoimmune diseases, as it is expressed on white blood cells that are involved in the disease, but not on “resting” cells.
SGN-75 is an ADC based on SGN-70, which is currently evaluated pre-clinically for Renal cell carcinoma. This disease, although not as common as prostate and lung cancers, represents a large market opportunity with over 43,000 new cases and almost 13,000 deaths expected in 2007 in the US alone. Although surgical resection of the kidney has high chances to prevent the disease from spreading, nearly one third of patients are diagnosed at advanced stage, where the cancer has spread to additional organs. In addition, more than 30% of patients who undergo resection will eventually develop metastatic disease, for which very few therapeutic options exist. SGN-75 is expected to enter the clinic only in 2009.
CD 19, which is expressed mainly on NHL and several leukemias, is one of the hottest targets in the ADC market. Two such candidates are currently in the clinic: Sanofi’s SAR3419 based on Immunogen’s technology, and Micromet’s (MITI) & MedImmune’s MT103, which has demonstrated surprisingly impressive results. Additional companies that are evaluating anti-CD19 ADCs pre-clinically are Genentech, which has chosen the same non cleavable linker used in its Herceptin-DM1, courtesy of Immunogen, and Medarex (MEDX). Seattle Genetics uses a non cleavable linker for its anti-CD19 ADC as well, unlike the peptide-based linker used in most of its ADCs. Another interesting factor is the slightly modified chemo drug the company uses, MMAF. This drug proved to be more potent in several preclinical platforms, probably due to its inability to diffuse or to be secreted out of the cell, upon ADC internalization. MMAF is likely to be used by the company in some of its future clinical programs.
Multiple undisclosed candidates – Partnership with Genentech
As the prominent antibody company in the industry, Genentech is Seattle Genetics’ most important partner. Although the two companies are not involved in any clinical stage ADC program, it seems like there is plenty of activity going on behind the scenes. Genentech, which has openly expressed its enthusiasm regarding ADCs, is currently evaluating more than 20 ADC compounds. The number of projects in which Seattle Genetics is involved is unknown, but Genentech has published several scientific articles that describe ADCs powered by Seattle Genetics’ technology, including an anti-CD79 ADC targeted at NHL and anti-MUC16 ADC targeted at ovarian cancer. Interestingly, according to published scientific articles and the Herceptin-DM1 clinical program, Genentech’s scientists seem to prefer noncleavable linkers, rather than the cleavable linkers, commonly used by Seattle Genetics and Immunogen.
Seattle Genetics has partnered with numerous other companies including Bayer, PDL, Celera and Agensys, which was recently acquired by Astellas Pharma, Japan’s second- largest drugmaker. Even though success rates in oncology are quite modest, we believe Seattle Genetics’ broad pipeline preclinical pipeline poises the company for an exciting decade and hopefully several clinically approved products.
Author is long SGEN & MITI