In our drive to improve targeted therapies of diseases, we have assembled significant expertise in antibody engineering, particularly proprietary CDR-grafting methods, antibody production, immunochemistry, molecular biology, antibody conjugation, peptide chemistry, synthetic organic chemistry, and protein engineering.
Beginning with our unique grafting technique to produce humanized antibodies, our antibody humanization platform has produced a diverse portfolio of therapeutic agents that are in multiple clinical trials for the therapy of cancer and autoimmune diseases. These humanized antibodies not only have good safety profiles and are well tolerated by patients, they also have low immunogenicity and trigger only very minor immune responses against them.
Using the successful humanized antibody platform as a foundation, we have built a robust antibody-drug conjugate (ADC) program. Leading this program is the doxorubicin conjugate of milatuzumab, which is being evaluated as a therapy for multiple myeloma, followed closely by the SN-38 conjugate of labetuzumab for the treatment of colorectal cancer. Other ADC agents for the therapy of solid cancers, including cancer of the ovary, breast, lung and pancreas, are currently in preclinical development.
Linking a drug directly to a targeting agent such as an antibody is but one way of drug delivery. We have also pioneered a novel delivery method called pretargeting, in which the therapeutic agent and the antibody are administered to the patient in 2 separate steps. This delivery method has been shown to produce very high tumor/normal tissue ratios of uptake. More importantly, with pretargeting, we can apply both imaging and therapy in the same patient: first to qualify the patient for our targeted therapy, then monitor the patient’s response and progress. We believe strongly that pretargeting has the potential to bring us closer to personalized medicine.
Pretargeting requires the use of bispecific antibodies that recognize two targets. These antibodies are produced by our new protein engineering platform technology called DOCK-AND-LOCKTM (DNLTM) that combines conjugation chemistry and genetic engineering. The first DNLTM product, TF2, is currently in clinical trials for pretargeted imaging and therapy of colorectal cancer. In addition to bispecific antibodies, DNLTM has allowed us to broaden our research and development activities to include targeted vaccines against cancer and infectious diseases.
Pretargeting also requires a new class of diagnostic imaging agents to work alongside bispecific antibodies. To that end, we have recently patented a novel and facile method of labeling peptides with fluorine-18 (F-18) for use in the imaging of diseases using positron-emission tomography (PET), and are working toward developing a single-vial kit that can be validated for commercial use.