In my remarks last year, I reported on the exciting development of a new platform technology for protein engineering, termed the Dock-and-Lock methodology (DNL), which has the potential of constructing a considerable number of active biological molecules.  I am pleased to report that we have made significant advances with this technology and created an array of new and potentially improved biotechnology products.

One of the key features of DNL and its main advantage over other protein engineering platform technologies is its versatility.  As depicted on the cover of this year’s Annual Report, a myriad of components, biologically active and/or otherwise, can be conjugated to the linker modules either chemically or recombinantly.  Moreover, when allowed to mix together, the two modules fuse with each other exclusively and in a quantitative manner, thus simplifying production.  Another unique characteristic of DNL is that one of the two parent components is always present in two copies in the final construct, thereby potentially making the DNL products more potent than the original molecules.  For the first time in our history, we are now making molecules that are not antibody-based, since the DNL technology allows us to construct many different potential products, such as cytokines and vaccines. But to remain focused, we have selected one cytokine immunomodulator to demonstrate the properties and potential of DNL, so we can eventually offer this as a platform technology to the biotechnology/pharmaceutical industry.

During this past year, our scientists also have worked diligently on creating novel versions of antibody molecules, and demonstrated their stability and activity both in vitro and in vivo.  In all, we have constructed more than 20 new DNL-derived antibodies, and presented some of them at major medical conferences.  To develop these products effectively and to ensure we will have several candidates for a specific indication, we are focused on four different types of DNL constructs for further preclinical development.

For bispecific antibody pretargeting, which we believe is an improved method of delivering imaging and therapeutic isotopes, as well as possibly cytotoxic drugs, to cancers, we are advancing TF2 (tri-Fab-2), a DNL construct that contains two copies of the CEA-binding antibody, labetuzumab, for pretargeted imaging and therapy of colorectal, breast and lung cancers. 

I have emphasized mostly advanced research and preclinical projects, but this is not to minimize the extensive product testing we have in the clinic with epratuzumab, veltuzumab, milatuzumab, labetuzumab, and PAM4 humanized monoclonal antibodies for the therapy of lymphoma, multiple myeloma, chronic lymphocytic leukemia, acute lymphoblastic leukemia, colorectal cancer, and pancreatic cancer, as well as certain autoimmune diseases.  Some of these are company-sponsored trials, some are sponsored by National Cancer Institute study groups, and others are investigator-sponsored studies. But all contribute to our gaining a better understanding of how our products can help in the treatment of patients with cancer or serious autoimmune disease.

I am proud of these achievements, and of the scientists and clinicians at our company and at collaborating institutions, who are contributing to these developments. But most of all, we have to recognize the patients who have shown their trust and enthusiasm by participating in such investigational trials.

Sincerely,

David M. Goldenberg, Sc.D., M.D.
Chairman of the Board and
Chief Strategic Officer