Medarex, Inc. (PRINCETON, NJ), a developer of fully human antibody-based therapeutics, and GenPat77 Pharmacogenetics AG (BERLIN, Germany), a privately-held biopharmaceutical company focused on the development of immune modulatory products, have entered into a collaborative agreement to develop fully human therapeutic antibody products. The two parties plan to use Medarex's UltiMAb Human Antibody Development System® to generate antibodies to GenPat77's novel therapeutic targets for autoimmune diseases.

Under the terms of the agreement, Medarex and GenPat77 plan to share product development and commercialization responsibilities for any antibody products resulting from this collaboration. Other financial terms of the agreement were not disclosed.

GenPat77 is focused on the development of innovative immune modulatory products for rheumatoid arthritis (RA), multiple sclerosis (MS), inflammatory bowel disease (IBD), cancer, and the prevention of transplant rejection. The Company was founded in 1998 based on exclusively licensed intellectual property rights on novel targets for specific immune modulation identified by Nalân Utku, MD (cofounder and CEO), Edgar Milford, MD, and Steven Gullans, PhD, at Brigham and Women's Hospital, Harvard Medical School, Boston, Mass. Positive preclinical efficacy data have been generated by GenPat77 for several antibodies in different indications, and the Company is advancing drug candidates for several novel proprietary targets including monoclonal antibodies against T-cell immune response cDNA 7 (TIRC7, for autoimmune diseases such as RA, MS, IBD, and transplant rejection), carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1, for IBD), and GP3 (for autoimmunity and cancer).

The Company's most advanced product candidate is derived from the TIRC7 program. TIRC7 is a cell surface molecule that is expressed in T- and B lymphocytes and negatively regulates their function. TIRC7-deficient mice exhibit immune hyperactivity of both T- and B-cells. Targeting of TIRC7 with a monoclonal antibody is effective in inhibiting T-cell proliferation and Th1 cytokine expression, and is associated with an up-regulation of cytotoxic T lymphocyte antigen 4 (CTLA4), a key negative regulator of T-cell function. TIRC7 is up-regulated in infiltrating lymphocytes in knee joint tissues of patients with active RA, and in synovial fluid lymphocytes obtained from patients with RA. In contrast, TIRC7 expression was not observed in joint tissues obtained from patients with osteoarthritis.

Monoclonal antibody targeting of TIRC7 results in significant therapeutic effects on T- and B-cell response in collagen-induced arthritis (CIA) in mice, resulting in the inhibition of the induction and progression of CIA and the anticollagen IgG1 and IgG2a antibody response. Studies in mice with CIA showed that antibody targeting of TIRC7 results in significant therapeutic efficacy as both a monotherapy and in combination with a tumor necrosis factor (TNF)-α receptor-Ig fusion protein (ENBRELR, etanercept) wherein an additive effect was observed. The combination of anti-TIRC7 monoclonal antibody with TNF blockade resulted in decreased levels of Ig and TNF-α, and unchanged levels of interleukin (IL)-4 and IL-10 secretion.

Studies with CEACAM1 demonstrated its role in the suppression of experimental murine colitis. In mice, administration of CEACAM1 fusion protein promoted suppression in the proliferation of T-cells and maintained low Th1-type cytokine responses following challenge with Staphylococcal enterotoxin B compared with control. The GP3 program is currently in early preclinical stage and comprises the development of antibodies and fusion proteins for undisclosed indications in autoimmunity and cancer.

Medarex applies its UltiMAb technology and product development and clinical manufacturing experience to generate, support, and potentially commercialize a broad range of fully human antibody therapeutic product candidates for inflammation, autoimmune disorders, cancer, and infectious diseases, for itself and its partners. Thirty-three of these investigational agents derived from Medarex technology are in human clinical testing or have had investigational new drug applications for such trials, with five of the most advanced product candidates currently in phase III clinical trials.

— A. Techman

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