Cytogen Corporation and Dowpharma today announced a collaboration to create a targeted oncology product designed to treat prostate and other cancers. Under the agreement, Dowpharma's proprietary MeO-DOTA bifunctional chelant technology will be used to radiolabel Cytogen's prostate-specific membrane antigen (PSMA) antibody with a therapeutic radionuclide. PSMA is a protein highly expressed on the surface of prostate cancer cells and the neovasculature of many solid tumors.
"We are extremely pleased to expand our long-standing relationship with this well respected and established company," said Michael D. Becker, Cytogen's President and Chief Executive Officer. "We believe that Dowpharma's MeO-DOTA technology is a perfect complement to Cytogen's expertise in developing and commercializing innovative molecules and this agreement marks a significant step in the development of our therapeutic franchise in oncology."
Under the agreement, proprietary chelation technology and other capabilities, provided through ChelaMed(SM) radiopharmaceutical services from Dowpharma, will be used to attach a therapeutic radioisotope to the same murine monoclonal antibody utilized in Cytogen's PROSTASCINT(R) (capromab pendetide) molecular imaging agent. This antibody, called 7E11-C5.3 (or 7E11), is directed against an intracellular epitope of PSMA. The 7E11 antibody was excluded from the PSMA technology licensed to the PSMA Development Company LLC, the Company's joint venture for PSMA product development. Consequently, the joint venture is not involved in this development initiative.
"We are delighted that we are applying our capabilities in chelation, conjugation, process and radiochemistry to enable Cytogen to develop this novel cancer therapy," said Nick Hyde, Business Director, Dowpharma. "Monoclonal antibodies labeled with radionuclides have proven successful for both the diagnosis and treatment of several tumors."
Dowpharma's MeO-DOTA bifunctional chelant will be utilized to attach the beta emitting radionuclide lutetium-177 as a payload to the 7E11 antibody, enabling targeted delivery of this cytotoxic agent. The Company intends to develop the resulting innovative molecule for the treatment of various cancers, initially in prostate, that express the PSMA marker.
"DOTA-based bifunctional chelating agents have been shown to provide exceptional stability to insure that therapeutic radionuclides do not separate from the monoclonal antibodies that target them to tumors," said William Goeckeler, Ph.D., Senior Vice President of Operations at Cytogen. "Dow is a world leader in the development of this technology and having the opportunity to collaborate with them should hasten the development process for our therapeutic radiolabeled 7E11 product candidate."
Cytogen's PROSTASCINT molecular imaging agent is the first and only commercial product targeting PSMA. PROSTASCINT consists of the 7E11 monoclonal antibody directed against PSMA that is linked to the radioisotope Indium-111. Due to the selective expression of PSMA, the PROSTASCINT molecular imaging procedure can detect the extent and spread of prostate cancer using a standard gamma camera. Clinical studies have demonstrated that overexpression of PSMA determined by immunohistochemical staining using 7E11 in primary prostate cancer not only correlates with other adverse traditional prognostic factors, but can independently predict disease recurrence.