Dow and Cytogen Agree to Develop PSMA Antibody for Treatment of Cancer
[Urche: did you do any more digging on this program as you said you might?
Do you or anyone still consider CYTO’s PSMA programs a threat to DNDN? Does CYTO’s approach of targeting a fairly general tumor antigen make as much sense as DNDN’s approach of targeting an antigen highly specific to the (non-cancerous) prostate? Since the prostate is not an essential organ, it seems to me that an organ-specific antigen may be the better approach.
By the way, today’s PR is not all that different from the one issued by CYTO only a month ago (#msg-5950633).]
>> Agreement Applies ChelaMed(SM) Radiopharmaceutical Services from Dowpharma(SM) to Cytogen's Proprietary 7E11.C5.3 Monoclonal Antibody
MIDLAND, Mich., and PRINCETON, N.J., May 10 /PRNewswire-FirstCall/ -- Cytogen Corporation (Nasdaq: CYTO ), a product-driven biopharmaceutical company, and Dowpharma(SM) contract manufacturing services, a business unit of The Dow Chemical Company (NYSE: DOW ), 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® (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. <<
>> Progenics and Cytogen Report Potent Anti-Tumor Activity for Experimental Prostate Cancer Drug
SCOTTSDALE, Ariz.--(BUSINESS WIRE)--Sept. 30, 2005--PSMA Development Company LLC (PDC), a joint venture of Progenics Pharmaceuticals, Inc. (Nasdaq: PGNX - News) and Cytogen Corporation (Nasdaq: CYTO - News), today announced positive preclinical findings of its novel prostate cancer drug, prostate-specific membrane antigen (PSMA) antibody-drug conjugate (ADC). The findings were reported today by Dangshe Ma, Ph.D., Progenics' Senior Investigator, at the 12th Annual Prostate Cancer Foundation Scientific Retreat.
In a mouse model of human prostate cancer, PSMA ADC significantly prolonged overall survival up to nine-fold as compared to untreated animals (p=0.0018, log-rank test, two-sided). Remarkably, established tumors in two of the five animals treated at the highest dose were eradicated and remained undetectable over 500 days through the completion of the study. No overt evidence of toxicity was observed in any of these animal model tests.
ADC drugs link a monoclonal antibody which targets specific cells in the body, such as cancer cells, with a cell-killing payload. PSMA ADC is a human monoclonal antibody targeting PSMA, which is abundantly expressed on the surface of prostate cancer cells, coupled to auristatin, a highly potent drug. As a result, PSMA ADC is targeted to prostate cancer cells and incorporated into them, releasing the drug payload inside the cancer cell. The technology to link the PSMA monoclonal antibody to auristatin is being developed by PDC in collaboration with Seattle Genetics, Inc. (Nasdaq: SGEN - News).
"Prostate-specific membrane antigen represents an excellent target in cancer therapy for many reasons. It is an integral membrane protein that is abundantly and preferentially expressed on the surface of prostate cancer cells," said Warren D.W. Heston, Ph.D., Director, Research Program in Prostate Cancer, The Cleveland Clinic Foundation. "PSMA expression is high in prostate cancers that no longer respond to hormonal therapies and for which there are few treatment options. In addition, PSMA is abundantly expressed on endothelial cells of new blood vessels that supply most other solid tumors. Once the PSMA monoclonal antibody has bound to the cancer cell, PSMA ADC is rapidly internalized, making it especially well suited for the 'armed antibody approach' of this compound. Today's findings represent a positive step toward developing PSMA ADC as a novel therapy for metastatic prostate cancer."
"PSMA ADC combines the tumor-targeting properties of our PSMA monoclonal antibody with the cell-killing properties of auristatin, a highly potent drug that disrupts the internal scaffolding that cancer cells require to grow and divide," said William C. Olson, Ph.D., Vice President of Research & Development at Progenics and senior author of the presentation. He added, "PSMA ADC can be considered a targeted form of chemotherapy where it attacks prostate cancer cells, but spares healthy tissues. PSMA ADC eradicated established tumors in some of the mice without any observed toxicity. The findings support further development of PSMA ADC for therapy of prostate and other cancers."
PSMA ADC was also tested in vitro and in animals for the ability to selectively eliminate prostate cancer cells. In laboratory studies, PSMA ADC killed PSMA-expressing prostate cancer cells at picomolar concentrations, whereas approximately 1000-fold higher concentrations were required to kill cells that lack PSMA. PSMA ADC was similarly active against prostate cancer cells that were either sensitive to or resistant to androgen deprivation. In addition to improving survival, PSMA ADC resulted in significant, 700-fold reductions (p = 0.0086, t-test, two-sided) in serum levels of prostate-specific antigen (PSA) in animal tests. PSA is a well-recognized surrogate marker of prostate cancer progression and response to therapy. <<
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