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The abstract (#2041), "Preclinical Validation of the Trp-p8 Ion Channel asa Target for Benign Prostatic Hyperplasia," is being presented at the AmericanUrological Association's 2008 Annual Meeting in Orlando, Fla., on Wednesday,May 21, 2008, at 2:50 PM ET.
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In a preclinical study, BPH was induced through subcutaneous injection oftestosterone propionate (TP). One week prior to initiation of testosterone,either D-3263 or finasteride, a current treatment for BPH, was administereddaily for four weeks. Following treatment, blood was sampled, prostates werecollected and weighed, and cross sections were stained with Trp-p8 antibody.
"We are encouraged by these data which demonstrate the potential forD-3263, our lead small molecule targeting Trp-p8, to serve as a drug candidatefor the potential treatment of BPH -- a disease affecting a substantial numberof men between 50 and 60 years of age," said David Urdal, chief scientificofficer of Dendreon. "We had previously shown that D-3263 specifically killscancer cells that express Trp-p8, and we look forward to filing aninvestigational new drug application later this year to initiate a studyexamining D-3263 in advanced cancer, including prostate cancer."
Results showed that the BPH-induced prostates expressed significantlyhigher levels of Trp-p8 compared to the normal prostates. In comparinguntreated BPH-induced prostates to those treated with D-3263, treatment withD-3263 resulted in a 39 percent reduction in prostate weight compared tocontrol (p=0.004). In addition, treatment with D-3263 resulted in a 98percent reduction (2221.2 pg/ml versus 43.1 pg/ml) in plasmadihydrotestosterone (DHT) levels (p=0.004) suggesting D-3263 is affectingandrogen metabolism, which is a known stimulant for BPH and prostate cancer.These effects were seen in a dose-dependent manner, achieving efficacycomparable to finasteride. Histopathological examination post treatment withD-3263 indicated that reduction of prostate size and weight was due to areturn to normalcy. Changes in Trp-p8 expression and plasma DHT levelscorrelated with both efficacy and dose.
About Trp-p8
Trp-p8 (also known as Trp-M8) was identified through Dendreon's in-housediscovery efforts. It is an ion channel that is triggered by cold temperaturesand small-molecule agonists. In normal human tissues Trp-p8 is expressedpredominantly in the prostate where it is over-expressed in BPH and prostatecancer, as well as a range of other cancers including breast, lung and colon.Dendreon has synthesized bioavailable small molecule agonists that activatethe Trp-p8 ion channel and induce cell death. The lead molecule, D-3263, isundergoing preclinical evaluation in anticipation of an investigational newdrug application to be filed with the U.S. Food and Drug Administration forclinical evaluation in cancer patients.
About Dendreon
Dendreon Corporation is a biotechnology company whose mission is to targetcancer and transform lives through the discovery, development andcommercialization of novel therapeutics to fight cancer. The Company appliesits expertise in antigen identification, engineering and cell processing toproduce active cellular immunotherapy product candidates designed to stimulatean immune response. Active cellular immunotherapy holds promise because it mayprovide patients with a meaningful clinical benefit, such as survival,combined with low toxicity. The Company has its headquarters in Seattle,Washington and is traded on the Nasdaq Global Market under the symbol DNDN.For more information abo
