CAMBRIDGE, Mass.--(EON: Enhanced Online News)--Tokai Pharmaceuticals, Inc., a biopharmaceutical company focused on developing new treatments for prostate cancer, today announced new preclinical data supporting that its lead candidate, galeterone (TOK-001) may represent the next-generation of therapy for patients with castration-resistant prostate cancer (CRPC) and disease that has progressed despite treatment with enzalutamide (Xtandi®). These data were presented today in a poster presentation titled, “Galeterone Suppresses Castration-Resistant and Enzalutamide-Resistant Prostate Cancer Growth in Vitro,” abstract number C89, at the AACR-NCI-EORTC 2013 International Conference on Molecular Targets and Cancer Therapeutics in Boston.
“Galeterone Suppresses Castration-Resistant and Enzalutamide-Resistant Prostate Cancer Growth in Vitro”
“These data demonstrate preclinical proof-of-principle that galeterone is a potent androgen receptor antagonist and may overcome the anti-androgen resistance mechanisms that are commonly observed in CRPC following treatment with other currently available agents,” commented Amina Zoubeidi, Ph.D., assistant professor, Department of Urologic Sciences, University of British Columbia and research scientist, Vancouver Prostate Centre, and co-author of the study.
Androgens, or male sex hormones, are known to fuel tumor growth in prostate cancer, and androgen deprivation therapy remains the standard treatment of metastatic prostate cancer. However, progression to CRPC occurs in the majority of patients and over 80% of CRPC tumors continue to express androgen receptor (AR) and androgen-responsive genes despite medical castration. Because the AR is still believed to play a role in CRPC, several new AR-targeting agents have been developed, including enzalutamide. Despite the clinical efficacy reported with enzalutamide, resistance to this therapy has been observed and new therapies are needed that prevent or treat anti-androgen resistance. Galeterone is a first-in-class multi-targeted treatment for CRPC that inhibits androgen signaling by three independent mechanisms of action: selectively inhibiting CYP17 lyase to prevent testosterone synthesis, antagonizing testosterone binding to the AR and degrading the AR protein.
In this study, Tokai and its collaborators evaluated the efficacy of galeterone to inhibit AR activity in preclinical models of enzalutamide resistant CRPC cells. Results showed that galeterone demonstrated anti-proliferative effects on human prostate cancer cells, including those that were selected for resistance to enzalutamide. Compared to enzalutamide treatment, galeterone induced a pronounced reduction in AR protein, and inhibition of AR nuclear translocation in all cell lines. These effects resulted in dramatic decreases in AR activity as evidenced by marked reductions in PSA protein and probasin luciferase reporter activity. Notably, these effects were still observed in enzalutamide resistant cells, which show no decrease in AR expression or nuclear translocation upon enzalutamide treatment.
“Tokai is currently investigating an improved formulation of galeterone in a Phase 2 clinical trial in four distinct CRPC patient populations, including those who have progressed following enzalutamide treatment, and we are eager to evaluate how these preclinical results may translate in the clinic,” said Douglas Jacoby, Ph.D., head of research, Tokai Pharmaceuticals and co-author of the poster. “Galeterone’s multi-targeted mechanism of action and unique ability to degrade the AR protein demonstrated in this study suggest its potential for clinical utility in patients with resistant disease.”
The poster presentation is available on Tokai’s website at www.tokaipharma.com/news-publications.php.
About Galeterone (TOK-001)
Galeterone is first in a new class of drugs designed for multi-targeted castration-resistant prostate cancer (CRPC) therapy. It is a proprietary small molecule, oral drug for the treatment of CRPC that inhibits androgen signaling, the key driver of CRPC, by three independent mechanisms of action. Preclinical studies have shown that galeterone selectively inhibits CYP17 lyase to prevent testosterone synthesis, antagonizes testosterone binding to the androgren receptor (AR) and degrades the AR protein. Galeterone is the only drug in development or on the market that acts to degrade the AR protein, and that employs all three of these mechanisms in one compound to treat CRPC.
Tokai is investigating galeterone as part of the ARMOR (Androgen Receptor Modulation Optimized for Response) clinical development program in patients with CRPC. Results from the ARMOR1 clinical trial showed that galeterone demonstrated clinical activity and was well tolerated in patients with CRPC. Following completion of ARMOR1, a new formulation of galeterone was developed to provide higher exposure and mitigate food effect. This improved formulation of galeterone is currently being evaluated in a Phase 2 study, ARMOR2, in four distinct populations of patients with CRPC. In addition, Tokai is exploring a pipeline of new indications for galeterone, including breast cancer, as both a single agent and combination therapy.
About Tokai Pharmaceuticals
Tokai Pharmaceuticals is a biopharmaceutical company focused on developing new treatments for prostate cancer. The company’s lead drug candidate, galeterone (TOK- 001), is first in a new class of drugs designed for multi-targeted castration-resistant prostate cancer (CRPC) therapy. Based in Cambridge, Massachusetts, Tokai is backed by Apple Tree Partners and Novartis Venture Fund. For more information on the company and galeterone, please visit www.tokaipharma.com.