Medivation Announces Publication in Science Describing MDV3100′s Novel and Potent Anti-Androgen Properties

- Seminal Research on Prostate Cancer Resistance Leads to Development of MDV3100, Novel Drug Candidate -

SAN FRANCISCO, April 7 /PRNewswire-FirstCall/ — Medivation, Inc. (Nasdaq: MDVN) today announced publication of an article in the April 9, 2009, issue of Science Express, the online version of the journal Science, presenting the discovery and novel mechanism of action of MDV3100, the Company’s androgen receptor antagonist drug candidate. MDV3100 has completed enrollment in a Phase 1-2 study and is expected to enter Phase 3 development this year in metastatic castration-resistant prostate cancer (CRPC).

Prostate cancer growth requires the male androgen sex hormone testosterone. When testosterone binds to its natural receptor, the androgen receptor moves into the nucleus of the prostate cancer cell (nuclear translocation), binds DNA and stimulates prostate cancer growth. In the castration-resistant state (also known as hormone refractory), current anti-androgen therapies, despite binding to the androgen receptor, do not block nuclear translocation, which allows the receptor to bind to prostate cancer cell DNA and stimulate the tumor to grow. Treatment options for patients with CRPC are limited.

In the Science article, researchers, utilizing various models of CRPC, provide evidence that MDV3100′s novel mechanism of action is unlike that of the leading anti-androgen therapy bicalutamide. Specifically, MDV3100:

• potently blocks the androgen receptor with greater binding affinity than bicalutamide;
• impairs nuclear translocation and blocks DNA binding of the androgen receptor, one of the key steps required for androgen-dependent prostate cancer growth and a step not blocked by bicalutamide; and,
• induces castration-resistant prostate tumor cell death, an effect not seen with bicalutamide.

These properties potentially explain why MDV3100 has demonstrated beneficial effects in patients whose tumors are no longer responding to the currently available treatments for prostate cancer, including bicalutamide.

“Because MDV3100 binds to the androgen receptor and blocks subsequent DNA binding, it can inhibit the growth of prostate cancer cells that have failed standard hormonal therapies and even chemotherapies,” said Charles L. Sawyers, M.D., lead author of the Science paper, a Howard Hughes Medical Investigator, and chair of the Human Oncology and Pathogenesis Program at Memorial Sloan-Kettering Cancer Center in New York. “I believe that MDV3100 is an important potential new approach to treating this disease and am encouraged that the drug is moving into Phase 3 clinical development.”

MDV3100 is based on work done by Dr. Sawyers at the University of California at Los Angeles, where he discovered overexpression of the androgen receptor in prostate cancer cells — a key mechanism associated with prostate cancer hormone resistance. This discovery prompted Dr. Michael Jung and his colleagues at UCLA to synthesize a series of organic small molecules that were shown by Dr. Sawyers’ group to bind to the androgen receptor.

“Publication of the MDV3100 manuscript in Science underscores the promise of this novel investigational drug. The mechanism of action of MDV 3100, elucidated in this article, suggests that it may have synergistic effects with other drugs targeting different pathways to treat prostate cancer,” said David T. Hung, M.D., president and chief executive officer of Medivation. “Given the encouraging results we have seen to date in our Phase 1-2 trial, we are pleased that we are on track to initiate patient enrollment in a Phase 3 trial of MDV3100 this year.”

MDV3100 Clinical Development

MDV3100 is being evaluated in an ongoing open-label, U.S., Phase 1-2 study of a total of 140 men with CRPC. Patients in this trial were heavily pretreated, with all having failed standard hormonal therapies and many having also failed docetaxel-based chemotherapy. MDV3100 has consistently demonstrated encouraging anti-tumor activity across dose levels and endpoints for both chemotherapy-naive and post-chemotherapy patients. Importantly, a significant number of patients with unfavorable circulating tumor cell (CTC) counts of five or higher were converted to favorable CTC counts at week 12. This CTC conversion rate is encouraging in light of recent studies that showed a post-treatment conversion to favorable CTC counts was associated with a survival benefit in CRPC patients. MDV3100 has been generally well tolerated at doses of up to and including 240 mg/day. The most frequently reported adverse event was fatigue. Patients are continuing on study drug until they experience an intolerable adverse event or until their disease progresses. Additional data from this trial is expected to be presented at upcoming medical conferences.

On March 19, 2009, Medivation announced that it had received written permission from the U.S. Food and Drug Administration to begin a pivotal Phase 3 trial of MDV3100 in patients with CRPC who have failed docetaxel-based chemotherapy. The randomized, placebo-controlled, double-blind, multinational trial will enroll approximately 1,200 patients, with overall survival as the primary endpoint.

About Prostate Cancer

Prostate cancer is the most common non-skin cancer in the United States and the third most common cancer worldwide. More than 1 million men in the United States have prostate cancer. In 2008, an estimated 186,320 new cases were expected to be diagnosed and approximately 28,660 men were expected to die from the disease. Castration-resistant prostate cancer (CRPC) is defined as prostate cancer that continues to grow despite all standard-of-care hormonal (anti-androgen) therapies. Patients with castration-resistant (also known as hormone-refractory) prostate cancer have few treatment options and a poor prognosis.

About Medivation

Medivation, Inc. is a biopharmaceutical company focused on the rapid development of novel small molecule drugs to treat serious diseases for which there are limited treatment options. Medivation aims to transform the treatment of these diseases and offer hope to critically ill patients and their caregivers. In September 2008, Medivation announced a global agreement with Pfizer Inc to develop and commercialize Dimebon for the treatment of Alzheimer’s and Huntington’s diseases. With Pfizer, the Company is conducting a broad Dimebon clinical development program, including a pivotal and confirmatory Phase 3 trial, known as the CONNECTION study, in patients with mild-to-moderate Alzheimer’s disease. The program also includes additional trials planned to begin this year in Alzheimer’s disease, as well as further development of Dimebon in patients with mild-to-moderate Huntington’s disease. In addition, a Phase 1-2 clinical trial of MDV3100 in patients with castration-resistant (also known as hormone-refractory) prostate cancer is ongoing. For more information, please visit us at http://www.medivation.com.

This press release contains forward-looking statements, including statements regarding the timing and potential results of Phase 3 trials of MDV3100, which are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Forward-looking statements involve risks and uncertainties that could cause Medivation’s actual results to differ significantly from those projected, including, without limitation, risks related to progress, timing and results of Medivation’s clinical trials, difficulties or delays in obtaining regulatory approval, enrollment of patients in Medivation’s clinical trials, partnering of Medivation’s product candidates, manufacturing of Medivation’s product candidates, competition with Medivation’s product candidates should they receive marketing approval, the adequacy of Medivation’s financial resources, unanticipated expenditures or liabilities, intellectual property matters, and other risks detailed in Medivation’s filings with the Securities and Exchange Commission, including its annual report on Form 10-K for the year ended December 31, 2008, filed with the SEC on March 16, 2009. You are cautioned not to place undue reliance on the forward-looking statements, which speak only as of the date of this release. Medivation disclaims any obligation or undertaking to update or revise any forward-looking statements contained in this press release.

SOURCE Medivation, Inc.