Microsoft word - tokai - asco gu pr final 21513.doc

FOR IMMEDIATE RELEASE

Tokai Pharmaceuticals to Present New Galeterone Mechanism of Action Data at
2013 ASCO GU
Galeterone Demonstrates Differentiated Profile with Potent and Selective CYP17 Lyase
CAMBRIDGE, Mass., February 15, 2013 — Tokai Pharmaceuticals, Inc., a
biopharmaceutical company focused on developing new treatments for prostate cancer,
today announced that new preclinical data demonstrating the differentiated potent and
selective CYP17 lyase inhibition mechanism of action of its lead candidate, galeterone
(TOK-001), will be presented today in a poster presentation titled, “Galeterone,
Abiraterone, Orteronel and Ketoconazole Exhibit Differential Inhibitory Effects on CYP17
and Steroidogenesis,” abstract number 184, at the 2013 American Society of Clinical
Oncology Genitourinary Cancers Symposium (ASCO GU) in Orlando, Fla.
Androgens, or male sex hormones, are known to fuel tumor growth in prostate cancer, and
therapies that reduce circulating androgen levels are the standard of care in early-stage
prostate cancer. The CYP17 enzyme plays a central role in androgen synthesis, and
therefore, drugs that inhibit CYP17 have been developed to treat castration-resistant
prostate cancer (CRPC). However, CYP17 has both hydroxylase and lyase catalytic
functions – lyase catalyzes androgen production and hydroxylase catalyzes
mineralocorticoid synthesis, which maintain the body’s water and salt balance. Thus,
selective hydroxylase inhibition causes build-up of progestogens and mineralocorticoids
and reduction in cortisol levels in CRPC patients, resulting in secondary mineralocorticoid
excess (ME), a clinical syndrome including edema, hypokalemia and hypertension. The
reduction in cortisol triggers an ACTH feedback loop which is addressed with concomitant
administration of the corticosteroid, prednisone. Because of prednisone’s poor tolerability
profile and potential to activate mutant androgen receptor (AR) in CRPC, considerable
interest has emerged in more selective CYP17 lyase inhibitors.
“We conducted these studies to gain a better understanding of CYP17 inhibition, one
facet of galeterone’s unique triple mechanism of action, which also includes AR
antagonism and AR degradation. CRPC patients treated with galeterone in our ARMOR1
Phase 1 trial did not exhibit dose-limiting toxicities or signs of ME, and did not require
concurrent prednisone administration,” said Martin D. Williams, president and chief
executive officer, Tokai Pharmaceuticals. “In these studies, galeterone exhibited potent
and selective CYP17 lyase inhibition with minimal evidence of steroid changes
associated with ME, which correlates to the Phase 1 clinical observations. Because ME is
a commonly reported adverse event requiring prednisone in CRPC patients treated with
other non-selective CYP17 inhibitors, such as abiraterone, we believe galeterone may
represent an important new treatment option for CRPC patients due to its differentiated
CYP17 inhibition and tolerability profile.”

Tokai analyzed the CYP17 inhibitors galeterone, abiraterone, orteronel and ketoconazole
to determine each drug’s effects on CYP17 hydroxylase and lyase activities, and the
steroidogenic pathway. Study results showed that all four drugs inhibited CYP17;
however, potency and selectivity for hydroxylase and lyase varied significantly. Galeterone
was the most potent CYP17 inhibitor that was also selective for CYP17 lyase, while
conserving CYP17 hydroxylase function, and exhibiting minimal evidence of deleterious
steroid changes associated with ME. These preclinical data recapitulate the Phase 1 clinical
experience with galeterone where no ME was observed and no prednisone was required in
CRPC patients. The poster presentation is available on Tokai’s website at
www.tokaipharma.com/news-publications.php.

About Galeterone (TOK-001)
Galeterone is a proprietary small molecule, oral drug for the treatment of prostate cancer
that disrupts androgen receptor signaling via a novel triple mechanism of action. In
preclinical studies, galeterone acted as a highly selective CYP17 lyase inhibitor, as a
potent androgen receptor antagonist, and decreased androgen receptor levels in prostate
tumors – the only drug in development that has been shown to exhibit all three of these
properties. Galeterone combines these three distinct mechanisms of action in one
therapeutic compound. Results from the ARMOR1 Phase 1 clinical trial showed that
galeterone demonstrated clinical activity and was well tolerated in patients with CRPC.
Galeterone is currently being evaluated in a Phase 2 study, ARMOR2, in patients with
CRPC as part of the ARMOR (Androgen Receptor Modulation Optimized for Response)
clinical development program.
About Tokai Pharmaceuticals
Tokai Pharmaceuticals is a U.S. biopharmaceutical company focused on developing new
treatments for prostate cancer. The company’s lead drug candidate, galeterone (TOK-
001), is the first investigational new drug that can decrease overall androgen receptor
levels in prostate tumors and in which three distinct mechanisms of action are combined
to disrupt androgen receptor signaling in one oncotherapeutic. 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.
Media Contact: Caton Morris Pure Communications, Inc. (910) 232-7166

Source: http://www.tokaipharmaceuticals.net/pdfs/Tokai-ASCOGU21513.pdf