Viamet Pharmaceuticals, Inc., announced today that dosing has begun in a Phase 1/2 clinical trial of VT-464, an oral, potent and lyase-selective CYP17 inhibitor for the treatment of castration-refractory prostate cancer (CRPC). VT-464 is a novel, non-steroidal, small molecule discovered by Viamet Pharmaceuticals using its proprietary Metallophile® Technology. In preclinical models VT-464 preferentially inhibits the lyase reaction of the CYP17 enzyme over the hydroxylase reaction, which differentiates it from approved agents such as abiraterone acetate.
"With the recent FDA approval of Zytiga® (abiraterone acetate), the inhibition of CYP17 is now a validated approach to the treatment of CRPC," said Robert Schotzinger, M.D., Ph.D., President and Chief Executive Officer of Viamet. "The lowering of adrenal androgens, which are known to drive tumor growth, has now become a key treatment goal for patients with CRPC. Inhibition of CYP17, a critical enzyme involved in the synthesis of adrenal steroids such as androgens, is important to reach that goal," he noted. "CYP17 catalyzes two distinct chemical reactions, a hydroxylase reaction and a lyase reaction. Non-selective inhibitors can disrupt the hydroxylase reaction leading to an increase in steroids such as the mineralocorticoids and a decrease in other essential steroids such as cortisol. This steroid imbalance results in the need to co-administer prednisone with these non-selective agents. Based on preclinical research conducted by Viamet and others, it is anticipated that a lyase-selective CYP17 inhibitor, such as VT-464, would display a favorable safety and tolerability profile compared to non-selective agents and will not require co-administration of prednisone," stated Dr. Schotzinger. "Our goal to develop an orally-active, small molecule which preferentially inhibits the lyase reaction of CYP17 has been achieved with VT-464 and we are excited to begin the clinical testing of this promising compound in patients with CRPC."
Viamet Pharmaceuticals, Inc.