RESEARCH TRIANGLE PARK, N.C.--()--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.
“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”
“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.”
VT-464 is the second novel, oral, clinical-stage compound discovered by Viamet using its Metallophile® Technology. The first, VT-1161, is in Phase 1 clinical testing for the treatment of a diverse range of fungal infections. Additional compounds in preclinical development include VT-1129, a potent, oral agent for the treatment of cryptococcal meningitis and a series of novel compounds in early-stage testing for the treatment of invasive mold infections.
About Viamet Pharmaceuticals, Inc. (www.viamet.com)
Viamet discovers and develops novel, best-in-class inhibitors of key metalloenzymes via an innovative and proprietary metal-binding approach, our Metallophile® Technology. Viamet’s disruptive Metallophile® Technology is based on our leading expertise in bioinorganic chemistry and metalloenzyme biology and allows Viamet to identify metalloenzyme targets with high therapeutic and commercial potential, leverage existing metalloenzyme inhibitors as the basis for our novel analogs, and rapidly generate superior clinical candidates by optimizing the metal-binding component of known inhibitors. Utilizing our Metallophile® Technology, Viamet has been able to rapidly discover and develop safe and effective compounds that address key unmet medical needs in the areas of oncology and infectious disease.