UTHSC's drug candidate for advanced prostate cancer goes to first clinical trial

A drug candidate developed by researchers at the University of Tennessee Health Science Center for advanced metastatic castration-resistant prostate cancer is now in its first clinical trial.

Ramesh Narayanan, PhD, deputy director of the Center for Cancer Research and the Muirhead Endowed Professor in the College of Medicine at UTHSC, and Duane Miller, PhD, Professor Emeritus in the Department of Pharmaceutical Sciences at UTHSC, have worked for more than a decade on therapies involving the hormone receptors that influence cancer progression. Their drug candidate, a molecule designed as a treatment for advanced metastatic prostate cancer, is now in its first clinical trial.

This is a very, very rare occurrence. If you take all the academic researchers in the United States, probably only an insignificant percent would have the luxury or the privilege of taking a drug all the way from concept to clinical trial."

Ramesh Narayanan, PhD, Deputy Director of the Center for Cancer Research and the Muirhead Endowed Professor in the College of Medicine at UTHSC

Biopharmaceutical company Oncternal Therapeutics, Inc., holds the license for the drug candidate, an androgen (male hormone) receptor inhibitor dubbed ONCT-534, developed at UTHSC by Drs. Narayanan and Miller. On October 5, the company announced the first patient had received ONCT-534. On October 26, Oncternal disclosed that the FDA granted fast-track designation for ONCT-534, which could potentially accelerate the clinical development process.

"If you look at prostate cancer, most of the time it occurs in patients over 40, and about 60% are over 60," Dr. Miller said. "And it turns out that black men have a higher incidence, like 70% of the diagnoses, than white men."

"We felt that there is a significant need for this patient population," Dr. Narayanan said.

Existing treatments for prostate cancer target androgens, extending survival for most patients. However, roughly 30 percent of tumors do not respond, and patients who initially respond often develop resistance.

"Enzalutamide is normally the drug that's chosen to give to men," Dr. Miller explained. "With time, it just doesn't work, and we tried to figure out what's going on there."

One of the primary reasons for treatment failure or relapse is a mutation of the receptor protein for androgens. Enzalutamide works on one area of the receptor.

ONCT-534 is a dual-action androgen receptor inhibitor that has shown activity in prostate cancer models against unmutated and mutated androgen receptors. The research on the drug candidate has been funded by the National Cancer Institute, Oncternal, and GTx Inc., the company that became Oncternal.

"It looks like our drug is a very strong candidate for treating these patients who have relapsed from current treatment options," Dr. Narayanan says. "It may potentially have the possibility to extend the survival."

Drs. Narayanan and Miller are collaborators on several projects, including the preclinical development of a molecule to treat Kennedy's Disease, a rare progressive neurodegenerative disease in younger men. Dr. Miller and his team are responsible for the chemistry, designing the molecules and testing and refining the structure. Dr. Narayanan and his team do the pharmacological testing to see how they perform in the lab.

As the licensee for ONCT-534, Oncternal has handled the lengthy process leading to FDA approval for clinical trials that will test safety, efficacy, and finally, how it compares against current standard treatments. Passing all three hurdles could advance a drug to market someday.