Essa Pharma’s Androgen Receptor Inhibitor, EPI-7386, Selected as Lead Candidate Therapy

EPI-7386, a new androgen receptor inhibitor, was selected as Essa Pharma‘s lead candidate therapy for metastatic castration-resistant prostate cancer (mCRPC), the company announced.

The company’s decision was supported by early preclinical data recently presented at the 2019 Genitourinary Cancers Symposium in San Francisco. The poster, “Next generation N-terminal domain androgen receptor inhibitors with improved potency and metabolic stability in castration-resistant prostate cancer models,” showed the treatment’s tolerability and efficacy in animal models of the disease.

“We are excited to announce the nomination of EPI-7386 as our lead clinical candidate for the treatment of mCRPC,” David Parkinson, Essa’s president and CEO, said in a press release.

Hormone therapies targeting male sex hormones, or androgens, are a mainstay in treating prostate cancer. Androgens bind to the androgen receptor activating signals that prostate cancer cells require to grow and proliferate.

However, patients often develop mutations in the androgen receptor that render it resistant to such therapies over time. New treatments that inhibit the activation of the androgen receptor through distinct mechanisms may help men with prostate cancer who no longer respond to the anti-androgen therapies.

Essa Pharma’s EPI-7386 works differently from current hormonal therapies by targeting a different region of the androgen receptor: instead of preventing androgens from binding the receptor, the candidate therapy binds to the N-terminal domain needed to activate the androgen receptor signaling cascade.

Through this novel mechanism, EPI-7386 is able to block the androgen receptor even in cells that acquired resistance to other androgen receptor inhibitors, like Xtandi (enzalutamide).

It also seems to be metabolically more stable than first-generation small molecule androgen receptor inhibitors being developed by Essa – including their EPI-506 (ralaniten acetate). EPI-7386 has a similar efficacy as Xtandi, but at double that therapy’s current dose.

“EPI-7386 represents a novel approach to targeting the androgen receptor, one of the most validated targets in oncology. We look forward to bringing this novel drug candidate to patients with mCRPC who have no other treatment options,” Parkinson said.

Essa is now conducting further studies, and expects to begin clinical trials for EPI-7386 by April 2020.