Tokai’s lead product candidate is galeterone, a highly-selective, oral small molecule with the potential to transform the treatment of prostate cancer. We are focusing our late-stage development of galeterone on the treatment of men with metastatic, castration-resistant prostate cancer, or CRPC, whose prostate tumor cells express the AR-V7 splice variant.

We are conducting ARMOR3-SV, a Phase 3 clinical trial of galeterone evaluating whether administration of galeterone results in a statistically significant increase in radiographic progression-free survival as compared to Xtandi^® (enzalutamide), an oral therapy currently approved for the treatment of CRPC, in AR-V7 positive metastatic CRPC patients. ARMOR3-SV is the first pivotal trial in prostate cancer to employ a precision medicine approach for patient selection. For more information regarding ARMOR3-SV, click here.

Galeterone has been studied in over 250 subjects in Phase 1 and Phase 2 clinical trials, including in CRPC patients with and without the AR-V7 splice variant. In these trials, galeterone demonstrated good tolerability and showed clinically meaningful reductions in levels of prostate specific antigen, or PSA, a biochemincal marker used to evaluate prostate cancer patients for signs of response to therapy.

We are currently focusing our late-stage development of galeterone on AR-V7 positive metastatic CRPC patients because it represents an unmet need in prostate cancer and our precision medicine approach provides an efficient development path. Based on the data we and our collaborators have produced to date, we also believe there is rationale for the broader clinical exploration of galeterone in the future.

Galeterone acts by disrupting the androgen receptor signaling pathway. This pathway is activated by the binding of male hormones (also known as androgens), such as testosterone and dihydrotestosterone (DHT) to androgen receptors in prostate cancer cells.

Galeterone disrupts the activation of the androgen receptor pathway in three ways:

• Androgen receptor degradation, which reduces the amount of androgen receptor protein in tumor cells. There are no currently marketed drugs whose mechanism of action entails degradation of the androgen receptor. Therefore, galeterone represents a potential first-in-class therapeutic opportunity.

• CYP17 enzyme inhibition, which blocks the synthesis of testosterone. This mechanism has been validated clinically by Zytiga (abiraterone). Zytiga must be co-administered with the steroid prednisone in order to minimize the risk of a potentially fatal side effect called mineralocorticoid excess. Unlike Zytiga, galeterone has not been shown in clinical trials to cause mineralocorticoid excess and, as a result, does not require co-administration of steroids. As a result, we believe that galeterone may be easier to administer, provide convenience for patients and enhance patient compliance.

• Androgen receptor inhibition, which blocks the binding of testosterone or DHT with the androgen receptor. This mechanism has been validated clinically by Xtandi^® (enzalutamide), which is also currently approved for the treatment of CRPC. Xtandi™ has shown a risk of grand mal seizures in clinical trials. We have not had any reports of seizures in clinical trials of galeterone and, therefore, galeterone may have certain safety advantages over Xtandi.

Tokai retains global rights to galeterone. We intend to commercialize galeterone in the United States on our own, and to seek a partner to further develop and commercialize galeterone outside of the United States.

Galeterone has been granted Fast Track designation by U.S. Food and Drug Administration for the treatment of CRPC. Fast Track designation is designed to facilitate the development and expedite review of drugs intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs.