Prostate cancer program, ADA-308
Prostate cancer is the most common cancer in men and the second leading cause of cancer death affecting millions of men worldwide. Prostate cancer cells need androgens to grow making androgen deprivation therapy the backbone of treatment for advanced prostate cancer. Androgen deprivation therapy can be achieved by lowering androgen levels either surgically or chemically via hormone therapy or androgen synthesis inhibitors, or blocking their action via androgen receptor, AR, antagonists. Collectively drugs targeting androgen axis are called anti-androgens.
While initially effective the response is often short-lived and disease progression occurs despite castrate levels of androgens hence the naming castration resistant prostate cancer, CRPC, for the most advanced form of the disease. At molecular level, progression to CRPC is characterized by increase in intratumoral androgen production, aberrant AR expression including AR gene amplifications, AR mutations and/or ligand-independent AR splice variants leading to persistent AR activation. Also activation of AR by growth factors and cytokines or the involvement of aberrant signaling pathways has been linked to development of treatment resistance. Though the molecular basis for the development of CRPC is complex and may vary, it has become clear that AR signaling continues to be one of the main drivers for disease progression.
The realization that persistent activation of AR signaling pathway underlies the development of CRPC has led to the development of potent next generation anti-androgens such as abiraterone and enzalutamide, which slow down disease progression and prolong the survival of CRPC patients. However, some CRPC patients remain unresponsive even for these novel agents and treatment resistance develops also in responsive ones overtime underlining the need for new treatment options.
Aranda’s lead asset, ADA-308, is an AR antagonist that retains antagonism in treatment-resistant cells making it suitable drug candidate for patients that have undergone treatment with 1st or 2nd generation AR antagonists. The program is in the late stage of preclinical development in the candidate selection phase.