VERU IS ENROLLING PATIENTS
To Evaluate the Safety and Tolerability of VERU-111 in Men with Advanced Metastatic Castration Resistant Prostate Cancer
In 2019, there were approximately 175,000 new cases of prostate cancer in the U.S. and about 25% will die from the disease1. In the U.S., 5% of men with prostate cancer will have metastatic cancer and up to 30% of men with high-risk, localized prostate cancer will develop metastatic cancer following initial therapy.2 The median survival of patients with metastatic prostate cancer ranges from 3.2-4.5 years. For these men, the 1st line therapy is ADT, or medical castration. Although most will initially respond, nearly all these patients will progress to metastatic castration resistant prostate cancer and have a poor prognosis with an average survival of 1.5 years.3,4 New 2nd line hormonal agents, like XTANDI® (enzalutamide) and ZYTIGA® (abiraterone/prednisone) have resulted in an additional four to five months of average survival, but again, nearly all men on these agents will eventually develop progressive metastatic prostate cancer.
Agents that target tubulin, the subunits of microtubules, have been shown to be one of the most effective targeted cytotoxic chemotherapies for the treatment of metastatic prostate cancer5. Microtubules are critical for cancer cell replication and to shuttle the androgen receptor into the nucleus where the receptor stimulates genes for cancer cell growth. Docetaxel and cabazitaxel are examples of FDA-approved chemotherapy drugs that are given intravenously (IV) that target tubulin to treat metastatic prostate cancer. Although effective, the challenges for this class of chemotherapy agents, also known as taxanes, include that they must be given intravenously (IV) and that the cancer cells develop resistance to taxanes. There are also serious safety concerns with IV taxanes which include serious hypersensitivity (allergic) reactions, myelosuppression (neutropenia) and neurotoxicity such as peripheral neuropathy and muscle weakness.
VERU-111 is an oral, next generation, first-in-class selective small molecule that targets and binds to the alpha and beta tubulin subunits of microtubules in cells. Microtubules are essential for cell division and for shuttling critical growth receptors into the nucleus where they stimulate cell proliferation. Unlike taxanes which bind to just the beta subunit of tubulin, VERU-111 binds strongly to both the alpha and beta tubulin subunits. Furthermore, VERU-111 inactivates by cleaving poly ADP ribose polymerase (PARP) which is important for DNA repair in cancer cells6. VERU-111 has high oral bioavailability; no expected allergic reactions; less possibility for drug resistance as it does not interact with multiple drug resistance proteins so it cannot be pumped out of the cancer cell; potential for minimal drug to drug interactions; and high activity against many tumor types including prostate cancer resistant to drugs like novel androgen-blocking agents (abiraterone and enzalutamide) and taxanes as well as triple negative breast cancer, ovarian cancer, cervical cancer, lung cancer, melanoma and pancreatic cancer. In preclinical and current clinical studies, VERU-111 appears to have no evidence of neurotoxicity and neutropenia, which are common side effects of taxanes and vinca alkaloids chemotherapy agents.