VERU IS ENROLLING PATIENTS
To Evaluate the Safety and Tolerability of VERU-111 in Men with Advanced Metastatic Castration Resistant Prostate Cancer
In 2020, there will be an estimated 191,930 new cases of prostate cancer and about 33,330 men will die from the disease making prostate cancer the second leading cause of cancer deaths according to the American Cancer Society. 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. The median survival of patients with metastatic prostate cancer ranges from 3.2-4.5 years.1,2 For these men with advanced prostate cancer, 1st line therapy is androgen deprivation therapy (ADT), or medical castration. ADT-induced estrogen deficiency side effects can cause men to delay, pause and/or discontinue ADT, increases morbidity and mortality, and can significantly impact quality of life. ADT-induced side effects include hot flashes, bone loss and fractures, fatigue and libido, and adverse lipid and metabolic changes. Although most will initially respond, nearly all these patients will progress to metastatic castration resistant prostate and have a poor prognosis with an average survival of 1.5 years. 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 become resistant to these agents and develop progressive metastatic prostate cancer.
Drugs that target tubulin have been shown to be the most effective cytotoxic chemotherapy for the treatment of metastatic prostate cancer. Tubulin, a component of microtubules, is required for cancer cell replication and to shuttle the androgen receptor into the nucleus where the receptor stimulates genes for cancer cell proliferation. 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 IV and that the cancer cells develop resistance to taxanes in a variety of ways: Cancer cells may (i) express multidrug resistance proteins which pump the taxane chemotherapy meant to kill the cancer cells, out of the cancer cells; (ii) develop tubulin mutations so taxanes are no longer able to bind to the mutated tubulin; and/or (iii) overexpress beta-tubulin so that there is plenty of tubulin present for cell replication even if some tubulin is bound by taxanes. There are also serious safety concerns with IV taxanes which include serious hypersensitivity reactions, neutropenia, myelosuppression and neurotoxicity such as peripheral neuropathy and muscle weakness.
VERU-111 is a novel, proprietary, next generation, first-in-class oral selective antitubulin agent that targets and disrupts alpha and beta tubulin subunits of microtubules. In cancer cells, microtubules are critical for transport of growth factor receptors, cellular proliferation, and metastases. In preclinical effectiveness and toxicity studies, orally administered VERU-111 demonstrated significant antitumor activity against castration and novel androgen blocking agent (abiraterone or enzalutamide) resistant human prostate cancer models. Furthermore, VERU-111 had significant antitumor effects against cancers that overexpress multidrug resistant proteins, like P-glycoprotein, a common mechanism by which cancer cells become resistant to cancer drugs. At oral doses that had significant antitumor effects, VERU-111 had a favorable safety profile as it did not cause neutropenia or myelosuppression, common dose limiting side effects of other classes of commercially available antitubulins such as intravenous taxanes or intravenous vinca alkaloids. In addition to prostate cancer, VERU-111 had antitumor effects in other cancer types including preclinical human models for triple negative breast cancer, ovarian cancer and pancreatic cancer that are sensitive and resistant to taxanes. VERU-111 has the potential to be the first FDA approved oral, selective antitubulin agent that targets and disrupts alpha and beta tubulin subunits of microtubules to treat cancer.
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