Glioblastoma is the most common and deadliest of the malignant primary brain tumors in adults. The number of new diagnoses made annually is about 3.2 per 100,000 people in the United States and Europe. In the United States, this is about 10,000 patients. Standard treatment is surgery, followed by radiation therapy or combined radiation therapy and chemotherapy. Even with the best available care, median survival for adults with glioblastoma is only about 15 months and the five-year survival rate is less than 10%.
Olig2 is a transcription factor that is essential to normal early brain development, but it is not actively expressed in the vast majority of normal adult brain cells and normal tissues outside the brain. In glioblastoma and other brain cancers, though, it is markedly over-expressed in the cancer stem cells and has been shown to be an important factor in initiating the tumor, driving tumor growth, promoting resistance to radiation, and driving the invasion of the cancer cells into healthy brain tissue.
Why is glioblastoma so hard to treat? The problem is that conventional therapy debulks the tumor, but the Olig2-expressing cancer stem cells, which are resistant to chemotherapy and radiation therapy, survive and, ultimately, give rise to tumor recurrence and death.
Curtana’s solution is to add an Olig2 inhibitor to conventional therapy at the time of diagnosis. This treatment strategy would not only debulk the tumor, but it would also eliminate the cancer stem cells, thereby markedly delaying or, ideally, preventing the recurrence of the cancer.
Curtana’s clinical candidate, CT-179, is a highly potent and selective small molecule inhibitor of Olig2 with excellent drug-like properties. The drug can be taken by mouth, administered once daily, readily crosses the blood-brain barrier, achieves very high concentrations in the brain, and significantly prolongs survival in animal models of brain cancer. At therapeutic doses, CT-179 has been found to be safe and well tolerated. It is Curtana’s belief that by directly killing the cancer stem cells responsible for tumor initiation, growth, and invasion, CT-179 will lead to significantly improved patient outcomes.