If a person inherits only one functional copy of the p53 gene from their parents, they are predisposed to cancer and usually develop several independent tumors in a variety of tissues in early adulthood. This condition is rare, and is known as Li-Fraumeni syndrome (LFS). However, mutations in p53 are found in most tumor types, and so contribute to the complex network of molecular events leading to tumor formation.
The lifetime risk for a person with LFS to develop any type of cancer is about 90%. Approximately 50% of these cancers will be diagnosed before age 30, and 40% will be diagnosed during childhood. However, some people with LFS will never develop cancer. Approximately 70% of families with LFS will have a p53 mutation.
COTI-2 is our clinical stage small molecule activator of misfolded mutant p53 protein. Extensive studies have demonstrated COTI-2's ability to restore mutant p53 function and thus induce cancer cell death in many common p53 mutations. Mutations of the p53 gene are the most common genetic alterations in human cancers, occurring in a wide range of cancers, including ovarian, lung, colorectal, breast, liver, bladder and other cancers. COTI-2's specific protein target, low toxicity, combination effectiveness with standard agents, and potential for longer term outpatient therapy as an oral agent, supports a dramatic change in the treatment of susceptible cancers.
Assuming that clinical trials are successful, COTI-2 could eventually become the first-line therapy for the treatment of LFS in many jurisdictions.