Avanish Vellanki, Cofounder and CEO at Rain Therapeutics, discusses the role of p53 and MDM2 in cancers like liposarcoma, the mechanism of action of milademetan, and the positive pre-clinical data presented at the 2021 World Conference of Lung Cancer.

As Mr. Vellanki explains, p53 regulates the cell cycle and is essential for tumor suppression. MDM2 is a crucial regulator of p53. If MDM2 is overexpressed, p53 can be inactivated, leading to tumor growth and cancer progression. Milademetan, Rain Therapeutics’ lead product candidate, inhibits MDM2, and, in doing so, is hypothesized to reactivate p53 and thus control cancer growth in approximately 50% of cancers without a p53 mutation.

Mr. Vellanki notes that MDM2 inhibition has been studied for a number of years. However, in the past, blood toxicity has been an issue. One reason for that is previous treatment regimens would allow the drug to accumulate in the tissues of patients. Milademetan does not accumulate in tissues when patients take milademetan for 3 days and then no treatment for 11 days. This allows the drug to be effective but prevents blood toxicity. This dosing schedule, according to Mr. Vellanki, has led to triple-to-quadruple the length of progression free survival compared to standard of care in liposarcoma, milademetan’s main indication.

At the 2021 World Conference of Lung Cancer, pre-clinical data suggested milademetan could also be safe and effective in treating malignant pleural mesothelioma. 

To learn more about liposarcoma and other rare cancers, visit checkrare.com/diseases/cancers/