Disease Need

Mutations in the Wnt/β-catenin pathway are responsible for millions of cases of cancer globally every year, but to date there have been no successful therapies targeting this pathway. These mutations are particularly prevalent in colorectal cancer: An estimated 80-90% of cases of colorectal cancer are caused by mutations in the Wnt/β-catenin pathway.^[1]

Colorectal cancer is the second-highest cause of global cancer deaths, according to the World Health Organization, with a toll of nearly 1 million deaths annually.^[2] It is becoming increasingly common in younger people, with approximately 10% of all new diagnoses of colorectal cancer occurring in people younger than 50.^[3]

Mutations in the Wnt/β-catenin pathway are present in the vast majority of  colorectal cancers. Unfortunately, there are no treatments that address this underlying disease biology today.

Metastatic colorectal cancer is an especially devastating malignancy that has seen few meaningful treatment advances in recent decades. There is a huge unmet need for life-extending treatment in this setting. Patients with metastatic disease face a 5-year survival rate of 15.6%.^[4]

The life expectancy and prognosis for colorectal cancer patients worsens as they progress through lines of treatment, with those who receive third or later line treatment for metastatic disease facing a dismal outcome. Available agents provide <2% response rates, fewer than 4 months of progression-free survival, and less than 8 months of survival.

Activating mutations in the Wnt/β-catenin pathway are present in a host of other tumor types, including:

• Desmoid tumors^[5]
• Adamantinomatous craniopharyngioma^[6]
• Endometrial and ovarian (endometrioid) cancer^[7]
• Adrenocortical carcinoma^[8]
• Hepatocellular carcinoma^[9]
• Metastatic castrate-resistant prostate cancer^[10]
• Gastric cancer^[11]
• Non-small cell lung cancer (NSCLC)^[12]
• Pancreatic cancer^[13]