At Ayala, we are focused on developing best in class targeted therapies for cancer patients bearing Notch activating mutations. We are currently focused on indications where we can make the most clinical impact.
We have a clinical program for adenoid cystic carcinoma (ACC) and are planning to initiate clinical trials in patients with tumors bearing Notch activating mutations in Triple Negative Breast Cancer (TNBC) and in T-cell Acute Lymphoblastic Leukemia (T-ALL).
Adenoid Cystic Carcinoma
Adenoid Cystic Carcinoma (ACC) is a rare malignancy of secretory glands, typically originating in the salivary glands though it does appear in other primary sites.
ACC is diagnosed in about 1,300 new cases each year and afflicts about 10,000 patients in the United States.
The median age at diagnosis for ACC patients is a decade younger than for all cancer patients.
This cancer progression is characterized by frequent recurrences and metastases to sites such as the lungs, liver and bones. Treatment typically includes surgery and radiation. No chemotherapies or targeted drugs have been approved for ACC, though some may be effective in some patients.
About 34% of recurrent or metastatic ACC patients harbor Notch mutations.
AL101 clinical trial for ACC patients
Ayala is evaluating the potential of a new investigation drug, AL101. AL101 is a small-molecule that inhibits gamma secretase, an enzyme which plays a key role in the activation of the Notch signaling pathway.
AL101 has completed preclinical and phase 1 studies. A phase 2 study (ACCURACY) for AL101 in patients with adenoid cystic carcinoma (ACC) bearing activated Notch mutations has been initiated.
Interested patients and physicians can contact Ayala Medical for more information at email ClinicalTrials.gov_Accuracy@ayalapharma.com or call +1-857-444-0553.
Triple negative breast cancer
Approximately 10-20% of the 1.7M patients diagnosed annually WW with breast cancer, are Triple Negative Breast Cancer (TNBC).
TNBC is a form of breast cancer that lacks expression of estrogen receptor (ER), progesterone receptor (PR) and does not overexpress HER2. The disease has a poorer short-term prognosis than other subtypes of breast cancer, in part because there are currently no targeted therapies for these tumors.
Early stage TNBC is treated with a combination of surgery, radiation and chemotherapy, which can often lead to a good prognosis. Once metastatic, patients with TNBC have shorter overall survival in comparison with patients with other subtypes. The lack of validated therapeutic targets severely limits treatment options. The main therapeutic options for patients with metastatic TNBC are currently cytotoxic chemotherapies.
Tumor genomic profiling is revealing involvement of Notch alterations in TNBC (mutations and translocations). In breast cancer, the Notch pathway is especially active in the cancer stem cell subpopulation.
A study evaluating AL101 in TNBC patients bearing Notch activating mutations is planned for 2020.