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Therapies to transform today’s treatment options for rare tumors and aggressive cancers

At Ayala, we’re focused on developing and commercializing small molecule therapeutics for patients living with rare tumors and aggressive cancers.

Our Targeted Approach to Treating Rare Cancers

Our current portfolio of investigational product candidates, AL101 and AL102, targets aberrant activation of the Notch-pathway with gamma secretase inhibitors.

When gamma secretase, the enzyme responsible for Notch activation, is inhibited, it turns off the Notch-pathway activation. Aberrant activation of the Notch-pathway has long been implicated in multiple solid tumor and hematological cancers and has often been associated with more aggressive cancers. Notch serves as a critical facilitator in processes, such as cellular proliferation, survival, migration, invasion, drug resistance and metastatic spread - all of which contribute to poorer patient prognosis.

AL101 and AL102 are designed to address the underlying key drivers of tumor growth by targeting Notch-pathway activation directly.

We’re working on therapies that, if approved by regulatory authorities, could transform today’s treatment options for people living with rare tumors and aggressive cancers.

Disease Focus Areas

Ayala is currently developing potential therapies to treat these rare tumors and aggressive cancer types

Desmoid Tumors

Desmoid tumors, also called aggressive fibromatosis or desmoid-type fibromatosis, are rare connective tissue tumors that typically arise in the upper and lower extremities, abdominal wall, head and neck area, mesenteric root and chest wall with the potential to arise in additional parts of the body. Desmoid tumors do not metastasize but often aggressively infiltrate neurovascular structures and vital organs. People living with desmoid tumors are often limited in their daily life due to chronic pain, functional deficits, general decrease in their quality of life and organ dysfunction.

Desmoid tumors have an annual incidence of approximately 1,700 patients in the United States and typically occur in patients between the ages of 15 and 60 years. They are most commonly diagnosed in young adults 30-40 years of age and are more prevalent in females.

Today, surgery is no longer regarded as the cornerstone treatment of desmoid tumors due to a high rate of recurrence post-surgery and there are currently no FDA-approved systemic therapies for the treatment of unresectable, recurrent or progressive desmoid tumors.


Ayala is currently conducting a Phase 2/3 clinical trial of AL102 for the treatment of progressing desmoid tumors.


Adenoid Cystic Carcinoma (ACC)

ACC is a rare malignancy of the secretory glands, most commonly of the salivary glands. ACC has an annual incidence of approximately 3,400 patients in the United States, approximately 1,700 of which are recurrent/metastatic (R/M) ACC patients. There are currently no FDA-approved therapies for this indication.

Based on scientific literature and our bioinformatics research, we estimate that 18% to 22% of R/M ACC patients have Notch-activating mutations. As the understanding of the biology of cancer and ACC specifically evolved, the importance of the Notch-pathway and Notch-activating mutations was established. ACC patients with Notch-activating mutations are more likely to present advanced-stage disease, and develop a distinctly different pattern of metastatic disease compared to those without.

For Notch patients, overall median survival rates can be significantly worse—roughly four times shorter than patients without Notch-activating mutations.

Ayala is currently in Phase 2 (ACCURACY) Clinical Trial for AL101 in patients with ACC bearing activated Notch mutations.

T-cell Acute Lymphoblastic Leukemia (T-ALL)

T-ALL is an aggressive, rare form of T-cell specific leukemia. T-ALL has an annual incidence of approximately 1,200 patients in the United States, of which an estimated 400 patients, including pediatric patients, present for the treatment of relapsed/refractory (R/R) T-ALL. Approximately 65% of all T-ALL patients have Notch-activating mutations. In addition, there is an incremental subset of patients with Notch-pathway activation who do not bare Notch-activating mutations.

T-ALL is characterized by chemotherapy resistance, induction failure and tendency for early relapse.

Ayala will soon commence Phase 2 clinical trial of AL102 for the treatment of R/R T-ALL.


  • Gounder, M., et al., Initial Results of Phase 2/3 Trial of AL102 for Treatment of Desmoid Tumors (DT). ESMO 2022 mini-oral presentation
  • Chan, D., et al., Activity of the Gamma Secretase Inhibitor AL101 in Desmoid Tumors: A Case Report of 2 Adult Cases. Curr Oncol, 2021. 28(5): p. 3659-3667
  • Ho, A.L., et al., ACCURACY: A phase II trial of AL101, a selective gamma secretase inhibitor, in subjects with recurrent/metastatic (R/M) adenoid cystic carcinoma (ACC) harboring Notch activating mutations (Notchmut): Results of 6-mg cohort. 2021.
  • Hapuarachi, B.S., et al., Clinical disease course and survival outcomes following disease recurrence in adenoid cystic carcinoma (ACC) with NOTCH signaling pathway activation. Journal of Clinical Oncology, 2021. 39(15_suppl): p. 6072-6072.
  • Ferrarotto, R., et al., 1789P - The gamma secretase inhibitor AL101 combined with other drugs for dual targeting of Notch dysregulated tumors. Annals of Oncology, 2021. 32: p. S1211-S1226.
  • Ferrarotto, R., et al., 919MO ACCURACY a phase II trial of AL101, a selective gamma secretase inhibitor, in subjects with recurrent/metastatic (R/M) adenoid cystic carcinoma (ACC) harboring Notch activating mutations (Notchmut). Annals of Oncology, 2020. 31: p. S663.
  • Ferrarotto, R., et al., ACCURACY: phase (P) 2 trial of AL101, a pan-Notch inhibitor, in patients (pts) with recurrent/metastatic (R/M) adenoid cystic carcinoma (ACC) with Notch activating mutations (Notchact mut). Journal of Clinical Oncology, 2019. 37(15_suppl): p. TPS6098-TPS6098.
  • Ferrarotto, R., et al., Abstract 4885: AL101 mediated tumor inhibition in Notch mutated ACC PDX models. Cancer Research, 2019. 79(13 Supplement): p. 4885-4885.
  • Broner, E.C., et al., AL101 mediated tumor inhibition in notch-altered TNBC PDX models. Journal of Clinical Oncology, 2019. 37(15_suppl): p. 1064-1064.
  • Aung, K.L., et al., A multi-arm phase I dose escalating study of an oral NOTCH inhibitor BMS-986115 in patients with advanced solid tumours. Invest New Drugs, 2018. 36(6): p. 1026-1036.
  • Morgan, K.M., et al., Gamma Secretase Inhibition by BMS-906024 Enhances Efficacy of Paclitaxel in Lung Adenocarcinoma. Mol Cancer Ther, 2017. 16(12): p. 2759-2769.
  • Knoechel, B., et al., Complete hematologic response of early T-cell progenitor acute lymphoblastic leukemia to the gamma-secretase inhibitor BMS-906024: genetic and epigenetic findings in an outlier case. Cold Spring Harb Mol Case Stud, 2015. 1(1): p. a000539.
  • Gavai, A.V., et al., Discovery of Clinical Candidate BMS-906024: A Potent Pan-Notch Inhibitor for the Treatment of Leukemia and Solid Tumors. ACS Med Chem Lett, 2015. 6(5): p. 523-7.

Learn more about Ayala


Investigational Therapies

Get Involved

Have a patient that may be a candidate for our clinical trials? Learn more about our ACC ACCURACY trial, and desmoid tumor RINGSIDE trial.

Patient Resources

Helpful links to more information and support organizations for patients.

- Gary Gordon, MD, PhD, Chief Medical Officer, Ayala Pharmaceuticals

“We're very excited for what the future may hold for AL101 and AL102. Our team of oncologists and researchers are hoping to change the landscape for how we can identify and address the underlying drivers of tumor growth. Through our unique approach, we’re striving to make a real difference for people living with rare and aggressive cancers.”