Ayala Pharmaceuticals to Present at ASCO Annual Meeting on Investigational Drug AL101 in Adenoid Cystic Carcinoma and Triple Negative Breast Cancer

  • Ongoing Phase 2 ACCURACY study to explore AL101 and its effect on tumor growth inhibition in people with Adenoid Cystic Carcinoma (ACC) tumors bearing Notch activated mutations
  • Preclinical data supports clinical development of AL101 in Triple Negative Breast Cancer (TNBC) tumors bearing Notch mutation

REHOVOT, Israel & WILMINGTON, Del.–(BUSINESS WIRE)–Ayala Pharmaceuticals, Inc., a clinical-stage company developing medicines for cancers that are genetically defined, today announced updates on AL101, a pan-Notch inhibitor, that will be presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Il.

The details of the poster presentations are as follows:

Title: 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)

Date and Time: Saturday, June 1 at 1:15 – 4:15 p.m. CT
Location: McCormick Place, Exhibit Hall A, Poster Section: Head and Neck Cancer
Poster Board Number: 82B
Abstract Number: TPS6098

AL101 mediated tumor inhibition in notch-altered TNBC PDX models

Date and Time: Sunday, June 2 at 8:00 – 10:00 a.m. CT
Location: McCormick Place, Exhibit Hall A, Poster Section: Breast Cancer – Metastatic
Poster Board Number: 145
Abstract Number: 1064

Ayala Pharmaceuticals is developing its investigational product AL101 for treatment of tumors with Notch activated mutations. Ayala has prioritized its research to focus on indications where the role of Notch activation is well characterized, such as ACC and TNBC. AL101 is a small-molecule that inhibits gamma secretase, an enzyme which plays a key role in the activation of the Notch signaling pathway by releasing the Notch intracellular domain (NICD) which migrates to the nucleus initiating a complex transcription program.

The FDA recently granted Orphan Drug Designation for AL101 for the treatment of ACC. The ACCURACY Phase 2 trial is a multicenter, open-label trial in ACC patients with Notch activated mutations. The primary endpoint of the trial is to assess overall response rate upon weekly administration of AL101 4 mg IV. Secondary endpoints include duration of response, progression free survival and overall survival. Twelve patients are currently being treated in stage one of the phase 2 ACCURACY trial.

“I’m very excited about this trial given the early signs of activity previously observed in Phase 1b study and in ACC Patient Derived Xenograft animal models with AL101 in tumors that harbor Notch activated mutations,” said Dr. Renata Ferrarotto, M.D., Associate Professor, Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center. “This trial is an important step toward understanding the role AL101 may have in treating ACC patients with Notch activating mutations.”

Additionally, Ayala Pharmaceuticals recently completed a preclinical study for TNBC, a sub-type of breast cancer associated with poor prognosis and limited availability of targeted therapies. The Notch pathway is activated during mammary gland development and has been implicated as a key driver in a subset of TNBC.

The preclinical data to be presented at ASCO demonstrate that the response to AL101 monotherapy correlates with Notch activating mutations and fusions. Specifically, nine patients derived xenograft (PDX) models of TNBC were selected, whereby two of the PDX models had wild type (WT) Notch, four PDX models had Notch activating mutations and/or fusions and three models had Notch mutations which were not predicted to result in activation. Mice were randomized to Vehicle or AL101 treatment arms and significant inhibition of tumor growth was observed only in models with Notch activating mutations and fusions. These data support the clinical development of AL101 as a targeted therapy for TNBC tumors bearing Notch activating mutations/fusions.

“We are passionate about bringing innovative treatment options to people living with ACC and TNBC. I’m pleased with the meaningful advances Ayala is making to offer new hope to those living with underserved cancers,” said Roni Mamluk, Ph.D., Chief Executive Officer at Ayala Pharmaceuticals. “Our clinical programs are advancing swiftly, in fact, by the end of this year, we expect to have initial response rates from 12 patients of the first stage of our ongoing ACCURACY study in ACC.”

About AL101

AL101 is a gamma secretase inhibitor developed as a Notch inhibitor for oncology indications. Notch signaling pathway plays an important role in tumorigenesis in several solid and hematological malignancies. Upon ligand binding of the Notch receptor, an important step in the activation of Notch receptors is cleavage by gamma secretase, which frees the Notch intracellular signaling domain.

AL101 is currently in Phase 2 for adenoid cystic carcinoma patients with tumor bearing Notch activating mutations (ACCURACY). For additional information about AL101 ACCURACY clinical trial, please go to www.clinicaltrials.gov. Interested patients and physicians can contact Medical Affairs at Ayala Pharmaceuticals for more information at: accuracy@ayalapharma.com or call +1-857-444-0553.

About Adenoid Cystic Carcinoma (ACC)

ACC is a rare form of cancer. In the U.S., there are approximately 566,000 people diagnosed with cancer each year, and only about 1,224 of them are diagnosed with ACC. According to the Adenoid Cystic Carcinoma Organization International, there are approximately 14,873 Americans alive today living with this disease. Current treatment options include surgery, chemotherapy and/or radiation therapy; however, there are no approved drugs for the treatment of ACC.

About Triple Negative Breast Cancer (TNBC)

TNBC is a heterogeneous disease entity constituting about 15 percent of breast cancer cases worldwide. TNBC is associated with poor prognosis and lack of sustained response to conventional chemotherapeutic agents. Patients with recurrent and/or metastatic TNBC has a median survival of approximately 13 months; therefore, there is an urgent need to identify new therapeutic strategies for these patients.

About Ayala Pharmaceuticals

Ayala Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company dedicated to developing targeted cancer therapies for people living with genetically defined cancers. Ayala is broadly developing its product candidates, AL101 and AL102, best-in-class gamma secretase inhibitors, with clinical and preclinical studies underway in both solid tumors (AL101) and hematologic malignancies (AL102).

As a precision oncology company, Ayala was founded in November 2017 with an experienced global management team and a strong investor base. For more information, visit www.ayalapharma.com.

Ayala Pharmaceuticals

Katie Dodge