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Ayala Pharmaceuticals’ preclinical data supports clinical development of AL101 in TripleNegative Breast Cancer (TNBC) tumors bearing Notch mutation

– 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

Title: 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.”

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