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Pipeline2019-11-05T13:43:36+00:00

Best in Class Gamma-Secretase Inhibitors

At Ayala, we are developing best-in-class gamma-secretase inhibitors (GSIs), which hold great promise
as targeted therapies in cancer.

Our GSIs are small-molecules that inhibit gamma secretase, an enzyme which plays a key role in the activation of the Notch signaling pathway by releasing the Notch intracellular domain (NICD) from the membrane, thus activating transcription programs involved in tumorigenesis. Our drugs are intended for the treatment of genomically defined cancers where Notch is a known oncogenic driver.

Ayala Pipeline Overview

Ayala Program Overview

Inhibiting activated notch signaling
may impede tumor growth

Ayala is evaluating the potential
of a new investigational drug, AL101

AL101 inhibits Notch signaling and potentially impede tumor growth in patients with aberrant Notch signaling.

We have completed preclinical and phase 1 studies with AL101, which provided proof of concept for our patient selection approach. The phase 2 study, ACCURACY, for patients with adenoid cystic carcinoma bearing Notch activating mutations, is open for enrollment.

Interested patients and physicians can contact Ayala Medical for more information at email
clinicaltrials.gov_accuracy@ayalapharma.com or call
+1-857-444-0553.

Notch Inhibition with AL101, AL102

  • 01 Notch Pathway In Normal State
  • 02 Notch Activation in Cancer
  • 03 AL101 Inhibits Notch Activation
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  • 01 Notch Pathway In Normal State

    Notch signaling plays a key role in normal cell proliferation, differentiation, and development

  • 02 Notch Activation in Cancer

    In cancer, activation of Notch results in uncontrolled proliferation and differentiation processes.

    *Illustration is representative of a classical gain of function (GOF) point mutation. GOF mutations can also occur via translocations, fusions, deletions, and stabilization of NICD.

  • 03 AL101 Inhibits Notch Activation

    AL101 and AL102 bind to and block gamma secretase, preventing cleavage of the Notch receptor and, hence, release of the NICD into the nucleus, which is necessary to initiate the transcription of the Notch target genes; thereby, inhibiting the activation of the Notch pathway

    *Illustration is representative of a classical gain of function (GOF) point mutation. GOF mutations can also occur via translocations, fusions, deletions, and stabilization of NICD.

Exploring the potential of AL102

 

Ayala is committed to developing new targeted therapies for genomically-defined cancers in patient populations with high unmet medical need. Ayala is evaluating AL102 as an inhibitor of the Notch pathway in cancers.

In addition to developing AL102 as a Notch inhibitor , AL102 is also under evaluation as an anti- B-cell maturation antigen (BCMA) therapy in multiple myeloma. AL102 is an oral small-molecule that inhibits gamma secretase, an enzyme which may be targeted to increase levels of BCMA, which is expressed in most multiple myeloma patients. BCMA is actively shed from multiple myeloma cells by gamma secretase, hence its inhibition by AL102 is envisioned to increase BCMA levels on multiple myeloma cells and decrease levels of circulating soluble BCMA.

Novartis holds an option to license AL102 for use in multiple myeloma.

Be informed