Using our deep understanding of the Notch pathway, we are developing potential therapies to address the underlying key drivers of tumor growth in patients where gamma secretase inhibitors (GSIs) of Notch may make a difference.
What’s our approach to treating rare cancers?
indications in which activated Notch pathway is known to be a tumorigenic driver
on indications with high unmet medical need and pursue development in an efficient manner
addressable patient population by developing diagnostic tools that cover all four Notch receptors, genetic mutations and gene rearrangements
How does our technology work in helping to inhibit the Notch signaling pathway?
See the difference between normal and tumorigenic signaling of Notch, and how our gamma secretase inhibitors (GSIs) AL101 and AL102 can impact Notch signaling.
The Notch pathway is involved in embryonic development and in the renewal and maintenance of adult tissues.
In cancers, Notch is known to serve as a critical facilitator in processes such as cellular proliferation, survival, migration, invasion, drug resistance and metastatic spread, all of which contribute to tumorigenesis and cancer progression.
Inhibition of Notch by γ-secretase inhibitors (GSIs) such as AL101/AL102 turns off the Notch pathway activation.
AL101 is a novel, injectable, potent and selective small molecule gamma secretase inhibitor (GSI). AL101 is currently being studied in Phase 2 ACCURACY clinical trial for recurrent/metastatic adenoid cystic carcinoma (R/M ACC) for patients bearing Notch-activating mutations.
Ayala is developing AL102 for the treatment of desmoid tumors, which are rare, debilitating, and often disfiguring types of soft tissue tumors. Ayala is currently conducting a Phase 2/3 RINGSIDE clinical trial of AL102 for the treatment of progressing desmoid tumors. In addition, we intend to commence a Phase 2 clinical trial of AL102 for the treatment of T-cell acute lymphoblastic leukemia (R/R T-ALL). Evaluation of AL102 as an inhibitor of the Notch pathway for additional indications is ongoing.
AL102 is also being evaluated in a Phase 1 clinical trial in combination with Novartis’ BCMA targeting agent, WVT078, in patients with relapsed/refractory multiple myeloma (R/R MM).