Ayala Pharmaceuticals, Inc. announced that new data from the RINGSIDE study evaluating its lead investigational candidate AL102 for the treatment of desmoid tumors (DT) are being presented at the European Society for Molecular Oncology (ESMO) Congress 2023, taking place October 20th to 24th in Madrid, Spain. The data are from Phase 2 (Part A) of the study and from the Open Label Extension (OLE). The results are featured in a poster being presented by Professor Robin Jones, Team Leader in Sarcoma Clinical Trials at The Institute of Cancer Research and Consultant Medical Oncologist at The Royal Marsden, UK.

The ongoing Phase 2/3 RINGSIDE clinical trial is a randomized, global multi-center study evaluating AL102 in patients with progressing desmoid tumors. The study consists of two parts: Phase 2 (Part A) is an open-label, dose regimen finding study, and Phase 3 (Part B) is a double blind, placebo-controlled study and Open Label Extension utilizing the 1.2 mg once daily dose regimen selected based on data from Phase 2. Patients in Phase 2 were randomized to one of three dose regimens of AL102 (n=14 each), including 1.2 mg once daily (QD), 4 mg twice a week (BIW) or 2 mg BIW. Patients in the intermittent dosing arms were allowed to rollover to the Open Label Extension to receive 1.2 mg once daily after evaluations were completed in the Phase 2 part.

The results presented at ESMO reflect a cut-off date as of July 5, 2023. Efficacy Results: 1.2 mg once daily achieved ORR of 83% per RECIST in the evaluable population as assessed by MRI BICR (Blinded Independent Central Review). ORR per RECIST was 64% in evaluable patients across the 3 dose arms (n=36).

Efficacy results continue to demonstrate a dose-response pattern favoring the 1.2 mg once daily arm. First Partial Responses (PRs) observed at 16 weeks and 21 additional PRs and 1 Complete Response across all dose arms. Early and deep volume (-52%) and T2 signal intensity (-58%) reductions within 16 weeks after starting 1.2 mg once daily. Best overall median reductions of 88% and 85% in volume and T2 signal intensity, respectively, in the 1.2 mg once daily arm at 16.6 months of median time on treatment.

Reductions in volume and T2 signal intensity were also observed across biweekly dose arms. 29 patients rolled over to the OLE between Oct 2022 and May 2023, with 27 still on study. Three patients from the 4 mg BIW arm achieved PR after rolling over to the OLE where they received 1.2 mg once daily. Safety: AL102 was generally well tolerated with a manageable safety profile across all dose arms. Adverse events (AEs) were consistent with gamma secretase inhibitors?

(GSI) mec anism of action. The most frequent treatment-related AEs with 1.2 mg once daily included diarrhea (92.8%), nausea (57.1%), fatigue (50%), dry skin (50%), alopecia (50%), stomatitis (50%) dermatitis acneiform (42.9%), dry mouth (42.9%), hypophosphatemia (42.9%), rash maculopapular (37.7%) and aspartate aminotransferase increased (28.6%). Regardless of dose regimen, AEs were Grade 1 or Grade 2 in >95% of the cases.

There was one Grade 4 unrelated AE and no Grade 5 AEs. There were no treatment-related serious AEs. Ovarian dysfunction was reported in 56% of pre-menopausal women in the 1.2 mg once daily arm and 61% of pre-menopausal women across all dose arms.