Ayala Pharmaceuticals, Inc. announced further results from the Phase 2 (Part A) segment of the RINGSIDE study evaluating AL102 in desmoid tumors. The results were presented in a Poster Discussion Session at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting on Saturday, June 3. AL102 is a once-daily, potent, selective, oral gamma-secretase inhibitor (GSI). RINGSIDE Poster Highlights: 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; Phase 3 (Part B) is a double blind, placebo-controlled study utilizing the 1.2 mg once daily dose regimen selected based on data from Phase 2. The study also includes an open label extension enrolling patients who were on active drug at the end of Phase 2, as well as crossover patients from Phase 3. In the Phase 2 segment of RINGSIDE, Patients were randomized to one of three dose regimens of AL102 (n=14 each): either 1.2 mg once-daily (QD), 4 mg twice a week (BIW) or 2 mg BIW. Enrollment of all 42 patients into Phase 2 was completed as of March 2022. As of January 3, 2023, median time on study was 10.3 months (range 0.8 – 14.7) and 30 patients were still on study,10 of whom rolled over to the open label extension.

In the intention-to-treat (ITT) population, partial responses were observed in 43% of patients (6/14) in the 1.2 mg QD group, 21.4% of patients (3/14) in the 4 mg BIW group, and 36% (5/14) in the 2 mg BIW group. There was a consistent pattern of deeper, more rapid and persistent tumor responses as measured by volume reduction, T2W signal intensity and RECIST with AL102 1.2 mg daily than with intermittent doses. The decrease in T2W, as measured by MRI, reflects a decrease in tumor cellularity and is considered a strong indicator of anti-tumor activity in desmoid tumors.

Tumor volume shrinkage consistently deepens over time and some patients who may not have had PRs by RECIST early in treatment may evolve to PRs with longer follow-up. Safety: AL102 was generally well tolerated with a manageable safety profile across all dose arms. The safety profile was consistent with the GSI class of drugs. Regardless of dose regimen, adverse events (AEs) were predominantly Grade 1 (~70%) or Grade 2 (~20%).

There were no Grade 4 or Grade 5 related AEs. Serious AEs were reported in 6 of 42 patients (14%) and assessed as unrelated to AL102 by investigators. There were no new safety signals.

Discontinuation due to AEs occurred in 6 of 42 (14%) patients. These were due to Grade 2 rash, keratitis, stomatitis, diarrhea, ALT elevation. All occurred within 3 months of treatment initiation.

Ovarian dysfunction was reported in 11 of 23 (48%) women of childbearing potential across all dose arms, but in only 3 of 9 (33%) women who received the 1.2 mg once-daily dose. The registration-enabling Phase 3 segment is enrolling patients globally.