ASCO abstract highlights 50% partial response and 100% disease control rates in evaluable desmoid tumor patients treated with AL102 1.2 mg once daily (the selected Phase 3 dose)

Tumor response, volume and T2 signal reduction were observed earlier in the 1.2 mg once daily group, with deeper and sustained treatment responses

Registration-enabling Phase 3 segment of RINGSIDE is enrolling patients globally.

REHOVOT, Israel and MONMOUTH JUNCTION, N.J., May 25, 2023 (GLOBE NEWSWIRE) -- Ayala Pharmaceuticals, Inc. (OTCQX: ADXS), a clinical-stage oncology company, today announced updated results from Phase 2 (Part A segment) of the RINGSIDE study evaluating AL102 in desmoid tumors. The results are summarized in an abstract published today for the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. More detailed results will be featured in a poster session at ASCO on Saturday, June 3. AL102 is a once-daily, potent, selective, oral gamma-secretase inhibitor (GSI).

“This latest data cut includes data from all 42 patients enrolled in the Phase 2 study portion of this trial and shows compelling evidence of anti-tumor activity for all tested dose regimens of AL102 across multiple measures, including RECIST-based response rate, disease control rate and reduction in tumor volume per blinded independent central review,” said Andres Gutierrez, MD, PhD, Executive Vice President & Chief Medical Officer of Ayala. “In addition, there appears to be a consistent pattern of deeper and faster responses in the 1.2 mg once-daily group, the selected Phase 3 dose, versus the biweekly regimen groups. We are also encouraged to see that AL102 continues to be generally well tolerated and has a manageable safety profile as seen in all three dose arms. There have been no new safety signals, and the safety results appear consistent with the GSI class. Overall, the data continuing to emerge from RINGSIDE support our belief that AL102 has the potential to become a valuable treatment option for people living with desmoid tumors as it may have important clinical advantages along with convenient once-daily dosing, which may improve treatment adherence and patient satisfaction.”

RINGSIDE Study 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, 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.

Enrollment of all 42 patients into Phase 2 was completed as of March 2022. Patients 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. 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.

Efficacy Results

• In the evaluable patient population, partial responses were observed in 50% of patients (i.e., 6 out of 12) in the 1.2 mg QD group, 23.1% of patients (3/13) in the 4 mg BIW group, and 45.5% of patients (5/11) in the 2 mg BIW group. Responses were assessed by blinded independent central review (BICR).
• In the intention-to-treat (ITT) population, partial responses were observed in 43% of patients (i.e., 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. Responses were assessed by BICR.
• Median volume changes, assessed by BICR, from baseline to week 16 were -51.9% for 1.2 mg QD,    -9.5% for 4 mg BIW, and -15.2% for 2 mg BIW.
• Median tumor volume changes from baseline to week 28 were -76.4%, -35.5%, and -51.2%, respectively, for the 1.2 mg QD, 4 mg BIW and 2 mg BIW dose groups.
• Similar patterns were observed for percentage changes from baseline in T2 signal intensity, suggesting reduction of cell density within the tumor.
• Disease control rates (partial response + stable disease) were 100%, 91%, and 97% in the evaluable patients in the 1.2mg QD, 4 mg BIW and 2 mg BIW dose groups, respectively.

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. For more information on RINGSIDE, please visit ClinicalTrials.gov and reference Identifier NCT04871282 (RINGSIDE).

Poster Presentation Details

The poster (abstract # 11515, Poster Bd # 449 in Hall A) will be available for viewing 1.15pm - 4:15pm CT Saturday, June 3, 2023. In addition to the presentation of the study in the poster hall, Elizabeth J. Davis, M.D. of Vanderbilt University Medical Center, will highlight and discuss this and other selected abstracts in the Poster Discussion Session S404 Primary track: Sarcoma, 4:30 pm CT on the same day. The focus of this session will be on how the findings apply to clinical practice and future research. Dr. Davis and the abstract presenters will answer questions during a moderated panel discussion.

A copy of the poster will be available on the Ayala corporate website, under Events & Presentations, following the presentation at ASCO.

About Desmoid Tumors

Desmoid tumors, also called aggressive fibromatosis or desmoid-type fibromatosis, are rare connective tissue tumors that typically arise in the upper and lower extremities, abdominal wall, head and neck area, mesenteric root, and chest wall, or other parts of the body. Desmoid tumors do not metastasize, but often aggressively infiltrate neurovascular structures and vital organs. People living with desmoid tumors are often limited in their daily life due to chronic pain, functional deficits, general decrease in their quality of life and organ dysfunction. Desmoid tumors have an annual incidence of approximately 1,700 patients in the United States and typically occur in patients between the ages of 15 and 60 years. They are most commonly diagnosed in young adults between 30-40 years of age and are more prevalent in females. Today, surgery is no longer regarded as the cornerstone treatment of desmoid tumors due to surgical morbidity and a high rate of recurrence post-surgery. There are currently no FDA-approved systemic therapies for the treatment of unresectable, recurrent or progressive desmoid tumors.

About AL102

AL102 is an investigational small molecule gamma secretase inhibitor (GSI) that is designed to potently and selectively inhibit Notch 1, 2, 3 and 4, and is currently being evaluated in the Phase 2/3 RINGSIDE clinical studies in patients with progressing desmoid tumors. AL102 is designed to inhibit the expression of Notch gene targets by blocking the final cleavage step by the gamma secretase required for Notch activation. Ayala obtained an exclusive, worldwide license to develop and commercialize AL102 from Bristol-Myers Squibb Company in November 2017. AL102 was granted U.S. FDA Fast Track Designation for the treatment of DT.

About Ayala Pharmaceuticals, Inc.

Ayala Pharmaceuticals, Inc. is a clinical-stage oncology company primarily focused on developing and commercializing small molecule therapeutics for people living with rare tumors and aggressive cancers and is also developing proprietary Lm-based antigen delivery products for patients suffering from more common cancers. The Company’s lead candidates under development are the oral gamma secretase inhibitor, AL102, for desmoid tumors; ADXS-504, a Lm-based therapy for early-stage prostate cancer; and the intravenous gamma secretase inhibitor, AL101, for adenoid cystic carcinoma. AL102 has received Fast Track Designation from the U.S. FDA and is currently in the Phase 3 segment of a pivotal study for patients with desmoid tumors (RINGSIDE). For more information, visit www.ayalapharma.com.

Contacts:

Ayala Pharmaceuticals:
+1-857-444-0553
info@ayalapharma.com 

Media:

Tim McCarthy
LifeSci Advisors, LLC
tim@lifesciadvisors.com
917-679-9282

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