ASCENTAGE-B (06855) announced that the company's self-developed Bcl-2 selective inhibitor lisaftoclax (trade name: Lestauva®; development code: APG-2575) in combination with azacitidine (AZA) for first-line treatment of newly diagnosed intermediate-high risk myelodysplastic syndrome (HR-MDS) patients has received approval from the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) to conduct the global Phase III clinical trial (GLORA-4). As the second global Phase III study approved by US and European regulatory agencies for Lestauva®, GLORA-4 (NCT06641414) will simultaneously enroll patients across multiple countries and centers, accelerating the drug approval process. As of this announcement date, Lestauva® is the only Bcl-2 inhibitor internationally advancing a Phase III registration trial for intermediate-high risk MDS. This study is expected to address the long-standing clinical gap in the intermediate-high risk MDS field and represents another important milestone in Lestauva®'s global clinical development.

GLORA-4 is an international multicenter, randomized, double-blind Phase III clinical trial designed to evaluate the efficacy and safety of Lestauva® combined with AZA versus placebo combined with AZA in newly diagnosed adult HR-MDS patients. The GLORA-4 study received clinical trial approval from CDE in 2024. The study is currently advancing patient enrollment globally and has completed first patient enrollment in China and Europe. The global leading principal investigators (Leading PI) are Professor Garcia Manero, Chief of Leukemia at The University of Texas MD Anderson Cancer Center (MDACC), and Professor Huang Xiaojun, Academician of the Chinese Academy of Engineering, Director of Peking University Institute of Hematology, and Chief of Hematology at Peking University People's Hospital.

As a myeloid clonal proliferative disease originating from hematopoietic stem cells, MDS has significant age-related characteristics. Global epidemiological studies show that its incidence increases exponentially with age (annual incidence rate of 22/100,000 in population over 65 years old), with a median diagnosis age of 70 years, and >75% of patients have complex conditions often accompanied by at least two comorbidities. The core risk of this disease lies in acute myeloid leukemia (AML) transformation caused by clonal evolution. Among intermediate-high risk groups (IPSS-R high risk/very high risk) patients, the 5-year AML transformation rate is as high as 40-60%, with extremely poor prognosis after transformation and median survival of less than 6 months.

Hypomethylating agents (HMAs) as the first-line standard regimen for intermediate-high risk MDS have an overall response rate (ORR) of only 30-40%, complete remission (CR) rate of only 10-17%, and median duration of response of only 9-12 months, showing insufficient treatment response. Although allo-HSCT can provide curative potential, it is limited by patients' median age, complex conditions, common hematopoietic stem cell reserve depletion in MDS, and transplant-related mortality (TRM) of 25-35%. Only 5-10% of suitable patients can receive transplantation, limiting curative options. The 5-year survival rate for IPSS-R high-risk patients remains stagnant at 16-24%, urgently requiring breakthrough therapies to rewrite the treatment paradigm.

Lestauva® is a novel oral Bcl-2 selective inhibitor independently developed by ASCENTAGE PHARMA GROUP. It achieves tumor treatment by selectively inhibiting Bcl-2 protein and restoring normal apoptosis processes in cancer cells. Currently, this product has been approved for market in China for adult chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) patients who have previously received at least one systemic treatment including Bruton's tyrosine kinase (BTK) inhibitors. Lestauva® is China's first domestically developed original Bcl-2 inhibitor approved for market.

Previously, at the 2024 American Society of Hematology (ASH) Annual Meeting and 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, data from Lestauva® combined with AZA for treatment-naïve (TN) MDS showed: Lestauva® combined with AZA achieved an ORR of 75% in TN MDS, significantly higher than HMAs, demonstrating excellent clinical benefit. The safety profile was favorable, with low incidence of severe hematologic toxicity and neutropenia-related infections, low proportion of patients requiring dose adjustments, and no treatment-related deaths reported within 60 days.