Ascentage Pharma’s Lisaftoclax Wins CDE Breakthrough Therapy Designation – Bcl‑2 Inhibitor Plus Acalabrutinib Tapped for First‑Line CLL/SLL

Ascentage Pharma (NASDAQ: AAPG; HKG: 6855) announced that lisaftoclax, its proprietary Category 1 innovative Bcl‑2 inhibitor, has been granted Breakthrough Therapy Designation (BTD) by the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) — for lisaftoclax in combination with acalabrutinib in the treatment of adult patients with previously untreated chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL/SLL).

Regulatory Milestone

Drug Profile & Mechanism of Action

• Molecule: Lisaftoclax — a novel, oral, selective Bcl‑2 inhibitor independently developed by Ascentage Pharma.
• Target: Bcl‑2 (B‑cell lymphoma‑2), the anti‑apoptotic protein overexpressed in CLL/SLL cells; selective inhibition restores programmed cell death in malignant B cells.
• Franchise Positioning: The first domestically developed original Bcl‑2 inhibitor approved in China and the second Bcl‑2 inhibitor approved globally — establishing Ascentage as the only non‑AbbVie player in this validated drug class.
• Approved Setting: China approval (July 2025) covers relapsed/refractory CLL/SLL in adults who have received at least one prior systemic therapy, including a BTK inhibitor.
• Combination Rationale: Pairing lisaftoclax with the BTK inhibitor acalabrutinib targets complementary survival pathways, the mechanistic backbone of modern chemo‑free CLL regimens — now being advanced into the first‑line setting.

Clinical Development – Global Phase III Program

• Four Global Registrational Phase III Trials: Ascentage Pharma is currently conducting four global registrational Phase III clinical trials for lisaftoclax, spanning multiple hematologic indications.
• GLORA‑2 (Lead First‑Line Study): The global registrational Phase III study GLORA‑2 is designed to evaluate lisaftoclax in combination with acalabrutinib as a first‑line treatment for CLL/SLL — the exact regimen recognized by the CDE’s BTD.
• BTD Implications: Breakthrough Therapy Designation provides expedited CDE review, rolling submissions and intensive guidance, potentially accelerating the path to a first‑line approval in China.
• Disclosures: GLORA‑2 enrollment status, interim data, and filing timelines were not disclosed in the announcement.

Market Impact & Outlook

• First‑Line Opportunity: Moving from relapsed/refractory into previously untreated CLL/SLL opens the largest patient pool in the indication, where Bcl‑2‑based chemo‑free combinations are the standard of care globally.
• Competitive Dynamics: Lisaftoclax competes with AbbVie/Roche’s venetoclax franchise; BTD for the lisaftoclax + acalabrutinib combination positions Ascentage to challenge in both the relapsed/refractory and first‑line segments of the world’s most common adult leukemia.
• Global Strategy: With four global Phase III trials underway, Ascentage is building an international registrational footprint — a rare profile among Chinese innovative drug developers in hematology.
• Regulatory Momentum: The designation adds to a string of milestones — China’s first domestic Bcl‑2 approval (2025) followed by first‑line BTD (2026) — compounding the asset’s regulatory credibility.
• Disclosures: Commercial forecasts, ex‑China filing plans, and revenue expectations were not disclosed.

Forward‑Looking Statements
This brief contains forward‑looking statements regarding the clinical development, regulatory review, and commercialization expectations for lisaftoclax, including the GLORA‑2 trial and potential first‑line approvals. Actual results may differ materially due to risks including clinical trial outcomes, CDE and other regulatory review timelines, competitive dynamics with existing Bcl‑2 and BTK therapies, and market adoption. Breakthrough Therapy Designation does not guarantee eventual approval.-Fineline Info & Tech