By Fineline Cube 
China‑based Ascentage Pharma (HKG: 6855) showcased data from its two flagship pipelines—olverembatinib (HQP1351), a first‑in‑China third‑generation BCR‑ABL inhibitor, and lisaftoclax (APG‑2575), an orally available BCL‑2 antagonist—at the American Society of Hematology (ASH) 2025 conference.
Olverembatinib
- POLARIS‑1, Global Phase 3
- Population: 53 newly diagnosed (ND) Philadelphia chromosome‑positive (Ph⁺) acute lymphoblastic leukemia (ALL) patients who were eligible for low‑intensity chemotherapy.
- Efficacy: 94.3 % (50/53) achieved complete remission (CR) or CR with incomplete hematologic recovery (CRi) by induction end‑point.
- Minimal Residual Disease (MRD): Best MRD‑negative rate = 66.0 %; MRD‑negative CR rate = 64.2 %.
- Safety: The combination was well tolerated with no new safety signals.
- 4‑Year Follow‑Up, Randomized Phase II
- Population: Tyrosine‑kinase‑inhibitor (TKI)‑resistant chronic‑phase chronic myeloid leukemia (CML‑CP).
- Outcome: Sustained durable responses and favorable safety mirror results of the Phase II second‑line study in non‑T315I‑mutant CML‑CP patients.
Lisaftoclax
- Phase II, R/R CLL/SLL
- Population: Relapsed/refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) heavily pre‑treated with BTK inhibitors.
- Oral BCL‑2 Inhibition: Independent review committee (IRC) confirmed an overall response rate (ORR) of 62.5 %.
- Durability: Median progression‑free survival (mPFS) reached 23.9 months—the longest PFS reported for a single‑agent BCL‑2 inhibitor in BTK‑refractory disease.
- Safety: Toxicity was manageable, with the most common adverse events being cytopenias and infusion‑related reactions, neither requiring dose escalation.
- Lisaftoclax + Azacitidine (AZA) – Myeloid Resilience
- Population: Newly diagnosed (ND) or venetoclax‑pre‑treated myeloid malignancies.
- Finding: The combination effectively overcomes venetoclax resistance, showing early clinical promise and encouraging further dosing exploration.
Market Implications
- Hematology Leadership: Ascentage’s ability to deliver the first Phase 3 data for a third‑generation BCR‑ABL inhibitor and compelling single‑agent BCL‑2 data positions it as a formidable competitor to established Western biotech players.
- Expansion Opportunities: Olverembatinib’s low‑intensity chemo backbone offers a tolerable regimen for younger patients, while lisaftoclax’s oral delivery meets the unmet need for convenient outpatient therapy in CLL/SLL.
- Strategic Partnerships: The favorable safety profiles and durable responses support Ascentage’s pursuit of global co‑development agreements, especially in the U.S. and Europe where BCR‑ABL and BCL‑2 inhibitors are in high demand.-Fineline Info & Tech