Ascentage Pharma Group International (NASDAQ: AAPG, HKG: 6855) announced that China’s National Medical Products Administration (NMPA) has granted clinical trial approval for APG‑3288, a BTK‑targeted protein degrader, in patients with relapsed/refractory hematologic malignancies. The asset previously received US IND clearance, marking Ascentage’s progress in dual‑jurisdiction development.
Regulatory Milestone
Item
Detail
Company
Ascentage Pharma Group International (NASDAQ: AAPG, HKG: 6855)
Agency
NMPA (China) / CDE (Center for Drug Evaluation)
Asset
APG‑3288 (BTK PROTAC protein degrader)
Approval
Phase I clinical trial authorization
Patient Population
Relapsed/refractory hematologic malignancies
Global Status
US IND previously cleared; China approval now secured
Technology Platform & Mechanism of Action
Platform:Proteolysis Targeting Chimera (PROTAC) – Ascentage proprietary protein degradation technology
Target:Bruton’s tyrosine kinase (BTK) – Critical signaling node in B‑cell receptor pathway, validated in lymphoid malignancies
Degradation Mechanism:
Forms ternary complex (BTK‑PROTAC‑Cereblon E3 ubiquitin ligase)
Recruits E3 ligase to tag BTK with ubiquitin
Proteasome‑mediated degradation eliminates BTK protein entirely
Therapeutic Advantage: Functional protein elimination (vs. reversible inhibition) may overcome resistance mutations seen with traditional BTK inhibitors
PROTAC Competitive Landscape: APG‑3288 enters a rapidly evolving BTK degrader race against Nurix (NX‑2127), C4 Therapeutics (CFT8916), and others, with first‑generation BTK inhibitors (ibrutinib, zanubrutinib) establishing target validation but facing resistance limitations.
Degrader Differentiation: Unlike reversible or covalent BTK inhibitors, PROTAC‑mediated degradation eliminates both wild‑type and mutant BTK proteins, potentially addressing C481S mutation‑driven resistance that limits incumbent therapies.
Dual‑Listing Advantage: Ascentage’s NASDAQ/HKEX dual listing provides access to US and Asian capital markets, supporting global trial expansion and potential US‑China parallel development strategy.
Hematology Pipeline Synergy: APG‑3288 complements Ascentage’s established BCL‑2 inhibitor (lisaftoclax) and MDM2‑p53 inhibitor (alrizomadlin) portfolio, creating combination potential in relapsed/refractory B‑cell malignancies.
Development Roadmap
Phase
Milestone
Anticipated Timing
Current
China Phase I initiation (NMPA approved)
Q1 2026
Parallel
US Phase I ongoing (previously cleared)
Active enrollment
Future
Dose expansion and combination cohorts
2026‑2027
Strategic
Potential Big Pharma partnership discussions
Data‑dependent
Forward‑Looking Statements This brief contains forward‑looking statements regarding APG‑3288 clinical development timelines, efficacy outcomes in hematologic malignancies, and Ascentage Pharma’s global regulatory strategy. Actual results may differ due to trial execution risks, competitive dynamics in the BTK degrader space, and regulatory review processes.-Fineline Info & Tech
By Fineline Cube