Ascentage Pharma (6855) Study update summary

Key study presentations and clinical trial updates

• Presented pivotal phase II data for lisaftoclax in BTK inhibitor-failed RR/CLL SLL patients, showing over 62% ORR and strong efficacy in high-risk subgroups, with no tumor lysis syndrome or drug-related deaths.

• Released updated results for lisaftoclax in AML and high-risk MDS, achieving 40% CR and 80% ORR in high-risk MDS, and 31% ORR in venetoclax-resistant AML/MDS when combined with azacitidine.

• Showcased POLARIS-1 phase III trial for first-line Ph-positive ALL, with part A showing 64% MRD-negative CR rate and over 94% overall CR rate, outperforming historical controls.

• Provided four-year follow-up data for olverembatinib in CML patients failing three TKIs, demonstrating durable efficacy and improved safety over time.

• Updated results for olverembatinib as second-line therapy in CML-CP patients resistant to prior TKIs showed 76.7% CCYR and 43.3% MMR, with responses deepening over time.

Differentiation and safety profile insights

• Lisaftoclax features a daily dose ramp-up, reaching target dose in five days, offering convenience and no need for BTK inhibitor lead-in.

• Demonstrated lower hematological toxicity and no DDI, with a shorter half-life compared to other BCL-2 inhibitors.

• No tumor lysis syndrome reported in pivotal trials, addressing a key concern with other BCL-2 inhibitors.

• Olverembatinib's safety profile is consistent with previous reports, with 89.4% experiencing TRAEs and 44.7% grade ≥3 TRAEs, but no new safety signals or deaths.

• Safety and efficacy advantages position lisaftoclax as a preferred option for monotherapy or combination regimens in CLL/SLL.

Strategic trial design and regulatory progress

• GLORIA-4 and POLARIS-1 trials designed with input from global regulatory agencies, using investigator choice for control arms and focusing on high-risk or previously untreated populations.

• Enrollment for POLARIS-1 expected to complete by early 2027, with NDA filing planned the same year.

• GLORIA-4 trial design incorporates lessons from VERONA, aiming for improved safety and efficacy in first-line high-risk MDS.

• Olverembatinib is the first third-generation BCR-ABL inhibitor approved in China for CML-CP and CML-AP with T3151 mutations and for CML-CP resistant/intolerant to first/second-generation TKIs.

• Three global registrational Phase III studies are ongoing for Olverembatinib in CML-CP, Ph+ ALL, and SDH-deficient GIST.