ASCO 2022 | Ascentage Pharma Releases Updated Data Demonstrating Lisaftoclax's (APG-2575) Therapeutic Potential in Patients with R/R CLL/SLL

SUZHOU,China and ROCKVILLE,Md.,June 8,2022 -- Ascentage Pharma (6855.HK),a global biopharmaceutical company engaged in developing novel therapies for cancers,chronic hepatitis B (CHB),and age-related diseases,today announced that it has released the updated results from a Phase Ib/II study of the Bcl-2 inhibitor lisaftoclax (APG-2575) in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (R/R CLL/SLL) in a Poster Presentation at the 58th American Society of Clinical Oncology (ASCO) Annual Meeting.

Entering the fifth consecutive year in which company's abstracts were selected for presentations by the ASCO Annual Meeting,Ascentage Pharma showcased results from multiple clinical trials of its five drug candidates,including favorable data of lisaftoclax,a key drug candidate of the company's apoptosis-targeted pipeline,in Chinese patients with R/R CLL/SLL showing an objective response rate (ORR) of 67.4%. Lisaftoclax was well tolerated,and all adverse events were manageable. No dose-limiting toxicity (DLT) were observed at up to 800 mg/day. The risk of clinical tumor lysis syndrome (TLS) in patients on daily dose ramp-up was minimal.

Prof. Jianyong Li,Director of the Hematology Department,Jiangsu People's Hospital,and the principal investigator of this study,said,"Lisaftoclax is a Bcl-2 selective inhibitor that can induce apoptosis and suppress the growth of tumor cells. In this Phase Ib/II study,lisaftoclax as a single agent showed favorable preliminary efficacy and safety,and a daily ramp-up schedule that is patients' friendly. We look forward to further evaluating the efficacy of lisaftoclax as a single agent and in combinations in patients with R/R CLL/SLL."

Dr. Yifan Zhai,Chief Medical Officer of Ascentage Pharma,commented,"Lisaftoclax is the first China-developed Bcl-2 inhibitor entering clinical development in China,also the world's second and China's first Bcl-2 inhibitor being investigated in pivotal trials. Data released at this year's ASCO Annual Meeting suggest that lisaftoclax may offer an effective,safe,and more 'user friendly' treatment alternative to patients with R/R CLL/SLL. We are taking firm steps forward with this clinical development program to allow patients to benefit from this novel therapeutic as soon as possible. Meanwhile,we are also evaluating lisaftoclax monotherapy and combinations in patients with solid tumors."

Dr. Zhai continued,"Furthermore,we are proud to be able to present clinical development progress for a number of Ascentage Pharma's drug candidates,which highlight our capabilities in global innovation. Honoring our mission of addressing unmet clinical needs in China and around the world,we are now accelerating our clinical programs to bring more safe and effective therapeutics to patients in need."

The highlights of this abstract on lisaftoclax are as follows:

A phase Ib/II study of lisaftoclax (APG-2575),a novel BCL-2 inhibitor (BCL-2i),in patients (pts) with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (R/R CLL/SLL).

Abstract: #7543

The aim of this multicenter,open-label study was to evaluate the safety,antitumor activity,PK,and pharmacodynamics (PD) of lisaftoclax in Chinese patients with R/R CLL/SLL.

As of January 25,2022,45 patients had been enrolled. Lisaftoclax was administered orally once daily at 3 dose cohorts (400,600,or 800 mg) in 28-day cycles,with 15 patients in each cohort.

Lisaftoclax monotherapy demonstrated favorable safety profiles in all three dose cohorts,and no DLT was observed during the Phase I study.

The risk of TLS in patients on daily dose ramp-up was extremely low,which was consistent with the observations of the Phase I study. The median duration of treatment was 7 cycles. and the ORR in the 43 efficacy evaluable patients with R/R CLL/SLL was 67.4%,including 1 complete response (CR) and 28 partial responses (PRs).

BCL-2i lisaftoclax was well tolerated up to 800 mg/day. There were no significant new or unmanageable safety findings. The recommended Phase II dose (RP2D) of lisaftoclax was determined as 600 mg. Lisaftoclax may offer a treatment alternative for patients with R/R CLL/SLL,with a daily ramp-up schedule that may be more convenient and "user friendly".

Appendix: A list of Ascentage Pharma's abstracts selected by this year's ASCO Annual Meeting

Drug Candidate

Abstract Title

Abstract #

Format

Olverembatinib（HQP1351）

Promising antitumor activity of olverembatinib (HQP1351) in patients (pts) with tyrosine kinase inhibitor- (TKI-) resistant succinate dehydrogenase- (SDH-) deficient gastrointestinal stromal tumor (GIST).

#11513

Poster discussion

Lisaftoclax (APG-2575)

A phase Ib/II study of lisaftoclax (APG-2575),in patients (pts) with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (R/R CLL/SLL).

#7543

Poster presentation

Phase Ib/II study of BCL-2 inhibitor lisaftoclax (APG-2575) safety and tolerability when administered alone or combined with a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor in patients with estrogen receptor-positive (ER⁺) breast cancer or advanced solid tumors.

#TPS1122

Poster presentation

Alrizomadlin (APG-115)

Newly updated activity results of alrizomadlin (APG-115),a novel MDM2/p53 inhibitor,plus pembrolizumab: Phase 2 study in adults and children with various solid tumors.

#9517

Poster discussion

APG-2449

First-in-human phase I results of APG-2449,a novel FAK and third-generation ALK/ ROS1 tyrosine kinase inhibitor (TKI),in patients (pts) with second-generation TKI-resistant ALK/ROS1 non-small-cell lung cancer (NSCLC) or mesothelioma.

#9071

Poster presentation

Pelcitoclax (APG-1252)

Updated study results of pelcitoclax (APG-1252) in combination with osimertinib in patients (pts) with EGFR-mutant non-small-cell lung cancer (NSCLC).

#9116

Poster presentation

First-in-human study of pelcitoclax (APG-1252) in combination with paclitaxel in patients (pts) with relapsed/refractory small-cell lung cancer (R/R SCLC).

e20612

Publication-Only

About Ascentage Pharma

Ascentage Pharma (6855.HK) is a globally focused biopharmaceutical company engaged in developing novel therapies for cancers,chronic hepatitis B,and age-related diseases. On October 28,2019,Ascentage Pharma was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code 6855.HK.

Ascentage Pharma focuses on developing therapeutics that inhibit protein-protein interactions to restore apoptosis,or programmed cell death. The company has built a pipeline of eight clinical drug candidates,including novel,highly potent Bcl-2,and dual Bcl-2/Bcl-xL inhibitors,as well as candidates aimed at IAP and MDM2-p53 pathways,and next-generation tyrosine kinase inhibitors (TKIs). Ascentage Pharma is also the only company in the world with active clinical programs targeting all three known classes of key apoptosis regulators. The company is conducting more than 50 Phase I/II clinical trials in the US,Australia,Europe,and China. Olverembatinib,the company's core drug candidate developed for the treatment of drug-resistant chronic myeloid leukemia (CML),was granted Priority Review status and a Breakthrough Therapy Designation (BTD) by the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) and is already approved for the indication. In addition,olverembatinib was also granted an Orphan Drug Designation (ODD) and a Fast Track Designation (FTD) by the US FDA,and an Orphan Designation by the EU. To date,Ascentage Pharma has obtained a total of 15 ODDs,2 FTDs,and 2 Rare Pediatric Disease (RPD) designations from the FDA and 1 ODD from the EU for four of the company's investigational drug candidates. Ascentage Pharma has been designated for multiple Major National R&D Projects,including 5 National Major New Drug Discovery and Manufacturing projects,1 New Drug Incubator status,4 Innovative Drug Programs,and 1 Major Project for the Prevention and Treatment of Infectious Diseases.

Leveraging its robust R&D capabilities,Ascentage Pharma has built a portfolio of global intellectual property rights and entered into global partnerships with numerous renowned biotechnology and pharmaceutical companies and research institutes such as UNITY Biotechnology,MD Anderson Cancer Center,Mayo Clinic,Dana-Farber Cancer Institute,Merck,AstraZeneca,and Pfizer. The company has built a talented team with global experience in discovering,developing,launching,and commercializing innovative drugs and is setting up world-class commercial manufacturing and Sales & Marketing teams. One pivotal aim of Ascentage Pharma is to continuously strengthen its R&D capabilities and accelerate its clinical development programs,in order to fulfil its mission of addressing unmet clinical needs in China and around the world for the benefit of more patients.

Forward-Looking Statements

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