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SUZHOU, China and ROCKVILLE, Md,, June 5, 2023 /PRNewswire/ -- Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancer, chronic hepatitis B (CHB), and age-related diseases, announced today that it has released preliminary results from a Phase Ib/II study of the Bcl-2 inhibitor, lisaftoclax (APG-2575), as a monotherapy or combined with ibrutinib or rituximab in patients with Waldenström macroglobulinemia (WM), in a Poster Presentation at the 59^th American Society of Clinical Oncology (ASCO) Annual Meeting that marked the first data readout from a multicenter global study of lisaftoclax in WM.

Showcasing progress in clinical development at the ASCO Annual Meeting for six consecutive years, Ascentage Pharma had clinical results from four clinical studies of four of the company's lead drug candidates selected for presentations in 2023. Among these results, the clinical data of lisaftoclax showed safety and efficacy of the drug candidate as a monotherapy and in combinations, including an overall response rate (ORR) of 100% in treatment-naïve patients,and low risk of tumor lysis syndrome (TLS) with the daily-dose ramp-up (3 days at fixed doses) with lisaftoclax plus ibrutinib. In addition, only negligible drug-drug interaction (DDI) was observed in the study.

WM is a rare, indolent, and incurable type of B lymphoplasmacytic cancer that is mostly treated with Bruton tyrosine kinase inhibitor (BTKi)- or rituximab-based regimens. However, there is currently no standard of care treatment for patients who are resistant or intolerant to first-line therapies and those who relapsed following responses to initial treatment. There is no Bcl-2 inhibitor has yet been approved for the treatment of WM.

"Lisaftoclax is a highly selective Bcl-2 inhibitor that is capable of inducing apoptosis and suppressing cell growth," said Sikander Ailamadhi, MD, the Principal Investigator of the Study from Mayo Clinic. "In this global Phase Ib/II study, lisaftoclax monotherapy showed encouraging antitumor activity and satisfactory safety profile in patients with relapsed/refractory (R/R) WM who had received prior treatment with BTKis. In addition, a response rate of 100% was achieved when in combination with BTKi for patients with treatment-naïve WM. This drug's other attributes include the patient friendly daily dose ramp-up schedule which allows for faster attainment of target therapeutic doses. We look forward to further exploring the efficacy and safety of lisaftoclax as a monotherapy and in combinations."

"The clinical results of lisaftoclax in patients with WM presented at this year's ASCO Annual Meeting highlighted the promising therapeutic utility of the drug candidate as a monotherapy or in combination in hematologic malignancies," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "In particular, the lisaftoclax plus BTKi regimen has demonstrated an impressive ORR that signalled exciting clinical potential. Looking ahead, we will accelerate this clinical development program and expedite the drug's journey to market to allow patients to benefit from this novel therapeutic as soon as possible."

* Lisaftoclax is an investigational drug that has not been approved in any country and region.

Highlights of the poster on lisaftoclax presented at this year's ASCO Annual Meeting:

Preliminary data of a phase 1b/2 study of BCL-2 inhibitor lisaftoclax (APG-2575) alone or combined with ibrutinib or rituximab in patients (pts) with Waldenström macroglobulinemia (WM).

• Abstract#: 7569
• Poster Board#: 120
• Session Title: Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia
• Highlights:
• This open-label, multicenter, global Phase Ib/II study was designed to evaluate the safety, tolerability, efficacy, and pharmacokinetics (PK) of the orally administered highly selective novel Bcl-2 inhibitor lisaftoclax (APG-2575) as monotherapy or in combination with ibrutinib or rituximab in patients with WM.
• As of April 12, 2023, a total of 46 patients were enrolled in the study and later enrolled into 3 arms as follows:

Arm A: lisaftoclax monotherapy in patients with WM resistant/intolerant to BTKis (n=14)

Arm B: lisaftoclax plus ibrutinib in treatment-naïve patients (n=24)

Arm C: lisaftoclax plus rituximab in ibrutinib and other BTKi-naïve relapsed/refractory patients (n=8)

The dose of lisaftoclax was escalated from 400 to 1,200 mg using a modified toxicity probability interval-2 (mTPI-2) design. Doses in Arms A, B, and C were escalated to up to 1,000 mg, 1,200 mg, and 800 mg, respectively.

•  
• Efficacy Results: The ORR (minor or deeper responses) and median time (range) to response (MTTR) for Arms A, B, and C were 50%, 100%, and 62.5%; 4.6 (1-9), 1 (1-5), and 4.4 (1-10) months, respectively. 2 very good partial responses (VGPRs) were observed in Arm B with a median time to VGPR of 3.1 (1.8-4.4) months. The study did not observe any significant difference between patients with and without the CXCR4 mutation.
• Safety Results: The dose-escalation of lisaftoclax did not meet the maximum-tolerated dose (MTD). At 1,200 mg, 1 grade 3 dose-limiting toxicity (DLT) (a grade 3 TLS) considered to be related to pre-existing renal impairment was observed in Arm B. Ventricular arrhythmias were not observed. 1 patient received dose reduction in lisaftoclax because of AEs, and 2 patients discontinued treatment because of AEs. Common lisaftoclax-related AEs (>10%) included neutropenia (36.9%), diarrhea (34.8%), leukocytopenia (21.7%), nausea (13.0%), anemia (13.0%), abdominal pain (10.9%), thrombocytopenia (10.9%), and decreased appetite (10.9%), with the most of these AEs being grade 1-2. The PK data indicated negligible drug- drug interaction (DDI) between lisaftoclax and ibrutinib.
• Conclusions: Lisaftoclax alone or combined with ibrutinib/rituximab demonstrated favorable safety and promising activity in patients with treatment-naïve or BTKi-refractory WM, with negligible risk of DDI between lisaftoclax and ibrutinib.

Appendix: The four posters on Ascentage Pharma's four lead drug candidates, including lisaftoclax, presented at this year's ASCO Annual Meeting.

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 9 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 40 Phase I/II clinical trials in the US, Australia, Europe, and China. Ascentage Pharma has been designated for multiple Major National R&D Projects, including five Major New Drug Projects, one New Drug Incubator status, four Innovative Drug Programs, and one Major Project for the Prevention and Treatment of Infectious Diseases.

Olverembatinib, the company's core drug candidate developed for the treatment of drug-resistant chronic myeloid leukemia (CML) and the company's first approved product, has been granted two Priority Review Designations and two Breakthrough Therapy Designations (BTDs) by the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA). To date, the drug had been included into the China 2022 National Reimbursement Drug List (NRDL). Furthermore, olverembatinib has been granted an Orphan Drug Designation (ODD) and a Fast Track Designation (FTD) by the US FDA, and an Orphan Designation by the EMA of the EU. To date, Ascentage Pharma has obtained a total of 16 ODDs from the US FDA and 1 Orphan Designation from the EMA of the EU for 4 of the company's investigational drug candidates.

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, MSD, and AstraZeneca. The company has built a talented team with global experience in the discovery and development of innovative drugs and is setting up its 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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SOURCE Ascentage Pharma