Live from ASH 2023 | Ascentage Pharma Releases the First Dataset of Bcl-2 Inhibitor Lisaftoclax in Patients with R/R MM, Demonstrating Encouraging ORR and VGPR

SUZHOU, China and ROCKVILLE, Md., Dec. 11, 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 the clinical data of lisaftoclax (APG-2575), one of the company's key drug candidates, combined with various novel therapies in patients with relapsed/refractory (R/R) multiple myeloma (MM) or immunoglobulin light-chain (amyloid light-chain [AL]) amyloidosis, in a Poster Presentation at the 65th American Society of Hematology (ASH) Annual Meeting, taking place in San Diego, CA, the United States. This is the first data readout of lisaftoclax for the treatment of patients with R/R MM.

The ASH Annual Meeting is one of the largest gatherings of the international hematology community, bringing together the most cutting-edge scientific research and latest data of investigational therapies that represent leading scientific and clinical advances in the global hematology field. Garnering growing interest from the global research community, multiple studies of Ascentage Pharma's key drug candidates (lisaftoclax and olverembatinib) have been selected for presentations at this year's ASH Annual Meeting, including two Oral Presentations.

These data signalled the favorable therapeutic potential and tolerability of lisaftoclax combination regimens in patients with hematologic malignancies such as R/R MM. Results showed an overall response rate (ORR) of 66.7% and a very good partial response (VGPR) rate of 28.6% in patients with R/R MM who received lisaftoclax combined with pomalidomide and dexamethasone; and an ORR of 100% and a VGPR rate of 50% in patients with R/R MM who received lisaftoclax combined with daratumumab, lenalidomide, and dexamethasone. Lisaftoclax was well tolerated at doses up to the maximum of 1,200 mg.

Prof. Sikander Ailawadhi, MD, from Mayo Clinic and the principal investigator of this study, commented, "It was the first time to issue efficacy of lisaftoclax in patients with R/R MM, with an outstanding overall response rate. Lisaftoclax was well tolerated even when the combination dose was escalated up to 1200 mg. At the same time, the efficacy of lisaftoclax for patients with AL amyloidosis is also showing up."

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, said, "At this year's ASH Annual Meeting, we presented data of lisaftoclax combinations in patients with malignant plasmocyte diseases such as R/R MM that demonstrated promising ORR, VGPR; and favorable tolerability at doses up to 1,200 mg. These results reaffirmed the global best-in-class potential and unique therapeutic utility of lisaftoclax. Remaining committed to the mission of addressing unmet clinical needs in China and around the world, we will expedite our clinical development programs to bring safe and effective therapies to patients in need."

Highlights of the study presented at ASH 2023:

First Report on the Effects of Lisaftoclax (APG-2575) in Combination with Novel Therapeutic Regimens in Patients with Relapsed or Refractory Multiple Myeloma (R/R MM) or Immunoglobulin Light-Chain (Amyloid Light-Chain [AL]) Amyloidosis

Format: Poster Presentation
Abstract: #2016
Session: 653. Multiple Myeloma: Prospective Therapeutic Trials: Poster I
Time: December 9, 2023, Saturday, 5:30 PM – 7:30 PM (Pacific Time) / December 10, 2023, Sunday, 9:30 AM – 11:30 AM (Beijing Time)
Highlights
Background: Lisaftoclax is an investigational, novel, potent, selective Bcl-2 inhibitor under clinical development for treatment of patients with hematologic malignancies or solid tumors and has shown clinical antitumor benefits. In a previous study on chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and other hematologic malignancies, lisaftoclax was shown to require only a short dose ramp-up to mitigate tumor lysis syndrome (TLS) and was associated with a low incidence of adverse events (AEs). This multicenter study was designed to evaluate the safety and efficacy of lisaftoclax combination regimens in patients with R/R MM or R/R AL amyloidosis.

Methods:

• This study has three treatment arms that included Arm A: lisaftoclax combined with pomalidomide and dexamethasone in patients with R/R MM; Arm B: lisaftoclax combined with daratumumab, lenalidomide, and dexamethasone in patients with R/R MM; and Arm C: lisaftoclax combined with pomalidomide and dexamethasone in patients with R/R AL amyloidosis.
• Lisaftoclax was administered orally once daily (QD) at 5 dose levels (400 mg, 600 mg, 800 mg, 1,000 mg, and 1,200 mg) without ramp-up in 28-day cycles. Pomalidomide, daratumumab, and lenalidomide were administered per label use. Dexamethasone 40 mg (20 mg for patients aged >75 years) was administered on Days 1, 8, 15, and 22 of 28-day cycles.

Patients: As of July 3, 2023, a total of 30 patients were enrolled. Among them, 22, 3, and 5 patients were enrolled into Arms A, B, and C, respectively. 66.7% of patients were male, and the median (range) age was 70.5 (24-88) years. All patients were previously exposed to multiple lines of treatment. 18 (60%) patients were triple-class-exposed, 7 (35%) had received pomalidomide and 3 (10%) harbored the t(11;14) chromosomal abnormality.

Efficacy results:

• In Arm A, 21 patients with R/R MM were efficacy evaluable, including 6 (28.6%) who have reached VGPRs and 8 (38.1%) who have reached partial responses (PRs), resulting in an ORR (PR + VGPR) of 66.7%.
• In Arm B, 1 patient with R/R MM achieved PR and another achieved VGPR, resulting in an ORR of 100%.
• In Arm C, 3 patients with R/R amyloidosis achieved a hematologic VGPR, resulting in an ORR of 60%; 1 patient achieved improvement in organ functions.

Conclusions: Lisaftoclax combination regimens were well tolerated and demonstrated potent antitumor activity (especially VGPRs and PRs) in patients with R/R MM and R/R AL amyloidosis.

* Lisaftoclax (APG-2575) is an investigational drug that has not been approved in any country and region.

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 Priority Review Designations and Breakthrough Therapy Designations 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, 2 FTDs, and 2 Rare Pediatric Disease (RPD) Designations 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.

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