EHA 2022 | Ascentage Pharma Releases Encouraging Results of Bcl-2 Inhibitor Lisaftoclax (APG-2575) in Chinese Patients with Relapsed/Refractory Non-Hodgkin Lymphoma

SUZHOU,China,and ROCKVILLE,MD,June 13,2022 -- 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 results from a Phase I study of the company's novel Bcl-2-selective inhibitor lisaftoclax (APG-2575) in Chinese patients with relapsed/refractory non-Hodgkin lymphoma (r/r NHL) at the 2022 European Hematology Association Hybrid Congress (EHA 2022).

The EHA Congress is the largest gathering of the hematology field in Europe. It showcases the most cutting-edge research and state-of-the-art innovative therapies,attracting over 10,000 clinical experts and researchers from more than 100 countries every year.

The data presented at this year's EHA Congress show that lisaftoclax was well tolerated at doses of up to 800 mg/day,without evidence of tumor lysis syndrome (TLS). In addition,lisaftoclax demonstrated preliminary efficacy in a range of relapsed/refractory hematologic malignancies,including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL),marginal zone lymphoma (MZL),mantle cell lymphoma (MCL),and T-cell NHL,having achieved 4 complete responses (CRs) and 8 partial responses (PRs) in 32 efficacy evaluable patients.

In the 11 efficacy evaluable patients with CLL (all of whom were heavily pretreated and had failed prior therapies such as chemoimmunotherapies and Bruton's tyrosine kinase [BTK] inhibitors,and the majority had at least 1 type of adverse prognostic factors such as 17p deletion/TP53 mutation),there were 8 efficacy evaluable patients in cohorts received 200 mg or higher doses,including 3 CRs and 4 PRs,thus demonstrating an ORR of 87.5%. In the 6 efficacy evaluable patients with MCL,the ORR was 33.3% (1 CR). In the 4 efficacy evaluable patients with MZL,the ORR was 50%. In the 3 efficacy evaluable patients with T-cell NHL,the ORR was 33.3%.

Lisaftoclax is a novel,orally administered small-molecule Bcl-2-selective inhibitor being developed by Ascentage Pharma to treat hematologic malignancies and solid tumors by selectively blocking the antiapoptotic protein Bcl-2 and hence restoring the normal apoptosis process in cancer cells. Lisaftoclax is the first Bcl-2 inhibitor developed and entering clinical development in China,and is also the second such agent entering pivotal trials globally. Lisaftoclax is being studied in multiple clinical studies encompassing a range of solid tumors and hematologic malignancies,and has shown high clinical potential.

Dr. Yifan Zhai,Chief Medical Officer of Ascentage Pharma,commented,"Lisaftoclax is a key drug candidate in Ascentage Pharma's apoptosis-targeted pipeline. It has shown favorable tolerability and efficacy in multiple clinical studies in patients with solid tumors and hematologic malignancies. The drug candidate's therapeutic potential was further validated by the data released at EHA 2022. We will press ahead with the clinical development of lisaftoclax in efforts to bring a much-needed new treatment option to patients."

Highlights of this abstract on lisaftoclax are as follows:

Preliminary Results of a Phase 1 Study of Novel Bcl-2 Inhibitor Lisaftoclax (APG-2575) in Chinese Patients (pts) with Relapsed or Refractory (r/r) Non-Hodgkin Lymphomas (NHLs)

Abstract: #P1106

Highlights:

This multicenter,single-agent,Phase I trial consists of a dose escalation and a dose expansion and is the first-in-human study of lisaftoclax in adults with R/R NHL in China. The objective of this study was to evaluate the safety,tolerability,pharmacokinetics (PK),pharmacodynamics (PD),and preliminary efficacy of lisaftoclax in Chinese patients with R/R NHL.

Patients were dosed with lisaftoclax orally once daily in 28-day cycles. A daily ramp-up schedule was used in patients with CLL or NHL with medium/high-risk TLS.

As of January 1,2022,40 patients had been treated with lisaftoclax (dose range 20-800 mg),including 20 who remain in the trial. NHL subtypes included: 12 CLL,9 follicular lymphoma (FL),7 MCL,4 MZL,4 T-cell lymphoma,2 diffuse large B-cell lymphoma,and 2 Waldenström macroglobulinemia.

With a median treatment duration of 4 cycles,4 of 32 evaluable patients achieved CR and 8 achieved PR,resulting in an ORR of 37.5%. In the 11 evaluable patients with CLL,the ORR was 63.6%,the CR rate was 27.3%,and the PR rate was 36.4%. In patients with CLL treated at doses ≥ 200 mg,the ORR was 87.5%. In the 6 evaluable patients with MCL,1 patient achieved CR and 1 achieved PR. In the 4 evaluable patients with MZL,2 achieved PR. In the 3 evaluable patients with T-cell NHL,1 achieved PR.

Lisaftoclax was generally well tolerated. Most treatment-emergent adverse events (TEAEs) were grade 1-2 (67.5%). Dose-limiting toxicity (DLT) and laboratory/clinical TLS were not observed in any of the dose cohorts,and there were no dose-reduction or discontinuation due to intolerance.

Conclusions:

Lisaftoclax showed promising antitumor activity and favorable responses in subtypes of NHL including CLL/SLL,MZL,MCL,T-cell NHL. In addition,lisaftoclax demonstrated a favorable safety profile,with no TLS or DLT observed during the dose ramp-up from 20 mg - 800 mg/day.

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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