Live from ASCO 2021 | Ascentage Pharma Delivers Oral Presentation Featuring Updated Data Demonstrating Promising Efficacy and Safety of Bcl-2 Inhibitor Lisaftoclax (APG-2575) in Patients with Relapsed or Refractory CLL/SLL

SUZHOU,China,and ROCKVILLE,MD,June 8,2021 -- Ascentage Pharma (6855.HK),a globally focused,clinical-stage biotechnology company engaged in developing novel therapies for cancers,chronic hepatitis B (CHB),and age-related diseases,today released updated results from the first-in-human study of the Bcl-2 inhibitor lisaftoclax (APG-2575) in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (R/R CLL/SLL) and other hematologic malignancies. The findings were reported in an oral presentation at the 57th American Society of Clinical Oncology (ASCO) Annual Meeting.

As one of the Chinese biotechnology companies that have been increasingly visible at international scientific congresses in recent years,Ascentage Pharma has entered the fourth year in which its clinical advances have been selected for presentations at the ASCO Annual Meeting. This year,results from four of the company's clinical trials were selected for presentations at the meeting,and of these data,the two oral presentations have received widespread and avid interest from research and medical communities. Updated data on lisaftoclax have demonstrated favorable preliminary safety and efficacy,including an objective response rate (ORR) of 80% and a favorable tolerability profile,with manageable adverse events (AEs) in patients with R/R CLL/SLL. Moreover,no dose-limiting toxicity (DLT) was observed at the maximum tested dose of 1,200 mg. The maximum tolerated dose (MTD) has not been reached,and no laboratory or clinical tumor lysis syndrome (TLS) has been reported.

Dr. Asher Chanan-Khan,of Mayo Clinic,and the Global Principal Investigator of this study,commented: "Lisaftoclax is a potent,selective Bcl-2 inhibitor which can both induce apoptosis and inhibit tumor cell growth. In this first-in-human study in the US and Australia,lisaftoclax showed a favorable safety profile and promising antitumor activity in patients with R/R CLL/SLL,and potential disease control in several other hematologic malignancies. In view of the preliminary safety and clinical activity observed in this Phase I study,we look forward to further evaluating the antitumor activity of lisaftoclax in individual hematologic malignancies and solid tumors."

"The initial objective response rate of 80%,together with a favorable safety profile and no TLS despite a daily dose ramp-up,demonstrated by lisaftoclax in patients with R/R CLL/SLL are particularly encouraging and once again support the best-in-class potential of lisaftoclax," said Dr. Yifan Zhai,Chief Medical Officer of Ascentage Pharma. "At this year's ASCO Annual Meeting,we have announced results from multiple studies,including that of lisaftoclax,in two oral presentations and two poster presentations. I am very proud of these advances,which attest to Ascentage Pharma's robust capabilities in global innovation. Moving forward,we willremain committed to our mission of addressing unmet clinical needs in China and around the world,and strive to accelerate our clinical programs in the hope of soon benefitting patients."

An overview of the four abstracts presented at the 2021 ASCO Annual Meeting:

Drug Candidate

Abstract Title

Abstract #

Format

Lisaftoclax

(APG-2575)

First-in-human study of lisaftoclax (APG-2575),a novel Bcl-2 inhibitor (Bcl-2i),in patients (pts) with relapsed/refractory (R/R) CLL and other hematologic malignancies (HMs)

7502

Oral

Presentation

Alrizomadlin

(APG-115)

Preliminary results of a phase II study of alrizomadlin (APG-115),a novel,small-molecule MDM2 inhibitor,in combination with pembrolizumab in patients (pts) with unresectable or metastatic melanoma or advanced solid tumors that have failed immuno-oncologic (I-O) drugs

2506

Oral

Presentation

Trial in progress: A phase I/II trial of novel MDM2 inhibitor alrizomadlin (APG-115),with or without platinum chemotherapy,in patients with p53 wild-type salivary gland carcinoma

TPS6094

Poster

Presentation

Pelcitoclax

(APG-1252)

Trial in progress: A multicenter phase Ib/II study of pelcitoclax (APG-1252) in combination with paclitaxel in patients with relapsed/refractory small-cell lung cancer (R/R SCLC)

TPS8589

Poster

Presentation

Highlights of the oral presentation on lisaftoclax at this year's ASCO Annual Meeting:

First-in-human study of lisaftoclax (APG-2575),in patients (pts) with relapsed/refractory (R/R) CLL and other hematologic malignancies (HMs)

Abstract: #7502

This first-in-human global Phase I study assessed the safety,pharmacokinetics (PK),pharmacodynamics (PD),efficacy,and MTD/recommended Phase II dose (RP2D) of lisaftoclax in patients with R/R CLL and other HMs. Lisaftoclax was orally administered once daily in a 28-day cycle. Patients with CLL or intermediate-high TLS risk were initiated on a daily ramp-up schedule until the dose assigned before the study cycles.

As of April 15,2021,36 patients had been enrolled and treated with lisaftoclax at doses ranging from 20 to 1,200 mg,with a median of 2 (range: 1-13) prior lines of treatment. These patients had been diagnosed with R/R CLL/SLL (n=15),multiple myeloma (MM,n=6),follicular lymphoma (FL,n=5),Waldenström macroglobulinemia (WM,n=5); and either acute myeloid leukemia (AML),mantle cell lymphoma (MCL),diffuse large B-cell lymphoma (DLBCL),myelodysplastic syndromes (MDS),or hairy cell leukemia (HCL; n=1 each). These patients received a median of 6 cycles (range: 1-24) of treatment with lisaftoclax.

Lisaftoclax was well tolerated,with manageable AEs. No DLT was observed even at the maximum dose of 1,200 mg. The MTD has not been reached,and no laboratory or clinical TLS has been reported. Hematologic treatment-related adverse events (TRAEs) of any grade in more than 10% patients included neutropenia and anemia,while nonhematologic TRAEs included fatigue,diarrhea,constipation,and nausea.

In the 15 evaluable patients with R/R CLL/SLL,7 (46.7%) each were assessed as Rai stage III-IV or intermediate-high per International Prognostic Index (IPI). Patients in this cohort received a median of 9 (range: 5-24) cycles of treatment,and 12 patients achieved partial responses (PRs),for an ORR of 80% and a median time to response of 2 (range: 2-8) treatment cycles.

Among 21 patients with R/R non CLL/SLL,who received a median of 3 (range: 1-13) prior lines of treatment,20 were evaluable. Of these individuals,1 with t (11;14)-mutant MM achieved minor response (MR) after 2 treatment cycles. A total of 10 (50%) patients in this cohort achieved stable disease (SD) or deeper responses.

The preliminary PK profile showed that exposures increased with lisaftoclax at doses ranging from 20 to 1,200 mg (average half-life: 4-5 hours). On BH3 profiling,lisaftoclax rapidly triggered changes in Bcl-2 complex in CLL/SLL patient samples,which were consistent with rapid clinical reductions in absolute lymphocyte counts (ALCs).

In conclusion,efficacy and safety data showed that the Bcl-2 inhibitor lisaftoclax offers a potential alternative treatment for patients with R/R CLL/SLL and other HMs,with a daily ramp-up schedule that may be more patient-friendly and a favorable preliminary safety profile.

About Ascentage Pharma

Ascentage Pharma (6855.HK) is a globally focused,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 40 Phase I/II clinical trials in the US,Australia,Europe,and China. Olverembatinib (HQP1351),the company's core drug candidate developed for the treatment of drug-resistant chronic myeloid leukemia (CML),has been granted an Orphan Drug Designation (ODD) and a Fast Track Designation (FTD) by the US FDA. A New Drug Application (NDA) for olverembatinib has been submitted and subsequently granted Priority Review status and a Breakthrough Therapy Designation (BTD) by the Center for Drug Evaluation (CDE) in China. To date,Ascentage Pharma has obtained a total of 11 ODDs from the US FDA for 4 of the company's investigational drug candidates.

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