ASCO 2021 | Ascentage Pharma to Announce Updated Data of Lisaftoclax (APG-2575) Demonstrating an ORR of Around 80% and Therapeutic Potential in Patients with R/R CLL/SLL in Oral Presentation

SUZHOU,China and ROCKVILLE,Md.,May 20,2021 -- 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 announced that an abstract reporting on the first-in-human study of the Bcl-2 inhibitor,lisaftoclax (APG-2575),in patients withrelapsed/refractory chronic lymphocytic lymphoma/small lymphocytic lymphoma (R/R CLL/SLL) and other hematologic malignancies has been published in the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting's official website. Results from this global Phase I study demonstrated an ORR of 85.7%,and favorable tolerability and safety profiles in patients with R/R CLL /SLL.

The updated results from this study will be released in an oral presentation at the ASCO Annual Meeting convening on June 4 to 8,2021. This year,abstracts reporting on four clinical studies of the Ascentage Pharma's three apoptosis-target drug candidates have been selected for presentations at the ASCO Annual Meeting,and two have been selected for oral presentations.

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

"As a Bcl-2 inhibitor that has demonstrated efficacy,lisaftoclax is the second in the world and the first in China. These data oflisaftoclax suggest the potential for a safe,efficacious,and 'patient-friendly' treatment alternative for patients with R/R CLL and other hematologic malignancies," said Dr. Yifan Zhai,Chief Medical Officer of Ascentage Pharma. "Moreover,these results which will be presented at the 2021 ASCO Annual Meeting are a testament to our progress in advancing the research and development of apoptosis-targeted therapeutics. We will strive to further accelerate global clinical development programs of these novel therapeutics to benefit patients in China and around the world as early as possible."

Those abstracts to be presented at this year's ASCO Annual Meeting are as follows (two abstracts on APG-115 are simultaneously published in a separate press release):

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

Format: Oral Presentation

Abstract: #7502

Time: 11:30 - 14:30 EDT,June 7,2021

Session Track: Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia

Highlights:

This first-in-human global Phase I study assessed the safety,pharmacokinetics (PK),pharmacodynamics (PD),efficacy,and maximum tolerated dose (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 tumor lysis syndrome (TLS) risk were initiated on a daily ramp-up schedule until the dose assigned before the study cycles.

As of January 7,2021,35 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=4); 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).

Lisaftoclax was well tolerated,with manageable adverse events (AEs). No dose-limiting toxicity (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 over 10% patients included neutropenia and anemia,while nonhematologic TRAEs included fatigue,diarrhea,and nausea.

12 of 14 evaluable patients with R/R CLL/SLL achieved partial response (PR),for an ORR of 85.7% and a median time to response of 3 treatment cycles (range: 2-7). Absolute lymphocyte counts (ALCs) were reduced at lisaftoclax doses as low as 20 mg/day.

The preliminary PK profile showed that exposures increased with lisaftoclax doses 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 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.

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)

Format: Poster Presentation

Abstract: #TPS8589

Time: 09:00 EDT,June 4,2021

Session Track: Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers

Highlights:

This open-label,multicenter Phase Ib/II study is assessing the safety of preliminary efficacy of pelcitoclax in combination with paclitaxel in patients with R/R SCLC.

Pelcitoclax is being administered by intravenous (IV) infusion on Days 1,8,and 15,with paclitaxel at the fixed-dose of 80 mg/m2 on Days 1 and 8 of a 21-day cycle.

The primary endpoints of the Phase Ib part of this study include MTD and RP2D. The efficacy of pelcitoclax combined with paclitaxel will be determined in the Phase II part of the study using a Simon two-stage design,with ORR as the primary endpoint. Other endpoints of the Phase II study include PK,progression-free survival,and overall survival.

This study was designed to enroll 58 patients. As of February 8,15 patients have been enrolled.

About Lisaftoclax (APG-2575)

Lisaftoclax is a novel,orally administered small-molecule Bcl-2‒selective inhibitor being developed by Ascentage Pharma. Lisaftoclax is designed to treat hematologic malignancies and solid tumors by selectively blocking antiapoptotic protein Bcl-2 to restore the normal apoptosis process in cancer cells. Lisaftoclax is the first China-developed Bcl-2 inhibitor entering clinical development in China. At present,lisaftoclax has been cleared and approved to enter multiple Phase Ib/II studies in the US,China,and Australia,and is being developed globally for the treatment of multiple hematologic malignancies.

About Pelcitoclax (APG-1252)

Pelcitoclax is a novel,highly potent,small-molecule drug designed to restore apoptosis through selective inhibition of Bcl-2 and Bcl-xL proteins. Multiple Phase Ib/II studies of pelcitoclax as a single agent or in combinations for the treatment of a range of advanced tumors,including small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC),are being conducted in China,Australia,and the US.

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,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 four of the company's investigational drug candidates.

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