ASCO 2022 | Ascentage Pharma Releases Updated Results Demonstrating the Therapeutic Potential of Alrizomadlin (APG-115) plus Pembrolizumab in Patients with Solid Tumors who Progressed on Immunotherapies

SUZHOU,China,and ROCKVILLE,Md.,June 7,2022 -- scentage 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 the updated results from a Phase II study of the MDM2-p53 inhibitor alrizomadlin (APG-115) plus pembrolizumab in adults and children with various solid tumors in a Poster Discussion session at the 58th American Society of Clinical Oncology (ASCO) Annual Meeting.

Entering the fifth consecutive year in which its abstracts were selected for presentations by the ASCO Annual Meeting,Ascentage Pharma showcased results from multiple clinical trials of its five drug candidates,including the much-anticipated data of alrizomadlin plus pembrolizumab,updated from the data at last year's oral presentation at the ASCO Annual Meeting. The updated results further validate the combination therapy's efficacy in patients with immuno-oncologic- (I-O) drug-resistant or recurrent melanoma,including two complete responses (CRs),an objective response rate (ORR) of 11% and a disease control rate (DCR) of 57%. The abstract also reports favorable clinical benefit in patients with malignant peripheral nerve sheath tumour (MPNST),demonstrated by a DCR of 50%. MPNST is a rare pediatric type of sarcoma lacking effective treatment options.

"Ascentage's novel oral MDM2 inhibitor (alrizomadlin APG-115) continues to be well tolerated in combination with pembrolizumab and provides clinical benefit in several I-O relapse refractory tumor types,specifically various melanoma subtypes as well as MPNST,a rare pediatric sarcoma tumor with no available approved therapies",said Dr Bartosz Chmielowski,MD,Associate Professor from the Melanoma and Sarcoma program at UCLA,who presented the updated results at ASCO 2022.

Dr. Yifan Zhai,Chief Medical Officer of Ascentage Pharma,commented,"Alrizomadlin,a China-developed novel drug with first-in-class potential,is the first MDM2-p53 inhibitor entering clinical studies in China. These data we presented at this year's ASCO Annual Meeting validates alrizomadlin's therapeutic potential in patients with solid tumors that progressed on I-O drugs,thus signaling a potential new treatment option for patients with solid tumors.Furthermore,we are proud to be able to present clinical development progress for a number of Ascentage Pharma's drug candidates,which highlight our capabilities in global innovation. Honoring our mission of addressing unmet clinical needs in China and around the world,we are now accelerating our clinical programs to bring more safe and effective therapeutics to patients in need."

The highlights of this abstract on alrizomadlin are as follows:

Newly updated activity results of alrizomadlin (APG-115),a novel MDM2/p53 inhibitor,plus pembrolizumab: Phase 2 study in adults and children with various solid tumors.

Abstract: #9517

This US/Australian multicenter trial evaluated the safety,tolerability,pharmacokinetics (PK),pharmacodynamics (PD),and antitumor activity of alrizomadlin in combination with pembrolizumab in patients with advanced solid tumors.

As of March 1,2022,150 patients had been enrolled in the Phase II study. Alrizomadlin was orally administered QOD at the recommended Phase II dose (RP2D) of 150 mg in combination with intravenously administered pembrolizumab. This study consists of 6 cohorts: PD-1/PD-L1-refractory melanoma (n=60),non-small cell lung cancer (NSCLC,n=19)/STK-11-mutant lung adenocarcinoma (n=7),ATM-mutant solid tumors (n=20); liposarcoma (n=17),urothelial cancer (n=13),and MPNST failed prior standard-of-care therapies (n=14).

Efficacy Results:

In the 46 efficacy evaluable (EE) patients with melanoma progressed on PD-1/PD-L1 inhibitors,the confirmed ORR was 10.9% (2CRs+3 partial responses [PRs]/46EEs). In the cutaneous and uveal melanoma sub-cohorts,confirmed ORRs were 20% (2CRs+2PRs/20EEs) and 6.7% (1PR/15EEs),and DCRs (including confirmed PR,CR,and stable disease ≥ 4 cycles) were 55% (2PRs+2CRs+7SDs/20EEs) and 73.3% (1PR+10SDs/15EEs),respectively.

In the MPNST cohort,the DCR was 50% (6SDs/12EEs).

The PD-1/PD-L1-refractory NSCLC,urothelial,and liposarcoma cohorts each reported 1 confirmed PR.

Common treatment-related adverse events (TRAEs; ≥ 10%) of any grade were nausea,thrombocytopenia,vomiting,fatigue,decreased appetite,diarrhea,neutropenia,and anemia.

Conclusions:

This Phase II study showed that alrizomadlin in combination with pembrolizumab was well tolerated.

Preliminary and interim results of the combination therapy demonstrated clinical benefit for patients with relapsed/refractory melanoma and high DCRs in the cutaneous and uveal melanoma sub-cohorts.

Alrizomadlin combined with pembrolizumab demonstrates clinical benefit in patients with MPNST,with a 50% DCR,an orphan pediatric indication with no effective standard of care.

Appendix: A list of Ascentage Pharma's abstracts selected by this year's ASCO Annual Meeting

Drug Candidate

Abstract Title

Abstract #

Format

Olverembatinib（HQP1351）

Promising antitumor activity of olverembatinib (HQP1351) in patients (pts) with tyrosine kinase inhibitor- (TKI-) resistant succinate dehydrogenase- (SDH-) deficient gastrointestinal stromal tumor (GIST).

#11513

Poster discussion

Lisaftoclax (APG-2575)

A phase Ib/II study of lisaftoclax (APG-2575),a novel BCL-2 inhibitor (BCL-2i),in patients (pts) with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (R/R CLL/SLL).

#7543

Poster presentation

Phase Ib/II study of BCL-2 inhibitor lisaftoclax (APG-2575) safety and tolerability when administered alone or combined with a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor in patients with estrogen receptor-positive (ER⁺) breast cancer or advanced solid tumors.

#TPS1122

Poster presentation

Alrizomadlin (APG-115)

Newly updated activity results of alrizomadlin (APG-115),plus pembrolizumab: Phase 2 study in adults and children with various solid tumors.

#9517

Poster discussion

APG-2449

First-in-human phase I results of APG-2449,a novel FAK and third-generation ALK/ ROS1 tyrosine kinase inhibitor (TKI),in patients (pts) with second-generation TKI-resistant ALK/ROS1 non-small-cell lung cancer (NSCLC) or mesothelioma.

#9071

Poster presentation

Pelcitoclax (APG-1252)

Updated study results of pelcitoclax (APG-1252) in combination with osimertinib in patients (pts) with EGFR-mutant non-small-cell lung cancer (NSCLC).

#9116

Poster presentation

First-in-human study of pelcitoclax (APG-1252) in combination with paclitaxel in patients (pts) with relapsed/refractory small-cell lung cancer (R/R SCLC).

e20612

Publication-Only

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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