ASCO 2021 | Ascentage Pharma to Announce Updated Results Demonstrating Clinical Potential of Alrizomadlin (APG-115) Plus Pembrolizumab in Patients with Advanced Solid Tumors that Had Failed Immunotherapies 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 abstracts reporting on two clinical studies evaluating the company's drug candidate,alrizomadlin (APG-115),have been published in the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting's official website. Of these,the Phase II study of alrizomadlin in combination with pembrolizumab in patients with unresectable or metastatic melanoma or advanced solid tumors that have failed immuno-oncologic drugs demonstrated favorable results,including a disease control rate (DCR) of 60.9% and an objective response rate (ORR) of 17.4% in the PD-1/PD-L1 inhibitor-resistant melanoma cohort.

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

"Alrizomadlin is a core drug candidate in our apoptosis-targeted pipeline with great potential in the treatment of advanced solid tumors. These data of alrizomadlin in combination with pembrolizumab are promising,as they suggest a potential new treatment option for patients with solid tumors," 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."

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

Preliminary results of a phase II study of alrizomadlin (APG-115),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

Format: Oral Presentation

Abstract: #2506

Time: 15:00 - 18:00 EDT,June 7,2021

Session Track: Developmental Therapeutics—Immunotherapy

Highlights:

This open-label,multicenter Phase II study in the US assessed the safety,tolerability,PK,PD,and antitumor activity of alrizomadlin in combination with pembrolizumab in patients with advanced solid tumors.

As of December 25,2020,84 patients had been enrolled in the Phase II part of the study and treated with alrizomadlin at the RP2D dose of 150 mg every other day,in combination with pembrolizumab. This study has 6 cohorts,including patients with: PD-1/PD-L1 inhibitor-resistant melanoma,non-small cell lung cancer (NSCLC),and urothelial carcinoma; or malignant peripheral nerve sheath tumor (MPNST),liposarcoma,and ATM mutant solid tumors that had failed any standard therapy.

Anti-tumor Effects:

In the PD-1/PD-L1 inhibitor-resistant melanoma cohort (n=26),there was 1 confirmed PR out of 5 patients with uveal (ocular) melanoma; 2 PRs (1 confirmed + 1 unconfirmed) of 5 patients with mucosal melanoma; and 1 PR (confirmed) of 11 patients with cutaneous melanoma. The ORR and disease control rate (DCR) in the melanoma cohort were 17.4% (4/23) and 60.9% (14/23),respectively.

In the MPNST cohort (n=3),1 ongoing PR (unconfirmed).

In the PD-1/PD-L1 inhibitor-resistant NSCLC (n=14 evaluable) and urothelial carcinoma (n=5 evaluable) cohorts,1 patient in each cohort achieved confirmed PR.

Common treatment-related adverse events (TRAEs) observed in over 10% of patients were nausea,thrombocytopenia,vomiting,fatigue,decreased appetite,diarrhea,neutropenia,and anemia.

In conclusion,alrizomadlin in combination with pembrolizumab is well tolerated and may restore antitumor effects in patients with cancer resistant to or intolerant of I-O drugs.

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

Format: Poster Presentation

Abstract: #TPS6094

Time: 09:00 EDT,June 4,2021

Session Track: Head and Neck Cancer

Highlights:

This open-label,multicenter Phase I/II trial in the US was designed to assess the safety,DLT,MTD,and antitumor activity of alrizomadlin with or without platinum chemotherapy in patients with wild-type TP53 salivary gland carcinoma.

This study has two parts:

Part One: a two-arm randomized study (allocated in a ratio of 1:2,n=42)

Arm A: alrizomadlin as a single agent (n=14)

Arm B: alrizomadlin plus platinum chemotherapy (n=28)

Part Two: a single-arm study (advanced from the most promising arm in Part One,n=20)

Study Endpoints:

DLT based on the TRAEs of grade 3 to 5 (by NCI CTCAE v5.0) within the first 6 weeks of treatments (2 cycles).

MTD based on DLTs over the same treatment period.

ORR based on the proportion of patients with confirmed CR or PR (per RECIST v1.1) at up to 12 months.

This study was designed to enroll 42 patients. As of January 27,2021,11 patients have been enrolled.

About Alrizomadlin (APG-115)

Being developed by Ascentage Pharma,alrizomadlin is an orally administered,selective,small-molecule inhibitor of the MDM2 protein. Alrizomadlin has strong binding affinity to MDM2 and is designed to activate tumor suppression activity of p53 by blocking the MDM2-p53 protein-protein interaction. Alrizomadlin is the first MDM2-p53 inhibitor entering clinical development in China and is currently being investigated in multiple Phase Ib/II studies in solid tumors and hematologic malignancies 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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