ASCO 2022 | Ascentage Pharma Releases for the First Time Results of its FAK/ALK/ROS1 inhibitor APG-2449 Demonstrating Safety and Efficacy in Patients with Advanced NSCLC

SUZHOU,China,and ROCKVILLE,MD,June 8,2022 --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 the results from its Phase I first-in-human (FIH) study of the company's novel FAK inhibitor and third-generation ALK/ROS1 tyrosine kinase inhibitor (TKI) APG-2449 in patients with second-generation TKI-resistant ALK/ROS1+ non-small-cell lung cancer (NSCLC) or mesothelioma in a Poster Presentation at the 58th American Society of Clinical Oncology (ASCO) Annual Meeting. APG-2449 is the first China-developed third-generation ALK inhibitorentering clinical studies.

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 first-time results of APG-2449 highlighting the company's promising pipeline in solid tumors. APG-2449 demonstrated preliminary efficacy in TKI-naïve patients or those whose disease was resistant to second-generation TKIs,with 4 partial responses (PRs) observed in the 14 patients with second-generation-TKI resistant and ALK-positive NSCLC. In the 10 TKI-naïve ALK/ROS1+ patients,the objective response rate (ORR) was 80%,and the disease control rate (DCR) was 100%.

Discovered and developed by Ascentage Pharma,APG-2449 is a novel,orally-available FAK/ALK/ROS1 inhibitor and the firstChina-developed third-generation ALK inhibitor entering clinical studies.

Prof. Hongyun Zhao of Sun Yat-sen University Cancer Center,who is the principal investigator of this study,said,"APG-2449 is a potent FAK/ALK/ROS1 inhibitor that can address drug resistance to second-generation ALK TKIs. In this FIH study,APG-2449 demonstrated favorable safety and antitumor activity in patients with advanced NSCLC,and showed on-target pharmacodynamic effects. Building on results from this Phase I study,we look forward to further evaluate APG-2449's efficacy in advanced NSCLC patients resistant to second-generation ALK inhibitor.

Dr. Yifan Zhai,Chief Medical Officer of Ascentage Pharma,commented,"APG-2449 is one of our key drug candidates,outside our pipeline of apoptosis-targeting assets. The data presented at this year's ASCO Annual Meeting demonstrated APG-2449's therapeutic potential in patients with advanced NSCLC and are indicative of our progress in the field of solid tumors. We will continue to take firm steps to advance this clinical development program. Furthermore,we are proud to be able to present clinical development progress for a number of Ascentage Pharma's drug candidates at this year's ASCO Annual Meeting,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 APG-2449 are as follows:

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.

Abstract: #9071

This dose-escalation and dose-expansion study was designed to assess the safety,tolerability,recommended Phase II dose (RP2D),pharmacokinetics (PK),pharmacodynamics (PD),and efficacy of APG-2449 in patients with second-generation TKI-resistant ALK/ROS1+ NSCLC or mesothelioma.

As of December 30,2021,84 Chinese patients with NSCLC or mesothelioma enrolled were treated with APG-2449 at doses ranging from 150 to 1,500 mg. APG-2449 was administered orally once daily on a 28-day cycle using a "3+3" dose escalation design.

4 PRs were observed in 14 ALK+ patients resistant to second-generation TKIs treated at the RP2D. Among 8 patients with brain metastases,1 complete response (CR) and 3 PRs were observed intracranially. In 10 TKI-naïve patients,the ORR was 80% (ALK+,6/8; ROS1+,2/2) and the DCR was 100%.

In addition,AGP-2449 demonstrated a favorable safety profile. The preliminary biomarker data showed decreased FAK phosphorylation in peripheral blood mononuclear cells and increased IFN-γ levels in serum after multiple doses of APG-2449.

Conclusions: APG-2449 has a favorable safety and PK profile. Preliminary efficacy was observed in patients whose disease was resistant to second-generation or TKI-naïve. Biomarker data indicated potential target engagement on FAK and the immunomodulatory effects of APG-2449.

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),a novel MDM2/p53 inhibitor,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

The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law,Ascentage Pharma undertakes no obligation to update or revise publicly any forward-looking statements,whether as a result of new information,future events,or otherwise,after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article,statements of,or references to,our intentions or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions may alter in light of future development.

View original content to download multimedia:https://www.prnewswire.com/news-releases/asco-2022--ascentage-pharma-releases-for-the-first-time-results-of-its-fakalkros1-inhibitor-apg-2449-demonstrating-safety-and-efficacy-in-patients-with-advanced-nsclc-301563283.html