Company Announcements

SUZHOU, China, and ROCKVILLE, Md., June 1, 2024 /PRNewswire/ -- Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancer, chronic hepatitis B (CHB), and age-related diseases, announced today that it has released updated data of its novel drug candidate AGP-2449, a FAK/ALK/ROS1 tyrosine kinase inhibitor (TKI), in patients with non-small-cell lung cancer (NSCLC) in a poster presentation at the 60th American Society of Clinical Oncology (ASCO) Annual Meeting taking place in Chicago, IL. This is the third consecutive year in which clinical data from this study of APG-2449 were selected for presentations at the ASCO Annual Meeting.

The ASCO Annual Meeting showcases the most cutting-edge research in clinical oncology and state-of-the-art advanced cancer therapies and is the world's most influential and prominent scientific gathering of the clinical oncology community. Presenting clinical development progress at the ASCO Annual Meeting for the seventh consecutive year, Ascentage had four clinical studies of three of the company's proprietary drug candidates selected for presentations, including an oral report, at ASCO 2024.

Results presented this year reaffirmed the therapeutic potential of APG-2449 in NSCLC, with data demonstrating preliminary efficacy in patients with NSCLC who were TKI naïve and resistant to second-generation ALK TKIs, as well as early antitumor activity in brain metastases. Biomarker analysis showed that, in patients with NSCLC resistant to second-generation ALK TKIs, phosphorylated FAK (pFAK) expression levels in tumor tissue at baseline and reduction in pFAK levels in peripheral blood mononuclear cells (PBMCs) were correlated with responses to APG-2449.

"APG-2449 is an effective multitargeted inhibitor that acts on FAK/ALK/ROS1. Compared to the data released at last year's ASCO Annual Meeting, the latest results presented this year continued to show manageable safety and favorable antitumor activity in patients with NSCLC," said Prof. Li Zhang, the principal investigator of this study from Sun Yat-sen University Cancer Center. "We are very encouraged by the preliminary efficacy observed in patients with resistance to second-generation ALK TKIs, as it suggests that multitargeted inhibition on FAK and ALK may offer a new strategy for the management of patients with NSCLC resistant to second-generation ALK TKIs. We hope that Ascentage Pharma will conduct further studies on APG-2449 and allow more patients to benefit from this novel therapeutic agent as soon as possible."

"These data of APG-2449 in patients with NSCLC revealed a connection between resistance to ALK inhibitors and the FAK pathway, thus suggesting that the multitargeted FAK/ALK/ROS1 TKI APG-2449 may bring renewed hope to patients with NSCLC who are resistant to second-generation ALK inhibitors. This finding is indeed very encouraging," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "Remaining committed to the mission of addressing unmet clinical needs in China and around the world, we will press forward with this clinical development program in order to bring a safe and effective new treatment option to patients in need."

Highlights of these data presented at ASCO 2024 are as follows:

Updated study results of novel FAK/ALK/ROS1 inhibitor APG-2449 in patients (pts) with non-small-cell lung cancer (NSCLC) resistant to second-generation ALK inhibitors.

Abstract#: 3124

Session Title: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

Date and Time: June 1, 2024, Saturday, 9:00 AM – 12:00 PM (Central Time)

First Author: Yuxiang Ma, MD, PhD, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.

Highlights:

Background: ALK inhibitors increase FAK pathway gene expression in ALK⁺ NSCLC cell lines, with the highest induced expression in drug-tolerant persister cells. This suggests that FAK pathway activation is involved in the mechanism that leads to ALK TKI resistance in ALK⁺ NSCLC. APG-2449 is an orally active FAK inhibitor and a third-generation ALK/ROS1 TKI that has shown potent antitumor activity in preclinical models. This poster reports further safety and efficacy data of APG-2449.

Patient enrollment and methods:

• This study comprises dose-escalation and dose-expansion portions. 1,200 mg daily (QD) was determined as the RP2D. There were two cohorts in the dose-expansion portion: Cohort 1 included patients with NSCLC who were resistant to second-generation ALK TKIs; Cohort 2 included patients with NSCLC who were ALK or ROS1 TKI naïve.
• As of April 2, 2024, a total of 144 patients with NSCLC, mesothelioma, or ovarian cancer were treated with APG-2449 at doses ranging from 150 – 1,500 mg. The median (range) age of patients was 53 (21-78) years, and 53.5% were female.

Efficacy results :

• The ORRs of APG-2449 in patients with ROS1+ and ALK+ TKI-naïve NSCLC (n=36) were 68.2% (15/22) and 78.6% (11/14), respectively. Of the 22 patients with NSCLC resistant to second-generation ALK inhibitors and without targetable bypass gene mutations (e.g., KRAS G12C, BRAF V600E), 10 achieved PRs (10/22; 45.5%). Among the patients treated at RP2D, 12 had brain metastasis at baseline, 9 of whom achieved intracranial PR, resulting in an intracranial ORR of 75.0%.
• Biomarker analysis found that, in patients with NSCLC that was resistant to second-generation ALK TKIs, responses to APG-2449 were correlated with pFAK levels in tumor tissues at baseline and reductions in pFAK levels in PBMCs.

Safety results: A total of 129 (89.6%) patients had treatment‑related adverse events (TRAEs), the most frequent (≥10%) of which were elevated serum creatinine (49.3%), increase in alanine aminotransferase (42.4%), increase in aspartate aminotransferase (36.1%); nausea (28.5%); vomiting (23.6%); diarrhea (22.9%); decreased leukocyte count (22.2%), decreased neutrophil count (17.4%) and rash (13.2%). In all, 20 (13.9%) TRAEs were grade ≥ 3.

Conclusions: APG-2449 demonstrated preliminary efficacy in patients with NSCLC whose disease was TKI naïve and resistant to second-generation ALK inhibitors, especially in brain metastases. Biomarker analysis showed that, in patients with NSCLC resistant to second-generation ALK TKIs, responses to APG-2449 PFS were correlated with pFAK levels in tumor tissues at baseline and reductions in pFAK levels in PBMCs.

*APG-2449 is an investigational drug that has not been approved in any country and region.

Appendix: The four clinical studies of Ascentage Pharma's three drug candidates, including lisaftoclax, presented at this year's ASCO Annual Meeting.

 

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 9 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, including 5 global registrational phase III studies, in the US, Australia, Europe, and China. Ascentage Pharma has been designated for multiple Major National R&D Projects, including five Major New Drug Projects, one New Drug Incubator status, four Innovative Drug Programs, and one Major Project for the Prevention and Treatment of Infectious Diseases.

Olverembatinib, the company's core drug candidate developed for the treatment of drug-resistant chronic myeloid leukemia (CML) and the company's first approved product in China, has been granted Priority Review Designations and Breakthrough Therapy Designations by the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA). To date, the drug had been included into the China 2022 National Reimbursement Drug List (NRDL). Furthermore, olverembatinib has been granted an Orphan Drug Designation (ODD) and a Fast Track Designation (FTD) by the US FDA, and an Orphan Designation by the EMA of the EU. To date, Ascentage Pharma has obtained a total of 16 ODDs from the US FDA and 1 Orphan Designation from the EMA of the EU for 4 of the company's investigational drug candidates.

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, MSD, and AstraZeneca. The company has built a talented team with global experience in the discovery and development of innovative drugs and is setting up its 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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