SUZHOU, China and ROCKVILLE, Md., June 6, 2023 /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 for the second consecutive year, it has released updated data of APG-2449, a novel FAK/ALK/ROS1 tyrosine kinase inhibitor (TKI) developed by Ascentage Pharma, in patients with non-small cell lung cancer (NSCLC), in a Poster Discussion session at the 59^th American Society of Clinical Oncology (ASCO) Annual Meeting.

Showcasing progress in clinical development at the ASCO Annual Meeting for six consecutive years, Ascentage Pharma had clinical results from four clinical studies of four of the company's lead drug candidates selected for presentations in 2023. Among these results, the updated clinical data of APG-2449 showed the potential as a new treatment option that can effectively overcome drug resistance through the targeted inhibition of FAK. These data indicated efficacy and safety of APG-2449 in patients with NSCLC, with 8 partial responses (PRs) in the 28 patients who had failed treatment with the second-generation ALK TKIs.

Developed by Ascentage Pharma, APG-2449 is an orally available, small-molecule FAK/ALK/ROS1 TKI and the first China-developed third-generation ALK inhibitor entering clinical development.

"APG-2449 is an effective multi-targeted inhibitor targeting FAK/ALK/ROS1. Compared to data released at the ASCO Annual Meeting last year, the updated results reported this year continuously indicated favourable safety and promising antitumor activity in patients with NSCLC, and the preliminary efficacy observed in patients who were resistant to second-generation ALK inhibitors was particularly encouraging," said Prof. Li Zhang, the Principal Investigator of this study from Sun Yat-Sen University Cancer Center. "We believe that FAK inhibition could be a new treatment strategy for patients with NSCLC resistant to second-generation ALK inhibitors."

"We are excited by the results presented at this year's ASCO Annual Meeting as they demonstrated APG-2449's therapeutic option in advanced NSCLC and the drug's potential in offering a safe and effective novel therapy to this underserved patient population," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "Moving forward, we will expedite this clinical development program, which hopefully can yield a safe and effective new treatment option to patients, fulfilling our mission of addressing unmet clinical needs in China and around the world."

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

Highlights of the poster on APG-2449 presented at this year's ASCO Annual Meeting:

FAK inhibition with novel FAK/ALK inhibitor APG-2449 could overcome resistance in NSCLC patients who are resistant to second-generation ALK inhibitors

• Abstract#: 9015
• Poster Board#: 3
• Session Title: Lung Cancer—Non-Small Cell metastatic
• Key Results:
  This open-label, multicenter, Phase I dose-escalation and dose-expansion study was designed to evaluate the safety/tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of APG-2449 in patients with ALK/ROS1⁺ NSCLC or other solid tumors.

• • As of December 9, 2022, 136 patients were enrolled and treated with APG-2449 at dose levels from 900 to 1,500 mg. The median (range) age of these patients was 53 (21-78) years, and 54.4% of them were female. After 1,200 mg daily (QD) was determined as the recommended Phase II dose (RP2D), patients with NSCLC were enrolled into 2 dose-expansion cohorts. Among them, Cohort 1 included patients who were resistant to second-generation ALK/ROS1⁺ TKIs, while Cohort 2 included those who were ALK/ROS1⁺ TKI-naive.
  • Efficacy Results: In the subgroup of patients with TKI-naive NSCLC (n = 33; 31 were efficacy evaluable), the overall response rate (ORR) and disease control rate (DCR = complete response [CR] rate + partial response [PR] rate + stable diseases [SD] rate) were 70.6% (12/17) and 88.2% (15/17), respectively, in ROS1⁺ treatment-naive patients; and were 78.6% (11/14) and 100% (14/14) in ALK⁺ treatment-naive patients. Among the 28 patients with ALK⁺ NSCLC that was resistant to second-generation ALK inhibitors, 8 achieved PR (8/28; 28.6%) when treated with APG-2449 at the RP2D.
  • Analysis of FAK Expression: Among the 48 patients with ALK+ NSCLC who were previously treated with second-generation ALK inhibitors, compared to baseline, those who experienced PR showed greater reduction in phosphorylated FAK (pFAK) levels in peripheral blood mononuclear cells (PBMCs) by Day 28 than patients who experienced SD and progressive disease (PD), thus suggesting that patients with higher FAK expression at baseline were likely to achieve deeper clinical responses to APG-2449.
  • Safety Results: A total of 123 (90.4%) patients experienced treatment-related adverse events (TRAEs), with the most frequent TRAEs (>20%) being elevated blood creatinine (46.3%), elevated alanine aminotransferase (ALT) (40.4%), and elevated aspartate aminotransferase (AST) (33.1%), as well as gastrointestinal disorders that included nausea (27.2%), vomiting (22.8%), and diarrhea (21.3%). A total of 19 (14%) patients experienced grade ≥ 3 TRAEs.
  • Conclusions: APG-2449 showed a favourable preliminary safety profile and antitumor efficacy in patients with NSCLC. Preliminary efficacy was observed in patients who were TKI naive and resistant to second-generation ALK inhibitors. FAK inhibition could be a novel approach to overcome ALK resistance in patients with NSCLC that is resistant to second-generation ALK inhibitors.

Appendix: The four posters on Ascentage Pharma's four lead drug candidates, including APG-2449, presented at this year's ASCO Annual Meeting.

Drug Candidates	Abstract Title	Abstract#	Format
APG-2449	FAK inhibition with novel FAK/ALK inhibitor APG-2449 could overcome resistance in NSCLC patients who are resistant to second-generation ALK inhibitors.	#9015	Poster Discussion
Olverembatinib (HQP1351)	Antitumor activity of olverembatinib (HQP1351) in patients (pts) with tyrosine kinase inhibitor (TKI)- resistant succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor (GIST).	#11540	Poster Presentation
Lisaftoclax (APG-2575)	Preliminary data of a phase 1b/2 study of BCL-2 inhibitor lisaftoclax (APG-2575) alone or combined with ibrutinib or rituximab in patients (pts) with Waldenström macroglobulinemia (WM).	#7569	Poster Presentation
APG-115 (Alrizomadlin)	A phase 2 study of alrizomadlin (APG-115) in combination with pembrolizumab in patients with unresectable or metastatic cutaneous melanoma that has failed immuno-oncologic (IO) drugs.	#9559	Poster Presentation

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 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, has been granted two Priority Review Designations and two Breakthrough Therapy Designations (BTDs) 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.

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