📰 What This Document Is

This document is a filing (6-K) and a voluntary announcement detailing scientific research presented by Ascentage Pharma Group International (AAPG). Essentially, the company is sharing its latest, most promising preclinical findings from a poster presentation at the American Association for Cancer Research (AACR) 2026 Annual Meeting. 🔬 You should expect a deep dive into how AAPG's current drug candidates are being tested in combination with existing chemotherapy agents to fight difficult-to-treat cancers.

👉 In short, AAPG is showcasing the potential of its multi-drug strategies to overcome cancer resistance, moving its pipeline closer to human trials.

🏢 What Ascentage Pharma Does

Ascentage Pharma is a global, commercial-stage, integrated biopharmaceutical company. 🌟 They are dedicated to the discovery, development, and commercialization of novel therapies designed to address critical unmet medical needs, particularly in oncology (cancer).

👉 They build their business by having an extensive "pipeline" (a portfolio of drug candidates) of innovative drugs, including next-generation kinase inhibitors and protein degraders, rather than relying on a single product.

🚀 High-Impact Scientific Announcements

The main purpose of this announcement is to detail four specific preclinical studies featuring three of their key drug candidates. These findings demonstrate the therapeutic potential of combining these drugs with standard-of-care treatments across various cancer types.

👉 The findings signal a strategic focus on combination therapy—using multiple drugs together—to enhance effectiveness and bypass the natural ways cancer develops resistance.

The Key Drug Candidates

The three drug candidates featured in these studies are:

• Olverembatinib (HQP1351): A multitarget kinase inhibitor that is currently approved in China for Chronic Myeloid Leukemia (CML).
• APG-2449: A potent and selective multi-kinase inhibitor that specifically targets FAK, ALK, and ROS1.
• APG-5918: An investigational EED inhibitor (a core component of the PRC2 complex).

🧪 Olverembatinib in Endometrial Carcinoma (EC)

This preclinical study examined if Olverembatinib can be used in treating Endometrial Carcinoma (EC), a common gynecological cancer. It tested the drug's ability to work alone or when combined with standard chemotherapy agents. 🌸

• Background: EC is the most common gynecologic malignancy in developed countries, and advanced stages often have limited treatment options. Olverembatinib, already approved in China for CML, targets multiple kinases (including VEGFR1–3, FGFR1–4, Src family kinases, RAF, KIT, RET, and PDGFR).
• Findings: The study showed that in both lab dish (in vitro) and animal models (in vivo), Olverembatinib was effective and showed synergy (working better together) with chemotherapy agents.
• Why it matters: Mechanistically, the combination suppressed critical signaling pathways (FGFR2, PI3K/AKT, and MEK/ERK), increased DNA damage, and boosted cell death (apoptosis). These results support future clinical testing of Olverembatinib for EC.

🩸 Olverembatinib in Mantle Cell Lymphoma (MCL)

This study investigated using Olverembatinib in combination with acalabrutinib, a BTK inhibitor, to treat MCL. 💡

• Background: MCL is a rare, aggressive non-Hodgkin lymphoma. While BTK inhibitors have helped treat it, using them alone sometimes isn't enough, prompting the search for combinations.
• Findings: Olverembatinib showed powerful inhibition of MCL cell growth in both vitro and in vivo models. When combined with acalabrutinib, the effect was synergistic.
• Why it matters: The combination significantly boosted cell death and caused a G0/G1 cell cycle arrest. The drugs work by dual inhibition of the Lyn and BTK pathways, providing a strong scientific basis for developing this combination treatment for MCL.

🛡️ APG-2449 for BRAF-Mutant Cancers

This research focused on addressing drug resistance by using APG-2449 in combination with existing inhibitors (dabrafenib and trametinib) for cancers (like CRC and melanoma) that have BRAF V600E mutations. ⚙️

• Background: Many cancers, including colorectal and melanoma, have BRAF V600E mutations. Existing treatments (BRAF and MEK inhibitors) can lead to resistance by activating backup pathways, such as FAK signaling.
• Findings: The results showed that APG-2449 selectively worked on BRAF V600E-mutant cell lines. Crucially, it successfully suppressed the compensatory signaling activation that normally happens when MAPK pathway blockade is used.
• Why it matters: APG-2449 synergistically boosted the antitumor activity of the established combination (dabrafenib + trametinib) in preclinical models, suggesting it could help patients who develop resistance.

🧬 APG-5918 in Small-Cell Lung Cancer (SCLC)

This preclinical study explored using APG-5918 (an EED inhibitor) with topoisomerase I inhibitors for SCLC, aiming to restore drug sensitivity. 🌿

• Background: SCLC often responds initially to chemotherapy but quickly becomes resistant. This resistance is partly because the cell uses epigenetic silencing (controlled by PRC2, which APG-5918 targets) to repress protective genes like Schlafen 11 (SLFN11).
• Findings: In SCLC models, the combination of APG-5918 and topoisomerase I inhibitors showed synergistic effects on cell death. In a favorable in vivo model, the combination worked well with irinotecan without causing significant body-weight loss.
• Why it matters: Mechanistically, APG-5918 reduced the repressive epigenetic mark (H3K27me3), allowing the cells to increase the expression of protective genes (SLFN11 and p21). This provides strong support for clinically testing APG-5918 with DNA-damaging agents.

🧬 Comprehensive Pipeline and Clinical Status

This section details the established products and ongoing clinical work, providing context on the company's commercial readiness.

Approved Products

• Olverembatinib: Approved by China’s NMPA for CML (multiple phases/mutations). It is also covered by the China National Reimbursement Drug List (NRDL).
• Lisaftoclax: Approved by China’s NMPA for treating CLL/SLL in adults who have previously received systemic therapy including BTK inhibitors.

Ongoing Global Trials (Phase III)

The company is conducting several large, global Phase III trials, indicating its commercial trajectory:

• POLARIS-2: Testing Olverembatinib for CML.
• POLARIS-1: Testing Olverembatinib for newly diagnosed Ph+ ALL.
• POLARIS-3: Testing Olverembatinib for SDH-deficient GIST patients.
• GLORA Studies (Lisaftoclax): Includes GLORA-2 (newly diagnosed CLL/SLL), GLORA-3 (newly diagnosed, elderly/unfit AML), and GLORA-4 (newly diagnosed higher risk MDS).

👉 These multiple, global, registrational Phase III trials confirm that AAPG is moving its key assets through established commercial development pathways.

📞 Contact and Investor Relations Details

For anyone interested in following Ascentage Pharma’s progress, the company provided specific contacts for investor and media inquiries. 🧑‍💼

• Investor Relations: Stella Yang ([email protected] | +1 (301) 792-6286)
• ICR Healthcare (Investor Relations): Stephanie Carrington ([email protected] | +1 (646) 277-1282)
• ICR Healthcare (Media Relations): Sean Leous ([email protected] | +1 (646) 866-4012)

🧠 The Analogy

Think of a highly resistant cancer cell as a fortress that has built multiple walls (drug resistance pathways). When traditional drugs attack one wall, the cell simply activates another, like building a new escape tunnel. Ascentage Pharma is not just sending one type of attack (Drug A); instead, they are deploying a coordinated team of specialists (Olverembatinib, APG-2449, APG-5918). This team attacks the fortress from multiple angles—at the main gate, the sewage system, and the power source simultaneously—making it impossible for the cell to withstand the combined pressure.

🧩 Final Takeaway

AAPG is executing a strategic pivot toward combination therapies, using its investigational drugs to specifically target and reverse the natural drug resistance mechanisms that plague advanced cancers, thereby enhancing the chances of successful clinical development.