Ascentage Pharma Announces Inclusion of Lisaftoclax and Olverembatinib in Chinese Society of Clinical Oncology (CSCO) 2025 Guidelines

Rhea-AI Summary

Ascentage Pharma (NASDAQ: AAPG) announced the inclusion of two proprietary drugs in the 2025 Chinese Society of Clinical Oncology (CSCO) Guidelines. Lisaftoclax, their novel oral Bcl-2 selective inhibitor, received its first CSCO recommendation for treating relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). It is the world's second Bcl-2 inhibitor to submit a New Drug Application and the first China-developed one to receive Priority Review.

Olverembatinib, their next-generation tyrosine kinase inhibitor, received an upgraded recommendation to Level I for treating children with Ph+ ALL harboring the T315I BCR-ABL1 mutation. The drug retained its recommendations in other CSCO Guidelines for various CML treatments. Notably, olverembatinib is included in China's National Reimbursement Drug List and is being jointly commercialized with Innovent Biologics.

Positive

• First CSCO Guidelines recommendation for Lisaftoclax, showing clinical validation
• Olverembatinib received upgraded recommendation to Level I for pediatric treatment
• Olverembatinib included in China's National Reimbursement Drug List, improving accessibility
• Strategic commercialization partnership with Innovent Biologics for Olverembatinib

Negative

• Lisaftoclax still pending regulatory approval in China and US
• to specific patient populations with certain mutations or treatment resistance

Insights

Pharmaceutical Analyst

Ascentage's drugs gaining CSCO recognition marks important regulatory progress, validating their pipeline and strengthening market positioning in China.

Ascentage Pharma has achieved a significant regulatory milestone with the inclusion of two proprietary drugs in the 2025 Chinese Society of Clinical Oncology Guidelines. Lisaftoclax (APG-2575), the company's Bcl-2 inhibitor, received its first CSCO recommendation for relapsed/refractory CLL/SLL treatment. This positions it as the only China-developed Bcl-2 inhibitor included in these influential guidelines.

The inclusion comes after lisaftoclax received Priority Review designation from China's NMPA for its New Drug Application in November 2024. This regulatory pathway could accelerate its market entry, though approval is still pending. Meanwhile, the drug is undergoing two registrational Phase III studies globally, exploring combination therapies that could expand its treatment potential.

Olverembatinib, the company's TKI, received an upgraded recommendation to Level I for treating children with Ph+ ALL harboring the T315I mutation. The drug maintained its other recommendations for various CML indications, reinforcing its established position. Unlike lisaftoclax, olverembatinib is already commercially available and included in China's National Reimbursement Drug List, which enhances accessibility and supports revenue generation. The joint commercialization with Innovent Biologics represents a strategic approach to maximize market reach in China.

Oncology Specialist

CSCO guideline inclusion validates lisaftoclax's safety profile and olverembatinib's efficacy against resistant mutations, addressing key treatment gaps.

The inclusion of lisaftoclax in the CSCO Guidelines represents significant clinical validation for this novel therapy. According to Prof. Jun Ma, the drug demonstrated a high overall response rate with rapid onset of action in CLL/SLL patients. Most notably, lisaftoclax showed substantially lower incidence of tumor-lysis syndrome compared to early data from other Bcl-2 inhibitors, potentially simplifying clinical risk management for these patients.

For olverembatinib, the upgrade to Level I recommendation for pediatric Ph+ ALL patients with the T315I mutation expands treatment options for this challenging population. The drug's ability to address a range of BCR::ABL1 mutations, including the notoriously resistant T315I mutation and complex/compound mutations, fills a critical treatment gap.

The drug maintained its Level I recommendations across multiple CML indications, including for patients who failed first-line treatment with nilotinib or dasatinib, and those intolerant to or failing multiple TKIs. This comprehensive coverage across hematological malignancies demonstrates the drug's versatility in addressing unmet needs, particularly for patients with treatment alternatives due to mutation-driven resistance.

ROCKVILLE, Md. and SUZHOU, China, April 21, 2025 (GLOBE NEWSWIRE) -- Ascentage Pharma (NASDAQ: AAPG; HKEX: 6855), a global biopharmaceutical company engaged in discovering, developing, and commercializing therapies to address global unmet medical needs primarily for hematological malignancies, today announced that two of its proprietary novel drugs have been included in the 2025 Chinese Society of Clinical Oncology (CSCO) Guidelines. Lisaftoclax (APG-2575), the company’s investigational novel oral Bcl-2 selective inhibitor, received its first recommendation in the CSCO Guidelines for the Diagnosis and Treatment of Lymphoid Malignancies. Olverembatinib, the company’s novel next-generation tyrosine kinase inhibitor (TKI), received an upgraded recommendation in the CSCO Guidelines for the Diagnosis and Treatment of Leukemias in Children and Adolescent, and retained its recommendations in the CSCO Guidelines for the Diagnosis and Treatment of Hematological Malignancies.

Bcl-2 inhibitor lisaftoclax (APG-2575) receives its first CSCO Guidelines recommendation

As the world’s second Bcl-2 inhibitor to submit a New Drug Application (NDA) and the first China-developed Bcl-2 inhibitor to submit an NDA and receive Priority Review designation in China, lisaftoclax (APG-2575), supported by its robust clinical data, has been recommended in the CSCO 2025 Guidelines for the Diagnosis and Treatment of Lymphoid Malignancies, as a monotherapy for the treatment of patients with relapsed/refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). This is the first CSCO Guidelines recommendation for lisaftoclax (APG-2575), making it the only China-developed Bcl-2 inhibitor recommended in the CSCO Guidelines. This marks a milestone achieved by Ascentage Pharma in advancing the development of this innovative drug to bring meaningful benefit to patients as well as a major breakthrough in the field of hematological malignancies.

Prof. Jun Ma, from Harbin Institute of Hematology and Oncology, stated: “These CSCO Guidelines recommendations for lisaftoclax (APG-2575) indicate recognition of the drug’s robust data by a top medical association in China. In the data, lisaftoclax (APG-2575) monotherapy showed a high overall response rate and a fast onset of action that can enable rapid disease control. Moreover, the incidence of tumor-lysis syndrome in patients treated with lisaftoclax (APG-2575) was far lower than was shown in the early data of other Bcl-2 inhibitors, highlighting a favorable tolerability profile that could potentially change the clinical risk management in CLL/SLL. We look forward to lisaftoclax (APG-2575)’s approval in China through the Priority Review pathway, which will bring this innovative therapeutic to patients in need.”

In November 2024, the NDA for lisaftoclax (APG-2575) monotherapy for the treatment of R/R CLL/SLL was accepted and granted the Priority Review designation by the Center for Drug Evaluation (CDE) of China National Medical Product Administration (NMPA). Globally, lisaftoclax (APG-2575) is being evaluated in two registrational Phase III studies for the treatment of CLL/SLL, including an international registrational Phase III study of lisaftoclax (APG-2575) combined with a BTK inhibitor in patients with CLL/SLL who had previously received BTK inhibitors (the GLORA Trial); and an international registrational Phase III study evaluating lisaftoclax (APG-2575) combined with acalabrutinib, versus immunochemotherapy in treatment-naïve patients with CLL/SLL (the GLORA-2 Trial). These studies were designed to further broaden the treatment window of lisaftoclax (APG-2575).

The first China-approved BCR-ABL inhibitor olverembatinib receives an upgraded recommendation in the CSCO Guidelines

In the CSCO 2025 Guidelines for the Diagnosis and Treatment of Leukemias in Children and Adolescent, the recommendation for olverembatinib for the treatment of children with Ph+ ALL who harbor the T315I BCR-ABL1 kinase domain mutation was upgraded to Level I, thus opening a whole new chapter for olverembatinib in pediatric hematology.

Prof. Xiaofan Zhu, from the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, noted, “As a China-developed third-generation TKI, olverembatinib has achieved a major breakthrough in the treatment of children with Ph+ ALL. In the CSCO 2025 Guidelines, the recommendation for olverembatinib in the treatment of patients with Ph+ ALL who harbor the T315I BCR-ABL1 kinase domain mutation or are intolerant to dasatinib has been upgraded to Level I, an update that reflects the drug’s promising clinical utility. Looking ahead, we hope to see more studies further evaluating olverembatinib’s long-term efficacy and searching for more optimized combinations of the drug that can bring greater hope for curative care to children with Ph+ ALL.”

In the CSCO 2025 Guidelines for the Diagnosis and Treatment of Hematological Malignancies, olverembatinib retained a number of major recommendations which solidified the drug’s vital role in the treatment of CML. In chronic-phase CML (CML-CP), olverembatinib retained a Level I recommendation for the treatment of all lines of T315I mutant CML-CP; a Level I recommendation for the second-line treatment of patients who had failed first-line treatment with nilotinib or dasatinib and the third-line treatment of patients who are intolerant to and/or failed on two or more TKIs. In progressive-phase CML, olverembatinib retained a Level I recommendation as a treatment option for patients with T315I mutant CML-AP, and those who progressed from CML-CP to CML-AP, or from CML-CP/AP to CML-BP. Moreover, the CSCO 2025 Guidelines emphasized olverembatinib’s advantages in addressing a range of BCR::ABL1 mutations (including T315I, V299L, F317L/V/I/C, T315A, Y253H, E255K/V, and F359C/V/I) and any other mutation (including complex/compound mutations).

In Ph+ ALL, olverembatinib has retained its Level I recommendation for response induction and the treatment of relapsed/refractory patients.

Olverembatinib is a novel drug developed by Ascentage Pharma with support from China’s National Major New Drug Development Program. As the first approved third-generation BCR-ABL inhibitor in China, olverembatinib is indicated for the treatment of adult patients with TKI-resistant CML-CP or -AP harboring the T315I mutation; and adult patients with CML-CP resistant to and/or intolerant of first- and second-generation TKIs. Furthermore, all approved indications of olverembatinib have been included in the China National Reimbursement Drug List (NRDL) which has greatly improved the drug’s accessibility to patients. Olverembatinib is being jointly commercialized in China by Ascentage Pharma and Innovent Biologics.

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, said, “CSCO Guidelines are among the most recognized clinical guidelines in China, providing crucial guidance to Chinese physicians on the diagnosis and treatment of malignancies. The recommendations for both olverembatinib and lisaftoclax (APG-2575) in the updated guidelines are a testament to our strong and innovative pipeline. In particular, the CSCO Guidelines’ very first recommendations for lisaftoclax (APG-2575), the second Bcl-2 inhibitor to reach NDA submission anywhere in the world, reflect the clinical experts’ forward-looking recognition of this innovative drug, providing much needed new guidance to clinical practices and the answer to a major treatment gap. Meanwhile, we are greatly encouraged by the Guidelines’ upgraded recommendation for olverembatinib in pediatric patients with ALL. In the future, we hope to see additional positive clinical data that can pave the way for upgraded recommendations for these two innovative drugs. We will continue to accelerate the clinical development and commercialization of our drug candidates for the benefit of more patients.”

*Lisaftoclax (APG-2575) and olverembatinib are investigational drugs and not yet approved in the US.

About Ascentage Pharma
Ascentage Pharma is a global, integrated biopharmaceutical company engaged in discovering, developing and commercializing therapies to address global unmet medical needs primarily in hematological malignancies. Ascentage Pharma has been listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code 6855.HK since October 2019 and has also been listed on the Nasdaq Global Market under the ticker symbol “AAPG” since January 2025.

The company has built a rich pipeline of innovative drug candidates that includes inhibitors targeting key proteins in the apoptotic pathway, such as Bcl-2 and MDM2-p53; and next-generation TKIs that target kinase mutants emergent during cancer treatment. Ascentage Pharma is also the only company in the world with active clinical programs targeting all known key apoptosis regulators.

Olverembatinib, one of the company’s lead assets, is already approved in China with all of its approved indications included into the China National Reimbursement Drug List (NRDL). Meanwhile, a New Drug Application (NDA) for another one of Ascentage Pharma’s key drug candidates, the novel Bcl-2 selective inhibitor lisaftoclax (APG-2575), has already been accepted and granted the Priority Review designation by the China CDE.

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 and other relationships with numerous leading biotechnology and pharmaceutical companies such as Takeda, AstraZeneca, Merck, Pfizer and Innovent; and research and development relationships with leading research institutions such as Dana-Farber Cancer Institute, Mayo Clinic, National Cancer Institute and the University of Michigan.

The company has built a talented team with a wealth of global experience in the discovery and development of innovative drugs and fully functional 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 fulfill its mission of addressing unmet clinical needs in China and around the world for the benefit of more patients.

Forward-Looking Statements
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. All statements, other than statements of historical facts, contained in this press release may be forward-looking statements, including statements that express Ascentage Pharma’s opinions, expectations, beliefs, plans, objectives, assumptions or projections regarding future events or future results of operations or financial condition. These forward-looking statements are subject to a number of risks and uncertainties as discussed in Ascentage Pharma’s filings with the SEC, including those set forth in the sections titled “Risk factors” and “Special note regarding forward-looking statements and industry data” in its Registration Statement on Form F-1, as amended, filed with the SEC on January 21, 2025 and the Form 20-F filed with the SEC on April 16, 2025, the sections headed “Forward-looking Statements” and “Risk Factors” in the prospectus of the Company for its Hong Kong initial public offering dated October 16, 2019, and other filings with the SEC and/or The Stock Exchange of Hong Kong Limited we made or make from time to time that may cause actual results, levels of activity, performance or achievements to be materially different from the information expressed or implied by these forward-looking statements. The forward-looking statements contained in this presentation do not constitute profit forecast by the Company’s management.

As a result of these factors, you should not rely on these forward-looking statements as predictions of future events. The forward-looking statements contained in this press release are based on Ascentage Pharma’s current expectations and beliefs concerning future developments and their potential effects and speak only as of the date of such statements. Ascentage Pharma does not undertake any obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.

Contact Information
Investor Relations:
Hogan Wan, Head of IR and Strategy
Ascentage Pharma
Hogan.Wan@ascentage.com
+86 512 85557777

Stephanie Carrington
ICR Healthcare
Stephanie.Carrington@icrhealthcare.com
(646) 277-1282

Media Relations:
Sean Leous
ICR Healthcare
Sean.Leous@icrhealthcare.com
(646) 866-4012

FAQ

What is the significance of Lisaftoclax's inclusion in CSCO 2025 Guidelines for AAPG?

It's the first China-developed Bcl-2 inhibitor recommended in CSCO Guidelines, marking a milestone for AAPG in hematological malignancies treatment and showing recognition of the drug's robust clinical data.

How does AAPG's Lisaftoclax compare to other Bcl-2 inhibitors in terms of safety?

Lisaftoclax shows a lower incidence of tumor-lysis syndrome compared to early data of other Bcl-2 inhibitors, demonstrating a favorable tolerability profile for CLL/SLL treatment.

What are the current clinical trials for AAPG's Lisaftoclax?

Lisaftoclax is being evaluated in two registrational Phase III studies: the GLORA Trial for CLL/SLL patients previously treated with BTK inhibitors, and the GLORA-2 Trial for treatment-naïve CLL/SLL patients.

What is the current status of Olverembatinib's approval and distribution for AAPG?

Olverembatinib is approved in China as the first third-generation BCR-ABL inhibitor, included in the National Reimbursement Drug List, and is being jointly commercialized with Innovent Biologics.