Full Press Release Details
Ascentage Pharma Announces Clinical Data of Lisaftoclax,
Which Shows Therapeutic Potential in
Venetoclax-Refractory Patients, Selected for Oral Report at ASCO 2025
ROCKVILLE, Md. and SUZHOU, China, May 22, 2025
- Ascentage Pharma (NASDAQ: AAPG; HKEX: 6855), a global biopharmaceutical company dedicated to addressing unmet medical needs
in cancers, today announced that new clinical data from two ongoing investigational studies evaluating lisaftoclax in various blood cancers
and alrizomadlin in solid tumors will be presented during an oral presentation and poster presentation, respectively, at the 2025 American
Society of Clinical Oncology (ASCO) Annual Meeting, taking place May 30 - June 3 in Chicago, Ill., USA. Both lisaftoclax and alrizomadlin
demonstrated antitumor activity, and the data support their further clinical development.
The Bcl-2 inhibitor lisaftoclax and the MDM2-p53 inhibitor
alrizomadlin are both key drug candidates in Ascentage Pharma's apoptosis-targeted pipeline. The oral report on lisaftoclax will
feature results from a Phase 1b/2 study evaluating lisaftoclax in combination with azacitidine in patients with treatment-na ve (TN)
or prior venetoclax-exposed myeloid malignancies. Data from this global, multicenter study that has enrolled nearly one hundred patients
show that lisaftoclax in combination with azacitidine was well tolerated with preliminary efficacy. Moreover, this study released the
first dataset of lisaftoclax in patients with venetoclax-refractory acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), and
it also demonstrated promising therapeutic potential.
Dr. Yifan Zhai, Chief Medical Officer of Ascentage
Pharma, commented: "We are pleased that results from the ongoing Phase 1b/2 study of lisaftoclax will be featured in an oral
presentation at the 2025 ASCO Annual Meeting, which will highlight how lisaftoclax demonstrated significant activity when combined with
azacitidine in patients with various myeloid malignancies. This novel Bcl-2 inhibitor has shown antitumor activity in both previously
untreated patients and those who were treated with venetoclax, addressing a critical treatment gap for these difficult-to-treat conditions.
The recent new drug application submission for lisaftoclax in China was a milestone for our program, and, if approved, lisaftoclax would
become the second Bcl-2 inhibitor to be approved anywhere in the world. We are grateful to the patients who participated in these trials
and the investigators for sharing our commitment to developing innovative therapies that can make a meaningful difference for patients
with cancer who have limited options."
Highlights of the two abstracts selected for presentations
at ASCO 2025 are as follows:
Phase 1b/2 Study of Lisaftoclax (APG-2575) Combined
with Azacitidine (AZA) in Patients with Treatment-Na ve or Prior Venetoclax-Exposed Myeloid Malignancies
The Phase 1b/2 study was designed to evaluate
the safety and efficacy of lisaftoclax in combination with azacitidine in patients with treatment-na ve (TN) or relapsed/refractory
(R/R) acute myeloid leukemia (AML)/mixed phenotype acute leukemia (MPAL) or high-risk myelodysplastic syndromes (HR-MDS)/chronic myelomonocytic
leukemia (CMML). Lisaftoclax is a novel investigational oral selective Bcl-2 inhibitor that has shown enhanced treatment response when
combined with azacitidine in prior preclinical and clinical studies.
The combination of lisaftoclax and azacitidine
was well tolerated, with initial signals of clinical activity. As of the data cutoff date of January 6, 2025, 97 patients were enrolled,
with a median treatment duration of two cycles. In patients with TN-MDS/CMML, the overall response rate (ORR) was 64%, with complete response
(CR) and marrow CR achieved by 29% and 36% of patients, respectively; in patients with R/R AML treated with lisaftoclax for 28 days or
14 days of repeated 28-day cycles, the ORRs were 39% and 50%, respectively, including CR rates of 28% and 37.5%, respectively; in patients
with diseases refractory to venetoclax, the ORR was 17% in patients with AML/MPAL and 50% in patients with HR-MDS.
The maximum tolerated dose (MTD) was not
reached, and no dose-limiting toxicities (DLTs) were observed. Common grade 3/4 treatment-emergent adverse events (TEAEs) included neutropenia
(40%), febrile neutropenia (31%), and thrombocytopenia (22%). Febrile neutropenia was the most commonly reported serious adverse event
(SAE) (26.8%). Only 3% of participants experienced neutropenia that led to a dose reduction of lisaftoclax. There was no reported 60-day
A Phase 2 Study of Novel MDM2 Inhibitor Alrizomadlin
(APG-115) with or without Toripalimab in Patients with Advanced Adenoid Cystic Carcinoma (ACC) or Other Solid Tumors
Alrizomadlin is a novel investigational
oral MDM2 inhibitor that has shown a manageable safety profile with initial clinical activity in ACC.
As of the data cutoff date of January 5,
2025, 54 patients with advanced ACC, malignant peripheral nerve sheath tumor (MPNST), liposarcoma (LPS), biliary-tract cancer (BTC) and
other tumors were enrolled. Alrizomadlin monotherapy showed antitumor activity in patients with advanced ACC or MPNST. Alrizomadlin in
combination with toripalimab was also well tolerated and demonstrated antitumor activity in patients with MPNST, BTC and LPS.
In the monotherapy arm, 14 patients were
efficacy-evaluable. The ORR was 22.2% and the disease control rate (DCR) was 100% in 9 patients with ACC. The DCR was 100% in all patients
with MPNST, all 5 of whom achieved stable disease (SD). Grade 3 or higher treatment-related adverse events (TRAEs) included neutropenia
(13.6%) and thrombocytopenia (9.1%). No treatment-related SAEs were reported.
In the combination arm, 28 patients were
efficacy-evaluable. The ORR was 20% and DCR was 80% in 5 patients with BTC. The ORR was 16.7% and DCR was 66.7% in 6 patients with LPS.
The ORR was 14.3% and DCR was 53.6% in patients with MPNST; furthermore, 2 patients with MPNST had confirmed partial responses (PR) with
prolonged progression free survival (PFS) of 60+ weeks and 96+ weeks, respectively. Grade 3 or higher TRAEs included thrombocytopenia
(38.5%) and neutropenia (34.6%). Treatment-related SAEs were reported in 8 patients, with thrombocytopenia being the most common (n=6).
One patient discontinued treatment because of grade 4 thrombocytopenia. No treatment-related deaths were reported.
About Ascentage Pharma
Ascentage Pharma (NASDAQ: AAPG; HKEX: 6855) is a global
biopharmaceutical company dedicated to addressing unmet medical needs in cancers. 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
The lead asset, olverembatinib, is the first third
generation BCR-ABL1 inhibitor approved in China for the treatment of patients with CML in chronic phase (CML-CP) with T315I mutations,
CML in accelerated phase (CML-AP) with T315I mutations, and CML-CP that is resistant or intolerant to first and second-generation TKIs.
It is covered by the China National Reimbursement Drug List (NRDL). The Company is currently conducting an FDA-cleared, global registrational
Phase 3 trial, or POLARIS-2, of olverembatinib for CML, as well as global registrational Phase 3 trials for newly diagnosed Ph+ ALL patients
and SDH-deficient GIST patients.
The second lead asset, lisaftoclax, is a novel Bcl-2
inhibitor for the treatment of various hematological malignancies. The NDA for the treatment of relapsed and/or refractory CLL and SLL
was accepted with Priority Review designation by China's National Medical Products Administration. The Company is currently conducting
an FDA-cleared, global registrational Phase 3 trial, or GLORA, of lisaftoclax in combination with BTK inhibitors for patients with CLL/SLL
previously treated with BTK inhibitors for more than 12 months with sub-optimal response, as well as global registrational Phase 3 trials
for newly diagnosed CLL/SLL, AML and MDS patients.
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, in addition to research
and development relationships with leading research institutions, such as Dana-Farber Cancer Institute, Mayo Clinic, National Cancer Institute
and the University of Michigan. For more information, visit https://ascentage.com/
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and Section 21E of the Securities Exchange Act of 1934, as amended. All statements, other than statements of historical facts, contained
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the Form 20-F filed with the SEC on April 16, 2025, the sections headed "Forward-looking Statements" and "Risk Factors"
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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