Ascentage Pharma (NASDAQ: AAPG; HKEX: 6855) is advancing its proprietary drug discovery platform of first- and best-in-class small molecule therapies to address unmet medical needs in cancers and other diseases.
“We are the only company in the world with active clinical programs targeting all three known classes of key apoptosis regulators that restore programmed cell death,” Dajun Yang, MD, Ph.D., co-founder, chairman, and CEO of Ascentage, says in an interview with BioTuesdays.
Dr. Yang highlights that Ascentage has built a rich pipeline of innovative drug candidates, including inhibitors targeting key proteins in the apoptotic pathway such as Bcl-2 and MDM2-P53, as well as next generation tyrosine kinase inhibitors (TKIs).
“Our lead assets—olverembatinib and lisaftoclax—have the potential to address major hematological malignancies, including chronic myeloid leukemia (CML), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), acute lymphocytic leukemia (ALL), myelodysplastic syndromes (MDS), and multiple myeloma (MM)—a market that is expected to exceed $166 billion by 2035,” he notes.
The company has thirteen completed or ongoing international registrational trials, including two regulated by the FDA.
Olverembatinib is the first novel third-generation BCR-ABL1 inhibitor approved in China for the treatment of patients with chronic phase CML (CP-CML) and accelerated phase CML (AP-CML) with T315 mutations, as well as CP-CML resistant or intolerant to first- and second-generation TKIs.
“Despite the advances made with TKIs in treating CML, a significant unmet need remains for patients whose disease is resistant or who develop hard-to-treat mutations after these therapies,” Dr. Yang explains.
Ascentage is currently conducting an FDA-cleared global Phase 3 registrational trial— POLARIS-2—of olverembatinib for CML, in addition to global Phase 3 trials for newly diagnosed Philadelphia chromosome-positive (Ph+) ALL and SDH-deficient gastrointestinal stromal tumors (GIST).
At the 2025 European Hematology Association (EHA) Annual Congress, multiple studies showcased olverembatinib’s broad therapeutic potential, particularly in treating Ph+ ALL. “Olverembatinib achieved high complete remission and complete molecular response rates, along with favorable tolerability in both newly diagnosed and relapsed/refractory Ph+ ALL,” Dr. Yang says. The drug also demonstrated clinical benefit in specific subtypes of hematologic malignancies, such as myeloid/lymphoid neoplasms with FGFR1 rearrangements.
In combination studies—including regimens such as venetoclax plus azacitidine, the vindesine and prednisone (VP) regimen, blinatumomab, or inotuzumab ozogamicin—olverembatinib has shown encouraging clinical results, further supporting its potential to improve outcomes for patients with Ph+ ALL.
In June 2024, Ascentage entered an exclusive global licensing agreement for olverembatinib with Takeda Pharmaceuticals (TSE: 4502; NYSE: TAK). If exercised, the option would allow Takeda to license exclusive global rights to develop and commercialize olverembatinib in all territories outside of—among others—mainland China, Hong Kong, Macau, and Taiwan. Under the agreement, Ascentage received $100 million from Takeda to acquire the option to license olverembatinib. Ascentage will also be eligible for an option exercise fee and additional potential milestones of up to approximately $1.2 billion. Additionally, Takeda has made a minority equity investment in Ascentage.
“Our partnership with Takeda enables us to leverage their global commercial expertise and oncology footprint to potentially expand olverembatinib’s impact worldwide,” Dr. Yang notes.
The company’s second lead asset, lisaftoclax, is a novel Bcl-2 inhibitor under development for various hematologic malignancies. Recently, China’s National Medical Products Administration (NMPA) approved lisaftoclax for the treatment of adult patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who have previously received at least one systemic therapy including Bruton’s tyrosine kinase (BTK) inhibitors. “This makes lisaftoclax the first Bcl-2 inhibitor to receive conditional approval and marketing authorization for the treatment of patients with CLL/SLL in China, and the second Bcl-2 inhibitor approved globally,” Dr. Yang says.
Ascentage is also conducting an FDA-cleared global Phase 3 registrational trial—GLORA—of lisaftoclax in combination with BTK inhibitors for patients with CLL/SLL who have suboptimal responses to BTK inhibitor therapy after more than 12 months, as well as trials in newly diagnosed CLL/SLL, AML, MDS.
At the 2025 American Society of Clinical Oncology (ASCO) meeting, results from the ongoing Phase 1b/2 study of lisaftoclax combined with azacitidine in blood cancers was featured in an oral presentation. “These results highlighted lisaftoclax’s significant activity, particularly in combination with azacitidine, in patients with various myeloid malignancies,” Dr. Yang points out.
“This next-generation Bcl-2 inhibitor has shown antitumor activity in both treatment-naïve and venetoclax-experienced patients, addressing a critical unmet need. The NDA submission in China marks a major milestone. If approved, lisaftoclax would become the second Bcl-2 inhibitor approved globally,” he adds.
Leveraging strong R&D capabilities, Ascentage has developed a robust portfolio of global intellectual property rights. “We are actively pursuing partnerships to accelerate the development and commercialization of our lead assets,” Dr. Yang says.
In addition to its partnership with Takeda, Ascentage has established global collaborations with a number of leading biopharmaceutical companies and has R&D relationships with premier research institutions such as the Dana-Farber Cancer Institute, Mayo Clinic, U.S. National Cancer Institute, and the University of Michigan.
Other innovative product candidates in Ascentage’s pipeline include:
- APG-2449, a multi-targeted inhibitor of ALK, FAK, and ROS1 in Phase 3 trials for ALK-positive NSCLC (both first-line and resistant cases);
- Alrizomadin, an orally bioavailable, selective MDM2-p53 inhibitor for rare tumors such as adenoid cystic carcinoma (ACC), malignant peripheral nerve sheath tumor (MPNST), AML, and pediatric solid tumors;
- Pelcitoclax, a Bcl-2/Bcl-xL inhibitor under investigation for NSCLC, SCLC, neuroendocrine tumors, and non-Hodgkin’s lymphoma (NHL);
- APG-5918, targeting embryonic ectoderm development (EED) with anemia and oncology applications. Data presented at EHA 2025 showed preclinical antitumor activity in T-cell lymphoma and support further clinical development.
Dr. Yang emphasizes that the past 18 months have been transformational for Ascentage, “We have significantly de-risked, expanded globally, and strengthened our financial position. In January, we were pleased to list on NASDAQ, raising $132.5 million in net IPO proceeds.”
“We are now positioned as a leading hematologic oncology company, with commercial-stage or NDA-review assets and FDA-cleared Phase 3 registration trials targeting six distinct diseases,” Dr. Yang concludes.
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