Following the announcement on November 17 that the domestic NDA for APG-2575, the core product of the apoptosis pipeline, was accepted and included in the priority review process, Yasheng Pharmaceutical-B (06855) once again announced favorable news within a week, which attracted the attention of the global industry and further boosted confidence in the secondary market.

On November 22, Yasheng Pharmaceutical announced that its core product, olevatinib (trade name: Nellick), the Phase Ib Overseas Clinical Study (NCT04260022) data for patients with chronic myeloid leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphocytic leukemia (ALL) has been successfully published in the November 2024 issue of “JAMA Oncology”, which once again reflects the international hematology community's high recognition of olevatinib as the best-in-class drug at the global level.

The Zhitong Finance App learned that “JAMA Oncology” is a leading and influential academic journal in the field of global oncology, with an impact factor (IF) of 28.4 in 2023. The journal has a wide readership in clinical oncology, with 6.4 million original downloads or views each year. In 2023, out of 2,223 research paper submissions received by the journal, only 155 (7%) were published.

Drug resistance and intolerance to TKI remains a global challenge in CML treatment. As a result, many CML patients face huge life difficulties and financial pressure, especially those who have received multiple treatment lines with poor results. For example, in the treatment of some second- and third-generation TKI drugs, an arterial occlusive event (AOE) is a significant safety challenge, often leading to dosage restrictions. Orebatinib, a third-generation BCR: :ABL1 inhibitor, is expected to meet the urgent needs of this group of patients.

In this study (NCT04260022), 80 patients with CML or Philadelphia chromosome-positive acute lymphocytic leukemia (Ph+ ALL) were randomly grouped and treated with oral 30, 40, or 50 mg olevatinib every other day. All enrolled patients have received multiple treatment lines in the past: about 18% of patients have received two types of TKI treatment, 28% have received three, and 54% have received at least four. Forty-six patients (57.5%) were previously treated with Ponatinib, 25 (31.3%) were treated with Asciminib, and 11 (13.8%) received these two medications.

Among all evaluable patients with chronic phase CML (CP-CML), the complete cytogenetic response (cCyR) rate was approximately 61% and the primary molecular response (MMR) rate was approximately 42%. Cytogenetic and molecular response rates are close regardless of whether patients carry T315I mutations that can cause resistance to imatinib and all second-generation TKI drugs.

It is worth mentioning that among patients who failed Ponatinib treatment, approximately 58% obtained cCyR and approximately 37% obtained MMR. Among patients resistant to Asciminib, the CCYR rate was 50%; the MMR rate was 33%.

Orebatinib is well tolerated. Adverse events (mostly mild and moderate) that occurred during treatment mainly included elevated creatine phosphokinase and thrombocytopenia. There were no fatal treatment-related adverse events in the study. The incidence of treatment-related arterial embolisms is low (3.8%), and they are all mild or moderate (grade 1 or 2).

The results of this study have been presented at several hematology and oncology conferences around the world, including the 29th European Hematology Association Annual Meeting (EHA Annual Meeting) held in Madrid on June 13-16, 2024; the 12th Hematologic Oncology Association Annual Meeting (SOHO Annual Meeting) held in Houston, USA on September 4-7; and the 26th John Goldman Chronic Myeloid Leukemia (Biology and Therapy) Conference held in Prague on September 27-29. The latest results of the study will be presented in the form of a poster presentation at the 66th American Society of Hematology (ASH) Annual Meeting to be held in San Diego, USA on December 8 this year (abstract number: 3151).

Dr. Elias Jabbour, professor of leukemia at the University of Texas MD Anderson Cancer Center, said, “The reason why olevatinib has good efficacy in Ponatinib and Asciminib resistant patients may be due to its extensive coverage of multiple mutations (pan-BCR: :ABL1 kinase domain). In studies to date, compared to other approved TKIS and stamp inhibitors asciminib, olevatinib is more sensitive and has better efficacy in patients with complex mutations (that is, two or more mutations on the same allele of the BCR: :ABL1 fusion gene).”

Nellick is Yasheng Pharmaceuticals' original Class 1 new drug. It is the first third-generation BCR:ABL inhibitor approved for marketing in China. As a novel drug with best-in-class (best-in-class) potential at the global level, this drug has outstanding effects on BCR:ABL and various BCR:ABL mutants, including the T315I mutation. As an original innovative drug in China with BIC potential, Nellick has received much attention from the global hematology community, and its clinical progress has been selected as an oral report at the ASH Annual Meeting for seven consecutive years. In February 2024, Nellick received permission from the US FDA to conduct a globally registered phase III clinical study.

At present, with the release of the potential of core products such as Nellick and APG-2575 in innovative R&D and commercialization, Yasheng Pharmaceutical has now built a good foundation in the global field of innovative drugs. However, in the current market environment where “more definitive enterprises” are preferred, as scarce high-value biomedical investment targets, Yasheng Pharmaceutical holds a number of major FIC/BIC potential assets, and their allocation value is constantly increasing.