On July 12, 2021 Akeso, Inc. reported that, CD47 monoclonal antibody (AK117), a second-generation novel drug for immuno-oncology therapy independently developed by the Company, has completed phase I dose escalation trial in Australia (Press release, Akeso Biopharma, JUL 12, 2021, View Source [SID1234584790]). AK117 resulted in no dose-limiting toxicity (DLT) and no anemia of clinical significance in subjects in all dose escalation cohorts (with 0.3 mg/kg to 45 mg/kg administered once-weekly (QW)), and was well tolerated by subjects in all cohorts. Low-dose priming was not required.
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Akeso has obtained approval from the National Medical Products Administration (NMPA) of China to initiate phase Ib/II clinical trial of AK117 in combination with azacitidine for the treatment of acute myeloid leukemia (AML). AK117, a second-generation CD47 monoclonal antibody, has a significantly improved safety profile compared to the first-generation CD47 monoclonal antibody, and AK117 in combination with azacitidine is expected to perform better than similar drugs in the treatment of AML. Previous studies of AK117 in myelodysplastic syndromes (MDS) have shown its advantages of safety and the majority of MDS patients had hematologic improvement while receiving AK117 treatment. To date, clinical trials of AK117 in both solid tumors and hematologic tumors have been initiated and began patient dosing.
AML is a group of highly heterogeneous diseases with clonal proliferation abnormalities of hematopoietic stem cells and is the most common type of adult acute leukemia. CD47 is highly expressed on the surface of several tumor cells, including solid tumors and hematologic tumors, and is associated with poor prognosis. CD47 blockade stimulates phagocytosis of tumor cells by macrophages and promotes adaptive immune response. Preclinical data showed that CD47 monoclonal antibody in combination with azacitidine can further induce endogenous expression of calreticulin on the cell surface, thereby further enhancing the phagocytosis of tumors by macrophages. At the same time, there are clinical data showing that CD47 monoclonal antibody in combination with azacitidine is significantly more effective than azacitidine alone in treating AML subjects who are not suitable for chemotherapy at first treatment, and is safe and well tolerated.
Information about AK117 (CD47 Monoclonal Antibody)
AK117 is a novel humanized IgG4 mAb independently developed by the Company. It can bind with CD47 expressed on tumor cells to prevent the interaction between CD47 and its receptor, SIRPα, expressed on macrophages so as to enhance phagocytosis to inhibit the growth of tumor cells. Previously published data demonstrated exceptional safety profile. AK117 resulted in no DLT and no anemia of clinical significance in subjects in all doseescalation cohort (the highest dose cohort was 45 mg/kg QW), and was well tolerated by subjects in all cohorts. The CD47 receptor occupancy rate (RO) of the peripheral blood T cells has reached and maintained at 100% in the 3 mg/kg cohort.