It is understood that Yimingang-B (01541) recently gave an oral presentation on two Phase II clinical data on its core product Timdarpacept (project number: IMM01) at the 2024 annual meeting of the American Society of Clinical Oncology (ASCO).

Among them, in terms of the indication of IMM01 combined with azacitidine for the initial treatment of high-risk myelodysplastic syndrome (HR-MDS), among the 51 evaluatable patients, the complete remission rate (CR) reached 33.3%, and the overall response rate reached 64.7%; among the 34 patients who were treated for more than 4 months, the CR rate reached 50.0% and the ORR reached 85.3%; while among the 29 patients who were treated for more than 6 months, the CR rate reached 58.6% and the ORR reached 89.7%. Response improves as treatment time increases. The median observation time is 15.9 months, and the median progression-free survival (mPFS) and median overall survival (mOS) have not been reached. The 12-month OS is 71.1%.

In the aspect of hematological toxicity, which is most concerned by the industry, the report shows that after IMM01 combined with azacitidine treatment, 38.8% of patients had a significant increase in hemoglobin compared to baseline, and 45.2% of patients had a significant increase in platelets compared to the baseline level. 21.9% of patients had a significant increase in neutrophils compared to the baseline level. At the same time, it significantly reduced the transfusion dependence of red blood cells and platelets. With the prolongation of treatment time, no increase in hematological toxicity was found.

Significant recovery of hemoglobin and platelets was observed in patients after IMM01 combined with azacitidine treatment

Dependency on red blood cells and platelets for transfusion decreased after treatment

In addition, compared with the safety data of the Chinese MDS-002 single-arm study (72 patients with azacitidine monotherapy for the same indication), it can be found that azacitidine combined with IMM01 does not increase the incidence of treatment-related adverse events, indicating that the safety of IMM01 is good.

Another oral report is the use of IMM01 combined with Torayleyzumab to treat classical Hodgkin's lymphoma (cHL) after failure of previous PD-1 antibody treatment. The data show that among the 33 evaluable patients (with an average of 4 treatment lines previously received), the ORR reached 66.7%, and the CR rate reached 24.2%. A reduction in the size of the target lesions was observed in 29 patients (87.9%). The median observation time is 6.87 months, and the median time to remission is 1.6 months, and the median progression-free survival and median duration of remission have not been reached.

In terms of safety, the vast majority of drug-related adverse reactions (TRAE) are grade 1-2 hematological adverse reactions. Among them, grade 3-4 leukopenia, thrombocytopenia, neutropenia, and anemia were 12.1%, 12.1%, 12.1%, and 6.1% respectively. After symptomatic treatment, they can be completely recovered or restored to grade 1/baseline level. No hemolysis cases occurred. No patients were permanently discontinued from the study drug or died due to TRAE, indicating that this treatment scheme has excellent safety.

Yimingang has announced the permission to conduct Phase III clinical trials for the two indications mentioned above by the National Medical Products Administration (CDE) on April 17 and May 17 respectively. In addition, the company also announced on May 31 that the IMM01 combined with azacitidine for the initial treatment of chronic myelomonocytic leukemia (CMML) phase III clinical study plan has been approved by the CDE.

On the road of developing CD47 targeted drugs, many multinational pharmaceutical companies have successively failed. At this year's ASCO annual meeting, Yimingang's two Phase II data successfully selected for oral presentations have received high attention at the conference site, indicating that the industry authorities highly recognize the clinical data of this project and have great expectations for the development prospects of CD47 targeted drugs.

When it comes to the differentiation and advantages of IMM01, Dr. Tian Wenzhi, founder of Yimingang, said: "IMM01 is a SIRPα-Fc fusion protein. In order to solve the safety problem of the CD47 molecule, IMM01 uses an engineered human SIRPα structure domain in the CD47 binding region. In vitro studies have shown that this structure domain does not bind to human red blood cells and has strong safety advantages. In addition, the company has also adopted deglycosylation modification on this structure domain to reduce the immunogenicity of the molecule. IMM01 fully activates macrophages through a dual mechanism of action, that is, interfering with the CD47/SIRPα interaction to block the "Don't eat me" signal and transmitting the "Eat me" signal by activating the Fcγ receptor of macrophages. In comparison, the affinity of IMM01 is ~3nM, which is about one thousandth of Magrolimab. The moderate affinity of IMM01 maintains the peripheral blood receptor occupancy at the level of 10-15% (while that of Magrolimab is over 90% after 14 days of medication), thereby avoiding the antigen silencing effect common to CD47 antibody drugs. The recommended Phase II dose of IMM001 is only 2.0mg/kg, while the dose of CD47 antibody is usually between 20 and 45mg/kg."