Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)
ADC ID
DRG0QJUWT
ADC Name
AGS-62P1
Synonyms
AGS 62P1; AGS-62P1; AGS62 P1; AGS62P1; ASP-1235; ASP1235
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Organization
Astellas Pharma, Inc.
Drug Status
Phase 1 (Terminated)
Indication
In total 1 Indication(s)
Acute myeloid leukaemia
Phase 1
Clinical Trial
Drug-to-Antibody Ratio
2
Structure
Antibody Name
A human IgG1 monoclonal antibody against FLT3
  Antibody Info 
Antigen Name
Receptor-type tyrosine-protein kinase FLT3 (FLT3)
  Antigen Info 
Payload Name
AGD-0182
  Payload Info 
Therapeutic Target
Microtubule (MT)
  Target Info 
Conjugate Type
Undisclosed
Puchem SID
472419727 , 404720331
ChEBI ID
CHEMBL4297893
General Information of The Activity Data Related to This ADC
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 4 Activity Data Related to This Level
Standard Type Value Units Cell Line Disease Model
Tumor Growth Inhibition value (TGI) 
27
%
THP-1 cells
Childhood acute monocytic leukemia
Tumor Growth Inhibition value (TGI) 
35.1
%
THP-1 cells
Childhood acute monocytic leukemia
Tumor Growth Inhibition value (TGI) 
38
%
THP-1 cells
Childhood acute monocytic leukemia
Tumor Growth Inhibition value (TGI) 
84
%
THP-1 cells
Childhood acute monocytic leukemia
Revealed Based on the Cell Line Data
Click To Hide/Show 1 Activity Data Related to This Level
Standard Type Value Units Cell Line Disease Model
Half Maximal Inhibitory Concentration (IC50) 
0.20-12.00
nM
Acute myeloid leukemia cells
Acute myeloid leukemia
Full List of Activity Data of This Antibody-drug Conjugate
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 4 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) 27.00% Positive FLT3 Expression (FLT3+++/++)
Method Description
The in vivo antitumor activity of ASP1235 was evaluated in a FLT3 positive THP-1 xenograft model. THP-1 cells were subcutaneously inoculated in the right frank of mice at 5 x106 cells/head. The vehicle of each drug is shown as follows: ASP1235 (20 mM Histidine/L-Histidine-HCl, 5.5% trehalose dihydrate, 0.01% Polysorbate 20, pH6.0), venetoclax (60% phosal 50PG, 30% PEG400, 10% ethanol), azacitidine (PBS). ASP1235 was intravenously administrated to each mouse once per week. One day before ASP1235 treatment, each mouse received intraperitoneal injection of 20 mg/kg of nonspecific human IgG1 antibody. Venetoclax was orally administered daily at 100 mg/kg. Azacitidine was intravenously injected at 3 mg/kg for five consecutive days in the first week of treatment.

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In Vivo Model FLT3-expressing THP-1 xenograft model
In Vitro Model Childhood acute monocytic leukemia THP-1 cells CVCL_0006
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) 35.10% Positive FLT3 Expression (FLT3+++/++)
Method Description
The in vivo antitumor activity of ASP1235 was evaluated in a FLT3 positive THP-1 xenograft model. THP-1 cells were subcutaneously inoculated in the right frank of mice at 5 x106 cells/head. The vehicle of each drug is shown as follows: ASP1235 (20 mM Histidine/L-Histidine-HCl, 5.5% trehalose dihydrate, 0.01% Polysorbate 20, pH6.0), venetoclax (60% phosal 50PG, 30% PEG400, 10% ethanol), azacitidine (PBS). ASP1235 was intravenously administrated to each mouse once per week. One day before ASP1235 treatment, each mouse received intraperitoneal injection of 20 mg/kg of nonspecific human IgG1 antibody. Venetoclax was orally administered daily at 100 mg/kg. Azacitidine was intravenously injected at 3 mg/kg for five consecutive days in the first week of treatment.

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In Vivo Model FLT3-expressing THP-1 xenograft model
In Vitro Model Childhood acute monocytic leukemia THP-1 cells CVCL_0006
Experiment 3 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) 38.00% Positive FLT3 Expression (FLT3+++/++)
Method Description
The in vivo antitumor activity of ASP1235 was evaluated in a FLT3 positive THP-1 xenograft model. THP-1 cells were subcutaneously inoculated in the right frank of mice at 5 x106 cells/head. The vehicle of each drug is shown as follows: ASP1235 (20 mM Histidine/L-Histidine-HCl, 5.5% trehalose dihydrate, 0.01% Polysorbate 20, pH6.0), venetoclax (60% phosal 50PG, 30% PEG400, 10% ethanol), azacitidine (PBS). ASP1235 was intravenously administrated to each mouse once per week. One day before ASP1235 treatment, each mouse received intraperitoneal injection of 20 mg/kg of nonspecific human IgG1 antibody. Venetoclax was orally administered daily at 100 mg/kg. Azacitidine was intravenously injected at 3 mg/kg for five consecutive days in the first week of treatment.

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In Vivo Model FLT3-expressing THP-1 xenograft model
In Vitro Model Childhood acute monocytic leukemia THP-1 cells CVCL_0006
Experiment 4 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) 84.00% Positive FLT3 Expression (FLT3+++/++)
Method Description
The in vivo antitumor activity of ASP1235 was evaluated in a FLT3 positive THP-1 xenograft model. THP-1 cells were subcutaneously inoculated in the right frank of mice at 5 x106 cells/head. The vehicle of each drug is shown as follows: ASP1235 (20 mM Histidine/L-Histidine-HCl, 5.5% trehalose dihydrate, 0.01% Polysorbate 20, pH6.0), venetoclax (60% phosal 50PG, 30% PEG400, 10% ethanol), azacitidine (PBS). ASP1235 was intravenously administrated to each mouse once per week. One day before ASP1235 treatment, each mouse received intraperitoneal injection of 20 mg/kg of nonspecific human IgG1 antibody. Venetoclax was orally administered daily at 100 mg/kg. Azacitidine was intravenously injected at 3 mg/kg for five consecutive days in the first week of treatment.

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In Vivo Model FLT3-expressing THP-1 xenograft model
In Vitro Model Childhood acute monocytic leukemia THP-1 cells CVCL_0006
Revealed Based on the Cell Line Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 0.20-12.00 nM Positive FLT3 Expression (FLT3+++/++)
Method Description
The cytotoxic activity of AGS-62P1 was evaluated against a panel of AmL cell lines in vitro.
In Vitro Model Acute myeloid leukemia Acute myeloid leukemia cells Homo sapiens
References
Ref 1 Anti-tumor effect of antibody drug conjugate ASP1235 targeting Fms-like tyrosine kinase 3 with venetoclax plus azacitidine in an acute myeloid leukemia xenograft mouse model. Oncotarget. 2022 Dec 20;13:1359-1368.
Ref 2 AGS62P1, a novel site-specific antibody drug conjugate targeting FLT3 exhibits potent anti-tumor activity regardless of FLT3 kinase activation status.