Antibody-drug Conjugate Information
General Information of This Antibody-drug Conjugate (ADC)
| ADC ID |
DRG0IZKGD
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| ADC Name |
wO2025019776A2ADC-13
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| Synonyms |
WO2025019776A2ADC-13
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| Organization |
EXELIXIS, INC.
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| Drug Status |
Investigative
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| Drug-to-Antibody Ratio |
8
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| Structure |
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| Antibody Name |
M2
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Antibody Info | ||||
| Antigen Name |
Inactive tyrosine-protein kinase transmembrane receptor ROR1 (ROR1); Tyrosine-protein kinase transmembrane receptor ROR2 (ROR2)
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Antigen Info | ||||
| Payload Name |
Belotecan
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Payload Info | ||||
| Therapeutic Target |
DNA topoisomerase 1 (TOP1)
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Target Info | ||||
| Linker Name |
Undisclosed
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| Conjugate Type |
Random conjugation through reduced inter-chain cysteines.
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| Combination Type |
IIa
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ADC-specific functional property(2027 Update)
Binding Affinity
| Dissocation Constant (Kd) | Binding Target | Description | Reference |
|---|---|---|---|
| 10.66 nM |
ROR1-Fc
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ELISA was performed to evaluate the binding affinities to ROR1 of ADC-13 with MMP-9 activation.
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[1]
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| 0.836 nM |
ROR1-Fc
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ELISA was performed to evaluate the binding affinities to ROR1 without MMP-9 activation.
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[1]
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| 4.083 nM |
ROR2-His
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ELISA was performed to evaluate the binding affinities to ROR2 of ADC-13 with MMP-9 activation.
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[1]
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| 0.359 nM |
ROR2-His
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ELISA was performed to evaluate the binding affinities to ROR2 without MMP-9 activation.
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[1]
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General Information of The ADMET Data Related to This ADC(2027 Update)
Absorption
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Maximum Observed Concentration (Cmax) | 88.9 | ug/mL |
Sprague-Dawley rats were dosed intravenously with a single dose of 5mg/kg of the tested ADCs on Day 0 after 16 hours of fasting.The rats'body weights were taken on Day- 3.Day 0,Day 7,Day 14,and Day 21.100 uL plasma was collected at 30 min (on Day 0),6h (on Day 0),24h (on Day 1),48h (on Day 2),Day 4,Day 7,Day 10,and Day 14,saved in bullet tubes with K2EDTA and stored at-20°C until end of the study.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 355 | day xug/mL |
Sprague-Dawley rats were dosed intravenously with a single dose of 5mg/kg of the tested ADCs on Day 0 after 16 hours of fasting.The rats'body weights were taken on Day- 3.Day 0,Day 7,Day 14,and Day 21.100 uL plasma was collected at 30 min (on Day 0),6h (on Day 0),24h (on Day 1),48h (on Day 2),Day 4,Day 7,Day 10,and Day 14,saved in bullet tubes with K2EDTA and stored at-20°C until end of the study.
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[1] |
Distribution
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 355 | day xug/mL |
Sprague-Dawley rats were dosed intravenously with a single dose of 5mg/kg of the tested ADCs on Day 0 after 16 hours of fasting.The rats'body weights were taken on Day- 3.Day 0,Day 7,Day 14,and Day 21.100 uL plasma was collected at 30 min (on Day 0),6h (on Day 0),24h (on Day 1),48h (on Day 2),Day 4,Day 7,Day 10,and Day 14,saved in bullet tubes with K2EDTA and stored at-20°C until end of the study.
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[1] |
Metabolism
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 355 | day xug/mL |
Sprague-Dawley rats were dosed intravenously with a single dose of 5mg/kg of the tested ADCs on Day 0 after 16 hours of fasting.The rats'body weights were taken on Day- 3.Day 0,Day 7,Day 14,and Day 21.100 uL plasma was collected at 30 min (on Day 0),6h (on Day 0),24h (on Day 1),48h (on Day 2),Day 4,Day 7,Day 10,and Day 14,saved in bullet tubes with K2EDTA and stored at-20°C until end of the study.
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[1] |
Excretion
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 355 | day xug/mL |
Sprague-Dawley rats were dosed intravenously with a single dose of 5mg/kg of the tested ADCs on Day 0 after 16 hours of fasting.The rats'body weights were taken on Day- 3.Day 0,Day 7,Day 14,and Day 21.100 uL plasma was collected at 30 min (on Day 0),6h (on Day 0),24h (on Day 1),48h (on Day 2),Day 4,Day 7,Day 10,and Day 14,saved in bullet tubes with K2EDTA and stored at-20°C until end of the study.
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[1] |
| Clearance (CL) | 14.2 | mL/day/kg |
Sprague-Dawley rats were dosed intravenously with a single dose of 5mg/kg of the tested ADCs on Day 0 after 16 hours of fasting.The rats'body weights were taken on Day- 3.Day 0,Day 7,Day 14,and Day 21.100 uL plasma was collected at 30 min (on Day 0),6h (on Day 0),24h (on Day 1),48h (on Day 2),Day 4,Day 7,Day 10,and Day 14,saved in bullet tubes with K2EDTA and stored at-20°C until end of the study.
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[1] |
| Elimination Half-Life (t1/2) | 5.96 | day |
Sprague-Dawley rats were dosed intravenously with a single dose of 5mg/kg of the tested ADCs on Day 0 after 16 hours of fasting.The rats'body weights were taken on Day- 3.Day 0,Day 7,Day 14,and Day 21.100 uL plasma was collected at 30 min (on Day 0),6h (on Day 0),24h (on Day 1),48h (on Day 2),Day 4,Day 7,Day 10,and Day 14,saved in bullet tubes with K2EDTA and stored at-20°C until end of the study.
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[1] |
General Information of The Activity Data Related to This ADC
Discovered Using Cell Line-derived Xenograft Model
| Standard Type | Value | Units | Cell Line | Disease Model |
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| Tumor Growth lnhibition value (TGl) |
> 50
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%
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Undisclosed | Undisclosed |
| Tumor Growth lnhibition value (TGl) |
> 60
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%
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Undisclosed | Undisclosed |
Revealed Based on the Cell Line Data
| Standard Type | Value | Units | Cell Line | Disease Model |
|---|---|---|---|---|
| Half Maximal inhibitory Concentration (lC50) |
0.1-1
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nM
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CVCL_M624
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Endocervical adenocarcinoma
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Full List of Activity Data of This Antibody-drug Conjugate
Discovered Using Cell Line-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth lnhibition value (TGl) | > 50% | Positive ROR1 expression (ROR1+++/++) | ||
| Method Description |
CB.17 female SCID mice were inoculated subcutaneously in the right up flank region with Jeko-1 tumor cells (5×10 6)in 0.1 mL of PBS with Matrigel (1:1)for tumor development.When the tumor volumes reached about 150~250 mm 3on Day 1,mice were randomized into respective treatment groups (8 mice per group).The mice then received intravenous injections of vehicle or the tested ADC-13 at 7.5mg/kg on Day 1 and Day 8.PBS vehicle was tested in parallel,serving as a control.
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| In Vivo Model | JEKO-1 MCL Xenograft Model | ||||
| Experiment 2 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth lnhibition value (TGl) | > 60% | Positive ROR1 expression (ROR1+++/++) | ||
| Method Description |
CB.17 female SCID mice were implanted (flank)with 1.0x10 7of MDA-MB-231 tumor cells in 50%MATRIGELR (Corning Life Sciences)matrix (1:1 cell to Matrigel) on Day -13.When the average tumor volume reached about 200 mm 3on Day 1,mice were randomized into respective treatment groups (10 mice per group).The mice then received intravenous injections of the tested ADC-13 at 7.5 mg/kg on Day 1 and Day 8.PBS vehicle was tested in parallel,serving as a control.Body weight and tumor volume were measured twice per week.The study was ended on Day 45.
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| In Vivo Model | MDA-MB-231 TNBC Xenograft Model | ||||
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) | 0.1-1 nM | Positive ROR1 expression (ROR1+++/++) | ||
| Method Description |
In vitro cytotoxicity of the ADC-00 was assessed on hROR1 expressing HEK cells with a top concentration of 10 nM, and ADC-00 was serially diluted 1:4, The treated cells were incubated for 5 days.The cell viability reading was taken. In order to activate the masked ADCs,an enzyme digestion system MMP9 was added.
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| In Vitro Model | Endocervical adenocarcinoma | HEK cells | CVCL_M624 | ||
References