Antibody-drug Conjugate Information
General Information of This Antibody-drug Conjugate (ADC)
| ADC ID |
DRG0KGBYK
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| ADC Name |
wO2025019776A2ADC 33-2
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| Synonyms |
WO2025019776A2ADC 33-2
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| Organization |
EXELIXIS, INC.
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| Drug Status |
Investigative
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| Drug-to-Antibody Ratio |
2
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| Structure |
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| Antibody Name |
A33
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Antibody Info | ||||
| Antigen Name |
Interleukin-13 receptor subunit alpha-2 (IL13RA2)
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Antigen Info | ||||
| Payload Name |
Monomethyl auristatin E
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Payload Info | ||||
| Therapeutic Target |
Microtubule (MT)
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Target Info | ||||
| Linker Name |
WO2025019776A2, ADC 22-2, Linker
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Linker Info | ||||
| Conjugate Type |
Random conjugation through nucleophilic lysines
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| Combination Type |
Vb-82a
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General Information of The ADMET Data Related to This ADC(2027 Update)
Absorption
| Standard Type | Value | Units | Description | Reference |
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| Area Under the Concentration-Time Curve (AUC) | ≈5000000 | hr*ng/mL |
Male JVC/FVC cannulated Sprague-Dawley rats (5 per group)were dosed intravenously with a single dose of 5mg/kg of the tested ADC on Day 1 after 16 hours of fasting.100uL K2EDTA plasma was collected at 30 min,4h,24h (on Day 2),168h (on Day 8),240h (on Day 11),336h (on Day 15),and 504h (on Day 22)post-dose,saved in bullet tubes and stored at -22°C until end of the study.
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Distribution
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | ≈5000000 | hr*ng/mL |
Male JVC/FVC cannulated Sprague-Dawley rats (5 per group)were dosed intravenously with a single dose of 5mg/kg of the tested ADC on Day 1 after 16 hours of fasting.100uL K2EDTA plasma was collected at 30 min,4h,24h (on Day 2),168h (on Day 8),240h (on Day 11),336h (on Day 15),and 504h (on Day 22)post-dose,saved in bullet tubes and stored at -22°C until end of the study.
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Metabolism
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | ≈5000000 | hr*ng/mL |
Male JVC/FVC cannulated Sprague-Dawley rats (5 per group)were dosed intravenously with a single dose of 5mg/kg of the tested ADC on Day 1 after 16 hours of fasting.100uL K2EDTA plasma was collected at 30 min,4h,24h (on Day 2),168h (on Day 8),240h (on Day 11),336h (on Day 15),and 504h (on Day 22)post-dose,saved in bullet tubes and stored at -22°C until end of the study.
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Excretion
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | ≈5000000 | hr*ng/mL |
Male JVC/FVC cannulated Sprague-Dawley rats (5 per group)were dosed intravenously with a single dose of 5mg/kg of the tested ADC on Day 1 after 16 hours of fasting.100uL K2EDTA plasma was collected at 30 min,4h,24h (on Day 2),168h (on Day 8),240h (on Day 11),336h (on Day 15),and 504h (on Day 22)post-dose,saved in bullet tubes and stored at -22°C until end of the study.
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[1] |
| Clearance (CL) | ≈0.9 | mL/hr/kg |
Male JVC/FVC cannulated Sprague-Dawley rats (5 per group)were dosed intravenously with a single dose of 5mg/kg of the tested ADC on Day 1 after 16 hours of fasting.100uL K2EDTA plasma was collected at 30 min,4h,24h (on Day 2),168h (on Day 8),240h (on Day 11),336h (on Day 15),and 504h (on Day 22)post-dose,saved in bullet tubes and stored at -25°C until end of the study.
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| Elimination Half-Life (t1/2) | ≈110 | hr |
Male JVC/FVC cannulated Sprague-Dawley rats (5 per group)were dosed intravenously with a single dose of 5mg/kg of the tested ADC on Day 1 after 16 hours of fasting.100uL K2EDTA plasma was collected at 30 min,4h,24h (on Day 2),168h (on Day 8),240h (on Day 11),336h (on Day 15),and 504h (on Day 22)post-dose,saved in bullet tubes and stored at -25°C until end of the study.
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General Information of The Activity Data Related to This ADC
Discovered Using Cell Line-derived Xenograft Model
Revealed Based on the Cell Line Data
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) | 37.50% | Positive IL13Ra2 expression (IL13Ra2+++/++) | ||
| Method Description |
Each female BALB/c Nude mouse was inoculated subcutaneously in the right upper flank region with 0.5x10 6of SK-MES-1 tumor cells (a non-small cell lung cancer (NSCLC)cell line having an IL13Ra2 copy number of about 4x104)in 0.1 mL of PBS for tumor development.When the mean tumor size reached about 80-150 mm 3,mice were randomized into respective treatment groups (8 mice per group)and received intravenous injections of PBS vehicle or a single dose of the tested ADC 33-2 at 1 mg/kg on Day 1. The end of the study was day 44.
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| In Vivo Model | CDX Model-SK-MES-1 | ||||
| Experiment 2 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth lnhibition value (TGl) | 55% | Positive IL13Ra2 expression (IL13Ra2+++/++) | ||
| Method Description |
Each female BALB/c Nude mouse was inoculated subcutaneously in the right upper flank region with 0.5x10 6of SK-MES-1 tumor cells (a non-small cell lung cancer (NSCLC)cell line having an IL13Ra2 copy number of about 4x104)in 0.1 mL of PBS for tumor development.When the mean tumor size reached about 80-150 mm 3,mice were randomized into respective treatment groups (8 mice per group)and received intravenous injections of PBS vehicle or a single dose of the tested ADC 33-2 at 3 mg/kg on Day 1. The end of the study was day 44.
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| In Vivo Model | CDX Model-SK-MES-1 | ||||
| Experiment 3 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth lnhibition value (TGl) | 82.20% | Positive IL13Ra2 expression (IL13Ra2+++/++) | ||
| Method Description |
Each female BALB/c Nude mouse was inoculated subcutaneously in the right upper flank region with 0.5x10 6of SK-MES-1 tumor cells (a non-small cell lung cancer (NSCLC)cell line having an IL13Ra2 copy number of about 4x104)in 0.1 mL of PBS for tumor development.When the mean tumor size reached about 80-150 mm 3,mice were randomized into respective treatment groups (8 mice per group)and received intravenous injections of PBS vehicle or a single dose of the tested ADC 33-2 at 6 mg/kg on Day 1. The end of the study was day 44.
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| In Vivo Model | CDX Model-SK-MES-1 | ||||
| Experiment 4 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth lnhibition value (TGl) | 88.60% | Positive IL13Ra2 expression (IL13Ra2+++/++) | ||
| Method Description |
Each female BALB/c Nude mouse was inoculated subcutaneously in the right upper/lower flank region with 1x10 7of H2228 tumor cells (an NSCLC cell line having an IL13Ra2 copy number of about 2,000)in 0.1 mL of PBS mixed with MATRIGELR (1:1)for tumor development.When the mean tumor size reached about 80-150 mm 3,mice were randomized into respective treatment groups (10 mice per group)and received intravenous injections of vehicle or a single dose of the tested ADCs at 10 mg/kg on Day 1. Body weights and tumor volumes were measured twice per week until the end of the study (Day 48).
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| In Vivo Model | CDX Model-H2228 | ||||
| Experiment 5 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth lnhibition value (TGl) | 100% | Positive IL13Ra2 expression (IL13Ra2+++/++) | ||
| Method Description |
Each female BALB/c Nude mouse was inoculated subcutaneously in the right upper flank region with 0.5x10 6of SK-MES-1 tumor cells (a non-small cell lung cancer (NSCLC)cell line having an IL13Ra2 copy number of about 4x104)in 0.1 mL of PBS for tumor development.When the mean tumor size reached about 80-150 mm 3,mice were randomized into respective treatment groups (8 mice per group)and received intravenous injections of PBS vehicle or a single dose of the tested ADC 33-2 at 10 mg/kg on Day 1. The end of the study was day 44.
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| In Vivo Model | CDX Model-SK-MES-1 | ||||
| Experiment 6 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth lnhibition value (TGl) | 101.10% | Positive IL13Ra2 expression (IL13Ra2+++/++) | ||
| Method Description |
Each female BALB/c Nude mouse was inoculated subcutaneously in the right upper flank region with 0.5x10 6of SK-MES-1 tumor cells (a non-small cell lung cancer (NSCLC)cell line having an IL13Ra2 copy number of about 4x104)in 0.1 mL of PBS for tumor development.When the mean tumor size reached about 80-150 mm 3,mice were randomized into respective treatment groups (10 mice per group)and received intravenous injections of PBS vehicle or a single dose of the tested ADCs at 10 mg/kg on Day 1. The end of the study was day 49.
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| In Vivo Model | CDX Model-SK-MES-1 | ||||
| Experiment 7 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth lnhibition value (TGl) | 111% | Positive IL13Ra2 expression (IL13Ra2+++/++) | ||
| Method Description |
Each female NOD.Cg-Prkdcscid II2rgmIVst/Vst (NPG)mouse was inoculated subcutaneously in the right upper flank region with 1x10 7of H1792 tumor cells (an NSCLC cell line having an IL13Ra2 copy number of about 47000)in 0.1 mL of PBS mixed with MATRIGELR (1:1)for tumor development.When the mean tumor size reached about 80-150 mm 3,mice were randomized into respective treatment groups (10 mice per group)and received intravenous injections of vehicle or a single dose of the tested ADCs at 10 mg/kg on Day 1. Body weights and tumor volumes were measured twice per week until the end of the study (Day 57).
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| In Vivo Model | CDX Model-H1792 | ||||
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) | 0.01 nM | High hIL13Ra2 expression (hIL13Ra2 +++) | ||
| Method Description |
The cytotoxic activity of ADC 33-2 was determined against cancer cell lines A375.FITC and anti-Hen egg-white lysozyme isotype control antibody (HEWL)conjugated to the same linker payloads.
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| In Vitro Model | Amelanotic melanoma | A375 cells | CVCL_0132 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) | 0.02-0.03 nM | Positive hIL13Ra2 expression (hIL13Ra2+++/++) | ||
| Method Description |
The cytotoxic activity of ADC 33-2 was determined against cancer cell lines H1792.FITC and anti-Hen egg-white lysozyme isotype control antibody (HEWL)conjugated to the same linker payloads.
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| In Vitro Model | Lung adenocarcinoma | H1792 cells | CVCL_1495 | ||
| Experiment 3 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) | 0.04-0.08 nM | Positive hIL13Ra2 expression (hIL13Ra2+++/++) | ||
| Method Description |
The cytotoxic activity of ADC 33-2 was determined against cancer cell lines H2228.FITC and anti-Hen egg-white lysozyme isotype control antibody (HEWL)conjugated to the same linker payloads.
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| In Vitro Model | Lung adenocarcinoma | H2228 cells | CVCL_1543 | ||
| Experiment 4 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) | 3-63 nM | Positive hIL13Ra2 expression (hIL13Ra2+++/++) | ||
| Method Description |
The cytotoxic activity of ADC 33-2 was determined against cancer cell lines SK-MES-1.FITC and anti-Hen egg-white lysozyme isotype control antibody (HEWL)conjugated to the same linker payloads.
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| In Vitro Model | Lung squamous cell carcinoma | SK-MES-1 cells | CVCL_0630 | ||