Linker Information

General Information of This Linker
Linker ID
LIN0NKIHY
Linker Name
Stable cleavable peptide linker
Linker Type
Cathepsin-cleavable linker
Antibody-Linker Relation
Cleavable
Structure
Formula
C21H32N4O9S
Isosmiles
O=C(O)[C@@H](NC([C@H](NC([C@@H](NC(CCCSC1CC(N(C1=O)CCCC(O)=O)=O)=O)C)=O)C)=O)C
InChI
InChI=1S/C21H32N4O9S/c1-11(18(30)23-12(2)19(31)24-13(3)21(33)34)22-15(26)6-5-9-35-14-10-16(27)25(20(14)32)8-4-7-17(28)29/h11-14H,4-10H2,1-3H3,(H,22,26)(H,23,30)(H,24,31)(H,28,29)(H,33,34)/t11-,12+,13-,14?/m0/s1
InChIKey
USLOMACHKOSHSN-WJLOJVBCSA-N
Pharmaceutical Properties
Molecule Weight
516.573
Polar area
199.28
Complexity
799.8949464
xlogp Value
-0.9092
Heavy Count
35
Rot Bonds
15
Hbond acc
8
Hbond Donor
5
Each Antibody-drug Conjugate Related to This Linker
Full Information of The Activity Data of The ADC(s) Related to This Linker
Opugotamig olatansine [Phase 2]
 ADC Info 
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)
100%
Low FOLR1 expression (FOLR1+; IHC H-score=30)
Method Description
IMGN151 activity was characterized against cell lines and xenograft models with a wide range of FR expression and compared to IMGN853.
In Vivo Model OV-90 CDX model
In Vitro Model Ovarian adenocarcinoma OV-90 cells CVCL_3768
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI)
100%
Moderate FOLR1 expression (FOLR1++; IHC H-score=100)
Method Description
IMGN151 activity was characterized against cell lines and xenograft models with a wide range of FR expression and compared to IMGN853.
In Vivo Model Ishikawa CDX model
In Vitro Model Endometrial adenocarcinoma Ishikawa cells CVCL_2529
Experiment 3 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI)
100%
Moderate FOLR1 expression (FOLR1++; IHC H-score=140)
Method Description
IMGN151 activity was characterized against cell lines and xenograft models with a wide range of FR expression and compared to IMGN853.
In Vivo Model IGROV-1 CDX model
In Vitro Model Ovarian endometrioid adenocarcinoma IGROV-1 cells CVCL_1304
Experiment 4 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI)
100%
High FOLR1 expression (FOLR1+++; IHC H-score=300)
Method Description
IMGN151 activity was characterized against cell lines and xenograft models with a wide range of FR expression and compared to IMGN853.
In Vivo Model KB CDX model
In Vitro Model Human papillomavirus-related endocervical adenocarcinoma KB cells CVCL_0372
Identified from the Human Clinical Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [2]
Patients Enrolled
Inclusion Criteria: ECOG PS 0-1, histologically confirmed recurrent/metastatic gynecologic cancers (specific requirements per cohort including prior therapy limits). Measureable disease by RECIST v1.1 (optimization/expansion phases), willingness to provide tumor tissue, recovery from prior toxicities (≤Grade 1), adequate organ function. Exclusion Criteria: Certain histologic subtypes, primary platinum-refractory disease (cohort B), >Grade 1 peripheral neuropathy, active ocular disorders, uncontrolled cardiac disease, CNS metastases, prior FRalpha-targeting agents (except cohort C), other malignancies within 3 years, pregnancy/lactation.

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Administration Dosage
IMGN151 is administered via intravenous (IV) infusion on Day 1 of Cycle 1 every 3-week cycle (Q3W).
Related Clinical Trial
NCT Number NCT05527184  Clinical Status PHASE1
Clinical Description
A Phase 1, First-in-Human, Open-Label, Dose-Escalation and Expansion Study of IMGN151 (Anti-FRalpha Antibody-drug Conjugate) in Adult Patients With Recurrent Gynaecological Cancers
Primary Endpoint
The study evaluates safety and tolerability of IMGN151 monotherapy through adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs) within the first cycle (21 days). The recommended dose is determined over approximately 2 years.
Other Endpoint
Pharmacokinetics (PK) of IMGN151 are assessed via maximum plasma concentration (Cmax), time to Cmax (Tmax), and area under the curve (AUC0-inf). Immunogenicity is measured through anti-drug antibodies (ADAs). Efficacy endpoints include objective response rate (ORR) and duration of response (DOR) per RECIST v1.1, evaluated over approximately 3 years.

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References
Ref 1 IMGN151-A next generation folate receptor alpha targeting antibody drug conjugate active against tumors with low, medium and high receptor expression. Cancer Res (2020) 80 (16_Supplement): 2890.
Ref 2 First in Human Study of IMGN151 in Recurrent Gynaecological Cancers