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M-9140

Investigational
Precemtabart tocentecan; M9140; Precem-TcT
Sponsor
Merck KGaA / EMD Serono
Indication
Metastatic colorectal cancer (irinotecan-refractory)
Target family
Nectin / Ig-CAM
RP2D dose
2.4 and 2.8 mg/kg Q3W (recommended doses for expansion); MTD 2.8 mg/kg Q3W
Every 3 weeks (Q3W)Pooled
01
Multi-organ toxicity

Fingerprint & organ drill-down

Also reported
0%severity100%
0
Assessed · clear
true 0%
No data
never assessed
1 adverse-event term

Ocular

Any-grade
0%
G3+
0%
Pooled
sagittal schematic · -
↳

Tissues shaded by reported adverse-event rate.

Cornea
AE
-
Express.
0.03%
Limbus
AE
-
Express.
0.7%
Conjunctiva
AE
-
Express.
10.55%
Lens
AE
-
Express.
-
Retina / RPE
AE
-
Express.
0%
0 nTPM
Dominant tissue
-
Surface subtype
None
Reversibility
-
Reported ocular events
Any ocular toxicity (explicitly assessed and absent)0%
02
Construct

Molecular anatomy

Antibody
IgG1
Humanized
Linker
Peptide (glucuronide)
Cleavable
8
DAR
Payload
Exatecan
DNA topoisomerase I (TOP1) inhibitor
Linker structureC22H25N3O12
O=C(CCN1C(=O)C=CC1=O)NCC(=O)Nc1cc(CO)ccc1O[C@@H]1O[C@H](C(=O)O)[C@@H](O)[C@H](O)[C@@H]1O
Payload structureC24H22FN3O4
CC[C@@]1(C2=C(COC1=O)C(=O)N3CC4=C5[C@H](CCC6=C5C(=CC(=C6C)F)N=C4C3=C2)N)O
03
Antibody

Antibody & Fc engineering

Antibody
Undisclosed anti-CEACAM5 monoclonal antibody
Isotype
IgG1
Origin
Humanized
Fc modifications
Fc protein engineering to limit FcgammaR binding and prevent C1q interaction
Glycoengineering
-
Effector silencing
Fc engineered to limit FcgammaR binding and prevent C1q interaction (effector-attenuated)
FcγR binding
Retained
C1q binding
Unknown
04
Linker & conjugation

Linker chemistry

Linker profile
Linker
Mal-glucuronide-PABC (beta-glucuronide-exatecan)
Class
Peptide (glucuronide)
Cleavage
Cleavable
Attachment
Cysteine (interchain)
Conjugation
Random cysteine conjugation (reduced interchain disulfides)
Symmetry
Symmetric
DAR (mean)
8
DAR homogeneity
-
Plasma t½
-
Cleavage trigger
beta-glucuronidase (lysosomal)
Release control
Conditional
Hydrophilicity mask
Sugar
Formula
C22H25N3O12
Linker MW
523.451 Da
Linker TPSA
232.26 Ų
Linker xLogP
-3.1803
ADCdb linker
LIN0DIGYN
In-vitro stability
-
05
Payload

Payload & physicochemistry

Payload profile
Payload
Exatecan
Class
Topoisomerase I inhibitor
Mechanism
DNA topoisomerase I (TOP1) inhibitor
Released catabolite
Exatecan
Mechanistic subtype
TopoI
Stereochem / salt
-
Bystander
Yes
PAMPA rank
-
MW
435.5 Da
XLogP3
1.5
logD₇.₄
-
TPSA
91.7 Ų
pKa
-
Charge pH 7.4
0
H-bond donors
2
H-bond acceptors
7
IC50 (HCEC)
-
Formula
C24H22FN3O4
PubChem CID
151115
ADCdb payload
PAY0LEIGJ
06
Dosing & regimen

Dosing

RP2D dose
2.4 and 2.8 mg/kg Q3W (recommended doses for expansion); MTD 2.8 mg/kg Q3W
Schedule
Every 3 weeks (Q3W)
Route
IV
Fractionated
No
n at RP2D
40
Dose basis
TBW
Trial phase
Phase 1
Dose-OAE available
-
Tox summary basis
dose-escalation
07
Ocular & expression

Ocular profile & eye-tissue target expression

Target profile
OAE any-grade
0 %
OAE grade 3+
0 %
OAE data status
documented-absent
Severity (weighted)
0
Keratopathy
-
Conjunctival
-
Dry eye
-
Blurred vision
-
Dominant tissue
-
Surface subtype
None
Grading scale
CTCAE v5
Reversibility
-
Target expression in eye tissues (HCA detection · HPA bulk)
Cornea (central)
0.03 %
Cornea (limbal)
0.7 %
Conjunctiva
10.55 %
RPE
0 %
Retina (HPA)
0 nTPM
Cross-trial comparability · source-verified
Ascertainment: Systematic eye examsScale: CTCAE v5Denominator: RP2D
08
Identity & registry

Identifiers, registry & notes

ADC id
m-9140
Approval status
Investigational
Approval year
-
UniProt
P06731
ADCdb ADC
DRG0VIUMF
ADCdb antibody
-
ADCdb target
TAR0MKNCY
Primary source
Nature Medicine 2025;31:3504-3513 (PROCEADE-CRC-01 Ph1)
Aliases & development codes
Precemtabart tocentecan; M9140; Precem-TcT
Notes
M-9140 = precemtabart tocentecan (Precem-TcT; formerly M9140), an anti-CEACAM5 IgG1 ADC with a cleavable Mal-glucuronide-PABC (beta-glucuronide) linker, exatecan TOP1i payload, DAR 8, random-cysteine conjugation, and Fc engineering to limit FcgammaR binding/prevent C1q interaction. Sponsor Merck KGaA/EMD Serono. PROCEADE-CRC-01 phase 1 dose escalation (N=40, irinotecan-refractory mCRC, IV Q3W, dose levels 0.6-3.2 mg/kg); RDEs 2.4 and 2.8 mg/kg Q3W, MTD 2.8 mg/kg. 7/40 DLTs (febrile neutropenia, sepsis, neutrophil/platelet decreased, anemia), one treatment-related death (sepsis). Confirmed explicit-zero ocular: 'no cases of ILD or ocular toxicities were reported' / 'no interstitial lung disease or ocular toxicity' (abstract, Safety Overview, Discussion). Safety is heme-dominant. Grade>=3 TRAE percentages from Nature Medicine Table 3 (these supersede the lower escalation-cohort hint numbers in the working-input file). Exact any-grade % for the heme PTs were not isolated in the fetched table (only grade>=3 given as Table 3 counts), so any-grade heme rows omitted rather than approximated; GI rows are any-grade. Payload physchem are standard PubChem exatecan values (CID 9938202); logD7.4 and pKa not populated to avoid imputation. Linker physchem from ADCdb LIN0DIGYN.