ADC TOXICITY ATLAS
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DMOT4039A

Investigational
anti-MSLN-vcMMAE
Sponsor
Genentech
Indication
MSLN+ solid tumors
Target family
GPI-anchored
RP2D dose
2.4 mg/kg
Q3WRP2D
01
Multi-organ toxicity

Fingerprint & organ drill-down

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

Ocular

Any-grade
0%
G3+
0%
RP2D
sagittal schematic · Unknown
↳

Tissues shaded by reported adverse-event rate.

Cornea
AE
-
Express.
13.34%
Limbus
AE
-
Express.
19.42%
Conjunctiva
AE
-
Express.
55.48%
Lens
AE
-
Express.
-
Retina / RPE
AE
-
Express.
-
0.6 nTPM
Dominant tissue
-
Surface subtype
None
Reversibility
Unknown
Reported ocular events
No granular adverse-event rows recorded for this system.
02
Construct

Molecular anatomy

Antibody
IgG1
Humanized
Linker
Cleavable
Cleavable
3.5
DAR
Payload
MMAE
Tubulin inhibitor
Linker structureC28H40N6O7
[H]OC([H])([H])c1c([H])c([H])c(N([H])C(=O)[C@@]([H])(N([H])C(=O)[C@@]([H])(N([H])C(=O)C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])N2C(=O)C([H])=C([H])C2=O)C([H])(C([H])([H])[H])C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])N([H])C(=O)N([H])[H])c([H])c1[H]
Payload structureC39H67N5O7
CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@@H]([C@@H](C)C(=O)N[C@H](C)[C@H](C2=CC=CC=C2)O)OC)OC)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC
03
Antibody

Antibody & Fc engineering

Antibody
anti-MSLN (DMOT4039A)
Isotype
IgG1
Origin
Humanized
Fc modifications
None
Glycoengineering
Standard
Effector silencing
None
FcγR binding
Retained
C1q binding
Retained
04
Linker & conjugation

Linker chemistry

Linker profile
Linker
MC-vc-PAB (vedotin)
Class
Cleavable
Cleavage
Cleavable
Attachment
Cysteine (interchain)
Conjugation
Conventional interchain Cys
Symmetry
Symmetric
DAR (mean)
3.5
DAR homogeneity
Heterogeneous
Plasma t½
5.0 d
Cleavage trigger
Cathepsin B (Val-Cit)
Release control
Conditional
Hydrophilicity mask
None
Formula
C28H40N6O7
Linker MW
572.663 Da
Linker TPSA
200.03 Ų
Linker xLogP
0.6769
ADCdb linker
LIN0SQEDQ
In-vitro stability
-
Stability note
Inherited from MC-vc-PAB conventional Cys class (Lyon 2014). Weekes MCT 2016 Ph1 N=71 mesothelin Q3W reports dose-proportional acMMAE and total Ab exposures but does not tabulate explicit clinical t½ in d in the open-access PDF
05
Payload

Payload & physicochemistry

Payload profile
Payload
MMAE
Class
Auristatin
Mechanism
Tubulin inhibitor
Released catabolite
MMAE (free/unconjugated monomethyl auristatin E)
Mechanistic subtype
Tubulin-auristatin
Stereochem / salt
-
Bystander
Yes
PAMPA rank
1
MW
718 Da
XLogP3
4.1
logD₇.₄
2.7
TPSA
150 Ų
pKa
9.1 pKa
Charge pH 7.4
+1
H-bond donors
4
H-bond acceptors
8
IC50 (HCEC)
-
Formula
C39H67N5O7
PubChem CID
11542188
ADCdb payload
PAY0FSXOW
Hydrophobicity · logD₇.₄
hydrophilic −2+2.7+4 lipophilic
06
Dosing & regimen

Dosing

RP2D dose
2.4 mg/kg
Schedule
Q3W
Route
IV
Fractionated
No
n at RP2D
71
Dose basis
TBW
Trial phase
Phase 1
Dose-OAE available
No
Tox summary basis
RP2D
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
Unknown
Reversibility
Unknown
Target expression in eye tissues (HCA detection · HPA bulk)
Cornea (central)
13.34 %
Cornea (limbal)
19.42 %
Conjunctiva
55.48 %
RPE
-
Retina (HPA)
0.6 nTPM
Cross-trial comparability
Ascertainment: Symptom-driven reportingScale: UnknownDenominator: RP2D⚠ OAE rate not directly comparable across trials
08
Identity & registry

Identifiers, registry & notes

ADC id
dmot4039a
Approval status
Investigational
Approval year
-
UniProt
Q13421
ADCdb ADC
DRG0FXFDD
ADCdb antibody
ANI0QVKDP
ADCdb target
TAR0NEZUA
Primary source
Weekes Mol Cancer Ther 2016 PMID 26823490
Aliases & development codes
anti-MSLN-vcMMAE
Notes
Same target as anetumab (DM4, 37% OAE); MMAE on MSLN → 0% OAE