ADC TOXICITY ATLAS
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MRG-004A

Investigational
MRG004A; MRG 004A
Sponsor
Shanghai Miracogen Inc. / Lepu Biopharma Co., Ltd.
Indication
TF-positive advanced/metastatic solid tumors (pancreatic cancer lead)
Target family
Other
RP2D dose
2.0 mg/kg
Q3W (Day 1 every 3 weeks)RP2D
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
27%
G3+
-
RP2D
sagittal schematic · -
↳

Tissues shaded by reported adverse-event rate.

Cornea
AE
-
Express.
8.16%
Limbus
AE
-
Express.
21.91%
Conjunctiva
AE
27%
Express.
66.36%
Lens
AE
-
Express.
-
Retina / RPE
AE
-
Express.
51.39%
67.1 nTPM
Dominant tissue
Conjunctiva
Surface subtype
Conjunctival (on-target)
Reversibility
-
Reported ocular events
Conjunctivitis27%
n=63
02
Construct

Molecular anatomy

Antibody
Linker
Cleavable
Cleavable
3.8
DAR
Payload
MMAE
Tubulin inhibitor
Linker structure
structure not applicable
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
-
Isotype
-
Origin
-
Fc modifications
-
Glycoengineering
-
Effector silencing
-
FcγR binding
Retained
C1q binding
Retained
04
Linker & conjugation

Linker chemistry

Linker
-
Class
Cleavable
Cleavage
Cleavable
Attachment
Site-specific (enzymatic/non-natural AA)
Conjugation
GlycoConnect site-specific (Synaffix; enzymatic Fc N297 glycan remodeling + metal-free click)
Symmetry
Site-specific (paired)
DAR (mean)
3.8
DAR homogeneity
Homogeneous
Plasma t½
-
Cleavage trigger
-
Release control
Conditional
Hydrophilicity mask
-
Formula
-
Linker MW
-
Linker TPSA
-
Linker xLogP
-
ADCdb linker
-
In-vitro stability
-
05
Payload

Payload & physicochemistry

Payload profile
Payload
MMAE
Class
Auristatin
Mechanism
Tubulin inhibitor
Released catabolite
-
Mechanistic subtype
Tubulin-auristatin
Stereochem / salt
-
Bystander
Yes
PAMPA rank
-
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
2.0 mg/kg
Schedule
Q3W (Day 1 every 3 weeks)
Route
IV
Fractionated
No
n at RP2D
63
Dose basis
TBW
Trial phase
Phase 1/2
Dose-OAE available
No
Tox summary basis
RP2D
07
Ocular & expression

Ocular profile & eye-tissue target expression

Target profile
OAE any-grade
27 %
OAE grade 3+
-
OAE data status
reported
Severity (weighted)
-
Keratopathy
-
Conjunctival
27 %
Dry eye
-
Blurred vision
-
Dominant tissue
Conjunctiva
Surface subtype
Conjunctival (on-target)
Grading scale
CTCAE v5
Reversibility
-
Target expression in eye tissues (HCA detection · HPA bulk)
Cornea (central)
8.16 %
Cornea (limbal)
21.91 %
Conjunctiva
66.36 %
RPE
51.39 %
Retina (HPA)
67.1 nTPM
Cross-trial comparability
Ascertainment: Monitoring unknownScale: CTCAE v5Denominator: RP2D⚠ OAE rate not directly comparable across trials
08
Identity & registry

Identifiers, registry & notes

ADC id
mrg-004a
Approval status
Investigational
Approval year
-
UniProt
P13726
ADCdb ADC
DRG0LCOWD
ADCdb antibody
-
ADCdb target
TAR0ZIMMG
Primary source
MRG004A FIH Ph1/2, ASCO 2024 (J Clin Oncol 2024;42(16_suppl):3002), NCT04843709
Aliases & development codes
MRG004A; MRG 004A
Notes
MRG-004A (Shanghai Miracogen / Lepu Biopharma): anti-tissue factor (F3/CD142) ADC, MMAE payload, DAR 3.8, GlycoConnect site-specific conjugation (Synaffix; enzymatic Fc N297 glycan remodeling + metal-free click). 3rd GlycoConnect ADC to enter the clinic. COMPOSITION GAPS: antibody name/isotype/origin not disclosed (ADCdb = 'Undisclosed'); isotype is almost certainly IgG1 and origin likely humanized given the GlycoConnect (Fc-glycan-dependent) Miracogen platform, but neither is stated -> left blank per convention. Linker NOT disclosed (ADCdb has no LIN entry) -> adcdb_linker_id and all linker physchem (SMILES/formula/MW/TPSA/xLogP) left blank; linker_class/linker_cleavage marked 'Cleavable (inferred)' from the membrane-permeable MMAE payload, NOT directly sourced. CLINICAL (ASCO 2024 FIH Ph1/2 abstract 3002; JCO 2024;42(16_suppl):3002; NCT04843709, study completed): 63 treated = 43 dose-escalation across 8 levels (0.3-2.6 mg/kg) + 20 expansion (15 at 2.0 mg/kg, 5 at 2.4 mg/kg); IV Q3W; MTD not reached; RP2D 2.0 mg/kg Q3W (per MSK/Wungki Park PRNewswire coverage). IMPORTANT: reported any-grade TRAEs are POOLED across ALL dose levels (n=63), not RP2D-specific -> n_rp2d set to the full safety population (63) so the percentages match their denominator; RP2D expansion cohort itself was n=15. TRAEs (any grade): conjunctivitis 27% (17/63, single most common; classified Conjunctival/on-target, TF+MMAE class cf. tisotumab vedotin), anemia 17% (11/63), hypoalbuminemia 13% (8/63 - no matching organ_system bucket so omitted from toxicity_rows). Serious AEs 7.9% (5/63). Only DLT = one Grade 3 Stevens-Johnson Syndrome at 1.8 mg/kg (severe cutaneous AE; resolved; no matching organ_system bucket, omitted from rows). Coverage notes a 'marked reduction in bleeding events' vs prior TF agents (no bleeding % given). NOT reported in the abstract (-> left blank, never 0): G3+ ocular, neutropenia, thrombocytopenia, GI, hepatic, pulmonary/ILD, peripheral neuropathy, infusion reactions, and ocular reversibility. CTCAE version not stated (v5.0 assumed for trial era). Efficacy context (not schema fields): pancreatic cancer ORR 33.3% (4/12) at 2.0 mg/kg, 80% (4/5) in high-TF subset; TNBC ORR 25% (1/4); cervical 1 PR + 1 SD of 2. Overall tier D (conference abstract); composition tier C (ADCdb); payload physchem tier C (standard MMAE).