ADC TOXICITY ATLAS
AtlasPayloads and LinkersPayloadsTargetsMethods
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MEN-1309 (OBT076)

Investigational
MEN-1309; MEN1309; OBT076; OBT-076
Sponsor
Menarini Ricerche / Oxford BioTherapeutics
Indication
CD205-positive advanced solid tumors
Target family
Other
RP2D dose
3.0 mg/kg
Q3W (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
2 adverse-event terms

Ocular

Any-grade
5.9%
G3+
0%
RP2D
sagittal schematic · -
↳

Tissues shaded by reported adverse-event rate.

Cornea
AE
-
Express.
-
Limbus
AE
-
Express.
-
Conjunctiva
AE
-
Express.
-
Lens
AE
-
Express.
-
Retina / RPE
AE
-
Express.
-
Dominant tissue
Retina
Surface subtype
Visual
Reversibility
-
Reported ocular events
Eye disorders (treatment-related), incl. retinal pigment epitheliopathy5.9%
n=3
Retinal pigment epitheliopathy-
n=1
02
Construct

Molecular anatomy

Antibody
Humanized
Linker
Disulfide
Cleavable
3.7
DAR
Payload
DM4 (ravtansine)
Microtubule inhibitor (tubulin polymerization inhibitor)
Linker structureC13H14N2O4S2
[H]c1nc(SSC([H])([H])C([H])([H])C([H])([H])C(=O)ON2C(=O)C([H])([H])C([H])([H])C2=O)c([H])c([H])c1[H]
Payload structureC38H54ClN3O10S
C[C@@H]1[C@@H]2C[C@]([C@@H](/C=C/C=C(/CC3=CC(=C(C(=C3)OC)Cl)N(C(=O)C[C@@H]([C@]4([C@H]1O4)C)OC(=O)[C@H](C)N(C)C(=O)CCC(C)(C)S)C)\C)OC)(NC(=O)O2)O
03
Antibody

Antibody & Fc engineering

Antibody
MBH-1309 (humanized anti-CD205 monoclonal antibody)
Isotype
-
Origin
Humanized
Fc modifications
-
Glycoengineering
-
Effector silencing
-
FcγR binding
Retained
C1q binding
Retained
04
Linker & conjugation

Linker chemistry

Linker profile
Linker
SPDB (N-succinimidyl 4-(2-pyridyldithio)butanoate)
Class
Disulfide
Cleavage
Cleavable
Attachment
Lysine
Conjugation
Random lysine conjugation
Symmetry
Symmetric
DAR (mean)
3.7
DAR homogeneity
Heterogeneous
Plasma t½
-
Cleavage trigger
Intracellular reductive cleavage of the disulfide (SPDB) bond
Release control
N/A
Hydrophilicity mask
None
Formula
C13H14N2O4S2
Linker MW
326.399 Da
Linker TPSA
76.57 Ų
Linker xLogP
2.2093
ADCdb linker
LIN0VZYER
In-vitro stability
-
05
Payload

Payload & physicochemistry

Payload profile
Payload
DM4 (ravtansine)
Class
Maytansinoid
Mechanism
Microtubule inhibitor (tubulin polymerization inhibitor)
Released catabolite
Lysine-SPDB-DM4 / DM4 (S-methyl-DM4 after intracellular reduction and methylation)
Mechanistic subtype
Tubulin-maytansinoid
Stereochem / salt
-
Bystander
Yes
PAMPA rank
-
MW
794.4 Da
XLogP3
3.6
logD₇.₄
-
TPSA
157 Ų
pKa
-
Charge pH 7.4
0
H-bond donors
3
H-bond acceptors
11
IC50 (HCEC)
-
Formula
C38H54ClN3O10S
PubChem CID
11686439
ADCdb payload
PAY0GTSVM
Bioactivity note
ADCdb in vitro IC50: mantle cell lymphoma 100 pM, marginal zone lymphoma 110 pM, DLBCL 200 pM. EC50: HPAF-II (pancreatic) 0.10 nM, SW780 (bladder) 0.26 nM (range up to 36.23 nM in HT-1197). In vivo PDX tumor growth inhibition up to 98.9% (pancreatic HPAFII model). Source: ADCdb D
06
Dosing & regimen

Dosing

RP2D dose
3.0 mg/kg
Schedule
Q3W (every 3 weeks)
Route
IV
Fractionated
No
n at RP2D
51
Dose basis
TBW
Trial phase
Phase 1
Dose-OAE available
Yes
Tox summary basis
RP2D
07
Ocular & expression

Ocular profile & eye-tissue target expression

Target profile
OAE any-grade
5.9 %
OAE grade 3+
0 %
OAE data status
reported
Severity (weighted)
1.77
Keratopathy
-
Conjunctival
-
Dry eye
-
Blurred vision
-
Dominant tissue
Retina
Surface subtype
Visual
Grading scale
CTCAE v5
Reversibility
-
Target expression in eye tissues (HCA detection · HPA bulk)
Cornea (central)
-
Cornea (limbal)
-
Conjunctiva
-
RPE
-
Retina (HPA)
-
Cross-trial comparability
Ascertainment: Partial / unspecified monitoringScale: CTCAE v5Denominator: RP2D
08
Identity & registry

Identifiers, registry & notes

ADC id
men-1309
Approval status
Investigational
Approval year
-
UniProt
O60449
ADCdb ADC
DRG0RARRJ
ADCdb antibody
ANI0ZITFA
ADCdb target
TAR0BVXLX
Primary source
AACR 2025 Abstract CT044 (Cancer Res 2025;85(8_Suppl_2):CT044), OBT076 Phase 1b Part B expansion
Aliases & development codes
MEN-1309; MEN1309; OBT076; OBT-076
Notes
Anti-CD205/LY75 (DEC-205) maytansinoid (DM4) ADC; first-in-class. Two clinical data sources: (1) SHUTTLE Phase 1 dose-escalation (NCT03403725, n=28; posted CT.gov results, accrued 2017-2020) which shows NO eye-disorder SOC entries (heme/GI/febrile-neutropenia dominant), and (2) AACR 2025 Phase 1b Part B expansion at 3.0 mg/kg IV Q3W (n=51) which IS where the ocular signal appears: three treatment-related eye-disorder events (max Grade 2), including 1 patient with Grade 2 retinal pigment epitheliopathy. Triage anchored oae_any_pct=5.9 (single retinal-pigment-epitheliopathy PT among ~51 evaluable = 1/51 = 1.96% per PT; the 5.9% appears to be the eye-disorder SOC rate = 3 events/51 = 5.9%; retained as triage-reported max-across-PT value). Ocular subtype classified Visual (retinal pigment epitheliopathy is a posterior-segment/retinal finding, not corneal/conjunctival surface). DM4 ADCs are not classically corneal-tropic (unlike MMAF/mafodotin), consistent with a retinal rather than ocular-surface presentation. RP2D/primary cohort = 3.0 mg/kg Q3W (Part B). DAR 3.7 from ADCdb (random-lysine SPDB conjugation). Antibody isotype not explicitly stated in ADCdb (MBH-1309); preclinical lit describes a fully humanized anti-CD205 mAb (IgG1 by class) — left conservative. Reversibility of ocular events not explicitly stated in the abstract. Toxicity rows for the RP2D cohort (Part B, n=51) use abstract-reported any-grade rates: neutropenia 41%, anemia 41%, fatigue 39%, febrile neutropenia 39%; grade splits not broken out in the abstract snippet, so logged as Any with febrile neutropenia additionally as a serious/G3+ class event by clinical convention but kept as Any to avoid over-claiming grade.