Anetumab ravtansine

Discontinued

BAY 94-9343

Target

Mesothelin · MSLN

Sponsor

Bayer

Indication

MSLN+ mesothelioma

Target family

GPI-anchored

RP2D dose

6.5 mg/kg

Q3WRP2D

Multi-organ toxicity

Fingerprint & organ drill-down

Also reported

0%severity100%

Assessed · clear

true 0%

No data

never assessed

4 adverse-event terms

Ocular

Any-grade

37%

G3+

RP2D

sagittal schematic · Reversible

↳

Tissues shaded by reported adverse-event rate.

Cornea

37%

Express.

13.34%

Limbus

Express.

19.42%

Conjunctiva

Express.

55.48%

Lens

Express.

Retina / RPE

Express.

0.6 nTPM

Off-target signature

37% corneal toxicity, yet the Mesothelin target is detected in only 13.34% of central cornea - toxicity is not explained by target expression.

Dominant tissue

Cornea

Surface subtype

Corneal (off-target)

Reversibility

Reversible

Reported ocular events

Keratitis29%

G3+ 5%n=38

Vision blurred29%

G3+ 3%n=38

Dry eye21%

G3+ 0%n=38

Keratitis/keratopathy (Grade 4)-

Construct

Molecular anatomy

Antibody

IgG1

Human

Linker

Cleavable

3.2

DAR

Payload

DM4 (free)

Tubulin 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

Antibody

Antibody & Fc engineering

Antibody

MF-T (anetumab)

Isotype

IgG1

Origin

Human

Fc modifications

None

Glycoengineering

Standard

Effector silencing

None

FcγR binding

Retained

C1q binding

Retained

Linker & conjugation

Linker chemistry

Linker profile

Linker

SPDB / sulfo-SPDB

Class

Cleavable

Cleavage

Cleavable

Attachment

Lysine

Conjugation

Conventional Lys (SPDB)

Symmetry

Asymmetric

DAR (mean)

3.2

DAR homogeneity

Heterogeneous

Plasma t½

5.5 d

Cleavage trigger

GSH/reductive (disulfide)

Release control

Conditional

Hydrophilicity mask

None

Formula

C13H14N2O4S2

Linker MW

326.399 Da

Linker TPSA

76.57 Å²

Linker xLogP

2.2093

ADCdb linker

LIN0VZYER

In-vitro stability

Stability note

Average t½ 5.5 d in Hassan JCO 2020 Ph1 N=148 mesothelin-positive solid tumors; dose-proportional PK 0.15–7.5 mg/kg

Payload

Payload & physicochemistry

Payload profile

Payload

DM4 (free)

Class

Maytansinoid

Mechanism

Tubulin inhibitor

Released catabolite

DM4 and S-methyl-DM4 (DM4-Me)

Mechanistic subtype

Tubulin-maytansinoid

Stereochem / salt

Bystander

Yes

PAMPA rank

780.4 Da

XLogP3

3.2

logD₇.₄

TPSA

157 Å²

pKa

10.3 pKa

Charge pH 7.4

H-bond donors

H-bond acceptors

IC50 (HCEC)

Formula

C38H54ClN3O10S

PubChem CID

11686439

ADCdb payload

PAY0GTSVM

Hydrophobicity · logD₇.₄

hydrophilic −2+3+4 lipophilic

Bioactivity note

ADCdb reports payload/ADC potency IC50 ranging from 1.0 nM (MIA PaCa-2) to 42.4 nM (NCI-ADR-RES) across cell lines; clinical objective response rates 9.6%-42.1% (mesothelin-expression dependent), median PFS 4.3-8.5 months in Phase 2. Source: ADCdb DRG0EPHMC.

Dosing & regimen

Dosing

RP2D dose

6.5 mg/kg

Schedule

Q3W

Route

Fractionated

n at RP2D

148

Dose basis

TBW

Trial phase

Phase 2

Dose-OAE available

Tox summary basis

RP2D

Ocular & expression

Ocular profile & eye-tissue target expression

Target profile

OAE any-grade

37 %

OAE grade 3+

2 %

OAE data status

reported

Severity (weighted)

12.5

Keratopathy

37 %

Conjunctival

Dry eye

Blurred vision

Dominant tissue

Cornea

Surface subtype

Corneal (off-target)

Grading scale

Unknown

Reversibility

Reversible

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 · source-verified

Ascertainment: Systematic eye examsScale: UnknownDenominator: RP2D⚠ OAE rate not directly comparable across trials

Identity & registry

Identifiers, registry & notes

ADC id

anetumab-ravtansine

Approval status

Discontinued

Approval year

UniProt

Q13421

ADCdb ADC

DRG0EPHMC

ADCdb antibody

ANI0JGMTX

ADCdb target

TAR0NEZUA

Primary source

Hassan JCO 2020 PMID 32213105

Aliases & development codes

BAY 94-9343

Notes

DM4 class; high conjunctival expression doesn't increase severity vs low-expression DM4 ADCs. V3.1: n_rp2d=148 retained (pooled Ph1 across cohorts; label/paper uses this denominator for OAE%). Light chain λ not explicitly verified — retained from literature.