Zilovertamab vedotin

Investigational

MK-2140; anti-ROR1-MMAE

Target

ROR1 · ROR1

Sponsor

VelosBio/Merck

Indication

ROR1+ NHL

Target family

Receptor tyrosine kinase

RP2D dose

2.5 mg/kg

Q3WRP2D

Multi-organ toxicity

Fingerprint & organ drill-down

Also reported

0%severity100%

Assessed · clear

true 0%

No data

never assessed

1 adverse-event term

Ocular

Any-grade

G3+

RP2D

sagittal schematic · Unknown

↳

Tissues shaded by reported adverse-event rate.

Cornea

Express.

1.09%

Limbus

Express.

3.42%

Conjunctiva

Express.

4.09%

Lens

Express.

Retina / RPE

Express.

Dominant tissue

Surface subtype

None

Reversibility

Unknown

Reported ocular events

Ocular toxicity (any; keratopathy/dry eye/blurred vision)0%

n=32

Construct

Molecular anatomy

Antibody

IgG1

Humanized

Linker

Cleavable

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

Antibody

Antibody & Fc engineering

Antibody

anti-ROR1 (zilovertamab)

Isotype

IgG1

Origin

Humanized

Fc modifications

None

Glycoengineering

Standard

Effector silencing

None

FcγR binding

Retained

C1q binding

Retained

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)

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 Å²

Linker xLogP

0.6769

ADCdb linker

LIN0SQEDQ

In-vitro stability

Stability note

Inherited from MC-vc-PAB conventional Cys class. Wang NEJM Evidence 2022 PMID 38319241 Ph1 N=32 R/R MCL/CLL Q3W does not tabulate clinical t½ in d in open abstract; PK reportedly dose-proportional

Payload

Payload & physicochemistry

Payload profile

Payload

MMAE

Class

Auristatin

Mechanism

Tubulin inhibitor

Released catabolite

MMAE (monomethyl auristatin E)

Mechanistic subtype

Tubulin-auristatin

Stereochem / salt

Bystander

Yes

PAMPA rank

718 Da

XLogP3

4.1

logD₇.₄

2.7

TPSA

150 Å²

pKa

9.1 pKa

Charge pH 7.4

H-bond donors

H-bond acceptors

IC50 (HCEC)

Formula

C39H67N5O7

PubChem CID

11542188

ADCdb payload

PAY0FSXOW

Hydrophobicity · logD₇.₄

hydrophilic −2+2.7+4 lipophilic

Bioactivity note

No payload IC50 listed on ADCdb/PubChem pages. ADCdb reports clinical ORR ~30-60% (indication/line-dependent) and preclinical xenograft TGI ~0-100% correlating with ROR1 expression. MMAE is a potent antimitotic (tubulin inhibitor).

Dosing & regimen

Dosing

RP2D dose

2.5 mg/kg

Schedule

Q3W

Route

Fractionated

n at RP2D

Dose basis

TBW

Trial phase

Phase 2/3

Dose-OAE available

Tox summary basis

RP2D

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)

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)

1.09 %

Cornea (limbal)

3.42 %

Conjunctiva

4.09 %

RPE

Retina (HPA)

Cross-trial comparability · source-verified

Ascertainment: Symptom-driven reportingScale: UnknownDenominator: RP2D⚠ OAE rate not directly comparable across trials

Identity & registry

Identifiers, registry & notes

ADC id

zilovertamab-vedotin

Approval status

Investigational

Approval year

UniProt

Q01973

ADCdb ADC

DRG0ZMZUD

ADCdb antibody

ANI0CQMLX

ADCdb target

TAR0LTTSS

Primary source

Wang ML NEJM Evidence 2022;1(1):EVIDoa2100001 (PMID 38319241)

Aliases & development codes

MK-2140; anti-ROR1-MMAE

Notes

ROR1 low cornea/conjunctiva expression; 0% OAE explicitly verified in Wang 2022 NEJM Evidence ('did not observe instances of ocular toxicities'). V3.1: first author corrected Byrd→Wang.