XMT-1660 (Emiltatug ledadotin)

Investigational

Emi-Le; XMT-1660; emiltatug ledadotin; ledadotin

Target

B7-H4 (B7x; B7S1; VTCN1) · VTCN1

Sponsor

Mersana Therapeutics

Indication

Triple-negative breast cancer (also HER2-low/negative breast, ovarian, endometrial; advanced/metastatic solid tumors)

Target family

Other

RP2D dose

67.4 mg/m2

Every 4 weeks (q4w)RP2D

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 · -

↳

Tissues shaded by reported adverse-event rate.

Cornea

Express.

Limbus

Express.

Conjunctiva

Express.

Lens

Express.

Retina / RPE

Express.

Dominant tissue

None

Surface subtype

None

Reversibility

Reported ocular events

Ocular toxicity (any eye disorder)0%

n=130

Construct

Molecular anatomy

Antibody

IgG1

Human

Linker

Peptide

Cleavable

DAR

Payload

Auristatin F-hydroxypropylamide (AF-HPA; ledadotin; DolaLock/Dolasynthen payload)

Microtubule polymerization inhibitor; AF-HPA is membrane-permeable and is intracellularly converted to the membrane-impermeable active catabolite auristatin F (controlled bystander effect)

Linker structureC71H119N17O31

[H][C@@]12CCc3[nH]nnc3CC[C@]1([H])[C@@H]2COC(=O)NCCOCCOCCNC(=O)CCC(=O)NCC(=O)NCCOCCC(=O)NCCC(=O)NCC(=O)NCC(=O)NCC(=O)NCC(=O)N[C@@H](COC(=O)NCCC(=O)N[C@@H](CCC(=O)N[C@@H](C)C(=O)O)C(=O)O)C(=O)NCCOCCOCCOCCOCCOCCOCCOCCOC

Payload structureC43H74N6O8

CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@@H]([C@@H](C)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)NCCCO)OC)OC)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)N(C)C

Antibody

Antibody & Fc engineering

Antibody

Emiltatug (XMT-1604; anti-B7-H4 mAb)

Isotype

IgG1

Origin

Human

Fc modifications

Glycoengineering

Glycan-remodeled

Effector silencing

FcγR binding

Retained

C1q binding

Retained

Linker & conjugation

Linker chemistry

Linker profile

Linker

Dolasynthen cleavable ester linker (alanine ester; ADCdb LIN0OVBRO)

Class

Peptide

Cleavage

Cleavable

Attachment

Site-specific (enzymatic/non-natural AA)

Conjugation

Site-specific glycan remodeling (GlycoConnect); homogeneous DAR-6 Dolasynthen construct. NOTE: ADCdb lists conjugation as 'Reactive Cysteines' which conflicts with the peer-reviewed preclinical paper (site-specific glycan remodeling); glycan method recorded here per Mol Cancer Ther 2023.

Symmetry

Site-specific (paired)

DAR (mean)

DAR homogeneity

Homogeneous

Plasma t½

Cleavage trigger

Ester cleavage (esterase/hydrolytic) within Dolasynthen scaffold

Release control

Conditional

Hydrophilicity mask

Discrete-PEG-spacer

Formula

C71H119N17O31

Linker MW

1706.821 Da

Linker TPSA

643.56 Å²

Linker xLogP

-7.7695

ADCdb linker

LIN0OVBRO

In-vitro stability

Payload

Payload & physicochemistry

Payload profile

Payload

Auristatin F-hydroxypropylamide (AF-HPA; ledadotin; DolaLock/Dolasynthen payload)

Class

Auristatin

Mechanism

Microtubule polymerization inhibitor; AF-HPA is membrane-permeable and is intracellularly converted to the membrane-impermeable active catabolite auristatin F (controlled bystander effect)

Released catabolite

Auristatin F-HPA released, then intracellularly converted to active catabolite auristatin F (AF; C40H67N5O8, MW ~746, PubChem CID 67472795)

Mechanistic subtype

Tubulin-auristatin

Stereochem / salt

Bystander

Partial

PAMPA rank

803.1 Da

XLogP3

4.3

logD₇.₄

TPSA

170 Å²

pKa

Charge pH 7.4

H-bond donors

H-bond acceptors

IC50 (HCEC)

Formula

C43H74N6O8

PubChem CID

71135741

ADCdb payload

PAY0BGBQM

Dosing & regimen

Dosing

RP2D dose

67.4 mg/m2

Schedule

Every 4 weeks (q4w)

Route

Fractionated

n at RP2D

Dose basis

BSA

Trial phase

Phase 1

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

None

Surface subtype

None

Grading scale

CTCAE (unversioned)

Reversibility

Target expression in eye tissues (HCA detection · HPA bulk)

Cornea (central)

Cornea (limbal)

Conjunctiva

RPE

Retina (HPA)

Cross-trial comparability · source-verified

Ascertainment: Systematic eye examsScale: CTCAE (unversioned)Denominator: RP2D

Identity & registry

Identifiers, registry & notes

ADC id

xmt-1660

Approval status

Investigational

Approval year

UniProt

Q7Z7D3

ADCdb ADC

DRG0FPQOM

ADCdb antibody

ANI0QYT011

ADCdb target

TAR0LCGUX

Primary source

Mersana Phase 1 (NCT05377996); ESMO 2025 abstract 298MO; ADCdb DRG0FPQOM

Aliases & development codes

Emi-Le; XMT-1660; emiltatug ledadotin; ledadotin

Notes

Composition fully resolved from ADCdb (DRG0FPQOM / linker LIN0OVBRO) plus the peer-reviewed preclinical paper (Mol Cancer Ther 2023;22(9):999, PMC10477829) and ADC Review drugmap. Antibody = human IgG1 kappa anti-B7-H4 (VTCN1); payload = AF-HPA (auristatin F-hydroxypropylamide), a microtubule inhibitor with a controlled bystander effect (membrane-permeable AF-HPA -> membrane-impermeable active auristatin F catabolite); DAR 6; Dolasynthen site-specific platform. CONJUGATION DISCREPANCY: ADCdb lists 'Reactive Cysteines,' but the primary preclinical publication describes site-specific N-glycan remodeling (GlycoConnect / strain-promoted azide-alkyne click chemistry); the peer-reviewed glycan method is recorded in composition.conjugation_method, with the ADCdb value noted. Linker physchem (SMILES/formula C71H119N17O31/MW 1706.821/TPSA 643.56/xLogP -7.7695) taken verbatim from ADCdb. Payload physchem from PubChem CID 71135741 (AF-HPA: C43H74N6O8, MW 803.1, XLogP3 4.3, TPSA 170); released active catabolite auristatin F = PubChem CID 67472795 (C40H67N5O8, MW ~746). Clinical: Phase 1 NCT05377996, n=130 (dose-escalation + backfill); RP2D 67.4 mg/m2 q4w selected for TNBC expansion (note: dose is body-surface-area mg/m2, not mg/kg). Top TRAEs (any grade): AST increase 38% (G3 14%), proteinuria 31% (G3 9%), nausea 29%, fatigue 28%; no Grade 4/5 TRAEs; dose discontinuation 2.3%, reductions 9.2%, delays 12.3%. OCULAR: explicitly assessed and ABSENT -> oae_any_pct=0, subtype=None, ae_grading_scale=CTCAE; anchored to triage eye_statement ('no dose-limiting treatment-related neutropenia, neuropathy, ocular toxicity, interstitial lung disease or thrombocytopenia'), which Mersana highlights as a Dolasynthen differentiator. Explicit-zero absence rows for ocular, neutropenia, thrombocytopenia, neuropathy and ILD tagged tier C because they are reported as notable absences ('no dose-limiting...') rather than enumerated 0.0% line items. CTCAE version not stated in available sources. ESMO Open 298MO fulltext returned HTTP 403; clinical figures drawn from the corroborating Mersana GlobeNewswire press release (Jan 10 2025) and secondary coverage of the same dataset. Derived columns (stability cond/uncond, FcgammaR/C1q, severity, HCA/HPA, dna_damage subtype, oae_data_status) intentionally left for downstream computation.