FS-1502

Investigational

LCB14-0110; anti-HER2-β-glucuronide-MMAF

Target

HER2 · ERBB2

Sponsor

LegoChem/Foshan Health

Indication

HER2+ breast

Target family

Receptor tyrosine kinase

RP2D dose

2.3 mg/kg

Q3WRP2D

Multi-organ toxicity

Fingerprint & organ drill-down

Also reported

0%severity100%

Assessed · clear

true 0%

No data

never assessed

6 adverse-event terms

Ocular

Any-grade

55.3%

G3+

2.7%

RP2D

sagittal schematic · Reversible

↳

Tissues shaded by reported adverse-event rate.

Cornea

18%

Express.

46.2%

Limbus

Express.

61.99%

Conjunctiva

14%

Express.

61.13%

Lens

Express.

Retina / RPE

Express.

5.48%

7.5 nTPM

Dominant tissue

Cornea

Surface subtype

Mixed

Reversibility

Reversible

Reported ocular events

Eye disorders (composite ocular TEAE)55.3%

G3+ 2.7%n=150

Dry eye24%

G3+ 1.3%n=150

Keratitis18%

n=150

Conjunctivitis14%

n=150

Dry eye syndrome11.3%

G3+ 0.7%n=150

Vision blurred-

G3+ 0.7%n=150

Construct

Molecular anatomy

Antibody

IgG1

Humanized

Linker

Cleavable

DAR

Payload

MMAF (free)

Tubulin inhibitor

Linker structure

structure not applicable

Payload structureC39H65N5O8

CCC(C)C(C(CC(=O)N1CCCC1C(C(C)C(=O)NC(CC2=CC=CC=C2)C(=O)O)OC)OC)N(C)C(=O)C(C(C)C)NC(=O)C(C(C)C)NC

Antibody

Antibody & Fc engineering

Antibody

anti-HER2 (trastuzumab biosimilar)

Isotype

IgG1

Origin

Humanized

Fc modifications

C-terminal CaaX motif for prenylation

Glycoengineering

Standard

Effector silencing

None

FcγR binding

Retained

C1q binding

Retained

Linker & conjugation

Linker chemistry

Linker profile

Linker

β-glucuronide + PAB

Class

Cleavable

Cleavage

Cleavable

Attachment

Site-specific (enzymatic/non-natural AA)

Conjugation

Enzymatic transglutaminase (prenyl-transferase CaaX)

Symmetry

Site-specific (paired)

DAR (mean)

DAR homogeneity

Homogeneous

Plasma t½

3.5 d

Cleavage trigger

beta-glucuronidase

Release control

Conditional

Hydrophilicity mask

Sugar

Formula

Linker MW

Linker TPSA

Linker xLogP

ADCdb linker

In-vitro stability

85.38%@7d/rat-plasma

Stability note

Median terminal t½ 2.4–4.8 d at C1 doses ≥1.0 mg/kg in Li Q Nat Commun 2024 Ph1a/b N=150; nonlinear at <1.0 mg/kg with shorter t½ 0.6–2.3 d; time-dependent CL (mean CL drops from 13.0 to 8.75 mL/d/kg from C1 to C3 at 2.3 mg/kg). Highly stable in plasma — low unconjugated MMAF (Park 2020 LCB14 chemistry: β-gluc-MMAF >80 d in rat plasma stability per Jeffrey 2006)

Payload

Payload & physicochemistry

Payload profile

Payload

MMAF (free)

Class

Auristatin

Mechanism

Tubulin inhibitor

Released catabolite

MMAF (free / unconjugated monomethyl auristatin F)

Mechanistic subtype

Tubulin-auristatin

Stereochem / salt

Bystander

PAMPA rank

732 Da

XLogP3

2.1

logD₇.₄

0.9

TPSA

167 Å²

pKa

3.5 pKa

Charge pH 7.4

Zwitterion

H-bond donors

H-bond acceptors

IC50 (HCEC)

Formula

C39H65N5O8

PubChem CID

10395173

ADCdb payload

PAY0QLDVX

Hydrophobicity · logD₇.₄

hydrophilic −2+0.9+4 lipophilic

Dosing & regimen

Dosing

RP2D dose

2.3 mg/kg

Schedule

Q3W

Route

Fractionated

n at RP2D

150

Dose basis

TBW

Trial phase

Phase 1/2

Dose-OAE available

Yes

Tox summary basis

RP2D

Ocular & expression

Ocular profile & eye-tissue target expression

Target profile

OAE any-grade

55.3 %

OAE grade 3+

2.7 %

OAE data status

reported

Severity (weighted)

18.48

Keratopathy

18 %

Conjunctival

14 %

Dry eye

24 %

Blurred vision

Dominant tissue

Cornea

Surface subtype

Mixed

Grading scale

CTCAE v5

Reversibility

Reversible

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

Cornea (central)

46.2 %

Cornea (limbal)

61.99 %

Conjunctiva

61.13 %

RPE

5.48 %

Retina (HPA)

7.5 nTPM

Cross-trial comparability

Ascertainment: Partial / unspecified monitoringScale: CTCAE v5Denominator: RP2D

Identity & registry

Identifiers, registry & notes

ADC id

fs-1502

Approval status

Investigational

Approval year

UniProt

P04626

ADCdb ADC

DRG0WGVKF

ADCdb antibody

ANI0FIZAK

ADCdb target

TAR0THKZD

Primary source

Li Q Nat Commun 2024 PMID 38886347

Aliases & development codes

LCB14-0110; anti-HER2-β-glucuronide-MMAF

Notes

Cleavable β-gluc linker releases FREE MMAF (zwitterion) vs belantamab Cys-mcMMAF (-1) → dramatically lower G3+ (2.7 vs 77)