Vadastuximab talirine

Discontinued

SGN-CD33A; anti-CD33 PBD

Target

CD33 · CD33

Sponsor

Seagen

Indication

CD33+ AML

Target family

Siglec

RP2D dose

40 mcg/kg

Q3W (or D1+D4 split)RP2D

Multi-organ toxicity

Fingerprint & organ drill-down

Also reported

0%severity100%

Assessed · clear

true 0%

No data

never assessed

0 adverse-event terms

Ocular

Any-grade

G3+

RP2D

sagittal schematic · Unknown

↳

Tissues shaded by reported adverse-event rate.

Cornea

Express.

0.07%

Limbus

Express.

0.03%

Conjunctiva

Express.

0.06%

Lens

Express.

Retina / RPE

Express.

0.46%

0.2 nTPM

Dominant tissue

Surface subtype

None

Reversibility

Unknown

Reported ocular events

No granular adverse-event rows recorded for this system.

Construct

Molecular anatomy

Antibody

IgG1

Humanized

Linker

Cleavable

DAR

Payload

SG3199 (PBD dimer)

DNA cross-linker

Linker structureC18H27N3O6

[H]OC(=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])N1C(=O)C([H])=C([H])C1=O)C([H])(C([H])([H])[H])C([H])([H])[H])C([H])([H])[H]

Payload structureC42H39N5O7

COC1=CC=C(C=C1)C2=CN3[C@@H](C2)C=NC4=CC(=C(C=C4C3=O)OC)OCCCOC5=C(C=C6C(=C5)N=C[C@@H]7CC(=CN7C6=O)C8=CC=C(C=C8)N)OC

Antibody

Antibody & Fc engineering

Antibody

anti-CD33 (vadastuximab)

Isotype

IgG1

Origin

Humanized

Fc modifications

EC-mAb engineered Cys

Glycoengineering

Standard

Effector silencing

None

FcγR binding

Retained

C1q binding

Unknown

Linker & conjugation

Linker chemistry

Linker profile

Linker

VA dipeptide + engineered Cys (EC-mAb)

Class

Cleavable

Cleavage

Cleavable

Attachment

Site-specific (engineered Cys)

Conjugation

Site-specific engineered Cys (EC-mAb)

Symmetry

Site-specific (paired)

DAR (mean)

DAR homogeneity

Homogeneous

Plasma t½

7.0 d

Cleavage trigger

Cathepsin B (Val-Ala)

Release control

Conditional

Hydrophilicity mask

None

Formula

C18H27N3O6

Linker MW

381.429 Da

Linker TPSA

132.88 Å²

Linker xLogP

0.2019

ADCdb linker

LIN0ENDIF

In-vitro stability

Stability note

Inherited from VA-PBD class. Stein Blood 2018 PMID 29196412 Ph1 N=131 R/R AML at 40 mcg/kg RP2D does not tabulate explicit clinical acAb t½ in d in the open-access full text; engineered-Cys EC-mAb platform (Kung Sutherland Blood 2013) is more homogeneous than conventional Cys but not necessarily longer-t½

Payload

Payload & physicochemistry

Payload profile

Payload

SG3199 (PBD dimer)

Class

PBD dimer

Mechanism

DNA cross-linker

Released catabolite

SGD-1882 (free PBD dimer; DNA interstrand cross-linker)

Mechanistic subtype

DNA-crosslinker-PBD

Stereochem / salt

Bystander

Partial

PAMPA rank

584.7 Da

XLogP3

2.8

logD₇.₄

2.5

TPSA

102 Å²

pKa

5 pKa

Charge pH 7.4

H-bond donors

H-bond acceptors

IC50 (HCEC)

Formula

C42H39N5O7

PubChem CID

45257190

ADCdb payload

PAY0AKDAM

Hydrophobicity · logD₇.₄

hydrophilic −2+2.5+4 lipophilic

Bioactivity note

ADCdb reports IC50 ~0.10 ng/mL in high-CD33-expressing AML cell lines (e.g., MV4-11) and primary AML samples, rising to >110 ng/mL (up to >5000 ng/mL) in CD33-low/negative lines, indicating CD33 target-dependent cytotoxicity. PBD-dimer payload acts as a DNA minor-groove cross-lin

Dosing & regimen

Dosing

RP2D dose

40 mcg/kg

Schedule

Q3W (or D1+D4 split)

Route

Fractionated

Yes

n at RP2D

131

Dose basis

TBW

Trial phase

Phase 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

CTCAE v4

Reversibility

Unknown

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

Cornea (central)

0.07 %

Cornea (limbal)

0.03 %

Conjunctiva

0.06 %

RPE

0.46 %

Retina (HPA)

0.2 nTPM

Cross-trial comparability · source-verified

Ascertainment: Systematic eye examsScale: CTCAE v4Denominator: RP2D

Identity & registry

Identifiers, registry & notes

ADC id

vadastuximab-talirine

Approval status

Discontinued

Approval year

UniProt

P20138

ADCdb ADC

DRG0WXQJL

ADCdb antibody

ANI0MDDEU

ADCdb target

PATR0RIOXT

Primary source

Stein Blood 2018 PMID 29196412

Aliases & development codes

SGN-CD33A; anti-CD33 PBD

Notes

PBD on CD33 (like gemtuzumab calicheamicin); both 0% OAE. V3.1: 0% OAE supportable — Stein 2018 Blood has no ocular AEs. n=131 is total Ph1; 18 at 40 µg/kg RP2D.