Denintuzumab mafodotin (NHL)

Discontinued

SGN-CD19A; NHL cohort

Target

CD19 · CD19

Sponsor

Seagen

Indication

CD19+ NHL

Target family

Immunoglobulin superfamily

RP2D dose

3 mg/kg

Q3W + Q6W mixed (52+10)RP2D

Multi-organ toxicity

Fingerprint & organ drill-down

Also reported

0%severity100%

Assessed · clear

true 0%

No data

never assessed

5 adverse-event terms

Ocular

Any-grade

84%

G3+

RP2D

sagittal schematic · Reversible

↳

Tissues shaded by reported adverse-event rate.

Cornea

84%

Express.

Limbus

Express.

Conjunctiva

Express.

Lens

Express.

Retina / RPE

Express.

0.05%

0 nTPM

Off-target signature

84% corneal toxicity, yet the CD19 target is detected in only 0% of central cornea - toxicity is not explained by target expression.

Dominant tissue

Cornea

Surface subtype

Corneal (off-target)

Reversibility

Reversible

Reported ocular events

Keratopathy (superficial microcystic; corneal exam + symptoms composite)84%

n=62

Blurred vision65%

n=62

Dry eye52%

n=62

Photophobia27%

n=62

Keratopathy / corneal AEs (Grade 3-4)-

G3+ 9%

Construct

Molecular anatomy

Antibody

IgG1

Humanized

Linker

Non-cleavable

DAR

Payload

Cys-mcMMAF

Tubulin inhibitor

Linker structureC10H13NO4

O=C(O)CCCCCN1C(=O)C=CC1=O

Payload structureC52H83N7O13S

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)O)OC)OC)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)N(C)C(=O)CCCCCN3C(=O)CC(C3=O)SC[C@@H](C(=O)O)N

Antibody

Antibody & Fc engineering

Antibody

SGN-CD19 (denintuzumab)

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 (non-cleavable)

Class

Non-cleavable

Cleavage

Non-cleavable

Attachment

Cysteine (interchain)

Conjugation

Conventional interchain Cys

Symmetry

Symmetric

DAR (mean)

DAR homogeneity

Heterogeneous

Plasma t½

14.0 d

Cleavage trigger

Non-cleavable

Release control

Unconditional

Hydrophilicity mask

None

Formula

C10H13NO4

Linker MW

211.217 Da

Linker TPSA

74.68 Å²

Linker xLogP

0.5564

ADCdb linker

LIN0TAFAV

In-vitro stability

Stability note

Terminal t½ ~2 weeks reported for SGN-CD19A in Fathi Blood 2015 ASH abstract (R/R B-NHL); accumulation observed with multiple doses. Same mc-MMAF chemistry as belantamab/depatux-m

Payload

Payload & physicochemistry

Payload profile

Payload

Cys-mcMMAF

Class

Auristatin

Mechanism

Tubulin inhibitor

Released catabolite

Cys-mcMMAF (cysteine-maleimidocaproyl-MMAF)

Mechanistic subtype

Tubulin-auristatin

Stereochem / salt

Bystander

PAMPA rank

1046.3 Da

XLogP3

1.4

logD₇.₄

-1

TPSA

301 Å²

pKa

3.5 pKa

Charge pH 7.4

-1

H-bond donors

H-bond acceptors

IC50 (HCEC)

Formula

C52H83N7O13S

PubChem CID

86278355

ADCdb payload

PAY0QLDVX

Hydrophobicity · logD₇.₄

hydrophilic −2-1+4 lipophilic

Bioactivity note

When delivered extracellularly, the intact SGN-CD19A-class ADC is ~1000-fold more potent than the free active catabolite Cys-mcMMAF, demonstrating the antibody's intracellular targeting requirement and the poor bystander activity of the released metabolite (the charged/membrane-i

Dosing & regimen

Dosing

RP2D dose

3 mg/kg

Schedule

Q3W + Q6W mixed (52+10)

Route

Fractionated

n at RP2D

Dose basis

TBW

Trial phase

Phase 1

Dose-OAE available

Tox summary basis

RP2D

Ocular & expression

Ocular profile & eye-tissue target expression

Target profile

OAE any-grade

84 %

OAE grade 3+

OAE data status

reported

Severity (weighted)

Keratopathy

84 %

Conjunctival

Dry eye

52 %

Blurred vision

65 %

Dominant tissue

Cornea

Surface subtype

Corneal (off-target)

Grading scale

Unknown

Reversibility

Reversible

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

Cornea (central)

0 %

Cornea (limbal)

0 %

Conjunctiva

0 %

RPE

0.05 %

Retina (HPA)

0 nTPM

Cross-trial comparability

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

Identity & registry

Identifiers, registry & notes

ADC id

denintuzumab-mafodotin-nhl

Approval status

Discontinued

Approval year

UniProt

P15391

ADCdb ADC

DRG0OVAOS

ADCdb antibody

ANI0VYXVW

ADCdb target

TAR0EBTXG

Primary source

Moskowitz Blood 2015;126(23):182 (NHL, NCT01786135)

Aliases & development codes

SGN-CD19A; NHL cohort

Notes

CD19 absent from cornea but 84% OAE via MMAF macropinocytosis. V3.1: schedule clarified as mixed Q3W (52 pts) + Q6W (10 pts) per Fathi 2015. All ocular AE rates verified exactly. Photophobia 27% noted (not in schema).