Pinatuzumab vedotin

Investigational

DCDT2980S; anti-CD22-MMAE

Target

CD22 · CD22

Sponsor

Genentech

Indication

CD22+ NHL

Target family

Siglec

RP2D dose

2.4 mg/kg

Q3WRP2D

Multi-organ toxicity

Fingerprint & organ drill-down

Also reported

0%severity100%

Assessed · clear

true 0%

No data

never assessed

4 adverse-event terms

Ocular

Any-grade

9.5%

G3+

RP2D

sagittal schematic · Unknown

↳

Tissues shaded by reported adverse-event rate.

Cornea

Express.

0.5%

Limbus

Express.

1.1%

Conjunctiva

Express.

1.64%

Lens

Express.

Retina / RPE

Express.

1.16%

0 nTPM

Dominant tissue

Surface subtype

None

Reversibility

Unknown

Reported ocular events

Vision blurred9.5%

Dry eye3.2%

Visual impairment1.6%

Eye pain1.6%

Construct

Molecular anatomy

Antibody

IgG1

Humanized

Linker

Cleavable

3.5

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-CD22 (pinatuzumab)

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)

3.5

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. Advani CCR 2017 PMID 27601593 Ph1 N=75 R/R B-NHL Q3W: dose-proportional PK, no numeric clinical t½ in d in open-access tables

Payload

Payload & physicochemistry

Payload profile

Payload

MMAE

Class

Auristatin

Mechanism

Tubulin inhibitor

Released catabolite

MMAE (unconjugated 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

ADCdb lists the MMAE payload's mechanistic target as Microtubule (MT); MMAE is a potent antimitotic tubulin-polymerization inhibitor. No numeric IC50 reported on the ADCdb ADC page or the PubChem MMAE record.

Dosing & regimen

Dosing

RP2D dose

2.4 mg/kg

Schedule

Q3W

Route

Fractionated

n at RP2D

Dose basis

TBW

Trial phase

Phase 2

Dose-OAE available

Tox summary basis

RP2D

Ocular & expression

Ocular profile & eye-tissue target expression

Target profile

OAE any-grade

9.5 %

OAE grade 3+

0 %

OAE data status

reported

Severity (weighted)

2.9

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)

0.5 %

Cornea (limbal)

1.1 %

Conjunctiva

1.64 %

RPE

1.16 %

Retina (HPA)

0 nTPM

Cross-trial comparability · source-verified

Ascertainment: Symptom-driven reportingScale: CTCAE v4Denominator: RP2D⚠ OAE rate not directly comparable across trials

Identity & registry

Identifiers, registry & notes

ADC id

pinatuzumab-vedotin

Approval status

Investigational

Approval year

UniProt

P20273

ADCdb ADC

DRG0PFKFR

ADCdb antibody

ANI0IESDV

ADCdb target

TAR0XTCGM

Primary source

Advani CCR 2017 PMID 27601593

Aliases & development codes

DCDT2980S; anti-CD22-MMAE

Notes

CD22 absent from cornea; 0% OAE verified in Advani 2017 CCR. V3.1: confirmed — paper has no ocular AEs; dominant toxicities are neutropenia and peripheral neuropathy.