Inotuzumab ozogamicin

FDA-approved

Besponsa; CMC-544

Target

CD22 · CD22

Sponsor

Wyeth/Pfizer

Indication

CD22+ ALL

Target family

Siglec

RP2D dose

1.8 mg/m² cycle 1 (0.8 D1 + 0.5 D8 + 0.5 D15)

D1+D8+D15 Q3-4WRP2D

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.

0.5%

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

No granular adverse-event rows recorded for this system.

Construct

Molecular anatomy

Antibody

IgG4

Humanized

Linker

Cleavable

DAR

Payload

Calicheamicin gamma1

DNA strand break

Linker structureC12H15NO3

CC(=O)c1ccc(OCCCC(N)=O)cc1

Payload structureC55H74IN3O21S4

CCN[C@H]1CO[C@H](C[C@@H]1OC)O[C@@H]2[C@H]([C@@H]([C@H](O[C@H]2O[C@H]3C#C/C=C\C#C[C@@]\4(CC(=O)C(=C3/C4=C\CSSSC)NC(=O)OC)O)C)NO[C@H]5C[C@@H]([C@@H]([C@H](O5)C)SC(=O)C6=C(C(=C(C(=C6OC)OC)O[C@H]7[C@@H]([C@@H]([C@H]([C@@H](O7)C)O)OC)O)I)C)O)O

Antibody

Antibody & Fc engineering

Antibody

G5/44 (inotuzumab)

Isotype

IgG4

Origin

Humanized

Fc modifications

None

Glycoengineering

Standard

Effector silencing

None

FcγR binding

Retained

C1q binding

Reduced

Linker & conjugation

Linker chemistry

Linker profile

Linker

AcBut hydrazone + disulfide

Class

Cleavable

Cleavage

Cleavable

Attachment

Lysine

Conjugation

Conventional Lys (NHS)

Symmetry

Asymmetric

DAR (mean)

DAR homogeneity

Heterogeneous

Plasma t½

12.3 d

Cleavage trigger

pH/acid (hydrazone) + GSH/reductive (disulfide)

Release control

Conditional

Hydrophilicity mask

None

Formula

C12H15NO3

Linker MW

221.256 Da

Linker TPSA

69.39 Å²

Linker xLogP

1.5335

ADCdb linker

LIN0KWKDL

In-vitro stability

Stability note

Terminal t½ 12.3 d in N=234 R/R ALL — much longer than gemtuzumab despite same AcBut chemistry, attributable to higher per-Ab loading (DAR 6 vs 2.5) and IgG4-class pharmacokinetics; calicheamicin metabolite (N-Ac-γ-cal-DMH) below limit of quantitation in serum due to extensive reduction

Payload

Payload & physicochemistry

Payload profile

Payload

Calicheamicin gamma1

Class

Calicheamicin

Mechanism

DNA strand break

Released catabolite

N-acetyl-gamma-calicheamicin dimethylhydrazide

Mechanistic subtype

DNA-strand-break

Stereochem / salt

Bystander

Partial

PAMPA rank

1368.4 Da

XLogP3

logD₇.₄

TPSA

410 Å²

pKa

Charge pH 7.4

H-bond donors

H-bond acceptors

IC50 (HCEC)

Formula

C55H74IN3O21S4

PubChem CID

10953353

ADCdb payload

PAY0RZSDY

Hydrophobicity · logD₇.₄

hydrophilic −2+2+4 lipophilic

Bioactivity note

ADCdb reports ADC in vitro cytotoxicity IC50 from ~5 pM (Daudi) to ~750 pM (HL-60 control); Phase 3 ALL CR ~73.8%. Free calicheamicin gamma1 binds DNA minor groove causing double-strand breaks (sub-nM potency).

Dosing & regimen

Dosing

RP2D dose

1.8 mg/m² cycle 1 (0.8 D1 + 0.5 D8 + 0.5 D15)

Schedule

D1+D8+D15 Q3-4W

Route

Fractionated

Yes

n at RP2D

164

Dose basis

BSA

Trial phase

Approved

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

Mixed

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

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

Identity & registry

Identifiers, registry & notes

ADC id

inotuzumab-ozogamicin

Approval status

FDA-approved

Approval year

2017

UniProt

P20273

ADCdb ADC

DRG0SXFSY

ADCdb antibody

ANI0RLBTI

ADCdb target

TAR0XTCGM

Primary source

FDA Besponsa label; INO-VATE NEJM 2016

Aliases & development codes

Besponsa; CMC-544

Notes

Hematologic target; VOD/SOS dominant toxicity; 0% ocular AEs in label