MEDI2228

Discontinued

anti-BCMA PBD site-specific

Target

BCMA · TNFRSF17

Sponsor

AstraZeneca/MedImmune

Indication

BCMA+ myeloma

Target family

TNF receptor superfamily

RP2D dose

0.14 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

53.7%

G3+

17.1%

RP2D

sagittal schematic · Reversible

↳

Tissues shaded by reported adverse-event rate.

Cornea

Express.

0.4%

Limbus

Express.

0.6%

Conjunctiva

Express.

0.06%

Lens

Express.

Retina / RPE

Express.

0.1 nTPM

Dominant tissue

Visual

Surface subtype

Visual

Reversibility

Reversible

Reported ocular events

Photophobia43.9%

G3+ 17.1%n=107

Dry eye20.6%

n=107

Vision blurred12.1%

n=107

Keratopathy0%

n=41

Construct

Molecular anatomy

Antibody

IgG1

Human

Linker

Cleavable

DAR

Payload

SG3199 (PBD dimer)

DNA cross-linker

Linker structureC41H65N5O15

[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])OC([H])([H])C([H])([H])OC([H])([H])C([H])([H])OC([H])([H])C([H])([H])OC([H])([H])C([H])([H])OC([H])([H])C([H])([H])OC([H])([H])C([H])([H])OC([H])([H])C([H])([H])N([H])C(=O)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])[H])c([H])c1[H]

Payload structureC33H36N4O6

CC1=CN2[C@@H](C1)C=NC3=CC(=C(C=C3C2=O)OC)OCCCCCOC4=C(C=C5C(=C4)N=C[C@@H]6CC(=CN6C5=O)C)OC

Antibody

Antibody & Fc engineering

Antibody

anti-BCMA (MEDI2228)

Isotype

IgG1

Origin

Human

Fc modifications

None

Glycoengineering

Standard

Effector silencing

None

FcγR binding

Retained

C1q binding

Retained

Linker & conjugation

Linker chemistry

Linker profile

Linker

VA dipeptide + site-specific (MEDI2228)

Class

Cleavable

Cleavage

Cleavable

Attachment

Site-specific (engineered Cys)

Conjugation

Site-specific engineered Cys

Symmetry

Site-specific (paired)

DAR (mean)

DAR homogeneity

Homogeneous

Plasma t½

7.5 d

Cleavage trigger

Cathepsin B (Val-Ala)

Release control

Conditional

Hydrophilicity mask

Discrete-PEG-spacer

Formula

C41H65N5O15

Linker MW

867.991 Da

Linker TPSA

247.85 Å²

Linker xLogP

-0.2829

ADCdb linker

LIN0YRUBS

In-vitro stability

Stability note

Mean t½ 6–9 d at doses ≥0.05 mg/kg per Lee LeukLymph 2024 Ph1 R/R MM N=82; site-specific engineered Cys conjugation of tesirine-like PBD dimer; free warhead <1% intact MEDI2228 (very stable)

Payload

Payload & physicochemistry

Payload profile

Payload

SG3199 (PBD dimer)

Class

PBD dimer

Mechanism

DNA cross-linker

Released catabolite

SG3199

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

C33H36N4O6

PubChem CID

90132565

ADCdb payload

PAY0LZRXU

Hydrophobicity · logD₇.₄

hydrophilic −2+2.5+4 lipophilic

Bioactivity note

SG3199 free payload highly potent (in vitro IC50 sub-pM to low-pM across cancer lines per ADCdb payload page: EoL-1 0.79 pM, Ramos 5.83 pM, SU-DHL-1 12.11 pM, HuT 78 12.98 pM, L-540 14.8 pM). MEDI2228 ADC: EC50 189.7 ng/mL on RPMI-8226 (BCMA+ myeloma); tumor growth inhibition 67.

Dosing & regimen

Dosing

RP2D dose

0.14 mg/kg

Schedule

Q3W

Route

Fractionated

n at RP2D

107

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

53.7 %

OAE grade 3+

17.1 %

OAE data status

reported

Severity (weighted)

25.1

Keratopathy

0 %

Conjunctival

Dry eye

20.6 %

Blurred vision

12.1 %

Dominant tissue

Visual

Surface subtype

Visual

Grading scale

Unknown

Reversibility

Reversible

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

Cornea (central)

0.4 %

Cornea (limbal)

0.6 %

Conjunctiva

0.06 %

RPE

0 %

Retina (HPA)

0.1 nTPM

Cross-trial comparability · source-verified

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

Identity & registry

Identifiers, registry & notes

ADC id

medi2228

Approval status

Discontinued

Approval year

UniProt

Q02223

ADCdb ADC

DRG0PQJDH

ADCdb antibody

ANI0TEFTG

ADCdb target

TAR0KQONX

Primary source

Dimopoulos MA Leuk Lymphoma 2024;65(12):1789 (PMID 39404476)

Aliases & development codes

anti-BCMA PBD site-specific

Notes

Photophobia dominant (44%), NO keratopathy (0%) - opposite pattern to belantamab on same BCMA target