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

Per-trial detail

Adverse events by trial

MEDI2228 phase 1 FIH (NCT03489525)Phase 10.0125-0.20 mg/kg (all dose levels pooled) Q3W or Q6Wn=107CTCAE CTCAE v4.03PooledBto verify

Dimopoulos, Leuk Lymphoma 2024 (PMID 39404476) PMID 39404476 / NCT03489525

12 adverse-event terms · 1 system · expand a system below

Other12

Photophobia

43.9%G3+ 10.3%

47/107

Rash

29%G3+ 1.9%

31/107

Thrombocytopenia

19.6%G3+ 15.9%

21/107

Pleural effusion

15.9%G3+ 3.7%

17/107

Anemia

15%G3+ 9.3%

16/107

Dry eye

15%G3+ 2.8%

16/107

Fatigue

14%G3+ 0.9%

15/107

Gamma-glutamyl transferase increased

13.1%G3+ 11.2%

14/107

Edema peripheral

12.1%G3+ 0.9%

13/107

Neutropenia

11.2%G3+ 9.3%

12/107

Blepharitis

10.3%G3+ 0.9%

11/107

Vision blurred

10.3%G3+ 0%

11/107

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

Platform

AstraZeneca/MedImmune cysteine-insertion

Conjugation site

Engineered cysteine inserted after heavy-chain S239

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

Free base

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)

0.1515 nM

Formula

C33H36N4O6

PubChem CID

90132565

ADCdb payload

PAY0LZRXU

Potency IC50 (nM)

151.5

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

ADA rate (%)

8.4 %

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

CTCAE v4.03

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⚠ Not comparable: symptom-driven ascertainment + grading scale not documented

Dose & schedule → ocular toxicity · keratopathy (any-grade) by cohort

0.14 mg/kg

Q3W

70.7%

n=41 · MEDI2228 phase 1 FIH

0.14 mg/kg

Q3W

n=41 · NCT03489525 (MEDI2228 FIH)

0.0125-0.20 mg/kg (all dose levels pooled)

Q3W or Q6W

57%

n=107 · MEDI2228 phase 1 FIH

0.0125-0.20 mg/kg (all levels)

Q3W

43.9%

n=107 · NCT03489525 (MEDI2228 FIH)

0.0125-0.20 mg/kg (all dose levels pooled)

Q3W or Q6W

10.3%

n=107 · MEDI2228 phase 1 FIH

real-world (MEDI2228 monotherapy)

per clinical use

49%

n=43 · Mayo Clinic BCMA-ADC real-world cohort (Rees 2026)

real-world (MEDI2228 monotherapy)

per clinical use

n=43 · Mayo Clinic BCMA-ADC real-world cohort (Rees 2026)

real-world (MEDI2228 monotherapy)

per clinical use

n=43 · Mayo Clinic BCMA-ADC real-world cohort (Rees 2026)

Per-cohort rates from the per-trial extraction, sorted by dose. Cross-trial comparison is subject to ascertainment / scale differences (see comparability above) — e.g. an early symptom-driven trial can read lower than a later systematic-exam trial at a higher dose.

Ocular AE grading reference — interspecialty consensus · 6 scales + dose modification

Identity & registry

Identifiers, registry & notes

ADC id

medi2228

Approval status

Discontinued

Approval year

UniProt

Q02223

ADCdb ADC

DRG0PQJDH

ADCdb antibody

ANI0TEFTG

ADCdb target

TAR0KQONX

Trial (NCT)

NCT03489525

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