STRO-001

Discontinued

STRO-001; bezetabart; SP7219-SC236; anti-CD74 ADC (Sutro)

Target

HLA class II histocompatibility antigen gamma chain (CD74 / invariant chain / Ii) · CD74

Sponsor

Sutro Biopharma, Inc. (co-dev BioNova Pharmaceuticals; Piramal Pharma Solutions)

Indication

B-cell non-Hodgkin lymphoma (DLBCL, follicular, mantle cell)

Target family

Other

RP2D dose

Day 1 of every 3-week cycle (Q3W); initially Days 1 and 15 of 28-day cyclePooled

Multi-organ toxicity

Fingerprint & organ drill-down

Also reported

0%severity100%

Assessed · clear

true 0%

No data

never assessed

1 adverse-event term

Ocular

Any-grade

G3+

Pooled

sagittal schematic · Reversible

↳

Tissues shaded by reported adverse-event rate.

Cornea

Express.

Limbus

Express.

Conjunctiva

Express.

Lens

Express.

Retina / RPE

Express.

Dominant tissue

Hematologic/lymphoid

Surface subtype

None

Reversibility

Reversible

Reported ocular events

Any ocular toxicity (explicitly assessed and absent)0%

n=18

Per-trial detail

Adverse events by trial

Unattributed cohort2.5 mg/kgRP2DB

Shah NN et al., ASH 2020 NHL poster (Paper 139829), TEAE table N=21: Fatigue 7 (33.3); by-grade G1 4 (19.0), G2 3 (14.3), G3 0, G4 0

7 adverse-event terms · 5 systems · expand a system below

General2

Fatigue

33.3%

Pyrexia

19%

GI2

Metabolic1

Neurologic (other)1

Pulmonary1

Construct

Molecular anatomy

Antibody

IgG1

Human

Linker

Non-cleavable

DAR

Payload

Maytansinoid

Tubulin polymerization inhibition / microtubule disruption -> mitotic arrest -> apoptosis

Linker structureC29H36N2O6

CCOCCOCCOCCOCCC(=O)NCCC(=O)N1Cc2ccccc2C#Cc2ccccc21

Payload structureC38H53ClN4O11

CNC(=O)CCCC(=O)N(C)C(C)C(=O)OC1CC(=O)N(C)c2cc(cc(OC)c2Cl)C/C(C)=C\C=C/C(OC)C2(O)CC(OC(=O)N2)C(C)C2OC12C

Antibody

Antibody & Fc engineering

Antibody

Bezetabart (anti-CD74 IgG1, clone SP7219)

Isotype

IgG1

Origin

Human

Fc modifications

Aglycosylated

Glycoengineering

Aglycosylated

Effector silencing

Aglycosylated IgG1 (lacks N297 glycan -> abrogated FcgammaR/effector function and silenced ADCC/CDC)

FcγR binding

Lacks Fc effector function

C1q binding

Lacks Fc effector function

Dev code

SP7219

Linker & conjugation

Linker chemistry

Linker profile

Linker

SC236

Class

Non-cleavable

Cleavage

Non-cleavable

Attachment

Site-specific (enzymatic/non-natural AA)

Conjugation

Site-specific conjugation (pAMF/SPAAC click chemistry; XpressCF+ cell-free platform)

Symmetry

Site-specific (paired)

DAR (mean)

DAR homogeneity

Homogeneous

Plasma t½

37 d

Cleavage trigger

None (non-cleavable linker; payload released via lysosomal antibody catabolism as lysine-linker-maytansinoid adduct)

Release control

Unconditional

Hydrophilicity mask

Discrete-PEG-spacer

Platform

XpressCF+ cell-free protein synthesis with pAMF non-natural amino acid; SPAAC copper-free click conjugation

Conjugation site

HC-F404

Cell line

Cell-free E. coli extract

Formula

C29H36N2O6

Linker MW

508.615 Da

Linker TPSA

86.33 Å²

Linker xLogP

2.9157

ADCdb linker

LIN0ZKOQW

In-vitro stability

Stability note

Site-specific click conjugation + non-cleavable linker confers improved serum stability vs stochastic ADCs

Payload

Payload & physicochemistry

Payload profile

Payload

Maytansinoid

Class

Maytansinoid

Mechanism

Tubulin polymerization inhibition / microtubule disruption -> mitotic arrest -> apoptosis

Released catabolite

Catabolites SC246

Mechanistic subtype

Tubulin-maytansinoid

Stereochem / salt

Bystander

Partial

PAMPA rank

794.4 Da

XLogP3

3.6

logD₇.₄

TPSA

157 Å²

pKa

~9.82 pKa

Charge pH 7.4

H-bond donors

H-bond acceptors

IC50 (HCEC)

Formula

C38H53ClN4O11

PubChem CID

5281828

ADCdb payload

PAY0ATCSD

Bioactivity note

STRO-001 in vitro cytotoxicity (EC50) on CD74+ multiple myeloma lines: MC/CAR 0.84 nM (90% kill), U266B1 8.8 nM (83%), MM.1S 12 nM (85%), ARP-1 23 nM (88%); ARD and OPM-2 not killed. Unconjugated SP7219 antibody non-cytotoxic. Released catabolites SC246 (major) and SC401 (minor)

Dosing & regimen

Dosing

RP2D dose

Schedule

Day 1 of every 3-week cycle (Q3W); initially Days 1 and 15 of 28-day cycle

Route

Intravenous

Fractionated

n at RP2D

Dose basis

TBW

Trial phase

Phase 1

Dose-OAE available

Tox summary basis

dose-escalation

ADA rate (%)

0 %

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

0 %

Conjunctival

Dry eye

Blurred vision

Dominant tissue

Hematologic/lymphoid

Surface subtype

None

Grading scale

CTCAE v4.03

Reversibility

Reversible

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

Cornea (central)

Cornea (limbal)

Conjunctiva

RPE

Retina (HPA)

Cross-trial comparability · source-verified

Ascertainment: Systematic eye examsScale: CTCAE (unversioned)Denominator: RP2D

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

0.05-0.91 mg/kg (7 dose levels, all pooled)

IV Days 1 & 15 of 28-day cycle

n=14 · STRO-001-BCM1

0.05-1.78 mg/kg (9 dose levels, all pooled)

IV (Days 1&15 q28d per earlier abstract; Day 1 q21d per registry)

n=18 · STRO-001-BCM1

0.05-2.5 mg/kg

Q3W (or D1+D15 Q28d)

n=18 · STRO-001-BCM1

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

stro-001

Approval status

Discontinued

Approval year

UniProt

P04233

ADCdb ADC

DRG0RJKWE

ADCdb antibody

ANI0QYT012

ADCdb target

TAR0KVKEF

Primary source

Shah et al., ASH 2020 (Paper 139829) / ASH 2019 (Blood 134 Suppl 1:5329), Phase 1 dose-escalation of STRO-001 (anti-CD74 ADC), NCT03424603

Aliases & development codes

STRO-001; bezetabart; SP7219-SC236; anti-CD74 ADC (Sutro)

Notes

STRO-001 = anti-CD74 maytansinoid ADC, INN bezetabart (Sutro Biopharma). Built using XpressCF+ cell-free protein synthesis with site-specific conjugation at heavy-chain F404 via the non-natural amino acid para-azidomethyl-L-phenylalanine (pAMF) and copper-free strain-promoted azide-alkyne cycloaddition (SPAAC/DBCO click chemistry); aglycosylated human IgG1 (clone SP7219). Payload-linker designated SC236, a non-cleavable DBCO-maytansinoid (DM4-class maytansine derivative); DAR 2. ADCdb DRG0RJKWE; linker LIN0ZKOQW (Cys-12 ADC linker, thiol-sensitive, uncleavable). OCULAR ANCHOR: Phase 1 explicitly reported NO ocular and NO neuropathy toxicity signals (assessed-absent), consistent with triage explicit-zero; oae_any_pct=0. Program later terminated. ASH 2020 NHL cohort n=18; broader study reported ~21 pts across B-cell malignancies (EHA/ASH 2019). MTD not reached (escalated to 2.5 mg/kg). ~90% of AEs were grade 1-2. One DLT: grade 3 thromboembolic event at 0.91 mg/kg. PubChem/SEC interim-data and ASH-publications full-text returned 403; toxicity rows below are abstract-level (>=20% grouped AEs reported without per-PT percentages), hence pct given as documented bucket counts/qualitative where exact % not published.