SYSA-1801

Discontinued

SYSA1801; EO-3021; EO3021; EO 3021; CPO-102; CPO102; CPO 102; Claudin 18.2-MMAE ADC

Target

Claudin-18.2 (CLDN18.2 isoform) · CLDN18

Sponsor

CSPC Pharmaceutical Group (CSPC Megalith Biopharmaceutical); licensed to Elevation Oncology

Indication

CLDN18.2-positive advanced solid tumors (gastric/GEJ cancer; pancreatic cancer)

Target family

Claudin / tight-junction

RP2D dose

2.0-2.5

Q3W (Day 1 of every 21-day cycle)RP2D

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

21.2%

G3+

RP2D

sagittal schematic · -

↳

Tissues shaded by reported adverse-event rate.

Cornea

Express.

Limbus

Express.

Conjunctiva

Express.

Lens

Express.

Retina / RPE

Express.

Dominant tissue

Cornea

Surface subtype

Corneal (off-target)

Reversibility

Reported ocular events

Dry eye29%

Dry eye syndrome21.2%

n=33

Corneal disorders21%

Keratopathy / corneal epitheliopathy / keratitis (identified ocular-risk cluster; protocol-managed)-

Per-trial detail

Adverse events by trial

EO-3021 Phase 1 (NCT05980416)Phase 12.0 mg/kg IV Q3W (every 3 weeks)n=42CTCAE NRRP2DB

CT.gov NCT05980416 posted results (serious AE) NCT05980416

18 adverse-event terms · 9 systems · expand a system below

GI5

Nausea

2.4%

1/42

Constipation

2.4%

1/42

Duodenal Obstruction

2.4%

1/42

Dysphagia

2.4%

1/42

Impaired Gastric Temptying

2.4%

1/42

Vascular3

Hepatic2

Metabolic2

Pulmonary2

Cardiac1

Infections1

Neoplasms1

Psychiatric1

Construct

Molecular anatomy

Antibody

IgG1

Human

Linker

Peptide

Cleavable

DAR

Payload

Monomethyl auristatin E (MMAE)

Tubulin inhibitor (microtubule polymerization inhibitor; antimitotic)

Linker structureC27H45N5O7

C=C(N[C@@H](CCCNC(N)=N)C(=O)Nc1ccc(CO)cc1)[C@@H](NC(=O)COCCOCCOCC)C(C)C

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-CLDN18.2 mAb (SYSA-1801) [ADCdb ANI0RSZBP]

Isotype

IgG1

Origin

Human

Fc modifications

None

Glycoengineering

None

Effector silencing

None

FcγR binding

Retained

C1q binding

Retained

Target KD (nM)

0.6

Linker & conjugation

Linker chemistry

Linker profile

Linker

PEG3-Val-Cit-PABC

Class

Peptide

Cleavage

Cleavable

Attachment

Glutamine-295

Conjugation

Site-specific, transglutaminase-mediated at glutamine-295

Symmetry

Site-specific at glutamine-295

DAR (mean)

DAR homogeneity

Homogeneous

Plasma t½

Cleavage trigger

Cathepsin B (lysosomal cysteine protease; cleaves Val-Cit dipeptide)

Release control

Conditional

Hydrophilicity mask

Discrete-PEG-spacer

Platform

Microbial transglutaminase site-specific

Formula

C27H45N5O7

Linker MW

551.685 Da

Linker TPSA

173.27 Å²

Linker xLogP

1.2483

ADCdb linker

LIN0KCPHV

In-vitro stability

Payload

Payload & physicochemistry

Payload profile

Payload

Monomethyl auristatin E (MMAE)

Class

Auristatin

Mechanism

Tubulin inhibitor (microtubule polymerization inhibitor; antimitotic)

Released catabolite

MMAE (free monomethyl auristatin E)

Mechanistic subtype

Tubulin-auristatin

Stereochem / salt

Bystander

Yes

PAMPA rank

717.98 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 ADC page reports Phase 1 clinical efficacy: overall confirmed ORR ~38.1% across dosing cohorts and ORR 47.1% in the gastric/gastroesophageal cancer subset (0.5-3.0 mg/kg Q3W). Payload MMAE is a potent antimitotic tubulin-polymerization inhibitor (sub-nanomolar to low-nanomo

Dosing & regimen

Dosing

RP2D dose

2.0-2.5

Schedule

Q3W (Day 1 of every 21-day cycle)

Route

Fractionated

n at RP2D

Dose basis

TBW

Trial phase

Phase 1

Dose-OAE available

Tox summary basis

Ocular & expression

Ocular profile & eye-tissue target expression

Target profile

OAE any-grade

21.2 %

OAE grade 3+

OAE data status

reported

Severity (weighted)

Keratopathy

Conjunctival

Dry eye

21.2 %

Blurred vision

Dominant tissue

Cornea

Surface subtype

Corneal (off-target)

Grading scale

CTCAE v5.0

Reversibility

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

Cornea (central)

Cornea (limbal)

Conjunctiva

RPE

Retina (HPA)

Cross-trial comparability · source-verified

Ascertainment: Partial / unspecified monitoringScale: CTCAE v5Denominator: RP2D

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

1.0 mg/kg

IV Q3W (every 3 weeks)

33.3%

n=3 · EO-3021 Phase 1

2.0 mg/kg

IV Q3W (every 3 weeks)

26.2%

n=42 · EO-3021 Phase 1

2.0 mg/kg

IV Q3W (every 3 weeks)

7.1%

n=42 · EO-3021 Phase 1

2.0 mg/kg

IV Q3W (every 3 weeks)

4.8%

n=42 · EO-3021 Phase 1

2.5 mg/kg

IV Q3W (every 3 weeks)

38.2%

n=34 · EO-3021 Phase 1

2.5 mg/kg

IV Q3W (every 3 weeks)

14.7%

n=34 · EO-3021 Phase 1

2.5 mg/kg

IV Q3W (every 3 weeks)

11.8%

n=34 · EO-3021 Phase 1

2.9 mg/kg

IV Q3W (every 3 weeks)

16.7%

n=6 · EO-3021 Phase 1

—

Q3W

21.2%

n=33 · SYSA1801 Ph1

—

Q3W

21%

· EO-3021 global Ph1

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

sysa-1801

Approval status

Discontinued

Approval year

UniProt

P56856

ADCdb ADC

DRG0XFQVE

ADCdb antibody

ANI0RSZBP

ADCdb target

TAR0IBZAS

Primary source

SYSA1801 FIH Ph1, ASCO 2023 (J Clin Oncol 41:16_suppl 3016), NCT05009966; corrob. EO-3021 global Ph1 (NCT05980416)

Aliases & development codes

SYSA1801; EO-3021; EO3021; EO 3021; CPO-102; CPO102; CPO 102; Claudin 18.2-MMAE ADC

Notes

SYSA-1801 = EO-3021 = CPO-102: fully-human anti-CLDN18.2 mAb, SITE-SPECIFIC MMAE ADC, DAR 2, cleavable PEG3-Val-Cit-PABC linker (cathepsin-B; PABC self-immolative; discrete PEG3 hydrophobicity masking; releases free MMAE). Developed by CSPC (CSPC Megalith); licensed to Elevation Oncology. CLINICAL (two trials, same molecule): (1) SYSA1801 China FIH Ph1 (NCT05009966; CSPC; ASCO 2023, J Clin Oncol 41:16_suppl 3016): n=33 (26 gastric/GEJ, 7 pancreatic), IV Q3W, escalation 0.5/1/2/3/4.5/6 mg/kg (modified 3+3), expansion at 2.0 & 2.5 mg/kg Q3W. Most-common TRAEs (>20%): nausea 42.4%, vomiting 36.4%, dry eye syndrome 21.2%, anaemia 21.2%. 2 DLTs (G3 nausea, G3 vomiting) at 3 mg/kg. Any-grade TRAE 75.8%, >=G3 24.2%. ADCdb lists this Phase-1 arm as terminated. (2) EO-3021 global Ph1 (NCT05980416; Elevation): dose-escalation n=32 (26 gastric/GEJ), 1.0-2.9 mg/kg Q3W, RP2D 2.0 & 2.5 mg/kg Q3W; 4 DLTs at 2.9 mg/kg (G3 fatigue, G3 encephalopathy, appetite). Corroborates ocular signal: dry eye 29%, corneal disorders 21%. Explicitly NO neutropenia and NO peripheral neuropathy/hypoesthesia; no G4/5 TRAEs; <10% discontinued for toxicity. Early efficacy in CLDN18.2+ gastric/GEJ (ORR ~42.8%). OCULAR ASSESSMENT: off-target corneal/ocular-surface auristatin toxicity (dry eye dominant; corneal disorders in the global trial). oae_any_pct set to 21.2 (max ocular PT, dry eye, in the named primary SYSA1801 China cohort); the global EO-3021 trial shows a somewhat higher dry-eye rate (29%) and adds corneal disorders (21%), both captured as corroborating rows. EVIDENCE/TIER CAVEAT: All clinical (dosing, toxicity, ocular) data are conference-abstract/press-release level (Tier D) — no full peer-reviewed primary publication located. Composition/linker physchem (ADCdb) and payload physchem (standard MMAE) are Tier C. antibody_isotype left blank (fully human; specific isotype not disclosed). linker_attachment left blank (site-specific confirmed -> captured in conjugation_method; the reactive attachment chemistry is not explicitly disclosed). Hepatic / pulmonary-ILD / infusion-reaction AEs not reported in available sources -> left blank (not 0).