ADC TOXICITY ATLAS
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OBI-999

Discontinued
OBI 999; OBI999; Globo-H ADC
Target
Globo H (globo-H hexasaccharide; tumor-associated glycosphingolipid antigen, not a protein) · -
Sponsor
OBI Pharma
Indication
Advanced solid tumors (CRC, esophageal/GEJ, pancreatic, basket); FDA orphan-drug designation in gastric cancer
Target family
Other
RP2D dose
1.2 mg/kg
Q3W (once every 21 days, day 1)RP2D
01
Multi-organ toxicity

Fingerprint & organ drill-down

Also reported
0%severity100%
0
Assessed · clear
true 0%
No data
never assessed
2 adverse-event terms

Ocular

Any-grade
0%
G3+
0%
RP2D
sagittal schematic · N/A

Tissues shaded by reported adverse-event rate.

Cornea
AE
0%
Express.
-
Limbus
AE
-
Express.
-
Conjunctiva
AE
0%
Express.
-
Lens
AE
-
Express.
-
Retina / RPE
AE
-
Express.
-
Dominant tissue
None
Surface subtype
None
Reversibility
N/A
Reported ocular events
No treatment-emergent ophthalmologic abnormality (formal ophthalmology exam)0%
Eye disorders SOC (any term)0%
02
Construct

Molecular anatomy

Antibody
IgG1
Humanized
Linker
Cleavable
4
DAR
Payload
Microtubule/tubulin polymerization inhibitor (antimitotic)
Linker structure
structure not applicable
Payload structureC39H67N5O7
CCC(C)C(C(CC(=O)N1CCCC1C(C(C)C(=O)NC(C)C(C2=CC=CC=C2)O)OC)OC)N(C)C(=O)C(C(C)C)NC(=O)C(C(C)C)NC
03
Antibody

Antibody & Fc engineering

Antibody
OBI-888
Isotype
IgG1
Origin
Humanized
Fc modifications
-
Glycoengineering
-
Effector silencing
-
FcγR binding
Retained
C1q binding
Retained
04
Linker & conjugation

Linker chemistry

Linker profile
Linker
ThioBridge Val-Cit-PAB (mc-vc-PAB type)
Class
Peptide
Cleavage
Cleavable
Attachment
Cysteine (interchain)
Conjugation
ThioBridge interchain-disulfide rebridging (cysteine); homogeneous DAR4 (>95%)
Symmetry
Symmetric
DAR (mean)
4
DAR homogeneity
Homogeneous
Plasma t½
-
Cleavage trigger
Cathepsin B (lysosomal cysteine protease; cleaves Val-Cit dipeptide)
Release control
Conditional
Hydrophilicity mask
None
Formula
-
Linker MW
-
Linker TPSA
-
Linker xLogP
-
ADCdb linker
-
In-vitro stability
-
05
Payload

Payload & physicochemistry

Payload profile
Payload
Monomethyl auristatin E (MMAE)
Class
Auristatin
Mechanism
Microtubule/tubulin polymerization inhibitor (antimitotic)
Released catabolite
MMAE (free monomethyl auristatin E, after Val-Cit cleavage + PAB self-immolation)
Mechanistic subtype
Tubulin-auristatin
Stereochem / salt
-
Bystander
Yes
PAMPA rank
-
MW
717.98 Da
XLogP3
4.1
logD₇.₄
2.5
TPSA
150 Ų
pKa
9 pKa
Charge pH 7.4
+1
H-bond donors
4
H-bond acceptors
8
IC50 (HCEC)
-
Formula
C39H67N5O7
PubChem CID
11542188
ADCdb payload
PAY0FSXOW
Hydrophobicity · logD₇.₄
hydrophilic −2+2.5+4 lipophilic
Bioactivity note
ADCdb reports only in vivo xenograft tumor growth inhibition (TGI ~34-99%) for OBI-999; no payload IC50 or ADC binding-affinity (Kd) value is given on the ADCdb page. ADCdb classifies the payload's therapeutic mechanism as a microtubule (MT) inhibitor (consistent with MMAE's tubu
06
Dosing & regimen

Dosing

RP2D dose
1.2 mg/kg
Schedule
Q3W (once every 21 days, day 1)
Route
IV
Fractionated
No
n at RP2D
6 (Part A escalation at 1.2 mg/kg); ~35 total treated at 1.2 mg/kg incl. Part B expansion (44 enrolled total)
Dose basis
TBW
Trial phase
Phase 1/2
Dose-OAE available
Yes
Tox summary basis
RP2D
07
Ocular & expression

Ocular profile & eye-tissue target expression

OAE any-grade
0 %
OAE grade 3+
0 %
OAE data status
documented-absent
Severity (weighted)
0
Keratopathy
0 %
Conjunctival
0 %
Dry eye
0 %
Blurred vision
0 %
Dominant tissue
None
Surface subtype
None
Grading scale
CTCAE v5
Reversibility
N/A
Target expression in eye tissues (HCA detection · HPA bulk)
Cornea (central)
-
Cornea (limbal)
-
Conjunctiva
-
RPE
-
Retina (HPA)
-
Cross-trial comparability
Ascertainment: Systematic eye examsScale: CTCAE v5Denominator: RP2D
08
Identity & registry

Identifiers, registry & notes

ADC id
obi-999
Approval status
Discontinued
Approval year
-
UniProt
-
ADCdb ADC
DRG0SNURI
ADCdb antibody
ANI0DKNXJ
ADCdb target
TAR0RBHCF
Primary source
OBI-999 FIH Phase 1, JCO Precis Oncol 2023;7:e2200496 (PMID 36701651; NCT04084366)
Aliases & development codes
OBI 999; OBI999; Globo-H ADC
Notes
OBI-999 = anti-Globo H ADC: antibody OBI-888 (humanized IgG1) bearing MMAE via a ThioBridge Val-Cit-PAB cathepsin-B-cleavable linker, cysteine (interchain disulfide-rebridged) conjugation, homogeneous DAR4 (>95%). Sponsor OBI Pharma. ADCdb DRG0SNURI (antibody ANI0DKNXJ; payload PAY0FSXOW; ADCdb maps the target to "Microtubule (MT)" which is the payload MoA, not the antigen). No ADCdb linker (LIN) detail page exists for this ADC, so the adcdb{} linker physchem fields (SMILES/formula/MW/TPSA/xLogP) are left blank. Target Globo H is a globo-series tumor-associated CARBOHYDRATE antigen (hexasaccharide glycosphingolipid), not a protein, so target_gene is left blank. OCULAR (the reason this ADC qualifies) is a documented NEGATIVE, from two independent sources: (1) FIH Phase 1 (JCO PO 2023) - 13/15 (87%) had prespecified baseline + on-study ophthalmology exams with "no treatment-emergent ophthalmologic abnormalities vs baseline"; all patients used topical lubrication; (2) CT.gov posted results - NO Eye disorders SOC AE reached the 5% reporting threshold in any of the 7 groups (N=44). The per-PT ocular zeros (corneal/dry eye/blurred vision/conjunctival) are inferred from the global "no ophthalmologic abnormalities" finding plus the absence of any Eye disorders SOC term, not from per-PT enumeration. ocular_surface_subtype=None. DOSING: MTD/RP2D 1.2 mg/kg IV q3w (D1 of 21-day cycle, 60-min infusion). Dose-escalation tested 0.4/0.8/1.2/1.6 mg/kg (n=3/3/6/3). Part B expansion (pancreatic n=11, CRC n=10, basket n=8) all used 1.2 mg/kg; 44 enrolled total. Trial TERMINATED for insufficient efficacy. TOXICITY notes: Paper Tier-B grade-resolved (n=15 escalation): neutropenia G3+ 3/15 (20%, ALL grade 4, ALL at 1.6 mg/kg above RP2D; one was the only DLT, G4 x11 days; none at RP2D 1.2); anemia G3+ 2/15 (13.3%). Notably NO peripheral neuropathy (0/15) despite MMAE - distinguishes OBI-999 from other MMAE ADCs (corroborated by CT.gov: no Nervous-system PN PT >=5%). CT.gov Tier-A any-grade rows are per-cohort with different denominators, all at the 1.2 mg/kg RP2D dose; reporting threshold 5%, assessment NON_SYSTEMATIC. CTCAE/MedDRA version not specified in the publication or the CT.gov record. No pulmonary (ILD/pneumonitis) or infusion-reaction AE met the 5% threshold and the paper did not report them, so those organ systems are left blank (NOT asserted as 0, since below-threshold absence is not a documented zero). MMAE physchem from PubChem CID 11542188 (standard shared payload): formula C39H67N5O7, MW 717.98 (PubChem displays 718.0 g/mol), XLogP3 4.1, TPSA 150 A^2; cationic (+1) basic secondary amine at pH 7.4; bystander-active (preclinical OBI-999 showed bystander killing of low-Globo-H cells, Mol Cancer Ther 2021;20(6):1121). logD7.4 ~2.5 and pKa ~9-10 are literature/derived estimates (tier C); PubChem reports logP (XLogP3) not logD.