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)
IV infusion over 60 min, day 1 of each 21-day cycle (Q3W)
0%
n=13 · OBI-999 FIH Phase 1/2
0.4-1.6 mg/kg (incl. RP2D 1.2)
IV q3w (D1/21d)
0%
· OBI-999-001 FIH
0.4-1.6 mg/kg
IV q3w (D1/21d)
0%
· NCT04084366 (Part A+B, posted results)
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.
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.