Notes
XB-002 (samatatug zovodotin; ICON-2) = anti-tissue-factor (F3/CD142) ADC; fully human anti-TF mAb 'samatatug' (clone 25A3, coagulation-silent: does not affect FX activation or thrombin generation even at 100 nM) conjugated via the Zymeworks zovodotin linker-payload (Mc-PEG3-Val-Cit / MT-vc; cathepsin-B Val-Cit cleavable; stochastic partial-reduction interchain-Cys/maleimide) to ZD02044, a proprietary N-acyl sulfonamide auristatin (tubulin/microtubule polymerization inhibitor), reported less hydrophobic than MMAE/vedotin. Same ZD02044/zovodotin payload as ZW49 (zanidatamab zovodotin). Developer Exelixis (asset from Iconic Therapeutics; payload from Zymeworks). Development DISCONTINUED (unlikely to improve on tisotumab vedotin / other TF ADCs).
CLINICAL (JEWEL-101, NCT04925284, Ph1 dose-escalation, ENA 2022 / EJC 2022;174(S1) abstr): N=19 across 5 dose levels IV Q3W (0.16 n=3, 0.5 n=3, 1.0 n=6, 1.5 n=3, 2.0 mg/kg n=4); NO DLTs; RP2D/MTD NOT determined (program terminated) -> rp2d_dose left blank, n_rp2d=19 set to the full dose-escalation safety population that the % denominators derive from (8/19=42.1% anticoagulant use, 8/19=42% ocular, 5/19=26% conjunctivitis, 3/19=16% dry eye all reconcile to N=19). 42% had grade-3 TEAEs (none grade 4/5); 63% treatment-related AEs, all grade <=2 except one grade-3 hypertension. OCULAR: any ocular TEAE 42% = noninfective conjunctivitis 26% + dry eye 16% (both treatment-related); dose-dependent (75% at 2 mg/kg vs ~33% at lower levels); investigators observed NO corneal toxicity (ae_corneal_pct=0, documented); all ocular events grade 1-2 and reversible with lubricating/vasoconstrictive/corticosteroid/antibiotic eyedrops -> oae_g3plus_pct=0 (documented), ae_reversibility=Reversible, subtype Conjunctival (on-target; matches TF conjunctival expression and the tisotumab-vedotin conjunctival profile, contrasting MMAE corneal keratopathy). No bleeding events despite anticoagulant use in 8/19.
CAVEATS / left blank (never 0 unless documented): (1) Antibody subclass not explicitly stated for XB002 ('human IgG', isolated from a full-length human IgG library) -> antibody_isotype blank; likely IgG1 (Zymeworks platform; ZW49 same payload is IgG1) but not source-confirmed. (2) DAR = 3.8 from the peer-reviewed preclinical paper (HPLC); ADCdb lists 3.3 -> used 3.8 (primary publication). (3) Payload ZD02044 physchem (MW/xLogP3/logD7.4/TPSA/pKa/charge/bystander) NOT in PubChem (proprietary; no public CID; linker-payload MT-vc-ZD02044 CAS 1800462-96-7) -> payload_physchem numerics blank. Bystander not definitively characterized for ZD02044 (cleavable auristatin -> bystander mechanistically plausible/partial, but unsourced). (4) Non-ocular organ AEs (hepatic/heme/GI/pulmonary/PN/infusion) NOT itemized in the available dose-escalation summary -> all blank, not 0. (5) CTCAE version not stated (era ~2022 -> likely v5.0) -> ae_grading_scale=Unknown. (6) Linker plasma t1/2 not quantified; clinical PK shows intact-ADC and total-antibody PK similar with low free payload (qualitatively stable) -> linker_plasma_t_half and in_vitro_stability_pct_at_timepoint blank. (7) Patients with significant ocular disease were excluded per protocol. (8) NOTE: the ADC Review 'ICON-2' drugmap page erroneously conflates XB002 with tisotumab's TF-011 antibody and calls the payload MMAE -> DISREGARDED in favor of the peer-reviewed preclinical paper (clone 25A3 / ZD02044). Tiers: composition & chemistry B (peer-reviewed preclinical paper), linker physchem C (ADCdb computed), clinical/ocular & dosing D (conference abstract, corroborated by Oncologist 2024 OAE review); overall C.