Notes
ARX-305 (ARX305; NCB-002), Ambrx/NovoCodex anti-CD70 MMAF-class ADC. Composition (ADCdb DRG0BWCTV + Ambrx AACR 2023 #6318 / ESMO 2023 71P): humanized anti-CD70 antibody (isotype not disclosed; likely IgG1 on Ambrx pAF platform but left blank), site-specifically conjugated at the non-natural amino acid para-acetyl-phenylalanine (pAF) via a stable oxime bond to a non-cleavable Oxime-PEG3 linker (ADCdb LIN0BDQFG), DAR 2 (homogeneous). Payload is AS269 (Amberstatin 269), a potent, membrane-impermeable MMAF (auristatin F) derivative; ADCdb maps the payload to MMAF (PAY0QLDVX). Released catabolite is pAF-AS269. Membrane-impermeable + charged free carboxylate => no bystander effect.
LINKER PHYSCHEM CAVEAT: ADCdb's LIN0BDQFG "Oxime-PEG3" entry catalogs only the methoxy-PEG3-oxyamine fragment (C7H17NO4, MW 179.216, TPSA 62.94, xLogP -0.4437), representing the oxime-PEG linker chemistry, not the full linker-payload. ADCdb displayed the SMILES as "MOCCOCCOCCON" - corrected here to "COCCOCCOCCON" per the listed InChI (InChIKey UPZRLQLRXOQKOM; methoxy-triethyleneglycol-aminooxy). ADCdb cross-references the same linker to ARX-517.
PAYLOAD PHYSCHEM: reported as MMAF standard values (PubChem CID 10395173): MW 731.97, formula C39H65N5O8, XLogP3 2.1, TPSA 167, formal charge 0 (zwitterionic at pH 7.4; anionic carboxylate drives membrane impermeability). logD7.4 and pKa not reported with a citable value (left blank). Actual payload is the AS269/amberstatin MMAF derivative, so MMAF values are a close proxy.
CLINICAL (ESMO 2025 abstr 959P; tier D, conference abstract): China first-in-human Phase 1, advanced solid tumors, ARX305 0.24-4.2 mg/kg IV Q3W, Bayesian Optimal Interval dose-escalation; 41 patients enrolled Oct 2022-May 2025 (RCC 70.7%; also liver, ampulla of Vater, colorectal, nasopharyngeal, parotid). RP2D/MTD NOT yet determined (escalation ongoing) - so rp2d_dose left as "not determined" and n_rp2d blank; all reported rates are POOLED across the full 41-patient dose-escalation safety population (this single pooled cohort is the primary/headline cohort, tagged accordingly in line_context). CD70 by IHC: >=1% = positive, >=50% = high.
SAFETY: TRAE 85.4%; grade>=3 39.0% (16/41); no grade 5. Ocular (priority; all grade 1-2, none >=G3): dry eye 46.3%, vision blurred 43.9%, keratopathy 41.5% - classic off-target MMAF-class corneal epitheliopathy triad (=> ocular_surface_subtype "Corneal (off-target)"; oae_any_pct 46.3 = max PT; oae_g3plus_pct 0 documented). Other common TRAEs: AST increased 58.5% (Hepatic), proteinuria 58.5% (renal), anaemia 43.9% (Heme), hyponatremia 34.1% (metabolic), fatigue 31.7% (general), thrombocytopenia 29.3% (Heme). NOT mapped to toxicity_rows because organ_system enum lacks a category: proteinuria (renal), hyponatremia (metabolic), fatigue (general/constitutional). No GI, pulmonary/ILD, peripheral-neuropathy, or infusion-reaction events reported among common TRAEs (consistent with low-PN MMAF profile) - left blank (= not in literature). Per-PT grade>=3 breakdown not available in accessible sources; toxicity_rows n values are back-calculated from reported % x N=41 (all clean integers). EFFICACY: ORR 26.1% (6/23) in CD70-positive evaluable; 42.9% (6/14) in high-CD70 RCC.
SOURCE ACCESS NOTE: annalsofoncology.org fulltext and the Larvol mirror both returned HTTP 403; clinical figures were extracted from the indexed search abstract content (corroborated by the curated wave1 oae_hint), ADCdb, adcreview.com, and Ambrx preclinical disclosures. Tiers: composition/adcdb/payload_physchem/chemistry = C (ADCdb + PubChem-computed + company abstracts); dosing/ocular/toxicity = D (conference abstract).