Notes
MYTX-011 (Mythic Therapeutics) is a pH-dependent anti-cMET, site-specific DAR2 vc-MMAE ADC; the pH-dependent binding dissociates cMET in the acidic early endosome for preferential lysosomal payload delivery. Source triangulation: ADCdb DRG0CDYJL (composition + linker LIN0SQEDQ Mc-Val-Cit-PABC physchem), ASCO 2025 poster #8613 / Heist et al. JCO 2025;43(16_suppl):8613 + Mythic press release (KisMET-01, NCT05652868) for dosing/toxicity, and standard MMAE (PubChem CID 11542188) payload physchem.
COHORT NUANCE (important): headline OAE rates (blurred vision 47%, keratopathy 41%, keratitis 32%, dry eye 12%; G3+ 20/18/11/2%) are from the POOLED >=4.0 mg/kg Q3W efficacious-dose safety population (n=66), exactly as the poster/press release report them; rows tagged line_context='RP2D' reflect this primary cohort. The FORMAL RP2D selected was 5.0 mg/kg Q3W with a 2-on/1-off dose break (every 3rd cycle skipped to allow corneal epithelial regeneration), with 4.0 mg/kg Q3W as an alternative Part 2 dose; a discrete 5.0-mg/kg-only safety cohort was not broken out. MTD not reached up to 8.3 mg/kg (escalation stopped after 3 pts at 8.3). All-cause across n=66: 94% any TRAE, 56% >=Grade 3 TRAE.
OCULAR: eye disorders were the most common TRAEs; events limited to the cornea, reversible, manageable with temporary dose hold; >=Grade 3 ocular events more frequent at >=5.8 mg/kg (blurred vision 60%/keratopathy 52% any-grade in that stratum). Ocular AEs caused discontinuation in 4 pts (6%); 3 of 4 at >=5.8 mg/kg, all 4 predated the most updated prophylaxis. Prophylaxis similar to approved MMAE ADCs (e.g., enfortumab vedotin) was implemented and updated during escalation. Ophthalmic exam required at baseline, before every other cycle, and on ocular symptoms. dose_oae_available=TRUE (ocular rates reported at two dose strata: 4.0 & 5.0 mg/kg n=33 and >=5.8 mg/kg n=33; dose strata sum exactly to the n=66 totals, confirming extraction).
NOT REPORTED (left blank, not zero): anemia, thrombocytopenia, pneumonitis/ILD, and infusion-related reactions were not in the >=10% any-grade / >=5% G3+ Table 3 (poster states hematologic toxicity, pneumonitis, GI symptoms, peripheral neuropathy and peripheral edema 'were low'). Also reported but outside the organ-system buckets: fatigue 23% (3/66 G3+), decreased appetite 15%, AST 21%/ALT 15% captured under Hepatic. Antibody isotype, origin, and Fc engineering NOT disclosed by Mythic or ADCdb (left blank; effector-silencing/FcgR status not determinable). Conjugation is site-specific (DAR2) via maleimidocaproyl (mc) chemistry; the exact attachment residue (engineered Cys vs interchain) is not explicitly named in public sources. CTCAE version not stated in the poster or the NCT05652868 record. Linker physchem (SMILES/formula C28H40N6O7/MW 572.663/TPSA 200.03/xLogP 0.6769) are ADCdb-computed values for the Mc-Val-Cit-PABC moiety (PubChem CID 57544445). No intact-ADC plasma half-life (days) reported; poster notes 'excellent stability' qualitatively. Primary clinical evidence is a conference poster/abstract -> overall tier D.