Mechanistically, ATX020 blocks KIF18A's plus-end movement on spindle fibers, increasing spindle length, resulting in chromosomal mis-segregation, aneuploidy, and DNA damage. Our findings suggest that ATX020 inhibits CIN+ HGSOC cells mainly by inducing mitotic arrest and DNA damage, disrupting KIF18A's function crucial for mitosis.

ATX020 is a potent KIF18A inhibitor with a high degree of kinesin selectivity, favorable in vitro and in vivo ADME properties, and robust efficacy in the OVCAR-3 cell-derived xenograft (CDX) model. A high-resolution crystal structure of the KIF18A-tubulin complex and an experimentally guided model of ATX020 bound to the complex are provided, supporting future structure-based drug design of KIF18A inhibitors.

P1, N=83, Not yet recruiting, Axcynsis Therapeutics Pte Ltd | Initiation date: Aug 2025 --> Nov 2025

Collagen and silicone punctal plugs were placed and the patient was started on preservative free artificial tears, topical loteprednol 0.5 %, later replaced with topical prednisolone acetate 1 % drops, and brimonidine 0.2 % in both eyes. Ocular symptoms and exam findings waxed and waned with continued infusions of the ADC. This case reports an incidence of corneal pseudomicrocysts associated with TORL-1-23 treatment, which should be recognized as a potential adverse effect of this novel therapy.

P1, N=88, Active, not recruiting, Daiichi Sankyo | Recruiting --> Active, not recruiting

P1, N=90, Recruiting, TORL Biotherapeutics, LLC | Trial primary completion date: Apr 2025 --> Aug 2026 | Trial completion date: Nov 2025 --> Nov 2026

P1, N=256, Not yet recruiting, Qilu Pharmaceutical Co., Ltd.

P1, N=90, Recruiting, TORL Biotherapeutics, LLC | Trial primary completion date: Nov 2024 --> Apr 2025

P1, N=78, Not yet recruiting, Axcynsis Therapeutics Pte Ltd

P2, N=230, Recruiting, TORL Biotherapeutics, LLC | Not yet recruiting --> Recruiting

P2, N=230, Not yet recruiting, TORL Biotherapeutics, LLC

P1, N=85, Recruiting, Daiichi Sankyo | N=125 --> 85