YolTech Therapeutics announced updated data from its ongoing Phase I/IIa clinical trial of YOLT-201, a first-in-class CRISPR/Cas9-based in vivo gene-editing therapy for ATTR amyloidosis. The trial has completed dosing in eight participants, including six patients with ATTR amyloidosis with polyneuropathy (ATTR-PN) and two patients with ATTR amyloidosis with cardiomyopathy (ATTR-CM), across two dose cohorts. No Grade 3 adverse events (AEs), dose-limiting toxicities (DLTs), or serious adverse events (SAEs) leading to treatment discontinuation have been observed.

All ATTR-PN participants across both dose cohorts have completed dosing and follow-up. Preliminary data indicate that participants in the higher dose cohort achieved over 90% reductions in circulating TTR protein levels, with the therapy demonstrating robust safety and tolerability.

Following discussions between investigators and the study sponsor during the Safety Review Committee (SRC) meeting, the higher dose was identified as the optimal biologically active dose (OBD) based on the available safety and efficacy data. Consequently, the SRC has decided to conclude dose-escalation studies for ATTR-PN patients and advance directly to the dose-expansion phase, further evaluating YOLT-201's therapeutic potential in a broader patient population. 

YT-YOLT-201-101 trial is a multicenter, open-label, single-dose phase I/IIa clinical study evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamic parameters of YOLT-201 in patients with transthyretin amyloidosis polyneuropathy (ATTR-PN) and transthyretin amyloidosis cardiomyopathy (ATTR-CM). The trial consists of two stages: the first stage is an open-label, single-dose, dose-escalation study to determine the optimal biological dose (OBD) of YOLT-201; the second stage is an open-label, single-dose, dose-expansion study to preliminarily assess the safety and preliminary efficacy of YOLT-201 at the OBD.