Yoltech Therapeutics has announced positive data from its Phase I/IIa clinical trial of YOLT-201, a first-in-class CRISPR/Cas9-based in vivo gene-editing therapy for transthyretin amyloidosis (ATTR). The trial, which included patients with both ATTR amyloidosis with polyneuropathy (ATTR-PN) and ATTR amyloidosis with cardiomyopathy (ATTR-CM), showed promising results in terms of safety and efficacy.
The study involved eight participants across two dose cohorts. Encouragingly, no Grade 3 adverse events (AEs), dose-limiting toxicities (DLTs), or serious adverse events (SAEs) leading to treatment discontinuation were observed.
Significant TTR Reduction
Data from the trial indicated that all ATTR-PN participants in both dose cohorts completed dosing and follow-up. Notably, preliminary data revealed that participants in the higher dose cohort achieved over 90% reductions in circulating TTR protein levels. This substantial reduction suggests a strong pharmacodynamic effect of YOLT-201.
Optimal Biological Dose Identified
Following a thorough review of the safety and efficacy data, the Safety Review Committee (SRC) identified the higher dose as the optimal biologically active dose (OBD). As a result, the SRC has decided to conclude dose-escalation studies for ATTR-PN patients and proceed directly to the dose-expansion phase. This decision will allow for further evaluation of YOLT-201's therapeutic potential in a larger patient population.
About the YOLT-201-101 Study
The YT-YOLT-201-101 trial is a multicenter, open-label, single-dose phase I/IIa clinical study. It aims to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic parameters of YOLT-201 in patients with ATTR-PN and ATTR-CM. The trial is structured in two stages: a dose-escalation phase to determine the OBD, followed by a dose-expansion phase to assess safety and preliminary efficacy at the OBD.
Mechanism of Action
YOLT-201 utilizes lipid nanoparticles (LNPs) to deliver mRNA and sgRNA. Upon intravenous injection, these LNPs are taken up by liver cells, where the mRNA is translated into an editor protein. This protein, guided by the sgRNA, modifies the TTR gene, preventing its transcription into mRNA and thus halting the production of the TTR protein. This mechanism aims for a one-time administration leading to a comprehensive cure for ATTR diseases.
Yoltech Therapeutics' Focus
Yoltech Therapeutics is dedicated to developing gene-editing medicines for serious diseases. The company has a high-throughput evolution platform and an innovative LNP delivery system. With a pipeline of over 10 genetic medicines, Yoltech is targeting cardiovascular, metabolic, and infectious diseases, among others. Clinical trial clearance has been received for its leading asset, YOLT-201.
