SHANGHAI, Dec. 21, 2024 /PRNewswire/ — YolTech Therapeutics today 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.
**About the YOLT-201-101 Study**
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.
**About YOLT-201**
YOLT-201 Injection utilizes several lipid components including ionizable lipids as primary excipients to encapsulate mRNA and sgRNA raw materials, forming lipid nanoparticles (LNP). Upon intravenous injection into the body, plasma ApoE protein binds to the surface of LNP particles. Liver cells expressing the LDLR receptor recognize ApoE protein and engulf the LNP through endocytosis, forming endosomes. The decrease in pH within endosomes promotes electrostatic interactions between ionizable lipids and endosomal membranes, leading to membrane disruption and the release of mRNA and sgRNA. mRNA, in the cytoplasm, binds to ribosomes, translating the editor protein. The editor protein, in combination with sgRNA, enters the cell nucleus. sgRNA specifically locates the editor to the TTR gene sequence, and the editor protein modifies the target TTR gene, preventing its normal transcription into mRNA. This process stops the production of the TTR protein, achieving the goal of a one-time administration for a comprehensive cure of ATTR diseases.
**About YolTech**
YolTech Therapeutics is a pioneering gene editing company dedicated to develop a robust gene editing medicines to treat patients with serious diseases, which has built leading high-throughput evolution platform and innovative LNP deliver system. It possesses strong capability of novel Cas and base editor discovery and exceptional in-house LNP production capacity for GMP manufactory, with independent intellectual property rights and core patent protection globally. It has created a pipeline with 10+ genetic medicines focusing on cardiovascular diseases, metabolic diseases, infectious diseases as well as more common and rare diseases. Clinical trial clearance has been received for its leading asset.
For more information, please visit: www.yoltx.com
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SOURCE YolTech Therapeutics
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