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
