Shanghai, China, December 21, 2024 — YolTech Therapeutics today announced that its proprietary in vivo gene-editing drug, YOLT-201, has successfully completed the dose-escalation phase in Phase I clinical trials for the treatment of transthyretin amyloidosis (ATTR) and is set to enter the dose-expansion phase.
YOLT-201: A Novel Gene-Editing Therapy for ATTR
YOLT-201, developed by YolTech Therapeutics, is a new generation of in vivo gene-editing drugs that delivers the CRISPR-Cas9 gene-editing system in the form of mRNA via lipid nanoparticles (LNP). This therapy aims to efficiently and specifically edit the transthyretin (TTR) target gene in the human liver, with the potential to permanently reduce TTR protein levels in the blood and offer a lifelong treatment for ATTR.
Clinical Trial Design and Initial Results
The ongoing I/IIa phase clinical trial of YOLT-201 is designed to assess the safety, tolerability, and preliminary efficacy of the therapy in patients with ATTR-PN (ATTR polyneuropathy) and ATTR-CM (ATTR cardiomyopathy). The trial is an open-label, multicenter, dose-escalation, and dose-expansion study. To date, the trial has enrolled eight subjects (six with ATTR-PN and two with ATTR-CM) and successfully administered doses in two cohorts. Preliminary data indicate that subjects in the high-dose group experienced a reduction of over 90% in TTR protein levels in the blood, demonstrating good safety and tolerability. There were no grade 3 adverse events (AEs), dose-limiting toxicities (DLTs), or serious adverse events that interrupted dosing.
SRC Meeting Outcomes and Next Steps
In a meeting between researchers and sponsors, the high dose was identified as the optimal biologically active dose (OBD) based on existing safety and efficacy data. Consequently, the SRC decided to conclude the dose-escalation study for ATTR-PN patients and proceed to the dose-expansion phase to further evaluate the efficacy and safety of YOLT-201 in a larger subject group.
About the YOLT-201 Phase I Clinical Trial (YT-YOLT-201-101)
YT-YOLT-201-101 is a multicenter, open-label, single-dose Phase I/IIa clinical study evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of YOLT-201 in patients with ATTR-PN and ATTR-CM. The trial is divided into two stages: the first stage is an open-label, single-dose, dose-escalation trial to determine the OBD of YOLT-201; the second stage is an open-label, single-dose, dose-expansion trial to further assess the safety and preliminary efficacy of YOLT-201 at the OBD.
About YOLT-201
YOLT-201 injection liquid medication uses ionizable lipids and other lipid components as the main excipients to encapsulate mRNA and sgRNA, forming lipid nanoparticles (LNP). After intravenous injection, the medication is recognized by the LDLR receptor expressed on liver cells, leading to the release of mRNA and sgRNA into the cell cytoplasm. This process results in the translation of gene-editing proteins that, in combination with sgRNA, specifically target and edit the TTR gene sequence, silencing the gene and halting the production of TTR protein, with the goal of achieving a “one-time treatment, complete cure” for ATTR.
About YolTech Therapeutics
YolTech Therapeutics is an innovation-driven biotechnology company focused on developing in vivo gene-editing drugs based on mRNA-LNP delivery. Established in 2021, the company has developed next-generation gene editors, YolCas™ and base editors, YolBE®, and proprietary lipid nanoparticles, YOL-LNPs®, achieving more efficient in vivo delivery. With a Shanghai R&D center and GMP production base, YolTech Therapeutics possesses advanced mRNA-LNP production processes and a comprehensive platform for the production and quality control of in vivo gene-editing drugs. The company’s first clinical trial for an ATTR gene-editing drug was approved by the National Medical Products Administration’s Center for Drug Evaluation (CDE) in March 2024, and the first patient was enrolled in June 2024, marking the entry of China’s first LNP-mediated in vivo gene-editing drug into the clinical stage. Additionally, gene-editing projects for familial hypercholesterolemia (FH) and primary hyperoxaluria (PH1) have successfully initiated investigator-sponsored clinical studies, achieving promising initial clinical results.-Fineline Info & Tech
