Initial Dosing Begins in YOLT-201 Phase I Trial

YolTech Therapeutics, a biotechnology company based in Shanghai, has announced a significant milestone in the development of its in vivo gene editing therapy, YOLT-201. The first patient has been successfully enrolled in the Phase I clinical trial for YOLT-201, marking a crucial step forward in the clinical pathway of this innovative therapeutic candidate.

ATTR, or transthyretin amyloidosis, is a severe genetic disorder caused by the misfolding of the transthyretin (TTR) protein. This misfolding leads to the formation of amyloid fibrils that deposit in various organs and tissues, including the heart and peripheral nerves. This disease can manifest in individuals as young as their teens and 20s when the mutation is hereditary (hATTR), although other forms typically affect individuals over 50.

YolTech's YOLT-201 is at the forefront of in vivo gene editing therapies, utilizing advanced lipid nanoparticle (LNP) delivery systems. Preclinical studies in non-human primates have demonstrated that a single infusion of YOLT-201 can safely and effectively reduce TTR protein levels in the serum. This reduction could potentially offer lifelong clinical benefits to patients suffering from ATTR.

For the clinical trial, eligible patients with ATTR are being recruited from across the nation. The first patient received their initial dose on June 28, 2024, and two weeks post-dosing, the patient was reported to be in good health with no significant adverse events related to the drug observed.

Dr. Yuxuan Wu, the Founder and CEO of YolTech, highlighted the importance of this milestone, stating, "The completion of the first patient dosing and safety assessment is a critical milestone in the clinical development of YOLT-201." He added that the early clinical trials have shown excellent safety and efficacy for YOLT-201, and he believes it has the potential to revolutionize the treatment landscape for ATTR diseases globally.

Earlier this year, on March 1, 2024, YolTech announced that the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) had approved the clinical trial application for YOLT-201. Significantly, this marks the first clinical trial approval in China for an in vivo gene editing drug mediated by lipid nanoparticles.

The YT-YOLT-201-101 trial is a multicenter, open-label, single-dose Phase I/IIa clinical study aimed at 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: an initial dose-escalation phase to determine the optimal biological dose (OBD) of YOLT-201, followed by a dose-expansion phase to preliminarily assess the safety and efficacy of YOLT-201 at the OBD.

YOLT-201 Injection incorporates several lipid components, including ionizable lipids, to encapsulate mRNA and sgRNA raw materials, forming lipid nanoparticles. Upon intravenous administration, these particles interact with plasma ApoE protein, which facilitates their uptake by liver cells. Once inside the cells, the mRNA is translated into the editor protein that, in combination with sgRNA, modifies the TTR gene, halting its normal function and stopping the production of TTR protein. This gene-editing mechanism aims to achieve a one-time, comprehensive cure for ATTR diseases.

YolTech Therapeutics is committed to pioneering gene editing medicines targeting a range of serious diseases. The company boasts a high-throughput evolution platform and an innovative LNP delivery system, with strong capabilities in discovering novel Cas and base editors. It has built a robust pipeline of over ten genetic medicines addressing cardiovascular, metabolic, and infectious diseases, as well as both common and rare conditions.