YolTech Therapeutics Secures Tens of Millions in Angel Funding to Pioneer LNP-Delivered In Vivo Gene Editing

VCBeat (WeChat: vcbeat) has learned at the earliest opportunity that, focusing onCombined with LNP(lipid nanoparticle, LNP)YolTech Therapeutics: A Biotech Company Specializing in Delivery and Gene Editing TechnologiesCompleted an angel round of financing in the tens of millions, exclusively invested by Xianfeng Qiyun.

YolTech Therapeutics develops in vivo gene editing therapeutics for genetic and cardiovascular diseases by continuously developing and optimizing CRISPR-Cas, base editing, and other next-generation gene editing tools, as well as through innovative improvements to next-generation mRNA production platforms and lipid nanoparticle (LNP) assembly processes.

Founded just six months ago, the team at YolTech Therapeutics has already achieved in vivo validation across multiple animal models. In mouse liver tissue, the editing efficiency reachedover 80%, approaching the upper limit of the organization’s editing efficiency;In non-human primate (NHP) experiments, the liver tissue editing efficiency reached a level comparable to that of leading global companies.A single injection achieves 60%–70% knockdown of the target gene;Furthermore, YolTech Therapeutics has utilized its proprietary gene-editing tool mining platform to screen for and identifyNovel Editing Tool with International Patent, poised to become the first company in China to advance an in vivo gene editing pipeline into clinical trials.

The ability to rapidly achieve striking development results is because YolTech Therapeutics established, from its inception, a robust framework for“Academia + Industry” Dual-Background, Well-Rounded Founding Team, the three scientists on the team possess both a background in basic research and extensive management experience gained from years of exploration in the industry.

Dr. Wu Yuxuan, Founder of YolTech Therapeutics and Researcher at the School of Life Sciences, East China Normal University, is a renowned scientist in the field of gene editing. From 2015 to 2018, while working at Harvard Medical School, Dr. Wu developed and optimized a CRISPR-Cas-based gene editing system for hematopoietic stem cells (HSCs). This represented the world’s first virus-free, CRISPR-Cas-based gene therapy strategy for hemoglobin disorders.

Upon returning to China, Wu Yuxuan led in 2020World’s First Treatment of β Using Ex Vivo CRISPR-Cas Editing Technology⁰/β⁰Clinical Success Cases of Severe Thalassemia.By employing CRISPR-Cas gene-editing technology to target specific genetic loci in hematopoietic stem cells (HSCs) followed by autologous transplantation of the edited HSCs, this clinical trial enabled patients’ hemoglobin levels to return to the normal range, thereby eliminating lifelong dependence on blood transfusions.

Thalassemia is a monogenic inherited disorder. In severe cases, patients require regular blood transfusions to alleviate anemia; however, this can lead to iron overload from hemoglobin in vital organs, resulting in organ damage. During this clinical trial, Dr. Wu Yuxuan witnessed firsthand how pediatric patients were cured and freed from the risk of premature death. This experience strengthened his resolve to further translate experimental findings into practical applications that genuinely benefit patients. At the same time, he also recognized the limitations of ex vivo gene editing in the treatment of genetic diseases.

First, the application areas of ex vivo editing are relatively limited; currently, it is only well-established in the field of hematopoietic stem cell applications, with indications concentrated on blood disorders.In vivo gene editing has a broader range of indications, with the liver, muscles, and eyes serving as potential target organs.; secondly, ex vivo editing requires the modification of each patient’s autologous cells, making it difficult to establish a standardized, industrialized drug production system, which further increases costs.In vivo editing delivers editing tools to target organs and cells via vectors, facilitating the establishment of standardized and stable manufacturing processes at a lower cost.

Globally, the trend from ex vivo editing to in vivo editing has become increasingly evident. In 2021, Intellia Therapeutics, a representative company in gene editing, announced positive results from the Phase I clinical trial of NTLA-2001, its first in vivo gene editing program delivered via lipid nanoparticles (LNPs): it successfully treated six patients with transthyretin amyloidosis (ATTR), a severe rare genetic disorder. This marked the first clinical validation of efficacy for non-viral vector-based in vivo editing, signaling that in vivo gene editing has opened up new possibilities for disease treatment. Since then, international pharmaceutical giants have also actively positioned themselves in the field of in vivo editing. On January 10, 2022, pharmaceutical giant Pfizer and Beam Therapeutics, a leading company in base editing, announced a four-year exclusive collaboration to develop in vivo base editing therapies for genetic diseases affecting the liver, muscles, and central nervous system. On the same day, Bayer also announced a partnership with Mammoth Biosciences, a unicorn company in the gene editing sector, to develop innovative in vivo gene editing therapies.

In Wu Yuxuan’s view, in vivo gene editing technology comprises three core pillars:Gene editing platforms, delivery systems, and manufacturing processes.In terms of gene editing platforms, YolTech Therapeutics focuses on developing next-generation editing tools represented by Base Editing, achieving comprehensive functionalities such as gene deletion, replacement, and insertion through diverse gene editing strategy options. Notably, YolTech Therapeutics’ proprietaryThe high-throughput mining, screening, and molecular evolution platform currently screens 20 million variants per week and has identified novel editing tools eligible for international patents.

In terms of delivery systems, YolTech Therapeutics has chosen to focus on non-viral vectors, represented by lipid nanoparticles (LNPs). Compared with viral vectors, LNP-based in vivo delivery is more suitable for gene editing tools.Instant Expression, effectively reducing the risk of off-target effects, avoiding the risk of random integration of viral elements into the genome associated with viral therapies, and overcoming immunogenicity issues related to delivery systems such as adeno-associated virus (AAV) vectors. Furthermore, LNP delivery systems offer simpler manufacturing and scale-up processes compared to viral vectors, with more controllable costs.

However, in vivo gene editing is still in its early stages of development globally, forProduction SystemThe requirements are extremely stringent, and the development difficulty is high. Among global companies, only Intellia Therapeutics, Beam Therapeutics, and Verve Therapeutics have successfully applied LNP delivery to achieve efficient in vivo gene editing in their projects. In contrast, the development of LNP-mediated in vivo gene editing in China is still in its early stages, with a scarcity of industry talent and significant challenges in establishing manufacturing processes. One of the co-founders of YolTech Therapeutics previously worked at renowned North American gene editing and mRNA vaccine companies, where he was responsible for delivery system development and industrial-scale production, accumulating many years of experience in LNP and mRNA process development and scale-up. Currently, YolTech Therapeutics has carried out batch preparation and purification of mRNA, batch assembly and production of LNPs, and the establishment of a GMP manufacturing platform, while also developing dozens of quality control standards relevant to clinical trial applications.

YolTech Therapeutics has settled in Shanghai Wendu Technology Park, with a 2,000-square-meter R&D laboratory, including a pilot workshop, now operational. It is reported that YolTech Therapeutics plans to commence construction of its GMP production facility in 2022 and officially initiate preclinical pharmacology and toxicology studies by mid-year.

Looking ahead, YolTech Therapeutics’ strategy will continue to center on its core competency in in vivo gene editing. In terms of editing tools, the company will continuously screen and develop next-generation gene editors that are both highly efficient and safe, to comprehensively meet diverse editing needs. Regarding delivery methods, YolTech plans to persistently research and develop various lipid materials with independent intellectual property rights, thereby enriching its portfolio of delivery vectors targeting the liver and other tissues and organs. On the manufacturing front, the company aims to establish a world-class, proprietary GMP production system to lay the foundation for the large-scale manufacturing of mRNA and lipid nanoparticles (LNPs) required for gene-editing therapies. Furthermore, in pipeline development, YolTech will concentrate its efforts on advancing project progress, focusing in the near to medium term on tackling rare genetic diseases. In the long term, the company seeks to continuously expand its indications, applying in vivo gene editing to diseases with higher prevalence.