TOKYO & WALTHAM, Mass.--(BUSINESS WIRE)--Modalis Therapeutics Corporation (Tokyo Stock Exchange: 4883), a pioneering company developing innovative drugs for the treatment of rare genetic diseases, utilizing its proprietary CRISPR-based epigenome editing technology CRISPR-GNDM®, posted the preprint paper titled “Efficient and durable gene activation by Cas9-mediated epigenome editing in vivo” on bioRxiv.

东京和沃尔瑟姆，马萨诸塞州。-（商业新闻短讯）--Modalis Therapeutics Corporation（东京证券交易所：4883），一家开拓性公司，利用其专有的基于CRISPR的表观基因组编辑技术CRISPR-GNDM®，开发用于治疗罕见遗传病的创新药物，在bioRxiv上发布了题为“通过Cas9介导的体内表观基因组编辑进行高效持久的基因激活”的预印本。

The company reported data demonstrating exceptional durability, robust efficacy and safety in dyW mouse disease model of LAMA2-CMD and in adult and juvenile NHPs..

该公司报告的数据显示，在LAMA2-CMD的dyW小鼠疾病模型以及成人和青少年NHP中，具有非凡的耐久性，强大的功效和安全性。。

LAMA2-CMD is a severe, early onset congenital muscular dystrophy caused by the absence of the LAMA2 protein. Despite significant advances in gene therapy and the approval of about a dozen therapies, the size of the disease-causing gene of LAMA2-CMD, which exceeds 3,000 amino acids, hinders the conventional gene therapy approach using AAV vectors to deliver the healthy version of the mutated gene.

LAMA2-CMD是由缺乏LAMA2蛋白引起的严重的早发性先天性肌营养不良症。尽管基因治疗取得了重大进展，并且批准了大约十几种疗法，但LAMA2-CMD致病基因的大小超过3000个氨基酸，阻碍了使用AAV载体传递突变基因健康版本的常规基因治疗方法。

No approved therapies to address the root cause of this condition exist or are in clinical trials. Modalis’ proprietary CRISPR-GNDM®, is capable of specific modulation of the expression of disease-relevant genes, without introducing double-strand DNA breaks, and our MDL-101 is potentially the first-in-class therapeutics to solve the challenge and provide life-changing therapeutics for the patients of LAMA2-CMD..

目前还没有批准的治疗方法来解决这种情况的根本原因，或者正在进行临床试验。Modalis专有的CRISPR-GNDM®能够特异性调节疾病相关基因的表达，而不引入双链DNA断裂，我们的MDL-101可能是解决这一挑战并为LAMA2-CMD患者提供改变生活的治疗方法的一流疗法。。

'We are thrilled to post our comprehensive preclinical data supporting the development of MDL-101 on bioRxiv. This study represents one of the first demonstrations of successful systemic epigenome editing in NHPs in a viable therapeutic format, as evidenced by significant target engagement and induction of LAMA1 gene expression across muscle tissues,” said Haru Morita, CEO of Modalis.

“我们很高兴在bioRxiv上发布支持MDL-101开发的综合临床前数据。Modalis首席执行官Haru Morita说：“这项研究代表了以可行的治疗形式在NHP中成功进行系统表观基因组编辑的首批证明之一，这可以通过显着的靶标参与和跨肌肉组织诱导LAMA1基因表达来证明。”。

“Additionally, our study is among the first to show that systemic Cas9 expression can be safe and well-tolerated in NHPs. These findings underscore the potential of CRISPR-GNDM® technology as a next-generation gene therapy platform for a variety of neuromuscular and other genetic disorders”..

“此外，我们的研究首次表明全身Cas9表达在NHP中是安全且耐受性良好的。这些发现强调了CRISPR-GNDM®技术作为各种神经肌肉和其他遗传疾病的下一代基因治疗平台的潜力。”。。

About bioRxiv (bioRxiv - the preprint server for Biology)

关于bioRxiv（bioRxiv-生物学预印本服务器）

bioRxiv is a preprint server for life science, medical, and biological journals. It allows for early publication without waiting for long peer review periods. Most of the leading journals in life science, medical, and biology area are partnered with bioRxiv, so manuscript files and metadata submitted to bioRxiv can be directly transmitted to partnered journals when we submit.

bioRxiv是生命科学、医学和生物学期刊的预印本服务器。它允许早期发布，而无需等待长时间的同行评审。生命科学，医学和生物学领域的大多数领先期刊都与bioRxiv合作，因此提交给bioRxiv的稿件文件和元数据可以在我们提交时直接传输到合作期刊。

In addition, papers submitted to bioRxiv are assigned a DOI and are eligible for citation..

此外，提交给bioRxiv的论文被分配了DOI，并且有资格被引用。。

About MDL-101

关于MDL-101

MDL-101 is an experimental, epigenetic editing therapy under investigation for the treatment of LAMA2-Congenital Muscular Dystrophy (LAMA2-CMD). MDL-101 is comprised of a guide nucleotide targeting LAMA1 gene, a highly homologous sister gene of the disease-causing gene LAMA2, enzyme-null Cas9 (dCas9) fused with trans-activating domain driven by a muscle-specific promoter and coded in a muscle-specific AAV vector.

MDL-101是一种正在研究的实验性表观遗传编辑疗法，用于治疗LAMA2先天性肌营养不良症（LAMA2-CMD）。MDL-101由靶向LAMA1基因的指导核苷酸，致病基因LAMA2的高度同源姐妹基因，与肌肉特异性启动子驱动的反式激活结构域融合的酶无效Cas9（dCas9）组成，并编码在肌肉特异性AAV载体中。

MDL-101 upregulates LAMA1 gene products in patients’ muscle tissue to compensate for loss-of-function caused by mutation of LAMA2, and therefore has the potential to provide a one-time, durable treatment to benefit people living with LAMA2-CMD..

MDL-101上调患者肌肉组织中的LAMA1基因产物，以补偿LAMA2突变引起的功能丧失，因此有可能提供一次性，持久的治疗方法，使LAMA2-CMD患者受益。。

About Modalis:

关于Modalis：

Modalis Therapeutics develops precision genetic medicines using epigenome editing technology. Modalis is pursuing therapies for orphan genetic diseases using its proprietary CRISPR-GNDM® technology which enables the gene/locus-specific modulation of gene expression or epigenome editing without the need for DNA cleavage or altering DNA sequence.

Modalis Therapeutics使用表观基因组编辑技术开发精确的遗传药物。Modalis正在使用其专有的CRISPR-GNDM®技术寻求孤儿遗传疾病的治疗方法，该技术可以实现基因表达或表观基因组编辑的基因/基因座特异性调节，而无需DNA切割或改变DNA序列。

Headquartered in Tokyo with all research and development operations in Waltham Massachusetts, the company is listed on the Tokyo Stock Exchange’s Growth market. For additional information, visit www.modalistx.com..

该公司总部位于东京，所有研发业务均位于马萨诸塞州沃尔瑟姆，在东京证券交易所的成长型市场上市。有关更多信息，请访问www.modalistx.com。。