● ART001, an in vivo gene editing product delivered by LNP for the treatment of Transthyretin amyloidosis (ATTR), became the first-in-kind to enter clinical stage (IIT) in China in August, 2023.

● ATTR patients treated with a single dose of ART001 achieved over 90% reduction in serum TTR level after 4 weeks.

● ART001 demonstrates an outstanding safety profile. No infusion-related reaction was observed in any of the patients treated. No >Grade 1 liver enzyme elevation was observed.

● In studies using primary human hepatocytes, no off-target editing was observed in ART001 even at up to ~80 times of EC90.

● ART001 shows the potential to be the best-in-class in vivo gene editing product for ATTR.

The on-going IIT (investigator-initiated trial) study for ART001, a single-course, intravenously administered treatment for transthyretin amyloidosis (ATTR), is sponsored by AccurEdit Therapeutics and carried out by Dushu Lake Hospital Affiliated to Soochow University. The trial is supported by the Chinese Organization for Rare Disorders.

A total of 10 patients have been treated at doses up to 1.0 mg/kg body weight (mpk) by far. Based on available data, all patients treated at 1.0 mpk achieved >90% serum TTR reduction after 4 weeks. All patients dosed at 0.5 mpk and 0.7 mpk also achieved at least 80% serum TTR reduction after 4 weeks. ART001 is well-tolerated and demonstrated an overall outstanding safety profile.

ATTR amyloidosis is a rare, progressive and fatal disease, which occurs when mutation in the TTR gene causes the liver to produce structurally unstable transthyretin proteins with a propensity to misfold, resulting in the formation of amyloid fibrils that deposit in various organs and peripheral nerves and cause them to function abnormally.

Currently existing treatments for ATTR include small molecule-based stabilizers and RNAi, both of which require repeated dosing for as long as the patients live. In vivo gene editing represents a new class of treatment that has the potential to treat ATTR with a single dose for lifetime.

Leveraging its end-to-end technical platform for in vivo gene editing, AccurEdit developed ART001, which delivers the CRISPR genome editing components to the liver by lipid nanoparticles (LNP) to carry out the editing of the TTR gene, inactivating the production of the TTR protein.

ART001 is well tolerated by all patients treated and demonstrates an outstanding safety profile. No >Grade 1 liver enzyme elevation was observed in any of the patients treated. So far, no patient in the study experienced infusion-related reaction, which was observed in 38% of the patients treated with a similar product previously.

Off-target editing is often one of the major concerns for gene editing product. Prior to the initiation of the IIT clinical study, ART001 has been tested extensively to ensure the risk of off-target editing is minimized. In studies using primary human hepatocytes, no off-target editing was observed after treating with ART001 at doses up to ~80 times of EC90. 

"Currently, there are very limited treatment options for ATTR patients in China and many parts of the world. " said Prof. Yonggang Hao, the coordinating investigator of the ART001 IIT study, "ART001 is a landmark product in China that demonstrates satisfying safety profile and remarkable potential of efficacy according to the data obtained. Developed as a single dose therapy, ART001 provides an innovative treatment which not only benefits the patients medically, but also enables significant cost reduction to the patients and the healthcare system. We will continue to advance the clinical research on ART001 to provide an accessible treatment to the underserved populations."

Rufang Huang, founder and director of Chinese Organization for Rare Disorders, said, "We are keenly aware of the critical medical needs of struggling patients with rare diseases like ATTR. Driven by these ever-growing needs, our team worked consistently to facilitate research and development of innovative therapies for the past decade. The fact that AccurEdit Therapeutics is able to provide the patients a cutting edge ATTR treatment based on its global leading CRISPR/Cas9 technology within just 2 years impressed us greatly. We are thrilled to see ART001’s safety and TTR reduction data and look forward to working together to advance it to later stages of clinical trials!"

"We greatly appreciate all the patients and their families, Prof. Hao and his team, as well as Mr. Huang and Chinese Organization for Rare Disorders to make this study possible. " stated Dr. Wang Yongzhong, founder, chairman and CEO of AccurEdit Therapeutics. "The AccurEdit team is extremely encouraged as ART001 became the ground-breaking product in the field of in vivo gene editing in China and demonstrated the potential to be the best-in-class product for ATTR in the world. We are happy to see that ART001 is showing potential to benefit patients in China and hope to bring it to patients outside of China in the near future.”