On June 7, 2023, our company successfully completed the enrollment of 240 subjects for the ulcer indication in the Phase III clinical trial of our “Recombinant Human Hepatocyte Growth Factor Naked Plasmid Injection” (code name NL003), which is intended for the treatment of severe lower-limb ischemic disease.

Lower limb ischemic disease refers to a group of conditions characterized by narrowing or occlusion of the lower limb arteries due to various causes, resulting in insufficient blood flow and leading to ischemic manifestations such as intermittent claudication, rest pain, ulcers, and gangrene in the lower limbs. Based on the degree of ischemia, clinicians use the Rutherford classification system to grade lower limb ischemic disease from mild to severe, ranging from Grade 0 to Grade 6; Grades 4 through 6 are classified as severe lower limb ischemic disease (CLI). NL003 is specifically designed to conduct clinical studies targeting two indications: rest pain associated with lower limb arterial ischemia (Rutherford Grade 4) and ulcers (Rutherford Grade 5).

This Phase III clinical trial adopts a nationwide, multicenter, randomized, double-blind, placebo-controlled study design. The trial is conducted simultaneously under two separate protocols: the resting pain trial plans to enroll 300 patients, while the ulcer trial plans to enroll 240 patients, for a total of 540 enrolled participants. Led by Peking Union Medical College Hospital, the trial involves 24 research centers across China and aims to evaluate the efficacy and safety of NL003 in treating patients with severe lower-limb ischemic disease.

NL003 is a Class 1 gene therapy drug—a therapeutic biological product independently developed by our company—and is supported under the national “Major New Drug Development” initiative. By locally injecting NL003 into the ischemic site via intramuscular administration, plasmid DNA is transfected into striated muscle cells, enabling them to continuously express and secrete hepatocyte growth factor (HGF), a protein with angiogenic properties. This promotes the regeneration of new blood vessels, establishes collateral circulation at the ischemic site, and creates a “molecular bridging” mechanism, thereby enhancing blood flow to the ischemic area and achieving the goal of treating ischemic diseases. According to relevant data, China has approximately 45 million patients with peripheral arterial disease (PAD) and over 4 million patients with critical limb ischemia (CLI). Currently, there are no effective treatments available worldwide. In previously completed preliminary clinical trials, NL003 has demonstrated promising clinical efficacy.

Xu Songshan, Chairman of the company, stated that the completion of patient enrollment for the ulcer indication is of great significance to the company. This clinical trial was launched in July 2019 and, over the past three years amid the pandemic, has faced numerous challenges. Thanks to the company’s meticulous organization and the concerted efforts of all participating researchers, we have now been the first to complete enrollment of all subjects for the ulcer indication, marking an important milestone in this clinical trial. We extend our heartfelt gratitude to all the researchers for their hard work and dedication. The company will continue to press ahead with high quality, completing the subsequent data cleaning and summarization tasks for the ulcer indication. At the same time, we will remain fully committed to advancing the resting pain trial and strive to complete enrollment as soon as possible. We look forward to the early successful development of NL003, providing patients with lower-limb arterial ischemic disease a brand-new, safe, and effective treatment option, thereby breaking the current situation of limited therapeutic choices in this field.