On July 12, 2024, our company’s independently developed Class 1 therapeutic biological product—a new drug called Donaperminogene Seltoplasmid Injection—“Recombinant Human Hepatocyte Growth Factor Naked Plasmid Injection (code name NL003)” received the “Notice of Acceptance” issued by the National Medical Products Administration (NMPA), with acceptance number CXSS2400066. This marks the official acceptance of the NL003 New Drug Registration Application and its entry into the new drug registration review process.

NL003 is a Class 1 therapeutic biological product that has not been listed either domestically or internationally. It is an innovative gene therapy drug intended for the treatment of severe lower-limb ischemic disease (CLI). In the ischemic area of the lower limbs...   During local intramuscular injection, this product—a naked plasmid—enters skeletal muscle cells. Leveraging the cell’s protein-expression machinery, it expresses the target gene carried by the plasmid and secretes two isoforms of HGF protein, thereby promoting the formation of new blood vessels and collateral circulation, increasing local blood flow to ischemic areas, and ultimately achieving therapeutic effects for lower-limb arterial ischemic disease.

Peripheral arterial disease (PAD) is a group of conditions characterized by narrowing or occlusion of the arteries in the lower limbs due to various causes, leading to insufficient blood flow and resulting in ischemic manifestations such as intermittent claudication, ulcers, and gangrene in the lower limbs. Epidemiological data indicate that PAD affects the physical and mental health of more than 200 million people worldwide, with lower-limb PAD being the most common type of peripheral arterial disease. According to the 2022 China Cardiovascular Health and Disease Report, the prevalence of lower-limb PAD among the general population aged over 35 in China is 6.6%, corresponding to approximately 45.3 million cases. Severe lower-limb ischemia (CLI) represents the most advanced stage of PAD. Literature suggests that about 10% of patients with lower-limb PAD will progress to CLI. CLI has a high incidence, long disease course, and high disability rate; its 5-year mortality rate exceeds 50%, significantly higher than that of many serious diseases, including most cancers.

Currently, there are no effective therapeutic drugs available worldwide. Clinical treatment primarily relies on surgical interventions such as interventional procedures and vascular bypass surgery, but the treatment outcomes are less than ideal, leaving a significant unmet medical need. Compared with existing treatment approaches, the NL003 therapeutic strategy is innovative—it can address distal ischemia caused by vascular occlusion through therapeutic angiogenesis, thereby achieving the desired therapeutic effect and preventing the condition from progressing to a life-threatening stage or severely compromising the patient’s quality of life. As a result, it can deliver sustained clinical benefits.

The Phase III clinical trial of NL003 is being conducted simultaneously under two separate study protocols: one for ulcers and the other for rest pain. The indication submitted for approval this time is limb ulcers caused by severe lower-limb ischemia (including atherosclerotic occlusive disease of the lower limbs, thrombo-obliterative vasculitis, and diabetic lower-limb ischemia). The results of the Phase III clinical trial have met expectations: compared with placebo, the treatment demonstrated statistically significant efficacy in the primary clinical endpoint—complete ulcer healing rate (P < 0.0001). Moreover, the treatment achieved the primary endpoint in all subgroups of patients with different underlying conditions, including atherosclerotic occlusive disease, thrombo-obliterative vasculitis, and diabetic lower-limb ischemia. To date, this is the first global study of a similar drug to confirm its efficacy through a large-scale Phase III trial. The rest-pain indication for this project also completed enrollment of the last subject at the end of June. Currently, data cleaning and statistical analysis are underway. If the results meet expectations, we plan to submit a new drug application within this year.

The receipt of the New Drug Registration Application Acceptance Notice for NL003’s ulcer indication represents a significant milestone for this project, marking the completion of all R&D activities and signaling a crucial step toward the commercial launch of the new drug. Our company will fully cooperate with the drug regulatory authorities in carrying out on-site inspections and other related tasks. Meanwhile, the company is actively advancing the industrialization project of bioengineering and conducting research on sales strategies. We look forward to NL003 receiving market approval at an early date, bringing new hope to the many patients suffering from lower-limb ischemic diseases.