Northland Biotech Enters Harvest Phase as Its First Gene Therapy Drug NL003 Initiates Phase III Clinical Trials

In December 2017, the U.S. FDA approved Luxturna, a gene therapy drug for the treatment of Leber congenital amaurosis (LCA) caused by RPE65 gene mutations. This brought the total number of officially approved novel gene therapies worldwide to eight. The efficacy and reliability of gene therapy have been clinically validated, and gene therapy developers are accelerating their efforts. According to the "2018 Global Gene Therapy Research Report" released by international think tank Jain PharmaBiotech, there were more than 2,000 gene therapy pipelines under development globally as of the end of 2016, covering areas such as genetic disorders, cancer, and cardiovascular diseases. Northland’s investigational new drug, "Recombinant Human Hepatocyte Growth Factor Naked Plasmid Injection" (NL003), is a gene therapy product. Phase III clinical trials have been initiated, with patient enrollment expected to be completed by the end of 2021.

Northland, founded in 2004 and headquartered in Beijing. Mr. Xu Songshan, the founder of Northland, told VCBeat: “Twenty years ago, competition among domestic pharmaceutical companies in the generic drug market was extremely fierce. At that time, we felt that China needed the research, development, and production of new drugs to inject fresh blood into the pharmaceutical industry, and that innovative drug R&D held promising prospects.”

Since its inception, Northland has positioned itself as a biopharmaceutical R&D enterprise. After defining its R&D direction, the company promptly initiated new drug development efforts and achieved phased results. Between 2006 and 2008, Northland successively licensed out the overseas development rights for three in-house pipeline projects to multinational pharmaceutical companies. The upfront payments and milestone receipts from these technology transfers supplemented the company’s R&D funding. In 2008, NL003, a Class 1 innovative drug under development by the company, entered Phase I clinical trials. As its independently developed pipeline continued to advance, Northland completed two rounds of financing. In December 2017, NL003 (Recombinant Human Hepatocyte Growth Factor Naked Plasmid Injection), a Class 1 innovative gene therapy drug independently developed by Northland for the treatment of severe lower limb arterial ischemic disease, was approved by the National Medical Products Administration (NMPA) to formally enter Phase III clinical trials. In early 2019, the company completed an RMB 80 million Series C financing round. Currently, the company is developing six new drugs for ten indications. Among them, NL003 for the treatment of severe lower limb arterial ischemia is in Phase III clinical trials, and NL002 for the treatment of chemotherapy-induced thrombocytopenia is also in Phase III clinical trials.

High investment and long development cycles are challenges faced by most R&D-driven biopharmaceutical companies. In addition to external financing, Northland has also actively sought other revenue-generating avenues. On one hand, the company generates partial revenue by licensing out its pipeline candidates through technology transfers; on the other hand, it establishes joint ventures to build production facilities for revenue generation, such as the Phase I project of Northland’s industrialization base. “Since the implementation of the new Good Manufacturing Practice (GMP) standards in 2010, the regulatory requirements for eye drops have been elevated from those for topical medications to those for sterile preparations, marking a new starting line.” Capitalizing on this favorable opportunity, Northland formed a joint venture with a South Korean pharmaceutical company to establish Beijing Huien Land Pharmaceutical Co., Ltd., introducing world-leading blow-fill-seal (BFS) integrated eye drop production lines. In 2016, Huien Land’s first multi-dose eye drop production line received GMP certification, enabling the commencement of drug production and sales. It was disclosed that another product developed by the company, a daily disposable 0.3% sodium hyaluronate eye drop, received drug approval in 2019.

“Gene therapy, as a new generation of biotechnology, has demonstrated its druggability after more than two decades of development and has entered the stage of practical application,” stated Mr. Xu Songshan, Chairman of Northland. Over the past decade, Northland has successfully developed several core technology platforms, including prokaryotic cell culture, eukaryotic (animal) cell culture, biomacromolecule purification, and gene vector technologies. Leveraging these multiple core platforms, Northland is able to simultaneously develop multiple product pipelines and explore different indications for the same product.

Among these, Northland’s core technology platform—the gene vector technology platform—can screen for target genes and optimize target proteins to construct naked plasmids for gene therapy that enable efficient expression of the target protein in the human body. The company’s core product, NL003, is a naked plasmid gene therapy drug developed via this platform, intended for local injection treatment of severe lower extremity arterial ischemic diseases. Naked plasmid gene therapy drugs are pharmaceuticals developed using naked plasmids as vectors for target genes, representing a relatively common approach to gene therapy. Another prevalent type of gene therapy drug utilizes viruses (typically adeno-associated viruses, or AAV) as vectors.

“The vector for gene therapy drugs is selected based on the therapeutic principles of the disease. Naked plasmid drugs exhibit lower cellular transfection efficiency compared to viral vector-based gene therapies, making it difficult for them to be effective when administered systemically. However, NL003, a naked plasmid drug under development by our company, is designed for local administration in cases of lower extremity arterial occlusion. By injecting the drug into the skeletal muscles surrounding the ischemic local vascular lesions, the naked plasmids carrying the target gene enter the skeletal muscle cells and secrete/express two naturally occurring human hepatocyte growth factor (HGF) proteins, thereby promoting local angiogenesis. While exerting its therapeutic effect, this product, as a naked plasmid drug, demonstrates a favorable safety profile,” explained the company’s technical director.

Furthermore, the NL003 project is conducting a Phase III clinical trial across 15–20 clinical trial centers nationwide, with Peking Union Medical College Hospital serving as the lead site.

The company’s other Class 1 innovative drug, recombinant human thymosin β4, is a recombinant protein therapeutic developed based on a prokaryotic cell culture technology platform, indicated for the treatment of ischemia-reperfusion injury caused by acute myocardial infarction. The product is currently in Phase II clinical trials.

Regarding its product R&D strategy, Northland prioritizes independent research and development, supplemented by international collaborative R&D. Currently, the company has established strategic partnerships with multiple institutions, including the Shanghai Institute of Materia Medica, Joinn Laboratories, and QuintessenceBio. It outsources preclinical animal studies and clinical trials to professional organizations, while its core team focuses on platform screening, modification and optimization, and pharmaceutical research for early-stage gene therapy drugs. Furthermore, the company engages in academic collaborations with Tsinghua University and Beijing Normal University, covering basic scientific research and the joint training of graduate students.

Currently, Northland is conducting its Series C+ financing round and conducting in-depth research on the new policies regarding the tiered structure and public offerings on the New Third Board, so as to accelerate the company’s IPO process. The funds raised will be used to advance its R&D pipeline and expedite the market launch of its drugs, thereby providing patients with safe and effective medications.

For those interested in the company, please contact the financing assistant Xiao Yun: DongMai_Investent