Lepu Bio's Anti-PD-1 Antibody HX-008 NDA Accepted Prior to Hong Kong IPO Filing

The Center for Drug Evaluation of China’s National Medical Products Administration has accepted the New Drug Application (NDA) for HX-008 (putalimab), an anti-PD-1 antibody candidate from Lepu Biopharma Co., Ltd. The company had previously submitted a marketing application in Hong Kong.

HX-008 is a humanized antagonistic monoclonal antibody targeting human PD-1. The company has prioritized registration trials for this candidate drug in melanoma and in MSI-H and dMMR solid tumors.

To date, Phase I and Phase II clinical trials have demonstrated that HX-008 exhibits efficacy and a favorable safety profile across multiple indications. In the Phase II trial for melanoma, the overall response rate (ORR) and disease control rate (DCR) reached 18.5% and 44.5%, respectively. In the Phase II trial for MSI-H/dMMR solid tumors, the ORR and DCR reached 44.8% and 66.7%, respectively.

Dr. Sui Ziye, CEO of Lepu Biopharma, stated that despite the fierce competition in the PD-1 targeted therapy market, he believes HX-008 can still secure a place.

Dr. Sui told BioWorld, “The molecular design of HX-008 has helped us achieve robust clinical data. Meanwhile, we plan to establish a sales and marketing team before the approval of the New Drug Application (NDA) for HX-008 next year. We also intend to submit Investigational New Drug (IND) applications for combination therapies involving candidate drugs in our pipeline.”

The unique molecular design of this drug candidate confers distinct advantages.

Dr. Fang Lei, Vice President of Lepu Biopharma, told BioWorld, “We discovered that HX008 recognizes a highly unique epitope on PD-1 and incorporated design features to enhance the antibody’s half-life during molecular engineering, thereby differentiating HX-008 from its competitors.”

Lepu Biopharma submitted its listing application to the Hong Kong Stock Exchange in April 2021. In its prospectus, the company stated that it intended to allocate 13.3% of the proceeds from the initial public offering to the development of HX-008.

Lepu Biopharma raised RMB 261.1 million (USD 40.4 million) in its Series C financing round in April 2021. Prior to this, the company raised RMB 1.291 billion in its Series B financing round last year, and RMB 900 million in its Series A financing round in July 2019.

Dr. Pu Zhongjie, founder of Lepu Group Co., Ltd., established Lepu Biopharma in 2018. At the time of its establishment, he held an 80% stake in the company (currently 43%), while Lepu Medical Technology (Beijing) Co., Ltd. held the remaining 20% (currently 15%).

Dr. Sui stated, “We are a fully integrated biopharmaceutical industry platform, encompassing R&D, clinical trials, manufacturing, and commercialization.”

Lepu Biopharma, founded by Dr. Pu Zhongjie, aims to build a fully integrated biopharmaceutical company focused on innovative drugs. Its pipeline encompasses cancer immunotherapies, antibody-drug conjugates (ADCs), and oncolytic viruses (OVs). Its immunotherapy portfolio, including anti-PD-1 and anti-PD-L1 antibody candidates, serves as the cornerstone of its pipeline.

Currently, the company’s pipeline includes eight clinical-stage candidate drugs, three preclinical candidate drugs, and three clinical-stage combination therapies. Its independently developed antibody-drug conjugates (ADCs) are at the forefront in China, with the most robust pipeline candidates comprising MRG-003, MRG-001, MRG-002, and MRG-004A. The company stated that MRG-003 and MRG-001 have the potential to become first-in-class ADC therapeutics targeting EGFR and CD20, respectively.

MRG-003 is currently undergoing Phase II clinical trials. According to Frost & Sullivan, it is the first-in-class EGFR-targeting antibody-drug conjugate (ADC) in China that is in the clinical research stage. It aims to address the clinical need for EGFR-targeted therapies, including the treatment of EGFR-positive solid tumors with drug resistance.

Furthermore, MRG-002 is a HER2-targeted antibody-drug conjugate (ADC) whose preclinical studies have demonstrated superior efficacy to trastuzumab emtansine (T-DM1) in various patient-derived xenograft (PDX) models of gastric and breast cancer with HER2 overexpression or low expression that are resistant to Herceptin.

MRG-001 is a drug in Phase Ia clinical trials for non-Hodgkin lymphoma (NHL), while MRG-004A is a drug in the preclinical stage for TF-positive advanced or metastatic solid tumors.

CMG-901 is another ADC candidate jointly developed by the company and Keymed Biosciences Inc. According to Frost & Sullivan, it is the first CLDN18.2-targeted ADC worldwide to receive IND approval.

Looking ahead, Lepu Biopharma aims to build its product pipeline through independent R&D and collaborations, strengthen its in-house manufacturing capabilities, achieve domestic commercialization of its pipeline by establishing a professional sales and marketing team, and expand its pipeline into international markets through partnerships with overseas companies.

Lepu Biopharma has previously expanded its pipeline through mergers and acquisitions and in-licensing arrangements, but will focus on independent R&D in the future.

Dr. Sui stated, “We have established independent R&D capabilities and platforms. Currently, we operate two R&D engines: an antibody discovery platform led by Dr. Fang Lei, and an ADC development platform led by Dr. Hu Chaohong.”

Dr. Sui also added that the company is seeking licensing and collaboration opportunities to expand globally, starting with mature markets such as the United States and Europe.

Dr. Fang Lei stated, “We aim to establish a complete commercialization chain, from R&D to commercialization, in China over the coming years, and to pursue product licensing and strategic partnerships in the global market.”

Dr. Hu Chaohong, Co-CEO of Lepu Biopharma, stated that the company has also built and put into operation a GMP production line in Beijing, and is currently constructing a commercial-scale manufacturing facility in Shanghai.

Source: Bioworld report