The China NMPA’s Center for Drug Evaluation accepted Lepu Biopharma Co. Ltd.’s new drugapplication (NDA) for anti-PD-1 antibody candidate HX-008 (pucotenlimab). That comes after thecompany filed for an IPO in Hong Kong.

HX-008 is a humanized antagonist monoclonal antibody to human PD-1. The company has prioritized theregistration trials for the candidate in melanoma and MSI-H and dMMR solid tumors. So far, HX-008emonstrated efficacy and safety in phase I and II trials in multiple indications. The overallresponse rate (ORR) and disease control rate (DCR) in the phase II trial in melanoma reached 18.5%and 44.5%, respectively. The ORR and DCR in the phase II trial in MSI-H/dMMR solid tumors reached44.8% and 66.7%, respectively.

Lepu CEO Sui Ziye said she believes HX-008 can win its market share, despite the fierce PD-1-targeted drugs market.

“The molecular design of HX-008 helped us achieved good clinical data. Meanwhile, we plan toestablish a sales and marketing team next year before the NDA of HX-008 is approved. We also plan toseek investigational new drug approval for combination therapies of the candidates within our ownpipeline,” Sui told BioWorld.

The differentiated molecular design of the candidate gives it an edge.

“We have identified a very unique epitope of PD-1 and enhanced the half-life of antibodies inmolecular design, which differentiated the HX-008 from its competitors,” Fang Lei, Lepu vicepresident, told BioWorld.

Lepu filed for its IPO listing on the Hong Kong Stock Exchange in April 2021. In its prospectus, thecompany stated an intention to use 13.3% of the proceeds to develop HX-008.

Lepu raised ¥261.1 million (US$40.4 million) in a series C round in April 2021. Prior to that, itraised ¥1.291 billion in a series B round last year, and ¥900 million in a series A in July 2019.Apart from HX-008, the other drug candidate in its immune-oncology pipeline is LP-002, a humanizedmonoclonal antibody against PD-L1.

The company is conducting phase I trials of LP-002 in advanced solid tumors and digestive systemtumors, and in the process ofstarting phase II trials in extensive-stage small-cell lung cancer(ES-SCLC) in China. The candidate has demonstrated encouraging results in safety and efficacy inthe preliminary data from the clinical trials covering indications such as solid tumors and ES-SCLC.LP-002 has shown a safety profile in a phase Ia study in advanced solid tumors, with an ORR of 15.2%and an overall DCR of 51.5%.

Pu Zhongjie, the founder of Lepu Group Co. Ltd., launched Lepu Biopharma in 2018. At the time offounding, he held 80% of the shares in the firm (now 43%), with Lepu Medical Technology (Beijing)Co. Ltd. holding the remaining 20% of shares (now 15%).

“We are a fully integrated biopharmaceutical industry platform, from R&D, clinical trial, toproduction and commercialization,” said Sui.

Set up as the biotech arm of Lepu Medical Technology, Lepu Biopharma focuses on immunotherapy andtargeted therapy for oncology. Its pipeline covers immune-oncology, antibody-drug conjugates (ADCs)and oncolytic viruses (OVs). Its immunotherapy, including anti-PD-1 and anti-PD-L1 antibodycandidates, forms the backbone of its pipeline.

Currently, it has eight clinical-stage drug candidates, three preclinical candidates and threeclinical-stage combination therapies in its pipeline. Its in-house ADC drug candidates are MRG-003,MRG-001, MRG-002 and MRG-004A. The company said MRG- 003 and MRG-001 are potentially first-in-classADC drug products targeting EGFR and CD20, respectively.

MRG-003, currently in phase II trials, is the first EGFR-targeted ADC in clinical-stage developmentin China, according to Frost & Sullivan. It aims to address medical needs for EGFR-targeted drugs,including treatment of EGFR-positive solid tumors with drug resistance.

Meanwhile, MRG-002 is a HER2-targeted ADC that showed better efficacy in preclinical studies ascompared to trastuzumab emtansine (T-DM1) in multiple Herceptin-resistant HER2-overand low-expressing patient-derived xenografts models of the gastric cancer and breast cancer.

MRG-001 is in phase Ia trials for non-Hodgkin lymphoma (NHL), while MRG-004A is in preclinical phasefor TF-positive advanced or metastatic solid tumors.Another ADC drug candidate, being co-developed with Keymed Biosciences Inc., is CMG-901, the firstCLDN18.2-targeted ADC that has received the IND approval globally, according to Frost & Sullivan.

Moving forward, Lepu Biopharma aims to develop its pipeline by combining in-house R&D andcollaborations, strengthening inhouse manufacturing and commercializing its pipeline products inChina through sales and marketing forces and internationally via partnerships.

Previously, Lepu Biopharma expanded its pipeline via M&A and in-licensing deals. Moving forward, thecompany will focus on independent R&D.

“We have established independent research and development capabilities and platforms,” Sui said.“We currently have two R&D engines, including the discovery platform for antibodies led by Fang andthe R&D platform for ADC led by Hu.”

The company is also seeking partnerships and out-licensing opportunities in order to expand inglobal markets, starting in mature markets like the U.S. and Europe, she added.

“We aim to build a complete commercialization chain in China, from R&D to commercialization in thenext few years, and license out our products and form partnerships in the global market,” Fangsaid.

The company also has its production line in Beijing and is building a production base in Shanghai,said Lepu Biopharma co-CEO Hu Chaohong.

Source from BioWorld