Shanghai, China, February 1^st, 2023 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the first subject was dosed for a phase 1 clinical trial of the company's independently developed daratumumab biosimilar HLX15 (recombinant anti-CD38 fully human monoclonal antibody injection) in China.

HLX15 is a fully human anti-CD38 IgG1κ monoclonal antibody independently developed by Henlius. The indication to be developed for HLX15 is multiple myeloma (MM), which is an incurable clonal plasma cell dysplasia, the second most hematological malignancy which mainly develops in elderly population^[1]. According to the epidemiologic data disclosed by World Health Organization (WHO) in 2020, for MM, the second most common hematological malignancy, more than 450,000 patients in 5 years as of 2020, more than 176,000 new patients and more than 117,000 deaths have been reported worldwide in 2020. In China, there are more than 51,000 patients in 5 years as of 2020, more than 21,000 new patients and more than 16,000 deaths have been reported^[2-4].

CD38, also known as cyclic adenosine diphosphate (ADP) ribose hydrolase, is usually expressed in plasma cells, lymphoid cells, and myeloid cells. CD38 is a multifunctional enzyme that can degrade nicotinamide adenine dinucleotide (NAD) and regulate intracellular NAD homeostasis. It plays a very important role in a variety of biological processes, including the regulation of metabolism under normal physiological levels and the cause of diseases under pathological conditions, including ageing, obesity, diabetes mellitus, heart disease, etc^[5]. High expression of CD38 is present in varied of hematologic malignancies and all stages along disease progression of multiple myeloma. Considering the expression profile of CD38, it is thought to be a cell surface marker of hematological malignancies and an ideal target for the treatment of multiple myeloma^[6-7].

On one hand, HLX15 can directly bind to CD38 expressed on the surface of tumour cells, inducing tumour cell lysis and apoptosis through complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), and several other pathways such as Fc mediated cross linking to achieve a quick response of tumour cells. In addition, HLX15 can also reduce multiple myeloma cells by reducing myeloid-derived suppressor cells and depleting CD38-positive immunomodulatory T and B cells. In accordance with the Technical Guidelines of Development and Evaluation of Biosimilar Drugs and EMA Guideline on Similar Biological Medicinal Products, HLX15 has been developed strictly following the principles of stepwise development, comparability and similarity assessment and has been compared head to head with reference daratumumab via analytical studies and preclinical studies. The results of these preclinical studies showed that HLX15 is highly similar to reference daratumumab.

Underpinned by the patient-centric strategy, Henlius has built an innovative product pipeline with high market potential targets, including PD-1/L1, LAG-3, TIGIT, BRAF, etc., and has been pushing its early R&D research capabilities further while also upgrading the technology platform. Looking forward, Henlius will preserve its momentum for innovation by further strengthening the in-licensing and collaboration on external innovative assets and will continue strive for breakthroughs to bring more affordable and quality biologics to patients around the globe.

About NCT05679258

This phase 1 clinical study compares the pharmacokinetics, safety, tolerability, and immunogenicity between HLX15 and daratumumab injection in healthy Chinese male subjects. The study consists of two parts. Part 1 is a single-centre, randomised, open-label, two-arm phase 1a study. 24 subjects will be enrolled and randomly assigned (1:1) to receive single intravenous infusion of 8 mg/kg of HLX15 or China-sourced daratumumab (trade name Zhaoke). A safety run-in period is included in the early phase of part 1, during which an additional 3–6 subjects will be enrolled to receive HLX15 intravenous infusion and followed up for 1 week for safety observation. Part 2 is a multi-centre, randomised, double-blind, three-arm phase 1b study. A total of 204 subjects will be randomly assigned (1:1:1) to receive single intravenous infusion of 8 mg/kg of HLX15, US-sourced daratumumab (trade name DARZALEX^®), or China-sourced daratumumab (trade name Zhaoke). The primary endpoint is the area under the serum drug concentration-time curve from time 0 to infinity (AUC0-inf). Secondary endpoints include other pharmacokinetic parameters, safety, and immunogenicity.

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