Shanghai, China, November 11, 2022, - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the investigational new drug (IND) application for phase 1b/2 clinical trial of HLX208, a BRAF V600E inhibitor, in combination with anti-PD-1 monoclonal antibody (mAb) HANSIZHUANG (serplulimab injection) and its related combination therapies (HLX208 in combination with HANSIZHUANG +/- cetuximab or trametinib) for the treatment of BRAF V600E or BRAF V600 mutation-positive advanced solid tumours was approved by the National Medical Products Administration (NMPA).

BRAF is a member of the RAF kinase family and a critical upstream regulator in the RAS-RAF-MEK-ERK mitogen-activated protein kinase (MAPK) cell signaling pathway downstream of EGFR. Its mutation can activate the downstream MEK and ERK protein, which induces the proliferation and invasion of tumour cells^[1]. Among all BRAF mutation types, BRAF V600E mutation is the most common one. The BRAF mutation frequently occurs in colorectal cancer, thyroid cancer, melanoma and other types of cancers, which often predicts poor prognosis. Currently, targeted combination therapy represented by BRAF inhibitors has become one of the main treatments in different kinds of BRAF mutation-positive solid tumours^[2,3]. With the development of immuno-oncology therapy, immune checkpoint inhibitors have shown good therapeutic effects in solid tumours, such as non-small cell lung cancer and melanoma, and a number of studies have shown that BRAF inhibitors combined with immunotherapy antibodies demonstrating a synergistic effect in inhibiting tumour growth^[4,5].

HLX208 is a potential “best-in-class” BRAF inhibitor with a proprietary novel chemical structure that is different from other marketed BRAF inhibitors. It exhibited a single crystal morph, high bioavailability, and excellent anti-tumour efficacy in preclinical studies. Subsequent early clinical data also demonstrated preliminary efficacy and good safety and tolerability in patients with cancer, warranting further clinical development. In January 2022, the IND of Phase 1b/2 clinical trials of HLX208 as monotherapy or in combination therapy for the treatment of BRAF V600 mutation-positive advanced solid tumours has been approved by NMPA, and the first patient has been dosed in the phase 2 clinical trial of HLX208 in adult patients with BRAF V600E mutation Langerhans Cell Histiocytosis (LCH) and Erdheim-Chester disease (ECD). And the combination of immuno-oncology therapy HANSIZHUANG and targeted therapy will enable Henlius to explore more effective treatment options for patients with BRAF V600 mutation-positive solid tumours.

Underpinned by the patient-centric strategy, Henlius has built an innovative product pipeline with many emerging targets, including PD-1/L1, LAG-3, GARP, TIGIT, and BRAF. Regarding antibody technology as a core, Henlius will continue conducting clinical studies for more innovative products in bispecific antibodies, antibody-drug conjugates (ADC), and fusion proteins and exploring combination therapies with improved efficacy to provide patients with quality and affordable biologics.

Reference

[1] Huang Z, Wu Y. Huang Z, Wu Y. Mutation of the BRAF genes in non-small cell lung cancer. Zhongguo Fei Ai Za Zhi. 2012;15(3):183-186.

[2] 《黑色素瘤治疗指南（2022年版）》, 国家卫生健康委办公厅.

[3] 《中国临床肿瘤学会（CSCO）结直肠癌诊疗指南2022》[M]. 人民卫生出版社.

[4] Sanlorenzo M, Vujic I, Floris A, et al. BRAF and MEK Inhibitors Increase PD-1-Positive Melanoma Cells Leading to a Potential Lymphocyte-Independent Synergism with Anti–PD-1 AntibodyBRAF and MEK Inhibitors Increase PD-1–Positive Melanoma[J]. Clinical Cancer Research, 2018, 24(14): 3377-3385.

[5] Trojaniello C, Vitale M G, Ascierto P A. Triplet combination of BRAF, MEK and PD-1/PD-L1 blockade in melanoma: the more the better?[J]. Current Opinion in Oncology, 2021, 33(2): 133-138.