Shanghai, China, January 18th, 2022 - Shanghai Henlius Biotech, Inc. (2696.HK) today announced that the National Medical Products Administration (NMPA) has approved HLX208, a small-molecule inhibitor the company licensed from NeuPharma, to be investigated in Phase 1b/2 clinical trials as monotherapy or in combination therapy for the treatment of BRAF V600E or BRAF V600 mutation-positive advanced solid tumours.
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[1], and its mutation can activate the downstream MEK and ERK protein, which induces the proliferation and invasion of tumour cells. BRAF V600E is the most prevalent BRAF mutation, commonly seen in colorectal cancer (CRC), melanoma, thyroid cancer, lung cancer, glioma, and other malignancies, and is associated with a poor prognosis.
HLX208 has a proprietary new chemical structure distinct from other marketed BRAF inhibitors. It exhibited a single crystal morph, high bioavailability, and excellent anti-tumour efficacy in preclinical studies, eyeing to be the best-in-class. Early clinical data also revealed preliminary efficacy and a low profile for side effects and tolerance in patients with cancer, providing strong argument for further clinical development. The R&D of HLX208 will further expand Henlius' layout, and may have a synergy with Henlius' proprietary EGFR or PD-1 targeted antibodies to enhance a high-quality, innovative and differentiated product portfolio for the treatment of various cancer types, bringing precise and comprehensive treatment options to BRAF V600E mutant patients. The company also explores therapies targeted on the EGFR protein, the upstream receptors of the MAPK pathway, including HLX07, which is an independently developed recombinant anti-EGFR humanised monoclonal antibody injection now under China Phase 1b/2 clinical trial and has demonstrated preliminary efficacy. In addition, research has shown that tumours with BRAF V600E mutations are often associated with a high microsatellite instability (MSI)[2], and the company's novel anti-PD-1 mAb serplulimab, for the treatment of unresectable or metastatic microsatellite instability-high (MSI-H) solid tumours that fail to respond to the standard therapy, is expected to be approved in 2022 H1 by the NMPA. It has the potential to be used in combination with BRAF inhibitors to enhance the efficacy.
Fully leveraging the global research and development platform, Henlius has built a diversified product pipeline in monoclonal antibodies, bispecific antibodies, and the antibody-drug conjugates (ADC). Looking forward, Henlius will continue its momentum for innovation, further strengthening the in-licensing and collaboration on external innovative assets, and bringing more high-quality and affordable therapies to patients worldwide.
References
[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] Grothey A, Fakih M, Tabernero J. Management of BRAF-mutant metastatic colorectal cancer: a review of treatment options and evidence-based guidelines. Ann Oncol. 2021;32(8):959-967.