Chi-Med presents pre-clinical data for selective Syk inhibitor HMPL-523 at ASH meeting

• Syk, a non-receptor type of tyrosine kinase, plays a pivotal role in the regulation of the B-cell receptor (BCR) signalling pathway, which regulates proliferation, differentiation and survival of B lymphocytes. The abnormal activation of BCR signalling is closely related to transformation and development of B-cell lymphoma.
• In vitro in B-cell lymphoma cell lines with Syk/BCR dysregulation, HMPL-523 was found to block phosphorylation of B-cell linker protein as well as inhibit cell viability by inhibiting cell survival and increasing apoptotic rate. HMPL-523 also showed synergistic anti-tumour activity on human diffused large B-cell lymphoma cells, in combination with other drugs such as Phosphoinositide-3-Kinase d inhibitors, B-cell lymphoma 2 family inhibitors, or chemotherapies. Potent anti-tumour activity was also demonstrated in nude mice bearing B-cell lymphoma xenograft tumours with Syk/BCR dysregulation.
• In haematological malignancies, HMPL-523 is currently being studied in a phase I dose escalation study, which was initiated in Australia in January 2016 and is expected to complete in the first half of 2017. This study is in patients with relapsed and/or refractory B-cell non-Hodgkin’s lymphoma or chronic lymphocytic leukaemia for whom there is no standard therapy.
• HMPL-523 is also being studied in immunological indications. Clinical data for HMPL-523 in a phase I dose-escalating study in healthy volunteers in Australia was recently presented at the 2016 Annual Meeting of the American College of Rheumatology/Association of Rheumatology Health Professionals, which was held in November 2016. 
• The BCR signalling pathway regulates proliferation, differentiation and survival of B lymphocytes, a major cellular component of the immune system. The abnormal activation of BCR signalling is closely related to transformation and development of haematological cancers (i.e. B-cell malignancies) including lymphoma and leukaemia, as well as autoimmune diseases, such as rheumatoid arthritis. Targeted B-cell receptor signalling therapies, including monoclonal antibodies and small molecules, have been proven to be clinically effective for the treatment of B-cell malignancies, leading to scientific and commercial success.
• Syk is a key protein involved in the B-cell signalling pathway.
• Chi-Med is an innovative biopharmaceutical company which researches, develops, manufactures and sells pharmaceuticals and healthcare products. 

Chi med presents, pre clinical data, selective syk inhibitor hmpl, ash meeting