CStone Pharmaceuticals (Suzhou) Co., Ltd, a biopharmaceutical company, announced that a formal application for clinical trial approval has been submitted to Human Research Ethics Committees of Linear Clinical Research Center in Australia for CS3006, a small-molecule inhibitor of mitogen-activated protein kinase kinase (MEK). CS3006 is CStone's second independently-developed novel oncology drug candidate soon to reach the clinical development stage, following the anti-programmed death ligand-1 (PD-L1) antibody CS1001.

"The successful clinical trial application for CS3006 in Australia is CStone's first overseas filing for an innovative drug, and an important step for the company's global R&D strategy. Concurrent with this, we plan to make regulatory filings to initiate international studies for a number of novel drug candidates in our pipeline in the near future." Noted by Dr. Frank Jiang, chief executive officer (CEO) of CStone, "CS3006 is a strategically important program for CStone's development of combination therapies. We are very much looking forward to the initiation of clinical trials in Australia, which will provide a wealth of clinical data as we begin to explore the most effective combinations for treating cancer."

CS3006 is an independently developed, highly selective small molecule kinase inhibitor, designed to inhibit the growth of cancer cells by binding to key enzymes, MEK 1/2, in the MAPK signaling pathway (RAS-RAF-MEK-ERK). Preliminary studies have shown that CS3006 demonstrated good pharmacokinetic properties, and has produced promising synergistic activity when combined with an anti-PD-1 antibody in animal models.

"Evidence from early clinical trials for competitor drugs in the same class indicates that MEK inhibitors in combination with immunotherapy can produce breakthrough antitumour activities in indications that are typically insensitive to PD-1 or PD-L1 monotherapy." Commented Dr. Jason Yang, chief medical officer (CMO) of CStone, "As a highly specific MEK inhibitor, CS3006 can combine both with the company's immunotherapy backbone products and with other targeted therapies in our pipeline. We hope these combination therapies will lead to more effective treatments for multiple tumor types with severe unmet medical needs".

CStone Pharmaceuticals focuses on the development of therapeutic drugs for oncology, and has independently developed CS1001, China's first full-length, fully human anti-PD-L1 monoclonal antibody candidate. CS1001 has received clinical trial approval by the China Food and Drug Administration (CFDA) in June 2017 and is currently in Phase I clinical trial in patients with advanced solid tumor and lymphoma.

The RAS-RAF-MEK-ERK signal transduction pathway is among the most fundamental intracellular signaling pathways, found in the majority of cells and responsible for regulating key cellular activities such as cell growth, proliferation, survival, and apoptosis. MEK1 and MEK2 are serine/threonine protein kinases that act downstream of RAS and RAF to activate ERK. The inhibition of MEK can affect tumor cell survival, proliferation, and differentiation.

Currently, two MEK inhibitors have been approved and marketed globally: Novartis's Mekinist (trametinib) and Roche's Cotellic (cobimetinib). In 2013, trametinib was approved by the FDA as a single agent for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations. In 2014, trametinib, in combination with dabrafenib, was also approved for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations. In June of 2017, trametinib received an expanded new indication, in combination with dabrafenib, for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with BRAF V600E mutation. Cobimetinib was approved by the FDA for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, in combination with vemurafenib in 2015. In pre-clinical tests, CStone's CS3006 has shown comparable kinase inhibition activity to trametinib while demonstrating more potent inhibition of cell proliferation.

CStone Pharmaceuticals is a biopharmaceutical company devoted to the development of a new generation of innovative drugs. With its broad immuno-oncology pipeline, CStone is pursuing a development strategy focusing on combination therapy.