SUZHOU, China /PRNewswire/ -- CStone Pharmaceuticals (SuZhou) Co. LTD (CStone), a privately-held biopharmaceutical company devoted to developing next-generation innovative drugs, announced today that the China National Drug Administration (CNDA) has approved the first clinical trial application (CTA) in China for CS1003, a self-developed and wholly-owned anti-programmed death-1 (PD-1) monoclonal antibody (mAb). CS1003's CTA filing was entered into the new process by the CNDA and approved after less than four months of review by the Center for Drug Evaluation. CStone will initiate a multi-center Phase I clinical trial to assess the safety, tolerability and preliminary anti-tumor activity of CS1003 in Chinese patients with advanced cancers.
"We are pleased to begin the development of CS1003 in China, which follows a first-in-human dose escalation trial initiated in Australia in May this year," said Dr. Frank Jiang, Chief Executive Officer at CStone. "The start of clinical evaluation for CS1003 in China is an important step in the development path for this molecule, which is a key component of CStone's immunotherapy strategy and will form the backbone of combination therapies. Alongside the programmed death-ligand 1 (PD-L1) mAb CS1001, CS1003 is the second CStone pipeline candidate to be tested in Chinese patients."
"PD-1 and PD-L1 immunotherapies have demonstrated significant clinical benefits for patients with various cancers, and we look forward to assessing the safety and efficacy of this high-quality PD-1 candidate in Chinese cancer patients," commented Dr. Jason Yang, Chief Medical Officer at CStone. "CS1003 is cross-reactive with both human and mouse PD-1, which enables pre-clinical proof-of-concept experiments to quickly determine its anticancer activity, especially in combination with various anticancer modalities. The results of these early experiments have demonstrated that CS1003 has strong potential as a monotherapy and in combination with multiple anticancer agents."
About CS1003 and the PD-1/PD-L1 pathway
CS1003 is a humanized anti-PD-1 IgG4 monoclonal antibody developed by CStone using an internationally leading hybridoma platform. CS1003 has shown good tolerability and efficacy profile in preclinical in vivo studies. In contrast with other anti-PD-1 mAbs, CS1003 recognizes both human and murine PD-1, providing a unique competitive advantage during efficacy testing in syngeneic mouse tumor models particularly for development of effective combination therapies.
PD-1, or programmed death-1, is an inhibitory checkpoint receptor expressed on T cells. Under normal circumstances, it binds with its ligands, programmed death ligand-1 or ligand 2 (PD-L1/PD-L2), inhibiting T cell and cytokine activation, serving to dampen the immune response and prevent damage to healthy tissues. However, studies have shown that PD-L1 can be abundantly expressed on the surface of many solid tumors as well as hematological malignancies. Cancer cells can therefore make use of the PD-1/PD-L1 pathway to avoid immune system recognition and attack. Targeting of the PD-1/PD-L1 checkpoint by anti-tumor drugs can block the "tumor immune evasion mechanism" and restore anti-cancer immune ability in patients.
Currently, there are two anti-PD-1 antibodies approved globally: Opdivo® (nivolumab) from Bristol-Myers Squibb and Keytruda® (pembrolizumab) from Merck, Sharp & Dohme. Opdivo® became the first PD-1 mAb to gain marketing approval in China in June 2018.