On January 24, 2020 CStone Pharmaceuticals ("CStone" or the "Company", HKEX: 2616) reported that it has dosed the first patient in Australia in a clinical trial of CS1001, an investigational PD-L1 inhibitor developed by CStone, in combination with regorafenib, an oral multi-kinase inhibitor developed by Bayer Healthcare LLC ("Bayer") (Press release, CStone Pharmaceauticals, JAN 24, 2020, View Source [SID1234553543]). This is the first global proof-of-concept study carried out as a collaboration between CStone and Bayer. It is designed to assess the safety, tolerability, pharmacokinetics, and antitumor activity of the CS1001 plus regorafenib combination in patients with advanced solid tumors including gastric cancer, and to determine the recommended dose for subsequent studies.

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CS1001 is an investigational anti-PD-L1 monoclonal antibody discovered by CStone. The drug candidate is being investigated in a number of clinical trials, including one Phase I bridging study in the U.S., one multi-arm Phase Ib study, two Phase II registrational studies and four Phase III studies in China for several tumor types. The Phase Ia/Ib results released at the 2019 Chinese Society of Clinical Oncology (CSCO) Annual Meeting have shown CS1001 to be well tolerated with promising antitumor activities across multiple cancers.

Developed by Bayer, regorafenib is an oral multi-kinase inhibitor that potently blocks protein kinases including VEGFR, FGFR, and CSF1R. Regorafenib has been approved in more than 90 countries, including China, for the second- or later-line treatment of patients with metastatic colorectal cancer, metastatic gastrointestinal stromal tumors, and advanced hepatocellular carcinoma.

In May 2019, CStone and Bayer entered into a global clinical collaboration in which CStone will sponsor clinical studies of the CS1001 in combination with regorafenib. Bayer will provide regorafenib for CStone-sponsored studies.

There is a large body of evidence demonstrating the clinical benefits of monotherapy with kinase inhibitor or anti-PD-1/L1 antibody in multiple malignancies. Preclinical studies revealed that targeted therapies such as regorafenib could bolster the efficacy of immune checkpoint inhibitors in select solid tumors through modulating the tumor immune microenvironment, implicating possible synergistic antitumor effects between the two mechanisms of action.

"Our collaboration with Bayer in this clinical program marks an important milestone in the implementation of CStone’s global strategy I am very pleased that the first patient has been dosed in this combination study.," said Dr. Frank Jiang, Chairman and CEO of CStone. "We hope this clinical program will strengthen CStone’s pipeline, and above all demonstrate the utility of this combination in improving the clinical outcomes for cancer patients who lack effective treatments."

"Preclinical studies in animal models have shown enhanced antitumor activity by the CS1001 plus regorafenib combination, lending evidential support to the design of this proof-of-concept study. In addition, a range of global studies of similar immuno-combination therapies have generated promising results in advanced or metastatic solid tumors," said Dr. Archie Tse, Chief Translational Medicine Officer at CStone. "We hope results from this trial will further validate the combination of multi-kinase inhibitors and immunotherapy in select tumors."

About Regorafenib (Stivarga)

Regorafenib is an oral multi-kinase inhibitor that potently blocks multiple protein kinases involved in tumor angiogenesis (VEGFR1, -2, -3, TIE2), oncogenesis (KIT, RET, RAF-1, BRAF), metastasis (VEGFR3, PDGFR, FGFR) and tumor immunity (CSF1R).

Regorafenib is a compound developed by Bayer. In 2011, Bayer entered into an agreement with Onyx, now an Amgen subsidiary, under which Onyx receives a royalty on all global net sales of regorafenib in oncology.

Regorafenib is approved under the brand name Stivarga in more than 90 countries worldwide, including the U.S., countries of the EU, China and Japan for the treatment of metastatic colorectal cancer (mCRC) and metastatic gastrointestinal stromal tumors (GIST) and second-line treatment of advanced hepatocellular (HCC).

About CS1001

CS1001 is an investigational monoclonal antibody directed against PD-L1 being developed by CStone. Authorized by the U.S. based Ligand Corporation, CS1001 is developed by the OMT transgenic animal platform, which can generate fully human antibodies in one step. As a fully human, full-length anti-PD-L1 monoclonal antibody, CS1001 mirrors natural G-type immune globulin 4 (IgG4) human antibody, which can reduce the risk of immunogenicity and potential toxicities in patients, potentially representing a unique advantage over similar drugs.

CS1001 has completed a Phase I dose-escalation study in China, in which CS1001 showed good tolerability and produced sustained clinical benefits during the Phase Ia stage of the study.

CS1001 is being investigated in a number of ongoing clinical trials, including one Phase I bridging study in the U.S., one multi-arm Phase Ib study, two Phase II registrational studies and four Phase III studies in China for several tumor types.