On November 29, 2018 Hutchison China MediTech Limited ("Chi-Med") (AIM/Nasdaq: HCM) reported that it has entered into four collaboration agreements to evaluate the safety, tolerability and efficacy of Chi-Med’s surufatinib (HMPL-012 or sulfatinib) and fruquintinib in combination with checkpoint inhibitors (Press release, Hutchison China MediTech, NOV 29, 2018, https://www.chi-med.com/a181129/ [SID1234531708]). It is an important part of Chi-Med’s strategy to explore the potential synergies of its drug candidates in combination with other anti-cancer treatments. These four new immunotherapy collaborations add to our ongoing studies combining savolitinib, Chi-Med’s highly selective c-Met inhibitor, with AstraZeneca PLC’s checkpoint inhibitor, durvalumab (Imfinzi).

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Today, Chi-Med is announcing the first steps to develop its vascular endothelial growth factor receptor ("VEGFR") inhibitors, surufatinib and fruquintinib, in combination with various programmed cell death protein-1 ("PD-1") monoclonal antibodies in several solid tumor settings:

A global collaboration to evaluate the combination of surufatinib with toripalimab (JS001), a PD-1 monoclonal antibody being developed by Shanghai Junshi Biosciences Co. Ltd.;
A global collaboration to evaluate the combination of fruquintinib with sintilimab (IBI308), a PD-1 monoclonal antibody being developed by Innovent Biologics (Suzhou) Co. Ltd.;
A collaboration in China to evaluate the combination of surufatinib with HX008, a PD-1 monoclonal antibody being developed by Taizhou Hanzhong Pharmaceuticals, Inc.; and
A collaboration in China to evaluate the combination of fruquintinib with genolimzumab (GB226), a PD-1 monoclonal antibody being developed by Genor Biopharma Co. Ltd.
The global market for angiogenesis inhibitors was over US$18 billion in 2017, based on their use in around 30 different tumor settings. Each of the agreements announced today will pursue different initial indications within the field of solid tumors.

"Recent innovations in solid tumor drugs have focused on targeted therapies and immunotherapies which, as monotherapies, have both provided improved patients outcomes," said Christian Hogg, Chief Executive Officer of Chi-Med. "We believe that the future of oncology treatments increasingly lies in combining therapies, utilizing multiple mechanisms of action ("MOA") to confront tumors. Our unique next-generation anti-angiogenesis VEGFR inhibitors, with high selectivity and tolerability, make them ideal candidates for such combinations with immunotherapy agents such as PD-1/L1 monoclonal antibodies to prolong and expand the benefits of these therapies to more patients."

Chi-Med’s proof-of-concept studies have already demonstrated the benefits of combinations with other kinase inhibitors or with chemotherapy.

Surufatinib (HMPL-012 or sulfatinib) is a novel, oral angio-immuno kinase inhibitor that inhibits VEGFR and fibroblast growth factor receptor (FGFR) which both inhibit angiogenesis, and colony stimulating factor-1 receptor (CSF-1R) which regulates tumor-associated macrophages, promoting the body’s immune response against tumor cells. This dual angiogenesis-checkpoint inhibitor’s MOA may be very suitable for combination use with other immunotherapies. Surufatinib, as a monotherapy, is in late-stage clinical trials in China and began proof-of-concept clinical trials in the United States in July 2018.

Fruquintinib is a highly selective and potent oral inhibitor of VEGFR. Its unique kinase selectivity has been shown to reduce off-target toxicity thereby allowing possible use in combination with other agents. It was first approved for colorectal cancer in China in September 2018. It is in several late-stage clinical trials for lung and gastric cancer, including in combination with chemotherapy such as paclitaxel (Taxol) and other kinase inhibitors such as gefitinib (Iressa), and is in a Phase I clinical trial in the United States.