On August 22, 2019 CStone Pharmaceuticals ("CStone" or the "Company", HKEX: 2616) reported that the 22nd Annual Meeting of the Chinese Society of Clinical Oncology (CSCO, 2019 CSCO Annual Meeting) has accepted three abstracts on the clinical trials of CS1001 (Anti-PD-L1 antibody), CS1002 (Anti-CTLA-4 antibody), and CS1003 (Anti-PD-1 antibody), the Company’s three backbone immunotherapy candidates. Meanwhile, three late-breaking abstracts on the CS1001-101 Phase Ib clinical trial have also been submitted for presentation (Press release, CStone Pharmaceauticals, AUG 22, 2019, View Source [SID1234538945]).

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CS1001-101 Trial

The CS1001-101 trial is a Phase Ia/Ib open-label, multiple-dose, dose-escalation, and dose-expansion study assessing the safety, tolerability, pharmacokinetics, and anti-tumor efficacy of CS1001 in Chinese patients with advanced solid tumors or lymphomas. Currently, CS1001 is being investigated in multiple clinical trials in China and the U.S., and over 650 patients have been enrolled in these studies.

The results that will be released in poster presentation at the 2019 CSCO Annual Meeting include:

The safety data from the CS1001-101 Phase Ia/Ib clinical trial, and the efficacy data from the Phase Ib trial in cholangiocarcinoma (Abstract #4763).
Three late-breaking abstracts have also been submitted for oral presentation at the meeting include:

The safety and efficacy data from the CS1001-101 Phase Ib trial in patients with esophageal carcinoma.
The safety and efficacy data from the CS1001-101 Phase Ib trial in patients with gastric cancer.
The safety and efficacy data from the CS1001-101 Phase Ib trial in patients with MSI-H cancers.
CS1002-101 Trial

The CS1002-101 trial is an open-label, multiple-dose, dose-escalation, and dose-expansion study conducted in Australia assessing the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor efficacy of CS1002 in patients with advanced solid tumors. At present, the study has completed the dose-escalation stage of CS1002 monotherapy. The dose-escalation of combination with CS1003 in solid tumors and the dose-expansion of the combination in selected tumor types have been planned.

The data that will be released in oral presentation at the 2019 CSCO Annual Meeting includes:

Preliminary safety, pharmacokinetics and pharmacodynamics results from a Phase Ia study of CS1002 in patients with advanced solid tumors (Abstract #4756).
CS1003-102 Trial

The CS1003-102 trial is a multi-center Phase I study evaluating the safety, tolerability, and preliminary anti-tumor activity of CS1003 in Chinese patients with advanced solid tumors and lymphomas. CS1003 is currently undergoing Phase I clinical studies in China and Australia, and received an Investigational New Drug (IND) approval from the U.S. Food and Drug Administration (FDA) in October 2018.

The results that will be released in oral presentation at the 2019 CSCO Annual Meeting include:

Preliminary safety, pharmacokinetics and efficacy results from a phase I study of CS1003 in Chinese patients with advanced solid tumors or lymphoma (Abstract #4847).
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. In China, its clinical program includes one multi-arm Phase Ib study, two pivotal Phase II studies, and three Phase III studies for several tumor types.

About CS1002 and the CTLA-4 pathway

CS1002 is an investigational anti-CTLA-4 monoclonal antibody being developed by CStone.

Cytotoxic T lymphocyte associated antigen 4 (CTLA-4), also known as CD152, is a transmembrane protein encoded by the CTLA-4 gene that can down-regulate the activity of T cells when binding with its ligand, B7, a pathway also used by tumor cells to avoid T lymphocyte attack. Consequently, blockade of the CTLA-4 pathway can stimulate T cell activation and proliferation to induce or enhance anti-tumor immune responses. CTLA-4 provides a new immuno-therapeutic approach to a number of diseases, including tumors.

Presently, Bristol-Myers Squibb’s Yervoy (ipilimumab) is the only anti-CTLA-4 antibody to gain a market approval worldwide, although Yervoy has not yet been approved in China. Pre-clinical tests have shown that CS1002 has a relatively strong affinity to CTLA-4 and is expected to match Yervoy in terms of efficacy.

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. Unlike 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 in order to 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 successfully avoid immune system recognition. 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.