The preclinical data indicate:
(Shanghai, China, May 15th, 2020) —CStone Pharmaceuticals Co.,Ltd. (“CStone” or the “Company”, HKEX: 2616) today announced that the Company will present pre-clinical data from its pipeline drugs CS1001 (Anti-PD-L1 monoclonal antibody), CS3002 (CDK4/6 selective small molecule inhibitor), and CS3003 (HDAC6 selective small molecule inhibitor). These results will be featured in 3 E-poster presentations for the first time at AACR Virtual Annual Meeting II to be held from June 22-24,2020. All three drug candidates have entered clinical stage of development, in which CS1001 is being investigated in two phase II and four phase III registrational studies.
CS1001 (PD-L1)
CS1001 is an investigational anti-PD-L1 monoclonal antibody being developed by CStone. It inhibits tumor growth and enhances anti-tumor immunity by blocking the interactions between PD-L1 and PD-1. Preliminary results from clinical trials on CS1001 previously presented on the 2019 annual meetings of Chinese Society of Clinical Oncology, European Society of Medical Oncology, and American Society of Hematology have shown promising efficacy and safety of the drug in a variety of solid tumors and lymphomas.
The pre-clinical data to be presented at the 2020 AACR Virtual Annual Meeting II will indicate that in addition to reinvigorating the dysfunctional and exhausted T cells by blockade of the PD-1/PD-L1 interaction, CS1001 can also alter the myeloid cell profile within the tumor microenvironment (TME) to benefit anti-tumor immune responses.
E-poster Presentation Details
Title: Preclinical characterization of CS1001, an anti-PD-L1 IgG4 monoclonal antibody, and its activity beyond T cell regulation（Abstract # 3260）
Date: June 22, 2020
CS3002
CS3002 is a selective small molecule inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6) and currently under clinical development in PhI trial by CStone Pharmaceuticals. Currently, only one CDK4/6 inhibitor—palbociclib—has been approved in China. CS3002 induces cell cycle arrest of tumor cells through direct inhibition of the activity of CDK4/6 kinases. Preclinical studies have shown that both in vitro and in vivo activities of CS3002 are comparable to those of palbociclib. In mouse models, CS3002 in combination with anti-PD-1 monoclonal antibody therapy or endocrine therapy has shown improved tumor-suppressing activities compared to monotherapies. A Phase I study of CS3002 has started in Australia, and its IND application has also been approved in China.
The preclinical data to be presented at the 2020 AACR Virtual Annual Meeting II further illustrate the anti-tumor effect of CS3002 in cancer cells selected for resistance to CDK4/6 inhibitors, as well as its inhibitory activity in acute myeloid leukemia cells, indicating that CS3002 may have broad therapeutic potentials in multiple tumor types and combination therapies.
E-poster Presentation Details
Title: CS3002, a novel CDK4/6 inhibitor with a unique kinase inhibition profile, potentially expands target disease indications including acquired drug resistance（Abstract #：4844）
Date: June 22, 2020
CS3003
CS3003 is a small molecule inhibitor that selectively targets histone deacetylase 6 (HDAC6). By inhibiting HDAC6-mediated degradation of misfolded proteins and increasing cellular stress, it induces tumor cell apoptosis to achieve anti-tumor effects and anti-tumor immunity. Preclinical studies have shown that the combined use of HDAC6 selective inhibitors and proteasome inhibitors in multiple myelomas resulted in improved efficacy and better safety over pan-HDAC inhibitors. In present, a Phase I clinical trial to evaluate the safety and efficacy of CS3003 in advanced solid tumors and relapsed/ refractory multiple myeloma has been approved in both China and Australia.
The pre-clinical data to be presented at the 2020 AACR Virtual Annual Meeting II demonstrate the improved efficacy of CS3003 in combination with the proteasome inhibitor or the anti-PD-1 therapy over mono-therapies, and reveal its unique modulation of gene expression as compared to other HDAC inhibitors.
E-poster Presentation Details
Title: CS3003, an HDAC6-selective inhibitor with distinct profiles of HDAC inhibition and transcriptional regulation, enhances anti-tumor efficacy of the proteasome inhibitor and anti-PD-1 therapy (Abstract #: 4441)
Date: June 22, 2020
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About CS1001
CS1001 is an investigational monoclonal antibody directed against PD-L1 being developed by CStone. It is developed on OmniRat®, a Ligand licensed transgenic animal platform used in the discovery of fully human therapeutic antibodies. As a fully human, full-length anti-PD-L1 monoclonal antibody, CS1001 mirrors natural immunoglobulin G4 (IgG4), which potentially reduces the risk of immunogenicity and toxicities, making it uniquely positioned in terms of safety as compared to other drugs of the same class.
The Phase I dose-escalation study of CS1001 has been completed in China, in which CS1001 demonstrates good anti-tumor activity and tolerability across multiple indications in both Ia and Ib studies.
CS1001 is being investigated in a number of ongoing trials, including one Phase I bridging study in the U.S. In China, its clinical program includes one multi-arm Phase Ib study involving different tumor types, two pivotal Phase II studies, and four Phase III studies respectively targeting stage III & stage VI NSCLC, gastric cancer and esophageal cancer.
About CS3002
Developed by CStone, CS3002 is a new generation of highly selective CDK4/6 inhibitor with potentially favorable safety and tolerability profiles.
CDK4/6 belongs to the cyclin-dependent kinase family. CDK4/6 plays a crucial role in regulating cellular transition from the G1 phase of the cell cycle to the S phase. Upon activation of the cell proliferation signal, D cyclins heterodimerize with CDK4/6 to form kinase complexes, which phosphorylate and inactivate retinoblastoma (Rb) protein, and finally driving cell cycle progression from the G1 phase to the S phase. Aberrant CDK activity is a common feature of most cancer types. CDK4/6 inhibitors can suppress the activities of CDK4/6 and the phosphorylation of Rb protein, thereby inhibiting tumor cell growth by interrupting the cell cycle transition from the G1 phase to the S phase. The fact that dysregulation of the cyclin D-CDK4/6-INK4-Rb is frequently observed in many types of cancer and that CDK4/6 inhibitors have the potential to augment anti-tumor immunity indicates CDK4/6 inhibitors have broad application prospects when used in the treatment of various solid tumors and in immune-oncology combination therapies.
About CS3003
CS3003 is a small molecule inhibitor that selectively targets histone deacetylase 6 (HDAC6). Unlike the other HDAC family members, HDAC6 is mainly located in the cytoplasm and has little effect on DNA histone acetylation. HDAC6 inhibition can increase microtubule acetylation, destroy the autophagy degradation pathway of unfolded or misfolded proteins, thereby promoting cell apoptosis. It has been shown that selective inhibition of HDAC6 can produce better efficacy and improved safety over pan-HDAC inhibitors in treating multiple myeloma. In addition, CS3003 also has the potential to be used in combination with anti-PD-(L)1 antibody drugs in solid tumor treatment, contributing to extended clinical application of immune checkpoint inhibitors.
About CStone
CStone Pharmaceuticals (HKEX: 2616) is a biopharmaceutical company focused on developing and commercializing innovative immuno-oncology therapies and prevision medicine to address unmet medical needs for cancer patients in China and worldwide. Since the Company’s inception in 2015, CStone has assembled a world-class management team with extensive experience in innovative drug development, clinical research, and commercialization. The company has built an oncology-focused pipeline of 15 drug candidates with a strategic emphasis on immuno-oncology combination therapies. Currently, 5 drug candidates are at pivotal late-stage development. With an experienced team, a rich pipeline, a robust clinical development-driven business model and a strong financial position, CStone's vision is to become a globally recognized, leading Chinese biopharmaceutical company by bringing innovative oncology therapies to cancer patients from all over the world.
To learn more about CStone Pharmaceuticals, please visit: www.cstonepharma.com
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The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, we undertake no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions may alter in light of future development.
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