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Pancreatic ductal adenocarcinoma (PDAC), myelodysplastic syndrome (MDS), acute myelogenous leukemia (AML), hepatocellular carcinoma (HCC)
- Completed Phase 2 clinical studies for PDAC patients
- Phase 2 clinical study in progress for patients with MDS
- AML and HCC clinical studies in development
Best-in-class (i.e., best inhibitor effect amongst similar HDAC inhibitors)
Improved efficacy compared to existing treatments based on Phase 2 clinical study for PDAC
(Disease control rate 93.8%, overall survival rate 10.8 months)
Significantly improved safety compared to existing treatments in PDAC based on Phase 2 clinical study results
(3등급 이상의 비혈액학적 부작용이 현저히 적게 나타남)
FDA orphan drug designation:
HCC, AML, PDAC
MFDS developmental orphan drug
Deacetylation of histone protein
Regulates the expression of genes by managing the process of DNA condensation around histone proteins
Abnormal HDAC expression
Induction of persistent histone protein de-acetylation (promotes DNA condensation)
Decreased expression of cancer suppressor genes
Infinite growth of mutant cells
Anticancer effect, epigenetic homeostasis recovery
- Promoting cancer suppressor gene expression by inhibiting overexpressed HDACs
- Inhibiting tumor cell proliferation (increases P21 expression, induces P53 acetylation) or induces tumor cell suicide
- Restoring anticancer drug efficacy (Gemcitabine, 5-Fu) - i.e., chemoresistance is removed and cancer cells are once again sensitive to chemotherapy
Immunomodulation effect that promotes the anti-tumor immune response of the body
- Increasing cytotoxic T cells, promoting NK cell activity
- Inhibiting proliferation of immunosuppressed cells (M2 macrophages, MDSC (Myeloid-Derived Suppressor Cells), Regulatory T cells)
- Inducting synergistic effect against immune checkpoint inhibitor (anti-PD-1 antibody)
Kim, Y.D. et al. HDAC Inhibitor, CG-745, enhances the anti-cancer effect of anti-PD-1 immune checkpoint inhibitor by modulation of the immune microenvironment. J. Cancer. 11, 4059-4072 (2020).
Kim, Y.S. et al. The anti-fibrotic effects of CG-745, an HDAC inhibitor, in bleomycin and PHMG-induced mouse models. Molecules 24, 2792 (2019).
Yoon, G.E. et al. Histone deacetylase inhibitor CG200745 ameliorates high-fat diet-induced hypertension via inhibition of angiotensin II production. Naunyn-Schmiedebergs Arch. Pharmacol. 393, 491-500 (2020).
Oh, E.T. et al. Novel histone deacetylase inhibitor CG200745 induces clonogenic cell death by modulating acetylation of p53 in cancer cells.
Invest. New Drugs 30, 435-442 (2012).
Jung, D.E. et al. CG200745, an HDAC inhibitor, induces anti-tumour effects in cholangiocarcinoma cell lines via miRNAs targeting the hippo pathway. Sci. Rep. 7, 10921 (2017).
Lee, H.S. et al. A novel HDAC inhibitor, CG200745, inhibits pancreatic cancer cell growth and overcomes gemcitabine resistance. Sci. Rep. 7, 41615 (2017).