Chidamide (trade name: Epidaza®) is an innovative molecular entity drug discovered exclusively by the company, featuring a novel mechanism. It is the world's first subtype-selective histone deacetylase (HDAC) inhibitor and the first oral therapeutic drug approved for treating peripheral T-cell lymphoma and advanced hormone receptor-positive breast cancer. As an epigenetic regulator, Chidamide represents a significant advancement in the field.

Chidamide is a subtype-selective benzamide inhibitor of histone deacetylase (HDAC) primarily targeting subtypes 1, 2, 3 of class I HDAC and subtype 10 of class IIb HDAC. Mechanistically, Chidamide modulates abnormal epigenetic regulation of chromatin remodeling in cancer by inhibiting relevant HDAC subtypes and increasing the acetylation level of chromatin histones, resulting in alterations to gene expression (i.e., epigenetic changes) in multiple signal transduction pathways, as well as cell cycle inhibition and apoptosis induction of tumor cells. 

In addition, Chidamide can induce the differentiation of tumor stem cells and reverse the epithelial-mesenchymal transition (EMT) of tumor cells through epigenetic regulatory mechanisms, thereby potentially playing pivotal roles in restoring the sensitivity of drug-resistant tumor cells as well as preventing cancer metastasis and recurrence.Specifically, Chidamide's general mechanism of action includes 1) direct inhibition of tumor cell cycles and induction of apoptosis; 2) induction and activation of tumor killing mediated by natural killer (NK) cells and antigen-specific cytotoxic T cells (CTL); and 3) inhibition of phenotypic transformation of tumor cells and pro-drug resistance/pro-transfer activity in the microenvironment.

Figure. The molecular mechanisms of action of Chidamide (Epidaza®)

• In December 2014, Chidamide was approved for the treatment of peripheral T-cell lymphoma by the CFDA (now NMPA), filling a gap in lymphoma therapy in China.
• In July 2017, Chidamide was included in China’s national medical insurance coverage, bringing its benefits to more patients.
• In November 2019, Chidamide was approved by the NMPA in combination with an aromatase inhibitor for the treatment of post-menopausal patients with hormone receptor-positive, HER2-negative, recurrent or progressive locally advanced or metastatic breast cancer previously treated with endocrine therapy. This approval made Chidamide the first epigenetic drug approved for solid tumor therapy in the world, following groundbreaking evidence that Chidamide can effectively prevent tumor resistance in combination with other targeted drugs.
• In April 2021, a new drug application for Chidamide in the treatment of peripheral T-cell lymphoma (PTCL), the second indication for Chidamide in Japan, was successfully submitted to the Pharmaceuticals and Medical Devices Agency (PMDA).
• In June 21, a marketing application for Chidamide in the treatment of adult T-cell leukemia (ATL) was accepted by the PMDA, marking the first time a Chinese-developed drug had ever been approved for marketing oversea.
• In Jun. 2021, Chidamide monotherapy to treat Adult T-cell Leukemia/Lymphoma (ATL) was approved for marketing in Japan. 
• In Dec. 2021, Chidamide monotherapy to treat Relapsed/Refractory (R/R) Peripheral T-cell Lymphoma (PTCL) was approved for marketing in Japan, which was a new indication approved following ATL in Jun. 2021 in the country. 
• In Mar. 2023, Chidamide in combination with exemestane was approved in Taiwan, China, for the treatment of patients with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, post-menopausal locally advanced or metastatic breast cancer that has relapsed or worsened following endocrine therapy.
• In Apr. 2024, Chidamide in combination with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) was approved in China for the treatment of therapy-naive patients with MYC- and BCL2-positive diffuse large B-cell lymphoma (DLBCL).
• In Dec. 2024, Chidamide was included into the National Drug Reimbursement List for the first time for the indication of diffuse large B-cell lymphoma (DLBCL).

Exploration of Other Indications Worldwide

• In Mar. 2024, the CAPability-01 study led by Professors Ruihua Xu and Feng Wang from the Sun Yat-Sen University Cancer Center was published in Nature Medicine, a premier academic journal with an impact factor of 82.9. The study showed that for patients with microsatellite stable or proficient mismatch repair (MSS/pMMR) metastatic colorectal cancer (mCRC), the three-drug regimen of Chidamide + sintilimab + bevacizumab for third-line and beyond treatment achieved an 18-week PFS rate of 64.0%, an ORR of 44.0%, and a median PFS of 7.3 months, which is a promising treatment option for patients with advanced MSS/pMMR mCRC. In Jun. 2024, this indication was officially included in the "Breakthrough Therapy Category" by the Center for Drug Evaluation (CDE) of the NMPA. In Jul. 2024, the application for a phase 3 clinical trial of Chidamide in combination with sintilimab and bevacizumab for treating patients with advanced microsatellite stable or proficient mismatch repair (MSS/pMMR) colorectal cancer who have failed ≥ 2 lines of standard treatment were approved. A total of 430 subjects were planned to be enrolled in this trial and 200 subjects had been enrolled by Apr. 3, 2025.
• In Nov. 2024 the application for a randomized, double-blind, placebo-controlled, multicenter, phase 3 clinical trial of Chidamide in combination with CHOP for treatment-naive peripheral T-cell lymphoma with T follicular helper phenotype (PTCL-TFH) was accepted, and the approval letter for this clinical trial was issued in Feb. 2025.
• HUYABIO, an international partner of the company, completed the enrollment of a randomized, double-blind, active-controlled phase 3 clinical trial evaluating Chidamide combined with nivolumab as a first-line treatment for advanced melanoma across 17 countries worldwide. HUYABIO reported the follow-up results of a phase 2 clinical trial evaluating Chidamide combined with nivolumab as a first-line treatment for melanoma at the 2024 Annual Meeting of the Society for Immunotherapy of Cancer (SITC). The treatment in 39 patients achieved an ORR of 65.8%, a CR of 15.8%, and an mPFS of 36.9 months, showing excellent potential for efficacy.
• In addition to the above trials, the company is conducting several investigator-initiated clinical studies of Chidamide monotherapy and combination immunotherapy or with other drugs in hematological tumors, solid tumors, etc.

For more details, please visit the Epidaza® website (www.epidaza.com) , or scan the QR code below and follow 【Chipscreen Biosciences】&【 Epidaza Medical Information Platform 】by Wechat.