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BET inhibitor

JAB-8263 class 1 innovative drug that is a Bromodomain and Extra-Terminal motif (BET) inhibitor independently developed by Jacobio. Preclinical studies have shown that JAB-8263 can effectively inhibit tumor growth at very low concentrations. In addition to solid tumors, hematological tumors are particularly sensitive to JAB-8263. Patients with hematological tumors and some types of solid tumors may benefit from the treatment of JAB-8263. Jacobio is currently conducting multicenter, open-label, phase I/IIa clinical studies in China and the United States.

Mechanism of Action

JAB-8263 is a potent BET inhibitor with a strong affinity to BET protein in vitro. BET is a protein family composed of four members (BRD2, BRD3, BRD4, BRDT) with similar functions. BET is an important histone acetylation recognition protein. The recognition of histone by BET can recruit transcription factors to DNA and initiate gene transcription. The activity of BET can lead to the expression of the oncogenic protein MYC.

There have been few drugs to date that effectively interfere with the activity of the MYC pathway in tumor cells. JAB-8263 effectively reduces the expression of MYC in tumor cells and as a result exerts favorable anti-tumor effects of inhibition of tumor cell growth and proliferation, and induction of apoptosis.

Indications

Current available clinical study data show that preliminary anti-tumor activities have been observed in a variety of advanced solid tumors, including NUT midline cancer, non-small cell lung cancer, small cell lung cancer, castration resistant prostate cancer, ovarian cancer, and colorectal cancer. Additionally, preliminary anti-tumor activities of BET inhibitors have also been noted in hematological tumors, including relapsed/refractory diffuse large B-cell lymphoma, acute myeloid leukemia and myelofibrosis.

Clinical Trials
Asset Region Phase Indication Registration information
JAB-8263 U.S.  I Advanced solid tumors ClinicalTrials: NCT04587479
China  I/IIa Advanced solid tumors CDE number: CTR20210017
ClinicalTrials: NCT04686682
R/R AML
MF naïve to JAK inhibitor
 
References
  1. Saenz, D.T., et al., BET protein bromodomain inhibitor-based combinations are highly active against post-myeloproliferative neoplasm secondary AML cells. Leukemia, 2017. 31(3): p. 678-687.
  2. Kleppe, M., et al., Dual Targeting of Oncogenic Activation and Inflammatory Signaling Increases Therapeutic Efficacy in Myeloproliferative Neoplasms. Cancer Cell, 2018. 33(4): p. 785-787.
  3. Bechter, O. and P. Schoffski, Make your best BET: The emerging role of BET inhibitor treatment in malignant tumors. Pharmacol Ther, 2020. 208: p. 107479.