HBI-8000: A novel histone deacetylase (HDAC) inhibitor for cancer
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Low nanomolar inhibitor of cancer-associated HDACs, one of the few with activity on class II 10 with no activity on class II 6 (often associated with cardiac toxicity)
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Long half-life with Cmax and AUC in the range of enzyme inhibition, large volume of distribution and prolonged pharmacodynamic activity compared with first generation inhibitors
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China Phase 1 data highly encouraging; >50% response or stable disease in a large percentage of tumors with a good safety profileA Phase 2 registration trial in peripheral T-cell lymphoma (PTCL) and a Phase 2 trial in cutaneous T-cell lymphoma (CTCL) underway in China – best in class response for CTLC and among the best for PTCL based on preliminary results
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Phase 2 trials in solid tumors approved by the sFDA in China: A non-small cell lung trial was initiated March 2011 and breast and prostate trials are scheduled to begin shortly
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HUYA completed IND-enabling studies in the US and initiated Phase 1 dosing under an IND in June 2010
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Co-development partnership with Quintiles
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Entering Phase 2 in the U.S.: HBI-8000 in combination with an EGF receptor kinase inhibitor in non-small cell lung carcinoma patients using volumetry end point
About HDACs and HDAC inhibitors
HDAC inhibitors work by controlling how tightly DNA is wound around histone proteins. By deacetylating (removing an acetyl group from) histones, HDACs appear to promote tighter winding of DNA around these proteins, leading to reduced access by gene transcription factors. This results in decreased expression of proteins involved in cell differentiation, cell cycle arrest, tumor immunity, and apoptotic elimination of damaged cells, all of which contribute to the development of cancer. HDAC inhibitors are able to restore expression of tumor suppressor and other anti-tumor genes in a selective manner. Treatment with HDAC inhibitors also leads, indirectly, to inhibition of the expression of angiogenesis factors, helping to choke off the blood supply to tumors. Although significant preclinical and clinical activity has been observed with HDAC inhibitors, most have characteristics which may limit their potential for clinical success or broad applicability. In contrast, HBI-8000 has selectivity, potency, PK and side effect profiles that make it more suitable for use as a stand-alone therapeutic, as well as in combination with a wide variety of marketed anti-tumor agents. Worldwide licensing rights ex-China are available.