|Targets:||Class I & IV HDAC Inhibitor
|Indications:||NSCLC and other solid tumors
The overall five year survival rate for patients with NSCLC is only 16.8% and NSCLC results in the greatest number of cancer deaths in the United States. Over recent years, new therapies have been approved that target gene pathways implicated in progression of NSCLC, including EGFR kinase inhibitors, EML4-ALK inhibitors, and immune checkpoint inhibitors. However, these targets represent only a fraction of the growing list of cancer genes that play a role in NSCLC. There remains a significant unmet medical need to develop new therapies that inhibit multiple targets, particularly those that also inhibit novel targets for which no therapy exists. Backed by a strong scientific rationale, we believe that Mocetinostat (MGCD103), combined with durvalumab (an investigational anti-PD-L1 immune checkpoint inhibitor), may result in synergistic and immune enhancing anti-tumor effect.
Mocetinostat (MGCD103) has completed 13 clinical trials which have enrolled more than 400 patients with hematologic malignancies and solid tumors.
A Phase 1-2 study of Mocetinostat (MGCD103), in combination with durvalumab (an investigational anti-PD-L1 immune checkpoint inhibitor), is anticipated to start in 2016. The study will evaluate the safety and efficacy of the combination in patients with non-small cell lung cancer (NSCLC).
In combination with immunotherapy
Preclinical data suggests that spectrum-selective HDAC inhibitors, such as Mocetinostat (MGCD103), may enhance the anti-tumor activity of checkpoint inhibiting antibodies (anti-programmed cell death (PD-1) and anti-programmed cell death ligand (PD-L1) inhibitors) by increasing tumor cell immunogenicity and decreasing cell types that limit the T-cell mediated tumor immune response. In addition, evidence suggests that Mocetinostat (MGCD103) enhances tumor cell immunogenicity by selectively inhibiting Class I HDACs, which results in increased human leukocyte antigen (HLA) expression, can increase PD-L1 expression, and decrease immunosuppressive tumor myeloid derived suppressor cells and T regulatory cells. Lastly, in contrast to other HDAC inhibitors, Mocetinostat (MGCD103) does not inhibit Class II HDACs which may limit the efficacy of immunotherapy and are associated with significant side effects. These data indicate that Mocetinostat (MGCD103) could potentially be used to enhance the efficacy of immune check-point inhibitors, such as PD-1 or PD-L1 antagonists.
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