have expanded their collaboration related to anticancer treatments based on histone deacetylase enzyme (HDAC) inhibitors. MethylGene could make up to $101 million in various milestone payments from this deal.
The latest agreement adds a new target, Class III HDACs called sirtuins, to be studied. The companies will work on small molecule inhibitors of sirtuins that will be developed as either a monotherapy or a combination treatment. MethylGene reports that it has identified a series of potent lead compounds, and Pharmion expects to file an IND application within the next 24 to 30 months.
Sirtuins, including SIRT1, reportedly have been shown to deacetylate histone proteins and numerous transcription factors, leading to promotion of normal cell survival and aberrant gene silencing in cancer cells. Inhibition of sirtuins allows reexpression of silenced tumor suppressor genes, leading to reduced growth of cancer cells.
Synergies in gene reexpression have been demonstrated by combining SIRT1 inhibition with either standard cytotoxics or other epigenetic modifying drugs, including inhibitors of DNA methylation and histone deacetylation.
Pharmion will fund preclinical research, including approximately $5 million in full-time equivalent (FTE) support to MethylGene over an 18-month period. MethylGene will cover 40% of clinical development costs, and Pharmion will provide the rest.
Pharmion's milestone fees to MethylGene could reach $22 million based on the achievement of development and regulatory goals. The nearest milestone of $2 million will be paid upon enrollment of the first patient in a Phase I trial. In addition, MethylGene could receive up to $79 million upon the achievement of sales milestones and royalties.