Tiziana’s late-stage oral CDK inhibitor, milciclib, has recently completed two Phase II studies for thymoma and thymic carcinoma for which it has orphan drug status. Treatment with milciclib was safe, well-tolerated and met the primary endpoints achieving disease stabilisation in a majority of patients.
The current focus is on milciclib alone or in combination with other drugs for treatment of HCC, the most common primary malignancy of the liver in adults.
HCC is the fifth most common cancer in men and the eighth most common cancer in women in the US. Liver cancer incidence and death rates are steadily rising with the highest average annual percent increase of the top 15 cancers by incidence.
Most HCC patients present with advanced disease and do not benefit from transplantation, surgical resection, and locoregional therapies and there is only one chemotherapeutic agent approved for advanced HCC patients. As a result, its lethality makes it the third most common cause of cancer death worldwide.
The primary risk factor for HCC is hepatic cirrhosis with an estimated 78% of HCC cases and 57% of cases of liver cirrhosis caused by chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV). Recently, the combination of insulin resistance, hypertension, dyslipidemia, and obesity, termed “metabolic syndrome,” has been recognized as a cause of nonalcoholic fatty liver disease (NAFLD), cirrhosis, and HCC. Linking our two main focus areas together, NAFLD looks to be a common underlying liver disease not only in progressing to non-alcoholic steatohepatitis (NASH) but also in patients with hepatocellular carcinoma.
Cancer is primarily due to deficiencies in cell cycle control, eventually resulting in transformation of normal cells to rapidly growing cancer cells. Therapeutic intervention to control cell cycle has long been anticipated as effective cancer therapies. Cyclin-dependent kinases (CDKs) are the specific enzymes that promote transition through the cell cycle ultimately drive cell proliferation.
Tiziana Life Sciences (TILS) acquired milciclib from Nerviano Medical Sciences. Milciclib (a.k.a PHA-848125 or PHA-848125AC) is a small molecular inhibitor of cyclin-dependent kinases (CDKs) and Src family of kinases, and a limited number of additional kinases.
The compound is an oral drug candidate that inhibits cyclin-dependent kinase 2 (CDK2) and also exhibits inhibitory activity against other CDKs including CDK1 and CDK4 to produce potent anti-cancer activity (1-5). Preclinical studies conducted by scientists in Nerviano indicate that milciclib is a potent anti-cancer drug candidate for treatment of a variety of cancers including cancers of thymic, liver and breast cancer (6).