Tiziana’s Milciclib is a potent, small molecule inhibitor of multiple cyclin-dependent kinases (CDKs), tropomycin receptor kinases and Src family kinases controlling cell growth and malignant progression of cancer. Milciclib has demonstrated safety in 316 patients with advanced solid cancers in Phase 1 and 2 studies and shown indications of efficacy. In two, completed, Phase 2 thymic cancer trials, Milciclib successfully increased overall survival and met both primary and secondary endpoints. While the current standard of care for hepatocellular carcinoma (HCC), the most common liver cancer, is only effective in a small percentage of patients, Milciclib has the potential to be broadly effective because it targets the underlying cause of disease.
A unique feature of Milciclib is its ability to reduce microRNAs, miR-221 and miR-222, that promote the formation of blood vessels (angiogenesis) to facilitate the spread of cancer cells. Levels of these microRNAs are consistently increased in HCC patients and may contribute towards resistance to treatment with Sorafenib. In July and September 2019, we reported Phase 2a safety, tolerability and efficacy data of Milciclib as a monotherapy in patients with advanced HCC. Milciclib was well tolerated with manageable toxicities and no recorded drug related deaths, thereby meeting the trial's primary endpoint. Both median TTP and PFS were 5.9 months. More than 60% of evaluable patients showed Stable Disease. The Clinical Benefit Rate was >64.3%.
Safety and clinical activity of combination treatment of Milciclib with Regorafenib in liver transplant patients with recurrent HCC has also been evaluated in an investigator originated liver transplant patient recurrent HCC trial. Combination treatment was well tolerated with manageable toxicities. Safety and clinical activity data were presented at Virtual ASCO 2020 conference. Tiziana intends to initiate Phase 2b clinical trial in liver transplant recurrent HCC patients with Milciclib in combination with a Regorafenib in Q2 2021.