On August 21, 2020 Tiziana Life Sciences plc (Nasdaq: TLSA; AIM: TILS) ("Tiziana" or the "Company"), a biotechnology company focused on innovative therapeutics for oncology, inflammation and infectious diseases, reported that the United States Patent and Trademark Office ("USPTO") has granted a patent on use of Milciclib in combination with tyrosine kinase inhibitors (TKIs) such as Sorafenib (Nexavar), Regorafenib (Stivarga) and Lenvatinib (Lenvima) for the treatment of hepatocellular carcinoma (HCC) and other cancers in humans (Press release, Tiziana Life Sciences, AUG 21, 2020, View Source [SID1234568595]). This patent will be published by the USPTO on 1 September 2020 as Patent No. 10,758,541 (Inventor: Kunwar Shailubhai). Like most human cancers, HCC is a complex multi-factorial cancer with multiple underlying mechanisms causing enormous heterogeneity in patient populations. Consequently, patients with HCC often develop resistance towards the monotherapies of existing therapeutics. Thus, there is an urgent need for combination drug treatment approaches targeting different mechanisms to achieve better clinical outcomes.
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Recently, the Company presented two posters on clinical evaluation of Milciclib at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2020 (ASCO2020). The poster on Phase 2a clinical evaluation of Milciclib, a broad-spectrum inhibitor of cyclin dependent kinases, indicated that the treatment was well-tolerated, and it produced encouraging clinical activity in sorafenib-resistant patients of HCC(1). The second poster was on the evaluation of Milciclib in combination with Regorafenib, a specific TKI drug, in liver transplant patients with HCC recurrence in the MiHRCO (Milciclib and Half Regorafenib CO administration) trial. The combination treatment was safe and produced promising clinical response(2) in these delicate and difficult to treat patients. Additionally, the Company earlier reported data from an animal study suggesting that the combination of Milciclib with Sorafenib, both acting via different mechanisms, suppressed expression of protooncogene c-Myc to produce pronounced synergistic anti-HCC activity(3).
Dr. Kunwar Shailubhai, CEO & CSO of Tiziana Lifesciences, commented, "Advanced cases of patients with HCC have limited therapeutic options because of the heterogeneity of the multiple mechanisms underlying the development of drug resistance and limited clinical responses. Thus, combination of drugs with different mechanism of actions are necessary to achieve superior clinical outcome. We are delighted that we now have this key patent on use of Milciclib in combination with other HCC drugs, including a TKI. Issuance of this patent strengthens our clinical strategy as we move forward with the combination of Milciclib and a TKI for the clinical evaluation of advanced cases of HCC as well as in patients with recurrent HCC after liver transplantation."
The person who arranged for the release of this announcement was Dr Kunwar Shailubhai, Chief Executive Officer and Chief Scientific Officer of the Company
Cited References:
1. Villa, E., Piscaglia, F., Geva, R., Dalecos, G., Papatheodoridis, G., Ciomei, M., Davite, C., Crivori, P., Palejwala, V., Jacob, J., Hamzeh, F., Shailubhai, K., Santoro, A., and A., S. (2020) Phase 2a Safety and Efficacy of Milciclib, a Pan-Cyclin Dependent Kinase Inhibitor, in Unresectable, Sorafenib-Refractory or -Intolerant Hepatocellular Carcinoma Patients. ASCO (Free ASCO Whitepaper) Abstract #29856
2. Pivetti, A., Di Marco, L., Bristot, L., Milosa, F., Maria Critelli, R., De Maria, N., Di Benedetto, F., Palejwala, V., Jacob, J., Shailubhai, K., and Villa, E. (2020) Safety and Clinical Activity of Combination Treatment with Regorafenib and Milciclib in Liver Transplant Patients with Hepatocellular Carcinoma Recurrence. ASCO (Free ASCO Whitepaper) Abstract #307309
3. Jindal, A., Palejwala, V. a., and Shailubhai, K. (2018) Oral Treatment with Milciclib Either Alone or in Combination with Sorafenib Inhibited Tumor Growth in an Orthotopic Model of Hepatocellular Carcinoma. Hepatology 68, 879A
About Milciclib (TZLS-201)
Milciclib (PHA-848125AC) is a small molecule inhibitor of several cyclin dependent kinases such as CDK1, CDK2, CDK4, CDK5 and CDK7. CDKs are serine threonine kinases that play crucial roles in progression of the cell cycle from G1 to S phase. Overexpression of CDKs and other downstream signaling pathways that regulate cell cycles have been frequently found to be associated with development of resistance towards chemotherapies. In a phase I study, oral treatment with Milciclib was found to be well-tolerated and the drug showed promising clinical responses in patients with advanced solid malignancies such as in NSCLC, pancreatic and colon cancer, thymic carcinoma and thymoma.