On October 16, 2018 Tiziana Life Sciences plc (AIM: TILS), a clinical stage biotechnology company developing targeted drugs for cancer and inflammatory diseases, reported that it will present results from preclinical studies demonstrating synergistic activity of milciclib with sorafenib (NexavarR) to suppress tumor growth in an orthotopic mouse model of HCC (Press release, Tiziana Life Sciences, OCT 16, 2018, View Source [SID1234530004]). Additional preclinical studies will be presented which also demonstrated synergism between Milciclib and other tyrosine kinase inhibitors (TKIs) such as Regorafenib (StivargaR) and Lenvatinib (LenvimaR). The presentation will take place at the American Association for the Study of Liver Diseases (AASLD) Meetingin San Francisco on 9-11 November 2018.

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The details of the presentation are:

Poster #1543 entitled "Oral Treatment with Milciclib Either Alone or in Combination with Sorafenib Inhibited Tumor Growth in an Orthotopic Model ofHepatocellular Carcinoma"will be presented at the Poster Session III on November 11, 2018.

The data results from pre-clinic studies in mouse models which will inform future research but the information to be presented is an extension of previously announced research and does not, in the view of the Company and its directors, constitute material data requiring dissemination via a regulatory news service. According this information is being released via RNS Reach to inform interested parties of the direction and results of our continuing research activity.

MAJOR HIGHLIGHTS OF THE DATA

· Oral treatment with milciclib (30mg/kg/day) in combination with sorafenib (20mg/kg/day) produced synergistic effect on reduction of HCC-tumor growth in an orthotopic animal model. Since, the doses of milciclib and sorafenib used were sub-optimal, it is possible that the combination treatment at sub-optimal doses may reduce the toxicities of sorafenib or other TKIs.

· While treatment with milciclib as a single agent significantly suppressed growth in cell cultures as well as in animal models, it also exhibited strong synergistic anti-HCC effects with TKIs such as sorafenib, regorafenib and lenvatinib in other pre-clinical studies

· Mechanism of action studies suggest that milciclib exhibits broad-spectrum anti-HCC activity through a different mechanism from TKIs to produce the pronounced synergism.

"We reported earlier that oral treatment with Milciclib was found to be well-tolerated and it achieved both primary and secondary clinical endpoints in two separate phase 2 trials in thymic carcinoma and thymoma. The new pre-clinical research data demonstrating synergism with TKIs is exciting and suggests the potential of Milciclib in combination with one of these approved TKIs to develop a safe and an improved treatment option for HCC patients" said Gabriele Cerrone, Chairman of Tiziana Life Sciences

The complex multi-factorial etiology of HCC warrants an immediate need for drugs with different mechanisms that may produce improved efficacy and safety. The data we have announced from the interim analysis of the ongoing phase 2a clinical study of orally administered milciclib in sorafenib-resistant patients suggests that the treatment is well-tolerated and seems to provide clinical benefits to these patients. We are pleased to see that milciclib produces strong synergistic anti-HCC activity in preclinical studies as these data are important milestones to move forward in our evaluation the potential of Milciclib in combination with one of the approved TKIs to improve safety, efficacy and clinical response rate in HCC patients" said Kunwar Shailubhai, CEO & CSO of Tiziana Life Sciences.

About Hepatocellular Carcinoma

Hepatocellular cancer is the 5th most common cancer and the 3rd cause of cancer mortality worldwide. In 2007 the approval by the European Medical Agency (EMA) and Food and Drug Administration (FDA) of sorafenib in HCC represented the first systemic therapy for improving outcome in patients unsuitable for loco-regional and surgical therapies and created a new standard of treatment for the disease. However, although significant in respect to placebo, the benefits of sorafenib are modest; the response rate is less than 3%, the improvement in median survival is 2-3 months and the drug-related symptoms are not ordinary. Therefore, more effective systemic therapy is required for both naive patients presenting with unresectable, advanced stage and those who suffer recurrence after curative treatments (resection, ablation and transplantation).

About Milciclib

Milciclib (PHA-848125AC) is a small molecule inhibitor of several cyclin dependent kinases such as CDK1, 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.

A phase 2a multi-centre and multi-country clinical trial (CDKO-125A-010) in sorafenib-refractory or -intolerable patients with unresectable or metastatic HCC is currently being conducted in Greece, Italy and Israel.