TILS.L Regulatory News (TILS)

Tiziana Life Sciences plc

("Tiziana" or the "Company")

Tiziana Life Sciences Announces Initiation of a Phase IIa Clinical Trial with Milciclib in Patients with Hepatocellular Carcinoma

Milciclib, a novel inhibitor of pan-CDKs, has shown clinical responses inrefractory cancer patients

London, 19 July, 2017 - Tiziana Life Sciences plc (AIM: TILS), a clinical stage biotechnology company developing targeted drugs for cancer and inflammatory diseases, today announces the enrolment of the first patient in its phase IIa clinical trial with milciclib, a novel inhibitor of cyclin-dependent kinases (CDKs), in patients with refractory hepatocellular carcinoma ("HCC"). Top line data from this trial, being conducted in Italy, Israel, Greece and Turkey, is expected in Q4 2018. The primary objective of this multi-centre, multi-country and dose-ranging phase IIa clinical study is to evaluate the safety of milciclib in HCC patients who fail to respond to or are intolerant to the existing standard of care treatment. Subsequently, a phase IIb is planned with the combination of milciclib with the standard of care treatment sorafenib in HCC patients.

Milciclib is an inhibitor of several cyclin-dependent kinases (CDKs), which are commonly overexpressed in tumours resistant to chemotherapy. Accordingly, the investigational therapy will be tested in patients who have failed to respond to the standard of care treatment, sorafenib (NexavarÒ). Preclinical studies conducted strongly suggest that milciclib acts primarily through downregulation of microRNA (miR) 221 and 222, which are known to be associated with hepatocarcinogenesis and overexpression of these miRs is also believed to be associated with development of resistance to sorafenib in HCC patients.

In previous phase I clinical studies, oral treatment with milciclib was found to be safe and well-tolerated in patients with advanced solid tumours such as thymoma and thymic carcinoma, pancreatic carcinoma and colon cancer.1 The combination of milciclib with gemcitabine, a well-known nucleoside analogue, in a phase I dose-escalation study showed favourable clinical responses in approximately 36% of patients with advanced/metastatic tumours, including patients previously considered to be resistant to gemcitabine.2

Gabriele Cerrone, Chairman of Tiziana Life Sciences, commented: "HCC is a real unmet medical need due to its growing incidence and lack of effective therapy. It is the fifth most common cancer worldwide and the second most common cause of death from cancer worldwide."

Kunwar Shailubhai, CEO & CSO of Tiziana Life Sciences, commented: "Oral treatment with milciclib has been well-tolerated in previous studies with cancer patients. We strongly believe, based on its unique mechanism of action, that the drug may have potential to be developed either as a monotherapy or combo-therapy with sorafenib for treatment of HCC."

Dr. Ilan Yaron, Director of the Department of Medicine at Hebrew University Hadassah Medical Center, Israel and Chief Medical Officer of Tiziana Life Sciences, added: "The prognosis for liver cancer is very poor due to lack of effective therapy.  We believe that milciclib holds promise as an effective anti-cancer treatment with a high safety profile."

About HCC

Hepatocellular carcinoma is the fifth most common cancer in men and the ninth in women. Additionally, it is the fifth most common cancer worldwide and the second most common cause of death from cancer worldwide.3 The tumour is associated with chronic hepatitis B and chronic hepatitis C infections, as well as with nonalcoholic steatohepatitis. The prognosis for liver cancer is very poor due to lack of effective therapy.

About Milciclib

Milciclib (PHA-848125AC) is a small molecule inhibitor of several cyclin dependent kinases (CDKs) 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 signalling pathways that regulate cell cycles have been frequently found to be associated with development of resistance towards chemotherapies. Oral treatment with milciclib was found to be effective in reducing tumour growth in animal models of HCC, possibly through downregulation of miR-221 and miR-222. 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 thymic carcinoma, pancreatic carcinoma and colon cancer.

About Tiziana Life Sciences

Tiziana Life Sciences plc is a UK biotechnology company that focuses on the discovery and development of novel molecules that treat human disease in oncology and immunology. The Company is focused on its lead compound milciclib. The Company is also in clinical development of foralumab. Foralumab is the only fully human engineered anti-human CD3 antibody in clinical development. This phase II compound has potential application in a wide range of autoimmune and inflammatory diseases, such as nonalcoholic steatohepatitis (NASH), primary biliary cholangitis (PBS), ulcerative colitis, multiple sclerosis, type-1 diabetes (T1D), inflammatory bowel disease (IBD), psoriasis and rheumatoid arthritis, where modulation of a T-cell response is desirable.

Cited References

1. Weiss GJ, Hidalgo M, Borad MJ, et al. (2012) Phase I study of the safety, tolerability and pharmacokinetics of PHA-848125AC, a dual tropomyosin receptor kinase A and cyclin-dependent kinase inhibitor, in patients with advanced solid malignancies. Invest New Drugs 30:2334-43. doi: 10.1007/s10637-011-9774-6.

2. Aspeslagh, S., Shailubhai, K., Bahleda, R. et al. Cancer Chemother Pharmacol (2017). Phase I dose-escalation study of milciclib in combination with gemcitabine in patients with refractory solid tumors. Cancer Chemother Pharmacol. 79:1257-1265.

3. Sahil Mittal and Hashem B. El-Serag (2013) Epidemiology of HCC: Consider the Population. J Clin Gastroenterol. 2013 Jul; 47(0): S2-S6.

For more information go to http://www.tizianalifesciences.com

This announcement contains inside information for the purposes of Article 7 of EU Regulation 596/2014.

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