Tiziana Life Sciences (AIM:TILS) Phase II Clinical Trial Update

Tiziana Life Sciences plc (AIM: TILS), a clinical stage biotechnology company developing targeted drugs for cancer and inflammatory diseases, today announces that milciclib, a small molecular pan-inhibitor of cyclin dependent kinases (“CDKs”), met its primary endpoints in the two phase II clinical trials in patients with thymic carcinoma and thymoma. The treatment regimen with milciclib (150mg/day; 7days On/7days Off) was safe and well-tolerated in these patients with continuing exposure of up to 5 years.

MAJOR HIGHLIGHTS OF THE CLINICAL DATA

· Two separate phase II multi-centered clinical trials (CDKO-125A-006: 72 patients and CDKO-125A-007: 30 patients) in patients with thymic carcinoma and thymoma, respectively, were conducted in the USA, France and Italy. Thymic carcinoma is a metastatic malignancy which is generally accepted as being more difficult to treat than thymoma.

· Both clinical studies demonstrated that treatment with milciclib was efficacious and met progression free survival (“PFS”) as the primary endpoint and overall survival (“OS”) as a secondary endpoint.

· In the trial CDKO-125A-006, 56 of 72 treated patients had median PFS of 5.78 months with upper and lower 95% confidence limits of 3.48 and 7.89 months, respectively. In trial CDKO-125A-007, 18 of 30 treated patients had median “PFS” of 5.65 months with upper and lower 95% confidence limits of 3.94 and 17.45 months, respectively.

· The OS secondary endpoint was also met in both trials. In trial CDKO-125A-006, 36 of 72 (50%) treated patients had median OS of 24.44 months with upper and lower 95% confidence limits of 22.05 and 53.55 months, respectively. In trial CDKO-125A-007, 18 of 30 patients had an OS (54.5%) of 48 months. As a median was not reached, the 95% confidence limits could not be calculated.

· Seven patients (5 patients in the CDKO-125A-006 study and 2 patients in the CDKO-125A-007) have been continuing treatment with milciclib for more than 2 years with excellent safety profile. Among these, 2 patients have been treated with milciclib for approximately 5 years, demonstrating safety of the drug for long term treatment.

Gabriele Cerrone, Chairman of Tiziana Life Sciences, commented:

“Thymic carcinoma and thymoma are unmet medical needs with no approved therapies. It is very promising that milciclib has again been shown to be a safe and efficacious drug. Milciclib could potentially be the first single agent for long-term treatment of these rare cancers.”

Kunwar Shailubhai, CEO & CSO of Tiziana Life Sciences, commented:

“Data from these two clinical studies demonstrating efficacy and long-term safety is a major milestone in clinical development of milciclib. We will work with regulatory agencies in US and Europe to develop plans to bring these first-in-class therapies to patients in need as soon as possible.”

In parallel, milciclib is also being evaluated in a phase II HCC trial as a single agent to assess primarily its safety and preliminary clinical responses. Further clinical development of milciclib in combination with other drugs to treat HCC are being planned.

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 non-small cell lung cancer (NSCLC), pancreatic carcinoma, colon cancer, thymoma and thymic carcinoma1,2. Importantly, combination of milciclib with gemcitabine, a widely-used chemotherapeutic drug, in a phase I dose-escalation study showed favorable clinical responses in approximately 36% of patients with refractory solid and metastatic tumors, suggesting that the treatment with milciclib may be able to overcome resistance of cancers towards other chemotherapeutic drugs2.

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.

About Thymoma and Thymic Carcinoma

Thymomas and thymic carcinomas are thymus tumors of epithelial origin. The incidence of thymic malignancies is approximately 1.5% of all malignancies with an overall incidence of 0.15 cases per 100,000. Thymic carcinomas are invasive and represent 0.06% of all thymic cancers, whereas thymomas tend to recur locally and are less likely to metastasize (https://www.cancer.gov/types/thymoma/hp/thymoma-treatment-pdq).

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.

About Tiziana Life Sciences

Tiziana Life Sciences plc is a UK biotechnology company that focuses on the discovery and development of novel molecules to treat human disease in oncology and immunology. In addition to milciclib, the Company is also developing foralumab for liver diseases. Foralumab is the only fully human anti-CD3 monoclonal antibody in clinical development in the world. 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.



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