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Tiziana Life Sciences Announces Safety of Milciclib in a Phase 2a Trial in Unresectable or Metastatic Hepatocellular Carcinoma (HCC) Patients


Demonstration of safety, a pre-requisite to initiate a Phase 2b
trial evaluating combination of Milciclib with sorafenib (Nexavar®;
Bayer Germany) in HCC patients, is an important milestone

Tiziana Life Sciences plc (AIM: TILS), a clinical stage biotechnology
company developing targeted drugs for cancer and inflammatory diseases,
today announces that the independent data monitor committee (IDMC)
completed interim analysis of the safety and pharmacokinetic data from
the first six patients and concluded that treatment with Milciclib was
safe and well-tolerated with no drug-related serious adverse events
(SAEs) in patients with unresectable or metastatic HCC. The IDMC
recommended continuing with the trial.

  • This Phase 2a multi-center and multi-country clinical trial
    (CDKO-125A-010) in patients with unresectable or metastatic HCC was
    conducted in Israel, Italy and Greece. Since, this was the first trial
    with Milciclib in HCC patients, an interim analysis was scheduled to
    ensure safety of patients with underlying liver cirrhosis.
  • Establishment of safety in HCC patients was a key pre-requisite to
    move forward with the further clinical development of Milciclib. The
    treatment regimen with Milciclib (100mg/day; 4 days On/3 days Off,
    every 4 weeks) was safe and well-tolerated with no drug-related SAEs
    in patients with unresectable or metastatic HCC.
  • As a next step, a Phase 2b trial to evaluate safety and clinical
    activity of Milciclib in combination with sorafenib (Nexavar®; Bayer
    Germany) in HCC is expected to start in Q2, 2018.

Gabriele Cerrone, Chairman of Tiziana Life Sciences, commented:
"unresectable or metastatic HCC is an aggressive type of liver cancer
for which no satisfactory treatment is currently available. The
establishment of Milciclib's safety is a significant milestone as it
paves way to move forward with clinical studies evaluating Milciclib in
combination with sorafenib (Nexavar®; Bayer) or nivolumab (Opdivo®;
Bristol Myers Squibb) for treatment of HCC."

Kunwar Shailubhai, CEO & CSO of Tiziana Life Sciences, commented:
"Safety findings of Milciclib in HCC are consistent with the findings
reported earlier on the long-term safety and clinical activity of
Milciclib in thymic carcinoma, thymoma1 and other solid
cancers2. Results from these clinical studies will facilitate
the further clinical development of Milciclib for treatments of HCC and
other cancers".

Cited References

1. 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.

2. Press Release on announcement of clinical data in thymoma and thymic

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

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. 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-CD3
antibody in clinical development. This phase 2 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.

For more information go to

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

The content of this announcement has been reviewed and approved for
publication by Dr Kunwar Shailubhai, CEO & CSO of the Company.

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