Tiziana Life Sciences Announces Initiation of a Phase IIa Clinical Trial with Milciclib in Patients with Hepatocellular Carci...
July 19 2017 - 7:41AM
Business Wire
Milciclib, a novel inhibitor of pan-CDKs,
has shown clinical responses in refractory cancer patients
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 (Nexavar®). 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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version on businesswire.com: http://www.businesswire.com/news/home/20170719005732/en/
Tiziana Life Sciences plcGabriele Cerrone, Chairman and
founder+44 (0)20 7493 2853orCairn Financial Advisers LLP
(Nominated adviser)Liam Murray+44 (0)20 7213 0883orBeaufort
Securities Limited (Broker)Saif Janjua+44 (0)20 7382
8300orFTI ConsultingSimon Conway / Natalie
Garland-Collins+44 (0)20 3727 1000
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