Tiziana Reports Encouraging Interim Clinical Data from an Ongoing Phase 2a Clinical Trial with Milciclib in Patients With Advanced Liver Cancer

• 80% of patients who completed treatment within the trial’s
  timeframe requested to continue treatment on compassionate use grounds
• Independent Data Monitoring Committee finds no unexpected signs
  or signals of toxicity
• Top line data expected Q3 2019

NEW YORK & LONDON–(BUSINESS WIRE)–Tiziana Life Sciences plc (NASDAQ: TLSA / AIM: TILS), a biotechnology
company focusing on the discovery and development of innovative
therapeutics for inflammation and oncology indications, today announced
results from the interim safety review conducted by the Independent Data
Monitoring Committee (“IDMC”) on 21 March 2019. The IDMC reviewed safety
data from patients as of 26 February 2019, and concluded that the
administration of milciclib to patients with advanced hepatocellular
carcinoma (“HCC”) was not associated with unexpected signs or signals of
toxicity. Additionally, a number of patients are continuing with
treatment under compassionate use. Topline data from this multi-center
trial is expected to be available by the end of Q3 2019.

Tiziana’s Milciclib Phase 2a clinical trial is a single-arm,
repeated-dose (100 mg once daily; 4 days on/3 days off every 4 weeks
defining each cycle), 6-month duration study to evaluate the safety,
tolerability and anti-tumor activity of Milciclib in
Sorafenib-refractory or intolerant patients with unresectable or
metastatic advanced HCC, the most common form of liver cancer.
Enrollment of 31 patients in Italy, Greece, and Israel was completed on
30 November 2018.

The IDMC evaluated data from 28 out of the 31 patients who were
evaluable. As of 16 April 2019, a total of 10 out of 27 patients have
completed the study per protocol (6 cycles, 6 months). Four patients are
still under treatment, while 3 are in cycle 6 and 1 is in cycle 5. Eight
out of the 10 patients who completed treatment initially expressed
interest to continue with treatment. Seven of these 8 patients were
approved to continue with treatment under compassionate use by their
respective ethical committees. Three of the patients under compassionate
use have completed 9, 13, and 16 months of treatment with Milciclib. The
other 4 patients are continuing with treatment.

To date, no drug-related deaths have been recorded. Overall, the
treatment with Milciclib is well-tolerated with manageable drug-related
toxicities. These safety and clinical activity are consistent with the
earlier reported long-term safety and clinical activity of Milciclib in
thymic carcinoma, thymoma and other solid cancers.

“Demonstration of safety and clinical activity is an important milestone
to move forward with strategic options for further clinical development
of Milciclib either as a single agent or in combination with one of the
FDA approved drugs for treatment of HCC patients,” said Dr Kunwar
Shailubhai, CEO & CSO of Tiziana. “We previously reported data from
preclinical studies demonstrating that Milciclib produced pronounced
synergistic anti-HCC activity in combination with any one of the U.S.
Food and Drug Administration approved drugs such as sorafenib
(Nexavar®), regorafenib (Stivarga®), and lenvatinib (Lenvima®).”

The person who arranged for the release of this announcement on behalf
of the Company was Dr Kunwar Shailubhai, CEO of Tiziana.

Cited References

Besse, B,, Garassino, M,, Rajan, A., Novello, S.,Mazieres, J., Weiss,
G., Kocs, D., Barnett, J, Davite, C, Crivori, P and G. Giaccone.
Efficacy of Milcicilib (PHA-848125AC), a pan-cyclin D -dependent kinase
inhibitor in tow phase II studies with Thymic carcinoma and B3 thymoma
patients. (2018) J. Clin. Onc 36 (15 suppl): 8519

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

Jindal, A., Palejwala, V. and Shailubhai, K. (2018). Oral treatment
with milciclib either alone or in combination with sorafenib inhibited
tumor growth in an orthotopic model of hepatocellular carcinoma.
Hepatology 68 Number 1 (Suppl): 879A (Abstract 1543)

About HCC

HCC is the fifth most common cancer and the third highest cause of
cancer mortality worldwide. In 2007, the approval by the European
Medical Agency and U.S. Food and Drug Administration of Sorafenib
(Nexavar®), an inhibitor of several receptor tyrosine kinases, 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, with a
response rate less than 3%, an improvement in median survival of 2-3
months and drug-related symptoms that are not ordinary. More recently,
lenvatinib (Lenvima ®), another multi-tyrosine kinase inhibitor was also
approved for first line treatment of HCC. The complex multi-factorial
etiology of HCC warrants a need for systemic therapies that target
different signaling cascades to provide improved efficacy and safety 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
associated with development of resistance towards chemotherapies. In a
Phase 1 study, oral treatment with Milciclib was 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. Additionally, milciclib met its primary endpoint
in two separate Phase 2 multi-center clinical trials (CDKO-125A-006: 72
patients and CDKO-125A-007: 30 patients) in thymic carcinoma and thymoma
patients.

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 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.

Contacts

For further enquiries:
Tiziana Life Sciences plc
Gabriele
Cerrone, Chairman and founder
+44 (0)20 7493 2853

Cairn Financial Advisers LLP (Nominated adviser)
Liam
Murray / Jo Turner
+44 (0)20 7213 0880

Stockdale Securities Limited (Broker)
Andy Crossley /
Antonio Bossi
+44 (0)20 7601 6125