Full Press Release Details
Results for the Year Ended 31 December 2018
4 April 2019 - Tiziana Life Sciences plc (AIM: TILS), the clinical stage biotechnology company focused on targeted drugs
to treat diseases in oncology and immunology, today announces its financial results for the year ended 31 December 2018.
| Tiziana Life Sciences plc Gabriele Cerrone, Chairman and founder | +44 (0)20 7493 2853 |
| Cairn Financial Advisers LLP (Nominated adviser) Liam Murray / Jo Turner / Richard Nash | +44 (0)20 7213 0880 |
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 human anti-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.
more information go to http://www.tizianalifesciences.com
announcement contains inside information for the purposes of Article 7 of EU Regulation 596/2014.
CHAIRMAN'S STATEMENT
am pleased to report on the Company (Tiziana Life Sciences PLC) and its subsidiaries, together the Group', results
for the year ended 31 December 2018.
Life Sciences plc is a publicly-listed (NASDAQ: TLSA; AIM: TILS) biotechnology company focused on the discovery and clinical development
of innovative therapeutics for cancers, autoimmune and inflammatory diseases. The Group combines field-leading medical scientists,
providing deep knowledge and novel insights into disease mechanisms, together with a highly experienced clinical development team.
Since its foundation in 2013, Tiziana Life Sciences has expanded its pipeline of assets to include clinical stage development
therapeutic candidates in both oncology and immunology, as well as a pre-clinical drug discovery pipeline of small molecule New
Group is focused on targeting large markets with a high unmet medical need. Driven by an obesity and diabetes epidemic, non-alcoholic
fatty liver disease (NAFLD) has become the most common liver disease, affecting one-third of the Western world. Between 3% and
5% of NAFLD patients progress to a more severe form of inflammatory disease, known as NASH (non-alcoholic steatohepatitis), a
progressive disease associated with chronic inflammation, fibrosis and cirrhosis in the liver. Based on data from US adult Liver
Transplant (LT) databases, since 2004 the number of adults with NASH awaiting LTs has almost tripled. In 2013, NASH became the
second-leading disease among liver transplant waiting list registrants, after the Hepatitis C virus. It is predicted that NASH
may become the leading cause of liver transplantation in the United States by 2020.
market for NASH therapies is estimated to reach 16.2 billion by 2025 (10.7% CAGR from 2015 to 2025). This anticipated growth
has resulted in several high-profile M&A transactions, including four announced deals in 2016 totalling more than 2.3
billion in value. Around 20% of NASH patients progress further to cirrhosis of the liver, which may ultimately develop into fatal
HCC, the primary cause of obesity-related cancer death in middle-aged men in the U.S. Liver transplants are the only effective
option for end-stage patients, including HCC patients. More effective therapeutic agents to treat Hepatocellular Carcinoma ("HCC")
are needed. Currently approved therapeutic agents are marginally effective and have significant safety issues.
Life Sciences is focused on developing novel drugs for treatment of liver diseases with a pipeline of two clinical-stage drug
candidates, Foralumab and Milciclib:
(TZLS-401 / NI-0401)
is a fully human engineered anti-CD3 monoclonal antibody (mAB). It was in-licensed in December 2014 from Novimmune. In January
2016, Tiziana outlined its clinical development plan for Foralumab with initial plans to evaluate the drug in two clinical indications:
non-alcoholic steatohepatitis (NASH) and inflammatory bowel disease (IBD).
the only fully human engineered human anti-CD3 mAB in clinical development, Foralumab has significant potential advantages such
as a shorter treatment duration and reduced immunogenicity. With completion of the intravenous dosing for our Phase 2a trial in
Crohn's Disease, Foralumab's ability to modulate T-cell response enables potential extension into a wide range of
other autoimmune and inflammatory diseases, such as GvHD, ulcerative colitis, multiple sclerosis, type-1 diabetes (T1D), inflammatory
bowel disease (IBD), psoriasis and rheumatoid arthritis.
is being developed as both an immunosuppressive and immunomodulatory agent, with therapeutic benefits of rendering T-cells unable
to orchestrate an immune response and induction of immune tolerance via maintenance of regulatory T-cells. There is further potential
for Foralumab to be combined with the Company's TZLS-501, a fully human anti-IL-6R mAB in development to target autoimmune
and inflammatory diseases.
November 2016, Tiziana announced new data for oral efficacy in humanized mouse models with Foralumab, a major milestone and a
potential breakthrough for the treatment of NASH and autoimmune disease. This unique oral technology stimulates the natural gut
immune system and potentially provides a therapeutic effect in inflammatory and autoimmune diseases with greatly reduced toxicity.
Positive therapeutic effects with Foralumab were consistently demonstrated in animal studies conducted by Prof. Kevan Herold (Yale
University) and Prof. Howard Weiner (Harvard University).
April 16, 2018, the Group entered into an exclusive license agreement with The Brigham and Women's Hospital, Inc. relating
to a novel formulation of Foralumab dosed in a medical device for nasal administration. An investigational new drug application
(IND) for the first-in-human evaluation of the nasal administration of Foralumab in healthy volunteers was filed in the second
quarter of 2018, and a Phase 1 trial to evaluate biomarkers of immunomodulation of clinical responses was initiated in November
2018. The study is expected to be completed by May 2019.
enteric-coated capsule formulation using a proprietary and novel technology has been developed for oral administration of Foralumab.
cGMP manufacturing of clinical trial materials for a Phase 1 study has been completed and an IND has been submitted in March 2019.
Tiziana's lead small molecule drug, was exclusively licenced in January 2015 from Nerviano Medical Sciences. Milciclib is
an orally bioavailable, broad spectrum inhibitor of Cyclin Dependent Kinases (CDKs): 1, 2, 4, 5 and 7 and Src family kinases.
Cyclin dependent kinases are a family of highly conserved enzymes that are involved in regulating the cell cycle. Src family kinases
regulate cell growth and potential transformation of normal cells to cancer cells. A unique feature of Milciclib is its ability
to reduce microRNAs, miR- 221 and miR-222, which silence gene expression. miR-221 and miR-222 promote the formation of blood vessels
(angiogenesis) that are important for the spread of cancer cells (metastasis). Levels of these microRNAs are consistently increased
in HCC patients and may contribute towards resistance to treatment with Sorafenib. As a result, the Group are investigating Milciclib
both as a monotherapy and as a combination treatment with Sorafenib.
date, Milciclib has been studied in a total of eight completed and ongoing Phase 1 and 2 clinical trials in 316 patients. In these
trials, Milciclib was observed to be well-tolerated and showed initial signals of anti-tumour action. Prior to in-licensing, Milciclib
was granted orphan designation by the European Commission and by the U.S. Food and Drug Administration ("FDA") for
the treatment of malignant thymoma and an aggressive form of thymic carcinoma in patients previously treated with chemotherapy.
In two Phase 2a trials, CDKO-125a-006 and CDKO125a-007, Milciclib showed signs of slowing disease progression and acceptable safety.
Group initiated a Phase 2a trial (CDKO-125a-010) of Milciclib safety and tolerability as a single therapy in Sorafenib-resistant
patients with HCC in the first half of 2017. In May 2018, the Independent Data Monitor committee (IDMC) completed an interim analysis
of tolerability data from the first eleven treated patients and recommended expansion of the initial cohort to an additional 20
patients to complete the trial enrolment, which was completed in December 2018. Top-line data is expected in the second quarter
of 2019. This trial is conducted in Sorafenib-resistant HCC patients. Typically, this population of patients have an advanced
form of the disease with poor prognosis and an average overall survival expectancy of 3-5 months. It is important to emphasize
that 4 out of the 11 patients on treatment, completed 6 months in the trial and then requested continued treatment on a compassionate
use basis. Subsequently, 3 patients were approved under the compassionate use program by the respective ethical committees. Among
these three patients, one patient completed 9 months, and another completed 13 months of treatment with no apparent signs of toxicity.
The third patient continued to receive the treatment and recently reached 16 months of treatment.
data presented at the AASLD meeting in November 2018, demonstrated significant tumour reduction in an orthotopic mouse model of
HCC following five weeks of treatment with Milciclib (-20% reduction, 30mg/kg/day)), Sorafenib (-20% reduction, 20 mg/kg/day)
and the combination of Milciclib and Sorafenib (-38% reduction) relative to vehicle control.
on the expected synergistic anti-tumour effect of Milciclib and Sorafenib, the Group expects to initiate a Phase 2b trial (TZLS
(201)-125a-011) dosing Milciclib in combination with Sorafenib (the standard of care) in patients with HCC in 2019.
pre-clinical development, the Group has two programmes:
is a fully human engineered mAb targeting the interleukin-6 receptor (IL-6R). Tiziana Life Sciences licensed the intellectual
property from Novimmune in January 2017. This fully human mAb has a unique mechanism of action that binds to both the membrane-bound
and soluble forms of the IL-6R resulting in lowering of circulating levels of IL-6 in the blood. Excessive production of IL-6
is regarded as a key driver of chronic inflammation, associated with autoimmune diseases such as multiple myeloma, oncology indications
and rheumatoid arthritis, and the Group believes that TZLS-501 may have potential therapeutic value for these indications.
preclinical studies, TZLS-501 demonstrated the potential to overcome limitations of other IL-6 blocking pathway drugs. Compared
to tocilizumab and sarilumab, while binding to the membrane-bound IL-6R complex TZLS-501 has shown a higher affinity for the soluble
IL-6 receptor as seen from the antibody binding studies conducted in cell culture. TZLS-501 also demonstrated the potential to
block or reduce IL-6 signalling in mouse models of inflammation. The soluble form of IL-6 has been implicated to have a larger
role in disease progression compared to the membrane-bound form. (Kallen, K.J. (2002). "The role of transsignalling via
the agonistic soluble IL-6 receptor in human diseases". Biochimica et Biophysica Acta. 1592 (3): 323-343.).