Therapeutic Focus

Therapeutic Focus

We focus on serious diseases of high unmet need, where large market potential exist for effective therapeutics. Our interest is in truly disease modifying treatments rather than palliatives, and through our collaboration with field-leading scientists, our approach is to use deep insights into biology to interfere with fundamental mechanisms that are at the heart of cancers and autoimmune disease progression.

We have an innovative and potent small molecule as well as fully human biotherapeutic candidates in clinical development for the treatment of cancers, chronic inflammatory (NASH) and autoimmune (neurodegenerative) disorders. The current focus of milciclib (TZLS-201), our small molecule program is hepatocellular carcinoma (HCC), a common primary liver malignancy and a leading cause of cancer-related death worldwide. Our biotherapeutic clinical programmes (TZLS-401, foralumab) in autoimmune and inflammatory diseases target; non-alcoholic steatohepatitis (NASH), Crohn's disease, neurodegenerative diseases such as multiple sclerosis using novel oral and nasal formulations.

 

Hepatocellular Carcinoma

Hepatocellular Carcinoma

Overview

Tiziana’s late-stage oral CDK inhibitor, milciclib, has recently completed two Phase II studies for thymoma and thymic carcinoma for which it has orphan drug status. Treatment with milciclib was safe, well-tolerated and met the primary endpoints achieving disease stabilisation in a majority of patients.

The current focus is on milciclib alone or in combination with other drugs for treatment of HCC, the most common primary malignancy of the liver in adults.

HCC is the fifth most common cancer in men and the eighth most common cancer in women in the US. Liver cancer incidence and death rates are steadily rising with the highest average annual percent increase of the top 15 cancers by incidence.

Most HCC patients present with advanced disease and do not benefit from transplantation, surgical resection, and locoregional therapies and there is only one chemotherapeutic agent approved for advanced HCC patients. As a result, its lethality makes it the third most common cause of cancer death worldwide.

The primary risk factor for HCC is hepatic cirrhosis with an estimated 78% of HCC cases and 57% of cases of liver cirrhosis caused by chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV). Recently, the combination of insulin resistance, hypertension, dyslipidemia, and obesity, termed “metabolic syndrome,” has been recognized as a cause of nonalcoholic fatty liver disease (NAFLD), cirrhosis, and HCC. Linking our two main focus areas together, NAFLD looks to be a common underlying liver disease not only in progressing to non-alcoholic steatohepatitis (NASH) but also in patients with hepatocellular carcinoma.

Therapeutic Approach​

Cancer is primarily due to deficiencies in cell cycle control, eventually resulting in transformation of normal cells to rapidly growing cancer cells. Therapeutic intervention to control cell cycle has long been anticipated as effective cancer therapies. Cyclin-dependent kinases (CDKs) are the specific enzymes that promote transition through the cell cycle ultimately drive cell proliferation.

Tiziana Life Sciences (TILS) acquired milciclib from Nerviano Medical Sciences. Milciclib (a.k.a PHA-848125 or PHA-848125AC) is a small molecular inhibitor of cyclin-dependent kinases (CDKs) and Src family of kinases, and a limited number of additional kinases.

The compound is an oral drug candidate that inhibits cyclin-dependent kinase 2 (CDK2) and also exhibits inhibitory activity against other CDKs including CDK1 and CDK4 to produce potent anti-cancer activity (1-5). Preclinical studies conducted by scientists in Nerviano indicate that milciclib is a potent anti-cancer drug candidate for treatment of a variety of cancers including cancers of thymic, liver and breast cancer (6).

Autoimmune Disease

Overview

Autoimmune diseases are primarily due to a malfunction when the immune system attacks certain cells in the body as foreign invaders. This can result in irreparable damage to critical organs and tissues eventually resulting in autoimmune diseases.

Tiziana Life Sciences has recently acquired foralumab, a unique asset which we are investigating for orally administered treatment of autoimmune diseases. Foralumab is a fully human anti-CD3 monoclonal antibody which has been shown to modulate immune response and has potential applications for inflammatory bowel diseases, type I diabetes and lupus.

Therapeutic Approach​

The therapeutic use of anti-CD3 remains an attractive strategy for broader applications in chronic inflammatory and autoimmune diseases with high unmet medical needs such as non-alcoholic steatohepati

Current treatments for patients with autoimmune diseases include immune suppressive drugs that inhibit the cells of the immune system. These cells are also normally responsible for our protective responses to foreign invaders and tumors, and therefore, inhibiting them can often have severe side effects.

Immune tolerance therapies have been shown to be promising in animal models as well as human clinical trials and are increasingly becoming attractive approaches to reprogramme the immune system to stop the immune attack on self-tissue while continuing to maintain immune surveillance to fight infection (5,6).

AIM:TILS

Listed on UK Aim Market

2013

First founded

2014

Listed on AIM

R&D Pipeline

Our Pipeline

The company has a pipeline of assets that includes lead clinical stage development therapeutic candidates in both oncology and immunology and a small molecule NCE.

We are developing a late stage CDK inhibitor, milciclib for treatment of HCC and thymic cancer, for which it has orphan drug status. Milciclib recently completed two Phase II studies for thymic cancer and a Phase II trial as monotherapy for HCC is ongoing.

We have acquired foralumab, a fully human anti-CD3 antibody a unique asset for treatment of chronic autoimmune and inflammatory diseases such as NASH and neurodegenerative diseases such as multiple sclerosis.

Clinical Programmes

Clinical Programmes

* The trial in Crohn’s Disease (IV administration) conducted by Novimmune produced encouraging clinical response. TILS strategy is to pursue oral administration with foralumab in NASH and CD.

** We will seek guidance from regulatory authorities for next steps

Milciclib (TZLS-201)

The Company’s lead compound, milciclib, is a molecule which blocks the action of specific enzymes called cyclin-dependent kinases (CDK) involved in cell division as well as a number of other protein kinases.

Milciclib is currently completing phase II clinical trials for epithelial thymic carcinoma and/or thymoma in patients previously treated with chemotherapy and has filed an IND to enroll patients in an exploratory trial in hepatic cellular carcinoma (HCC).

This candidate may have potential in other cancers, such as liver carcinoma and breast cancer.

Foralumab (TZLS-401)​

Foralumab (TZLS-401) has significant potential as the only fully human engineered anti-human CD3 antibody in clinical development with advantages of short duration of treatment regimen and reduced immunogenicity.

With Phase II development for Crohn’s Disease completed, modulation of T-cell response provides potential extension into a wide range of other autoimmune and inflammatory diseases, such as NASH, PBC, ulcerative colitis, multiple sclerosis and autoimmune Type-1 diabetes. Foralumab 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.

Pre-Clinical Programmes

Pre-Clinical Programmes

TZLS-501

TZLS-501 is a fully human anti IL-6R monoclonal antibody with a novel mechanism of action. The mAb possesses a high affinity for IL-6R and the IL-6/IL-6R complex and effectively blocks the complex even at high IL-6 circulating levels, showing superiority and overcoming the limitations of other IL-6 pathway drugs. Therefore, TZLS-501 demonstrates a decreased potential for adverse events with improved efficacy in patients with high circulating levels of IL-6 and controlling chronic inflammation in diseases such as multiple myeloma, rheumatoid arthritis and other autoimmune diseases.

References: (1) Thomas MB, Jaffe D, Choti MM, et al. Hepatocellular Carcinoma: Consensus Recommendations of the National Cancer Institute Clinical Trials Planning Meeting. Journal of Clinical Oncology. 2010;28(25):3994-4005. doi:10.1200/JCO.2010.28.7805.