TILS.L Regulatory News (TILS)

Tiziana Life Sciences plc

("Tiziana" or the "Company")

Tiziana Life Sciences announces an exclusive license agreement for novel technology relating to nasal administration of Foralumab for the treatment of neurodegenerative diseases

London, 16 April 2018 - Tiziana Life Sciences plc (AIM: TILS, the "Company"), a clinical stage biotechnology company developing targeted drugs for cancer and autoimmune diseases, announces that it has entered into an exclusive license agreement for novel technology discovered by Dr Howard Weiner at the Brigham and Women's Hospital ("BWH"), Harvard Medical School. Highlights of this novel technology are:

· Data from animal studies demonstrate proof-of-concept of nasal administration of foralumab, a fully human anti-CD3 mAb, for treatment of neurodegenerative diseases such as Lou Gehrig's disease (ALS), progressive multiple sclerosis and traumatic brain injury.

· An Investigational New Drug (IND) application for the first-in-human (FIH) evaluation of nasal administration of foralumab in healthy volunteers will be submitted shortly.

· A formulation of foralumab in a medical device has been developed for nasal administration.

· The FIH study will be a dose-ranging in healthy volunteers to evaluate biomarkers of immunomodulation of clinical responses.

Tiziana has agreed to pay certain milestone payments up until 31 December 2033, dependent on the outcome of clinical trials, in addition to a low single digit percentage of net sales to BWH in royalties.

One of the major components of brain neurodegenerative diseases is neuroinflammation that involves microglia cells and astrocytes in the brain. During disease, these brain innate immune cells develop an inflammatory phenotype and actively contribute to central nervous system (CNS) damage. Dr Weiner has discovered that the nasal administration of anti-CD3 mAb induces regulatory T cells (Tregs) in the cervical lymph nodes that travel to the brain and suppress neuroinflammation. Nasal anti-CD3 induced Tregs work by secreting the anti-inflammatory cytokine IL-10, which suppresses inflammation of microglial and astrocytes in the CNS. This unique mechanism of action does not require nasally administered anti-CD3 to enter the brain because it induces Tregs in the periphery that they enter the brain to exert their anti-inflammatory effects.

"Nasal administration of foralumab is an innovative immunotherapy which has potential for treatment of neurodegenerative diseases such ALS and progressive MS" commented Gabriele Cerrone, Chairman of Tiziana Life Sciences, "New data demonstrating efficacy of nasal treatment with anti-CD3 mAb in animals is a major milestone opening a novel avenue for treatment of neurodegenerative and autoimmune diseases"

"Nasal administration with biologics such as fully human foralumab mAb is a potential game changer for immunotherapies enhancing drug safety while potentiating immunomodulation to provide clinical responses," said Kunwar Shailubhai, CEO and CSO of Tiziana Life Sciences. "New data demonstrating clinical benefits of nasal treatment in animal studies with anti-CD3 mAb is a major milestone further supporting our proprietary immunotherapeutic approach." Previously, we reported that orally administered foralumab was also efficacious in animal models2. Thus, these breakthrough data pave path forward for submission of INDs for nasal as well as oral treatment with foralumab."

Further animal studies conducted by a member of Tiziana's Scientific Advisory Board, Dr Howard Weiner, in his laboratory at Brigham and Women's Hospital, Harvard Medical School, further supports the potential of nasal treatment with foralumab for the treatment of neurodegenerative diseases in humans. "Our data suggest that nasal treatment with anti-CD3 mAb induces an anti-inflammatory response through induction of regulatory T cells (Tregs) that then affects microglial cells in the brain," noted Dr Weiner, "This proof of concept in animal models demonstrates that this approach could be used successfully in humans as well."

Cited References

1. Chitnis T, Weiner HL. CNS inflammation and neurodegeneration. J Clin Invest. 2017, 127:3577-3587.

2. Ogura M, Deng S, Preston-Hurlburt P, Ogura H, Shailubhai K, Kuhn C, Weiner HL, Herold KC. Oral treatment with foralumab, a fully human anti-CD3 monoclonal antibody, prevents skin xenograft rejection in humanized mice. Clin Immunol. 2017, 183:240-246. 

About Neurodegenerative Diseases

The greatest risk factor for neurodegenerative diseases is aging. Many of these diseases are late-onset, meaning there is some factor that changes as a person ages for each disease. One constant factor is that in each disease, neurons gradually lose function as the disease progresses with age. Many neurodegenerative diseases - including progressive multiple sclerosis, ALS, Traumatic brain injury and Alzheimer's - occur as a result of neurodegenerative processes. Such diseases are incurable, resulting in progressive degeneration and/or death of neuron cells. As research progresses, many similarities appear that relate these diseases to one another. Discovering these similarities offers hope for therapeutic advances that could ameliorate many diseases simultaneously.

About Howard L. Weiner, MD

Howard L. Weiner is the Robert L. Kroc Professor of Neurology at the Harvard Medical School, Director and Founder of the Partners Multiple Sclerosis (MS) Center and Co-Director of the Ann Romney Center for Neurologic Diseases at Brigham & Women's Hospital in Boston. He has pioneered immunotherapy in MS and has investigated immune mechanisms in nervous system diseases including MS, Alzheimer's disease, amyotrophic lateral sclerosis, stroke and brain tumours. He has also pioneered the investigation of the mucosal immune system for the treatment of autoimmune and other diseases and the use of anti-CD3 to induce regulatory T cells for the treatment of these diseases.

About Brigham & Women's Hospital, Harvard University

Brigham and Women's Hospital (BWH, "The Brigham") is located adjacent to Harvard Medical School, of which it is the second largest teaching affiliate. It is the largest hospital of the Longwood Medical and Academic Area in Boston, Massachusetts, USA. With Massachusetts General Hospital, it is one of the two founding members of Partners HealthCare, the largest healthcare provider in Massachusetts. Brigham and Women's Hospital conducts the second largest hospital-based research program in the world, with an annual research budget of more than $630 million. Pioneering milestones include the world's first successful heart valve operation and the world's first solid organ transplant.

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, 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 Hepatocellular Carcinoma (HCC) in EU.

The Company is also in clinical development of foralumab. Foralumab is the only fully human anti-human CD3 antibody in clinical development. This phase II asset has potential application in a wide range of autoimmune and inflammatory diseases, such as inflammatory bowel diseases, non-alcoholic steatohepatitis (NASH), multiple sclerosis, type-1 diabetes (T1D), and neurodegenerative diseases, where modulation of a T-cell response is desirable.

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.

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

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