Tiziana Submits IND Application for Oral Formulation of Foralumab for Treatment of NASH

NEW YORK and LONDON, March 20, 2019 (GLOBE NEWSWIRE) -- Tiziana Life Sciences plc (the "Company", "Tiziana Life Sciences" or "Tiziana") (NASDAQ: TLSA; AIM: TILS), a US and UK biotechnology company that focuses on the discovery and development of novel molecules to treat human diseases in oncology and immunology, today announced that it has submitted^* an Investigational New Drug application ("IND") to the U.S. Food and Drug Administration (FDA) to initiate a Phase 1 clinical trial of enteric-coated capsules of Foralumab in healthy volunteers. Foralumab, a fully human anti-CD3 monoclonal antibody (mAb), is being developed for the treatment of autoimmune and inflammatory diseases such as nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD).

This single-site clinical study is expected to enroll 36 subjects and it will be conducted at the Brigham and Women's Hospital (BWH), Harvard Medical School. The primary objective of this study is to evaluate safety, tolerability and immunomodulatory effects of orally administered Foralumab in healthy volunteers with a dose-escalating regimen comprising of placebo, 1.25, 2.50 and 5.0 mg/day for 5 consecutive days. The trial will also investigate the established biomarkers with anti-inflammatory effects and stimulation of T regulatory cells (Tregs). Following successful completion of this study, the Company plans to launch additional clinical trials to study the potential of the oral administration of Foralumab in NASH, NAFLD and Crohn’s Disease.

"Data from multiple preclinical studies^1-3 has demonstrated that oral treatment with anti-CD3 mAb induces an anti-inflammatory response through induction of Tregs", commented Prof. Howard Weiner, MD. "Separately, proof-of-concept data from a Phase 2 study of OKT3, a murine anti-CD3 mAb, in NASH patients⁴ has established potential for orally administered therapeutics. Therefore, we believe oral immunotherapy with foralumab, a first-in-class fully human anti-CD3 mAb, has the potential to be a groundbreaking approach for targeted immunomodulation without eliciting immunosuppression throughout the body.”

"Our approach, administering Foralumab orally for site-targeted clinical responses while improving efficacy and minimizing toxicity, can be a game changing treatment option for NASH and other autoimmune diseases. We are excited about the successful development of a proprietary oral formulation and submission of this IND application, which represent major milestones for advancing this groundbreaking approach forward,” said Kunwar Shailubhai, Chief Executive Officer & Chief Scientific Officer of Tiziana.

Cited References

1. 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 Oct; 183:240-246. doi: 10.1016/j.clim.2017.07.005. Epub 2017 Jul 21.
2. Kuhn C, Weiner HL. Therapeutic anti-CD3 monoclonal antibodies: from bench to bedside. Immunotherapy. 2016 Jul;8(8):889-906. doi: 10.2217/imt-2016-0049. Epub 2016 May 10. Review.
3. Kuhn C, Rezende RM, da Cunha AP, Valette F, Quintana FJ, Chatenoud L, Weiner HL.
   Mucosal administration of CD3-specific monoclonal antibody inhibits diabetes in NOD mice and in a preclinical mouse model transgenic for the CD3 epsilon chain. J Autoimmun. 2017 Jan; 76:115-122. doi: 10.1016/j.jaut.2016.10.001. Epub 2016 Oct 10.
4. Lalazar G, Mizrahi M, Turgeman I, Adar T, Ben Ya'acov A, Shabat Y, Nimer A, Hemed N, Zolotarovya L, Lichtenstein Y, Lisovoder N, Samira S, Shalit I, Ellis R, Ilan Y. Oral Administration of OKT3 MAb to Patients with NASH, Promotes Regulatory T-cell Induction, and Alleviates Insulin Resistance: Results of a Phase IIa Blinded Placebo-Controlled Trial. J Clin Immunol. 2015 May;35(4):399-407. doi: 10.1007/s10875-015-0160-6. Epub 2015 Apr 17.

*Once the IND is submitted, the sponsor must wait 30 calendar days before initiating any clinical trials. During this time, FDA has an opportunity to review the IND for safety to assure that research subjects will not be subjected to unreasonable risk.

About Dr. Howard Weiner

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

About Harvard Medical Centre and BWH

BWH is located adjacent to Harvard Medical School. 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 is a UK biotechnology company that focuses on the discovery and development of novel molecules to treat human disease in oncology and immunology. We believe Foralumab is the only fully human anti-CD3 mAb in clinical development in the world. This compound has potential application in a wide range of autoimmune and inflammatory diseases, such as NASH, primary biliary cholangitis (PBS), ulcerative colitis, MS, type-1 diabetes (T1D), inflammatory bowel disease (IBD), psoriasis and rheumatoid arthritis, where modulation of a T-cell response is desirable.

Forward-looking statements

This news release contains forward-looking statements that reflect Tiziana Life Science's current expectations regarding future events, including statements regarding financial performance, the timing of clinical trials, the timing and outcomes of regulatory or intellectual property decisions, the clinical benefits of Foralumab and the safety profile and commercial potential of Foralumab. Forward-looking statements involve risks and uncertainties. Actual events could differ materially from those projected herein and depend on a number of factors, including, inter alia, the success of the Company's research strategies, the applicability of the discoveries made therein and the successful and timely completion and uncertainties related to the regulatory process. A further list and description of risks and uncertainties associated with an investment in Tiziana Life Sciences can be found in its filings with the U.S. Securities and Exchange Commission. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Tiziana Life Sciences undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.

For more information go to http://www.tizianalifesciences.com 

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Contact Information:
Tiziana Life Sciences
The Ruth Group
Lee Roth/ Janhavi Mohite
646-536-7012/ 7026        
lroth@theruthgroup.com/ jmohite@theruthgroup.com