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

20th March 2019


Tiziana Life Sciences plc

(the “Company”, “Tiziana Life Sciences” or “Tiziana”)

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

Tiziana Life Sciences plc (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 patients (4) 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

“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

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


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 (Nominated broker)

Antonio Bossi / Andy Crossley

+44 (0)20 7601 6125