Tiziana Life Sciences plc (AIM: TILS, the "Company"), the
clinical stage biotechnology company developing targeted drugs for
cancer and autoimmune diseases, announces new data from animal
studies demonstrating the potential of its novel oral therapy with
foralumab (NI-0401) for NASH, diabetes and other life-threatening
inflammatory diseases. Tiziana’s foralumab is the only fully human
engineered anti-CD3 monoclonal antibody (mAb) in clinical
development to date.
Highlights
- Oral efficacy in humanized mouse
models with foralumab (NI-0401), is a major milestone and a
potential breakthrough for treatment of NASH and autoimmune
disease
- Unique oral technology that
stimulates the natural gut immune system and potentially provides a
therapeutic effect in inflammatory and autoimmune diseases with
virtually no toxicity
- Positive therapeutic effects of
foralumab were consistently demonstrated in animal studies
conducted by Prof. Kevan Herold (Yale University) and Prof. Howard
Weiner (Harvard University)
"Until recently it has been generally accepted that despite the
convenience and appeal of oral therapies, immunotherapies could not
be administered orally because they would be degraded and
inactivated by the harsh conditions in the gastrointestinal tract,”
commented Gabriele Cerrone, Chairman of Tiziana Life Sciences. “New
data demonstrating oral efficacy in animals with foralumab is a
major milestone and potential game-changer for the treatment of
NASH and autoimmune diseases.”
Foralumab, a long half-life therapeutic mAb candidate, with high
affinity and potency for CD3 epsilon, has shown consistent efficacy
via oral administration in pre-clinical studies conducted by Prof.
Kevan Herold, a member of Tiziana’s Scientific Advisory Board, at
Yale University. “This study demonstrates that oral administration
works consistently in our pre-clinical models with human immune
cells. This suggests that oral CD3-specific mAb has the potential
for treating NASH, diabetes, and other autoimmune diseases in
humans – an entirely novel approach for the treatment of currently
unmet needs,” commented Prof. Kevan Herold.
Further animal studies conducted by a member of Tiziana’s
Scientific Advisory Board, Prof. Howard Weiner, in his laboratory
at Harvard University supports the potential of oral treatment with
foralumab for the treatment of autoimmune and inflammatory diseases
in humans. A recent publication in J. Autoimmunity1
(https://www.ncbi.nlm.nih.gov/pubmed/27745778) by Prof. Weiner
provides additional support to this novel approach utilizing a
murine anti-CD3 mAb (OKT3) in mouse models. “Our data suggest that
oral treatment with anti-CD3 mAb induces an anti-inflammatory
response through induction of regulatory T cells (Tregs),” noted
Prof. Weiner, “This proof of concept of foralumab in humanized mice
demonstrates that this approach could be used successfully in
humans as well.”
In prior published studies, oral therapy with anti-CD3 mAb
(OKT3) to patients with NASH was safe and well tolerated, and the
therapy produced positive clinical effects in several hepatic,
metabolic and immunologic parameters. These recently published
findings in J. Clin Immunol2,3.
(https://www.ncbi.nlm.nih.gov/pubmed/25876706), provide further
support for future clinical trials to investigate the effect of
oral treatment with foralumab in patients with NASH and autoimmune
diseases. “We are very excited with these recent findings and are
now moving forward to conduct a proof-of-concept clinical
trial in NASH patients with foralumab, said Dr. Ilan Yaron,
Director of the Department of Medicine at Hebrew University
Hadassah Medical Center, Israel. "Oral immunotherapy using anti CD3
holds promise as an effective anti-inflammatory treatment with high
safety profile enabling chronic use of the drug".
References
Ref (1): C. Kuhn, et al., Mucosaladministration of CD3-specific
monoclonal antibody inhibits diabetes in NOD mice and a preclinical
mouse model transgenic for the CD3 epsilon chain, Journal of
Autoimmunity (2016),
http://dx.doi.org/10.1016/j.jaut.2016.10.001
Ref (2): G. Lalazar et al., 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
Ref (3): Ilan Y et al, Induction of regulatory T cells decreases
adipose inflammation and alleviates insulin resistance in ob/ob
mice. Proc Natl Acad Sci U S A. 2010 May 25;107(21):9765-70. doi:
10.1073/pnas.0908771107.
About NASH
Non-alcoholic fatty liver disease (NAFLD) is one of the causes
of fatty liver, which occurs when fat is deposited (steatosis) in
the liver due not related to alcohol use. It affects 30% of the
western world population. Non alcoholic steatohepatitis (NASH) is a
severe type of NAFLD. NASH occurs when the accumulation of liver
fat is accompanied by inflammation and cellular damage. The
inflammation can lead to fibrosis (scarring) of the liver and
eventually progress to cirrhosis, portal hypertension, liver cancer
and liver failure. According to a market research report
Nonalcoholic Steatohepatitis Treatment Market 2015-2025 published
by iHealthcareAnalyst, Inc., the global nonalcoholic
steatohepatitis treatment market is estimated to reach USD 19.5
Billion in 2025, expanding at a current annual growth rate of 10.0%
from 2016 to 2025. Currently there is no approved therapy for
NASH.
About Kevan Herold, MD
Dr. Kevan Herold is Professor of Immunobiology and of Medicine
(Endocrinology) as well as Deputy Director, Yale Center for
Clinical Investigation, Director of the Yale Diabetes Center and
the TrialNet Center at Yale. His investigative work has focused on
developing new ways to prevent and treat autoimmune diseases, using
novel translational immunologic strategies. He is a leader
particularly in the field of Type 1 diabetes and had led several
investigative trials for prevention and treatment. He is involved
with national and international consortia that are developing new
treatments for diabetes and other immune system disorders. His
laboratory studies focus on understandings the mechanisms of
autoimmune disease and the treatments that are being developed. His
clinical interests are as an endocrinologist who specializes in
management and treatment of diabetes.
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 Ilan Yaron, MD
Prof. Ilan Yaron is the Director of the Department of Medicine
at the Hadassah-Hebrew University Medical Center in Jerusalem
Israel and served as the Vice Dean of the Hebrew
University-Hadassah Medical School. He has pioneered the
development of oral immunotherapy for NASH, diabetes, and
inflammatory bowel diseases. He developed several products which
target the immune system of the gastrointestinal tract as a mean
for alleviating immune-mediated disorders without the need for
immunosuppression. He holds over 50 patents for discoveries based
on his research mainly in oral immunotherapy and mucosal
immunology. His clinical interests are in the management of NASH
and diabetes by targeting the inflammation-associated with these
diseases by using products with high safety profile enabling their
chronic use. He is involved in multiple clinical trials using oral
immunotherapy-based compounds.
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
Hepatic Cellular Carcinoma (HCC).
The Company is also in clinical development of foralumab.
Foralumab is the only fully human engineered anti-human CD3
antibody in clinical development. This phase II compound has
potential application in a wide range of autoimmune and
inflammatory diseases, such as 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.
Tiziana Life Sciences' clinical development teams are working on
its Bcl-3 candidate; which has a prominent role in the metastasis
of mammary cancers, and has elucidated the mechanism of Bcl-3
action to be a regulator of cancer cell motility and has also
determined that Bcl-3 inhibition suppresses cell motility in
triple-negative, HER-2-positive PR- and ER-positive breast cancer
sub-types, suggesting that Bcl-3 may be a master regulator of this
metastatic property not only in aggressive breast cancers, but
across the clinical spectrum of breast disease. The Company is
preparing the IND package with the intention of progressing to
clinical trials early 2017.
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.
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version on businesswire.com: http://www.businesswire.com/news/home/20161116005678/en/
Tiziana Life Sciences plcGabriele Cerrone, Chairman and
founder+44 (0)20 7493 2853orCairn Financial Advisers LLP
(Nominated adviser)Liam Murray+44 (0)20 7148 7900orBeaufort
Securities Limited (Broker)Saif Janjua+44 (0)20 7382
8300orFTI ConsultingSimon Conway / Natalie
Garland-Collins+44 (0)20 3727 1000
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