Tiziana Reports Phase 1 Clinical Data Demonstrating Nasal Treatment with Foralumab was Well-tolerated & Produced Positive Tre...
September 10 2019 - 7:00AM
Business Wire
THE INFORMATION CONTAINED IN THIS ANNOUNCEMENT IS DEEMED BY THE
COMPANY TO CONSTITUTE INSIDE INFORMATION AS STIPULATED UNDER THE EU
MARKET ABUSE REGULATION (596/2014). UPON PUBLICATION OF THE
ANNOUNCEMENT VIA A REGULATORY INFORMATION SERVICE, THIS INFORMATION
IS CONSIDERED TO BE IN THE PUBLIC DOMAIN.
Tiziana Life Sciences plc (Nasdaq: TLSA) (“Tiziana” or the
“Company”), a biotechnology company focused on innovative
therapeutics for inflammatory diseases and cancers, is pleased to
report Phase 1 clinical data demonstrating that nasally
administered Foralumab, a fully human anti-CD3 monoclonal antibody
(mAb), was well-tolerated at all doses. Importantly, the treatment
showed significant positive effects on the biomarkers for
activation of mucosal immunity, which is capable of inducing
site-targeted immunomodulation to elicit anti-inflammatory effects.
These clinical data are consistent with the findings from numerous
pre-clinical studies.1-3
This Phase 1 trial, conducted at the Brigham and Women’s
Hospital, Harvard Medical School, Boston, MA, was a single-site,
double-blind, placebo-controlled, dose-ranging study with nasally
administered Foralumab at 10, 50 and 250 µg per day, consecutively
for 5 days in healthy volunteers for the treatment of progressive
multiple sclerosis (pMS). 18 subjects received Foralumab treatment
and 9 patient received placebo. All nasal doses were well
tolerated. Biomarker analysis showed significant positive immune
effects, that were most prominent in the 50 μg cohort
with minimal immunomodulatory effects at the 10 µg and 250 µg
doses.
Major Highlights
- Treatment was well-tolerated and no drug-related safety issues
were reported at any of the doses.
- No drug-related changes were observed in vital signs among
subjects at predose, during treatment and at discharge. The mean
blood pressure (BP) during the 5 days of treatment were; Cohort A
(10 µg/d):124/73, Cohort B (50 µg/d): 119/67 and Cohort C (250
µg/d):113/65 compared to placebo:118/67). Heart rates, respiratory
rates and oral temperatures were unchanged among the 3 cohorts
compared to the placebo.
- Nasally administered Foralumab at the 50 µg dose suppressed
cytotoxic CD8+ as well as perforin secreting CD8+ cells, which have
been implicated in neurodegeneration in multiple sclerosis
(MS).
- Treatment at 50 μg stimulated production of anti-inflammatory
cytokine IL-10 and suppressed production of pro-inflammatory
cytokine IFN-γ.
- Taken together, these results suggest stimulation of Tregs that
are needed to provide clinical benefits
“Nasal administration of Foralumab is a revolutionary approach
to treat patients with neurodegenerative diseases such as
progressive MS (pro-MS) and amyotrophic lateral sclerosis (ALS).
Extensive data from animal studies with intranasal delivery of
anti-CD3 demonstrate that this route of administration induces
anti-inflammatory and immunomodulatory effects. This study
demonstrates for the first-time that nasally administered
Foralumab, at the identified optimal dose of 50 μg,
induces immunomodulatory effects capable of providing clinical
benefit to treated subjects. This is a major accomplishment
providing the scientific rationale to move forward with further
clinical development of nasally administered Foralumab in patients
with neurodegenerative diseases,” commented Dr. Howard L. Weiner, a
member of scientific advisory board of Tiziana Life Sciences. He
added that “both oral and nasal administration routes are
physiologic approaches to stimulate the mucosal immune system to
induce disease modifying immunomodulation. Our immediate focus is
on developing Foralumab for treatment of pro-MS.”
“The demonstration of the positive immunomodulatory effects
provides the scientific rationale to move forward with further
studies in the pro-MS population, stated Dr. Tanuja Chitnis, the
study PI at the Brigham and Women’s Hospital.
“We are very pleased with what we believe is the first-ever
demonstration that nasally administered Foralumab is not only
well-tolerated, but it also exhibited significantly positive
immunomodulatory effects that are indicative of stimulation of
Tregs. We are excited as these results provide the scientific
rationale for the nasal and oral treatment with Foralumab, our core
proprietary platform technologies which could potentially
revolutionize treatment with antibodies” stated Kunwar Shailubhai,
CEO & CSO of Tiziana.
The person who arranged for the release of this announcement on
behalf of the Company was Dr Kunwar Shailubhai, CEO & CSO of
Tiziana.
About Foralumab
Foralumab (formerly NI-0401), the only entirely human anti-CD3
mAb, shows reduced release of cytokines after IV administration in
patients with Crohn's disease with decreases in the classic side
effects of cytokine release syndrome (CRS) and improves the overall
safety profile of Foralumab. In a humanized mouse model (NOD/SCID
IL2γc-/-), it was shown that while targeting the T cell receptor,
orally administered Foralumab modulates immune responses of the T
cells, enhances Tregs and thus provides therapeutic benefit in
treating inflammatory and autoimmune diseases without the
occurrence of potential adverse events usually associated with
parenteral mAb therapy (Ogura M. et al., 2017). Based on animal
studies, the nasal and oral administration of Foralumab offers the
potential for the immunotherapy of autoimmune and inflammatory
diseases in a safe manner by the induction of Tregs.
Preclinical studies on nasal and oral administration with
Anti-CD3 mAbs
Preclinical and clinical studies have shown that mucosal
induction of Tregs by oral or nasal administration of anti-CD3 mAbs
is an innovative approach to treat autoimmune and anti-inflammatory
diseases (Kuhn and Weiner 2016)4. Nasally administered
anti-CD3 mAbs were shown to ameliorate disease in an animal model
of multiple sclerosis by inducing IL-10+LAP+ (latency-associated
peptide) T cells3, demonstrating nasal anti-CD3 mAbs as a
new approach to treat progressive forms of multiple sclerosis and
other types of chronic CNS inflammation. Additionally, nasally
administered anti-CD3 mAbs suppressed lupus in lupus-prone mice
(BWF1) by inducing IL-10 and TGF-β dependent mechanisms associated
with a suppression of IL-17 and IL-21 pro-inflammatory
cytokines5.
About Tiziana Life Sciences
Tiziana Life Sciences plc is a UK biotechnology company that
focuses on the discovery and development of novel molecules to
treat human disease in oncology and immunology. In addition to
Milciclib, the Company is also developing Foralumab for liver
diseases. Foralumab is the only fully human anti-CD3 monoclonal
antibody in clinical development in the world. This Phase 2
compound has potential application in a wide range of autoimmune
and inflammatory diseases, such as nonalcoholic steatohepatitis
(NASH), ulcerative colitis, multiple sclerosis, type-1 diabetes
(T1D), crohn’s disease, psoriasis and rheumatoid arthritis, where
modulation of a T-cell response is desirable.
Forward-Looking Statements
Certain statements made in this announcement are forward-looking
statements. These forward-looking statements are not historical
facts but rather are based on the Company’s current expectations,
estimates, and projections about its industry; its beliefs; and
assumptions. Words such as ‘anticipates,’ ‘expects,’ ‘intends,’
‘plans,’ ‘believes,’ ’seeks,’ ‘estimates,’ and similar expressions
are intended to identify forward-looking statements. These
statements are not guarantees of future performance and are subject
to known and unknown risks, uncertainties, and other factors, some
of which are beyond the Company’s control, are difficult to
predict, and could cause actual results to differ materially from
those expressed or forecasted in the forward-looking statements.
The Company cautions security holders and prospective security
holders not to place undue reliance on these forward-looking
statements, which reflect the view of the Company only as of the
date of this announcement. The forward-looking statements made in
this announcement relate only to events as of the date on which the
statements are made. The Company will not undertake any obligation
to release publicly any revisions or updates to these
forward-looking statements to reflect events, circumstances, or
unanticipated events occurring after the date of this announcement
except as required by law or by any appropriate regulatory
authority.
Cited References
- Weiner HL et al. Oral tolerance. Immunol Rev. 2011;
241(1):241-259
- Ochi H, Abraham M, Ishikawa H et al. New immunosuppressive
approaches: Oral administration of CD3-specific antibody to treat
autoimmunity. J Neurol Sci 2008; 274(1- 2):9-12
- Mayo, L et al. IL-10-dependent TrI cells attenuate astrocyte
activation and ameliorate chronic central nervous system
inflammation. Brain. 2016: 139; 1939-1957
- Kuhn C. and Weiner HL. Therapeutic anti-DC3 monoclonal
antibodies: from bench to bedside. Immunotherapy 2016;
8(8):889-906
- Wu, H.Y, Quintana, F.J and Weiner, H.L. Nasal Anti-CD3 Antibody
Ameleorates Lupus by Inducing an IL-10-Secreting CD4+CD25-LAP+
Regulatory T cell and Is Associated with Down-Regulation of
IL-17+CD4+ICOS+CXCR5+ Follicular Helper T Cells. J Immunol 2008;
181:6038-6050
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Tiziana Life Sciences plc Gabriele Cerrone, Chairman and
founder +44 (0)20 7495 2379
Cairn Financial Advisers LLP (Nominated adviser) Liam
Murray / Jo Turner +44 (0)20 7213 0883
Shore Capital (Broker) Andy Crossley / Antonio Bossi +44
(0)20 7601 6125
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