Tiziana Reports Phase 1 Clinical Data Demonstrating Oral Treatment with Foralumab, a Fully Human Anti-CD3 Monoclonal Antibody...
09 January 2020 - 11:20PM
Business Wire
This announcement contains inside information
for the purposes of Article 7 of EU Regulation 596/2014.
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 completion of a Phase 1 clinical study of Foralumab, a fully
human anti-CD3 monoclonal antibody (“mAb”), in healthy subjects.
The proprietary oral formulation, comprising the lyophilized and
stabilized free-flowing powder of formulated Foralumab encapsulated
in an enteric-coated capsule, was well-tolerated at all doses
tested and there were no drug-related safety issues even at the
highest dose of 5 mg in this trial.
This Phase 1 trial, conducted at the Brigham and Women’s
Hospital, Harvard Medical School, Boston, MA, USA, was a
single-site, double-blind, placebo-controlled, single ascending
dose (“SAD”) study in healthy subjects in which Foralumab was
orally administered at 1.25, 2.5 and 5.0 mg per dose as
enteric-coated capsules. Each cohort comprised of 4 subjects, of
whom 3 received Foralumab treatment and 1 received a placebo
capsule. All subjects completed the trial without any safety
concerns at any of the doses.
It has previously been shown that orally administered Foralumab
to NOD/SCID IL2γc-/- mice (which have human immune systems) with
skin xenografts was well-tolerated up to 15 µg/day (n=20; human
equivalent dose of 3.66 mg/dose in a 60 kg human) for 5 days then
weekly, prevented skin xenograft rejection indefinitely. Clinical
studies conducted by other researchers have also shown that oral
administration of OKT3, a murine anti-CD3 mAb, was well-tolerated
up to 5 mg/day for 5 days to healthy subjects, to patients with
nonalcoholic steatohepatitis (“NASH”) for 30 days and to hepatitis
C virus (HCV) non-responders for 30 days. Data from a recently
completed clinical study indicated that oral administration of OKT3
was well tolerated at 1 mg/day for 30 consecutive doses in patients
with moderate-to-severe ulcerative colitis. Importantly, the
treatment resulted in clinical responses in 3 out of 6 patients,
including one patient with a complete clinical response.
“This is the first-ever study demonstrating that orally
administered Foralumab is well-tolerated at all doses up to 5.0
mg/dose. This ground breaking study opens a novel avenue for future
development of oral mAb therapeutics ” commented Dr. Howard L.
Weiner, a member of the scientific advisory board of Tiziana Life
Sciences. Recently, we also successfully demonstrated that nasally
administered Foralumab is not only well-tolerated but also produced
the desirable immunological responses. He added that “both oral and
nasal administration routes are physiologic approaches to stimulate
the mucosal immune system to induce disease modifying
benefits.”
“We are very pleased with the tolerability of both oral and
nasally administered Foralumab” added Dr. Tanuja Chitnis, Professor
of Neurology at Harvard Medical School, and study Principal
Investigator (PI).
“Successful completion of this study is a significant milestone
to validate our proprietary technologies of oral and nasal
administration of mAbs, which we believe could potentially be
transformational for future development of mAbs therapeutics. We
are excited to note that oral administration was well-tolerated and
that the treatment did not result in severe toxicities that are
commonly observed with intravenous (IV) administration of anti-CD3
mAbs. These findings provide the scientific rationale for our core
technologies of oral and nasal formulations of mAb therapeutics,
said Dr. Shailubhai, CEO & CSO of Tiziana Life Sciences.
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, demonstrated a 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
improved 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. 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 oral and nasal 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). Administration of anti-CD3
antibody orally in SLJ mice was shown to suppress autoimmune
encephalomyelitis and 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 cells,
demonstrating oral and nasal anti-CD3 mAbs as a new approach to
treat progressive forms of multiple sclerosis and other types of
chronic CNS inflammation. Additionally, mucosal administered
anti-CD3 mAbs suppressed lupus in lupus-prone mice (“BWF1”) by
inducing IL-10 and TGF-β (“Transforming Growth Factor”) dependent
mechanisms associated with a suppression of IL-17 and IL-21
pro-inflammatory cytokines.
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.
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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) Antonio Bossi / Fiona Conroy +44
(0)20 7601 6125
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