Newly Published Article Reporting Clinical Activity of Orally Administered OKT3, a Mouse Anti-CD3 Monoclonal Antibody, in Mod...
June 24 2019 - 1:26PM
Business Wire
Third party research conducted by leading U.S. institutions to
be published in a peer reviewed journal Crohn’s & Colitis 360
shows orally administered anti-CD3 resulted in anti-inflammatory
gene expression with no serious treatment related adverse events up
to a dose of 1 mg of OKT3
Tiziana’s platform oral monoclonal antibody (mAb) technology
applicable to mAb’s on the market today which are currently
available only through IV, addressing an enourmous market
potential.
Tiziana’s Foralumab is the first fully human anti-CD3 mAb which
has not shown anti-drug antibody (immune reaction) in humans
Tiziana Life Sciences plc (Nasdaq: TLSA / AIM: TILS) (“Tiziana”
or the “Company”), a biotechnology company focusing on the
discovery and development of innovative therapeutics for
inflammation and oncology indications, notes the advance
publication of a scientific article by third party researchers in
the peer reviewed journal Crohn’s & Colitis 360* titled,
“Immunologic alterations associated with oral delivery of
anti-CD3 (OKT3) monoclonal antibodies in patients with
moderate-to-severe ulcerative colitis”(1) The published study
was conducted at some of the leading medical research institutions
in the world, including Harvard Medical School, Massachusetts
General Hospital, and the Ann Romney Center for Neurologic Diseases
at Brigham & Women’s Hospital. These independent findings
suggest potential clinical activity and support the safety of
monoclonal antibodies (mAb’s) when administered orally.
Tiziana’s Foralumab, the only fully human anti-CD3 mAb, exhibits
potency and functionality similar to OKT3, which is a mouse
anti-CD3 (2). Therapeutic use of intravenously administered OKT3
and other humanized anti-CD3 mAbs is limited due to significant
adverse reactions, including life threatening cytokine release
syndrome. The Company is pioneering oral delivery of mAb’s for the
treatment of autoimmune and inflammatory diseases that is
applicable to the $100 billion market of mAb’s that are currently
only available through IV delivery.
“The safe and effective oral delivery of mAb’s has the potential
to transform the use of biologic medications. While the scientific
community has long recognized oral delivery of proteins and
peptides as a challenge, we believe our propeitary platform
technology is a breakthrough in oral delivery of mAb’s,” stated
Kunwar Shailubhai, CEO & CSO of Tiziana. “We are pleased to see
that some of the top researchers in the world are now validating
the concept of oral administration of mAbs. Oral administration
with Foralumab may have the potential to deliver superior safety
and efficacy results in autoimmune and inflammatory diseases such
as NASH and Crohn’s disease.”
Foralumab is currently in a Phase 1 trial at the Harvard Medical
School in healthy volunteers to study safety, tolerability and
biomarkers of neurodegenerative disease through nasal delivery. An
upcoming Phase 1 trial will evaluate oral Foralumab’s safety,
tolerability and biomarkers in Crohn’s disease and NASH. A Phase 2
trial in Crohn’s and NASH is expected to commence next year.
The aim of this pilot study was to determine the immunologic
effects and safety of orally delivered anti-CD3 antibody in
patients with moderate-to-severe ulcerative colitis (UC).
(1)
The primary endpoints were changes in immunologic parameters and
evaluation for safety. Six subjects received oral OKT3. The
biologic effects of oral anti-CD3 included significantly increased
proliferation in response to anti-CD3 and anti-inflammatory gene
expression profile in peripheral blood mononuclear cells. No
serious treatment-related adverse events occurred.
Cited References:
(1).Boden, E. K., Canavan, J. B., Moran, C. J., McCann, K.,
Dunn, W. A., Farraye, F. A., Ananthakrishnan, A. N., Yajnik, V.,
Gandhi, R., Nguyen, D. D., Bhan, A. K., Weiner, H. L., Korzenik, J.
R., Snapper, S. B. Immunologic alterations associated with oral
delivery of anti-CD3 (OKT3) monoclonal antibodies in patients with
moderate-to-severe ulcerative colitis. Crohn's & Colitis 360
(2019). 183: 240-246.
(2).Ogura M1, Deng S1, Preston-Hurlburt P1, Ogura H1,
Shailubhai K2, Kuhn C3, Weiner HL3, Herold KC4. 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.
About Foralumab
Foralumab (formerly NI-0401), the only entirely human anti-CD3
mAb, has shown 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 enhances the
overall safety profile of Foralumab. In a humanized mouse model ,
it was shown that while targeting the T cell receptor, orally
administered Foralumab modulates immune responses of the T cells,
enhances Tregs and thus has the potential to provide 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.
About OKT3
Muromonab-CD3 (Orthoclone OKT3) is a murine anti-human CD3
monoclonal antibody. OKT3 was developed by Johnson and Johnson and
it was the first monoclonal antibody approved by the FDA in 1985 to
be administered to humans via the intravenous route for the
trearment of acute, glucocorticoid-resistant rejection of allogenic
renal, heart and liver transplants. However, manufacture of OKT3
was voluntarily withdrawn from the market.
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), primary biliary cholangitis (PBS), 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.
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Tiziana Life Sciences plc Gabriele Cerrone, Chairman and
founder +44(0)2074932853 Stockdale Securities Limited
(Broker) Andy Crossley / Antonio Bossi +44(0)2076016125
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