Full Press Release Details
Tiziana Life Sciences PLC
("Tiziana" or "the Company")
Phase 1b/2 Clinical Trial - Crohn's
Tiziana Life Sciences announces collaboration
with Parexel Biotech to conduct phase 1b/2 clinical trial in patients with Crohn's Disease
First Ever Study with take-home capsules
of Foralumab, a Fully Human Anti-CD3 Monoclonal Antibody
- Potential to be a safer and effective
alternative to the intravenous immunotherapies currently used for Crohn's Disease
Therapeutics Market Size $4.7 Billion by 2025
clinical study to be conducted in the United States and several European countries
NEW YORK and LONDON, 11 November 2020 -
Tiziana Life Sciences plc (Nasdaq: TLSA; AIM: TILS) ("Tiziana" or the "Company"), a biotechnology company
focused on innovative therapeutics for oncology, inflammation and infectious diseases, today announced it is collaborating with
Parexel Biotech ("Parexel"), a division of a leading global clinical research organization ("CRO"), Parexel
International (IRL) Limited, to conduct a global Phase 1b/2 trial with enteric-coated capsules of formulated Foralumab, the only
fully human anti-CD3 monoclonal antibody ("mAb") - as a therapy for patients with moderate to severe Crohn's
Disease ("CD"). This clinical study will evaluate the safety, tolerability, and clinical activity of escalating doses
of orally administered capsules of Foralumab. The trial is a dose-ranging, open-label study that will enroll 60 patients in the
Dr. Howard L. Weiner, chairman of the
scientific advisory board of Tiziana Life Sciences, commented:
"We understand that this will be
the first-ever study with take-home' capsules of any mAb for immunotherapies for human diseases. We believe the scientific
rationale for oral treatment with Foralumab is logical to facilitate topical action at the inflamed sites in the gastrointestinal
tract. This potentially ground-breaking approach for immunotherapies originated in my laboratory and was subsequently reported
by other researchers in the field"
"Recently, we also successfully demonstrated
that nasally administered Foralumab is not only well-tolerated, but also produced desirable immunological responses. Oral and nasal
administration routes are both physiologic approaches to stimulate the mucosal immune system to induce disease modifying benefits."
The CD therapeutic market size will be
worth $4.7 Billion by 2025, according to Grand View Research 1. CD is a chronic disorder of the immune system
that causes inflammation throughout the digestive tract. Although the specific causes of CD are still not clearly understood, severe
gut inflammation caused by an overactive immune system attacking the intestines, colon and other organs appears to contribute to
disease pathology. Thus, immunosuppressive agents and anti-TNF (Tumour Necrosis Factor) immunotherapies represent the main therapeutic
options to maintain remission in CD. However, severe toxicities and poor patient compliance limit the long-term use for intravenous
immunotherapies. Oral administration with take-home capsules of Foralumab is a very attractive approach as it may provide local
action to treat gut inflammation in patient with CD. Additionally, oral capsules provide the convenience of home use, and increase
patient compliance by eliminating the need for infusions in a clinic or hospital setting.
"The prevalence of inflammatory bowel
disease is rising globally, imposing a significant burden both on patients as well as healthcare systems worldwide," said
Sy Pretorius, MD, Parexel Executive Vice President and Chief Medical & Scientific Officer.
"We're excited to be collaborating with Tiziana to support the development of a novel, oral therapy that could provide
Crohn's patients with another option in their repertoire of treatments to combat this devastating disease."
Recently, Tiziana announced positive results
from its Phase 1 study showing that oral treatment with Foralumab was well-tolerated in healthy volunteers, with no drug-related
safety issues even at the highest dose of 5 mg2. Oral administration of
anti-CD3 monoclonal antibody is a novel approach to induce an anti-inflammatory immune response to suppress inflammation by inducing
T regulatory (Tregs) cells in animal studies3,4. Importantly, oral treatment with OKT3, a mouse anti-CD3 mAb,
showed clinical responses which were reversed following discontinuation of treatment, suggesting oral treatment with OKT3 may have
potential for treatment of moderate to severe ulcerative colitis5.
Dr. Shailubhai, CEO & CSO of Tiziana
Life Sciences, commented:
"Previously, we reported that oral
administration of Foralumab was well-tolerated and that the treatment did not result in severe toxicities that are so commonly
observed with intravenous (IV) administration of anti-CD3 mAbs, suggesting that oral administration may be able to minimize toxicities
and thereby improve clinical outcome. Our patent on the core formulation technologies covering alternative routes of administration
for immunotherapies has been already granted in the USA and it is pending in other countries world-wide. We believe switching to
oral, nasal and inhalational administration of mAbs from the traditional intravenous administration could potentially be transformational
for the future development of immunotherapies."
This announcement contains inside information
for the purposes of Article 7 of EU Regulation 596/2014. The person who arranged for the release of this announcement on behalf
of the Company was Dr Kunwar Shailubhai, Chief Executive Officer and Chief Scientific Officer of the Company.
1. Grand View Research August 2018 (https://www.grandviewresearch.com/press-release/global-crohns-disease-therapeutics-market).
2. Tiziana Life Sciences January 9, 2020
3. da Cunha, A. P., and Weiner, H. L. (2012)
Induction of immunological tolerance by oral anti-CD3. Clin Dev Immunol 2012, 425021
4. Ogura, M., Deng, S., Preston-Hurlburt,
P., Ogura, H., Shailubhai, K., Kuhn, C., Weiner, H. L., and Herold, K. C. (2017) Oral treatment with foralumab, a fully human anti-CD3
monoclonal antibody, prevents skin xenograft rejection in humanized mice. Clin Immunol 183, 240-246
5. 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., and Snapper, S. B. (2019) Immunologic Alterations Associated With Oral Delivery of Anti-CD3 (OKT3) Monoclonal
Antibodies in Patients With Moderate-to-Severe Ulcerative Colitis. Crohn's & Colitis 360, Volume 1, Issue 2, July 2019,
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 IL2 c-/-), 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.
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. The
company is accelerating development of anti-Interleukin 6 receptor (IL6R) mAb, a fully human monoclonal antibody for treatment
of IL6-induced inflammation, especially for treatment of COVID-19 patients.
Parexel Biotech is a division of leading
global clinical research organization (CRO), Parexel International (IRL) Limited, and provides tailored solutions for biotech and
medical device companies to accelerate their development goals and help them achieve faster market access.
Parexel is focused on supporting the development
of innovative therapies to improve patient health. During the COVID-19 crisis, we continue to be committed to our customers'
business while putting the safety of patients, client partners and our employees at the heart of everything we do. To learn more
about our efforts related to COVID-19, as well as the experts, innovations and processes we have in place to navigate the rapidly
Forward-Looking Statements
Certain statements made in this announcement