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Tiziana Life Sciences #TILS – Phase 1 Clinical Data Demonstrating Oral Treatment with Foralumab is Well-tolerated in Healthy Volunteers
New York/London, 9 January 2020 – 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.
Contacts:
|
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 |
Receive news and updates from Tiziana Life Sciences plc by signing up to get email alerts straight to you on https://ir.tizianalifesciences.com
Tiziana Life Sciences #TILS – Initiates Phase 1 Clinical Trial with Orally Administered Foralumab, a Fully Human anti-CD3 monoclonal antibody, in Healthy Volunteers
London/New York, 4 December 2019 – Tiziana Life Sciences plc (Nasdaq: TLSA / AIM: TILS), a clinical-stage biotechnology company focused on developing innovative therapeutics for inflammatory diseases and cancers, is pleased to announce initiation of a Phase I clinical trial in healthy volunteers with a proprietary oral formulation of Foralumab encapsulated in enteric-coated capsules. The primary objective of this single ascending dose (SAD) phase 1 study, being led by Dr. Tanuja Chitnis at the Brigham and Women’s Hospital, Harvard Medical School, Boston, MA USA, is to determine safety and tolerability of orally administered Foralumab. The clinical protocol also includes evaluation of pharmacokinetics to determine if there is any systemic absorption of Foralumab following oral administration.
“Oral administration of Foralumab in enteric-coated capsules is a novel approach to upregulate T regulatory cells (Tregs) that have the capability to cross-through blood brain barrier and provide clinical benefits. Successful demonstration of safety in this study will facilitate immediate evaluation of orally administered Foralumab in a phase 2 clinical study in patients with progressive multiple sclerosis, a neurodegenerative disease for which there are limited treatment options”, said Dr. Howard Weiner
“We are excited to initiate this trial because this is the first-ever clinical study with orally administered Foralumab in enteric-coated capsules. The oral route of administration is expected to minimize toxicities associated with intravenous administration of anti-CD3 mAbs and it may also improve the clinical outcome through activation of gut mucosal immunity. Our proprietary oral formulation technology has the potential to be useful for treatment of neurodegenerative and gastrointestinal diseases,” commented Kunwar Shailubhai, CEO and CSO of Tiziana.
About Dr. Howard Weiner
Dr. 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 tumors. 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 Tregs for the treatment of these diseases.
About Dr. Tanuja Chitnis
Dr. Tanuja Chitnis is a Professor of Neurology at the Harvard Medical School, and Director of the Translational Neuroimmunology Research Center at Brigham & Women’s Hospital in Boston. She has led studies including the testing of nasal Foralumab in healthy volunteers and a study of fingolimod in pediatric MS that led to FDA approval.
About Harvard Medical Centre
Brigham and Women’s Hospital (BWH) is located adjacent to Harvard Medical School, of which it is the second largest teaching affiliate. It is the largest hospital of the Longwood Medical and Academic Area in Boston, Massachusetts, USA. With Massachusetts General Hospital, it is one of the two founding members of Partners HealthCare, the largest healthcare provider in Massachusetts. BWH conducts the second largest hospital-based research program in the world, with an annual research budget of more than $630 million. Pioneering milestones include the world’s first successful heart valve operation and the world’s first solid organ transplant.
About Neurodegenerative diseases
Neurodegenerative diseases include Alzheimer’s, multiple sclerosis, Huntington’s disease, Parkinson’s disease, ALS and others. Among these, Alzheimer’s is the most prevalent disease. In 2013 the global market for AD was 4.9 billion and expected to rise to 13 billion by the end of 2023. Current treatments for neurodegenerative diseases are mainly symptomatic, but new disease-modifying drugs to slow or stop the progression of the disease are now emerging. Three AChE inhibitors are currently in use for AD, i.e. donepezil (Aricept), rivastigmine (Exelon) and galantamine (Reminyl) and cladribine (Mavenclad) for MS. It is recognized that inflammation plays a critical role in neurodegenerative diseases of the CNS. Immune-directed therapies for neurodegenerative diseases target immune system cells such as the T cells that cause inflammatory and autoimmune disease in MS and microglia in ALS and show promise. It has been shown in animal models of progressive MS that anti-CD3 antibody targeting T cells ameliorates disease. These effects were shown to be IL-10 dependent, mediated by regulatory T cells leading to suppression of the disease. There is great promise in ongoing studies of inflammation-targeted neuroprotective strategies, which may ultimately be used across neurodegenerative diseases.
About Tiziana Life Sciences
Tiziana 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 mAbs in clinical development in the world. This compound has potential application in a wide range of autoimmune and inflammatory diseases, such as crohn’s disease (CD), 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.
For more information go to http://www.tizianalifesciences.com
The person who arranged for the release of this announcement on behalf of the Company was Kunwar Shailubhai, CEO of Tiziana.
Contacts:
|
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 |
Tiziana Life Sciences #TILS Announces FDA Approval to Initiate Phase I Clinical Trial with Orally Administered Foralumab in Healthy Volunteers
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 Announces FDA Approval to Initiate Phase I Clinical Trial with Orally Administered Foralumab in Healthy Volunteers.
A breakthrough approach for treatment of autoimmune and inflammatory diseases
London, 16 September, 2019– Tiziana Life Sciences plc (NASDAQ:TLSA and AIM: TILS), a clinical stage biotechnology company focused on developing targeted drugs for cancer and inflammatory diseases, is pleased to announce (further to the announcement made on 1 May 2019) that the U.S. Food and Drug Administration (FDA) has allowed the initiation of a Phase I clinical trial in healthy volunteers using a novel oral enteric-coated capsule formulation of Foralumab, a fully human monoclonal antibody (mAb), in collaboration with the Brigham and Women’s Hospital (BWH), Harvard Medical School, Boston, MA. We believe this is the first clinical trial in which Foralumab will be administered orally to healthy subjects. Our objective is to develop orally administered Foralumab for treatment of autoimmune and inflammatory diseases.
The scientific rationale for this approach was originally discovered by Dr. Howard Weiner, professor at the Brigham and Women’s Hospital, Harvard Medical School. Dr. Weiner discovered that oral or nasal administration of anti-CD3 mAb induces mucosal tolerance to upregulate T regulatory cells (Tregs) capable of providing site-targeted immunomodulation to suppress inflammation. Therefore, this scientific concept could be effective for the treatment of a variety of autoimmune and inflammatory diseases1-5.
“The therapeutic approach of oral administration with Foralumab greatly enhances our ability to treat neurodegenerative and inflammatory diseases. We have also explored the nasal administration of Foralumab for the treatment of progressive MS. We believe nasal and oral administration with Foralumab opens innovative avenues to treat inflammatory and autoimmune diseases by inducing different classes of Tregs. Thus, mucosal activation stimulating Tregs is a physiological mechanism which we think might be safer than other treatment approaches,”commented Dr. Weiner.
Cited References
- Wu HY, Maron R, Tukpah AM, Weiner HL. Mucosal anti-CD3 monoclonal antibody attenuates collagen-induced arthritis that is associated with induction of LAP+ regulatory T cells and is enhanced by administration of an emulsome-based Th2-skewing adjuvant. J Immunol. 2010; 185(6):3401-3407.
- Ochi, H.,et al.,Oral CD3-specific antibody suppresses autoimmune encephalomyelitis by inducing CD4+CD25-LAP+ T cells. Nature Medicine 2006: 12: (6); 627-635
- Lior Mayo, Andre Pires Da Cunha, Asaf Madi, Vanessa Beynon, Zhiping Yang,Jorge I. Alvarez, Alexandre Prat, Raymond A. Sobel, Lester Kobzik, Hans Lassmann, Francisco J. Quintana and Howard L. Weiner. IL-10-dependent Tr1 cells attenuate astrocyte activation and ameliorate chronic central nervous system inflammation. Brain 2016: 139; 1939–1957
- Chantal Kuhn, Rafael M. Rezende, Andre Pires da Cunha, Fabrice Valette, Francisco J. Quintana, Lucienne Chatenoud, Howard L. Weiner. Mucosal administration of CD3-specific monoclonal antibody inhibits diabetes in NOD mice and in a preclinical mouse transgenic for the CD3 epsilon chain. Journal of Autoimmunity (2016) 76: 1-8
- Ogura M, et al., Prevention of human xenograft rejection with oral anti-CD3 mAb. Clinical Immunology 183: 2017; 240-246
About Howard Weiner
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 Harvard Medical Centre
Brigham and Women’s Hospital (BWH, “The Brigham”) is located adjacent to Harvard Medical School, of which it is the second largest teaching affiliate. It is the largest hospital of the Longwood Medical and Academic Area in Boston, Massachusetts, USA. With Massachusetts General Hospital, it is one of the two founding members of Partners HealthCare, the largest healthcare provider in Massachusetts. Brigham and Women’s Hospital conducts the second largest hospital-based research program in the world, with an annual research budget of more than $630 million. Pioneering milestones include the world’s first successful heart valve operation and the world’s first solid organ transplant.
About Autoimmune Diseases and Foralumab
Autoimmune diseases constitute a major medical problem and include diseases such as multiple sclerosis, type 1 diabetes, rheumatoid arthritis and inflammatory bowel disease. Other diseases, that have inflammatory components include diseases such as NASH, atherosclerosis and stroke. The induction of regulatory cells at mucosal surfaces by the oral or nasal administration of antigens has been shown to treat a large variety of autoimmune and inflammatory diseases in animal models with minimal toxicity. Foralumab was developed by Novimmune and has been acquired by Tiziana Life Sciences PLC. Foralumab (formerly NI-0401) is thus far 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-/-) developed in Dr Kevan Herold’s laboratory, it was show that while targeting the T cell receptor, orally administered foralumab modulates immune responses of the T cells, enhances regulatory T cells 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 regulatory T cells.
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 compound has potential application in a wide range of autoimmune and inflammatory diseases, such as non-alcoholic 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.
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
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.
Contacts:
| 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 (Nominated brokers)
Antonio Bossi / Andy Crossley
|
+44 (0)20 7408 4050 |
Receive news and updates from Tiziana Life Sciences plc by signing up to get email alerts straight to you on https://ir.tizianalifesciences.com