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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
Tiziana Life Sciences #TILS Reports Phase 1 Clinical Data Demonstrating Nasal Treatment with Foralumab was Well-tolerated and Produced Positive Trend in Biomarkers
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
Tiziana Reports Phase 1 Clinical Data Demonstrating Nasal Treatment with Foralumab was Well-tolerated and Produced Positive Trend in Biomarkers of Immunomodulation and Anti-inflammation in Healthy Volunteers
New York, 10 September 2019 – 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 mg 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 mg 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 mg, 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
For further enquiries:
Tiziana Life Sciences plc +44 (0)20 7495 2379 Gabriele Cerrone, Chairman and founder
Cairn Financial Advisers LLP (Nominated adviser) +44 (0)20 7213 0883
Liam Murray / Jo Turner
| Shore Capital (Broker)
Andy Crossley / Antonio Bossi
|
+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 – Proposed US Public Offering
THIS ANNOUNCEMENT CONTAINS INSIDE INFORMATION FOR
THE PURPOSES OF ARTICLE 7 OF REGULATION (EU) NO 596/2014
NOT FOR RELEASE, PUBLICATION OR DISTRIBUTION, IN WHOLE OR IN PART, IN OR INTO OR FROM ANY JURISDICTION WHERE TO DO SO WOULD CONSTITUTE A VIOLATION OF THE RELEVANT LAWS OF SUCH JURISDICTION
Tiziana Announces Publication of Registration Statement on Form F-1 and Proposed U.S. Public Offering of ADSs
New York and London, August 6, 2019 – Tiziana Life Sciences plc (NASDAQ: TLSA; AIM: TILS) (the “Company” or “Tiziana”), a U.S. and U.K. biotechnology company that focuses on the discovery and development of novel molecules to treat human disease in oncology and immunology, today announces the commencement of an underwritten public offering in the United States of American Depositary Shares (“ADSs”), representing ordinary shares of nominal value £0.03 each in the capital of the Company (“Ordinary Shares”) on the NASDAQ Global Market (the “Offering”). There can be no assurance as to whether or when the Offering may be completed, or as to the actual size or terms of the Offering. The price for the Offering has not yet been determined.
All ADSs to be sold in the Offering will be offered by the Company. The number of Ordinary Shares represented by ADSs comprised in the Offering will be within existing shareholder authorities.
ThinkEquity, a division of Fordham Financial Management, Inc., is acting as the representative of the underwriters in the Offering.
The Offering is being made only by means of a prospectus, which, for the avoidance of doubt, will not constitute a “prospectus” for the purposes of the Prospectus Regulation (as defined below) and has not been reviewed by any competent authority in any Member State (as defined below).
When available, copies of the preliminary prospectus relating to and describing the terms of the Offering may be obtained from ThinkEquity, a division of Fordham Financial Management, Inc., 17 State Street, 22nd Floor, New York, New York 10004, by telephone at (877) 436-3673, or by email at prospectus@think-equity.com. Electronic copies of the preliminary prospectus will also be available on the website of the SEC at www.sec.gov.
A registration statement relating to these securities has been filed with the SEC but has not yet become effective. These securities may not be sold, nor may offers to buy these securities be accepted, prior to the time the registration statement becomes effective. This announcement shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.
The person who arranged for the release of this announcement on behalf of the Company was Tiziano Lazzaretti, Chief Financial Officer of Tiziana.
About Tiziana Life Sciences plc
Tiziana Life Sciences is a UK biotechnology company that focuses on the discovery and development of novel molecules to treat human disease in oncology and immunology. We believe Foralumab is the only fully human anti-CD3 mAb in clinical development in the world. This compound has potential application in a wide range of autoimmune and inflammatory diseases, such as NASH, primary biliary cholangitis (PBS), ulcerative colitis, MS, type-1 diabetes (T1D), inflammatory bowel disease (IBD), psoriasis and rheumatoid arthritis, where modulation of a T-cell response is desirable.
For readers in the European Economic Area
In any member state in the European Economic Area (each, a “Member State”), this announcement is only addressed to and directed at qualified investors in that Member State within the meaning of the Prospectus Regulation. The term “Prospectus Regulation” means Regulation (EU) 2017/1129.
For readers in the United Kingdom
This announcement, in so far as it constitutes an invitation or inducement to enter into investment activity (within the meaning of section 21 of the Financial Services and Markets Act 2000, as amended) in connection with the securities which are the subject of the Offering described in this announcement or otherwise, is being directed only at (i) persons who are outside the United Kingdom or (ii) persons who have professional experience in matters relating to investments who fall within Article 19(5) (“Investment professionals”) of the Financial Services and Markets Act 2000 (Financial Promotion) Order 2005, as amended (the “Order”) or (iii) certain high value persons and entities who fall within Article 49(2)(a) to (d) (“High net worth companies, unincorporated associations etc.”) of the Order; or (iv) any other person to whom it may lawfully be communicated (all such persons in (i) to (iv) together being referred to as “relevant persons”). The ADSs offered in the Offering are only available to, and any invitation, offer or agreement to subscribe, purchase or otherwise acquire such ADSs will be engaged in only with relevant persons. Any person who is not a relevant person should not act or rely on this announcement or any of its contents.
Forward-Looking Statements
Certain statements made in this announcement are forward-looking statements including with respect to the creation of a trading market for ADSs representing the Ordinary Shares in the United States. 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.
END
For further enquiries:
Tiziana Life Sciences plc
Gabriele Cerrone, Chairman and founder
+44 (0)20 7495 2379
ThinkEquity, a division of Fordham Financial Management, Inc.
Ramnarain Jaigobind / Priyanka Mahajan
(877) 436-3673
Cairn Financial Advisers LLP (Nominated adviser)
Liam Murray / Jo Turner
+44 (0)20 7213 0880
Shore Capital (Broker)
Andy Crossley / Antonio Bossi
+44 (0)20 7601 6125
Tiziana Life Sciences (TILS) Reports Phase 2a Clinical Data with Milciclib Monotherapy in Sorafenib-refractory or -intolerant patients with unresectable or metastatic Hepatocellular Carcinoma
- Milciclib was well tolerated and no drug related deaths were reported
- 28 out 31 treated patients were evaluable, with 14 patients completing the 6-month study duration
- 9 patients continued treatment under compassionate use, of which 5 are currently continuing with treatment
New York/London, 22 July 2019 – Tiziana Life Sciences plc (NASDAQ: TLSA / AIM: TILS), a biotechnology company focusing on the discovery and development of innovative therapeutics for inflammation and oncology indications, today announced preliminary topline clinical data from a Phase 2a trial of Milciclib as a monotherapy in patients with advanced hepatocellular carcinoma (HCC), the most common form of liver cancer. The primary endpoint of the study was overall safety. Oral treatment with Milciclib was well tolerated with manageable toxicities. Under compassionate use, a few patients continued with the treatment for up to 16 months. Overall, treatment with Milciclib was well-tolerated and no drug-related deaths were recorded. Secondary endpoints of efficacy including progression-free survival (PFS) and time to progression (TPP) are currently being evaluated and will subsequently be reported.
This Phase 2a trial with Milciclib monotherapy was a multi-centered, single-arm, repeated-dose (100 mg once daily; 4 days on/3 days off every 4 weeks; defining each cycle), 6-month duration study to evaluate the safety, tolerability and anti-tumor activity of Milciclib in sorafenib-refractory or intolerant patients with unresectable or metastatic advanced HCC. This multi-centered trial enrolled 31 patients in Italy, Greece, and Israel.
Among the 28 evaluable patients, 14 completed the 6-month duration study. Oral treatment with Milciclib was well-tolerated with manageable toxicities. The most frequent adverse events such as diarrhea, nausea, fatigue, asthenia, chills, ataxia, headache, and rash were manageable.
Nine out of the 14 patients, after completing the 6-month trial period, requested to continue the treatment under compassionate use and were approved by their respective ethical committees. Four of the patients received Milciclib for a total of 9, 11, 13 and 16 months. The remaining 5 patients are continuing treatment with Milciclib are at 8th, 9th, 9th, 9th and 11th months currently.
Objective tumor assessments according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) guideline and the conventional RECIST 1.1 criteria are being conducted by Independent Central Review and data will be available in September 2019.
“We are very pleased with the clinical activity and tolerability of Milciclib in these advanced cases of HCC. It is an important milestone to move forward with further clinical development of Milciclib either as a single agent or in combination with other HCC drugs,” said Dr. Kunwar Shailubhai, CEO & CSO of Tiziana.
These safety and clinical activity data are consistent with the earlier reported long-term safety and clinical activity of Milciclib in thymic carcinoma, thymoma1 and other solid cancers2.
Liver cancer is the fifth most common cancer worldwide and HCC accounts for 75-90% of all primary liver cancer cases. The global market for liver cancer drugs is estimated to reach $1.47 billion by 2022. Current standard of care drugs are not entirely satisfactory due to low response rates and severe toxicities. Importantly, patients often become resistant or unresponsive to the treatment. Milciclib works though a unique mechanism of action and the Company therefore believes it may have the potential for long-term efficacy with a good safety profile in a larger subset of patients.
The person who arranged for the release of this announcement on behalf of the Company was Dr Kunwar Shailubhai, CEO of Tiziana.
Cited References
- Besse, B,, Garassino, M,, Rajan, A., Novello, S.,Mazieres, J., Weiss, G., Kocs, D., Barnett, J, Davite, C, Crivori, P and G. Giaccone. Efficacy of milcicilib (PHA-848125AC), a pan-cyclin D -dependent kinase inhibitor in tow phase II studies with Thymic carcinoma and B3 thymoma patients. (2018) J. Clin. Onc 36 (15 suppl): 8519
- Aspeslagh, S., Shailubhai, K., Bahleda, R. et al. (2017). Phase I dose-escalation study of Milciclib in combination with gemcitabine in patients with refractory solid tumors. Cancer Chemother Pharmacol. 79:1257-1265.
Contacts:
| Tiziana Life Sciences plc
Gabriele Cerrone, Chairman and founder |
+44 (0)20 7493 2853 |
| Cairn Financial Advisers LLP (Nominated adviser)
Liam Murray / Jo Turner |
+44 (0)20 7213 0883 |
| Stockdale Securities (Nominated brokers)
Antonio Bossi / Andy Crossley |
+44 (0)20 7601 6125 |
For further enquiries:
Tiziana Life Sciences plc +44 (0)20 7493 2853
Gabriele Cerrone, Chairman and founder
Cairn Financial Advisers LLP (Nominated adviser) +44 (0)20 7213 0880
Liam Murray / Jo Turner
Stockdale Securities Limited (Broker) +44 (0)20 7601 6125
Andy Crossley / Antonio Bossi
About HCC
HCC is the fifth most common cancer and the third highest cause of cancer mortality worldwide. In 2007, the approval by the European Medical Agency and U.S. Food and Drug Administration of Sorafenib (Nexavar®), an inhibitor of several receptor tyrosine kinases, in HCC represented the first systemic therapy for improving outcome in patients unsuitable for loco-regional and surgical therapies and created a new standard of treatment for the disease. However, although significant in respect to placebo, the benefits of Sorafenib are modest, with a response rate less than 3%, an improvement in median survival of 2-3 months and drug-related symptoms that are not ordinary. More recently, lenvatinib (Lenvima ®), another multi-tyrosine kinase inhibitor was also approved for first line treatment of HCC. The complex multi-factorial etiology of HCC warrants a need for systemic therapies that target different signaling cascades to provide improved efficacy and safety for both naive patients presenting with unresectable, advanced stage and those who suffer recurrence after curative treatments (resection, ablation and transplantation).
About Milciclib
Milciclib (PHA-848125AC) is a small molecule inhibitor of several cyclin dependent kinases such as CDK1, CDK2, CDK4, CDK5 and CDK7. CDKs are serine threonine kinases that play crucial roles in progression of the cell cycle from G1 to S phase. Overexpression of CDKs and other downstream signaling pathways that regulate cell cycles have been frequently associated with development of resistance towards chemotherapies. In a Phase 1 study, oral treatment with Milciclib was well-tolerated and the drug showed promising clinical responses in patients with advanced solid malignancies such as in NSCLC, pancreatic and colon cancer, thymic carcinoma and thymoma. Additionally, milciclib met its primary endpoint in two separate Phase 2 multi-center clinical trials (CDKO-125A-006: 72 patients and CDKO-125A-007: 30 patients) in thymic carcinoma and thymoma patients.
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.