An Innovative Platform in Oral and Nasal Antibody Administration
A Novel Approach for Treatment of Hepatocellular Carcinoma
January 2020
TLSA : TILS:
DISCLAIMER AND FORWARD LOOKING STATEMENTSThe content of this presentation has been prepared for the purpose of providing general information about, and an overview of, the Company and its business. It is notintended to be a complete review of all matters concerning the Company and nor has it been independently verified . Whilst the presentation has been prepared in goodfaith and the Company has taken all reasonable care to ensure the information and facts contained in this presentation are accurate and up-to-date, it does not make anyrepresentation or warranty, express or implied, as to the accuracy or completeness of any information included in this presentation . Neither the Company nor any of itsdirectors, officers, employees or agents shall be liable for any loss arising directly or indirectly from the use of or reliance upon this presentation or in relation to theadequacy, accuracy, completeness or reasonableness of the information it contains. All and any such liability is expressly excluded to the fullest extent permitted by law.The information in this presentation is subject to updating, completion, revision, further verification and amendment without notice .This presentation does not constitute or form part of any offer for sale or solicitation of any offer to buy or subscribe for any securities including ordinary shares in theCompany nor does it constitute an invitation or inducement to engage in investment activity in relation to any securities, including the ordinary shares of the Company . Itdoes not purport to contain information that shall form the basis of or be relied upon in making such investment decisions. If you require any advice, please consult with aprofessional financial adviser. All investments are subject to risk. The value of securities may go down as well as up. Past performance cannot be relied on as a guide forfuture performance .
This presentation may contain certain forward -looking statements concerning the financial condition, results of operations and businesses of the Company . All statementsother than statements of historical fact are, or may be deemed to be, forward -looking statements . Forward -looking statements are statements of future expectations thatare based on management’s curre nt e xpe ctations and assum ptions and involve known and unknown risks and unce rtaintie s that could cause actual re sults, pe rform anceor e ve nts to d iffe r m ate rially from those e xpre sse d or im plie d in the se state m e nts. All forward-looking state m e nts containe d in this pre se ntation are e xpre ssly qualifie d inthe ir e ntire ty by the cautionary state m e nts containe d or re fe rre d to in this se ction. You should not p lace undue re liance on forward -looking state me nts. Each forward -looking state m e nt spe aks only as of the date of this pre se ntation. The Com pany doe s not unde rtake any obligation to publicly update or re vise any forward -lookingstate m e nt as a re sult of ne w inform ation, future e ve nts or othe r inform ation. In light of the se risks, re sults could d iffe r m ate rially from those state d , im plie d or infe rre d fromthe forward -looking state m e nts containe d in this pre se ntation.
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EXECUTIVE TEAM
Key Strengths of the Management Team
Successful credentials in entrepreneurship
Strong history in biotechnology deals
Proven ‘Bench to market’ record
Strong credentials in Science and Business
Co-founder , EVP & CSO of Synergy Pharmaceuticals, NASDAQ: SGYP
The pioneer of GC-C agonist technology
Inventor of TRULANCE® approved forChronic constipation and IBS -C
VP, Callisto Pharmaceuticals Group Leader, Monsanto Co.
Kunwar Shailubhai PhD, MBACEO & CSO
Previously Group Finance Director at Pharmentis –Teva Ratiopharm spin off
Executive Director at Alliance Boots, Snia, Accenture and FIAT Group
MBA, Bocconi University, Milan Corporate Finance, London Business
School. BSc Accounting and Finance
Tiziano Lazzaretti Chief Financial Officer
Gabriele CerroneExecutive Chairman
Prove n track re cord & e xpe rie nce in financing b iote chnology com panie s
Se rve d as chairm an of 2 b iote ch com panie s with m arke t cap ove r $2Bn
Inhib ite x sale $2.5Bn Syne rgy / Trovage ne / Ge nsignia /
Rasna / Contravir / Siga Te chnologie s MBA, Ste rn School of Busine ss, NY,
USA
SCIENTIFIC ADVISORY COMMITTEEHoward Weiner, MD
Professor of Neurology at Harvard Med Director and Founder of the Partners MS Center and Co -Director
of the Ann Romney Center for Neurologic Diseases Pioneered investigation of the mucosal immune system for the
treatment of autoimmune and other diseases
Napoleone Ferrara MD Inventor of Avastin® ($6.67Bn/ yr)*; 2010 Lasker Award Senior Deputy Director Basic Sciences, Moores Cancer Center,
UC San Diego Distinguished Prof of Pathology, School of Medicine, UC San
Diego
Kevin Herold, MD Professor of Immunobiology and Medicine and Deputy Director,
Yale Center for Clinical Investigation Director of the Yale Diabetes Center and Director of the TrialNet
Center at Yale Expert in autoimmune diseases and anti -CD3 monoclonal
antibody therapies
Arun Sanyal MD
Charles Caravati Distinguished Professor and Chair, Division of Gastroenterology, Hepatology and Nutrition at Virginia Commonwealth University School of Medicine
Leader in the field of liver diseases
Angelo Sangiovanni , MD Adjunct Professor of Gastroenterology at the University of Milan Leader in liver disease and gastroenterology Awarded Best Scientific Publication in clinical Hepatology in Italy
Fabio Piscaglia , MD
Associate Professor, Medical and Surgical Sciences at the University of Bologna
Leader in liver diseases and transplantation 2017 Winner of a National Institute of Health (NIH) of United
States of America grant
Erica Villa, MD
Professor and Chief GI Unit Chairman of the Department of Internal Medicine Universitaria di Modena, Policlinico , Modena, Italy Leader in Clinical Hepatology and Translational Medicine
Innovative platform technology for oral and nasal formulations can transform the administration of Monoclonal Antibodies (‘mAbs’)
Two de -risked assets in clinical evaluation that target the root causes of autoimmune/inflammatory diseases and cancer
Milciclib has received ‘Orphan Drug Designation’ in US and EU for treatment of thymic carcinoma/thymoma (TC/T)
Assets for unmet needs in a multi billion -dollar addressable market NASH - $35 billion Crohn’s Disease - $10 billion/year by 2025 Liver cancer - $1.5 billion/year by 2022
Strong intellectual property 255 patents approved and 30 pending Covers composition of matter, process and disease indications Oral formulation technology applicable to other mAbs therapeutics
Experienced and successful biotech management team
A leverageable biotechnology platform for use in additional therapeutics
INVESTMENT HIGHLIGHTS
Orphan Drug DesignationMet primary and secondary
endpoints in 2 separate Phase 2 trials in TC/T.
Phase 2a in sorafenib -resistant patients completed
Well -tolerated topline data reported July 2019
Nasal Trial: Phase 2 starting shortly.
Phase 1 trial completed
Data - August 2019
Oral Trial: FDA approved IND. Phase 1 oral trial to begin shortly
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Market potential for our technologies
Foralumab Nasal administration for Neurodegenerative diseases: Recent clinical data
indicates that foralumab was safe and produced an anti - inflammatory effect. A phase 2 trial in patients with progressive multiple sclerosis will commence shortly
Oral administration for digestive diseases (Crohn’s Disease and NASH)Our IND was approved by the FDA. A phase 1 trial in healthy volunteers will be completed by 4Q 2019.
Milciclib Hepatocellular carcinoma: Clinical data from a recently completed phase 2a
in sorafenib-resistant advanced cases of HCC suggests that milciclib is outperforming the existing therapies
Cholangiocarcinoma: Milciclib has the potential to treat this orphan cancer indication for which no treatment options are available. Our IP covers this disease indication.
• HCC• Cholangiocarcinoma
Oral:• Crohn’s Disease• Celiac Disease• NASH
Nasal:• Pro-MS• Neurodegenerative• Autoimmune
BIG PHARMA INTEREST
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platform enables…
A REVOLUTIONARY PLATFORM
Costly Infusion Center Poor patient compliance Higher toxicity Systemic treatment to affect
whole body Infusion related side effects
TODAY’S ANTIBODY ADMINISTRATION OPTIONS ARE MOSTLY I.V.
Antibodies (mAbs) reformulated for oral
administration
Antibodies (mAbs)reformulated for nasal
administration
Ease of useSuperior complianceTopical action in gut
Minimized toxicityTake home Rx
No costly infusion
PATIENT &PROVIDER BENEFITS
THE LARGE MARKET OPPORTUNITY
Marke t opportunity for m Ab the rape utics is
greater than
$86BILLION
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SWITCH ANTIBODY ADMINSTRATION FROM INTRAVENOUS TO ORAL AND NASAL ROUTES
ROUTE OF ORAL OR NASAL ADMINISTRATION DEPENDS ON DISEASES
HEALTHY LIVER NON-ALCOHOLIC FATTY LIVER DISEASE NAFLD
25-30% of Population
CIRRHOSIS
Irreversible Liver Damage
HEPATOCELLULAR CANCER
Immune cells infiltration
Foralumab (Anti -CD3) for NASH and Crohn’s Disease
NASH global market ~ $35 B/year Crohn’s Disease market: $10B /year by 2025 Oral/nasal delivery is a novel, completely differentiated approach Strong IP on the ‘Revolutionary’ approach with significant market
potential
THE MULTI BILLION DOLLAR MARKET FOR LIVER DISEASES AND CROHN’S DISEASE
EXCESSIVE FAT DEPOSITS LEAD TO LIVER INFLAMMATION INFLAMMATORY AND FIBROTIC PROCESSES LEAD TO MALIGNANCY
NON-ALCOHOLIC STEATOHEPATITIS NASH
Generally Asymptomatic Reversible
3- 5% of Population
Reversible
Milciclib for Liver Cancer
HCC ($1.5B / ye ar by 2022): Me d ical ne e d to have a safe r and e ffe c tive d rug with highe r re sponde r rate s
Milc ic lib : An oral d rug with com ple te ly d iffe re ntia te d MOA with long-te rm safe ty
Supe rior safe ty p rofile
20% Over 10 Years
HBV/HCV
X
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DISCOVERY LEADOPTIMIZATION PRE-CLINICAL IND PHASE 1 PHASE 2 PHASE 3
DEVELOPMENT PIPELINE
Intranasal formulation for Neurodegenerative diseaseNasal Administration
Enteric coated capsules * Oral Administration
Crohn’s disease I.V. Administration – Conducted by Novimmune
Thymic Carcinoma / ThymomaOrphan Drug Designation in U.S. and E.U
Milciclib + Gemcitabine in refractory solid tumorsPotential Adjuvant Treatment
HCC monotherapySorafenib Resistant Patient
HCC combination with a Tyrosine Kinase InhibitorPotentially for synergism
BEGINNING PHASE 2Nasal Trial
Pro-MS
BEGINNINGPHASE 2
Oral
Crohn’s
TWO PHASE 2 TRIALS
COMPLETED TC / T Oral
PHASE 2aCOMPLETED
HCC Oral Monotherapy
9 9*F i C h ’ Di C li Di d NASH
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PLATFORMTECHOLOGIES
NASAL ADMINISTRATION
Phase 1 trial completed for related neurodegenerative diseases such as
Progressive Multiple Sclerosis (Pro -MS) . Phase 2 trial in Pro-MS to start shortly
ORAL ADMINISTRATION
FDA has allowed initiation of clinical studies with enteric coated capsule for
oral administration with Foralumab. Phase 1 completed December, 2019.
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A BIOTECHNOLOGY PLATFORM ENABLING ORAL AND NASAL
ADMINISTRATION OF FORALUMAB AND OTHER MONOCLONAL ANTIBODIES
OKT3MUROMONAB
CHAGLYCD3 OTELIXIZUMAB
NUVION VISILIZUMAB
HOKT31(ALA-ALA) TEPLIZUMAB FORALUMAB
IgG2a IgG1*Agly
IgG2*AA
IgG2*AA
IgG1*AE
Fully Mouse Chimeric & Humanized
Humanized Humanized Fully Human
THE ONLY FULLY HUMAN ANTI-CD3 MAB
Approved by the FDA for solid organ transplantation immuno-suppression
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CD3-SPECIFIC MONOCLONAL ANTIBODIES IN CLINICAL DEVELOPMENT
Oral and Nasal Administration Market Opportunities
Tiziana’s platform of oral and nasalmAbs administration potentially
enhances efficacy and reduces toxicity
Foralumab is unique: functionally equivalent to OKT3 with minimal immune reactions when administered IV
PANETH CELL
Dendritic cells
M CELL
INTESTINAL EPITHELIAL CELLS
Lymphoid follicle
Mesentericlymph node
Treg cell induction
Site-targetedImmunomodulation
Gut Lumen
INNATE IMMUNE SYSTEM
Macrophages
NKT cells
Intraepithelial lymphocytes
NOVEL APPROACH FOR SITE-TARGETED IMMUNOMODULATIONHOW DOES OUR PLATFORM TECHNOLOGY WORK?
Lamnia Propria
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Patent covers and other mAbs
ANTI - CD3 ANTIBODY FORMULATIONSApplicant(s): Tiziana Life Sciences PLCInventor(s): SHAILUBHAI, Kunwar
US Non-Provisional Patent ApplicationNo.:62/ 380,652, filed August 29, 2016PCT Application PCT/US 2017/ 049211, filed, Aug 29, 2017
Patent estate Exclusive license for
composition of matter Composition of matter patent for oral
formulation Additional patent applications pending Oral formulation technology applicable to
other mAbs
Nasal administration of
Proof-of-concept demonstrated in animal studies
Phase 1 study for neurodegenerative diseases at Brigham and Women’s Hospital, Harvard Medical School; completed and well -tolerated up to 250 µg
Positive Top line data received August 2019, CSR in preparation
In-licensed nasal delivery technology from Brigham and Women’s Hospital, Harvard Medical School
ORAL AND NASAL FORMULATION PATENTS PENDING
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Phase 1 Trial Conducted at Brigham and Women’s Hospital Com ple te d De ce m be r 2019
Single Asce nd ing Dose , double -b lind , p lace bo-controlle d study in he althy subje cts
Foralum ab adm iniste re d at 1.25, 2.5 and 5.0 m g/ dose as stab ilize d powde r form ulation in e nte ric-coate d capsule s
KEY FINDINGS
1. Well -tolerated at all doses tested
2. No drug -related safety issues observed
Foralumab Enteric Capsules Safety Study
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Determined the immunologic effects and safety of orally delivered anti -CD3antibody in patie nts with m ode rate -to-se ve re ulce rative colitis (UC)
Six subje cts re ce ive d oral OKT3
* 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.
KEY FINDINGS
1. The biologic response to treatment with oral anti-CD3 were increased proliferation and anti-inflammatory gene expression profile in peripheral blood mononuclear cells
2. 3 of 6 patients had a clinical response including one patient in clinical remission
3. Treatment was well-tolerated with no serious treatment-related adverse events
FINDINGS SUPPORT TIZIANA’S ORAL PLATFORM
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THIRD PARTY RESEARCHERS IN PEER-REVIEWED, CROHN’S & COLITIS 360*
OKT3, a murine mAb, was withdrawn from the market due to severe side effects Foralumab is a fully human anti-CD3 mAb with minimal side effects
PROOF-OF-CONCEPT IN NASH PATIENTS
STUDY DESIGN SAFETY IMMUNOLOGICAL EFFICACY BIOMARKERS
36 subjects with NASH and type II diabetes
Randomized, single-blinded, placebo-controlled
9 per group, not powered for statistical significance
0.2, 1.0, 5.0 mg or placebo daily for 30 days
Primary endpoints: safety and trends in immunomodulation
Secondary endpoint: indication or trend of efficacy through biomarkers
Follow up: Days 0, 14, 30, 60
Hadassah Medical Center, Jerusalem Israel
Well tolerated by all patients in all groups
No systemic drug-related adverse events
No changes in vital signs, serum biochemistry and hematological parameters during treatment or follow-up periods (30-days post-treatment)
No changes in lymphocyte and CD+ cell counts
No changes in weight or BMI or HbA1C lipid GLP-1, or CRP levels in any of the groups
Increases in Treg markers consistent with induction of Tregs
Anti-inflammatory markers ↑
CD4+CD25+LAP+ Treg cells, TGFβ↑
Positive trends, some of which were statistically significant
AST ↓ – liver enzyme indicating reduced liver inflammation
Glucose ↓ – favorable for subjects with type-2 diabetes
Insulin ↓ – favorable for subjects with type-2 diabetes
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ORAL TREATMENT WITH MURINE ANTI-CD3 (OKT3) EFFECTIVE IN A PHASE 2 TRIAL WITH NASH1
Sources: 1) Lalazar, G., Mizrahi, M., Turgeman , I., Adar, T., Ya’Acov, A. B., Shabat, Y., . . . Ilan, Y. (2015). Oral Administration of OKT3 MAb to Patients with NASH, Promotes Regulatory T -cell Induction, and Alleviates Insulin Resistance: Results of a Phase IIa Blinded Placebo -Controlled Trial. Journal of Clinical Immunology, 35(4), 399 -407.
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KEY FINDINGS
1. Foralumab is as potent as OKT3
2. Treatment is effective in humanized mice studies
3. Mechanism of action is via activation of Tregs that systemically circulate to elicit targeted immunomodulation
FORALUMAB IS FUNCTIONALLY EQUIVALENT TO OKT3Oral Treatment prevents skin xenograft rejection in mice with human immune systemsMineko Ogura, Songyan Deng, Paula Preston-Hurlburt, Hideki Ogura, Kunwar Shailubhai, Chantal Kuhn, Howard L Weiner, and Kevan C. Herold
Clinical Immunol, 2017. 183: 240-246
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Anti -CD3 Monoclonal Antibodies Induce Regulatory T Cell (T reg) for the Treatment of Autoimmune and Inflammatory Diseases
Potential for treatment of Type 1 diabetes is well established
Preservation/protection of β-ce lls is de m onstrate d in p re -c linical stud ie s
Im prove d insulin re sistance and g lucose tole rance in Type 2 d iabe te s by induction of T re gs
Anti-CD3’s show pote ntial in p re ve nting g raft ve rsus host d ise ase (GvHD) in he m atopoie tic ste m ce ll transp lantation (HSCT) via induction of T re gs Patie nts with re nal allograft re je ction dose d IV with foralum ab , de laye d g raft
re je ction and im prove d re nal function Foralumab shows promise for successful stem cell/CAR -T transplantation
Anti-CD3 mediates immune tolerance by induction of T regs
mediated by IL -10 (nasal tolerance) and TGF-β and LAP complex leading to differentiation of T cells to T regs (oral tolerance)
LFA-1 (cell adhesion molecule critical for T reg homeostasis and function)
Induces apoptosis of effector T cells to normalize balance of Treg:Teff cells ratio
Anti-CD3 antibody increases T reg:Teff ratio
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KEY FINDINGS
1. Teplizumab (humanized OKT3), administered intravenously,significantly slowed progression to clinical Type 1 diabetes, with a median delay in the diagnosis of diabetes of 2 years
2. At the end of the trial, 57% of subjects treated with Teplizumab showed slowed progression to development of Type 1 diabetes, while 72% of the placebo-treated subjects progressed to clinical diabetes
POTENTIAL TO TREAT TYPE I DIABETES
New England Journal of Medicine* provides clinical evidence for the potential use of a humanized anti -CD3mAb for treatment of type 1 diabetes
*K. Herold, B. Bundy, S.A. Long, J. Bluestone, L. Dimeglio , M. Dufort , S. Gitelman, P. Gottlieb, J. Krischer, P. Linsley, J. Marks, W. Moore, A. Moran, H. Rodriguez, W. Russell, D. Schatz, J. Skyler, E. Tsalikian, D. Wherrett , A-G. Ziegler and C. Greenbaum. “ An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes,”. epub . NEJM.org June 9 2019
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A PAN-CDK INHIBITOR FOR TREATMENT OF HEPATOCELLULAR CARCINOMA AND SOLID TUMORS
Source: Petrick et.al. J. Clin. Onc 34 (15) (2016) pg 1787-1795
Incidence of HCC is steadily increasing in males and females and subpopulations in US
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SMALL MOLECULE PAN-CDK INHIBITOR
Orally -bioavailable small molecule with potent anti-tumor activity in a wide range of animal models
Inhibitor of kinases associated with cancer cell growth including CDK1, CDK2, CDK4 CDK5, CDK7and src-family kinases
Inhibits signaling pathways for hepato -carcinogenesis
Well tolerated in 316 patients
Improved toxicity profile over the current standard of care anticipated
A drug with completely differentiated MOA and long-term safety
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CLINICAL DATA FROM MILCICLIBTrial design : Oral administration (100 mg/day, consecutive 4 days a week in a 4 -week cycle). Total patients 30 to be enrolled. Duration 6 months
Primary end point: safety Secondary end points: PFS, ORR & TTPExploratory: AFP and miRNA profiling
Compassionate use : Upon request of patients with EC approval
Trial complete: Data from 28 out of 31 evaluable sorafenib -resistant HCC patients 14 patie nts com ple te d tre atm e nt as pe r p rotocol Nine approve d for com passionate use . Se ve n patie nts com ple te d
9, 9, 10 , 11, 13, 13 and 16 m onths , re spe ctive ly. No drug related deaths in the trial Tre atm e nt was we ll- tole ra te d Adve rse e ve nts we re m anage ab le Time to progression 5.9 months out of 6 months duration of trial Stabilized Disease (SD) 61% Clinical Benefit Response 64%
PHASE 2A TRIAL IN SORAFENIB-RESISTANT HCC PATIENTS
Two p a t ie nts cu rre nt ly cont inu ing com p a ss iona te use t re a tm e nt for 15 m onths
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THYMIC CARCINOMA AND THYMOMA UPDATES Two Phase 2 trials with Milciclib in US, Italy and France
o Trial 006: Thym ic carc inom a and Thym om a m ixe d population (72 patie nts)o Trial 007: Thym ic carc inom a and Thym om a m ixe d population (30 patie nts)
Rare cance rs with ve ry fe w case s: Orphan Dise ase Ind ications
Positive c linical data
Primary endpoint (progression free survival) and secondary endpoint (overall survival) met in both trials separately
Thym ic carc inom a is an aggre ssive m e tastatic cance r and it has no approve d the rapy
Milcic lib as a s ing le age nt m e t p rim ary as we ll as se condary e ndpoints in thym ic carc inom a in both trials
Under compassionate use, few patients continued the treatment for over five years
Se e king guidance from FDA/ EMA re gard ing cond itional m arke ting approval
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MILCICLIB OVERCOMES DRUG RESISTANCE
KEY FINDINGS
1. Milciclib well-tolerated with manageable side effects in patients with refractory solid tumors
2. Oral treatment in combination with gemcitabine demonstrated clinical activity in patients who were non-responder to existing chemotherapeutic drugs
3. Recommended Phase 2 dose (RPD) found to be 80mg/m2/day for milciclib and 1000mg/m2/day for Gemcitabine
4. Overall response rate was 36%
5. Results suggest further evaluation in other solid cancers either as monotherapy or combo-therapy
PATIENTS RAPIDLY ACQUIRE RESISTANCE TOWARDS CHEMOTHERAPIES
Phase 1 Dose-Escalation Study of Milciclib in Combination with Gemcitabine in Patients with
Refractory Solid Tumors*
Swimmerplot showing treatment duration. Tumor type was indicated for patients having a prolonged stable disease or a partial response. M Milciclib; G gemcitabine.
* Cancer Chemotherapy and Pharmacology, June 2017, 79(6), 1257-1265
INTELLECTUAL PROPERTY PORTFOLIO
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FAMILY SUBJECT PRIORITY STATUS EXPIRES JURISDICTION
TZLS-401
Methods of Use (Autoimmune or Inflammatory diseases and disorders) 2004 Issued 2025
Australia, Canada, China, Hong Kong, Israel, Japan, Mexico, Norway, Singapore, South Africa, Ukraine, Armenia, Austria, Azerbaijan, Belgium, Belarus, Switzerland, Germany, Denmark, Spain, France, United Kingdom, Ireland, Italy, Kyrgyzstan, Kazakhstan, Luxembourg, Moldova, Netherlands, Portugal, Russian Federation, Sweden, Tajikistan, Turkmenistan,
Composition and methods of use 2004 Issued/ Pending 2025
US, Armenia, Australia, Austria, Azerbaijan, Belarus, Canada, China, Denmark, France, Germany, Hong Kong, India, Israel, Italy, Japan, Kazakhstan, Kyrgyzstan, Mexico, Moldova, Netherlands, Norway, Republic of Korea, Russian Federation, Singapore, South Africa, Spain, Switzerland, Tajikistan, Turkmenistan, and Ukraine Pending: Brazil, Japan (divisional), Singapore (divisional), US (divisional)
Methods of Use (In combination with anti-IL-6/IL-6R antibodies) 2011 Pending 2032 US
Formulations and dosing regimen 2016 Pending 2037 US, Australia, Canada, China, Europe, Israel, Japan
Methods of Use (CNS disorders) 2017 Pending 2038 PCTMethods of Use
(gastrointestinal/autoimmune/inflammatory) 2018 Pending 2039 Provisional
T
TZLS-201
Composition of matter, methods of use, process of manufacturing 2003 Issued/
Pending 2024
US, Europe, Eurasia, Africa, Algeria, Antigua & Barbuda, Argentina, Australia, Barbados, Bosnia & Herzegovina, Brazil, Canada, Colombia, Costa Rica, Croatia, Cuba, Ecuador, Egypt, Georgia, Iceland, India, Indonesia, Israel, Japan, Korea, Kosovo, Malaysia, Mexico, Mongolia, Montenegro, New Zealand, Nicaragua, Norway, Pakistan, Philippines, Serbia, Singapore, South Africa, Sri Lanka, Taiwan, Thailand, Trinidad & Tobago, Tunisia, Ukraine, Uzbekistan, Venezuela, VietnamPending: Several in US and other countries
Methods of use (multiple indications) 2008; 2009 Issued 2029; 2030 US, EU, China, Hong Kong, JapanMethods of use (combination
therapies with cytotoxics) 2008; 2009 Issued 2029; 2030 US, EU, China, Hong Kong, JapanCompositions of related entities, formulations
and methods of treatment 2009 Issued 2030 US, EU, China, Hong Kong, JapanMethods of use (combination therapies
with therapeutic antibodies) 2006 Issued 2027 US, EU, China, Japan
Formulations of Milciclib and therapeutic combinations of the same for use in the
treatment of cancer2017 Pending 2038 US, PCT
Anti IL-6/IL-6R Antibody TZLS-501
Composition of Matter and Methods of use 2009 Issued/
Pending 2029US, Austria, Australia, Belgium, Canada, China, Denmark, France, Germany, Ireland, Italy, Japan Luxembourg, Mexico, Netherland, Spain, Sweden, Switzerland and UK . Pending: US (divisional), Japan (divisional), India
CATALYSTS GRO
WTH
OB
JECTIVESPRODUCT ACTION/OBJECTIVE DATE
Reported Phase 1 Nasal Dosing in Healthy Volunteers (Safety, Tolerability and Biomarkers of Immunomodulation)
2H 2019
Com ple te d Phase 1 Oral Tria l of Foralum ab in He althy Volunte e rs 2H 2019
Re porte d Top Line Safe ty, Efficacy and Exp loratory End Point Data from Phase 2a Monothe rapy Tria l
2H 2019
Initia te Phase 2b Live r Cance r Study of Milc ic lib in Com bination with a TKI
1H 2020
Re porte d Phase 1 Oral Dosing of Foralum ab in He althy Volunte e rs (Safe ty, Tole rab ility and Biom arke rs of Anti- inflam m ation)
1H 2020
Initia te Phase 2 in Crohn’s d ise ase and NASH with Oral Foralum ab 2H 2020
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CAPITAL STRUCTURE
Ordinary Issued Shares 136,654,516Warrants 5,086,561Options 17,134,403Convertible Loan Notes 3,512,671Fully Diluted Shares 162, 388,151
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ADS EQUIVALENT*
Ordinary Issued Shares 27,330,903Warrants 1,017,312Options 3,426,881Convertible Loan Notes 702,534Fully Diluted Shares 32,477,630
*Information prepared as of January 10, 2020. 1 ADS represents 5 ordinary shares.The company is contemplating/planning to migrate to Bermuda in the second quarter which will enable it to de-list from AIM, eliminate its ADR program and have
Bermuda common shares instead listed on Nasdaq.
An Innova tive Pla tform in Ora l and Nasa l Antib od y Ad m inis tra tion
A Dis tinc t Ap p roach for Tre a tm e nt of He p a toce llu la r Carc inom a
CONTACT USUS Headquarters
Tiziana Life Sciences Inc420 Lexington Avenue Suite 2525
New York, NY 10170
Research and Development CenterTiziana Life Sciences Inc
Pennsylvania Biotechnology Center of Bucks County3805 Old Easton RD
Doylestown, PA 18902 -8400
UK HeadquartersTiziana Life Sciences plc
55 Park LaneLondon W1K 1NAUnited Kingdom
+ 1 (267) 982 [email protected]
www.tizianalifewsciences.comTLSA: TILS: