TLSA: January 2020 - Tiziana Life Sciences
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TLSA : TILS:
An Innovative Platform in Oral and
Nasal Antibody Administration
A Novel Approach for Treatment
of Hepatocellular Carcinoma
January 2020
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2
EXECUTIVE TEAM
Kunwar Shailubhai PhD, MBA Tiziano Lazzaretti Gabriele Cerrone
CEO & CSO Chief Financial Officer Executive Chairman
Co-founder , EVP & CSO of Synergy Previously Group Finance Director at Prove n track re cord & e xp e rie nce in
Pharmaceuticals, NASDAQ: SGYP Pharmentis –Teva Ratiopharm spin off financing b iote chnolog y com p anie s
The pioneer of GC-C agonist Executive Director at Alliance Boots, Se rve d as chairm an of 2 b iote ch
technology Snia, Accenture and FIAT Group com p anie s with m arke t cap ove r $ 2Bn
Inventor of TRULANCE® approved for MBA, Bocconi University, Milan Inhib ite x sale $ 2.5Bn
Chronic constipation and IBS -C Corporate Finance, London Business Syne rg y / Trovag e ne / Ge nsig nia /
VP, Callisto Pharmaceuticals School. BSc Accounting and Finance Rasna / Contravir / Sig a Te chnolog ie s
Group Leader, Monsanto Co. MBA, Ste rn School of Busine ss, NY,
USA
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
3
SCIENTIFIC ADVISORY COMMITTEE
Howard Weiner, MD Angelo Sangiovanni , MD
Professor of Neurology at Harvard Med
Adjunct Professor of Gastroenterology at the University of Milan
Director and Founder of the Partners MS Center and Co -Director
of the Ann Romney Center for Neurologic Diseases Leader in liver disease and gastroenterology
Pioneered investigation of the mucosal immune system for the Awarded Best Scientific Publication in clinical Hepatology in Italy
treatment of autoimmune and other diseases
Kevin Herold, MD
Professor of Immunobiology and Medicine and Deputy Director, Fabio Piscaglia , MD
Yale Center for Clinical Investigation
Director of the Yale Diabetes Center and Director of the TrialNet Associate Professor, Medical and Surgical Sciences at the
Center at Yale University of Bologna
Expert in autoimmune diseases and anti -CD3 monoclonal Leader in liver diseases and transplantation
antibody therapies
2017 Winner of a National Institute of Health (NIH) of United
States of America grant
Arun Sanyal MD
Charles Caravati Distinguished Professor and Chair, Division of Erica Villa, MD
Gastroenterology, Hepatology and Nutrition at Virginia
Commonwealth University School of Medicine Professor and Chief GI Unit
Leader in the field of liver diseases Chairman of the Department of Internal Medicine
Universitaria di Modena, Policlinico , Modena, Italy
Leader in Clinical Hepatology and Translational Medicine
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
INVESTMENT HIGHLIGHTS
Innovative platform technology for oral and nasal formulations can transform the
administration of Monoclonal Antibodies (‘mAbs’)
Nasal Trial: Phase 2 starting shortly.
Two de -risked assets in clinical evaluation that target the root causes of Phase 1 trial completed
autoimmune/inflammatory diseases and cancer
Data - August 2019
Milciclib has received ‘Orphan Drug Designation’ in US and EU for treatment
Oral Trial: FDA approved IND. Phase
of thymic carcinoma/thymoma (TC/T) 1 oral trial to begin shortly
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
Orphan Drug Designation
255 patents approved and 30 pending
Met primary and secondary
Covers composition of matter, process and disease indications endpoints in 2 separate Phase 2
Oral formulation technology applicable to other mAbs therapeutics trials in TC/T.
Experienced and successful biotech management team Phase 2a in sorafenib -resistant
patients completed
A leverageable biotechnology platform for use in additional therapeutics
Well -tolerated topline data
reported July 2019
5 5
Market potential for our technologies BIG PHARMA INTEREST
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 Oral:
patients with progressive multiple sclerosis will commence shortly
• Crohn’s Disease
Oral administration for digestive diseases (Crohn’s Disease and NASH) • Celiac Disease
Our IND was approved by the FDA. A phase 1 trial in healthy volunteers will be completed by 4Q • NASH
2019. Nasal:
• Pro-MS
Milciclib • Neurodegenerative
Hepatocellular carcinoma: Clinical data from a recently completed phase 2a
in sorafenib -resistant advanced cases of HCC suggests that milciclib • Autoimmune
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
6
A REVOLUTIONARY PLATFORM
SWITCH ANTIBODY ADMINSTRATION FROM INTRAVENOUS PATIENT &
PROVIDER BENEFITS
TO ORAL AND NASAL ROUTES
Ease of use
Superior compliance
TODAY’S ANTIBODY ADMINISTRATION Topical action in gut
OPTIONS ARE MOSTLY I.V. Minimized toxicity
Take home Rx
No costly infusion
Antibodies (mAbs)
reformulated for oral
administration THE LARGE MARKET
OPPORTUNITY
platform enables…
Ma rke t op p ortunity for
m Ab the ra p e utic s is
Costly Infusion Center greater than
Poor patient compliance
Higher toxicity
86
Systemic treatment to affect
whole body $
Infusion related side effects
BILLIO N
Antibodies (mAbs)
reformulated for nasal
administration
ROUTE OF ORAL OR NASAL
ADMINISTRATION DEPENDS ON DISEASES
7 7
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
HEALTHY LIVER NON-ALCOHOLIC FATTY LIVER DISEASE NAFLD NON-ALCOHOLIC STEATOHEPATITIS NASH CIRRHOSIS HEPATOCELLULAR CANCER
25-30% of Population 3- 5% of Population 20% Over 10 Years
X
Generally Asymptomatic Reversible Reversible Irreversible Liver Damage
Immune cells HBV/
infiltration HCV
Foralumab (Anti -CD3) for NASH and Crohn’s Disease Milciclib for Liver Cancer
NASH global market ~ $35 B/year HCC ($ 1.5B / ye ar b y 20 22): Me d ic al ne e d to have a safe r and
Crohn’s Disease market: $10B /year by 2025 e ffe c tive d rug with hig he r re s p ond e r rate s
Oral/nasal delivery is a novel, completely differentiated approach Milc ic lib : An oral d rug with c om p le te ly d iffe re ntiate d MOA with
Strong IP on the ‘Revolutionary’ approach with significant market long -te rm safe ty
potential Sup e rior s afe ty p rofile
8
DEVELOPMENT PIPELINE BEGINNING
PHASE 2
Nasal Trial
LEAD
DISCOVERY PRE-CLINICAL IND PHASE 1 PHASE 2 PHASE 3 Pro-MS
OPTIMIZATION
Intranasal formulation for Neurodegenerative disease
Nasal Administration
BEGINNING
PHASE 2
Oral
Enteric coated capsules *
Crohn’s
Oral Administration
Crohn’s disease
I.V. Administration – Conducted by Novimmune
TWO PHASE 2
TRIALS
COMPLETED
TC / T Oral
Thymic Carcinoma / Thymoma
Orphan Drug Designation in U.S. and E.U
Milciclib + Gemcitabine in refractory solid tumors
Potential Adjuvant Treatment
HCC monotherapy PHASE 2a
Sorafenib Resistant Patient COMPLETED
HCC Oral
HCC combination with a Tyrosine Kinase Inhibitor Monotherapy
Potentially for synergism
9 9
NASAL ADMINISTRATION
PLATFORM
TECHOLOGIES Phase 1 trial completed for related
neurodegenerative diseases such as
Progressive Multiple Sclerosis (Pro -MS) .
Phase 2 trial in Pro-MS to start shortly
A BIOTECHNOLOGY PLATFORM ENABLING
ORAL AND NASAL
ADMINISTRATION OF FORALUMAB AND
ORAL ADMINISTRATION
OTHER MONOCLONAL ANTIBODIES
FDA has allowed initiation of clinical
studies with enteric coated capsule for
oral administration with Foralumab.
Phase 1 completed December, 2019.
10
10THE ONLY FULLY HUMAN ANTI-CD3 MAB
CD3-SPECIFIC MONOCLONAL ANTIBODIES IN CLINICAL DEVELOPMENT
OKT3 CHAGLYCD3 NUVION HOKT31(ALA- Oral and Nasal Administration
MUROMONAB OTELIXIZUMAB VISILIZUMAB ALA) TEPLIZUMAB FORALUMAB Market Opportunities
IgG2a IgG1 IgG2 IgG2 IgG1
*Agly *AA *AA *AE
Fully Mouse Chimeric & Humanized Humanized Fully Human
Humanized
Approved by the FDA for solid
organ transplantation
immuno-suppression
Tiziana’s platform of oral and nasal
mAbs administration potentially
enhances efficacy and reduces toxicity
Foralumab is unique: functionally equivalent to OKT3 with minimal immune reactions when administered IV
11HOW DOES OUR PLATFORM TECHNOLOGY WORK?
NOVEL APPROACH FOR SITE
-TARGETED IMMUNOMODULATION
Gut Lumen
PANETH CELL
M CELL
INTESTINAL
EPITHELIAL
CELLS
Intraepithelial Lamnia Propria
Lymphoid
lymphocytes follicle
Dendritic cells Mesenteric
lymph node
Treg cell
NKT cells induction
Macrophages
Site-targeted
Immunomodulation
INNATE IMMUNE SYSTEM
12ORAL AND NASAL FORMULATION PATENTS
PENDING
Nasal administration of Patent covers and other mAbs
Proof -of-concept demonstrated in ANTI - CD 3 ANTIBODY FORMULATIONS
Applicant(s): Tiziana Life Sciences PLC
animal studies Inventor(s): SHAILUBHAI,Kunwar
Phase 1 study for US Non-Provisional Patent Application
neurodegenerative diseases at No.:62/ 380,652 , filed August 29, 2016
Brigham and Women’s Hospital, PCT Application
PCT/US 2017/ 049211, filed, Aug 29, 2017
Harvard Medical School; completed
and well -tolerated up to 250 µg
Patent estate
Positive Top line data received Exclusive license for
August 2019, CSR in preparation composition of matter
Composition of matter patent for oral
formulation
In-licensed nasal delivery
technology from Brigham and Additional patent applications pending
Women’s Hospital, Harvard Medical Oral formulation technology applicable to
School other mAbs
13Foralumab Enteric Capsules Safety Study
Phase 1 Trial Conducted at Brigham and Women’s Hospital
Com p le te d De ce m b e r 20 19
Sing le Asce nd ing Dose , d oub le -b lind , p lace b o-controlle d
stud y in he althy sub je cts
Foralum ab ad m iniste re d at 1.25, 2.5 and 5.0 m g / d ose as
stab ilize d p owd e r form ulation in e nte ric-coate d cap sule s
KEY FINDINGS
1. Well -tolerated at all doses tested
2. No drug -related safety issues observed
14FINDINGS SUPPORT TIZIANA’S ORAL PLATFORM
THIRD PARTY RESEARCHERS IN PEER-REVIEW ED, CROHN’S & COLITIS 360*
Determined the immunologic effects and safety of orally delivered anti -CD3
antib od y in p atie nts with m od e rate -to-se ve re ulce rative colitis (UC)
Six sub je cts re ce ive d oral OKT3
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
* 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.
15PROOF-OF-CONCEPT IN NASH PATIENTS
ORAL TREATMENT WITH MURINE ANTI-CD3 (OKT3) EFFECTIVE IN A PHASE 2 TRIAL WITH NASH
1
STUDY DESIGN SAFETY IMMUNOLOGICAL EFFICACY BIOMARKERS
36 subjects with NASH and type II Well tolerated by all patients in all Increases in Treg markers Positive trends, some of which
diabetes groups consistent with induction of Tregs were statistically significant
Randomized, single-blinded, No systemic drug-related adverse Anti-inflammatory markers ↑ AST ↓ – liver enzyme indicating
placebo-controlled events reduced liver inflammation
9 per group, not powered for No changes in vital signs, serum CD4+CD25+LAP+ Treg cells,
statistical significance biochemistry and hematological TGFβ↑ Glucose ↓ – favorable for subjects
parameters during treatment or with type-2 diabetes
0.2, 1.0, 5.0 mg or placebo daily follow-up periods (30-days post-
for 30 days Insulin ↓ – favorable for subjects
treatment) with type-2 diabetes
Primary endpoints: safety and No changes in lymphocyte and
trends in immunomodulation CD+ cell counts
Secondary endpoint: indication or No changes in weight or BMI or
trend of efficacy through HbA1C lipid GLP-1, or CRP levels Sources: 1) Lalazar, G., Mizrahi, M.,Turgeman , I., Adar, T.,Ya’Acov, A. B.,Shabat, Y., . . . Ilan, Y. (2015). Oral Administration of
biomarkers in any of the groups
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.
Follow up: Days 0, 14, 30, 60
Hadassah Medical Center,
Jerusalem Israel
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
16FORALUMAB IS FUNCTIONALLY
EQUIVALENT TO OKT3
Oral Treatment prevents skin xenograft rejection in
mice with human immune systems
Mineko 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
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
17Anti -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-c e lls is d e m onstrate d in p re -c linic al stud ie s
Im p rove d insulin re sistanc e and g luc ose tole ranc e in Typ e 2 d iab e te s b y ind uc tion
of T re g s
Anti-CD3’s show p ote ntial in p re ve nting g raft ve rsus host d ise ase (GvHD) in
he m atop oie tic ste m c e ll transp lantation (HSCT) via ind uc tion of T re g s
Patie nts with re nal allog raft re je c tion d ose d IV with foralum ab , d e laye d g raft
re je c tion and im p rove d re nal func tion
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 Anti-CD3 antibody increases
ratio T reg:Teff ratio
18POTENTIAL TO TREAT TYPE I DIABETES
New England Journal of Medicine* provides clinical
evidence for the potential use of a humanized anti -CD3
mAb for treatment of type 1 diabetes
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
*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
19Incidence of HCC is steadily increasing in
males and females and subpopulations in US
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
20
20SMALL 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, CDK7
and 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
21CLINICAL DATA FROM MILCICLIB
PHASE 2A TRIAL IN SORAFENIB-RESISTANT HCC PATIENTS
Trial 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 & TTP
Exploratory: 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 p a tie nts c om p le te d tre a tm e nt a s p e r p rotoc ol
Nine a p p rove d for c om p a s s iona te us e . Se ve n p a tie nts c om p le te d
9, 9, 10 , 11, 13, 13 a nd 16 m onths , re s p e c tive ly.
No drug related deaths in the trial
Tre a tm e nt wa s we ll-tole ra te d
Ad ve rs e e ve nts we re m a na g e a b le
Time to progression 5.9 months out of 6 months duration of trial
Stabilized Disease (SD) 61%
Clinical Benefit Response 64%
Tw o p a t ie n t s c u rre n t ly c o n t in u in g c o m p a s s io n a t e u s e t re a t m e n t fo r 15 m o n t h s
22THYMIC CARCINOMA AND THYMOMA
UPDATES
Two Phase 2 trials with Milciclib in US, Italy and France
o Trial 0 0 6: Thym ic c arc inom a and Thym om a m ixe d p op ulation (72 p atie nts)
o Trial 0 0 7: Thym ic c arc inom a and Thym om a m ixe d p op ulation (30 p atie nts )
Rare c anc e rs with ve ry fe w c ase s: Orp han Dise ase Ind ic ations
Positive c linic al d ata
Primary endpoint (progression free survival) and secondary endpoint (overall survival) met in
both trials separately
Thym ic c arc inom a is an ag g re ssive m e tastatic c anc e r and it has no ap p rove d the rap y
Milc ic lib as a sing le ag e nt m e t p rim ary as we ll as se c ond ary e nd p oints in thym ic c arc inom a in
b oth trials
Under compassionate use, few patients continued the treatment for over five years
Se e king g uid anc e from FDA/ EMA re g ard ing c ond itional m arke ting ap p roval
23MILCICLIB OVERCOMES DRUG RESISTANCE
PATIENTS RAPIDLY ACQUIRE RESISTANCE TOWARDS CHEMOTHERAPIES
Phase 1 Dose-Escalation Study of Milciclib in
Combination with Gemcitabine in Patients with
KEY FINDINGS Refractory Solid Tumors*
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
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
24INTELLECTUAL PROPERTY PORTFOLIO
FAMILY SUBJ ECT PRIORITY STATUS EXPIRES J URISDICTION
Australia, Canada, China, Hong Kong, Israel, Japan, Mexico, Norway, Singapore, South
Africa, Ukraine, Armenia, Austria, Azerbaijan, Belgium, Belarus, Switzerland, Germany,
Methods of Use (Autoimmune or
Inflammatory diseases and disorders) 2004 Issued 2025 Denmark, Spain, France, United Kingdom, Ireland, Italy, Kyrgyzstan, Kazakhstan,
Luxembourg, Moldova, Netherlands, Portugal, Russian Federation, Sweden, Tajikistan,
Turkmenistan,
US, Armenia, Australia, Austria, Azerbaijan, Belarus, Canada, China, Denmark, France,
Germany, Hong Kong, India, Israel, Italy, Japan, Kazakhstan, Kyrgyzstan, Mexico, Moldova,
Issued/
Composition and methods of use 2004 Pending
2025 Netherlands, Norway, Republic of Korea, Russian Federation, Singapore, South Africa, Spain,
Switzerland, Tajikistan, Turkmenistan, and Ukraine Pending: Brazil, Japan (divisional),
TZLS-401 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 PCT
Methods of Use
(gastrointestinal/autoimmune/inflammatory) 2018 Pending 2039 Provisional
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,
Composition of matter, methods of Issued/
use, process of manufacturing 2003 Pending
2024 Montenegro, New Zealand, Nicaragua, Norway, Pakistan, Philippines, Serbia, Singapore,
South Africa, Sri Lanka, Taiwan, Thailand, Trinidad & Tobago, Tunisia, Ukraine, Uzbekistan,
Venezuela, Vietnam
T Pending: Several in US and other countries
Methods of use (multiple indications) 2008; 2009 Issued 2029; 2030 US, EU, China, Hong Kong, Japan
TZLS-201 Methods of use (combination
therapies with cytotoxics) 2008; 2009 Issued 2029; 2030 US, EU, China, Hong Kong, Japan
Compositions of related entities, formulations
and methods of treatment 2009 Issued 2030 US, EU, China, Hong Kong, Japan
Methods 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 2017 Pending 2038 US, PCT
treatment of cancer
Anti IL-6/IL-6R US, Austria, Australia, Belgium, Canada, China, Denmark, France, Germany, Ireland, Italy,
Composition of Matter and Issued/
Antibody Methods of use 2009 Pending
2029 Japan Luxembourg, Mexico, Netherland, Spain, Sweden, Switzerland and UK . Pending: US
(divisional), Japan (divisional), India
TZLS-501
25CATALYSTS
GROWTH OBJECTIVES
PRODUCT ACTION/OBJECTIVE DATE
Reported Phase 1 Nasal Dosing in Healthy Volunteers (Safety, 2H 2019
Tolerability and Biomarkers of Immunomodulation)
Com p le te d Pha s e 1 Ora l Tria l of Fora lum a b in He a lthy Volunte e rs 2H 2019
Re p orte d Top Line Sa fe ty, Effic a c y a nd Exp lora tory End Point Da ta 2H 2019
from Pha s e 2a Monothe ra p y Tria l
Initia te Pha s e 2b Live r Ca nc e r Stud y of Milc ic lib in Com b ina tion 1H 2020
with a TKI
Re p orte d Pha s e 1 Ora l Dos ing of Fora lum a b in He a lthy Volunte e rs 1H 2020
(Sa fe ty, Tole ra b ility a nd Biom a rke rs of Anti-infla m m a tion)
Initia te Pha s e 2 in Crohn’s d is e a s e a nd NASH with Ora l Fora lum a b 2H 2020
26CAPITAL STRUCTURE
Ordinary Issued Shares 136,654,516
Warrants 5,086,561
Options 17,134,403
Convertible Loan Notes 3,512,671
Fully Diluted Shares 162, 388,151
ADS EQUIVALENT*
Ordinary Issued Shares 27,330,903
Warrants 1,017,312
Options 3,426,881
Convertible Loan Notes 702,534
Fully 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. 27CONTACT US
US Headquarters
Tiziana Life Sciences Inc
420 Lexington Avenue Suite 2525
An Innova tive Pla tform in Ora l a nd New York, NY 10170
Na s a l Antib od y Ad m inis tra tion
Research and Development Center
Tiziana Life Sciences Inc
A Dis tinc t Ap p roa c h for Tre a tm e nt Pennsylvania Biotechnology Center of Bucks County
3805 Old Easton RD
of He p a toc e llu la r Ca rc inom a Doylestown, PA 18902 -8400
UK Headquarters
Tiziana Life Sciences plc
55 Park Lane
London W1K 1NA
United Kingdom
+ 1 (267) 982 9785
TLSA:
mpreiss@tizianalifesciences.com
TILS : www.tizianalifewsciences.comYou can also read
