Transcript Slide 1

Proven and Commercial
Core Technology To
Create Bio Better & Bio Superior Products
With Low Risk and Reduced Cost
Thomas Sai-Ying Ko
Chairman
Vital HealthPoint Group
Agenda
•
•
Vitapharm IP
Bio Better and Bio Superior Sublingual
Products
– Interleukin 2
•
•
–
•
7/17/2015
Anti Cancer
Anti Inflammatory
Exenatide ( Byetta®)
Corporate Objectives
– Alliance with CRO and Bio Pharmaceutical Co.
2
It’s your Choice
 Vitapharm is currently seeking global alliance opportunities with BioPharma and
CRO companies to maximize our sublingual tablet technology potential.
 Vitapharm’s technology can readily recycle patent-expired products to provide
enhanced therapeutic and market potential at lower cost and with minimal risk.
 Our technology recreates patent-expired biologic actives into patentable, stable
and more convenient Bio Better and Bio Superior sublingual tablets without any
structural changes to the basic molecule.
 More than 30 branded biologics worth $51 billion will lose patent exclusivity by
2015 ( Datamonitor, 2011 ). It is estimated to cost an average $100 million and up
to 8 years to develop a Bio Similar.
7/17/2015
3
Obstacles in Biological Commercialization
Protein Inherently Unstable
Delivery Mostly By Invasive Injection
Solution
Vitapharm
CSSR
User Friendly Sublingual Tablet
Room Temperature Stable
( Bio Better )
Advantages
• Expanded Treatment Indications
• Improved Efficacy & Reduce Toxicity
• New Patent Protection
7/17/2015
( Bio Superior )
Vitapharm CSSR Technology
Biological proteins
& peptides
7/17/2015
7/17/2015
CSSR Biocapsule
5 5
Off patent Bio active + Vitapharm CSSR
=
New Patent Bio Better & Bio Superior
7/17/2015
No change in original protein
6
Global market for biological drugs
= US$ 80.56 Billion in 2008
All Injections
www.pipelinereview.com
•
•
•
•
•
•
Anti inflammatory vaccines = US$16.36 billion
Anti cancer vaccines = US$15.59 billion
IFN = US$7.95 billion.
EPO = US$10 billion.
G-CSF = US$5.18billion
HGH = US$2.68 billion
Ref – Special Edition 1/2009 top 20 Biologics - 2008 Sales of Antibodies & Proteins
7/17/2015
7
Vitapharm China Projects
IL2
Calcitonin
Thymosine
EPO
Vitapharm
CSSR
Technology
Exenatide
G-CSF
IFN
HGH
7/17/2015
8
Successful Sublingual Delivery
of Interferon  For HBV & HCV
7/17/2015 7/17/2015
9
9
Vitapharm Bio Better
Vitapharm
CSSR
Technology
IL2
+
Anti inflammation
7/17/2015
+
+
EPO
G-CSF
Beijing
Four Rings
BeijingPharma
Four Rings
Bio-Pharma
Injections
IL2
Cancer
Vitapharm owns 45% equity of
Beijing Four Rings Pharma
10
Tom Ko intellectual property
Patent applied for
•
•
•
•
IL2 anti cancer patent
IL2 anti inflammatory patent
IL2 anti fungal patent
Sublingual Slow Release Drug
Delivery (CSSR) Patent
7/17/2015
11
Agenda
–Interleukin 2
•Anti Cancer
• Anti inflammatory
7/17/2015
12
The Cancer Market
Estimated Cancer Incidence, Mortality and Prevalence in
China and the World in 2002
Cancer Site
Incidence
Lung
Global
Mortality
Prevalence
Incidence
China
Mortality
Prevalence
1,352,132
1,178,918
543,184
396,368
340,360
127,053
Stomach
933,937
700,349
468,503
392,938
308,351
176,015
Liver
626,162
598,321
160,327
345,844
321,851
65,495
Oesophagus
462,117
385,892
175,949
253,752
200,092
89,619
1,151,298
410,712
1,060,042
126,227
36,630
107,198
679,023
221,002
604,506
10,125
5,919
6,112
6,119,944
3,228,693
3,868,991
665,369
387,847
388,225
11,324,613
6,723,887
6,881,502
2,190,623
1,601,050
959,717
Breast
Prostate
Other
TOTAL
7/17/2015
13
Vitapharm Bio Better
Vitapharm
CSSR
technology
IL2 Injection is indicted for kidney
Cancer and melanoma only
New indication
+
Liver
IL2
Cancer
New indication Stomach
7/17/2015
Renal
Melanoma
14
Summary of ( CSSR IL2 ) Animal Studies
(liver, kidney, stomach, lung and skin tumor )
N= 660
Cancer Type
% of Tumor
Size Reduction
IL2 injection
100 IU / dose
% of Tumor
Size Reduction
CSSR IL2 sublingual
100 IU / dose
Liver
Renal
Stomach
Lung
Melanoma
37% 35%
33%
61%
46%
*
*
55% 45%
*
55%
46%
**
71%
Sublingual CSSR IL2 is more effective than IL2 injection in supression of tumor weight.
Sublingual delivered CSSR IL2 has no obvious toxic side effects
7/17/2015
* p<0.05 ** p <0.01
15
Poster Number: 125
The Antineoplastic Activities of a Novel Oral Formulation of Interleukin-2 (IL-2)
Cytokine Sublingual Delivery System
(CSDS)
Sen Zhang1, Thomas Sai-Ying Ko2, Ricky Runjiang Qu2, Xiaoguang Chen1, Mark Sullivan2, 3
20th
20 Kingsley Close Rowville
Melbourne VIC Australia
3178
Tel: +61 3 97641744
Fax: +61 3 97641900
1 Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing, China
2 Kambridge Life Sciences, Melbourne, Australia
3 Medicines Development Limited, Melbourne, Australia
EORTC/NCI/AACR Symposium, Geneva,
Switzerland, 21-24, October, 2008
INTRODUCTION
Interleukin2 has been proven to be effective in
treatment of metastatic renal cell carcinoma,
metastatic melanoma and other cancers. However, IL2
administered by injection has significant side effects. A
novel oral (mucosal) formulation for cytokine delivery
is being developed for human administration: the
tumour growth inhibition efficacy of oral mucosally
(muc) administrated recombinant human (rh) IL-2 in
mice implanted with melanoma B16, murine renal
cancer RENCA, gastric cancer or H22 liver cancer
MATERIALS AND METHODS
was evaluated.
►Animal Tumor Models
www.kambridgelifescience.com.au
Tom Ko: [email protected]
► In Vivo Proteins or Peptides Dissolve and
Release
► Experimental Endpoint
• Body weights and extracted tumor weights recorded after
sacrifice
Weight of tumor control group – weight of tumor treatment group
• Inhibition
Rate calculated as the following:
Tumor
reduction % =---------------------------------------------------------------------------------
Fig. 3. Growth inhibition of murine kidney ( renal ) cancer after treatment by
rhIL-2. IR of 10IU and 100IU muc rhIL-2 were 40.9**% and 47.7**%, respectively.
IR of 100IU rhIL-2 sc was 32.3**%.
Weight of tumor in control group
RESULTS
Tumour Model
Cell Line
Animal
Species
Animal
Gender
Animal
Number
Animal
weight
Liver Cancer
H22 liver cancer
Kunming
female
10/group
18-22g
Skin Cancer
B16 melanoma
C57BL/6
male
10/group
18-22g
Kidney Cancer
Murine renal
cancer RENCA
C57BL/6
male
10/group
18-22g
Stomach
Cancer
MFC
C57BL/6
male
10/group
18-22g
► Antineoplastic Treatment Groups
•No treatment (Control)
•Isotonic Saline (Placebo)
•Subcutaneous injection rhIL-2 (100IU)
•Oral mucosal rhIL-2 (1, 10, 100 or 500IU)
► Microencapsulation of Proteins/Peptides into Tablets by CSDS
Significant tumour growth inhibition of muc rhIL-2 occurred in
a dose dependent manner (plateau between 10 and 100IU) and
was similar to sc rhIL-2 for all 4 cancer models. There was no
evidence of toxicity in any animal.
Fig. 4. Growth inhibition of murine stomach (gastric) cancer after treatment by
rhIL-2. IR of 10IU and 100IU muc rhIL-2 were 27.7**% and 54.5**%,respectively.
IR of 100IU rhIL-2 sc was 32.7**%.
All the above experiments were repeated once (results not
shown).
Conclusion
All the above results show muc rhIL-2 :
Fig. 1. Growth inhibition of murine liver cancer H22 after treatment by rhIL-2. IR
was 45.2**% for 10IU muc rhIL-2, 59.5**% for 100IU muc rhIL-2 while 100IU sc rhIL2 IR was 42.8**%.
results in significant growth inhibition of liver, renal,
melanoma and gastric cancer in the murine model
well tolerated and no side effects were observed
ADVANTAGE OF CSDS TECHNOLOGY
Proteins or Peptides
CSDS Biocapsule
User friendly dosage from
Replace freeze dry technology
Improved efficacy
Lower production cost
Fig.2. Growth inhibition of murine skin cancer (Melanoma B16) after
treatment by rhIL-2. IR was 10IU muc rhIL-2 was 44.4**% and 100IU muc rhIL2 was 67.0**%. 100IU rhIL-2 sc IR was 34.0**%.
Extended product life cycle
Expanded production cost
Prolonged patent protection
Melbourne Australia
CSSR IL2 Sublingual Tablets
7/17/2015
17
Agenda
–Interleukin 2
• Anti Cancer
•Anti Inflammatory
7/17/2015
18
Global Anti-Inflammatory Market
$35.5 billion
BBC Research : Therapeutics for Inflammatory Diseases: Current Challenges and Future Market Report Code: PHM048A
Rheumatoid arthritis
( RA) $12.25 billion
7/17/2015
19
Vitapharm Bio Superior
IL2 Sublingual Tablets as Anti inflammatory
Vitapharm
CSSR
Technology
IL2
Sublingual
Tab
7/17/2015
Sinusitis
Anti inflammatory
Rheumatoid
Arthritis
Psoriasis
20
Sublingual CSSR IL2
Rheumatoid Arthritis Animal Study
Swelling Day 23
N=50
Dose given twice daily
Swelling Index
6
**
5
**
**
**P<0.01 cf control
**
4
3
2
1
0
1
2
Control
No treatment
Sublingual
4000IU/Kg Bwt
3
Sublingual
12000IU/Kg Bwt
4
Injection
4000IU/Kg Bwt
5
Injection
16000IU/Kg Bwt
No toxicity observed in any treatment group.
IL2 injection or IL2 sublingual significantly reduce swelling and RA effects ** P>0.01
21
Sublingual CSSR IL2
Rheumatoid Arthritis Animal Study
RA Index Day 23
N=50
Dose given twice daily
6
5.5
**
RA Index
5
**
**
**P<0.01
4.5
**
4
3.5
3
2.5
2
1
7/17/2015
Control
No treatment
2
Sublingual
4000IU/Kg Bwt
3
Sublingual
12000IU/Kg Bwt
4
Injection
4000IU/Kg Bwt
5
Injection
16000IU/Kg Bwt
No toxicity observed in any treatment group. All IL2 treatment cf RA model group p<0.01 day 23
22
Sublingual IL2 provides earlier relief than injection. Higher dose provides best result on day 23
IL2 RA Experiment Markers
IL1β(pg/ml) ✔
*
IL-6 (pg/ml) ✔ *
TNF-α(pg/ml) ✔
*
CD4+CD25+:TReg ✔
* P<0.05 cf RA model
7/17/2015
*
23
IL2 as anti inflammatory
Global Anti-Inflammatory Market
For Rheumatoid Arthritis
•
Traditional chemical and steroid-based anti inflammatory drugs relieve
pain only and do not treat the cause of the disease.
•
They all have major side effects ( e.g. stomach bleeding & ulcers ).
•
Receptor based biological treatment slow down the disease : tiw
•
Market for receptor based treatment was $9.45 billion in last 12 months.
•
Sublingual IL2 Tablets are a new method to treat the cause of the
disease by eliminating the self reactive T cells.
•
Sublingual IL2 Tablet is ideal for Rheumatoid Arthritis ( RA) , Sinusitis,
Prostate inflammation and other chronic inflammatory diseases.
7/17/2015
24
Agenda
Diabetic Market
7/17/2015
25
Disadvantage of “Best” Drug
Byetta® ( Exenatide)
7/17/2015
26
Exenatide Sublingual Tablet
Exenatide
CSDS Biocapsule
39 amino-acid peptide
Formula: C184H282N50O60S
Molec Mass: 4186.6
7/17/2015
27
Da
y1
Da
y2
Da
y3
Da
y4
Da
y5
Da
y6
Da
y7
Da
y8
Da
y9
Da
y1
0
Da
y1
1
Da
y1
2
Da
y1
3
Da
y1
4
Da
y1
5
Da
y1
6
fasting plasma glucose level(mmol)
Fasting Plasma Glucose
Human patient data
14
13
7/17/2015
Metformin
Oral Exenatide
12
11
10
9
8
7
6
5
28
Plasma Glucose 2h after meal
Human patent data
16.00
Metformin
Oral Exenatide
15.00
Plasma Glucose 2h after dinner (mmol)
14.00
13.00
12.00
11.00
10.00
9.00
8.00
7.00
6.00
5.00
Day1
Day2
Day3
Day4
Day5
Day6
Day7
Day8
Day9 Day10 Day11
Contact us
Vitapharm Technology Development Co. Ltd.
Attention - Thomas S. Ko
Chairman & Group Chief Scientist - Vital HealthPoint Group
E mail : [email protected]
[email protected]
Mailing address:
Suite 868, Poly Plaza Office Building. 14 Dongzhimen, NanDaiJie, Beijing, P.R. China.
100027. Tel: +8610- 65008667 Fax: +8610-65084084
Office: Four Ring Pharma Building, 5 Jianan Rd., BDA, Beijing, P. R. China.
7/17/2015
30