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

• Anti Cancer• Anti Inflammatory

– Exenatide ( Byetta®®)• Corporate Objectives

– Alliance with CRO and Bio Pharmaceutical Co.

04/19/23 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.

04/19/23 3

Obstacles in Biological Commercialization

04/19/23

Solution

VitapharmVitapharmCSSRCSSR

User Friendly Sublingual TabletRoom Temperature Stable

( Bio Better )

Protein Inherently UnstableDelivery Mostly By Invasive Injection

• Expanded Treatment Indications • Improved Efficacy & Reduce Toxicity

• New Patent Protection

( Bio Superior )

Advantages

04/19/23 5

Vitapharm CSSR Technology

04/19/23 55

Biological proteins& peptides

CSSR Biocapsule

Off patent Bio active + Vitapharm CSSR =

New Patent Bio Better & Bio Superior

04/19/23 6No change in original protein

Global market for biological drugs = US$ 80.56 Billion in 2008

All Injections

www.pipelinereview.com

04/19/23 7

• 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

Vitapharm China Projects

04/19/23 8

IL2

EPO

G-CSF

HGH

Exenatide

Thymosine

IFN

Calcitonin

VitapharmCSSR

Technology

04/19/23 904/19/23 9

Successful Sublingual Delivery of Interferon For

HBV & HCV

Vitapharm Bio Better

04/19/23 10

VitapharmCSSR

Technology

Beijing Four RingsPharma

+Cancer

+

+Beijing Four Rings

Bio-PharmaInjections

Anti inflammation

IL2IL2

EPO

G-CSF

Vitapharm owns 45% equity of

Beijing Four Rings Pharma

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

04/19/23 11

Agenda

–Interleukin 2•Anti Cancer

• Anti inflammatory

04/19/23 12

The Cancer Market

04/19/23 13

Estimated Cancer Incidence, Mortality and Prevalence in China and the World in 2002

Global China Cancer Site Incidence Mortality Prevalence Incidence Mortality Prevalence

Lung 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

Breast 1,151,298 410,712 1,060,042 126,227 36,630 107,198

Prostate 679,023 221,002 604,506 10,125 5,919 6,112

Other 6,119,944 3,228,693 3,868,991 665,369 387,847 388,225

TOTAL

11,324,613 6,723,887 6,881,502 2,190,623 1,601,050 959,717

Vitapharm Bio Better

04/19/23 14

+Cancer

Liver

Renal

Stomach Melanoma

IL2

VitapharmCSSR

technology

IL2 Injection is indicted for kidney Cancer and melanoma

only

New indication

New indication

Summary of ( CSSR IL2 ) Animal Studies (liver, kidney, stomach, lung and skin tumor )

Cancer Type Liver Renal Stomach

Lung Melanoma

% of TumorSize Reduction

IL2 injection100 IU / dose

37% 35% 33% 61% 46%

% of TumorSize Reduction

CSSR IL2 sublingual

100 IU / dose

*55%

*45%

*55% 46%

**71%

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Sublingual CSSR IL2 is more effective than IL2 injection in supression of tumor weight.Sublingual delivered CSSR IL2 has no obvious toxic side effects

N= 660

* p<0.05 ** p <0.01

The Antineoplastic Activities of a Novel Oral Formulation of Interleukin-2 (IL-2)

Sen Zhang1, Thomas Sai-Ying Ko2, Ricky Runjiang Qu2, Xiaoguang Chen1, Mark Sullivan2, 3

1 Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing, China2 Kambridge Life Sciences, Melbourne, Australia

3 Medicines Development Limited, Melbourne, Australia

INTRODUCTION

MATERIALS AND METHODS

RESULTS

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 rhIL-2 IR was 42.8**%.

Conclusion

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 rhIL-2 was 67.0**%. 100IU rhIL-2 sc IR was 34.0**%.

All the above results show muc rhIL-2 :

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

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**%.

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 was evaluated.

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.

20 Kingsley Close RowvilleMelbourne VIC Australia

3178Tel: +61 3 97641744Fax: +61 3 97641900

www.kambridgelifescience.com.auTom Ko: tomkat888@gmail.com

Poster Number: 125

Cytokine Sublingual Delivery System Cytokine Sublingual Delivery System (CSDS)(CSDS)

20th EORTC/NCI/AACR Symposium, Geneva, Switzerland, 21-24, October, 2008

Tumour Model Cell LineAnimal 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 CancerMurine renal

cancer RENCAC57BL/6 male 10/group 18-22g

Stomach Cancer

MFC C57BL/6 male 10/group 18-22g

►Animal Tumor ModelsAnimal Tumor Models

►► Antineoplastic Antineoplastic Treatment GroupsTreatment Groups•No treatment (Control)

•Isotonic Saline (Placebo)•Subcutaneous injection rhIL-2 (100IU)

•Oral mucosal rhIL-2 (1, 10, 100 or 500IU)

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**%.

Proteins or PeptidesProteins or Peptides CSDS BiocapsuleCSDS Biocapsule

►► In Vivo Proteins or Peptides Dissolve and Release

►► Microencapsulation of Proteins/Peptides into Tablets by CSDSMicroencapsulation of Proteins/Peptides into Tablets by CSDS

►► Experimental Endpoint• Body weights and extracted tumor weights recorded after

sacrifice• Inhibition Rate calculated as the following:Tumor reduction % =

Weight of tumor control group – weight of tumor treatment group---------------------------------------------------------------------------------

Weight of tumor in control group

All the above experiments were repeated once (results not shown).

User friendly dosage from

Replace freeze dry technology

Improved efficacy

Lower production cost

Extended product life cycle

Expanded production cost

Prolonged patent protection

Melbourne Australia

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CSSR IL2 Sublingual Tablets

Agenda

–Interleukin 2• Anti Cancer

•Anti Inflammatory

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Global Anti-Inflammatory Market

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$35.5 billion BBC Research : Therapeutics for Inflammatory Diseases: Current Challenges and Future Market Report

Code: PHM048A

Rheumatoid arthritis

( RA) $12.25 billion

Vitapharm Bio Superior IL2 Sublingual Tablets as Anti inflammatory

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Anti inflammatoryRheumatoid

Arthritis

Sinusitis

Psoriasis

IL2Sublingual

Tab

VitapharmCSSR

Technology

No toxicity observed in any treatment group.

21

Sublingual CSSR IL2Rheumatoid Arthritis Animal Study

Swelling Day 23

Sublingual4000IU/Kg Bwt

Sublingual12000IU/Kg Bwt

Injection4000IU/Kg Bwt

Injection16000IU/Kg Bwt

IL2 injection or IL2 sublingual significantly reduce swelling and RA effects ** P>0.01

ControlNo treatment

Sw

elli

ng Index

N=50Dose given twice daily

**** **

**

**P<0.01 cf control

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22

Sublingual CSSR IL2 Rheumatoid Arthritis Animal

StudyRA Index Day 23

RA

In

dex

Sublingual4000IU/Kg Bwt

Sublingual12000IU/Kg Bwt

Injection4000IU/Kg Bwt

Injection16000IU/Kg Bwt

No toxicity observed in any treatment group. All IL2 treatment cf RA model group p<0.01 day 23

Sublingual IL2 provides earlier relief than injection. Higher dose provides best result on day 23

ControlNo treatment

N=50Dose given twice daily

**** **

**

**P<0.01

IL2 RA Experiment Markers

04/19/2323 

IL1β(pg/ml)

IL-6 (pg/ml)

TNF-α(pg/ml)

CD4+CD25+:TReg

✔

✔

✔

✔

* P<0.05 cf RA model

*

*

*

*

04/19/2324

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.

Agenda

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Diabetic Market

Disadvantage of Disadvantage of ““BestBest”” Drug Drug ByettaByetta®® ( ( Exenatide)

04/19/23 26

04/19/23 2727

Exenatide Sublingual Tablet

Exenatide CSDS Biocapsule

39 amino-acid peptideFormula:

C184H282N50O60S 

Molec Mass: 4186.6

Fasting Plasma GlucoseHuman patient data

04/19/23 28

5

6

7

8

9

10

11

12

13

14

Day1Day2

Day3Day4

Day5Day6

Day7Day8

Day9

Day10

Day11

Day12

Day13

Day14

Day15

Day16

fast

ing

pla

sma

glu

cose

lev

el(m

mo

l)

Metformin

Oral Exenatide

Plasma Glucose 2h after mealHuman patent data

5.00

6.00

7.00

8.00

9.00

10.00

11.00

12.00

13.00

14.00

15.00

16.00

Day1 Day2 Day3 Day4 Day5 Day6 Day7 Day8 Day9 Day10 Day11

Pla

sma

Glu

cose

2h

aft

er d

inn

er (

mm

ol)

Metformin

Oral Exenatide

Contact us

Vitapharm Technology Development Co. Ltd.

Attention - Thomas S. KoChairman & Group Chief Scientist - Vital HealthPoint Group

E mail : tomkat888@gmail.comtko@VHP.cn

Mailing address: Suite 868, Poly Plaza Office Building. 14 Dongzhimen, NanDaiJie, Beijing, P.R. China. 100027. Tel: +8610- 65008667 Fax: +8610-65084084Office: Four Ring Pharma Building, 5 Jianan Rd., BDA, Beijing, P. R. China.

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