Immuron Ltd — AGM Information 2009

Nov 26, 2009

27 November 2009

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ASX Release

Immuron Limited ABN 80 063 114 045

Presentation to Annual General Meeting by Medical Director of Immuron Limited Professor Yaron Ilan

Corporate Details:

ASX Code: IMC OTCQX Code: IMROY (U.S.)

Directors:

Chairman:

Prof. Colin Chapman Non-Executive Directors: Prof. Roy Robins-Browne Mr. Arie Nudel Mr. Simon Sallka Dr Elane Zelcer

Attached is the presentation given at the Immuron Annual General Meeting by Professor Yaron Ilan in respect of the progress with the Immuron oral immunotherapy technology. Professor Ilan is the Medical Director of Immuron and a Medical Director of Hadassah Medical Centre in Jerusalem.

The body of evidence in animals and humans presented by Professor Ilan is the reason that Immuron believes that there is a high likelihood of success of the Immuron preparations as human therapeutics against large market targets, such as Metabolic Syndrome.

Chief Executive Officer

Dr Grant Rawlin

Significant Shareholders: Hadasit Medical Research 19.8% Alaven Consumer H’care 3.8%

Immuron has commissioned Hadassah Medical Centre to conduct human trials using its technology.

In the presentation, Professor Ilan explains how oral antibodies are sampled by the immune system to benefit the patient’s immune system against the target– in this work with a particular focus on metabolic syndrome (e.g. Fatty liver disease) and tumours.

The most advanced work, showing successful treatment of fatty liver disease in an animal model, was recently presented at the American Association for the Study of Liver Diseases meeting in Boston with great interest.

Contact Details:

Immuron Limited Level 1 39 Leveson Street North Melbourne VIC 3051 Australia

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Dr Grant Rawlin Chief Executive Officer

Tel: +61 (0)3 9018 4880 Fax: +61 (0)3 9018 4881

Website: www.immuron.com

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**Oral

Immunotherapy**

Yaron Ilan, M.D. Department of Medicine Hebrew University-Hadassah Medical Center Jerusalem, Israel

November 2009

Confidential

1

Disclosure

• I
  am
  not
  in
  a
  posi+on
  to
  discuss
  any
  commercial issues
  or
  chances
  of
  success.

• • I
  will
  discuss
  data
  related
  to
  the
  scien+fic
  studies performed
  at
  Hadassah.

• • As
  with
  any
  new
  product
  there
  is
  uncertainty
  as
  to the
  poten+al
  of
  success
  and
  no
  guarantee
  can
  be given.

2

Oral Immunotherapy

• An attractive approach to treat autoimmune, infectious, malignant and inflammatory diseases. • An active process that uses the inherent ability of the GI tract's immune system to control unwanted systemic immune responses, by inducing regulatory T cells in an antigen-specific manner.

Oral Immunotherapy

• Not associated with general immune suppression

• No side effects or toxicity

• No risks of severe infection or malignancy

• Easily tolerated by patients

• Platform for a wide range of diseases

• Oral administration, painless

• Low cost

• Rapid development cycle

**The

immune
system
of
the
bowel**

• The gut mucosal immune system is the largest lymphoid organ.

• It differentiates the antigenic signals against the high background noise of food and bacterial antigens.

• Despite constant antigenic stimulation, suppression of inflammation is the rule.

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Antigen+adjuvant
M
cell
Lamina Propria DC
NKT DC
Macrophage Perifollicular area
DC
DC
Interfollicular T cell area B cell follicule
Th2 cell Tregs Th3 cell Tr1
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Regulatory lymphocytes

• Main controllers of the immune response in inflammatory, infectious and malignant disorders.

• Regulatory T cells are defective in many infectious, inflammatory and malignant disorders in humans

• No current therapy can correct this defect.

• Oral administration of hyper-immunized colostrum can correct the defect.

Colostrum is the first milk produced by lactating mammals

• Colostrum contains

• Immunoglobulins : Represent the mother’s exposure.

– Non-immunoglobulin adjuvants that affect cell functions:

• Lactoferrin

• Alarmins

• Glycolipids

• Growth factors

• Syntenin-1

The role of dietary gangliosides on immunity and the prevention of infection. Rueda R. Br J Nutr. 2007 Oct;98 Suppl 1:S68-73 Majumdar and Ghose.. Infect Immun. 1982 Jun;36(3):962-5 Hammer et al. J Dairy Sci. 2004 Jan;87(1):106-11. Sira et al. Int Immunol. 2009 Sep;21(9):1013-23. Epub 2009 Jul 10

Oral administration of colostrum-derived antibodies

• Oral passive and active immunity

• Naturally-occurring proteins

• Derived from colostrum of cows vaccinated with disease-specific antigens

• One platform across all indications

• Same safe risk profile

• Feeding of antibodies with adjuvants induces regulatory T cells

• Addressing infectious diseases, cancers and immune-mediated diseases

8

**The

metabolic
syndrome**

• Diabetes type 2

• Fatty liver disease

• Atherosclerosis

• Hyperlipidemia

Type II Diabetes

• Affects 9% of the western world’s population.

• Is the fifth leading cause of death.

• The biomedical industry is focused on metabolic

• disease as it represents one of the greatest areas of unmet need in medicine.

• The potential market for monitoring and treating is

• estimated to exceed $70 billion in 10 years .

Non-Alcoholic Steatohepatitis (NASH)

• The most common liver disease in the western world.

• Associated with obesity, diabetes, hyperlipidemia.

• Affects 5% of the lean population, 20% of the obese

• population, and 50% of morbidly obese people. • The total U.S. market potential reaches nearly $22 billion.

Oral anti-CD3 suppresses EAE given prior to EAE induction in a dose-dependent fashion

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Indirect immune fluorescence
0 0.5 hr 1 hr 3 hr
iv 3hr
Oral
IV
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Ochi, Nature Medicine, 2006

β -Glucosylceramide

GC

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Leptin deficient ObOb mice

• Features the metabolic syndrome: Non-alcoholic steatohepatitis, diabetes, obesity, hyperlipidemia.

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GC decreases serum transaminase levels

GC decreases serum triglyceride levels

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IU

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GC improves glucose tolerance test

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Lalazar, Am. J. Pathol., 2009

GC decreases hepatic fat accumulation

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Control Ob/Ob
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GC-treated Ob/Ob

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Control GC-treated Ob/Ob Ob/Ob

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~~*~~ Margalit, J. Exp. Therap. 2006

Oral GC suppresses hepatocellular carcinoma

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Tumor growth

GC
Survival (%) Tumor volume (mm [3] )
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Zigmond, Gut, 2007

Suppression of malignant melanoma by GC

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Control GC
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Tumor weight Apoptotic cells


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The combination of antibody + adjuvant is synergisitc

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Passive
Immunity
(Topical)
using
bovine
an+bodies
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Ac+ve
immunity
(Cellular)
triggered
by
oral
bioac+ves
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Address
major
medical
targets
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20

Passive Immunity (Topical)
using bovine an+bodies Address major medical Ac+ve immunity targets

Active naturally-derived and safe oral immunotherapy

Ac+ve immunity (Cellular) triggered
by oral
bioac+ves

21

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Target organs
•
Pancreas
•
Adipose tissue
•
Disease-specific antibody Liver
+ • Brain
Colostrum adjuvants
Presented in the bowel
Induction of regulatory cells
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Colostrum enriched with anti-insulin antibodies corrects diabetes in mice

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Following 4 weeks of oral therapy

Colostrum enriched with anti-insulin antibodies alleviates insulin resistance in mice

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Following 4 weeks of oral therapy

Colostrum enriched with anti-insulin antibodies alleviates liver damage in mice with NASH

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Following 4 weeks of oral therapy

Colostrum enriched with anti-insulin antibodies decrease serum lipids in mice with hyperlipidemia

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Following 4 weeks of oral therapy

Colostrum enriched with anti-insulin antibodies decrease the fat in the liver in mice

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Following 4 weeks of oral therapy

Proposed mechanism

• Colostrum enriched with anti-insulin antibodies acts in three major sites :

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The liver
The adipose tissue
BC
The
BC – Bovine
colostrum
gut
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**Preliminary

results**

• The
  use
  of
  colostrum
  enriched
  with
  an+ influenza
  an+bodies

• • The
  use
  of
  colostrum
  enriched
  with
  an+ hepa++s
  B
  virus
  an+bodies

29

Oral administration of colostrum derived anti-influenza antibodies with adjuvnats improve the anti-influenza immune response Oral antibody + colostrum derived adjuvants

Passive immunity Active immunity Decrease of suppressor cells Augment of anti-influenza cellular immunity

Advantages: Not viral strain specific One treatment for all influenza strains (?)

Colostrum enriched with anti influenza antibodies increase the anti influenza cellular immunity

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Colostrum enriched with anti influenza antibodies decrease suppressor cells

CD4+Foxp3+ CD4+CD25+ CD25 CD4 2.69 0.54 0.58 15.58 A1 1.96 0.42 0.47 15.2 A2 3.31 0.98 1.05 21.23 A3 1.7 1.02 1.06 19.49 A4	CD4	CD25	CD4+CD25+	CD4+CD25+	CD4+CD25+	CD4+CD25+	CD4+CD25+	CD4+Foxp3+	CD4+Foxp3+	CD4+Foxp3+	CD4+Foxp3+	CD4+Foxp3+
				.					.
AVG	17.88	0.79		0.74					2.42
0.73 0.30 0.31 2.96 STDev 0.48 0.44 0.54 3.88 B1 0.55 0.26 0.26 2.91 B2 0.61 0.37 0.47 2.24 B3 2.51 0.82 0.91 19.59 B4
					.					.
AVG	7.16	0.55			0.47					1.04
0.98 0.24 0.27 8.32 STDev

Colostrum enriched with anti heaptitis antibodies suppresses the growth of liver cancer in mice

Control Treated 10 µ g Treated 1 µ g

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Phase I clinical trial Oral administration of OKT3+GC Healthy male volunteers (3 per group) were orally administered mouse anti-human OKT3 at three doses: 0.2, 1.0, 5.0 mg/feeding.

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Feeding
0 1 2 3 4 5 6 7 8 9 10 30
Days
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Blood drawing

Ilan Y. J Clin Immunology, 2009

Effect of oral OKT3 on IgG repertoire

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Pt 1 Pt 2 Pt 3
0 5 10 30 0 5 10 30 0 5 10 30
Complement C3
Smith antigen
PPD
MMP3
Glutamine Synthetase
LIF
Neurofilament 200 kDa
5.0 T. gondii p30
4.0 HCV core antigen
S. minnesota LPS
3.0 H. pylori lysate
2.5 Ribonuclease
2.0 IL-13
HSP60 aa 496-515
1.5 Plasmin
IL-3
1.2
Kinetesin
MOG
1.0 CNP aa 181-199
0.9 CNP aa 195-214
HPS70 aa 121-140
0.8
Prealbumin
0.7 HSP70 aa 76-95
0.6 Glucagon
MMP2
0.5
ABPF aa 34-42
0.4 Phosphodiesterase
0.3 Tau 441
0.2 Squalene
HSP70 aa 361-380
0.1
ABPF aa 12-28
0.0
HSP60 aa 255-275
OSP aa 166-185
HSP40
MBP aa 84-94
HSP90
HSP60 aa 286-305
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The effect of an adjuvant Healthy volunteers were orally administered 7.5 mg of GC alone or in combination with 0.2 mg or 1.0 mg OKT3. Oral OKT3 with GC increases CD4+FoxP3+

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OKT3 OKT3+GC
0 5 10
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Safety and Effect of Oral Administration of β -D-glucosylceramide (EGS21) in Subjects with Non-Alcoholic Steatohepatitis

Study No. 04-815.R1 Protocol No. 815-01-0506

Study design: Double-blind, placebo-controlled Treatment regimen – every day Treatment duration – 40 weeks Dose: 7.5 mg of GC in 5 ml PBS

Effect of oral administration of β -glucosylceramide

Primar end oint - HbA1c y p

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Secondary endpoint - % Fat by MRI

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Effect of GC on NASH in humans Patient No. 905

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Week 0 Week 40

Status of Clinical Trials

Disease	Status	Estimated time to start	Expected results
Type 2 diabetes and fatty liver	IRB	1/2010	5/2010
Influenza	IRB	2/2010	5/2010
HCV	Approved

Future applications

Cancer	Cancer	• Melanoma • Hepatocellular carcinoma • Leukemia	• Melanoma • Hepatocellular carcinoma • Leukemia
	Cancer	• Melanoma • Hepatocellular carcinoma • Leukemia
	Infections	• HIV • Anthrax • HBV, HCV • Clostridium
	Immune disorders	• Rheumatoid arthritis • Multiple Sclerosis
Degenerative diseases	Degenerative diseases	• Alzheimer’s disease

Summary

• Orally-delivered natural antibodies with adjuvants derived from hyper-immune colostrum

• Established clinical record and safety profile

• Broad market opportunities

• Low manufacturing costs

• Not associated with immune suppression

• No side effects or toxicity

• Easily tolerated by patients

• Rapid development cycle

• Natural product regulated as medical food

41

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Thank you

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