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Corporate presentation, April 2012

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Adenium Biotech Management: - Peter Nordkild, MD, CEO, ex Novo Nordisk, Ferring, Egalet - Søren Neve, PhD, project director, ex Lundbeck, Novozymes

Board of Directors: - Khalid Islam, PhD, ex Arpida, chairman - Stephan Christgau, PhD, Novo A/S - Andreas Segerros, Sunstone Capital - Anker Lundemose, MD, ex Novo Nordisk, OSI Pharmaceuticals - Ejner Bech Jensen, MSc, VP R&D Novozymes A/S - Casper Tind Hansen, MSc, Novo A/S

Current Investor: - Novo A/S Special advisor: professor Brad Spellberg

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Bad Bugs – No Drugs (IDSA, 2004)

• The total US market of hospital acquired infections was in 2006 estimated at USD 7.9 billion.

• 65% of hospital acquired infections are caused by Gram-negative bacteria (Clin Infect Dis 2005;41:848–854)

Resistance

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ESKAPE pathogens

• Enterococcus faecium• Staphylococcus aureus Klebsiella species Acinetobacter baumannii Pseudomonas aeruginosa Enterobacter

E.coli E. aerogenes E. cloacae

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Nosocomial indications - volume/value

Source : Datamonitor 03/2007

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Key antibacterial needs 2011

Source: Datamonitor 02/2011.

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Competitive Gram-negative antibiotics in development

Company Development CompoundSpectrum

E.coli Klebsiella Pseudomonas Acinetobacter

Avibactam (Ceftatroline)

Forest/AstraZeneca/Novexel

PhII/III Cephalosporin CAZ104 AstraZeneca

/NovexelPhII β-lactamase

inhibitor () ()TP434 Tetraphase PhII Fluorocycline ÷ GSK 2251052 Anacor/GSK PhII

On holdNovel ÷

Plazomicin(ACH490)

Achaogen PhI Aminoglycoside ÷ ÷BAl30072 Basilea

PharmaceuticaPhI β-lactam antibiotic

MC1 Pfizer Preclinical β-lactam antibiotic ÷RX04 Sanofi Preclinical Novel RecA inhibitors Synerca Discovery Novel ? ? ? ?ME1070 Meiji Seika Discovery β-lactamase

inhibitor ?

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Arenicin-3 NZ17000

• Isolated from lugworm (Arenicola marina)• 21 amino acids• Very stable beta-hairpin structure• MW 2.613 kDa• pI ~ 11.27

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Arenicin program highlights• Novel mode of action, no cross resistance to existing antibiotics• Bactericidal on broad range of multidrug resistant Gram-negative

bacteria• Wide therapeutic window established in mice and pigs • No novel bactericidal Gram-negative antibiotics in clinical

development• Strong lead/back up product candidates• Stable IV formulations• Strong IP (2025-2030)• Addresses significant unmet Gram-negative clinical need• Large, growing and non-generic hospital market of USD 8 billion• Hospital and primarily ICU based specialist target group requiring

small sales force

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Wildtype has broad spectrum in vitro activity against clinical

isolatesMinimal inhibitory concentration (µg/ml) for NZ17000

Bacterial Strains # 0.063 0.125 0.25 0.5 1 2 4 8 16 32

Pseudomonas 24 6 7 7 3 1

Stenotrophomonas 8 3 1 2 2

Citrobacter 7 2 5

Enterobacter 5 1 3 1

Escherichia coli 24 1 11 9 3 1

Hafnia alvei 1 1

Klebsiella 9 4 4 1

Proteus mirabilis 3 1 1 1

Salmonella enterica 8 2 6

Serratia marcescens 2 2

Shigella 2 2

Achromobacter 3 2 1 Acinetobacter 4 2 1 Aeromonas 10 2 2 4 2 Alcaligenes 5 2 2 1

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MIC and protein binding of selected variants

  E.coli E.coli E. coli Klebsiella Enterobacter Pseudomonas

Pseudomonas Vibrio Stenotropho

monas Acinetobacter Moraxella Neisseria % Binding

ATCC25922

ATCC27853

wt 0,25 0,5 0,5 1 1 0,5 1 2 0,5 0,5 0,5 4 99

143 0,25 0,25 0,25 4 4 2 2 8 8 4 2 16 85211 0,5 2 0,5 8 8 4 4 16 8 4 2 >16 80

125 0,25 0,25 0,125 1 1 0,5 0,5 2 2 1 0,125 8 85

139 0,06 0,25 0,125 1 1 0,5 1 2 0,5 0,5 0,25 0,5 95

224 0,125 0,5 0,125 1 1 0,5 1 2 2 0,5 0,25 4 96

228 0,25 0,5 0,125 1 2 0,5 1 2 1 0,5 0,12 4 85

230 0,125 0,5 0,125 2 1 0,5 0,5 2 1 0,25 0,25 8 97

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MoA - localization of Arenicin

A. E. coli exposed for 30 min to NZ17000 and stained with TRITC. Treatment with NZ17000 results in influx of TRITC into the E. coli

B. E. coli exposed for 30 min with TRITC labelled NZ17000. Clusters of NZ17000 were localized in the bacterial membrane

0 16 64 256 1024 40960

5

10

15

20

25

Arcolpip

Extracellular ATP after 10 min

x MIC

Fold

cha

nge

Arenicin-3 (Ar), colistin (col), and piperacillin (pip) induced release of ATP from E. coli. Exponential cells were incubated with drug for 10 minutes and ATP measured. y-axis is fold change relative to untreated (0xmic) and x-axis is fold MIC applied.

• Perturbs the membrane potential increasing the permeability of the bacterial membrane.

• Inhibits the protein synthesis.

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Wildtype has low hemolytic and low cytotoxic activity

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Wildtype time to kill vs E.coli and Pseudomonas

Time kill kinetics for Escherichia coli ATCC25922NZ17000 in ca-Müller Hinton broth

0 30 60 90 120 150 180101

102

103

104

105

106

107

108

109

Growth control

10 x MIC Gentamicin (5µg/ml)10 x MIC Arenicin-3 (5µg/ml)

Time (minutes)

CFU

/ml

NZ17000 Time killing kinetics forPseudomonas aeruginosa ATCC27853

0 30 60 90 120 150 180101

102

103

104

105

106

107

108

Growth Control0.25 x MIC NZ17000 ( 0.125µg/ml)2 x MIC NZ17000 (1µg/ml)10 x MIC NZ17000 (5µg/ml)

Time (minutes)

CFU

/ ml o

f Pse

udom

onas

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Effect of NZ17143 in a 24 hour mouse pneumonia model against Klebsiella pneumoniae (ATCC 43816)

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Efficacy of NZ17143/NZ17211 against MDR E. coli in the murine Urinary Tract Infection model

2

3

4

5

6

7

8Urine day 2 post infection

Log 1

0C

FU/m

l

vehicl

e

NZ1714

3 12.5

mg/kg

NZ1721

1 20 m

g/kg

Meropen

em 40

mg/kg

2

3

4

5

6

7

8 Bladder day 3 post infectionLo

g 10

CFU

/ml

vehicl

e

NZ1714

3 12.5

mg/kg

NZ1721

1 20 m

g/kg

Meropen

em 40

mg/kg

1

2

3

4 Kidneys day 3 post infection

Log 1

0C

FU/m

l

Kidney 3 days post infectionBladder 3 days post infectionUrine 2 day post infection

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Dose response of NZ17211 in the UTI mouse model

ED50 ~0.2 mg/kg in urine and the bladder

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Pharmacokinetic properties after IV administration

Arenicin-3 variant Protein binding(%)

T½

(min)AUC

(min*ug/ml)Cmax

(ug/ml)Bioavailability(%, SC vs IV)

NZ17000 >99 130 532 7.7 12

NZ17143 85 69 324 7.5 70

NZ17211 80 60 432 9.9 60

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In vivo toxicological overview after 7 days of multiple dosing in pigs and mice

Variant NZ17000 NZ17143 NZ17211

MTD iv (mg/kg) 25 50 50

NOAEL iv (mg/kg) 10 30 40

HED (mg/kg) 9,5 28,5 38

E. coli ED50 Bladder (mg/kg) 1,8 0,4 0,2

NOAEL/ED50 Bladder 6 75 200

Protein binding 99 85 80

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Intellectual property

NZ familyWO #

Type Description Issued/priority Expires

10865WO07023163

Composition of matter

Arenicin-3 26.08.2005 26.08.2025

11526WO154525A1

Composition of matter

Arenicin-3 variants 12.06.2010 12.06.2030

11704WO070032A1

Medical use Treatment of UTI with Arenicin-3 11.12.2009 11.12.2029

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Arenicin summary• New mode of action• Spontaneous mutational frequency for E. coli is 3X10-9 and

P. aeruginosa <10-8 • Potent in vitro activity against a wide spectrum of MDR Gram-

negative bacteria• Rapidly bactericidal – MBCs ~ MICs• No cross resistance to known antibiotics• No or little inoculum effect• Favorable efficacy in experimental animal models of infection:

– Pneumonia against Klebsiella– UTI against E. coli– Septicemia against E. coli and P. aeruginosa– Thigh infections against E. coli.