Confidential

Presentation at BioEquity, Stockholm, May 2013

Developing novel antimicrobials against ”difficult to treat” multi drug resistant bacteria

Confidential

Summary – Adenium Biotech

• A spin-out from Novozymes, founded in 2011, strong VC syndicate• Management team with extensive experience, industry

experienced Board of Directors and strong Scientific Advisory Board of KOL´s

• ”First-in-class” Arenicin compounds with potent and selective activity against multi-drug resistant Gram-negative bacteria

- Selection of clinical candidate/initiation of tox/safety in October 2013

- ”First in man” by end of 2014• Funding requirement:

- USD 10 mio to progress through phase I

- USD 25 mio to progress through clinical ”proof of concept” in phase II

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Adenium Biotech ApS• Management:

- Peter Nordkild, MD, CEO, ex Novo Nordisk, Ferring, Egalet, ARTS Biologics

- Søren Neve, PhD, project dir, ex Lundbeck, Novozymes

• Investors:

- Novo Seeds - Sunstone Capital

• Board of Directors:

- Khalid Islam, PhD, ex Arpida, chairman

- Anker Lundmose, MD, ex Novo Nordisk, OSI Pharmaceuticals

- Andreas Segerros, MSc, MBA, Sunstone Capital

- Stephan Christgau, PhD, Novo Seeds - Casper Tind Hansen, MSc, Novo Ventures

- Ejner Bech Jensen, MSc, VP R&D Novozymes A/S

• Scientific advisory board:

- Prof Brad Spellberg, US - Prof David Livermore, UK - Dr Bruce Montgomery, US - Dr Frank Fildes, UK - Prof Matt Cooper, AUS

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Arenicin selection process. Adenium benefits from extensive AMP know how

Variant library generation(~250.000 variants)

~40 AMP’s identified

Several G+ but only one G- identified

> 500 organisms screened for antimicrobial activity

NZ17074

Second variant library (~90.000 variants)

1500 hits but only 10 variants selected

First HitLead

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Medical need for broad spectrum Gram-negative

antimicrobial• Bacteria are rapidly becoming resistant to known antibiotics

- 160.000 patients with nosocomial XDR Gram-negative

infections in 2011 in USA alone

- Carbapenem resistant Klebsiella increased from < 5 % to

29.6% in Italy over 5 years• Increasing resistance even to last and toxic resorts e.g. Colistin• GAIN legislation approved to grant priority review, fast track

status and extend market exclusivity period with 5 years• GAIN pathogens: Acinetobacter, Klebsiella, Pseudomonas and

E. Coli

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Ideal Target Product Profile for multidrug resistant broad spectrum Gram-negative antimicrobial

• Novel mode of action• Bactericidal• Selective and specific• Low frequency of resistance• Active against GAIN pathogens• Drugable

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Arenicin: Unique MoA and broad spectrum Gram-negative activity

• Arenicin is bactericidal with a novel, dual mode of action– Bacterial membrane penetration– Protein synthesis inhibition

• Selective and specific - no hemolytic or cytotoxic activity in mammalian cells

• Very low spontaneous mutational frequency and resistance• Broad spectrum activities against a wide range of XDR Gram-

negative pathogens• Wide therapeutic window. 50 – 100 fold difference between

effective dose and MTD in vivo• 21 AA peptide synthesized by standard solid phase synthesis

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P. aeruginosa incubated with 32 μg/mL AA143. Red arrow shows the membrane disruption. Blue arrow shows release of the cytoplasm.

TEM of P.aeruginosa after incubation with AA143

Arenicin and the cell membrane -MoA

0 16 64 256 1024 40960

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Arcolpip

Extracellular ATP after 10 min

x MIC

Fold

change

Arenicin (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 and x-axis is fold MIC applied.

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Arenicin interferes with the phospholipid homeostasis

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• MlaC is a periplasmic binding protein maintaining phospholipid homeostasis of the dual cell membrane

• Whole genome sequencing of E. Coli shows only one single L11R amino acid mutation in MlaC correlating well with the very low spontaneous mutational frequency

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Arenicin shows low potential for resistance development

Organism Isolate ID

Resistance Frequency (4 X MIC)

AA139 AA230

E. coli ATCC 25922≤ 2,50E-12 ≤ 2,50E-12

K. pneumoniae 3083583≤ 1,38E-11 ≤ 1,38E-11

P. aeruginosa ATCC 27853≤ 2,61E-12 ≤ 2,61E-12

A. baumannii 3083835≤ 2,65E-12 ≤ 2,65E-12

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Arenicin is selective and specific for bacteria with low

hemolytic and cytotoxic activity

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wt

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# strains AA139 AA230 Ceftazidime Ciprofloxacin Colistin Gentamicin Meropenem Tigecycline

N=325 MIC (µg/ml)

E.coli N=55 1 0.5 >32 >4 0.25 >32 4 0.5

K.pneumonia N=75 4 4 >32 >4 8 >32 >16 4

P.aeruginosa N=75 8 2 >32 >4 2 >32 >16 >8

A.baumanii N=120 2 2 >32 >4 8 >32 >16 4

Arenicin shows favorable efficacy compared to current

treatment optionsMIC90 determinations (MDR strains)

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Arenicin shows good activity in animal models of UTI and

Pneumonia

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• Arenicin shows good efficacy in the UTI model with ED50 at 1.8 mg/kg in the bladder

• Arenicin shows good efficacy in the Pneumonia model

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Arenicin is well tolerated with a wide therapeutic window

• Favorable MTD in mini-pigs and mice at 30-50 mg/kg

• No observed adverse effect level (NOAEL) at 30 mg/kg

• Therapeutic window (NOAEL/ED50 bladder) of 75

• Three times longer half-life than Meropenem in mini-pigs

• Well distributed with a high volume of distribution of 900 ml

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Indications Meropenem Colistin ArenicinPneumonia +++ +++ +++Complicated urinary tract infections +++ +++ +++Coverage

XDR E.coli ++ +++ +++XDR P.aeruginosa ++ +++ +++XDR A.baumannii + +++ +++KPC K.pneumonia - +++ +++Colistin G- Bacteria - - +++Administration

Oral no no noIV yes yes yesIT no yes ?

Renal/Hepatic yes yes yesNeurological no yes noHypersensitivity yes yes yes

Bactericidal yes yes yes

Product profiles of Meropenem, Colistin and Arenicin

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Milestone plan

• In vivo efficacy against key pathogens Pseudomonas, Acinetobacter and Klebsiella in pneumonia Completed

• Two leads identified for lead optimization Completed• Clinical candidate selection Oct 2013• IND enabling tox/safety completed Q4 2014• IND filing Q4 2014• First in man initiation Q1 2015• Initiation of clinical ”Proof of Concept” (phase II) Q2 2016• Completion of clinical PoC Q2 2017

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External activities and cost for development of Arenicin in

cUTITask 2013 2014 2015 2016 2017 2018 2019 CostMUSD

Lead candidate selection

Synthesis of 2 kg of cGMP material (Pre clin , phI) 2.0

Fill and finish ( phI ) 0.3

Pre-clinical tox/ safety 0.5

CTA/IND 0.1

Phase I (SAD/MAD) 2.0

cGMP production for ph II and III 10.0

Fill and finish (phII, phIII) 0.7

SPA meeting 0.3

Phase II (a and b) cUTI 6.0

Phase III studies cUTI 30.0

NDA submission 0.3

Total / Year 1.0 1.8 2.1 13.0 14.0 10.0 10.3 52.2

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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

EP12166275 Medical use Treatment of pneumonia with Arenicin-3 variants

01.05.2012 01.05.2033

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Broad IP portfolio with composition of matter and method of use patents.

Future patents on specific variants and formulations possible.

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Competitive Gram-negative antibiotics with novel MoA in

development

Compound Company Develop-ment Target

Spectrum

E.coli Klebsiella Pseudomonas Acinetobacter

Single pathogen

ACHN975 Achaogen PhI LpxC inhibitor ÷ ÷ ÷Pol 7080 Polyphor ltd PhI Membrane modulator ÷ ÷ ÷BioPhage PA BioControl pH2 Undefines

(Virus) ÷ ÷ ÷

IC 43 Novartis ph2 Immunostimulant(Vaccine) ÷ ÷ ÷

KB001 Sanofi Ph2 PcrV inhibitor ÷ ÷ ÷Broad Gram-Negative

GP-4 Trius Preclinical GyrB/ParE RX04 Sanofi Preclinical 50S ribisomal subunit

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Target company Buyer

Upfront Deal Value ($m)

Total Deal Value ($m)

Clinical Stage of

Lead Product

2012 Inhibitex, Inc. Bristol-Myers Squibb Company 2,5002011 Mpex Pharmaceuticals, Inc Aptalis Pharma Inc. 2242011 Inspire Pharmaceuticals, Inc. Merck 4302011 Adolor Cubist 190 4152011 Crucell N.V. Johnson & Johnson 2,2742010 Middlebrook Pharmaceuticals Victory Pharma 17 172009 Prolysis Biota 11 11 Pre-clinical2009 Targanta Therapeutics The Medicines Company 42 1002009 Genelabs Techn. GSK 57 572009 Calixa Cubist 93 403 22009 Novexel AstraZeneca 350 425 2

Antimicrobial deals 2009-2012

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Key Value Drivers for Investment

• Broad spectrum XDR Gram-negative first in class drug with unique MoA and strong patent position

• Significantly increased interest in antimicrobials area with GAIN Act/LPAD introduction

• No new MoA programs in clinical development• Good safety and tox properties and solid in vivo PoC package• Phase II data package to be established for USD 25 mio• Experienced team to execute development plan

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Contact details

Dr Peter NordkildMobile: + 45 25 47 16 46

Email: pno@adeniumbiotech.comWebsite: www.

Adeniumbiotech.com

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