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Confidential Corporate presentation, BIO, Chicago 2013 Developing novel antimicrobials against ”difficult to treat” multi drug resistant bacteria.

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Presentation on theme: "Confidential Corporate presentation, BIO, Chicago 2013 Developing novel antimicrobials against ”difficult to treat” multi drug resistant bacteria."— Presentation transcript:

1 Confidential Corporate presentation, BIO, Chicago 2013 Developing novel antimicrobials against ”difficult to treat” multi drug resistant bacteria

2 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 - Lead optimization w. selection of clinical candidate/back-ups in ”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 2

3 Confidential 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 3

4 Confidential Arenicin selection process: Adenium benefits from extensive know how ~40 AMP’s identified Several G+ but only one G- identified ! > 500 organisms screened for antimicrobial activity 4

5 Confidential Medical need for broad spectrum Gram-negative antimicrobial Bacteria are rapidly becoming resistant to known antibiotics 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 5

6 Confidential 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 Chemically amenable 6

7 Confidential 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 haemolytic 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 – 200 fold difference between effective dose and MTD in vivo 21 AA peptide synthesized by standard solid phase synthesis 7

8 Confidential 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-3 and the cell membrane -MoA 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. 8

9 Confidential Arenicin is selective and specific for bacteria with low hemolytic and cytotoxic activity 9 wt

10 Confidential # strainswtAA139AA143AA230CeftazidimeCiprofloxacinColistinGentamicinMeropenemTigecycline N=325MIC (µg/ml) E.coliN= >32>40.25> K.pneumoniaN= >32>48>32>164 P.aeruginosaN= >32>42>32>16>8 A.baumaniiN= >32>48>32>164 Arenicin shows favorable efficacy compared to current treatment options MIC 90 determinations 10

11 Confidential Arenicin shows low potential for resistance development OrganismIsolate ID Resistance Frequency (4 X MIC) wtAA139AA143AA230 E. coliATCC ≤ 3,57E-11 ≤ 2,50E-12≤ 3,57E-11≤ 2,50E-12 K. pneumoniae ≤ 5,00E-11 ≤ 1,38E-11≤ 5,00E-11≤ 1,38E-11 P. aeruginosaATCC ≤ 8,30E-11 ≤ 2,61E-12≤ 8,30E-11≤ 2,61E-12 A. baumannii ≤ 3,44E-11 ≤ 2,65E-12≤ 3,44E-11≤ 2,65E-12 11

12 Confidential Arenicin shows good activity in animal models of UTI and Pneumonia 12 Arenicin shows good efficacy in the UTI model with ED50 at 1.8 mg/kg in the bladder Arenicin exhibits bioload reduction similar to Meropenem in the Pneumonia model

13 Confidential Arenicin is well tolerated with a wide therapeutic window Favorable MTD in mini-pigs and mice at 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 13

14 Confidential Milestone plan In vivo efficacy against key pathogens Pseudomonas, Acinetobacter and Klebsiella in pneumonia Completed Three leads identified for lead optimization Completed Lead candidate selection Q IND enabling tox/safety completed Q IND filing Q First in man initiation Q Initiation of clinical ”Proof of Concept” (phase II) Q Completion of clinical PoC Q

15 Confidential 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 15

16 Confidential Plectasin – an MRSA/VISA/GISA opportunity MRSA is the largest XDR pathogen Very compelling Plectasin MICs against MRSA & GISA Plectasin superior to Daptomycin/Vancomycin in infectious endocarditis MRSA device/implant infections is a large unmet need 16

17 Confidential Plectasin superior to Vancomycin and Daptomycin in infectious endocarditis model Infection 52Days Treatment IV 340 Relapse 1 17

18 Confidential NZ2114NZ2138NZ2143 ParameterUnits Dosemg/kg 10 HL_Lambda_zMin Cmaxug/ml AUCallhr*ug/ml Cl_obsl/hr Protein Binding% NOAELmg/kg 30*<43** MIC 90 µg/ml 80.5 *2h iv infusion ** iv bolus administration In vitro efficacy, tox and kinetics of Plectasin variants

19 Confidential Contact details Dr Peter Nordkild Mobile: Website: www. 19

20 Confidential Additional information 20

21 Confidential External activities and cost for development of Arenicin in cUTI Task Cost MUSD 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

22 Confidential Intellectual property NZ family WO # TypeDescriptionIssued/priorityExpires WO Composition of matter Arenicin WO154525A1 Composition of matter Arenicin-3 variants WO070032A1 Medical useTreatment of UTI with Arenicin EP Medical useTreatment of pneumonia with Arenicin-3 variants Broad IP portfolio with composition of matter and method of use patents. Future patents on specific variants and formulations possible.

23 Confidential Competitive Gram-negative antibiotics with novel MoA in development CompoundCompany Develop- ment Target Spectrum E.coliKlebsiellaPseudomonasAcinetobacter Single pathogen ACHN975AchaogenPhILpxC inhibitor ÷÷ ÷ Pol 7080Polyphor ltdPhIMembrane modulator ÷÷ ÷ BioPhage PABioControlpH2Undefines (Virus) ÷÷ ÷ IC 43Novartisph2Immunostimulant (Vaccine) ÷÷ ÷ KB001SanofiPh2PcrV inhibitor ÷÷ ÷ Broad Gram-Negative GP-4TriusPreclinicalGyrB/ParE RX04SanofiPreclinical50S ribisomal subunit 23

24 Confidential Target companyBuyer Upfront Deal Value ($m) Total Deal Value ($m) Clinical Stage of Lead Product 2012 Inhibitex, Inc.Bristol-Myers Squibb Company2, Mpex Pharmaceuticals, Inc Aptalis Pharma Inc Inspire Pharmaceuticals, Inc.Merck AdolorCubist Crucell N.V.Johnson & Johnson2, Middlebrook PharmaceuticalsVictory Pharma ProlysisBiota11 Pre-clinical 2009 Targanta TherapeuticsThe Medicines Company Genelabs Techn.GSK CalixaCubist NovexelAstraZeneca Antimicrobial deals

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