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Presentation at BioEquity, Stockholm, May 2013

Developing novel antimicrobials against ”difficult to treat” multi drug resistant bacteria. Presentation at BioEquity, Stockholm, May 2013. Summary – Adenium Biotech. A spin-out from Novozymes, founded in 2011, strong VC syndicate

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Presentation at BioEquity, Stockholm, May 2013

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  1. Developing novel antimicrobials against ”difficult to treat” multi drug resistant bacteria Presentation at BioEquity, Stockholm, May 2013

  2. 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 2

  3. 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. Arenicin selection process.Adenium benefits from extensive AMP know how > 500 organisms screened for antimicrobial activity 1500 hits but only 10 variants selected Several G+ but only one G- identified NZ17074 Lead First Hit Second variant library (~90.000 variants) Variant library generation (~250.000 variants) ~40 AMP’s identified 4

  5. 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 5

  6. 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 6

  7. 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 7

  8. Arenicin and the cell membrane -MoA TEM of P.aeruginosa after incubation with AA143 Extracellular ATP after 10 min Fold change P. aeruginosaincubated with 32 μg/mL AA143. Red arrow shows the membrane disruption. Blue arrow shows release of the cytoplasm. x MIC Arenicin (Ar), colistin (col), and piperacillin (pip) induced releaseof 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. Arenicin interferes with the phospholipid homeostasis • MlaCis aperiplasmic 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 9

  10. Arenicin shows low potential for resistance development 10

  11. Arenicin is selective and specific for bacteria with low hemolytic and cytotoxic activity wt 11

  12. Arenicin shows favorable efficacy compared to current treatment options MIC90 determinations (MDR strains) 12

  13. Arenicin shows good activity in animal models of UTI and Pneumonia • 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 13

  14. 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 14

  15. Product profiles of Meropenem, Colistin and Arenicin 15

  16. 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 16

  17. External activities and cost for development of Arenicin in cUTI 5 3 9 3 12 6 3 3 12 18 6 17

  18. Intellectual property Broad IP portfolio with composition of matter and method of use patents. Future patents on specific variants and formulations possible. 18

  19. Competitive Gram-negative antibiotics with novel MoA in development 19

  20. Antimicrobial deals 2009-2012 20

  21. 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 vivoPoC package Phase II data package to be established for USD 25 mio Experienced team to execute development plan 21

  22. Contact details Dr Peter Nordkild Mobile: + 45 25 47 16 46 Email: pno@adeniumbiotech.com Website: www. Adeniumbiotech.com 22

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