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BIO Europe , November 2013

BIO Europe , November 2013. Antimicrobial peptides with novel mode of action. Adenium Biotech - Background. Antimicrobial peptides with novel mode of action. Spin-out from Novozymes, founded in 2011 Seed investment from Novo Seeds and Sunstone Capital

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BIO Europe , November 2013

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  1. BIO Europe, November 2013 Antimicrobial peptides with novel mode of action

  2. Adenium Biotech - Background Antimicrobial peptides with novel mode of action • Spin-out from Novozymes, founded in 2011 • Seed investment from Novo Seeds and Sunstone Capital • Seed company with experienced management, industry experienced Board of Directors, and top KOL scientific advisory board • ”First-in-Class” systemic Anti Microbial Peptide (AMP) with potent & selective activity against multi-drug resistant Gram-negative bacteria • Clinical Candidate, AA139, nominated and strong back-up candidate available • Bactericidal, new MoA, 2 week tox in pigs/rodents and efficacy in vivo completed • First-in-Man Phase I studies to be initiated by end of 2014 • Clear development plan • Funding requirement: • USD 8 M to progress AA139 through Phase I • USD 25 M to progress AA139 through Phase II • Additional AMP programs targeting Gram-positive pathogens 2

  3. Adenium Biotech - Key People Antimicrobial peptides with novel mode of action Management & Team CEO, Peter Nordkild. Biotech entrepreneur. Previously CEO of Arts Biologics and Egalet, SVP at Ferring and Novo Nordisk CSO, Sergio Lociuro. Previously director of Medicinal Chemistry and Int. Project Leader in GSK, Head of Peptide Epitope Mimetics in Polyphor Ltd and Head of Research in Arpida COO, SørenNeve. Previously project manager for the Arenicin-3 discovery activities in Novozymes Scientific Advisory Board Dr Bruce Montgomery (USA) Prof. Brad Spellberg (USA) Prof. David Livermore (UK) Prof. Matt Cooper (AUS) Dr Frank Fildes (UK) Tim Joslin, Defined Health. Commercial assessment Board of Directors Chairman, Khalid Islam, Gentium Anker Lundemose, Bionor Ejner Bech Jensen, Novozymes Andreas Segerros, Sunstone Stephan Christgau, Novo Seeds Casper Tind Hansen, Pcovery 3

  4. Bacterial Resistance- An escalating problem calling for new MoA antibiotics Antimicrobial peptides with novel mode of action • Resistance is increasing rapidly • Resistance is a high priority with US and EU authorities • Even Colistin, invented in the fifties and abandoned in the sixties due to neuro- and nephrotoxicity, is increasingly used but resistance is growing Carbapenem resistant enterobacteria 4

  5. Arenicin Program Antimicrobial peptides with novel mode of action • Most potent anti Gram-negative AMP identified by Novozymesthrough screening effort comprising more than 500 organisms • Arenicin-3 is a 21 AA peptide from the lugworm Arenicolamarina • New and dual MoA • Novozymeshas tested ≈ 250.000 Arenicinvariants • Adeniumhas subjected the 10 best to extensive characterization/ lead optimization and selected AA139 as the clinical candidate • GMP manufacture initiated October 2013 5

  6. Arenicin Program Targets Unmet Medical Need • GAIN legislation from 2012 grants priority review, fast track status and extend market exclusivity period with 5 years Antimicrobial peptides with novel mode of action ESKAPEpathogens Adenium Targets Gram neg GAIN act pathogens Enterobacter Staphylococcus Pseudomonas E coli Klebsiella Acinetobacter E coli Klebsiella Pseudomonas Acinetobacter Adenium LeadIndication UrinaryTractInfection (UTI) Pneumonia (HAP/VAP) Possible 2’ Indications IntraAbdominalInfection (IAI) 6

  7. Novel mode of action • Bactericidal • Selective and specific • Low frequency of resistance • Active against GAIN pathogens • Wide therapeutic window • Drugable • Target Product Profile for multidrug resistant broad spectrum Gram-negative antibiotic Antimicrobial peptides with novel mode of action 7

  8. Dual Mechanisms of Action – low spontaneous mutation frequencies Antimicrobial peptides with novel mode of action Arenicin also inhibits protein synthesis through inhibition of cytosolic processes Arenicin has a completely novel MoA: Distortion of phospholipid synthesis by interaction with MlaC Extracellular ATP after 10 min MlaCis aperiplasmic binding protein maintaining phospholipid homeostasis Fold change 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. Frequency of resistance <10-11 8

  9. Arenicin Clinical Candidate, AA139: Excellent PK properties and efficacy against Multi Drug Resistant GAIN Pathogens Antimicrobial peptides with novel mode of action • Arenicin efficacy likely driven by Cmax • AA139has highest Cmax and largest AUC of all Arenicin variants • Plasma half life of 4.3 hours • Limited effect of Survanta (mucin analogue) on activity • Protein binding 93% MIC90 determinations (Clinical MDR isolates) 9

  10. Arenicin Clinical Candidate, AA139: Low ED 50 against E. Coli and K. pneumonia in UTI Antimicrobial peptides with novel mode of action • Mice inoculated on day -3 • Treatment, twice daily, on day 1 and 2. Sacrificed on day 3 • Bladder analyzed for bacterial load E. coli K. pneumonia MIC: 0.5 µg/ml MIC: 1µg/ml Euprotec 2013 10

  11. Arenicin Clinical Candidate, AA139: Potent efficacy in UTI against E coli at 5xED50compared with Meropenem Antimicrobial peptides with novel mode of action • Mice inoculated on day -3 • Treatment, twice daily, on day 1 and 2. Sacrificed on day 3 • Tissues analyzed for bacterial load • Comparison with standard of care, Meropenem 11

  12. Arenicin Clinical Candidate, AA139: Excellent efficacy in pneumonia compared withColistin after aerosol admin. Antimicrobial peptides with novel mode of action • Mice inoculated on day 1 • Treatment, 3 ml aerosol for 10 min at 2, 12, 24 hour post infection • Lung harvest at 34 hour post infection • Compared with standard of care, Colistin Euprotec 2013 12

  13. Extensive Tox testing in rodentsand mini pigs confirm safety Antimicrobial peptides with novel mode of action (7 days of multiple dosing in mice and mini-pigs) • Histamine release and reversible proximal tubular damage only adverse event • No hERG or other cardiovascular toxicity 13

  14. Product profiles of Meropenem, Colistin and Arenicin Antimicrobial peptides with novel mode of action 14

  15. Very few new MoA Gram negative antibiotics – most in clinical development targets Pseudomonas Antimicrobial peptides with novel mode of action 15

  16. Externalactivities and cost for development of AA139 in cUTI Antimicrobial peptides with novel mode of action 16

  17. Additional programs target other GAIN pathogens Antimicrobial peptides with novel mode of action • The Arenicin platform provides opportunities for multiple clinical indications: • AA139 in other clinical indications than cUTI(e.g. HAP/VAP, IAI) • Other Arenicin variants for selected pathogens (i.e. variants with high activity against e.g. MDR N. Gonorrhoeae identified) • Adeniumis acquiring an additional AMP platform from Novozymes. AP114 has high activity against C. difficile • cGMP material AP114 available • AP114 program targeting C. difficile infection currently being developed • FIM studies possible in H2-2014 17

  18. Adenium Expands AMP platform • Lead program, AA139, will be advanced through phase II • Additional Arenicin programs will be developed with external funding • AP114 program will initiate phase I studies in H2 2014 Antimicrobial peptides with novel mode of action Compound Indication Partner Discovery Development Preclinical Phase I Preclinical Phase I In vitro In vivo In vitro In vivo AP114 MDR C. diff AA139 MDR GAIN pathogens DMID Arenicin MDR N. gonorrhea 18

  19. Plans for series A round • Development cost of USD 6 mio forAA139 through phase I • Development cost of USD 2 mio for AP114 through phase I • G&A cost of USD 2 mio • Company plans to raise a minimum of USD 10 mio in a series A round in H1 2014 • Current investors (Sunstone Capital and Novo) will participate in the series A round • Plan to attract 1 – 2 additional investors to the syndicate Antimicrobial peptides with novel mode of action 19

  20. Key Value Drivers for Investment • AA139, one of very few new MoA, broad spectrum MDR Gram-negative • First in class antibiotic with strong patenting through 2033 • Increasing resistance problem spurs interest in new anti-infectives • Regulatory guidelines (e.g. GAIN act) provides additional incentives for anti-infective development • Recent deal activity (e.g. Cubist – Trius/Optimer) confirms interest in antibiotics • Additional opportunities for AA139 in other indications • AP114 program targets C. diffinfection, a growing problem with rapidly aging populations and a GAIN pathogen Antimicrobial peptides with novel mode of action 20

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