Corporate presentation December 2013 Antimicrobial peptides with novel mode of action

A NTIMICROBIAL PEPTIDES WITH NOVEL MODE OF ACTION Adenium Biotech - Background 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: EUR 8 M to progress AA139 through Phase I EUR 20 M to progress AA139 through Phase II Additional AMP programs targeting Gram-positive pathogens 2

Adenium Biotech - Key People 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 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 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, Søren Neve. Previously project manager for the Arenicin-3 discovery activities in Novozymes CMC, Kim Hejnæs. Previously project director at CMC Biologics 3 A NTIMICROBIAL PEPTIDES WITH NOVEL MODE OF ACTION

Bacterial Resistance - An escalating problem calling for new MoA antibiotics 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 A NTIMICROBIAL PEPTIDES WITH NOVEL MODE OF ACTION

Arenicin Program Most potent anti Gram-negative AMP identified by Novozymes through screening effort comprising more than 500 organisms Arenicin-3 is a 21 AA peptide from the lugworm Arenicola marina New and dual MoA Novozymes has tested ≈ Arenicin variants Adenium has subjected the 10 best to extensive characterization/ lead optimization and selected AA139 as the clinical candidate GMP manufacture initiated October A NTIMICROBIAL PEPTIDES WITH NOVEL MODE OF ACTION

Arenicin Program Targets Unmet Medical Need GAIN legislation from 2012 grants priority review, fast track status and extend market exclusivity period with 5 years Klebsiella Acinetobacter PseudomonasE coli EnterobacterStaphylococcus ESKAPE pathogens Adenium Targets Gram neg GAIN act pathogens E coliKlebsiella PseudomonasAcinetobacter Urinary Tract Infection (UTI) Pneumonia (HAP/VAP) Intra Abdominal Infection (IAI) Adenium Lead Indication Possible 2’ Indications A NTIMICROBIAL PEPTIDES WITH NOVEL MODE OF ACTION 6

Novel mode of action Bactericidal Selective and specific Low frequency of resistance Active against GAIN pathogens Wide therapeutic window Drugable 7 A NTIMICROBIAL PEPTIDES WITH NOVEL MODE OF ACTION Target Product Profile for multidrug resistant broad spectrum Gram-negative antibiotic

Dual Mechanisms of Action – low spontaneous mutation frequencies 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 Arenicin also inhibits protein synthesis through inhibition of cytosolic processes MlaC is a periplasmic binding protein maintaining phospholipid homeostasis Arenicin has a completely novel MoA: Distortion of phospholipid synthesis by interaction with MlaC Frequency of resistance < A NTIMICROBIAL PEPTIDES WITH NOVEL MODE OF ACTION

9 Arenicin Clinical Candidate, AA139: Excellent PK properties and efficacy against Multi Drug Resistant GAIN Pathogens Arenicin efficacy likely driven by C max AA139 has highest C max 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% strainsAA139ColistinMeropenemCeftazidimeCiprofloxacinGentamicinTigecycline N=325MIC (µg/ml) E.coliN= RRR0.5 K.pneumoniaN=754RRRRR4 P.aeruginosaN=7582RRRRND A.baumaniiN=1202RRRRR4 A NTIMICROBIAL PEPTIDES WITH NOVEL MODE OF ACTION MIC 90 determinations (Clinical MDR isolates)

Arenicin Clinical Candidate, AA139: Low ED 50 against E. Coli and K. pneumonia in UTI Mice inoculated on day -3 Treatment, twice daily, on day 1 and 2. Sacrificed on day 3 Bladder analyzed for bacterial load E. coliK. pneumonia MIC: 0.5 µg/mlMIC: 1µg/ml Euprotec A NTIMICROBIAL PEPTIDES WITH NOVEL MODE OF ACTION

Arenicin Clinical Candidate, AA139: Potent efficacy in UTI against E coli at 5xED 50 compared with Meropenem 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 E.coli DSA443 Compound µg/ml AA Meropenem< A NTIMICROBIAL PEPTIDES WITH NOVEL MODE OF ACTION

Arenicin Clinical Candidate, AA139: Excellent efficacy in pneumonia compared with Colistin after aerosol admin. 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 A NTIMICROBIAL PEPTIDES WITH NOVEL MODE OF ACTION Klebsiella Pneumonia NCTC13442 Compound  log reduction MIC AA Colistin-1.751

A NTIMICROBIAL PEPTIDES WITH NOVEL MODE OF ACTION AA139 shows potent effect against MDR Gram negative bacteria in major animal models of infection 13 Good bioload reduction on par with Meropenem against E.coli in mouse thigh model following IV dosing E.coli DSA443 Variant  log reduction MIC (ug/ml) NZ Meropenem-1.6<0.06 Good bioload reduction on par with Meropenem against E.coli in bladder following IV dosing Potent bioload reduction superiour to Meropenem against E.coli in peritoneal fluid following IV dosing Moderate bioload reduction against P.aeruginosa in pneumonia following IV dosing Pseudomonas aeruginosa VL-98 Variant  log reduction MIC (ug/ml) NZ Meropenem E.coli AID172 Variant  log reduction MIC (ug/ml) NZ Meropenem E.coli AID172 Variant  log reduction MIC (ug/ml) NZ Meropenem

AA139 MTD iv (mg/kg)25 E. coli ED 50 Bladder (UTI) (mg/kg)1 MTD/ED 50 Bladder25 Protein binding93 Extensive Tox testing in rodents and mini pigs confirm safety Histamine release and reversible proximal tubular damage only adverse event No hERG or other cardiovascular toxicity 14 A NTIMICROBIAL PEPTIDES WITH NOVEL MODE OF ACTION (7 days of multiple dosing in mice and mini-pigs)

Indications MeropenemColistinAA139 Pneumonia +++ Complicated urinary tract infections +++ Coverage MDR E.coli MDR P.aeruginosa -+++ MDR A.baumannii KPC K.pneumonia --++ Colistin resistant G- Bacteria Administration Oral no IV yes Aerosol noyes Safety Renal/Hepatic (yes)yes(no) Neurological noyesno Hypersensitivity yes Action Bactericidal yes 15 Product profiles of Meropenem, Colistin and Arenicin A NTIMICROBIAL PEPTIDES WITH NOVEL MODE OF ACTION

Very few new MoA Gram negative antibiotics – most in clinical development targets Pseudomonas CompoundCompany Develop- ment Target Spectrum E.coliKlebsiellaPseudomonasAcinetobacter Single pathogen ACHN975AchaogenPhILpxC inhibitor ÷÷ ÷ Pol 7080Polyphor ltdPhIMembrane modulator ÷÷ ÷ BioPhage PABioControlPh2Bacteriophage (Virus) ÷÷ ÷ IC 43Intercell AG (Novartis) Ph2Immunostimulant (Vaccine) ÷÷ ÷ KB001KaloBios (Sanofi) Ph2PcrV antibody ÷÷ ÷ Broad Gram-Negative AA139AdeniumPreclinicalMlaC/protein synthesis GP-4Trius (Cubist)PreclinicalGyrB/ParE RX04Rib-X (Sanofi) Preclinical50S ribosomal subunit SASPject™ PT3.XPhicoPreclinicalInactivated bacterial DNA 16 A NTIMICROBIAL PEPTIDES WITH NOVEL MODE OF ACTION

Tasks Cost MUSD Lead candidate selection API synthesis (20 g) 0.1 API Preclin/Phase I production (1.7 kg) 1.9 Pre-clinical tox/safety 1.3 CTA/IND 0.3 Phase I (SAD/MAD) 2.0 cGMP production for ph II and III ( kg) 3.1 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 External activities and cost for development of AA139 in cUTI

Additional programs target other GAIN pathogens 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) The Plectasin platform provides opportunities for multiple MDR Gram positive clinical indications: AP114 is very potent against C. difficile (cGMP material is available/FIM studies to be initiated summer 2014) AP138 will be developed against cardio/osteo implant infections caused by MDR S. aureus 18 A NTIMICROBIAL PEPTIDES WITH NOVEL MODE OF ACTION

Adenium Expands AMP platform Lead program, AA139, will be advanced through phase II by midle of 2017 AP114 program will initiate phase I studies in H AP138 program will initiate phase I studies in summer 2016 Additional Arenicin programs will be developed with external funding 19 CompoundIndicationDiscoveryDevelopment In vitro In vivo Preclinical Phase I ArenicinMDR N. gonorrhea Partner In vitro In vivo Preclinical Phase I DMID MDR C. diff MDR G- cUTI/HAP&VAPAA139 AP114 A NTIMICROBIAL PEPTIDES WITH NOVEL MODE OF ACTION AP138MDR G+ implant infections

Plans for series A round Development cost of EUR 6 mio for AA139 through phase I Development cost of EUR 2 mio for AP114 through phase I G&A cost of EUR 2 mio Company plans to raise a minimum of EUR 10 mio in a series A round in H Current investors (Sunstone Capital and Novo) will participate in the series A round Plan to attract 1 – 2 additional investors to the syndicate 20 A NTIMICROBIAL PEPTIDES WITH NOVEL MODE OF ACTION

Key Value Drivers for Investment AA139, one of very few new MoA, broad spectrum MDR Gram-negative antibiotic 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 – acquisition of Trius/Optimer; Roche – license of POL7080) confirms interest in antibiotics Additional opportunities for AA139 in other indications AP114 program targets C. diff infection, a growing problem with rapidly aging populations and a GAIN pathogen 21 A NTIMICROBIAL PEPTIDES WITH NOVEL MODE OF ACTION