BIO Europe , November 2013

AdeniumBiotech

BIO Europe, November 2013

Antimicrobial peptides with novel mode of action

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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:

USD 8 M to progress AA139 through Phase IUSD 25 M to progress AA139 through Phase II

• Additional AMP programs targeting Gram-positive pathogens

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Adenium Biotech - Key People

Board of Directors

Chairman, Khalid Islam, GentiumAnker Lundemose, Bionor Ejner Bech Jensen, NovozymesAndreas Segerros, SunstoneStephan Christgau, Novo SeedsCasper 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 NordiskCSO, 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

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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

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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 ≈ 250.000 Arenicin variants• Adenium has subjected the 10 best to extensive characterization/

lead optimization and selected AA139 as the clinical candidate• GMP manufacture initiated October 2013

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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 Pseudomonas E coliEnterobacter Staphylococcus

ESKAPE pathogens Adenium Targets Gram neg GAIN act pathogens

E coli Klebsiella Pseudomonas Acinetobacter

Urinary Tract Infection (UTI)

Pneumonia (HAP/VAP)

Intra Abdominal Infection (IAI)

Adenium Lead Indication

Possible 2’ Indications

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

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NTarget Product Profile for multidrug resistant broad spectrum Gram-negative antibiotic

Dual Mechanisms of Action – low spontaneous mutation frequencies

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Arcolpip

Extracellular ATP after 10 min

x MIC

Fold

cha

nge

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 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 <10-11

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Arenicin Clinical Candidate, AA139: Excellent PK properties and efficacy against Multi Drug Resistant GAIN Pathogens

• Arenicin efficacy likely driven by Cmax

• AA139 has 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%

strains AA139 Colistin Meropenem Ceftazidime Ciprofloxacin Gentamicin Tigecycline

N=325 MIC (µg/ml)

E.coli N=55 1 0.25 4 R R R 0.5

K.pneumonia N=75 4 R R R R R 4

P.aeruginosa N=75 8 2 R R R R ND

A.baumanii N=120 2 R R R R R 4

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MIC90 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. coli K. pneumoniaMIC: 0.5 µg/ml MIC: 1µg/ml

Euprotec 2013

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Arenicin Clinical Candidate, AA139: Potent efficacy in UTI against E coli at 5xED50 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 DSA443Compound µg/ml

AA139 0.12Meropenem <0.06

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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 2013

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Klebsiella Pneumonia NCTC13442

Compound log reduction MICAA139 -3.89 1

Colistin -1.75 1

AA139

MTD iv (mg/kg) 25

E. coli ED50 Bladder (UTI) (mg/kg) 1

MTD/ED50 Bladder 25

Protein binding 93

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

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(7 days of multiple dosing in mice and mini-pigs)

Indications Meropenem Colistin AA139

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 no noIV yes yes yesAerosol no yes yesSafety

Renal/Hepatic (yes) yes (no)Neurological no yes noHypersensitivity yes yes yesAction

Bactericidal yes yes yes

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Product profiles of Meropenem, Colistin and Arenicin

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Very few new MoA Gram negative antibiotics – most in clinical development targets PseudomonasCompound Company Develop-

ment TargetSpectrum

E.coli Klebsiella Pseudomonas Acinetobacter

Single pathogen

ACHN975 Achaogen PhI LpxC inhibitor ÷ ÷ ÷Pol 7080 Polyphor ltd PhI Membrane modulator ÷ ÷ ÷BioPhage PA BioControl Ph2 Bacteriophage

(Virus) ÷ ÷ ÷IC 43 Intercell AG

(Novartis)Ph2 Immunostimulant

(Vaccine) ÷ ÷ ÷KB001 KaloBios

(Sanofi)Ph2 PcrV antibody ÷ ÷ ÷

Broad Gram-NegativeAA139 Adenium Preclinical MlaC/protein

synthesis GP-4 Trius (Cubist) Preclinical GyrB/ParE RX04 Rib-X

(Sanofi)Preclinical 50S ribosomal subunit

SASPject™ PT3.X Phico Preclinical Inactivated bacterial DNA

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External activities and cost for development of AA139 in cUTI

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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)

• Adenium is 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

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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

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Compound Indication Discovery Development

In vitro In vivo Preclinical Phase I

Arenicin MDR N. gonorrhea

PartnerIn vitro In vivo Preclinical Phase I

DMID

MDR C. diff

MDR GAIN pathogens

AA139

AP114

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Plans for series A round

• Development cost of USD 6 mio for AA139 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

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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. diff infection, a growing problem

with rapidly aging populations and a GAIN pathogen

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