Bild 1 - Aktiespararna

Company presentation,
Aktiespararna, Mars 2012
Ulf Boberg, CEO

Creative Antibiotics Sweden AB
• Creative Antibiotics Sweden AB (publ) incorporated in 2000
with the goal to develop novel antibiotics
• Company listed on AktieTorget since 2004
• Business model is to develop project to phase I/II data and
thereafter license to pharma companies for further
development and commercialization
• Highly qualified staff:
• 9 employees whereof 4 with PhD
• Collaborations with international CRO and universities
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Ägarsituationen
• Next2b, med Bengt Ågerup som ägare, har förvärvat 6 % av
bolaget aktie
• Största ägare:
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• Tuja Invest (Next2b), 6.2%
• Östersjöstiftelsen, 5.7%
• Sune Rosell m. fam, 5.0%
• L-försäkrningar VB, 4.8%
• L-försäkringar fonf AB 3.5%

Infektionssjukdomar
• Antibiotika
• Behandling av infektionssjukdomar förorsakade av bakterier
• Ej virus och svamp
• Baktericida eller bakteriostatiska
• Bredspektrum eller smalspektrum
• Grampositiva eller Gramnegativa
• Antibiotikaresistens och dess betydelse
• Bakterier, svampar, virus och bakteriofager har alltid påverkat varandra
• Bakterier utväxlar egenskaper/skyddsmekanismer
• Bakterien är resistent – inte personen
• Överförskrivning, djurfoder, kläder, hushållprodukter
• Framtiden antibiotika och behandlingsformer
• Trend mot kortare behandlingsregim med avdödande substanser
• Utveckling av smalspektrum (målsökande) substanser
• Förstärkning av egna immunförsvaret
• Snabbare och mer specifik diagnostik
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Läkemedelsutveckling
• Akademisk forskning, relativt låg kostnad, 1/10
• Grundläggande forskning som kartlägger biologiska/fysiologiska samband
• Har sällan produktperspektiv
• lärarundantaget
• Industriell discovery (3-5 år), ca 2-3/10
• Ofta samarbetet med akademi runt en upptäckt
• Fokus på produktutveckling: effekt, atoxisk, patenterbar
• Styrd av myndighetsregler
• Industriell development (4-7 år), ca 6-7/10
• Väger in säkerhet, effekt, produktion, marknad, myndighetskrav, konkurrenter
• Myndighetsgodkännande (2-4 år)
• Totalkostnad mellan 500 MUD – 2 000 MUD
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Kostnad för CAS att driva ett projekt
fram till klinik
• Totalt 25-35 MSEK/projekt
• Tidig discovery för att hitta bra läkemedelskandidater ~5 MSEK
• Optimering av dessa “lead-kandidater” ~6 MSEK
• Regulatoriska säkerhetsstudier ~7 MSEK
• Tillverkningsutveckling och kostnader ~7 MSEK
• Första fas-I kliniska studier på människa ~3 MSEK
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Resistance development since Flemming
(Clatworthy et al. 2007)

Market and competitive environment
• WHO ranks antibiotic resistance as the largest threat to
global health
• Europe: 1/4 of all hospital acquired infections are caused by resistant bacteria, every
year 25,000 patients die, total cost for society >€1.5 billion per year
• USA: 2 million hospital acquired infections, 90,000 patients die/year, 70% resistant
against at least one antibiotic. Cost for society US$ 5 billion per year.
• The market for antibiotics US$ 38.1bn (Datamonitor 2009)
• About 50% of sales come from generics
• Levaquin (J&J) market sales US$ 2.5 billions per year
•

Mission
• Unload the global burden of antibiotic resistance
Vision
• Develop targeted treatment of infectious diseases caused by
Gram-negative bacteria with a newly identified virulence
mechanism – the T3SS target protein and/or other virulence
mechanisms
Strategy
• Show general Proof-of-Concept in patients infected by
Pseudomonas aeruginosa
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Targeted antibiotics – definition
Only affect the pathogenic bacteria, leaving the
natural flora intact
– comparable with cancer treatment!!!
Virulence factors could be defined as essential in
vivo to:
• colonize,
• invade the host tissues,
• adapt to the various environments in the host,
• subvert host functions and overcome host defenses
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Targeted antibiotics – virulence systems
• Virulence systems
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• Inhibition of QS
• Inhibition of adhesion and colonization
• Pili formation
• Secretion systems
• Inhibition of sortase
• Inhibitors of iron metabolism
• Inhibition of the microbial resistance to
the host defenses innate immunity
• Resistance to oxidative stress
• Protection against cationic effectors of the innate
immunity

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Type III Secretion System

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Type III Secretion System
Bacterium
Cell membrane
Infected human cell

Targeted antibiotics – a new path to treat
bacterial infection
• Candidates effective against multi resistant Gram-negative
bacteria in vitro, ex vivo and in vivo
• Targeted antibiotics will only affect the pathogenic/virulent
microbes – less risk for resistance development and spread
• Three projects addressing the companies vision with large
market potential in different early preclinical phase
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• Natural products (INP-11252), T3SS inhibitor
• New screen 125 000 molecules, small molecules approx. 500 Da
• Novel peptides/protein binding T3SS

Technology – Inhibition of the Type III
Secretion System
• The bacteria will dock to the
host cell (macrophage) and
inject proteins that will stop
the phagocytosis capability of
the macrophage
• Same target mechanism, T3SS,
in all pathogenic Gramnegative
bacteria
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Bacterium
Cell membrane
Infected human cell

Technology – Inhibition of the Type III
Secretion System
• The small molecules of
Creative Antibiotics will bind to
the target mechanism and
block injection
• Creative Antibiotics has eight
different classes of small
molecules that that block the
T3SS
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Bacterium
Cell membrane

Development strategy
Compound library Virulence
systems as
targets
Natural
products
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Small
molecules
Peptides
T3SS/
Flagella
Bacteria
expressing T3SS
Shigella spp
Salmonella spp
Chlamydia
trachomatis
Chlamydia
pneumoniae
Yersinia pestis
Pseudomonas
aeruginosa
Diseases caused by the
bacteria
•Diarrhea
•Sterility
•Increased susceptibility for
sexually transmitted
infections
•Trachoma (eye infection)
•Pneumonia
•Bubonic plague
•Pneumonia in patients with
cystic fibrosis and chronic
obstructive pulmonary
disease
•Opportunistic infections
Compound for product development will be selected based on the following criteria:
safety and efficacy data
chemical and physical properties
patent and market exclusivity

HeLa cells infected with P. aeruginosa
• 5 h infection
• INP11252 added at time 0 h at 150, 100, 50 and 20µM
Controls
Uninfected
(T3SS - )
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INP11252
P.a. wt P.a. wt
+ 150µM
P.a. wt
+ 100µM
P.a. wt
+ 50µM
• INP11252 protected HeLa cells from a P. aeruginosa infection
P.a. wt
+ 20µM

Degree
of infection
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INP 400 Inhibits Chlamydia
0 µM 10 µM 15 µM 20 µM
Concentration of compound
Cell type: mouse fibroblast
Bacteria: Chlamydia trachomatis
Incubated for 24hr

Primary indications
• Pseudomonas aeruginosa related infections:
• Wounds (deep brun wounds)
• COPD
• Cystic fibrosis
• E. coli and related pathogens (EPEC, EHEC)
• Sepsis
• Urinary tract infection
• Diarrhea
• Other Gram-negative related infections
• Chlamydia infections (sexually transmitted)
• Diarrhea
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Natural products (INP-11252)
• Results so far
• In vitro and ex vivo
• Promising solubility and toxicity profile
• Good IP position
• Collaboration with Eskitis Institute
• Experience in natural product chemistry and development
• Possibility to apply for “soft funding”
• Chanel 9 News – attention in Australia
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Collaboration AMRI
• CRO with experience from infectious diseases
• Licensed recently a project to Genentech within the antibiotics
field
• Synthesis of new substances around the INP-1750
class of molecules
• Novel chemistry
• New IP
• New screen in diversified library (approx 140 000
molecules)
• New binders
• Novel chemistry after synthesis
• New IP
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• Proven technology
Collaboration Affibody
• Has been in humans
• Screen of new proteins binding to the tip protein
target
• Novel binders
• New IP
• Encouraged by the KaloBios results
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• Fab fragment binding to the tip protein target
• Results from CF patients with Pa infections
• Clinical relevant target

Current deals
• KaloBios – Sanofi-Pasteur, multi million $ deal
• GSK/Anacor, Gram-negative/Boron platform: $12 million up-front,
$252 million milestone, $331 million for each product candidate and
double-digit tiered royalties
• Genentech/AMRI, natural product
• Astellas/Optimer, Clostridium difficile/Gram-positiva (narrowspectrum):
Euro 165 million and double-digit royalty for EPO, ME,
Africa and Cw
• Cubist/Optimer, co-promotion in US
• Novartis/Cubist, collaboration
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Kostnad att driva ett projekt fram till
klinik
• Tidig discovery för att hitta bra läkemedelskandidater ~5 MSEK
• Optimering av dessa “lead-kandidater” ~6 MSEK
• Regulatoriska säkerhetsstudier ~7 MSEK
• Tillverkningsutveckling och kostnader ~6 MSEK
• Första fas-I kliniska studier på människa ~3 MSEK
• Totalt 25-30 MSEK
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Resultaträkning (Tkr)
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Finanser, Q4 2012
Okt-Dec Okt-Dec Jan-Dec Juli-Juni
2011 2010 2011 2009/2010
(12 mån) (12 mån)
Rörelsens intäkter
Nettoomsättning 12 15 2 17
Erhållna bidrag 0 -91 91 631
Rörelsens kostnader -5 174 -3 588 -13 773 -11 819
Av - och nedskrivningar -9 -11 -44 -45
Finansiella poster 217 233 741 12
Resultat efter finansiella poster -4 954 -3 442 -12 983 -11 204
Periodens resultat -4 954 -3 442 -12 983 -11 204

Balansräkning (Tkr)
Finanser, Q4 2011
2011-12-31 2010-12-31
Anläggningstillgångar
Inventarier 139 183
Finansiella tillgångar 0 0
Summa anläggningstillgångar 139 183
Omsättningstillgångar
Kortfristiga fordringar 830 556
Kortfristiga placeringar 26 007 39 533
Kassa och bank 2 175 1 209
Summa omsättningstillgångar 29 012 41 298
Summa tillgångar 29 151 41 481
Eget kapital 17 788 30 771
Långfristiga skulder 7 941 7 941
Kortfristiga skulder 3 422 2 769
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Summa eget kapital och skulder 29 151 41 481

Thanks!
www.creativeantibiotics.com