aRigen Pharmaceuticals, Inc.
Tsuneharu Baba, MD, PhD VP of Scientific Affairs
Photo of Mt. Fuji, Japan
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Company • Established in 2001, in Tokyo, Japan • Mr. Gensuke Tokoro, CEO and President • Raised US$ 56 Mn in total
Positioning • The only bioventure in Japan focusing on infectious diseases • 8 first-in-class new chemical entities (NCEs) in pipeline
Mission • Discover breakthrough compounds in Japan and develop
them for global health
aRigen at a Glance
Key products Antibacterials • WAP-8294A2 (MRSA) – IND completed • ARB-MGR06 (MRSA) - Preclinical • ARB-CF0223 (Cystic fibrosis) – POC • ARB-FV0127 (Respiratory) – Bridging into Japan Antivirals • ARYS-01 (Herpes Zoster) – Ph II/III Others • ARH-1029 (Anti-H. pylori with PPI, GI) – IND ready • ARH-1030 (Anti-H. pylori) – Preclinical • ARM-AK105 (Dyslipidemia) - Preclinical
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WAP-8294A2 A potent next-generation
anti-MRSA compound
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MRSA, a resistant strain to various antibiotics, is life-threatening.
Vancomycin of 50 year-history is still used as the 1st-choice drug.
Vancomycin is not a satisfactory MRSA drug in its efficacy.
No drugs have been proven to be superior to Vancomycin.
MRSA-specific and effective anti-MRSA drug is highly demanded.
Current status of MRSA infection
WAP-8294A2 – Key Highlights
NME (Depsipeptide)
Produced by fermentation
New mechanism of action
Narrow spectrum (MRSA, VISA, VRSA and MSSA)
Bactericidal antibiotic
Very fast onset of antimicrobial action
Strong patent protection (Substance and formulation)
IND completed
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(Photo from BBC News on 20th May 2009)
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Systemic infection mouse model with MRSA (ATCC33591)
Anti-microbial activity
MIC ED50
WAP-8294A2 0.1 µg/ml 0.06 mg/kg
Vancomycin 1.0 µg/ml 3.12 mg/kg
WAP-8294A2 Daptomycin Quinupristin/Dalfopristin Arbekacin Linezolid Teicoplanin Vancomycin
Clinical dose (mg/kg/day)
0.5 – 2.0 (expected)
4 - 6 22.5 4- 6 12 - 24 4 - 10 20 - 40
ED50 (mg/kg, mouse)
0.06 0.69 – 1.10 15 - 75 0.31 2.8 - 15 0.098 –
0.141 2.15 - 17
NOEL (mg/kg, rat) 9 4 - 6 2 - 60 6.25 20 10 40 - 80
MLD (mg/kg, rat) 60 > 100 28 150 - 169 > 400 60 -
LD50 (mg/kg, rat) - - - - - 86 - 90 740 - 760
Safty margin in animal models
(From published literatures and interview forms)
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3
0
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2
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Log 1
0 CFU
/mL
2 4
hours
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VISA 14009 VISA 14005
MRSA 14345 MRSA 14343 MRSA 14249
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-In Vitro Activity Study of WAP-8294A2 – R. M. Alden Research Laboratory (CA, USA)
Rapid action against MRSA and VISA
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Indication and Market size
Target indications MRSA infections
Potential market size
License deal Available for global and regional
Estimated launch year
Global market size
Global market size in launch
year
Potential global peak sales/year
Potential market share
2016-2017 $ 6 B * $ 6.6 B $ 1.12 B 17 %
* Year of 2012 by Data Monitor
ARH-1029 Anti-H. pylori compound with strong PPI action
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H. pylori is a cause of gastric ulcer and gastric cancer.
Current therapy requires combination of 3 drugs for 2 weeks.
Resistant-H. pylori to current therapy is increasing.
Eradication of H. pylori is the most effective prevention of gastric ulcer and gastric cancer.
Current status of H. pylori treatment (H. pylori)
ARH-1029 – Key Highlights
NME Specific anti-H. pylori compound for complete eradication
Strong PPI action
Stable in gastric acid
Ulcer-healing effect equal to the current triple therapy therapy
Effective against resistant H. pylori strains
Strong patent protection
IND ready
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Concept of compound
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A compound with dual actions
ARH-1029 Potent PPI action
Bactericidal action against H. pylori
3. As strong as Omeprazol
1. Specific only on H. pylori
2. Effective against resistant strains
Bactericidal action against H. pylori
No PPI action ARH-1030
A compound with single action
H. Pylori infected mouse study
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Incidence (%) of Peptic Ulcer
ARH-1029 ARH-1029
Bacterial eradication rate (%)
OME (10 mg) + CAM (10 mg) Current experiment
OME (10 mg) + CAM (10 mg) J Gastoroenterol 1998
(mg/kg/dose; b.i.d.)
Indications and Market size
Target indications H. pylori-associated gastric and duodenal ulcers, Gastric MALT, Early gastric cancer, (prevention of gastric cancer)
Potential market size
License deal Available for global (except Japan territory*)
Estimated launch year
Actual global market size
Global market size in launch
year
Potential global peak sales/year
Potential market share
2015 (Japan) $ 28 B (2006) $ 31 B $ 7.75 B 25 %
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* Licensed out to Taiho Pharamceutical, Co., Ltd., for Japan.
ARYS-01 A potent topical cream
for Herpes Zoster
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Approximately 1 out of 4-6 persons experience the disease.
The incidence increases with age both in women and men.
Pain and skin lesions are the major symptoms.
Oral repeated doses or i.v. doses of anti-viral agent is a current treatment of choice .
No effective topical anti-viral product is available for treatment of Shinglesʼ skin lesions.
Current status of Shingles
ARYS-01 – Key Highlights
Topical cream of thymidine analogue, Sorivudine
Anti-viral activity specifically against Varicella-zoster virus
2,000 times more potent vs. Acyclovir (in-vitro activity)
No systemic absorption
Successful Ph I results in Singles patients
Ph II/III study going on in USA
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Efficacy in comparison with Acyclovir
In-vitro • Anti VZV • Anti HSV-1 • Anti-HSV-2 • Cell growth
ARYS-01 >> Acyclovir (2,000 times) ARYS-01 > Acyclovir ARYS-01 << Acyclovir No inhibition
In-vivo (HSV-1 in mice) • Encephalitis (po, ip) • Systemic infection • Dermal infection (po) • Dermal infection (topical)
ARYS-01 >> Acyclovir ARYS-01 < Acyclovir ARYS-01 < Acyclovir ARYS-01 = Acyclovir
Systemic infection model of Simian-varicella virus in monkeys (po)
ARYS-01 >> Acyclovir
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Indication and Market size
Target indications Singles (Herpes zoster)
Potential market size
License deal Available for global and regional
Estimated launch year
Global market size
Global market size in launch
year
Potential global peak sales/year
Potential market share
2013 $ 2.5 B (2007) $ 2.75 B $ 0.68 B 25 %
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Thank you very much!
aRigen Pharmaceuticals, Inc.