aRigen Pharmaceuticals, Inc.

Tsuneharu Baba, MD, PhD VP of Scientific Affairs

tbaba@arigen.jp

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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Log 1

0 CFU

/mL

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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.