Financial Results Ended March 2012
Status of R&D Pipeline◇Progress and initiatives in fiscal 2012

May 10, 2012
Keiji Hirai
Director KYORIN Holdings,Director,Holdings Inc.
Inc
Representative Director,President and Chief Executive officer
KYORIN PharmaceuticalPh
i l Co.,C Ltd.
d0

Long-Term Vision「HOPE100」
To be a drug manufacturer that is trusted by patients and medical
professionals ,andp,
is recognized
gfor its presence
pin society.
y－Establish a strong presence in specialized fields －【 specialized fields 】 ◆ FC domain ： respiratory , otolaryngology , urology◆ Priority Fields ： IBD(inflammatory bowel disorder)－ Enhance and strengthen the product portfolio and R&D pipeline －◆Proprietary Drug Discovery : Fundamental research domains (inflammation/infectious
diseases/immunology) ⇒ Leverage open innovation◆In-licensed Products : Actively explore in-licensing in specified◆LCM ： NewN
fformulations,l ti
didirection
ti ffor usage anddd
dosages ffor mainstay
i t products;
d t
drug cultivation research
LCM：Life Cycle Management1

Drug Development Pipeline: Progress in FY2011 (In-House)
Product &development codePhⅠPhⅡKRP 108
KRP-108

PhⅢ

application

Approval/
LaunchPhⅢcompleted

Respiratory

KRP-AB1102
Urological

Uritos OD tablet

Otolaryngological

KRP-209
KRP AM1977X
KRP-AM1977XEntering PhⅡ
On market in 4/2011

Entering PhⅡ
PhⅠcompleted
Information in the dotted box are changes in FY2011

Infections

KRP-AM1977Y※Information colored red are changes since November 9/2011

Preparing for PhⅠ

Pentasa(UC)
( )

li i
applicaion

Once a day

Pentasa(UC)PhⅢcompleted

suppository

Other

KRP-203

PhⅠcompleted

KRP-110

discontinuation

AS-3201

Cancelled co-development

KRP-104

abeyance2Drug Development Pipeline: Progress in FY2012 (In-House)
Product &development code

PhⅠ

PhⅡ

PhⅢ

application

KRP 108
KRP-108
Respiratoryapplication

KRP-AB1102

PhⅡ

KRP AB1102F
KRP-AB1102F

Entering PhⅡEntering PhⅢ

Active In-Licensing and Joint Research

Urological

OtolaryngologicalApproval/
LaunchKRP 209
KRP-209
KRP-AM1977X

PhⅡ

臨床薬理試験(PhⅠ)

Infections

KRP-AM1977YEntering PhⅠ

Pentasa(UC) Once a day
IBD

Approval

Pentasa(UC) suppository

KRP-203application

Entering PhⅡ

3

Anti-asthmatic KRP-108 : Status of Development■Status of Development○Application: Aim to file application for approval in FY2012○Clinical trials: Phase III (Completed in Mar. 2012)

TOPICS

April 20, 2012

The Committee for Medicinal
Products for Human Use ((CHMP)) ofthe European Medicines Agency(EMA) recommended flutiform® forcommercial sale.

◆Study◆Sd Design:iA single-blinded
i l bli d d comparative
i study
d withi h an active
i comparator
Target disease: Adult bronchial asthma
Treatment duration: 8 weeks
Active comparator: Fluticasone
DDosageregimen:iI h l db
Inhaledby twice
i –a-dayd ddosingi ((two actuationsiper ddose))◆Study Design: A non-blinded, non-comparative open studyTarget disease: Adult bronchial asthma
Treatment duration: 52 weeks
Dosage regimen: Inhaled by twice-a-day dosing (two or four actuations per dose)

Favorable results seen in all major evaluation categories4

Pentasa: Status of Development for New Dosage Form
■Status of Development 【New Dosage Form】 ( Suppository)○Application Aim to file application for approval in FY2012○Application:○Clinical trials: Phase III (Completed in Feb. 2012 ）◆Study Design: A randomized, controlled, parallel comparative study
Target disease:TdiUl
Ulcerativei colitis
li i ini activei phasehComparator: Inactive placebo
Dosage regimen: Once a day (rectal insertion)

Efficacy: Substantively different from placebos
placebos, with highremission induction rate shown. (p=0.0000)
Safety: Product retains a high degree of safety.

5

COPD Treatment Agent: KRP-AB1102■KRP-AB1102

TOPICS

Action: Long-acting muscarine M3 antagonist (LAMA)
Active ingredient:g
Aclidinium Bromide
Formulation: Dry Powder Inhaler

February 24, 2012

○Clinical trials: Phase II (started in Feb. 2012 ）◆Study Design : A randomized, Duoble-Blind, Placebo controlled, Parallel-group Comparison Study
Target disease : COPD
Treatment duration : 4 week treatment
Active comparator : Inactive placebo
Dosage regimen : Inhaled by twice-a-day dosing

The Pulmonary-Allergyygy Drugs
gAdvisory Committee of the U.S.
Food and Drug Administration(FDA) has adopted arecommendation to approvegacridinium 400 micrograms(administered twice daily) after
verifying efficacy and safety.

■KRP
AB1102F : launched development of combination drug
■KRP-AB1102F
Fixed dose combination of LAMA and LABA(Long Acting Muscarinic Antagonist)◇LAMA : Aclidinium Bromide◇LABA : Formoterol

Dry powder inhaler: Genuair®

6

Main R&D Activities -１ (February 3 , 2012 Release)※Changes from the previous announcement(Feb.3, 2012)

Ph IIb Application submitted
Stage

Compound/C dCodeTherapy
area/Action/A iApplication
submitted(11/2011)

Pentasa(tablet)Ulcerative
colitisFerringPharmaceuticals

New dosage regimen for ulcerative colitis in theremission phase (once a day)Preparing forapplication※

Pentasa(suppository)

Ulcerative
colitisFerringPharmaceuticals

Consideration of a new dosage form for the active
phase of ulcerative colitis (once a day)・Development of a new
dosage form
・PhⅢcompleted(2/2012)※

JapanOverseas

OriginFeatures

Comments

Preparing forapplication※(US)SkyePharma: Application
submitted (3/2009)（Europe）
Mundipharma: Application
submitted (3/2010)

KRP-108(Inhalant)

Antiasthmatic

SkyePharma
PLC

An ICS/LABA combination product, which offers
better compliance and convenience to the patients・License agreement with
SkyePharma (4/2008)
・Domestic Ph II completed(4/2010)
・PhⅢcompleted(3/2012)※

PhⅡ（2/2008）

PhⅡ（9/2007）

KRP-104

Anti-diabetes
agent

In-house

A DPPIV inhibitor to reduce blood glucose throughsuppression of the degradation of insulin-releasing
hormone. Diabetic therapy with fewer side effects is
expected than existing treatments.

・Overseas Ph II b completed(3/2011)・Domestic Ph II b completed(3/2010)7

Main R&D Activities -2 (February 3 , 2012 Release)①※Changes from the previous announcement(Feb.3, 2012)

POC Project (Pre-clinical ~ Ph II)
Stage
Japan

Overseas

Compound/CodeTherapy
area/Action

OriginFeatures

Comments

PhⅠ（12/2010）

PhⅡ（POC)(12/2010)(Novartis)

KRP-203

Transplantation,
autoimmune
diseases,andIBDIn-house

An immunosuppressant with a novel mechanism
called an S1P-agonist. It may have a better safety
profile than previous ones as well as an excellent
effect under concomitant use with other types ofimmunomodulator.

License agreement with
Novartis (2/2006)
New license agreement
IBD (11/2010)

PhⅡ（8/2011）

PhⅢ
Merz

KRP-209

Tinnitus

Merz

KRP-209 (Neramexane) is expected to improve thepatients' annoyance and difficulties in their life
caused by tinnitus, mainly through its two
pharmacological properties: 1) NMDA antagonistic
activity and 2) Nicotinic acetylcholine antagonistic
activity

License agreement withMerz (11/2009)
Merz:Ph I clinical trial ofJapanese patients in US
completed (3/2010)

PhⅡ※（2/2012）（Europe）
Almirall: Preparing for
application(US)
FForestt
Pharmaceuticals: Preparing for
application

KRP-AB1102（Inhaled drug）

Chronic Obstructive
Pulmonary Disease(COPD)

Almirall- New Chemical Entity: Aclidinium Bromide- Long Acting Muscarinic Agonist (LAMA)- Twice Daily administration-Onset of Action on the first dayGenuair®
1) Designed
D id withith a feedbackf db k system,twhichhi h throughthha'colored control window' and an
audible click helps confirm that the patient has
inhaled correctly2) Counter for remaining doses
3) Safety features such as an anti-double-dosing
mechanism and an end
end-of-doseof dose locklock-out
out
system to prevent use of an empty inhaler

License agreement withAlmirall (2/2011)

Preparingfor clinical
trials(Europe & US)
Almirall: Ph Ⅲ
(US)ForestLaboratories: PhⅢ

KRP-AB1102F(Fixed dosecombination
inhaled drug)

Chronic Obstructive
Pulmonary Disease(COPD)

Almirall

Combination of aclidinium bromide with the longacting beta agonist formoterol :This combination is aimed at providing higher
efficacy than each component alone,as well as theimproved convenience of having the two products inthe same easy to use inhalation device.This iscurrently in phase Ⅲ clinical development.

※8

Main R&D Activities -2 (February 3 , 2012 Release)②※Changes from the previous announcement(Feb.3, 2012)

POC Project (Pre-clinical ~ Ph II)
Stage

Compound/CodeTherapy
area/Action

PhⅠ*（8/2011）

KRP-AM1977X(Oral agent）

New quinolonesynthetic
antibacterial agent

In-house

PhⅠ
preparations

KRP-AM1977Y(Injection）

New quinolone
synthetic
antibacterial agent

In-house

JapanOverseas

OriginFeatures

Comments①Superior ability to combat drug-resistant grampositive bacteria (incl. MRSA)②Outstanding ADME (oral absorption, tissuemigration)③High degree of safety expected since safety
hurdles cleared prior to clinical trials

others・AIPHAGAN
AIPHAGAN Ophthalmic Solution 0
0.1%
1% ： To be released on May 1111,2012
2012 ※
・Discontinued development of KRP-110 deleted it from the list of R&D activities. ※9

■ These forecast figures are based on information currently
available to the Company and may include uncertain factors orriski k thath affectff
our future
fperformance.
fAccordingly, actual business results may materially differ from theforecasted figures due to various factors in the future.