KYORIN Pharmaceutical Group New
Mid-Term Business PlanYYour
healthh lth isi KYORIN’s
KYORIN’ mission.
i i

HOPE 100 －Stage 1－(Fiscal 2010～2015)
R&D Strategy: Pipeline Status
May 12, 2010
Director KYORIN Co
Director,Co., Ltd.
LtdKYORIN Pharmaceutical Co., Ltd.
Representative Director,
P
President
id t andd Chief
Chi f ExecutiveEti Officer
Offi
K iji Hi
Keiji
HiraiiR&D Initiatives Focused on Time Frames
Initiatives to be taken under the medium-term business plan (stage 1) are labeled T1, T2,or T3 according to the stage at which results will materialize.
T1：Today–For Results in Stage 1
T2：Tomorrow–For Results in Stage 2
T3：The day after tomorrow–For Results in Stage 3

T1＜New drugs group＞■Maximize Popularity of Core Products (Kipres,(Kipres Uritos)■Early launch of the products under development ：KRP-108■Out-licensing of product under development：KRP-104■LCM (Uritos OD tablets)

Ethical Drugg BusinessE＜Original products group＞■LCM (Mucodyne DS 50%, new application/ dosage for Pentasa)

T2

T3＜New drugsg group＞
gp■Aim for early application and approval of newly developed products and enhanceand strengthen the pipeline
・Develop and promote KRP-209, KRP-203, AS-3201, KRP-110, and antibacterial agents・Secure licensed-in drugs (FC domain： respiratory medicine, otolaryngology and urology)＜New drugs group＞■Strengthen drug discovery capabilities： Create new global pharmaceuticals
・Actions
A ti
ffor fundamental
f dt l reform
foff drug
ddiscovery
disystemt
LCM： Life Cycle Management

1１

Provide Products to Market Quickly and Enhance
and Strengthen Product Pipeline
HOPE100－Stage 1－Fiscal 2010-2015
・FocusFefforts
ff t on LCM
・Aim to launch KRP-108 to market
in fiscal 2014
・Aim to license KRP-104

HOPE100－Stage－ 2
Fiscal 2016-2019

HOPE100－Stage 3－
Fiscal 2020-2023

Application
Ali ti andd approvall
for products underdevelopment Strengthen
and enhance pipeline

Global,Glb l originali i l
new drug discovery

Aim to secure licensed-in drugs
LCM
Products
UnderDevelopment＊Including inlicensed products

IIn-House
H
Drug
Discovery

Mucodyne DS 50 Uritos OD tablets
Pentasa New application/dosage (Once daily administration)
KRP-108 (Asthma treatment)
KRP-104 (Anti-diabetes agent)
Candidate compounds for in-licensing(respiratory, urological, etc.)

LCM： Life Cycle
Management

AS-3201 (Diabetic neuropathy treatment)
KRP-209 (Tinnitus treatment)
KRP-203
KRP
203 (Immunosuppressant)KRP-110 (Constipation, intractable pruritus treatment)
Antibacterial agents■W k to■Workt reformftheth R&D process basedbd on ththe ""market-in"
k t i " conceptt
・Promotion of partnering, in-licensing, LCM, research topic selection, review evaluation and decisionmaking related to products under development.

■Restructure the drug discovery network:・Reviewe e tthee functions
u ct o s oof ActivX
ctaandd KSRL
S(act(activelye y ututilize
e as ddrugug ddiscovery
sco e y bases in keyey dodomains)a s)
・Proactive external collaboration

In-House Drug Discovery Focus Domains
Respiratory, urological, infectious diseases, etc.

22Key Products Under Development
Long-Term Vision HOPE100
HOPE100－Stage 1－
Fiscal 2010-2015
Dev. code

HOPE100－Stage 3－
Fiscal 2020-2023

Dev. stage

Pentasa tablets

Ph III

Ulcerative Colitis

KRP-104

Ph IIb

Anti-diabetes agent

KRP-108

Ph IIｂ

Anti-asthmatic treatmentAS-3201
AS3201Ph IIb

Diabetic neuropathy

KRP-209

Ph II
In preparation

Tinnitus

KRP-203(Domestic) Ph I
In preparation

Immuno-modulator

Once dailyadministration

HOPE100－Stage 2－Fiscal 2016-2019(Overseas) PhⅠfinished;
Ph II in preparation

KRP-110

Ph I
In preparation

Opioid-induced
Oi id i dd constipation
ti ti/ intractable pruritus treatment
3

Development Status of KRP-108

Ph II completed
Ph III clinical trial in preparation
 Target indication
・Asthma New ethical combination product・Best combination of ICS and LABA
・Optimal device
・ ICS： Fluticasone propionate
・ LABA： Formoterol fumarate
・ Device： Pressurised Metered Dose
Inhaler (pMDI)

ICS： Inhaled steroid
LABA：Long-acting β2 stimulant

Development Status
Domestic：- Ph II clinical trials completed- In preparation for Ph-III clinical trial- Japanese NDA targeted for fiscal
2012
Overseas：
US ＜Abbott/SkyePharma＞
・NDA filed in March 2009
Europe＜Mundipharma＞
・ MAA submitted in March 201044

Development Status of KRP-104
Oversea Ph IIb ongoing
Domestic Ph IIb completed
TissueCirculation

DPP4Tissue

High safety expected

Development Status Domestic： Ph IIb clinical trial completed
・Results confirmed in February 2010
 Overseas：O erseas Multinational
M ltinational Ph IIb trial on going・ Started in November 2009
・ Expected to confirm results in 2011

Overview of Clinical Trials
 Domestic
 Target indication： TypeⅡdiabetes
・ Explored recommended clinical dose in Extremely low tissue penetration
Type II diabetes
and intracellular permeability; works
・ Twice daily dose for 12 weeks
by staying in the bloodstream,⇒ Confirmed safety as expected andwhich is target organ of DPP4i
confirmed robust effect at all doses (highlysignificant in all dose groups).
groups) Does not act on other DPP subtypes
Dose-dependent effects observed(ex, DPP8/9), less chance of side
 Overseaseffects
・ Exploring recommended clinical dose in In late-stage development
Type II diabetes uncontrolled with Metformin(Overseas and domestic)・Once daily dose for 24 weeks
55

Development Status of KRP-209
Ph I study (Japanese single PK) completed in the US
Ph II domestic clinical trial in preparation
 Target indication:
・ Subjective tinnitus First-in-class agent･ Medical field with high unmet needs with nofrontrunner in Japan･ A novel oral drug for tinnitus suppressing
abnormal spontaneous activity and nerve
action potential in the inner ear, nerves, andcerebral cortex

Development Status Domestic：・In preparation for Ph II clinical trial(Planned to start in 2011)
 Overseas：
Overseas Europe/US ＜Merz Pharma＞
・ Ph III clinical trials ongoing・ EU MAA targeted for 2011
・ US NDA targeted
gfor 201266

Development Status of KRP-110
Ph I clinical trials in preparation
 Characteristics of KRP-110･Highly selective μ opioid receptor antagonist･ Good oral absorption and high safety profile
expectedt d Target indications･Opioid-induced
Opioid-induced constipation
constipation*

Development Status
Overseas： In preparation for
PhⅠclinical trials･Planned to start in 2010(* Serious constipation induced by opioid analgesics)･Ideal mode of action to directly block the adverse effect of opioid analgesics･No inhibitory effect on analgesic effect of opioids･Contributes to pain treatment by alleviating constipation and associatedabdominal symptoms･Intractable pruritus**(** Systemic and chronic itching associated with end stage renal disease and cholestatic disease,disease andatopic dermatitis)･Blocks the pruritus signal transmitted by the opiod peptide･Effective even for ppruritus ineffective with existingg therapy
py･Improves QOL impaired by chronic pruritus
77

Main R&D Activities① （ May 11 , 2010 Release)＊：Describe the latest changes

Ph II～Application
Stage
Domestici

Overseas

Ph III(12/2009)

Compound/
Code

Therapy area/
ActionOriginFeatures

PENTASA
Tablets

Ulcerative colitis

FerringPharmaceuticals

New dosage regimen for ulcerative colitis in the remission
phase (once a day)CommentsPh II（3/2005）(Eisai: PhⅢ)

AS-3201（Tablets ）Diabetic
neuropathy

Dainippon
Sumitomo

Aldose reductase inhibitor to reduce the sorbitol accumulationin the cell, and improve diabetic neuropathy

Co-development withDainippon Sumitomo・PhⅡb（9/2007）

Ph II（2/2008）

PhⅡ（9/2007）

KRP-104
KRP
104

Anti-diabetes
Antidiabetes
agent

In-house
InhouseA DPPⅣ inhibitor to reduce blood glucose through suppressionof the degradation of insulin-releasing hormone. Diabetic
therapy with fewer side effects is expected than existingtreatments.

・PhⅡb
PhⅡb in overseas (11/2009)＊PhⅡb in domestic
completed （3/2010）

Ph II（8/2008）

US: Abbott
NDA filed(3/2009)

KRP-108

anti-asthmatic

SkyePharma
PLC

An ICS/LABA combination product, which offers better
compliance and convenience to the patients.

License Agreement withSkyePharmaSye a a ((4/2008)/ 008)＊Ph II completedin domestic (4/2010)

Europe:Mundipharma
MAA submitted(3/2010)

Other Comments※Orally Disintegrating Tablet of Immidafenasin（INN),
a Drug for Overactive Bladder※Mucoregulating drug “Mucodyne DS50%: Application(12/2009): Approval(1/2010)

8Main R&D Activities② （ May 11 , 2010 Release)
POC Project （Pre-clinical～Ph I）
Stage
Domestic＊Ph Iinpreparation

Overseas

Compound/
Code＊：Describe the latest changes

Therapy area/
ActionOriginFeatures

Comments

License agreementwith Novartis (2/2006)

Ph I(7/2007)

KRP-203

Transplantation andautoimmune
diseasestreatment

In-house

An immunosuppressant with novel mechanism
called 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

PhⅠ inpreparation

KRP-110Opioidinduced
constipation
andintractablepruritus

In-house

A highly selective μ-opioid receptor antagonist.
It is expected to block constipation induced byopioid analgesics without interrupting theanalgesic effect of opioids. It is orally effective invarious itching models, indicating potential of anovel anti-itch
anti itch drug for intractable pruritus.
pruritus※Amorolfine HCl Nail lacquer and KRP-105 have been deleted from the list of development pipeline since both product were discontinued
from the standpoint of our R&D strategy※The standard on the information disclosure has been changed and the products, which has been decided to enter the clinical stage, will bedisclosed. Therefore, KRP-107 and KRP-109 have been deleted from this list while the developments of KRP-107 and KRP-109 will becontinued.
In licensing
Stage
Domestic*Ph-IIin
preparation

Overseas
Ph-III(Merz)

Compound/
CodeKRP-209

Therapy area/
ActionTinnitus

OriginMerz

Features

KRP-209 (Neramexane) is expected to improve
the patients’ annoyance and difficulties in theirlife caused by tinnitus through mainly its two
pharmacological properties:
1)NMDA antagonistic activity and2)Nicotinic acetylcholine antagonistic activity

Comments

License Agreementwith Merz (11/2009)
PhⅠclinical trial inJapanese (single dosePK) in US completedby Merz (03/2010)
9Main R&D Activities③（ May 13 , 2009 Release)
Licensing development＊：Describe the latest changes

Product name・CodeStage

Licensee ・Collaborativeresearch

Therapy area/
ActionOriginComments

Alphagan/Alphagan P

Domestic
Ph III（7/2007）

Senju Seiyaku

Glaucoma

Allergan (US)・Licensed from Allergan（Cross license of gatifloxacin ophthalmicsolution ）・License out to Senju（5/2004）
・License-out

Ketas

Overseas
Ph II（8/2005）

MediciNova (US)

Cerebrovasculardisorders

In-house

・KYORIN grants MediciNova an exclusive
license in all countries worldwide except forJapan,China, South Korea and Taiwan todevelop, manufacture and sell the compoundand products for the multiple sclerosis
indication.(10/2004)
Result of PhⅡ was reported in April 2008.

KCA-757

Overseas
Ph III(Anti-bronchial
Asthma:11/2006)
Ph II/III(Interstitial
cystitis:y5/2005)

MediciNova (US)Anti-bronchialasthma andInterstitial cystitis
agent

In-house

・KYORIN grants MediciNova an exclusive
license in all countries worldwide except forJJapan,China,Chi
S th Korea
SouthKandd Taiwan
T itotdevelop, manufacture and sell the compoundand products・Interstitial cystitis:Results of PhⅡ/Ⅲ wasreported inJanuary 2007 and ceased development
・Bronchial asthma: Clinical trial oversea wasdiscontinued.

KRP-203

Overseas
Ph I（7/2007）

Novartis(Switzerland)

Transplantation
and autoimmune
didiseases
ttreatment
tt

In-house

An immunosuppressant with novel
mechanism called S1P-agonist. It may have ab tt safety
betterf t profile
fil ththan previous
iones aswell as an excellent effect under concomitant
use with other types of immunosuppressants.
10The End118