Interim Term Financial Results Ended
September 2011
Status of R&D Pipeline〇Progress and initiatives in fiscal 2011

November 9, 2011
Keiji Hirai
Director KYORIN Holdings,Director,Holdings Inc.
IncRepresentative Director,
President and Chief Executive officer
KYORIN PharmaceuticalPh
i l Co.,C Ltd.
d0

Long-Term Vision「HOPE100」～KYORIN Pharmaceutical Co., Ltd.～“Our determination toward a pharmaceutical company as
globally reliable presence
presence”－ Establish a strong presence in specialized fields◆Enhancement and strengthening development pipeline (inhouse,in(inhouse inlicense product) of FC domain（respiratory・otolaryngology・urology） and Priority Fields （IBD）－ Create original new grobal products for the patients1

2011/5 release

Drug Development Pipeline: Progress in FY2011 (In-House)～PhⅠ
Respirator
Respiratory

PhⅡ

KRP-AB1102

PhⅢ

Application

KRP-108(COPD)
Entering clinical trials(Asthma)

Uritos OD
tablets

Urological

Otolaryngolo
gicalApproval/Launch

On market in April
2011

KRP-209

KRP-209((Tinnitus))

KRP-AM1977
Infections(Antibacterial agent)Enteringg Ph IKRP-203
KRP-110
Other

Opioid-inducedconstipation treatment(overseas)

KRP-203(IBD)

KRP-104(diabetes)

Pentasa (UC)suppository
Pentasa (UC)once a day

Pentasa (UC)once a day

Aim toout-license

AS 3201
AS-3201(Diabetic neuropathy)

22011/11 release

Drug Development Pipeline: Progress in FY2011 (In-House)～PhⅠ
Respirator
Respiratory

PhⅡ

PhⅢ

KRP-AB1102

KRP-108
KRP
108

PreparingPiforfclinical trials

Application

Approval/Launch(Asthma)

Uritos OD
tablets

UrologicalOn market in April
2011

KRP-209

Otolaryngolo
gical

Ph II from Augustg

KRP-AM1977X

Information in the dotted box are changes since March 2011

Ph I from August
Infections

KRP-AM1977Y
Ph I preparations
Pentasa (UC)suppository

KRP-203

Pentasa (UC)once a day completed

Other

KRP 110
KRP-110
Opioid-induced constipation
treatment (overseas)

KRP-104(diabetes)* The Company has cancelled the AS-3201 (diabetic neuropathy) co-development agreement with Dainippon Sumitomo forstrategic reasons and has deleted AS-3201 from the list of R&D activities.

3

2011/11 foreast

Drug Development Pipeline: Progress in FY2011 (In-House)～PhⅠ
Respirator
Respiratory

PhⅡPhⅢ

KRP-AB1102

KRP-108

Entering clinical trials

Application

Approval/Launch(Asthma)
Ph III completed

Uritos ODtablets

UrologicalOn market in April
2011

KRP-209

Otolaryngolo
gical

Ph II from August
gKRP-AM1977X

Information in the dotted red box are changes
since November 9/2011

Ph I from August
Infections

KRP-AM1977Y
Ph I preparations

KRP-203
Ph I I preparations
Other

KRP 110
KRP-110
Opioid-induced constipation
treatment (overseas)

Pentasa (UC)suppository completed
Pentasa (UC)once a day application

KRP-104(diabetes)

4Anti-asthmatic KRP-108: Status of Development■Status of Development○Application: Aim to file application for approval in FY2012○Clinical trials: Phase III (started in Aug. 2010)◆Study Design: A single-blinded
single blinded comparative study with an active comparator(LSO in FY2011, earlier than the planned LSO target)
Target disease: Adult bronchial asthma
T tTreatment
tdduration:
ti : 8 weeks
kActive comparator: Fluticasone
Dosage regimen: Inhaled by twice –a-day dosing (two actuations per dose)◆Study Design: A non-blinded, non-comparative open study(LSO in FY2011, earlier than the planned LSO target)
Target disease: Adult bronchial asthma
Treatment duration: 52 weeks
osage regimen:eg e Inhaleda ed by twice-a-day
tw ce a day dosing
dos g (two oor fourou actuat
actuationso s peper dose)
Dosage5Pentasa: Status of Development for New Dosage
Regimen and New Dosage Form
■Status of Development 【New Dosage Regimen】 (Once-a-day oral administration)○Application:pp
Aim to file applicationpp
for approvalpp
in FY2011○Clinical trials: Phase III (started in Dec. 2009）◆Study Design：a randomized, controlled, parallel comparative study(LSO ini FY2011,FY2011 earlierli thanth theth plannedld LSO target)tt)
Target disease: Ulcerative colitis in remission phase
Comparative dosage regimen: Once a day vs. three times a day■Status of Development 【New Dosage Form】 ( Suppository)○Application: Aim to file application for approval in FY2012○Clinical trials
trials: Phase III (started in Nov
Nov. 2010）◆Study Design: A randomized, controlled, parallel comparative study(LSO in FY2011, earlier than the planned LSO target)
Target disease: Ulcerative colitis in active phase
Comparator: Inactive placebo
Dosage regimen: Once a day (rectal insertion)

6

Main R&D Activities① ( November 8 , 2011 Release)*Changes from the previous announcement(July 29, 2011)

Ph IIb Application submitted
StageCompound/C dCodeTherapy
area/Action/A iOrigin

PhⅢ(12/2009)

Pentasa(tablet)

Ulcerativecolitis

FerringPharmaceuticals

New dosage regimen for ulcerative colitis in theremission phase (once a day)PhⅢ
(11/2010)

Pentasa(suppository)

Ulcerativecolitis

FerringPharmaceuticals

Consideration of a new dosage form for the active
phase of ulcerative colitis (once a day)*Development of a newdosage form

Japan

OverseasFeatures

CommentsPhⅢ(8/2010)(US)
SkyePharma: Applicationsubmitted (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)

PhⅡ（2/2008）

PhⅡ（9/2007）

KRP-104

Antidiabetes
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 Activities② ( November 8 , 2011 Release)*Changes from the previous announcement (July 29, 2011)

POC Project (Pre-clinical ~ Ph II)
StageJapan

Overseas

Compound/
Code

Therapyarea/Action

OriginFeatures

Comments

PhⅡ（POC)(12/2010)(Novartis)

KRP-203

Transplantation,autoimmune
diseases,andIBD

In-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 of
immunomodulator.

PhⅠ（8/2010）

KRP 110
KRP-110

Opioid-inducedOi id i dd
constipation andintractable pruritus

I hIn-house

A hihighlyhl selectivel ti μ-opioid
i id receptor
t antagonist.
ti t It iis
expected to block constipation induced by opioid
analgesics without interrupting the analgesic effectof opioids. It is orally effective in various itchingmodels, indicating potential of a novel anti-itch drug
for intractable pruritus.

PhⅡ*（8/2011）

PhⅢ
Merz

KRP-209Tinnitus

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

Preparingfor clinical
trials（Europe）
Almirall: Preparing for
application(US)
Foresto est
Pharmaceuticals: Preparing forapplication

KRP-AB1102（Inhaled drug）

Chronic Obstructive
Pulmonary Disease(COPD)

AlmirallThis bronchodilating agent has an acetylcholine
receptor antagonist action that offers long-lasting
improvement for breathing difficulty and shortness ofbreath associated with COPD.
①Fewer sistemic side effects②Twice-daily②Twicedaily dosage offers a full
full-dayday
improvement in symptoms and respiratory
function③Short time required for the maximum effectLicense agreement withAlmirall (2/2011)

PhⅠ*（8/2011）

KRP-AM1977X(Oral agent）

New quinolone
synthetic
antibacterial
tib t i l agentt

In-house

PhⅠ
preparations

KRP-AM1977Y(Injection）

New quinolone
synthetic
antibacterial agentIn-house①Superior ability to combat drug-resistant grampositive bacteria (incl. MRSA)②O t t di ADME ((orall absorption,②Outstandingbtititissuemigration)③High degree of safety expected since safety
hurdles cleared prior to clinical trials

PhⅠ（12/2010）

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

8Main R&D Activities③ ( November 8 , 2011 Release)
Licensing Development
Stage

Compound/CodeLicensee/Collaborative
research

Therapy area/Action

OriginComments

Application
submitted（3/2011）

Alphagan/AlphaganP

Senju PharmaceuticalsGlaucoma

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

Overseas Ph II（8/2005）

KetasMediciNova (US)

CerebrovasculardisordersdidIn-house

・KYORIN grants MediciNova an exclusive license in
all countries worldwide except for Japan, China,
South Korea and Taiwan to develop, manufactureand sell the compound and products for the multiple
sclerosis indication (10/2004)
Result of Ph II was reported in April 2008

Overseas Ph III(Anti-bronchial
Asthma: 11/2006)
Overseas PhⅡ/Ⅲ(Interstitial
cystitis: 5/2005)

KCA-757

MediciNova (US)Bronchial asthma andinterstitial cystitis

In-house

・KYORIN grants MediciNova an exclusive license in
all countries worldwide except for Japan, China,
South Korea and Taiwan to develop and sell thecompound and products・Interstitial cystitis: Result of Ph II/III was reported inJanuary 2007 and development ceased
・Bronchial asthma: Clinical trial overseas wasdiscontinued.

Overseas PhⅡ（POC)（12/2010）

KRP-203

Novartis (Switzerland)

Transplantation,
autoimmune,andd IBD*In-house

・Kyorin grants the right to develop and commercialize
KRP-203 worldwide for use as an immunosuppressanti organ transplants,
inlandd righti h to develop
dl andd
commercialize KRP-203 worldwide except in Japan,Korea, China and Taiwan for the treatment ofautoimmune diseases and other diseases(February 2006)）
・New license agreement IBD (November 20109■ 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.