Nobelpharma Co., Ltd.

August 2017

Corporate Mission

Contribute to Society by

Providing Necessary but

Neglected Pharmaceuticals and

Medical Devices

August 2017 2

Management Policies - General

1. Share the Mission, Policies and Action Criteria among all stakeholders (employees, shareholders, officers)* Regular review is essential for sharing

2. Pursue evolutionof the Company, yet becoming larger is not our main goal

3. Comply with regulations and ethical codes

4. Ensure transparency and disclosure

5. Launch business overseas3August 2017

Number of Orphan Designations*1

- November 2003 to December 2016 -

4

*1 Simple arithmetic by company names as of designation*2 Including 1 medical device

*2

August 2017

Number of New Drug Approvals- Compounds listed in NHI Price Listing -

5*1 including 1 with NHI price not yet listed

Rank Company 2008 2009 2010 2011 2012 2013 2014 2015 2016 Total1 Novartis 2 6 3 4 2 2 1 3 4 272 Pfizer 5 3 4 2 3 3 3 1 0 243 GlaxoSmithKline 2 4 3 1 3 2 3 2 2 224 Takeda 0 1 5 2 2 2 3 4 1 205 Janssen 0 3 2 4 1 2 4 0 2 186 Sanofi 1 2 0 0 0 3 4 3 3 167 Bayer 5 0 1 0 2 1 2 1 3 15

Kyowa Hakko Kirin 0 0 1 2 2 4 2 1 1 13MSD 2 1 1 2 1 0 2 1 3 13

Nobelpharma 3 0 0 1 1 3 3 0 1 12Daiichi Sankyo 1 1 3 2 1 1 2 1 0 12

Otsuka 0 0 1 1 1 3 2 1 3 12Chugai 1 0 0 2 1 3 2 1 2 12Astellas 2 1 0 2 3 0 2 1 0 11

Nippon BI 0 1 1 3 0 0 1 3 2 11Shionogi 2 0 2 0 1 2 0 2 0 9

Ono 0 3 0 4 0 0 1 0 1 9Eli Lilly Japan 0 1 2 0 1 0 1 2 2 9Bristol-Myers 0 1 1 0 0 2 3 1 1 9

47 41 50 49 41 59 64 60 58 469

8

10

14

16

Annual Total

*1

August 2017

Products

6

Brand Name Indication Licensor Distributor Approval

Nobelzin®(zinc acetate) Wilson’s disease Teva direct sales 2008

Lunabell® LD(EE/NET) dysmenorrhea Janssen Nippon Shinyaku

Fuji Pharma2008

(LCM 2010)

Nobelbar®(phenobarbital)

neonatal seizures/ status epilepticus in-house direct sales 2008

Fostoin®(fosphenytoin)

status epilepticus/ prevention of convulsive seizure Pfizer Eisai 2011

Gliadel®(carmustine) glioma Eisai Eisai 2011

Lunabell® ULD(EE/NET) dysmenorrhea Janssen Nippon Shinyaku

Fuji Pharma 2013

Alabel®(5-ALA)

diagnosis ofmalignant glioma

SBI Pharma(medac) direct sales 2013

OD

OD

= orphan designationOD

OD

OD

August 2017

Products

7

Brand Name Indication Licensor Distributor Approval

Indacin®(indomethacin)

patent ductus arteriosus of prematurity Lundbeck direct sales MA transfer

2013

Cosmegen®(actinomycin D)

Wilms tumor/ chorionepithelioma/ pediatric

solid tumor, etc.Lundbeck direct sales MA transfer

2013

Unitalc®(talc)

prevention of malignant pleural effusion Novatech direct sales 2013

Respia®(caffeine) apnea of prematurity Nippon BI

(co-development)direct sales 2014

Rapalimus®(sirolimus)

lymphanogioleiomyomatosis(LAM) Pfizer direct sales 2014

Zanosar®(streptozocin)

gastroentero pancreatic neuroendocrine tumor Keocyt direct sales 2014

Nobelzin®(zinc acetate) hypozincemia in-house direct sales 2017

= orphan designationOD

OD

OD

OD

OD

August 2017

Pipeline

Compound Indication Partner IND End of Trial NDA Approval

Jun 2015 Sep 2016 Jun 2017 Dec 2017

Dec 2014 Jun 2016 Oct 2017 Sep 2018

P IIIIIT in progress

Oct 2013 Jun 2017 Oct 2017 Mar 2018

P II IITcompleted

Dec 2014 Apr 2017 Aug 2017 Jun 2018

P IIIin progress

Oct 2010 Oct 2017 Mar 2018 Dec 2018

P I (P III)

Gynecological Diseases

In-house

TranslationalResearch

InformaticsCenter

In-houseDistal Myopathy

NPC-17Titanium Bridge(medical device)

Spasmodic Dysphonia

NPC-18Myringa regeneration Tympanic Perforation

TranslationalResearch

InformaticsCenter

NPC-12Sirolimus for topicaluse

Angiofibroma(new indication)

NPC-09N-acetylneuraminicacid

In-houseNPC-16

Note: White cells are projectionsIIT = Investigator Initiated Trial 8

OD

OD

= orphan designationOD

SD

SD

= SAKIGAKE designationSDAugust 2017

PipelineCompound Indication Partner IND End of Trial NDA Approval

Feb 2016 Apr 2018 Aug 2018 Jun 2019

P III(P II in progress)

Jul 2013 Mar 2018 Sep 2018 Jun 2019

P IIIIT in progress

(P III)

Dec 2018 Mar 2019 Dec 2019

P IIb/III(ICT by Savara)

Pulmonary AlveolarProteinosis

NPC-07Additional Indicationof Alabel®

Diagnosis of bladdercancer

(undisclosed)

SBI Pharma(medac)

Duchenne MuscularDystrophy

(Trial by SBIin progress)

NPC-15Melatonin

Sleep Disorders inChildren withNeurodevelopmentalDisabilities

In-house

NPC-14Arbekacin

SavaramolgramostimMolgradex®

Note: White cells are projectionsIIT = Investigator Initiated Trial 9ICT = International Clinical Trial

OD

= orphan designationODAugust 2017

• SAKIGAKE Designation SystemTo put into practice innovative medicines/medical devices/regenerative medicines initially developed by Japan

• Designation CriteriaInnovativenessSeverity of target indicationProminent effectivenessIntention to achieve early development and NDA in Japan ahead of the rest of the world

• Designation AdvantagePrioritized Consultation: 2 months 1 month waiting timeSubstantial Pre-application ConsultationPrioritized Review: 12 months 6 monthsDedicated Review Partner at PMDASubstantial Post-marketing Safety Measures: Extended re-exam period

10

SAKIGAKE Fast-track Review System- Trial Implementation in 2015 -

August 2017

• NPC-17 Titanium Bridge (medical device): OtorhinolaryngologyUnique technology of curative treatment for adductor spasmodic dysphonia developed in Japan ahead of the world by Dr. Nobuhiko Isshiki, Professor Emeritus, Kyoto UniversityIndication: Adductor spasmodic dysphonia• One local dystonia of intractable neurological disease being unexplained refractory disorder • Dysphonia from involuntary intermittent spasm of intralaryngea muscle during phonation• No lesion nor paralysis in vocal cord• Phoniatrics and psychotherapy ineffective• No curative treatment available globallyThyroplasty type 2 with titanium bridge less invasivefor its procedure under local anesthesia without touching vocal cordQOL enhancement in patients with symptomatic improvements and lasting results1,012 newly diagnosed patients in 2 years (500/year) at investigated sites (655 sites) in Japan according to “Study on Spasmodic Dysphonia”Investor initiated trial started from July 2015 (Kumamoto Univ, etc.)

11

SAKIGAKE Designated Products- 2 out of 11 Total Designations -

hyoid bone epiglottis

thyrohyoid membrane

thyroid cartilage

median cricothyroid

ligamentcricoid cartilage

cricothyroid muscle

trachea

Larynx(anterior view)

August 2017

• NPC-12 Rapalimus® for topical use: DermatologyOriginal (collaboration with Osaka Univ) topical preparationIndication: Angiofibroma associated with tuberous sclerosis (TSC), etc.Angiofibroma: one of skin symptoms specific to TSC• Developed in central area of face including nose, nasolabial

sulcus and cheek (symmetrical) and lower jaw• Only surgical removal and laser therapy currently

availableCa. 7,500 – 14,000 patients in JapanPhase I/II (IIT) completed by Osaka UniversityOctober 2015: Start Phase III October 2015: First SAKIGAKE designationDecember 2015: Orphan drug designation

Wataya-Kaneda M. Br J Dermatol. 2011

SAKIGAKE Designated Products- 2 out of 11 Total Designations -

12

Japan's MHLW designates first batch of products under sakigake fast-track review system

Drug Company Indication

Sirolimus (NPC-12G)

Nobelpharma(Japan)

Angiofibroma associated with nodular sclerosis

NS-065/NCNP-01

Nippon Shinyaku (Japan)

Duchenne muscular dystrophy

S-033188 Shionogi (Japan) Influenza A or B virus infection

BCX7353 Integrated Development Associates (Japan)

Angioedema attacks in patients with hereditary angioedema

ASP2215 Astellas (Japan) First-relapsed or treatment-resistant FLT3 mutation-positive acute myeloid leukaemia

Pembrolizumab (Keytruda)

MSD (US) Unresectable, advanced or recurrent gastric cancer

Source: Pharma JapanAugust 2017

Regeneration of Tympanic Membrane: OtorhinolaryngologyBreakthrough therapy developed by Dr. Shin-ichi Kanemaru, Kitano Hospital (supported by Translational Research Informatics Center, TRI)Simple and less invasive procedure, possible in ambulatory care without frequent hospital visits

13

a b c

def

“This discovery is potentially the greatest advance in otology since the invention of the cochlear implant.”Prof. Robert K. Jackler (Stanford Univ) Otology & Neurotology, 33, 289, 2012

Indication: Tympanic Membrane PerforationApproximately 20,000 patients in Japan, with potential undiagnosed elderly patients December 2014 – June 2017: Investigator initiated (TRI)October 2017: Japanese NDA scheduled a. Local anesthesia applied

b. Fresh wounds created on TMP edgec-d. Gelatin sponge soaked with b-FGF and indwellede. Affected area sealed with fibrin gluef. Residual material removed after 3 weeks

Under Development

August 2017

1414

NPC-18 in natureOUTLINE

August 2017

BK-SE36 Malaria Vaccine: Global (travelers/children in affected countries)• One of Three Major Infections: 500,000 people victimized yearly, Africa/Southeast Asia/Latin

America/travelers to such countries• Collaboration of Osaka Univ and Research Foundation for Microbial Diseases of Osaka Univ⇒ NPC joined since 2014

• Unique mechanism: antigen of SERA5 with no genetic polymorphism, 80% efficacy expected• Treatment/prevention available; but with difficulties of adverse reactions, resistance strains,

financial conditions, etc.• World first development with investigator initiated trials in Japan and Africa• May 2015: P1b started in Burkina Faso (by Osaka Univ/European Vaccine Initiative; sponsored by

NPC; 2 years) ⇒ Data under analysis• Aug 2017: “Malaria Vaccine Development and Establishment of its Commercial Manufacturing”

selected for Cyclic Innovation for Clinical Empowerment (CiCLE) by AMED• Sep 2017: P1b (adults – children safety) with new nucleic acid adjuvant• Q1 2018: Start of challenge study in Germay (using AMED CiCLE fund)• Consultation with FDA started for indications and development plans

and also with EMA to be started soon• Under consultation with MHLW/PMDA for orphan designation

Source: WIKIPEDIA

15August 2017

Under Development

Company Profile

Name: Nobelpharma Co., Ltd.

Established: June 6, 2003

Capital: ¥11.71 million

Major Hisanaga & Co.Shareholders: Medipal Holdings Corporation

Inabata & Co., Ltd.

Headquarters: Kyodo Building (Horidome), 12-10, Nihonbashi-kobunacho, Chuo-ku, Tokyo

Employees： 249 (July 1, 2017)

16August 2017

Personnel: Total of 249

17August 2017

URL: http://www.nobelpharma.co.jp/E-mail: info@nobelpharma.co.jp

Headquarters & Sales Offices

18

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●

●

●

●

●●

Sapporo

Hokkaido-Tohoku

Kanshinetsu

YokohamaTokai-Hokuriku

★HeadquartersTokyo OfficeMinami-Kanto Office

KansaiKyushu

Chu-Shikoku

Yaesu (Sales Administration)★

August 2017

President & CEO

Research & Development

R&D Div 1

R&D Div 2

R&D Div 3

R&D Planning

International Clinical Research

Non-Clinical R&D

Regulatory Affairs

Liaison

Business Development &

Strategy

R&D Strategy

Business Development

Sales & Marketing

Marketing & Sales Administration

Product Marketing Div 1

Product Marketing Div 2

Product Marketing Div 3

8 Branches

Supply Chain & Manufacturing

Supply Chain Management

CMC Development

Pharmacovigilance & Quality Assurance

Product Quality Assurance

Pharmacovigilance

PMS Compliance

Post Marketing Surveillance

Corporate Planning & Administration Global Business

Board of Directors

Executive Officers GCP Audit Internal Audit

Organization

19August 2017

Item 2012 2013 2014 2015 20162017(plan)

Sales 5,056 6,542 6,628 7,435 6,791 7,514

Operating Income 467 419 262 △ 476 △ 233 92

Ordinary Income 659 462 577 △ 270 △ 56 233

Net Income 278 338 240 157 93 113

Total Assets 5,597 6,098 9,367 9,671 7,671 7,260

Net Assets*1) 516 728 1,238 984 691 832

Equity Ratio 9.2% 11.9% 13.2% 10.2% 9.0% 11.5%

Financial Status

1) Retroactive adjustment at settlement: -39 in FY2012, -44 in FY2013, 97 in FY2014, -17 in FY2015

(Million yen)

20August 2017

△ 30.0

△ 10.0

10.0

30.0

50.0

70.0

90.0

2008 2009 2010 2011 2012 2013 2014 2015 2016

Sales

Net Income before Tax

Net Income w/o Deferred R&D Costs

Carry-forward

Sales and Profits(Hundred million yen)

Accumulated Loss wiped-off

21August 2017

• Undertake new concept drugs/new compoundsin addition to license in US/Europe approved drugs

Some development failures unavoidable (at stages of non-clinical and clinical trials and approval reviews)Identify risks to minimize losses in cases of failure1) Utilize public development grants2) Disperse risks by joint investment

• Emphasize collaboration with academia

• Embark on international expansion (development and distribution)

Global clinical trial: Approval in US/EuropeMarketing in neighbor countries

Future Prospects- Business Strategies -

22August 2017