acucela inc. fy2015 q3 analyst meeting · 2016. 12. 1. · company overview acucela inc. [ticker:...

Acucela is a clinical-stage biotechnology

company that specializes in discovering and

developing novel therapeutics to treat and

slow the progression of sight-threatening

ophthalmic diseases affecting millions of

individuals worldwide.

Acucela Inc.

FY2015 Q3 Analyst Meeting

Tokyo

November 24, 2015

DISCLAIMER

This presentation contains forward-looking statements concerning our product development, our

technology, our competitors, our intellectual property, our financial condition and our plans for research and

development programs that involve risks, uncertainties and assumptions. These statements are based on

the current estimates and assumptions of the management of Acucela as of the date of this presentation and

are subject to uncertainty and changes in circumstances. Given these uncertainties, you should not place

undue reliance upon these forward-looking statements. Such forward-looking statements are subject to

risks, uncertainties, assumptions and other factors that may cause the actual results of Acucela to be

materially different from those reflected in such forward-looking statements.

Important factors that could cause actual results to differ materially from those indicated by such forward-

looking statements include, among others, those set forth in our reports on file with the Tokyo Securities

Exchange and the United States Securities and Exchange Commission. The Company does not undertake

any obligation to release publicly any revisions to these forward-looking statements to reflect events or

circumstances after the date hereof or to reflect the occurrence of unanticipated events. All statements

contained in this presentation are made only as of the date of this presentation.

Acucela Inc. [ticker: 4589] 2

Corporate Overview

Company Overview


An ophthalmology-focused, science-driven company

People and Strategy• Executive leadership with experience in health care

management, life science administration and technology

• Broad-skilled employee base in research, development and

operations

• Strategic plan to develop an innovative portfolio of

ophthalmology products

Partnership• Long-time partnership with Otsuka Pharmaceutical

• Potential high-reward alliance

• Acucela has rights for lead investigational candidate

(Emixustat) in Europe, South and Central America and most

of Africa

Technology• Unique mechanism of action in visual cycle modulation (VCM)

• Lead clinical trial program in geographic atrophy (GA)

associated with dry age-related macular degeneration (AMD);

no treatments currently available

• 110 granted patents; 175 pending patents (as of 11/10/15)

Financials• Successful 2014 IPO; $163M (gross) raised

• Cash, short-term and long-term investments for the three

months ended 9/30/15 was $166M ready to invest in

ongoing programs, business development and internal

research and development

FYE2015 Q3 Highlights

Recent Highlights


Date Highlights

Jul 2 Acucela Hires Roger Girard as Chief Strategy Officer

Aug 5 Acucela Hires Dr. Lukas Scheibler as Executive Vice President of Translational Medicine

Aug 25 Acucela Hires Dr. George Lasezkay as Executive Vice President of Legal Affairs

Nov 4 Acucela Validates Sampling Method That Could Pave Way for More Efficient Clinical Tests

Management Team


An experienced management team driving current and future

pipeline development, including device, pharma & biotech assets

George Lasezkay, PharmD, JD

EVP General Counsel

Allergan, Inc.

RetroSense Therapeutics,

Amakem Therapeutics NV,

Novagali Pharma, SA

Neurotech Pharmaceuticals, Inc.

Acuity Pharmaceuticals,

ISTA Pharmaceuticals, Inc.

Lukas Scheibler, PhD

EVP R&D

Alcon

Novartis PharmaceuticalsJohn Gebhart

Chief Financial OfficerQliance Medical Management Consultant to Remote

Medical International, Ventripoint, and others

Ted Danse, MBA

Chief Business Officer

Neurotech Pharmaceuticals, Inc.

ISTA Pharmaceuticals Inc., Allergan,

Inc., Coopervision, Bausch & Lomb ,

Schering-Plough

Roger Girard

Chief Strategy Officer

Xecutive Advisory Partners LLC

Terra Vista Software

CareCap, Bellevue,

Neuro-ID, IsoRay Medical

Ryo Kubota, MD, PhD

Chairman, President and CEO

Board of Directors

Directors Background

Ryo Kubota, MD PhD Chairman, President and Chief Executive Officer and also founder of Acucela Inc.

Shintaro AsakoChief Executive Officer - DeNA West

Previously, Chief Financial Officer - MediciNova, Inc.

Shiro Mita, PhDPresident and Chief Executive Officer - M’s Science Corporation

Previously: Executive Director of Drug Discovery, Director - Santen Pharmaceuticals Co., Ltd

Eisaku Nakamura

Director - Koinobori Associates Inc.

Previously: Director and General Manager - Bio Sight Capital Co., Ltd , Chief Executive Officer and

President - Berevno Corporation, Board of Directors - CanBas Corporation and Activus Pharma Co. Ltd.

Robert Takeuchi

President - RT Consulting, Inc.

Previously: President - SOFTBANK Finance, America Corporation, Director of International Equity Sales -

Credit Suisse First Boston, Board of Directors SBI Investment Co., Ltd. and Quark Pharmaceuticals, Inc.


Corporate Strategy

Treating Sight-Threatening Diseases

Vision R&D

Alliance

&In-

licensing

New

business

Current

pipeline

• Expanding internal

research

capabilities

• Emixustat and OPA-6566

• Optimizing asset

value

• Seeking innovative

approaches to treat

sight-threatening

diseases


FY2015 and Beyond


Continuous development of the current pipeline and increase in

business development activities to expand the portfolio

Current

Pipeline

Emixustat for GA associated with dry AMD

− 75% of enrolled patients have completed dosing in the Phase 2b/3 trial as of

October 2015

− No safety issues have been identified to date

− Obtained feedback from European regulatory agencies regarding registration

pathway for Emixustat in Europe

Emixustat for Additional Indications

− Evaluating the potential to develop Emixustat for additional indications including

diabetic retinopathy and/or Stargardt’s diseaseNew Business− Expanding internal research capabilities

Alliance &

In-licensing− Pursuing partnering and in-licensing opportunities focused on innovative ophthalmic

technologies

Organization− Hired Executive Vice President of Research and Development

− Hired Chief Business Officer

Partnership with Otsuka Pharmaceutical


Investigational Product

CandidatePotential Indication License Territory Financial Terms

Emixustat hydrochloride

(developed by Acucela)

Dry AMD and other

ophthalmic indications

Joint (50/50) - North America

Acucela - Europe, South and

Central America and most of

Africa

Otsuka – Asia-Pacific, some

countries in Africa/Middle East

• Otsuka paid $5M cash upfront payment to

Acucela

• Potential milestone payments: $258M total

• Currently Otsuka and Acucela are equally

sharing all development expenses; Otsuka

loans funds to Acucela for the payment of

Acucela’s share of the development expenses

through to product launch

OPA-6566

(developed by Otsuka)

Glaucoma and other

ophthalmic indications

United States • Currently evaluating next steps for the

program

Unchanged stable relationship with Otsuka Pharmaceutical

FY2015 Q3 Financial Summary

Overview of FY2015 Q3: P/L

FY2014Q3 FY2015Q3 FY2014Q3 FY2015Q3 Reasons for change

P/L Statement USD USD JPY JPY

Revenues from collaboration 27,751 21,524 3,329,010 2,582,019 Decrease due to fewer clinical activities related to Emixustat in 2015.

Expenses

R&D 19,974 17,764 2,396,081 2,130,969

Emixustat 19,191 16,569 2,302,196 1,987,619Decrease due to fewer clinical activities related to Emixustat clinical

trials.

In-licensed(1) 23 4 2,758 426

Internal research(2) 760 1,191 91,127 142,924

Increase in internal research activities and increase related to

severance and retention bonus payments s directly involved in

clinical operations and research.

General and administrative 7,272 21,772 872,349 2,611,770

General and administrative 7,272 10,272 872,349 1,242,270

$1.0M for implementation of new general ledger system, audit

services and equity compliance, new ERP system and others

including hiring of short-term contractors

May 1st Special Shareholder

Meeting and management

change

11,500 1,369,500

Severance cost (cash and stock compensation) of $7.7M, legal and

consulting fees of 1$.5M and others including retention costs and

executive hiring costs

Income (loss) from operations 505 (18,012) 60,580 (2,160,720)

Net income (1,411) (17,228) (169,263) (2,066,671)(1) In-Licensed: includes Rebamipide (program under the terminated Rebamipide Agreement) and OPA-6566 (program under the Glaucoma Agreement)

(2) Internal Research: includes costs and expenses associated with our discovery research activities related primarily to our VCM compounds

Note: 1 USD = 119.96 JPY as of September 30, 2015


(US$ and JP¥ in thousands)

Overview of FY2015 Q3: Cash Flow

FY2014Q3 FY2015Q3 FY2014Q3 FY2015Q3 Reasons for change

Cash flow Statement USD USD JPY JPY

Cash flows from operating activities 11,016 (18,609) 1,321,465 (2,232,315)

Cash outflow was primarily the result of a net loss of $17.2M

(¥2.1B), and a decrease in deferred revenue from

collaborations of $6.2M(¥747.5M).

Cash flows from investing activities (124,066) 9,138 (14,882,942) 1,096,152Changes were primarily the result of net purchases of

marketable securities.

Cash flows from financing activities 148,317 (1,140) 17,792,106 (136,755)Net cash used primarily for repurchase of restricted stock

units for employee tax withholdings.

Cash, cash equivalents and short and

long-term investments - end of period187,819 165,545 22,530,765 19,858,754

• Cash from operations and our existing cash and investment balances will be sufficient to fund our ongoing operating activities,

working capital, capital expenditures and other capital requirements for at least the next 12 months

• Our future capital requirements will depend on many factors, including our rate of revenue growth, the expansion of our resea rch and

development activities, the timing and extent of our elections to co -promote product candidates under our collaboration agreements

with Otsuka, and the timing of achievement of milestones under our collaboration agreements with Otsuka




Overview of FY2015 Q3: Balance Sheet



12/31/2014 9/30/2015 12/31/2014 9/30/2015 Reasons for change

Balance sheet statement USD USD JPY JPY

Current Assets 111,714 122,379 13,401,208 14,680,562

Cash, cash equivalents and short-

term investments103,786 108,342 12,450,167 12,996,683

Non-current Assets 85,252 58,455 10,226,829 7,012,261

Long-term investments 84,033 57,203 10,080,598 6,862,071

Total Assets 196,966 180,834 23,628,037 21,692,823

Current Liabilities 12,556 7,150 1,506,214 857,690

Long-term Liabilities 47 1,140 5,638 136,755Increase due to long-term deferred rent, lease

incentives and others

Shareholders‘ Equity 184,363 172,544 22,116,185 20,698,378


4,528 3,869 7,033 6,994

(188)

(21,952)(24,377)

(30,000)

(25,000)

(20,000)

(15,000)

(10,000)

(5,000)

-

5,000

10,000

FY10 FY11 FY12 FY13 FY14 FY15 Est

Operating Profit (Loss)

Financial Overview


(USD in thousands)

May 1st Special Shareholder Meeting and management change

34,809 41,495 47,024 54,048

196,966 180,834

-

50,000

100,000

150,000

200,000

250,000

FY10 FY11 FY12 FY13 FY14 FY15Q3

Total Assets

14,101 20,840 25,607 31,124

184,363 172,544

-

50,000

100,000

150,000

200,000

FY10 FY11 FY12 FY13 FY14 FY15Q3

Total Shareholder's Equity

36,457 34,226

46,424

52,947

35,396

23,000 25,500

-

10,000

20,000

30,000

40,000

50,000

60,000

FY10 FY11 FY12 FY13 FY14 FY15 Est

Revenues from Collaboration

IR Activities

Recent and Planned IR Activities


1 Total of 375 investors answered the questionnaire: 174 investors said they would consider purchasing and 27 said they will increase or purchase shares

Date IR Activities

Aug 26 FY2015Q2 Analyst Meeting (Large Meeting)

Aug 28-29

Nikkei IR Fair

• 54% investors made a positive response in purchasing or increasing

holdings of Acucela shares1

Aug 28Retail IR Website Update

• http://ir.acucela.jp/story/index.html

Oct 13-15NYC & Boston Non-deal Roadshow

• Met with Bio-tech focused foreign investors

Oct 23Issued article, “Hopes for saving patients who have sight threatening

diseases with an oral indication” on Japanese Investor

Nov 17London Non-deal Roadshow

• Met with Bio-tech focused foreign investors

Nov 18 Jefferies Healthcare Conference (London)

Nov 19 Barclays Japan Corporate Day (London)

Nov 24 FY2015Q3 Analyst Meeting (Small Meeting)

Dec 3 SBI Securities hosted “Internet-based Presentation for Retail Investors”

Dec 14 Ad in the Kaisha Jyoho (Investor Handbook) Vol 87. Japanese Investor Article – available on our website

2015 Nikkei IR Fair – Acucela Booth

http://ir.acucela.jp/story/index.html

Appendix

The Visual Cycle

The visual cycle is a biological process in which dietary vitamin A is converted to a light -sensitive

compound. This process takes place in a specialized tissue called the retinal pigment epithelium (RPE).

During exposure to bright light, the visual cycle is extremely active and can produce toxic by -products of

vitamin A that cannot be eliminated.


Retinal Pigment Epithelium

11-cis-retinal

11-cis-retinol

all-trans-retinyl ester

all-trans-retinol

Rod Photoreceptor

11-cis-retinal + Opsin

(Rhodopsin)

RPE65

all-trans retinal

Precursors

of vitamin A

toxins

• In the mammalian visual cycle, the Retinal Pigment Epithelium protein 65 (RPE65) plays a crucial role in the

conversion of dietary vitamin A to visual chromophore, 11-cis retinal.

• The visual chromophore combines with opsin in rod photoreceptors to form rhodopsin.

• Light activation of rhodopsin triggers an electro-chemical cascade which results in visual sensation.

• 11-cis retinal and the product of light-activated rhodopsin (all-trans retinal) have the potential to spontaneously

react with membrane lipids and form vitamin A toxins, such as A2E.

all-trans retinol

Emixustat


Formation of Vitamin A Toxins in the Visual Cycle

Visual Cycle Modulation Technology

Visual Cycle Modulation is the use of non-retinoid, small molecule compounds which target

specific proteins of the visual cycle. The intended effect of VCM compounds is to reduce retinal

toxins and preserve the integrity of retinal tissue. Acucela has established a leadership position

in this area as a result of our pioneering efforts to research, discover and develop proprietary

VCM compounds.

Emixustat


Emixustat

Hydrochloride

Emixustat Overview:

Lead Investigational Product Candidate

• Non-retinoid small molecule

• Oral administration

• Designed to modulate visual cycle

activity and reduce the accumulation of

toxins in the retina

• Targets a key rate-limiting enzyme of

the visual cycle

• Measureable pharmacologic effect in

the retina through ERG

(Electroretinography or ERG is an eye

test used to detect abnormal function of

the retina - the light-detecting portion of

the eye)


Emixustat

Hydrochloride

Drug Development Path Emixustat for GA associated with dry AMD:

Investigational compound based on Acucela’s proprietary VCM

2005 2007 2009 2012 2013

» Phase 2b/3 clinical trial commences

» Two-year treatment

» Toxicology

» Proof-of-concept in

preclinical model

» Medicinal chemistry

» Five phase 1 clinical trials completed

» One phase 2a clinical trial completed

(GA subjects)

» 179 total subjects exposed to Emixustat

» Fast track designation granted

» IND filed

» First human trial

2008

25

2014

» Phase 2b/3 clinical

trial enrollment

completed in 508

subjects

2016

» Phase 2b/3 clinical

trial top line results

expected


500

400

300

200

100

dark control

outer

nuclear

layer

Emixustat

(1 mg/kg),

single dose

pre-treatment

p 0.01

Protection from light damage

in mouse model

+8K lux light &

1mg/kg Emixustat

Preclinical Data (ERG following single dose)

Modified From: Bavik C, Henry SH, Zhang Y, Mitts K, McGinn T, Budzynski E, et al. (2015) Visual Cycle Modulation as

an Approach toward Preservation of Retinal Integrity. PLoS ONE 10(5): e0124940. doi:10.1371/journal.pone.0124940

Post-bleach time (min)

10 30 5040200

B-w

ave

ampl

itude

(µ

V)

Vehicle

Emixustat

Treatment:

0.1 mg/kg

0.3 mg/kg

1.0 mg/kg

3.0 mg/kg

Protects Outer Nuclear Layer with Dose

Dependent Reduction in Rod Activity


p 0.01

p 0.001

p 0.001

+8K lux light

30

25

20

15

10

5

Attenuation of A2E Accumulation in abca4-/-

Mice Treated 3 Months with Emixustat

Reduction of

A2E/lipofuscin

Emixustat

(3 mg/kg),

3-month

treatment

abca4-/-

abca4-/-

wild-type

Emixustat (mg/kg)

A2E

(pm

ole/

eye)

Modified From: Bavik C, Henry SH, Zhang Y, Mitts K, McGinn T, Budzynski E, et al. (2015) Visual Cycle Modulation as an Approach toward Preservation of Retinal Integrity. PLoS ONE 10(5): e0124940.

doi:10.1371/journal.pone.0124940

Veh. 0.03 0.1 0.3 1.0 3.0

Day 180Day 0

*

*

*


Emixustat Decreases Retinal Neovascularization in

Dose-dependent Fashion in the Oxygen-Induced

Retinopathy (OIR) Model

40

30

20

10

% N

eova

scul

ariz

atio

n

TreatmentED50 = 0.46 mg/kg

*

**

Modified From: Bavik C, Henry SH, Zhang Y, Mitts K, McGinn T, Budzynski E, et al. (2015) Visual Cycle Modulation as an Approach toward Preservation of Retinal Integrity. PLoS ONE 10(5): e0124940.

doi:10.1371/journal.pone.0124940

75% O2 + Emixustat

75% O2 + vehicle

Air

A

B

C

A

B

C


Emixustat Clinical Data:

Mean Oral PK Profiles

• Single-ascending dose; Phase 1

trial in healthy subjects

• AUC increased approximately

proportionally with dose

• Maximal plasma concentration

(Cmax) also increased linearly with

dose

• Emixustat was readily absorbed

from the GI tract


20

15

10

5

Time (h)

4 12 24201680

Mea

n P

lasm

a C

once

ntra

tion

(ng/

ml)

2mg/subject

7mg/subject

10mg/subject

20mg/subject

20mg/subject (cohort 4)

40mg/subject

60mg/subject

75mg/subject

Source: Kubota R, Al-Fayoumi S, Mallikaarjun S, Patil S, Bavik C, Chandler JW. Phase 1, dose-ranging study of emixustat hydrochloride (ACU-4429), a novel visual cycle modulator, in healthy volunteers. Retina. 2014

Mar;34(3):603-9

• Design

− Multi-center, randomized, double-masked, placebo-controlled, dose-escalation study of

the safety, tolerability, pharmacokinetics and pharmacodynamics of emixustat

– A total of 72 patients with geographic atrophy (GA) associated with dry AMD

– Completed in October 2012

• Primary objectives

− Assess the safety and tolerability of different dose levels of emixustat when administered

orally once daily for three months

− Explore the relationship of biologic activity of emixustat using ERG as biomarker

• Summary of Results

− Emixustat was generally safe and well-tolerated

− ERG data confirmed dose-dependent pharmacologic activity in the retina

− Data were published in the June 2015 edition of RETINA: The Journal of Retinal and

Vitreous Diseases


Phase 2a Dose Escalation Study

Minutes After Bleach

200

150

100

50

20 3010

Nor

mal

ized

ER

G R

ecov

ery

Prolonged Rod Visual Cycle Suppression with

Emixustat in Patients with GA (at Day 14)

31

Placebo (N=18)

2mg (N=12)

5mg (N=11)

7mg (N=11)

10mg (N=5)

DoseSuppression at

Minute 30

Placebo 2% ± 35%

2 mg 35% ± 42%

5 mg 54% ± 40%

7 mg 62% ± 35%

10 mg 85% ± 14%

Source: Dugel P, Novack R, Csaky K, Richmond P, Birch D, Kubota R. Phase II, randomized, placebo-controlled, 90-day study of emixustat hydrochloride in geographic atrophy associated with dry age-related macular

degeneration. Retina. June 2015; 35(6): 1173–1183

31Acucela Inc. [ticker: 4589]

• Administration of emixustat to GA

subjects resulted in a dose-dependent

suppression of mean ERG b-wave rod

recovery

• Mean ERG response functions at Days

14, 30 and 60 were comparable,

indicating steady-state inhibition of ERG

responses was achieved by Day 14

• Within 7 to 14 days after the last dose of

emixustat mean ERG b-wave responses

recovered approximately to baseline

-0.05

0

0.05

0.1

0.15

0.2

0.25

Emixustat Clinical: change in GA lesion area at day 90 in Phase 2a dose escalation GA

32Acucela Inc. [ticker: 4589]

Mea

n c

han

ge

in le

sio

n a

rea

fro

m b

asel

ine

to

mo

nth

3 (

mm

2 )

Pooled Emixustat Placebo

N = 23 N = 8

Numerical

difference of

0.23 mm2,

p 0.05

Pooled data from all Emixustat treated patients vs. placebo

for change in lesion area from baseline to month 3 (FAF)

Full Analysis Population – Acucela data on file

Source: Dugel P, Novack R, Csaky K, Richmond P, Birch D, Kubota R. Phase II, randomized, placebo-controlled, 90-day study of emixustat hydrochloride in geographic atrophy associated with dry age-related macular

degeneration. Retina. June 2015; 35(6): 1173–1183

Phase 2b/3 “SEATTLE” Study

• Design

− Two year, randomized, double-masked, dose-ranging study comparing safety and efficacy of

emixustat with placebo in patients with GA associated with dry AMD

− A total of 508 patients with GA associated with dry AMD were enrolled

• Objectives

− Primary: Determine if emixustat reduces lesion growth rate compared to placebo

− Secondary:

– Evaluate safety and tolerability

– Assess changes in best-corrected visual acuity

– Evaluate the effect on development of wet AMD

− Top-line 2-year trial results anticipated in mid-2016


Acucela’s Intellectual Property Position

Update in VCM and Emixustat

(Nov 10, 2015)

Emixustat related

patents

VCM related

patents

Other

patents

Total

patents

Region US Non-US US Non-US

Granted patents 3 15 16 49 27 110

Pending patents 4 52 11 107 1 175

Expiry year 2029 2028-2033 2028-2034 2028-2034


Acucela intends to aggressively protect and defend its intellectual

property position in Emixustat and VCM

• Strong patent portfolio is critical to our success

• Patents cover compositions of matter and methods of using the compositions

Major Press Coverage (Japanese)

• 東洋経済Online

アキュセラ､近く新たなパイプラインを発表、経営復帰から5カ月の窪田良CEOに聞く（2015年10月2日掲載）

• J-Wave 「JAM THE WORLD」ラジオ番組

「Breakthrough!」コーナーに窪田良が生出演。著書紹介、アキュセラの治療薬開発と挑戦を語る（2015年9月18日放送）

• ABCラジオ「おはようパーソナリティ道上洋三です」

「話のダイジェスト」コーナーに窪田良が生出演。起業の経緯、加齢黄斑変性、アキュセラの治療薬開発について語る（2015年9月17日放送）

• 日経ビジネスONLINE

キーパーソンに聞く「革新は“プロ経営者”より研究者の情熱が生む」（2015年9月7日掲載）

• 日経バイオテク

米Acucela社の第2四半期決算説明会、フェーズIIb/IIIで約250人の被験者の投薬終了（2015年8月29日掲載）

• 朝日新聞

（あの人とこんな話）成長には痛みが伴うが筋トレ同様、鍛えられる（2014年4月15日掲載）

• 日経新聞

「重い目の病に飲み薬」東証単独上場初の米企業に（2014年3月25日掲載）

• 週刊ダイヤモンド

米国で起業しマザーズ上場目のアルツハイマーを治す（2014年2月24日掲載）

• TBS 「夢の扉+」ドキュメンタリー

世界の1億2000万人を“失明の危機”から救え！日本人トップイノベーターが挑む “不治の病”の治療薬開発 (2013年10月27日放送)

• ウォール・ストリート・ジャーナル

世界を変える日本人―シアトルで起業した窪田良氏が挑む難病治療薬（2013年3月29日掲載）

• PRESIDENT Online

＜経営者の言葉：アキュセラCEO・窪田良＞開眼！「朝令暮改」仕事術（連載中）

その他メディア掲載については、当社ウェブサイトをご参照ください：wwww.acucela.jp


Acucela is a clinical-stage biotechnology

company that specializes in discovering and

developing novel therapeutics to treat and

slow the progression of sight-threatening

ophthalmic diseases affecting millions of

individuals worldwide.

acucela inc. fy2015 q3 analyst meeting · 2016. 12. 1. · company overview acucela inc. [ticker:...

Documents