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ESBATech case storyESBATech case story6 July 201110. Private Equity & Corporate Finance Conference

ESBATech AGWagistr. 21CH-8952 Zurich-SchlierenSwitzerland

phone +41-44-733 4900fax +41-44-733 4990e-mail [email protected] www.esbatech.com S t e a d eb esbatec co

Advancing antibody fragment therapeutics

Antibodies are the most successful drugs

New biopharmaceutical entity (NBE) New chemical entity (NCE)New biopharmaceutical entity (NBE) New chemical entity (NCE)

88% 88%

62%

93%

70%

80%

90%

100%88 88

93

70%

80%

90%

100%

Average annual sales [M$]

29%34%

51%

62%

40%

50%

60%

70%

29 34

51

62

40%

50%

60%

70%

8% 11%19%

0%

10%

20%

30%

Fi t t Fi t h Fi t ti t Fi t i t l Fi t

29

8 1119

0%

10%

20%

30%

Fi t t Fi t h Fi t ti t Fi t i t l Fi tFirst toxdose

First humandose

First patientdose

First pivotaldose

Firstsubmission

First toxdose

First humandose

First patientdose

First pivotaldose

Firstsubmission

Source: CMR Database Source: Datamonitor


Formats of antibody fragments

VVL

VVL

VH

CH1

CL

VHCL

CH1LucentisCimzia

CH2 CH2

VH VL

ESBA105ESBA1008

CH3

CH2 CH2

CH3

CH1 CL

SS

VHVL

Antibody

SS

FabFragment

Single-chainantibody fragment


Local therapy for safe and effective treatment

Eye CNS

0.01

0.1

1

ENTR

ATI

ON

Lung1E-05

0.0001

0.001

DR

UG

CO

NC

GI-Tract Skin

1E-08

1E-07

1E-06

Joint

TIME

Serum conc. following i.v. injection

Local conc following i v injectionJoint Local conc. following i.v. injection

Local conc. following local application

Serum conc. following local application


Fragments lacking drug like properties

Classical scFv

12 0014.0016.0018.0018.00

Monomer

Aggregates

4.006.008.00

10.0012.00

mA

U

-4.00-2.000.002.00

0.00 100.00 200.00 300.000.00 100.00 200.00 300.00

ml

• Low yield• Strong aggregation• Low stability


ESBATech’s unique approach

VH

VL

CVH

C

VL

CH1

CLCL

CH1 IgG gene segments Human

CH2 CH2

VH 1200

VL κ 850

CH3 CH3

L

λ 400

1 5 Mi f ll h f kIgG > 1.5 Mio fully human frameworks


Drug-like properties of ESBATech frameworks

Size-exclusion chromatography:

Mouse scFv: Humanized scFv:Mouse scFv:

• Low yield • High yield• Low yield• Strong aggregation

High yield• Low aggregation


ESBATech project portfolio before acquisition

Indications Target Research Preclinic Phase I Phase II Phase III

ESBA105 Uveitis TNFESBA105 Uveitis TNF

ESBA105 PK and post TNFpsurgical inflammation

ESBA105 Osteoarthritis TNF

ESBA1008 Angiogenesis VEGF

ESBA105 R i t TNFESBA105 Respiratory TNF


Anatomy of the eye

AnteriorOil layerAqueous layer

OpticNerve

Mucin layerCorneal epithelium:

Cut-off: 40kDa

Cornea Stroma: Cut-off: 150kDa

Retina Sclera Posterior

Descemt‘s membrane:Cut-off: 60kDa

RetinaCross section of human cornea at 160X(from: Anant Mathur, Univ. of Rochester, 2005)


Topical ESBA105 reaches therapeutic levels

100000

1000000Aqueous humourVitreous

10000

100000 VitreousNeuroretinaSerumRPE-choroidpg

/ml)

100

1000

BA

105

(p

TNF l l i AU

1

10ESB TNF level in AU

0 5 10 15 20 25 30 350.1

hoursTopical treatment Furrer et al. IOVS 2009


Phase I of ESBA105Phase I of ESBA105

27 healthy volunteersRandomized, vehicle-controlled, double-masked, ,Single and repeat doseDose escalation (up to 4 weeks, up to 16 daily topical dosings)


ESBA105: Phase II in progress

Regulatory clearance to start two phase Ib/IIa clinical trials:

• Human PK in cataract and vitrectomy surgery, post-surgicalHuman PK in cataract and vitrectomy surgery, post surgical inflammation

• Examining human PK in anterior/ posterior chamber• Early PD/ efficacy readout in post surgical inflammation• Early PD/ efficacy readout in post-surgical inflammation• Total 90 patients, different dosing, PD part double-blind, placebo controlled

Acute anterior uveitis• Acute anterior uveitis• Proof of clinical concept in AAU patients• Changes in the level of intraocular inflammation (anterior chamber cell count

according to SUN Working group criteria)according to SUN Working group criteria)• Enrollment of 25 patients• Open-label


Capital need

D S i I C i l i d [CHF]Date Series Investors Capital raised [CHF]

April 2000 Seed Novartis Venture Fund 1M

Sept 2001 Series A Lombard Odier 14 5MSept 2001 Series A Lombard OdierCredit SuisseBSINovartis Venture Fund

14.5M

BioMedinvestVI Partners

Aug 2006 Series B Clarus VenturesHBM P t

50MHBM PartnersSV Life SciencesNovartis Venture FundVI PartnersZKB

Aug 2007 Series B2 Same syndicate 23M

TOTAL 88.5M


Franchise deal

Ophthalmology VirologyCardiovascular

CancerAuto immune didisease


ESBATech, an Alcon Biomedical Research Unit

Non-ophthalmicSeptember 2009

Ophthalmology: USD 589MOphthalmology: USD 589MUSD 150M upfrontUSD 439M Milestones

ESBATech, an Alcon Biomedical Research Unit LLC 15


Acquisitions of antibody fragment companies

Company Acquirer Date Stage ValuationCompany Acquirer Date Stage ValuationESBATech Alcon 09 / 2009 Phase II USD 589M 1)

Adnexus BMS 09 / 2007 Phase I USD 430MDomantis GSK 12 / 2006 Preclinic USD 454MAvidia Amgen 09 / 2006 Phase I USD 290MNeuTec Novartis 06 / 2006 Phase III USD 575M

1) Ophthalmology franchise only


Maximizing platform value

Franchise deal of platform

De-merger allows further maximizing platform valueDe merger allows further maximizing platform value

Alcon / Novartis resource to maximally develop platform

Ophthalmology acquisition as validation for DelenexOphthalmology acquisition as validation for Delenex

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