ESBATech case storyESBATech case story · Aug 2006 Series B Clarus Ventures HBM P t 50M HBM...
Transcript of ESBATech case storyESBATech case story · Aug 2006 Series B Clarus Ventures HBM P t 50M HBM...
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
Advancing antibody fragment therapeutics
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
Advancing antibody fragment therapeutics
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
Advancing antibody fragment therapeutics
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
Advancing antibody fragment therapeutics
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
Advancing antibody fragment therapeutics
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
Advancing antibody fragment therapeutics
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
Advancing antibody fragment therapeutics
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)
Advancing antibody fragment therapeutics
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
Advancing antibody fragment therapeutics
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)
Advancing antibody fragment therapeutics
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
Advancing antibody fragment therapeutics
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
Advancing antibody fragment therapeutics
Franchise deal
Ophthalmology VirologyCardiovascular
CancerAuto immune didisease
Advancing antibody fragment therapeutics
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
Advancing antibody fragment therapeutics
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
Advancing antibody fragment therapeutics
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