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Business Development Case example: ESBATech
Dominik Escher 3 Dec 18
Business Development Dominik Escher Case example: ESBATech 3 Dec - - PowerPoint PPT Presentation
Business Development Dominik Escher Case example: ESBATech 3 Dec - - PowerPoint PPT Presentation
Business Development Dominik Escher Case example: ESBATech 3 Dec 18 1998 Start of ESBATech ESBATech AG Financing through collaboration Emerging new technologies Improved antibody formats Novel glycosylation Antibody fragment
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Financing through collaboration
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Improved antibody formats
Antibody fragment comprising natural antigen- binding pocket:
- Neutralization of endogenous proteins
- No ADCC required
- Short-in vivo half-life wanted
- High tissue penetration
Antibody fragment
Modified glycosylation of Fc part:
- Increased ADCC
- Oncology indications
Novel glycosylation
Emerging new technologies
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Issues of scFv antibody fragments
Hydrophobic surface patches VL-VH interface Domain stability
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Selecting the most stable variable regions
- f antibodies
VH VL CH1 CL CH3 CH2 VH CL CH2 CH1 CH3 VL
IgG IgG gene segments VH 1200 VL k 850 l 400 > 1.5 Mio fully human frameworks
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Screening to identify stable scFv domains
Auf der Maur et al., FEBS Letters, 2001 Auf der Maur et al., Methods, 2004
HIS3 LacZ DBD AD scFv
S S S S
human spleen cDNA library ~107 Antigen independent selection of stable scaffolds Identification of sequence features of stable scFvs
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Contribution of a stable scaffold on
- verall stability of
scFv
- 4.00
- 2.00
0.00 2.00 4.00 6.00 8.00 10.00 12.00 14.00 16.00 18.00 0.00 100.00 200.00 300.00 ml mAU
wt-scFv format of anti-TNF Ab
18.00
Monomer Aggregates
- 50.00
0.00 50.00 100.00 150.00 200.00 250.00 300.00 350.00 0.00 100.00 200.00 300.00 ml mAU
CDRs of anti-TNF Ab grafted on one
- f ESBATech’s stable Frameworks
Monomer
350.00
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Neovascular age- related macular degeneration
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Neovascular age- related macular degeneration
26 kDa
Lucentis Brolucizumab
48 kDa
Eylea
97 kDa
22 times more molar concentration 1.7 times more molar concentration Reference drug
Treatments Company Sales in 2016 (USD) Lucentis Novartis (ex US only) 1.8 Bn Eylea Regeneron / Bayer 4.8 Bn
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Single-chain antibodies scFvs: A 30 years long journey to come to market
Approval of first scFv Brolucizumab expected in 2019
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Biotech is very capital intensive
Date Round Investors Invested capital [CHF] April 2000 Seed Novartis Venture Fund 1M Sept 2001 1st Round Lombard Odier Credit Suisse BSI Novartis Venture Fund BioMedinvest VI Partners 14.5M Aug 2006 2nd Round Clarus Ventures HBM Partners SV Life Sciences Novartis Venture Fund BioMedinvest VI Partners ZKB 50M Aug 2007 2nd B Round Same investors 23M TOTAL 88.5M
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Acquisition of ESBATech
Ophthalmology: USD 589M USD 150M Upfront USD 439M Milestones September 2009 Everything outside ophthalmology July 2016 Trade sale
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Post-acquisition
NIBR
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ESBATech achievements
Brolucizumab: First scFv to come to market Highest molar amount to human eye: 6mg Highest concentration: 120 mg/ml ESBA105: First topical biologics