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 Antibody fragment comprising natural antigen- binding pocket: • Neutralization of endogenous proteins • No ADCC required Modified glycosylation of Fc part: • Short-in vivo half-life wanted • Increased ADCC • High tissue penetration • Oncology indications

V L -V H interface Hydrophobic surface patches Issues of scFv antibody fragments Domain stability

V L V L V H V H C L C L C H 1 C H 1 Selecting the most stable IgG gene segments variable regions C H 2 C H 2 V H 1200 of antibodies k C H 3 C H 3 V L 850 l 400 IgG > 1.5 Mio fully human frameworks

Antigen independent selection of stable scaffolds S S AD S S DBD scFv LacZ HIS3 Screening to human spleen cDNA library ~10 7 identify stable Identification of sequence features of stable scFvs scFv domains Auf der Maur et al., FEBS Letters, 2001 Auf der Maur et al., Methods, 2004

Contribution of a stable scaffold on wt-scFv format of anti-TNF Ab CDRs of anti-TNF Ab grafted on one of ESBATech’s stable Frameworks Aggregates Monomer overall stability of 18.00 18.00 Monomer 16.00 scFv 350.00 350.00 14.00 12.00 300.00 10.00 250.00 8.00 mAU 200.00 6.00 mAU 150.00 4.00 100.00 2.00 0.00 50.00 -2.00 0.00 -4.00 -50.00 0.00 100.00 200.00 300.00 0.00 100.00 200.00 300.00 ml ml

Neovascular age- related macular degeneration

Eylea Lucentis Brolucizumab 26 kDa 97 kDa 48 kDa Neovascular age- related macular degeneration 1.7 times more molar Reference drug 22 times more molar concentration concentration Treatments Company Sales in 2016 (USD) Lucentis Novartis (ex US only) 1.8 Bn Eylea Regeneron / Bayer 4.8 Bn

Approval of first scFv Brolucizumab expected in 2019 Single-chain antibodies scFvs: A 30 years long journey to come to market

Date Round Investors Invested capital [CHF] April 2000 Seed Novartis Venture Fund 1M 1 st Round Sept 2001 Lombard Odier 14.5M Credit Suisse BSI Novartis Venture Fund Biotech is very BioMedinvest VI Partners capital intensive 2 nd Round Aug 2006 Clarus Ventures 50M HBM Partners SV Life Sciences Novartis Venture Fund BioMedinvest VI Partners ZKB 2 nd B Round Aug 2007 Same investors 23M TOTAL 88.5M

September 2009 Everything outside ophthalmology Ophthalmology: USD 589M Acquisition of USD 150M Upfront USD 439M Milestones ESBATech July 2016 Trade sale

NIBR Post-acquisition

Brolucizumab: First scFv to come to market Highest molar amount to human eye: 6mg ESBATech Highest concentration: 120 mg/ml achievements ESBA105: First topical biologics