Swiss Re Ag · SIX:SREN
Swiss Re — Swiss Re Vaccine Webinar 2020
62 slides from Swiss Re's conference presentation, 2020
Slide 1: From Pasteur to mRNA vaccines: Bioinformatics & reverse vaccinology are next?
From Pasteur to mRNA vaccines: Bioinformatics & reverse vaccinology are next? Vaccines are most cost-effective public health interventions….. …. and therefore difficult to develop Thomas Kündig, Prof. Dr. med. Chairman Dermatology Department Zurich University Hospital
Slide 2: How did it start?
How did it start? Immune System ?
Slide 3: Immune system T cell memory
UniversitatsSpital Ge J zurich — “titector Sd direct _-——+ \.CDB T lEp)/ Memory \ cps Tim) / / Transitory % \ cD8 TE) ) \ cD8TiE) ( “Resting. | s) Q CD4T(R)
Slide 4: Zinkernagel et al. Immunol Rev 1997
Zinkernagel et al. Immunol Rev 1997
Slide 5: Intralymphatic Immunotherapy
Intralymphatic Immunotherapy Subcutaneous Into Spleen Johansen et al. Eur J Immunol 2005
Slide 6: Into lymph node vs Subcutaneous
Into Subcutaneous lymph node Senti et al. Curr Opin Allergy Clin Immunol 2009
Slide 7: Allergen Immunotherapy
Allergen Immunotherapy aka «Allergy Immunotherapy» aka «Desensitization»
Slide 8: Allergen Immunotherapy
Allergen Immunotherapy High rate of success Insect venoms 80-95% Pollen 70-80% Only causal treatment Stops progression of disease Long term effect As effective as pharmacotherapy
Slide 9: Allergen Immunotherapy
Allergen Immunotherapy Only 4% Allergen Dose 20 weeks 3-5 years (30-80 injections)
Slide 10: Intralymphatic Immunotherapy
Intralymphatic Immunotherapy neous phatic intralymphatic subcutaneous subcutaneous intralymphatic Subcutaneous subcutaneous intralymphatic subcutaneous B B Intralymphatisch (log10) 6.0 6.0 6.0 (log10) concentration (log10) Pollen Dose Maximum tolerated Maximum tolerated 5.5 5.5 5.5 concentration 56
Slide 11: Intralymphatische Immuntherapie
Intralymphatische Immuntherapie neous phatic intralymphatic subcutaneous subcutaneous intralymphatic subcutaneous intralymphatic subcutaneous B Subcutaneous B Intralymphatic (log10) 6.0 6.0 6.0 (log10) concentration (log10) Pollen Dose Maximum tolerated Maximum tolerated 5.5 5.5 5.5 concentration 56
Slide 12: 3 Injections
Y UniversitatsSpital G Zirich 3 Injections
Slide 13: Enhanced Antigen Presentation
Enhanced Antigen Presentation Martinez-Gomez et al. Allergy 2009
Slide 14: IL-10 and IgG4
IL-10 und IgG4 100 p=0.0004 p=n.s. IgG4 (Post/Pre) 10 1 1 10 1 10 IL-10 (Post/Pre) Senti et al. JACI 2012
Slide 15: Nasal Tolerance
Nasal Tolerance NPT 3 (Post/Pre log 1 0) Improvement 2 P<0.001 1 70x 0 Placebo Verum Treatment group Senti et al. JACI 2012
Slide 16: Lymph node injections provide safer, faster relief against hay fever
UniversitatsSpital Zurich DISCOVER MA GA Z Health & Medicine | Mind & Brain | Technology | Space |! Human Origins | Living World | Environment Not Exactly Rocket Science Lymph node injections provide safer, faster and easier relief against hay fever
Slide 17: Canine Atopic Dermatitis ILIT
Canine Atopic Dermatitis 3 x ILIT better than 30 x subcutaneous Hatzmann et al. Vet Dermatol 2011
Slide 18: Horse Asthma
UniversitatsSpital Zurich
Slide 19: Horse Asthma
UniversitatsSpital Zurich
Slide 20: Low-dose DNA vaccination into lymph nodes in ponies
UniversitatsSpital Zirich Low-dose DNA vaccination into the submandibular lymph nodes in ponies G. A. Landolt, S. B. Hussey, K. Kreutzer, A. Quintana, D. P. Lunn (a) 110,000 5 —® Vaccinated ponies 400,000 4 —@- Unvaccinated control ponies 7 —™- Experimentally challenged ponies 90,000 4 —~2- Commerci
Slide 21: Antibodies of all four isotypes increased
“Antibodies of all four isotypes, IgG1, IgG2, IgA, and IgM, increased in dry secretions following immunization via lymph node.”
Slide 22: 3 Injections
Y UniversitatsSpital G Zirich 3 Injections
Slide 23: Epicutaneous Immunotherapy
Epicutaneous Immunotherapy
Slide 24: Epicutaneous Immunotherapy
Epicutaneous Immunotherapy
Slide 25: Epicutaneous Immunotherapy
Epicutaneous Immunotherapy P = 0.04 P = 0.002 Senti et al. JACI 2009
Slide 26: 6 Patches
Y UniversitatsSpital G Zirich 6 Patches
Slide 27: 6 Patches
UniversitatsSpital Zirich 6 Patches
Slide 28: Virus Like Particles (VLP)
Virus Like Particles (VLP) N N O N O O N O O O N N O N O N O O O O N N N O N O O O O O N N O O O O O O N N O O O N N N N O O O O O O O N N N O N O N O O O O O O O N N O O O O O N O N N N O O SMPH chemical linker O N O N O N O N diameter = 30 nm
Slide 29: Virus Like Particles (VLP)
Virus Like Particles (VLP) QbG10 G10
Slide 30: Virus Like Particles (VLP)
Virus Like Particles (VLP) Organization high low absent Antibody response +++ ++ - Auto-antibodies +++ - - T help independent Type 1 Bachmann et al. Science 1993
Slide 31: Virus Like Particles (VLP)
Virus Like Particles (VLP) IgG (log10) Kündig JACI 2006
Slide 32: Fel d 1
Fel d 1 H1 H2 H3 H4 Chain 2 1 I I I C7 C48 C73 C162 C136 C95 Chain 1 162I I I H8 H7 H6 H5 cys C N H8 H5 H2 H1 H4 H6 H3 H7
Slide 33: VLP with Fel d 1
VLP with Fel d 1 antigen N N O N O O N O O O N N O N O N O O O O N N N O N O O O O O Cys N N O O O O O O N N O O O N N N N O O O O O O O N N N N N O O O O O O O O O N N O O O O O N O N N SMPH chemical linker N O O O N O N O N O N RNA → Ligand for TLR7/8 diameter = 30 nm
Slide 34: 1 Injection
Y UniversitatsSpital G Zirich 1 Injection
Slide 35: Fel d 1
Y UniversitatsSpital Zirich yen C-. \ Zygomatic Gland } —— " Parotid Gland Granule Mandibular Gland ‘amine leukotriene
Slide 36: Hi Res Cryo-Electron Microscopy
Hi Res Cryo-Electron Microscopy
Slide 37: Hypoallergenic Cat
Y UniversiestsSpital H yp O al | e rg e al | C C at . Capture ELISA . Indirect ELISA 8 105. 8 10 8 & rec Feld! 8 rec Feld! @ 10% > natFeld1 @ ~* nat Feld! ;" “EF g 3° # 102 #10 i) +] 10" 3 10" 4 10°. T T r 1 2 10°4 T 7 T 1 *. 0 100 «6200 | 300 400 6 100 «6200 §=6300 | 400 Days Days Binding Dissociat
Slide 38: Hypoallergenic Cat
Besse Hypoallergenic Cat i Day 0 Day 42 % p=0.012 p=0.0131 £100: = o > 2 3 50 77 5 i 3 Le ee oL 0 ELISA Mass Spec
Slide 39: 0 Injections
Y UniversitatsSpital G Zirich 0 Injections
Slide 40: UniversitatsSpital
UniversitatsSpital Zurich
Slide 41: Insect Bite Hypersensitivity (IBH)
Insect Bite Hypersensitivity (IBH) Culicoides spp. World wide: 60 Mio Horses Prevalence: 15 Mio Horses
Slide 42: Current Therapy
UniversitatsSpital Zurich
Slide 43: IgE vs. Eosinophils
IgE vs. Eosinophils Blood Skin Fettelschoss-Gabriel et al. JACI 2018
Slide 44: Antibody Response
Antibody Response Horse IL-5 Anti-IL-5 N N O N O O N O O O N N O N O N O O O O N N N O N O O O O O N N O O O O O O N N O O O N N N N O O O N N O O O O O O N N O O O O N O O N N N O O O N O N O N O N Fettelschoss-Gabriel et al. JACI 2018
Slide 45: Eczema
Eczema + anti-IL-31 Fettelschoss-Gabriel et al. JACI 2018
Slide 46: Hálka: Our Pet Horse
Hálka: Our Pet Horse Before Vaccination After Vaccination
Slide 47: Y UniversitatsSpital
Y UniversitatsSpital G Zirich
Slide 48: UniversitatsSpital
UniversitatsSpital Zurich
Slide 49: Canine Atopic Dermatitis
Canine Atopic Dermatitis USA + EU: 180 Mio dogs Prevalence: 30 Mio dogs
Slide 50: Canine Atopic Dermatitis
Canine Atopic Dermatitis Dog IL-31 N N O N O O N O O O N N O N O N O O O O N N N O N O O O O O N N O O O O O O N N O O O N N N N O O O N N O O O O O O N N O O O O N O O N N N O O O N O N O N O N 180 Mio - 30 Mio Bachmann et al. JACI 2018
Slide 51: Y UniversitatsSpital
Y UniversitatsSpital G Zirich
Slide 52: UniversitatsSpital
UniversitatsSpital Zurich
Slide 53: Psoriasis
iY Q & J e) a oO UniversitatsSpital G
Slide 54: Psoriasis Arthritis
Psoriasis Arthritis Peripheral type Tendinitis Axial type Enthesitis
Slide 55: Psoriasis and Depression
Psoriasis and Depression Frustration with therapy 90% Fear of getting worse 88% Shame 81% Unattractiveness 75% Depression 54% Thoughts of suicide 10% 0 10 20 30 40 50 60 70 80 90 100
Slide 56: Psoriasis and Cardiovascular Disease
Psoriasis and Cardiovascular Disease 127‘139 Psoriasis patients vs. 556‘995 other patients Adjusted relative risk of myocardial infarction x4
Slide 57: Psoriasis Treatment
Psoriasis Treatment Treatment cost: 20’000 CHF per year
Slide 58: Atopic Dermatitis
Atopic Dermatitis Weidinger, Novak Lancet 2016 Weidinger et al. Nat Rev Dis Primers 2018
Slide 59: Anti-Cytokine Vaccination in Humans
Anti-Cytokine Vaccination in Humans Human cytokines No! N N O N O O N O O O N N O N O N O O O O N N N O N O O O O O N N O O O O O O N N O O O N N N N O O O No! N N O O O O O O N N O O O O N O O N N N O O O N O N O N O N 180 Mio - 30 Mio
Slide 60: Market Size
universittspta Market Size (A) FDA and EMA approvals (C) Molecule analysis Otter (Eecherichin cl, or uniieclovec (E) Company market share QE 2012 2013 2018 2015 2016 2017 mI eoeeweese & & LL - 200 - ~ 160 = g j om $ 120 ~ Ft ex z 80 - -. J = 3” 5 het (ioe so me on oe ° g | 2018 2019 2020 2021 2022
Slide 61: Rolf Zinkernagel, Martin Bachmann, John Simard and related companies
Rolf Zinkernagel Martin Bachmann John Simard Gabriela Senti Pal Johansen Antonia Fettelschoss AlleCure Corp. Lars French CTLImmunoTherapies MannKind Corp. Cytos Biotechnology ImVision Colby Pharmaceuticals XBiotech Corp. HypoPet EVAX
Slide 62: Basic Copyright Notice & Disclaimer
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