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ASP7266 NON-CONFIDENTIAL SUMMARY -- Version dated October 23, 2020 EXECUTIVE SUMMARY 3 ⚫ Novel and highly potent antibody against thymic stromal lymphopoietin (TSLP) receptor ⚫ Market potential • Applicable to multiple inflammatory diseases including severe asthma, chronic rhinosinusitis with nasal polyp, atopic dermatitis, food allergy, eosinophilic esophagitis, allergic rhinitis • Effective on broader patient segments such as type 2 as well as non- type 2 endotypes ⚫ Differentiated antibody from competitors such as Dupilumab, Omalizumab, Benralizumab and Omalizumab ⚫ Favorable safety and ADME profile confirmed in Phase-1 SAD study ASP7266 NON-CONFIDENTIAL SUMMARY -- Version dated October 23, 2020 TSLP/TSLP RECEPTOR 4 TSLP: ◼ A cytokine secreted from such as epithelial cells, fibroblasts etc. ◼ Exhibit inflammatory effects through binding to the heterodimer composed of TSLP receptor (TSLPR) and IL-7 receptor-α (IL-7Rα) Dendritic cell maturation ILC2*, mast cell activation *Group 2 innate lymphoid cell Modified from Front Immunol. 2018 Jul 13;9:1595. ASP7266 NON-CONFIDENTIAL SUMMARY -- Version dated October 23, 2020 TSLP IS A MASTER REGULATOR OF TYPE 2 IMMUNE 5 RESPONSES Allergens, pollutants etc. ◼ Critical mediator of Th2 differentiation (Allergol Int. 2012 Mar;61(1):35-43) ◼ Regulates ILC2 TSLP ➢ Important roles in survival and Mast Cells proliferation of ILC2 (Allergol Int. 2019 Jan;68(1):9- 16) ILC2s ➢ TSLP confers corticosteroid resistance to mDCs Th2 ILC2 (JACI. 2018;141(1):257-268.e6) IL-4 Plasma Cells ◼ Pathogenic roles in multiple diseases ➢ Allergic diseases including severe asthma, IL-5 IL-13 chronic rhinosinusitis with nasal polyp, Th2: T helper 2 atopic dermatitis (Current Immunology Reviews, 2013, mDCs: myeloid dendritic cells 9, 214-221) Eosinophils ASP7266 NON-CONFIDENTIAL SUMMARY -- Version dated October 23, 2020 ASP7266 BLOCKS UPSTREAM OF TYPE 2 INFLAMMATORY 6 CASCADES Tezepelumab Epithelial damage/shedding CCL17 ASP7266 production ASP7266 blocks all the competitors pathways, IL-4, IL-5, IL-5R, and IL-13 which play important pathogenic roles in type 2 inflammation. ASP7266 is expected to show better efficacy while competitors block part of type 2 inflammation. Modified from Allergy. 2020;00:1–24 ASP7266 NON-CONFIDENTIAL SUMMARY -- Version dated October 23, 2020 TSLP MEDIATES TYPE 2 AND NON-TYPE 2 INFLAMMATION 7 ASP7266 will be an effective therapy on type 2 (T2) as well as non-type 2 (non-T2) inflammatory diseases, which are not controlled by current therapies Modified from Expert Opin Ther Targets. 2020 Jun 27:1-16 ASP7266 NON-CONFIDENTIAL SUMMARY -- Version dated October 23, 2020 TARGET INDICATIONS 8 T2 ASP7266 Non-T2 Tezepelumab Mepolizumab Severe asthma Benralizumab • Type 2 ratio: 60-70% (US), 50% (China) Omalizumab Chronic rhinosinusitis with nasal polyp • Type 2 ratio: 60% (US), 20% (China) Dupilumab Atopic dermatitis No effective therapy Food allergy Eosinophilic esophagitis, Allergic rhinitis, Others Allergic conjunctivitis, Chronic obstructive pulmonary disease (COPD) etc. ◆ Current therapies are effective only on T2 inflammation ◆ Opportunity may remain in non-T2 segments • Epi database • J Allergy Clin Immunol Pract. 2019 Mar;7(3):1010-1016 • Allergy. 2015 May;70(5):533-9 • TOXICOLOGICAL SCIENCES, 164(2), 2018, 627–643 • Allergol Int. 2019 April ; 68(2): 135–142 • Truven real world data • Annu Rev Pathol. 2017 January 24; 12: 331–357 • Clin Exp Allergy. 2018;48:981–989 • Clin Exp Biomed Environ Sci, 2019; 32(2): 96-106 ASP7266 NON-CONFIDENTIAL SUMMARY -- Version dated October 23, 2020 MARKET POTENTIAL 9 ➢ Severe asthma ⚫ 2.5M in US (T2: 1.6M, non-T2: 0.86M) ➢ (Chronic rhinosinusitis with nasal polyp) Target CRSwNP patients ⚫ 2.2M in US (T2: 1.3M, non-T2: 0.86M) ➢ Severe asthma in US ⚫ Biologics* for T2: *dupilumab, mepolizumab, benralizumab, omalizumab Estimated $3800M (2020) → $5900M estimated (2026) sales value ⚫ Non-T2: $3200M estimated (2026) ➢ Dupilumab global sales for multiple T2 indications: $9500M estimated (2026) Potential for ➢ ASP7266 has market potential for T2 as well as non- ASP7266 T2 for multiple indications • Epi database • Annu Rev Pathol. 2017 January 24; 12: 331–357 • Decision Resources • J Allergy Clin Immunol Pract. 2019 Mar;7(3):1010-1016 • Global data • Allergol Int. 2019 April ; 68(2): 135–142 ASP7266 NON-CONFIDENTIAL SUMMARY -- Version dated October 23, 2020 DIFFERENTIATION FROM OTHER BIOLOGICS 10 Development status Competitor’s profile Mechanism of Drug Target action Launch P3 Efficacy Dosing endotype Tezepelumab TSLP inhibitor Asthma High Q1M T2 & nonT2 Asthma, CRS, Moderate to Dupilumab IL-4/13R inhibitor EoE Q2W-Q1M T2 AD High CRS, COPD, Mepolizumab IL-5 inhibitor Asthma, CSS Moderate Q1M T2 AD (failed) CRS, COPD, Benralizumab IL-5R inhibitor Asthma Moderate Q2M T2 EoE CRS, Food Asthma, CRS, allergy, Omalizumab IgE inhibitor Seasonal AR, Moderate Q2W-Q1M T2 Cutaneous CIU mastocytosis Higher ASP7266 TSLPR inhibitor Q3M T2 & nonT2 (assumption) ASP7266 shows differentiated profiles relative to competitors Better efficacy Better convenience Higher responder rate More potent than Tezepelumab Once every 3 months dosing Effective on T2 and nonT2 AD: atopic dermatitis CIU: chronic idiopathic urticaria EoE: eosinophilic esophagitis AR: allergic rhinitis CSS: Churg-Strauss syndrome HS: hypereosinophilic syndrome ASP7266 NON-CONFIDENTIAL SUMMARY -- Version dated October 23, 2020 In-house data ASP7266 POTENTLY SUPPRESSED TSLP/TSLPR-MEDIATED 11 CELL FUNCTION: IN VITRO Ba/F3 cells* proliferation CCL17 production from DC 25 5×10 4 20 4×10 4 ●: ASP7266 15 3×10 4 ■: Tezepelumab (ng/mL) means ± SEM; n=4-5 ▲: Control Ab 10 2×10 4 0 / Em590 / 0 means ± SEM; n=5 4 5 1×10 4 CCL17 Ex5 0 0 - 3 3 3 3 0 3 3 3 0 (μg/mL) 0 1 2 3 4 5 6 m G 0 0 . 3 0 . 3 10 10 10 10 10 10 10 iu Ig 0 . 0 . 0 d . 0 0 e 0 Antibody Concentration (ng/mL) m ASP7266 Tezepelumab *Human TSLPR/ IL-7Rα-transfected TSLP IC (ng/mL) IC (ng/mL) IC50 (ng/mL) IC90 (ng/mL) 50 90 ASP7266 90.7 200 ASP7266 16.1 163 Tezepelumab 518 15300 Tezepelumab 67.0 855 • ASP7266 more potently inhibited TSLP-induced cell function than Tezepelumab • Target trough concentration of ASP7266 is set as 0.3 μg/ml based on IC90 value ASP7266 NON-CONFIDENTIAL SUMMARY -- Version dated October 23, 2020 In-house data ASP7266 INHIBITED TH2 DIFFERENTIATION AND ILC2 12 ACTIVATION: IN VITRO TSLP-stimulated human DC-mediated Th2 differentiation IL-5 production in human ILC2 IL-4 IL-5 5000 8000 IL-5 4000 6000 5000 3000 /mL /mL 4000 4000 pg pg 2000 2000 1000 3000 /mL 0 0 pg 2000 TSLP - + + TSLP - + + ASP7266 - - + ASP7266 - - + 1000 IL-13 TNF-α 40000 3000 0 0 0 0 0.03 0.1 0.3 1 3 10 30000 ASP7266 (μg/mL) 2000 /mL /mL TSLP 20000 pg pg 1000 IL-25, IL-33 10000 means ± SEM; n=6 0 0 TSLP - + + TSLP - + + ASP7266 - - + ASP7266 - - + ASP7266 effectively suppressed T2 cytokine responses ASP7266 NON-CONFIDENTIAL SUMMARY -- Version dated October 23, 2020 In-house data ASP7266 EFFECTIVELY SUPPRESSED ALLERGIC INFLAMMATION IN MONKEY MODELS: IN VIVO 13 -1 6 13 21 day 15 0 7 14 mm) 10 Δ Evaluation ( ASP7266 treatment 10mg/kg i.v. DNP-Ascaris i.p. + i.m. 5 Diameter 0 Wheal -5 Normal Control ASP7266 DNP-As 100 μg/mL N=6 (normal and control groups) or 5 (ASP7266-treated group). ASP7266 shows promise in human allergic diseases ASP7266 NON-CONFIDENTIAL SUMMARY -- Version dated October 23, 2020 In-house data TSLPR ANTIBODY STRONGLY SUPPRESSED MULTIPLE 14 MOLECULES RELATED TO T2 INFLAMMATION: IN VIVO OVA 0 (Day) -1 2 5 8 11 14 Administration Dissection IL-5 IL-13 IgE 30 100 300 80 20 200 60 /mL /mL ng/mL pg pg 40 Unpaired t test 100 10 *: p < 0.05 20 ✱ ✱ ✱✱ **: p < 0.01 0 0 0 l l l l b l l b a b a o a o ro A m tr A m tr A m t r n R r n R r n R o o P o o P o o P N C L N C L N C L S S S T T T Concentration in supernatant of spleen cells Plasma concentration TSLPR antibody is expected to show superior efficacy against T2 inflammation relative to other T2 biologics ASP7266 NON-CONFIDENTIAL SUMMARY -- Version dated October 23, 2020 In-house data TSLPR ANTIBODY EXHIBITED STRONGER EFFICACIES 15 COMPARED TO TSLP ANTIBODY: IN VIVO (A) Asthma model: House