ASP7266 NON-CONFIDENTIAL SUMMARY DISCLAIMER 2

This material includes forward-looking statements based on assumptions and beliefs in light of information currently available to the Astellas and subject to significant risks and uncertainties. This material contains information on pharmaceuticals (including compounds in research or under development) and other matters. Notwithstanding the foregoing, Astellas makes no representations, warranties, assurances or guarantees of any kind or nature whatsoever, whether expressed or implied, regarding the information in the materials (including, without limitation, no representations, warranties, assurances or guarantees as to the accuracy, sufficiency or completeness of any information, as to whether Astellas has rights to any such information or pharmaceuticals/compounds, as to whether any third party has or does not have any rights to any of such information or pharmaceuticals/compounds, as to the safety, efficacy, or effectiveness of any preparations described in this material, as to the regulatory status of or potential for regulatory agency action regarding any pharmaceuticals/ compounds described in this material, or as to any uses, including unapproved uses, of any such preparations in any fashion). This material does not provide medical advice of any kind. Astellas undertakes no obligation or duty to change, remove, add, clarify, correct or update any information in the materials at any time.

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, , 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 , , 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 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 dust mite allergy (B) ILC2 model: OVA/IL-33 induced airway inflammation

11

Airway responsiveness ILC2 number

1.5

N = 7-10, mean with SEM

e # s 1.0 Student-test was used for N = 8, mean with SEM

a statistical difference from One-way ANOVA with

b

/

# control Dunnett's multiple

H *: p < 0.05, **: p < 0.01 comparisons test n

e 0.5 ns: not significant P **: p < or = 0.01 ✱ ***: p < or = 0.001

0.0 l l ) ) ) a o 5 0 5 mg/kg mg/kg m tr 1 1 . r n ( ( (0 o o b b e N C A A n P R lo L P o S L is T S n #bronchoalveolar T d #enhanced pause re lavage fluid P

• TSLP Ab at 15 mg/kg and TSLPR Ab at 10 mg/kg were used as maximum effective dose • Prednisolone at 0.5 or 10 mg/kg were used as positive control, but not as clinically relevant doses

ASP7266 NON-CONFIDENTIAL SUMMARY -- Version dated October 23, 2020 In-house data

ASP7266 PROFILE: TOXICOLOGY 16

To date, the safety of ASP7266 has been evaluated in 6 GLP studies and 1 non-GLP study. Type of Study Species Dose Main fin or Conclusion Safety Perivascular inflammatory cell infiltration was observed 0, 3, 10, 100 pharmacology 4-week with 4-week Cynomolgus in systemic multiple organs in one high dose male. mg/kg/week recovery monkey NOAEL: 10 mg/kg/week for male (i.v.) 100 mg/kg/week for female Increased fibrinogen and total bilirubin levels as well 0, 25, 50, 100 13-week with 13-week Cynomolgus as elevated thyroid weight was noted at the 100 mg/kg mg/kg/week Repeat-dose recovery monkey dose. (i.v.) toxicity NOAEL: 50 mg/kg/week 0, 25, 50, 100 26-week with 13-week Cynomolgus No toxic findings were observed. mg/kg/week recovery monkey NOAEL: 100 mg/kg/week (i.v.) No toxicity findings and no discernible subcutaneous Single dose Local tolerance Cynomolgus 0, 10, 50 irritation at the injection site were noted at any dose toxicity assessment included monkey mg/kg, s.c. levels. No or minimal off-target cross-reactivity in human Tissue cross reactivity Human 0, 0.5, 5 µg/mL tissues Cytokine release ASP7266, at concentrations up to 100 µg/mL, did not 0, 10, 30, 100 assessment Human result in positive cytokine release from whole human µg/mL Others (non-GLP) blood. Immunofluorescence 0, 100 There were no indications of immune complex Cynomolgus Examination mg/kg/week deposition in the tissues of monkeys treated for 4- monkey (i.v.) weeks with ASP7266.

ASP7266 NON-CONFIDENTIAL SUMMARY -- Version dated October 23, 2020 ASP7266 PROFILE: CMC DRUG SUBSTANCE 17

➢ Physicochemical properties o Solubility ▪ >100 mg/mL in pH5 ~ 6 (viscosity: <10 mPa·s) o Stability ▪ ASP7266 drug substance was stable for 6 months at 5°C and for 5 years at ≤-70°C ➢ Documentation transfer can be offered for manufacturing clinical trial material of POC study with existing drug substance.

➢ Formulation for POC study: o 30 mg/mL of frozen liquid formulation (1mL/vial) to be stored at -20°C

There are no particular concerns in physicochemical properties

ASP7266 NON-CONFIDENTIAL SUMMARY -- Version dated October 23, 2020 PHASE1 SAD STUDY OUTLINE 18

Study number 7266-CL-0001 randomized, subject- and investigator- blinded, placebo-controlled, single Design ascending dose clinical study To evaluate the safety, tolerability, pharmacokinetics and Objectives pharmacodynamics of ASP7266 Subjects Healthy adult male and female subjects Control placebo Doses 0.03, 0.1, 0.3, 1.0, 3.0, 10 mg/kg iv and 1 mg/kg sc Formulation iv and sc Dosing Duration Single dose No. of Subjects 46 Assessments incl. Efficacy/Safety Safety, tolerability, PK, PD, ADA Parameters Study Period 2016/05 - 2017/07 (FSI - LSO), 2016/12 (PLR) Area US

ASP7266 NON-CONFIDENTIAL SUMMARY -- Version dated October 23, 2020 CLINICAL DEVELOPMENT SUMMARY 19

Safety ➢ ASP7266 was safe and well tolerated with no allergic/hypersensitivity reactions and no infusion/injection site reactions.

PK )

L m / 0.03 mg/kg iv

➢ AUClast, AUCinf, and Cmax increased g 1000

 (

dose proportionally after iv 0.1mg/kg iv n

o 100

administration. i 0.3 mg/kg iv

t

a r ➢ t1/2 was 8 to 21 days. t 1mg/kg iv

n 10 e

➢ Absolute bioavailability after an sc c 3mg/kg iv n

o 1

dose of 1 mg/kg ASP7266 was 70%. c 10mg/kg iv

m 1mg/kg sc

➢ Serum concentration of ASP7266 u 0.1

r e

after 1 mg/kg sc administration s

exceeded the estimated therapeutic n 0.01 a

e 0 20 40 60 80 100

target (0.3 µg/mL) at Day 60 and was M comparable at Day 90. Days iv: intravenous sc: subcutaneous

ASP7266 NON-CONFIDENTIAL SUMMARY -- Version dated October 23, 2020 INTELLECTUAL PROPERTY 20

➢ Astellas has filed two patent applications relating to ASP7266 (WO2015/020193 and WO2017/104778).

ASP7266 NON-CONFIDENTIAL SUMMARY -- Version dated October 23, 2020