CONFERENCE CALL:ENFORTUMAB VEDOTIN

Bernie Zeiher, M.D.
Chief Medical Officer
Astellas Pharma Inc.
October 1, 2019 (JST)Steven Benner, M.D.
President of Development

CAUTIONARY STATEMENT REGARDING FORWARDLOOKING INFORMATION

2

In this material, statements made with respect to current plans, estimates, strategies andbeliefs and other statements that are not historical facts are forward-looking statements about
the future performance of Astellas Pharma. These statements are based on management’s
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Information about pharmaceutical products (including products currently in development)
which is included in this material is not intended to constitute an advertisement or medicaladvice.

ONCOLOGYSIX GROWTH DRIVERS IN LATE-STAGE
DEVELOPMENT
enzalutamide

gilteritinib

enfortumab
vedotin

URO/NEPH

roxadustat

OTHERS

zolbetuximab

fezolinetant

3IndicationStage

M1 hormone-sensitive prostate cancer

Filed (US, EU, JP)

M0 hormone-sensitive prostate cancerP3

M1 castration-resistant prostate cancer

Filed (China)

Relapsed or refractory AML

Approved (US, JP)
Filed (EU)

Newly diagnosed AML, intensive chemo eligible

P3

Newly diagnosed AML, intensive chemo ineligible

P3

AML, post- HSCT maintenance

P3

AML, post-chemo maintenanceP3

mUC, platinum and PD-1/L1 inhibitor pretreated

Filed (US)P3 (EU, JP)

mUC, PD-1/L1 inhibitor pretreated

P2

mUC, 1st line

P1

Gastric and gastroesophageal junction carcinoma

P3

Pancreatic adenocarcinoma

P2

Japan, anemia associated with chronic kidney disease

Approved, on dialysis
P3, not on dialysis

EU, anemia associated with chronic kidney disease

P3

Chemotherapy-induced anemia

P2

Menopause-related vasomotor symptoms

P3

M0: Non-metastatic, M1: Metastatic, AML: Acute myeloid leukemia, HSCT: Hematopoietic stem cell transplant, mUC: Metastatic urothelial cancer

ENFORTUMAB VEDOTIN SUMMARY4•First and only antibody drug conjugate (ADC) that targets Nectin-4, which is highly
expressed in urothelial cancers•Developing in collaboration with Seattle Genetics as a potential treatment for patients withlocally advanced or metastatic urothelial cancer•

Data continues to demonstrate favorable benefit-risk profile across studies‒ Granted Breakthrough Therapy Designation by U.S. Food and Drug Administration(FDA) based on Phase 1 study data (March 2018)‒ Biologics License Application (BLA) filed with FDA based on Phase 2 study cohort 1data (July 2019)‒ Accepted for priority review by US FDA with March 2020 PDUFA date•

Exploring across spectrum of patient populations, including earlier lines of therapy as wellas earlier stages of urothelial cancer

ENFORTUMAB VEDOTIN IS THE FIRST AND ONLYADC TARGETING NECTIN-4

5

Transitional bladdercarcinoma with strong
expression of Nectin-4• The Nectin family of cell adhesion
molecules play a role in the formation ofcell-cell adherens junctions.1,2• Nectin-4 (PVRL4), a transmembrane
polypeptide belonging to the Nectin family,is expressed in many solid tumors.3

Transitional bladdercarcinoma with moderate
expression of Nectin-4• A total of 83% of bladder cancers on tissue
microarray were positive for Nectin-4
expression.3
Figures modified from Challita-Eid et al. Cancer Res. 2016;76(10):3003-3013

1. Samanta D, Almo SC. Cell Mol Life Sci. 2015;72:645–58; 2. Rikitake Y, Mandai K, Takai Y. J Cell Sci. 2012;125:3713–22; 3. Challita-Eid et al. Cancer Res. 2016;76:3003-13
ADC: Antibody-drug conjugate

ENFORTUMAB VEDOTIN: HOW IT WORKS

ADC: Antibody-drug conjugate

6

ENFORTUMAB VEDOTIN PROGRAM IS EXPLORING
THE FULL mUC TREATMENT LANDSCAPE
1st line

PD-1/L1 inhibitor
pretreatedPlatinum and PD-1/L1inhibitor pretreatedEV-301

cisplatineligible

EV-201 (Cohort 1)
Platinum and PD-1/L1
inhibitor pretreated

Gem-Cis• CPI• Gem-Carbo• Single-agent chemo• Single-agent chemo• Clinical trial• Palliative care

• PD-1/L1 inhibitor*• Gem-Carbo
cisplatin
ineligible*Patients with high PD-1 expression

EV-103

7EV-201 (Cohort 2)
PD-1/L1 inhibitor pretreated,
platinum naïveCombo w/ PD-1/L1
inhibitor and/or platinum

Overall treatment flow similar among regions, although standardof care and approved drugs can vary

mUC: Metastatic urothelial cancer, Gem-Cis: Gemcitabine and cisplatin, Gem-Carbo: Gemcitabine and carboplatin, CPI: Checkpoint inhibitor,
BLA: Biologics licensing application

BLA in US
submitted
based onthis data;
AcceptedandGrantedPriority
Review

ENFORTUMAB VEDOTIN IN PD-1/L1 INHIBITOR
PRE-TREATED POPULATION:

8EV-201 COHORT 1 DATA USED FOR U.S. BLA SUBMISSION
ORR was 44% in platinum and PD-1/L1 inhibitor pretreated patients

ORR per RECIST v1.1 assessed by BICR
Confirmed objective response rate
95% confidence interval1Patients (N=125)n (%)
55 (44)(35.1, 53.2)

Best overall response per RECIST v1.1, n (%)
Complete response

15 (12)

Partial response

40 (32)

Stable disease35 (28)Progressive disease23 (18)Not evaluable2

12 (10)1. Computed using the Clopper-Pearson method
2. Includes 10 patients who discontinued study prior to post-baseline response assessment, 1 patient who had uninterpretablepost-baseline assessment, and 1 patient whose post-baseline assessment did not meet the minimum interval requirement
for stable disease

Petrylak DP, et al., ASCO2019
BLA: Biologics licensing application, ORR: Objective response rate, RECIST: Response evaluation criteria in solid tumors, BICR: Blinded independent central review

ENFORTUMAB VEDOTIN IN PD-1/L1 INHIBITOR
PRE-TREATED POPULATION:

9EV-201 COHORT 1 DATA USED FOR U.S. BLA SUBMISSION
DOR was 7.6 months in this heavily pre-treated patient population
EV-201: Cohort 1 Safety data
• The most common TEAEs occurring in more than
40% of patients•

Fatigue, alopecia, rash, decreased appetite, taste
distortion and peripheral neuropathy• Treatment-related adverse events of interests
Events categorized based on queries for related MedDRA terms

N = 55; 23 EventsMedian DOR: 7.6 months(range: 0.95–11.30+)

Peripheral neuropathy: 50% any grade, 3% ≥Grade 3• 76% had resolution or events ongoing at Grade 1 atlast follow-up
Rash: 48% any grade, 12% ≥Grade 3• 93% resolution or improvement at last follow-up
Hyperglycemia: 11% any grade, 6% ≥Grade 3• 1 Grade 4 event, resolved, no need for ongoing
medication• 71% resolution or improvement at last follow-up

Petrylak DP, et al., ASCO2019
BLA: Biologics licensing application, DOR: Duration of response, TEAE: Treatment-emergent adverse event, MedDRA: Medical Dictionary for Regulatory Activities

EV-103: INITIAL RESULTS OFENFORTUMAB VEDOTIN PLUSPEMBROLIZUMAB FOR LOCALLYADVANCED OR METASTATIC
UROTHELIAL CARCINOMA
As presented at ESMO 2019

Christopher J. Hoimes, Jonathan E. Rosenberg, Sandy Srinivas,
Daniel P. Petrylak, Matthew I. Milowsky, Jaime R. Merchan,Mehmet A. Bilen, Shilpa Gupta, Anne-Sophie Carret, Nancy Yuan,
Amal Melhem-Bertrandt, Thomas W. FlaigSTUDY DESIGN: EV-103 (NCT03288545)

11An ongoing multi-cohort, open-label, multicenter, Phase 1 study
Dose Escalation Cohort

Locally
Advancedor
Metastatic
Urothelial
Cancer(la/mUC)

Dose Escalation
EV + pembro
cis-ineligible
1L or 2L

EV: enfortumab vedotin, pembro: pembrolizumab

Recommended EV dose

Patient
Population

Dose Expansion Cohorts
Cohort D

Cohort A
EV + pembro
cis-ineligible
1L

EV + cisplatin
1L

Cohort G

EV + cis/carbo+ pembro
Cohort E
EV + carboplatin
1L

Optional Cohort
B

Optional Cohort
F

EV + pembro

EV + gemcitabine

2L

1L or 2L

1L

ENFORTUMAB VEDOTIN + PEMBROLIZUMABCOHORTS12

EV 1.25 mg/kg + pembrolizumab (200 mg) in 1L la/mUC patients

PatientPopulation

Dose Escalation1

Dose Expansion
Cohort A

Dosing: EV days 1 and 8 of 3-wk cycle toalign with pembro (day 1 of 3-wk cycle)

Locally
Advancedor
Metastatic
UrothelialCancer(la/mUC)

EV 1.25 mg/kg+ pembro

EV + pembro

EV exposure: Comparable to EV
monotherapy on 4-wk schedule (EV Days
1, 8, and 15)2

cis-ineligible
1L

cis-ineligible
1L(n=5)(n=40)

Primary endpoints: AEs, lab abnormalities
Key secondary endpoints: DLTs, ORR,DCR, DOR, OS

1. Not included in the current analysis: three 1L patients treated with EV 1 mg/kg + pembro 200 mg and two 2L patients treatedwith EV 1.25 mg/kg + pembro 200 mg
2. Rosenberg et al. J Clin Oncol. Epub July 2019

KEY DEMOGRAPHICS AND DISEASE
CHARACTERISTICS
EV 1.25 mg/kg + pembrolizumab in 1L setting
18 June 2019 data cut-off
Male sex, n (%)
Age, yrs, Median (min, max)
ECOG performance status, n (%)
012
Primary tumor location, n (%) 1Lower tract
Upper tractMetastasis sites, n (%)
Lymph nodes only
Visceral disease
LiverPD-L1 status by combined positive score,2 n (%)<10≥10Not evaluable/Not available
1. One patient has primary disease site of origin ‘other’
2. PD-L1 tested using the using the 22C3 PharmDx assay from Agilent/Dako

13

Patients (N=45)n (%)
36 (80)69 (51, 90)

16 (36)23 (51)6 (13)
31 (69)13 (29)4 (9)41 (91)15 (33)19 (42)13 (29)13 (29)

SUMMARY OF DISPOSITION

14

18 June 2019 data cut-off

Patients (N=45)n (%)

Patients on treatment

24 (53)

Patients off treatment

21 (47)

EV 1.25 mg/kg + pembrolizumab in 1L setting

Reason for treatment discontinuation
Progressive disease

12 (27)Adverse event

5 (11)

Patient decision

4 (9)Patients off study

7 (16)

Reason for study discontinuation
Patient withdrawal of consent

2 (4)

Death

5 (11)Median follow-up (min, max)

7.7 months (0.7+, 15.5)

DURATION OF TREATMENT

15

EV 1.25 mg/kg + pembrolizumab in 1L setting
18 June 2019 data cut-off

Patients (N=45)

Duration of treatment (months)
Median6.0Min, Max

1, 13+

Number of treatment cycles per patientMedian7.0

Min, Max1, 17+

Patients on treatment n (%)

24 (53)

Patients off treatment n (%)

21 (47)

OBJECTIVE RESPONSE RATE
ORR per RECIST v1.1 by investigator
18 Jun 2019 data cut-off
Confirmed Objective Response Rate (ORR)
95% confidence interval

16

Patients (N=45)n (%)
32 (71)(55.7, 83.6)

Best Overall Response per RECIST v1.1
Complete response

6 (13)

Partial response

26 (58)Stable disease

10 (22)

Progressive disease

1 (2)Not evaluable12 (4)1. Two patients did not have post-baseline response assessments before end-of-treatment:
1 withdrew consent and 1 died before any post-baseline response assessment

MAXIMUM PERCENT REDUCTION FROM BASELINEIN SUM OF DIAMETERS OF TARGET LESIONS PERINVESTIGATOR

93%

PD-L1 tested using the 22C3 PharmDx assay from Agilent/Dako17

PERCENT CHANGE FROM BASELINE IN SUM OF
DIAMETERS OF TARGET LESIONS PERINVESTIGATOR

18• 91% of responses observed at
first assessment (Week 9±1week)• Median time to response:
2.0 months (range: 1.4 to 4.2)
• Duration of response range:
1 to 10.5 months and ongoing• 22 of 32 responders remain ontreatment

TREATMENT-RELATED ADVERSE EVENTS (TRAE)
TRAEs by preferred term
Any grade in ≥20% of patients and≥Grade 3 in ≥10% of patients

19Patients (N=45)n (%)
Any Grade≥Grade 3

Overall

43 (96)23 (51)

Fatigue22 (49)4 (9)Alopecia

21 (47)

N/A

Peripheral sensory neuropathy

21 (47)2 (4)4 treatment-related discontinuations ofEV + pembro due to AEs (9%)

Diarrhea

18 (40)2 (4)Decreased appetite

15 (33)0• Peripheral sensory neuropathy mostcommon: 2 patientsDysgeusia

14 (31)

N/A

Nausea13 (29)0Pruritus

12 (27)1 (2)Rash maculo-papular

12 (27)3 (7)Weight decreased

10 (22)0Anemia

9 (20)2 (4)Lipase increased

7 (16)

6 (13)

N/A: Non-applicable

7 patients had treatment-related
serious AEs (16%)

1 treatment-related death as reported
by investigator (2%)• Multiple organ dysfunction syndrome• Confounded by concomitant acute onsetof atrial fibrillation, corticosteroids, andamiodaroneTREATMENT-RELATED ADVERSE EVENTS OF
CLINICAL INTEREST (AECI)

20Rates of peripheral neuropathy, rash, and hyperglycemia similar to EV
monotherapy in post-platinum, post-PD-1/L1 mUC patients(EV-201, Cohort 1)1Patients (N=45)n (%)

Time to first onset (months)
median (min, max)

Any Grade≥Grade 3a

Any Grade

Peripheral neuropathy

22 (49)2 (4)2.2 (1, 6)

Rash

21 (47)5 (11)

0.4 (0, 7)

Hyperglycemia (non-fasting)

5 (11)3 (7)

0.5 (0, 3)

AECI: categorized by related MedDRA terms

a. No grade 5 events

Patients (N=45)n (%)
AECI: determined by investigator
Immune-mediated AE requiring systemic steroids

Any Grade≥Grade 3a9 (20)

5 (11)ba. No grade 5 events.
b. Events occurred in 1 patient each. Grade 3: pneumonitis, dermatitis bullous, lipase increased, tubulointerstitial nephritis; Grade 4: myasthenia gravis

1. Rosenberg et al. J Clin Oncol. Epub July 2019

EV-103 SUMMARY AND CONCLUSIONS

21•

High unmet need for effective and tolerable therapies in 1L cisplatin-ineligible la/mUCpatients•

Enfortumab vedotin + pembrolizumab demonstrates encouraging activity in 1L cisplatinineligible la/mUC patients in EV-103
 High ORR (71%)

 Rapid responses (91% at first assessment) that appear durable
 Activity regardless of PD-L1 expression
 Safety appears manageable and tolerable; AECI similar to monotherapy•

Enfortumab vedotin + pembrolizumab has the potential to become a platinum-free option
for cisplatin-ineligible la/mUC patients in the 1L settingNEXT STEPS

What we look forward tonext with enfortumabvedotin22•

Continue progressing EV clinical development program•Continue engagement with regulatory authorities globally•

Plan a Phase 3 study combining EV and pembrolizumab

THANK YOU
QUESTIONS