Updating the Lung Cancer Treatment Algorithms With Novel Antibody–Drug Conjugates: Are You Prepared for Change? State of the Science, Implications for Practice, and Future Prospects

Chair and Presenter Stephen V. Liu, MD, Melissa L. Johnson, MD, and Prof. David Planchard, MD, PhD, discuss NSCLC in this CME activity titled “Updating the Lung Cancer Treatment Algorithms With Novel Antibody–Drug Conjugates: Are You Prepared for Change? State of the Science, Implications for Practice, and Future Prospects.” For the full presentation, downloadable Practice Aids, and complete CME information, and to apply for credit, please visit us at https://bit.ly/3PRGCou. CME credit will be available until October 9, 2025.

1. Updating the Lung Cancer Treatment Algorithms
With Novel Antibody-Drug Conjugates:

Are You Prepared for Change?
State of the Science, Implications for Practice, and Future Prospects

Stephen V. Liu, MD Prof. David Planchard, MD, PhD
Associate Professor of Medicine Department of Medical Oncology
Director, Thoracic Oncology Head of the Thoracic Cancer Group
Head, Developmental Therapeutics Gustave Roussy

Lombardi Comprehensive Ñ Villejuif, France
Cancer Center $.

Georgetown University

Washington, District of Columbia

Melissa L. Johnson, MD
Director, Lung Cancer

Research Program

Sarah Cannon Research Institute
Nashville, Tennessee

Go online to access full CME information, including faculty disclosures.

100-2024, PeerView

2. Our Goals for Today

Augment your knowledge of the efficacy and safety
of ADCs in the treatment of lung cancer

Equip you with skills for integrating ADCs
into individualized treatment plans for patients with
lung cancer

Provide you with guidance for developing effective
strategies to identify and manage AEs associated with
novel ADCs in lung cancer

Copyright © 2000-2024,

3. Targeting HER2: The First ADC
to Enter the Lung Cancer
Treatment Arsenal

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4. HER2-Targeting ADC

Trastuzumab Deruxtecan

de 38 Proprietary drug linker
DA a iy,
20 o 220 +
1 cysteine residuo
O Dg ter

+ ADC with three components
— Humanized HER2-targeted mAb
— Topoisomerase | inhibitor “payload”
— Tetrapeptide-based cleavable linker

+ High drug-to-antibody ratio (-8:1)
Conjugation Chemistry + High potency payload that is
ee membrane permeable > nearby cells
SL in tumor targeted regardless of HER2
Payload (DXd) expression (“bystander antitumor effect’)
Exatecan derivative
IMR tena trap or PS Ope oe vga PeerView

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5. ously Treated

+ Unresectable/metastatic nonsquamous Cohort 1° (n = 49) Cohort 1a* (n = 41)
NSCLC L_| HER2 overexpressing HER2 overexpressing

+ Relapsed/refractory to standard (IHC 3+ or IHC 2+) (IHC 3+ or IHC 2+)
treatment T-DXd 6.4 mg/kg Q3W T-DXd 5.4 mg/kg Q3W

+ Measurable disease by RECIST v1.1
+ Asymptomatic CNS metastases

at baseline? on 5 a a o
. E 'ohort 2 (n = 42) ohort 2 (n = 49)
eee, HER2 mutation EE at HER2 mutated
: T-DXd 6.4 mg/kg Q3W T-DXd 6.4 mg/kg Q3W
(cohort 2) 6.4 mg/kg Q3 6.4 mg/kg Q:

+ Primary endpoint: confirmed ORR by ICR®

+ Secondary endpoints: DOR, PFS, OS, DCR, and safety

+ Exploratory endpoint: biomarkers of response

+ Pater wi ssetomat rin late rol equi onging se or ntc rap ware alowed 1 er ® HERZ ut documented sally fo au Dopey

‘ould not De used for enrolment." HERZ overexpression Mot known HERZ mutation was detomminod by loca assessment ol archival Ussuo and contraly cor
Por RECIST VL.

Y mips/etiatats ovisty NCTOSGOSTIO. 2. LAB at al N Engl J Med, 2022;306:241-251 PeerView

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6. Best Percentage Change in Tumor Size From Baseline i

HER

ated Population!»

Baseline in Sum of Diameters

Best Percentage Change From

3 8

40

50

80

0
|

vere rope

exc weitem He

Pier HERZ TKI therapy

HER2 mutation domain location
‘Kinase domain = Extracellular domain

ORR: 55% (95% Cl, 44-65)
(N=91)

ohana ena AD

Best change in tumor size by ICR or BS of 91 patients fr whom baseline and postbaseine data were avalabl,* The Oncomine™ Ox Target Test (Thermo Fisher mn used to
confirm local HERZ mutation status and determine HER2 ampiicaton satus. HERZ protein expression talus was determined by IHC using a modified PATHWAY ant-HERZ (4B5) (Ventana
[Medical Systems, Ic.) assay. Shown ks best (minimum) percentage change from baseline in ho sum of diameters for al target lesions: () negative; (+), postive I insertion N. no; S,
guet: Y yo, Blok cols (exept oe par HERZ TK rap ow) nate pont whose tumor amples wore na raul seres, The uper dashed horznal ino

Indeatas

in tumor sia nthe patients who had disease progression and te lower dashed ine Indicats a 30% decrease i tumor size (PR

FAT etal NE Med 2022300201281 PeerView

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7. Best Percentage Change From Baseline in Targe!
bgroup*?

the Prior Lines of Therapy

Patients With $2 Prior Lines of Therapy at Baseline

100
80
60
40

Best (Minimum) Change, %
N Median Minimum Maximum

58-440 -91 14

Best Percentage Change in
‘Sum of Diameters From Baseline

+ Tho rod line at 20% indicates progress
HUB at al ann Oncol 202208 8448-8864

PeerView.com/CES827

Best Percentage Change in

Sum of Diameters From Baseline

ve disease, and tho black ine at -30% indicates à paral response.

esions by ICR

Patients With >2 Prior Lines of Therapy at Baseline

100
80
60
40
20

o

20

40

-60

Best (Minimum) Change, %
N Median
27 430

Minimum
100

Maximum
6

PeerView

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8. PFS and OS in the Overall HER2-Mutated NSCLC Population’

Overall Population (N = 91)

wo
E
®
x So
4 q
E 35
5 5
& a »
»
PA » pun age nen
:
TIN INTO it OT TETE)
Time, mo Time, mo
cenamos 7709 ro E Ema o
LPS nn to CR uo RECI adn vers Kan rl. EX ll nado a cor Dire os Daños

to dots C1181 patos de ad prog dose nd 15 had Ged by D da cr dao. Ota 91 para were Cod as real y malo, PE were.
cancrad fy continue vostra! e
ELIBT et a A Eng! J Mod 2022:300241-251 PeerView

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9. n(%) Any Grade
Pi its with 21 di lated
TEAES => 88 (08.7) 42 (46.2) Drug-Related ILD/Pneumonitis
Drug-related TEAEs with 220% incidence in all patients Grad
Nausea 66 (72.5) 888) Any,
Fatigue 48 (62.7) 6 (66)
Alopecia 42 (46.2) 0 n(%) 3 15 4 2 24
(3.3) x 5
Vomiting 36 (39.6) 3(33) est ss) 04 FA [088
Neutropenia 32 (35.2) 17 (187)
INH EN 000) Median time to onset of first reported
n a s drug-related ILD/pneumonitis: 141 d
Dianhon 29 (81.9) 3(83) (range, 14-462 d), with a median duration
Decreased appetite 27 (29.7) Y of 43 d (95% Cl, 24-94 d)
Leukopenia 21 (23.1) 4 (4.4)
Constipation 20 (22.0) 0
1. UBTetal Eng! J Med 2022:386:241-251 PeerView

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10. DESTINY-Lung02: T-DXd in Previously Treated Metastatic
HER2-Mutated NSC

Patients and investigators were
blinded to the dose level

DESTINY-Lung02

Key eligibility criteria?

+ Metastatic HER2mut° NSCLC

+= 21 prior anticancer therapy, including
platinum-based chemotherapy

+ Measurable disease per RECIST v1.1

+ ECOG PS 0-1

T-DXd
5.4 mg/kg Q3W
n= 1022

T-DXd
6.4 mg/kg Q3W
n=50

Stratified by
+ Prior anti-PD-(L)1 treatment

+ Primary endpoint: confirmed ORR by BICR
+ Secondary endpoints: confirmed ORR by INV, DOR by BICR and INV, DCR by BICR and INV, OS, safety
+ Exploratory endpoints: PROs (ie, EQ-5D-5L, EORTC QLQ-C30, EORTC QLQ-LC13, NSCLC-SAQ)

1a ar dea ovo: August 282023. Parts wih sabe bran metastases Dasein anymelomat; nol ogg azote or anzonvsent testa) wre age,

Lg Het son anand aman ral urn sb ern osea! “One alan rio) sra PT 4 mg om
recov wesent because he patient sonics do to COVID-1 tra oc day
‘Ships encanta goto OT ima Peal ASCO 2024 Aboot 8345 PeerView

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11. Responses observed regardless of HER2 mutation type,
HER2 amplification status, and number or type of prior therapies
1. anne PA el. VILO 2023, Ana MAS 10.2 Goto K tal. J Cn Onc 2023414862409 eerView

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12. PFS and OS With T-DXd Across HER2-Mutated NSCLC Settings’?

PFS os
100
# 100
3 0 + Censoredcases bei
ra gs
©
So T-DXd 6.4 mg/kg $
2 T-DXd 5.4 mg/kg 2 60
3 0 so T-DXd 54 mglkg
a TOXd S4mglkg(n=102)T-OXAS.Amalkg (me) E as Imong (n=
2 204 rn mo 08% ee een E 201 mesa, m ee ee
à Le 4463.1) 20140) OSeventa nt) 37083) 1480)
o
01234567 8 91011121314 1516 17 18192021 01234567 8 9 1011121314 1516 17 18192021 22
Time,mo Time, mo

1. Jenne PA tal WLC 2023, AbstactMATS.10. 2. Goto ea J Gin Oncol 2028448524053, PeerView

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13. DESTINY-Lung02: Safety Summary’

Drug-olated TEAE, %
‘ny grado

Grade 23

‘Associated with drug dscontnuation
Associatod with dose reduction
Associated with drug intemuption
Associated with death

Adjudicated Drug-Related ILD

Safety Analysis Set

Adjudicated as Drug-Related ILD

ON LL LL |
ss | _|]
7-DXa 54 mg/kg SO T-DXd 6.4 mg/kg
ma RE (50)
OE
soll:
5 o 50 100

T-DXd 5.4 mg/kg T-DXd 6.4 mg/kg

Destiny-Lung01: 26% ie) “=
Any grade, n (%) 6 (5.9) 7 (14.0)
Grade 1 3 (3.0) 1 (2.0)
Grade 2 2 (2.0) 6 (12.0)
Grade 3 1 (1.0) o
Grade 4 o 0
Grade 5 0 o
1. Jenne PA eta WELC 2023. Abstract MAT3 10.2. Goto Ket a. J Cn Oncol 2029:414852:4803 PeerView

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14. Exploratory Pooled Brain Metastases Analyses

of DESTINY-Lung01 and DESTINY-Lung02*+

‘Cohort te ‘Cohort ta

Desri-ngor wera owegresung. || nero
A mens 4 >) RS)

noe roxas Su
+ lpredtetcoy o aa stan or
+ Measurable disease by RECIST v1.1 Endpoints
u IAB send tie + Inpatients with and
+ Locally reported HER? mutation (cohort 2° = > en És without baseline BM:

systemic CORR per BICR,
systemic DOR per BICR,
sites of progression per
BICR, TEAÉS

ooled T-DXd

6.4 malkg In patients with
5 DL-O1 HER2m/ — measurable baseline BMS:
. IC-CORR per BICR,
IC-DCR per BICR,
Non-BM (n IC-DOR per BICR

+ ata cot December, 202. CT or Mo the brin was required a screen; atenta win esymptomat BM a olmo wer ee ny dd net need ongoing cars or
«icons! voatmens; had recovered rom acto LR} toc, and 22 wooks had passed snce WERT. Dat Gaal December 23.2022. Pant ty tae Dan tants
bene fesplonet na rqurng conca or animent einen) ware sige «Acad HERZ malo documenid rom an aval tes anor eave sano D
ri es lboratoy asosimant "Ore pater randomly assigned o T-DX 5 mk am Gd nt recive Welmertbecavse the pat denied do to COVID-1 below cy
{Gay 1. BM wore ones messe Y ey wre 210 mer} dmanson on CT or MR. 142 pants wih baso BNF DOT and ANDA DL OZ had GM Mal wore megs.
responses wore evaluate mensura baslne BM per RECIST v1.1 nase on CT or MAI scan eer Dre 1 dy o acaonal cane were aque or oso ht
cine Bi es inealy name.

LOT etal ESVO 292) Arc 1321M0, 2 UBT aa. N Engl Med, 202239824151. 3. LBT ot ESMO 2022. .
4. Goo Ket a J Cin Ones 2023341 4852-4069. PeerView

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15. DESTINY-Lung01 and DESTINY-Lung02: IC Objective Response
Rates and Best Overall Response (BICR)!

Measurable BM at Baseline T-DXd 5.4 mg/kg

DL-02 BM
(0218)

Paria
96% cm an 147404

response
oR 2010 o
PR 4005 90
so 64429) 19433)
Po van 409)
Ne o 267) 4
Missing o 2167) Pooled T-DXd 6.4 mg/kg
1c:06R, m6 151829) 2033) (n= 279) Progressive
sx cm 051998 541977 dr
1C.00R. mot
Modan 95% Ci ssGene) 4429-102)
Paral
response

12/14 (86%) patients with measurable BM
receiving T-DXd 5.4 mg/kg and 21/27 (78%) in the pooled

6.4-mg/kg group experienced a reduction in brain lesion size
from baseline as their best overall response

= Deromnator fr prcotag is he numberof parts nr ul ana et who ave atest one target san at basa per BICR ases on ne Chpper- Pearson mao fr angle
proponen “For one patent deemed NE nthe 0-4 mak) group, twas not Pose 1 dev dbetve response du lo miesng ata alone target onthe pants bet overs reponse
however was elle rm avaiable lrpt lesion asassmonis an nchtad nie una LL Callate as tino rom Wr rsponss in ra nt progression nba, "Based on
Kaplan-Maer anaya and computes win he Brogkmeyer-Crouey menos, :
AUT oral ESMO 2023 Abstract 132100 PeerView

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16. FDA and EMA Approvals: First D

for HER2-Mutated NSCLC

On August 11, 2022, the FDA granted accelerated approval to fam-trastuzumab deruxtecan-nxki
for adult patients with unresectable or metastatic NSCLC whose tumors have
activating HER2 (ERBB2) mutations, as detected by an FDA-approved test, and who

have received a prior systemic therapy!

In September 2023, the EMA recommended trastuzumab deruxtecan for approval
as monotherapy for the treatment of adult patients with advanced NSCLC whose tumors
have an activating HER2 (ERBB2) mutation and who require systemic therapy following
platinum-based chemotherapy with or without immunotherapy?

DESTINY-Lung04*

+ First-line advanced NSCLC
+ HER2 ex19 or ex20 mutations
(N = 152)

+ Endpoint: PFS

Pembrolizumab +
pemetrexed + platinum

|: panne dogo man and gat ga clin oponer don ot too analog
2 bem ar supe alenheweinteing Dons come sal pease anse amp can 202
3 mos cheats ovstcyNCTOS048797, PeerView

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17. DESTINY-Lung01: Responses Observed With T-DXd
HER2-Overexpressing Metastatic NSCLC’

Cohort 1 Cohort 1a
Trastuzumab Deruxtecan 6.4 mg/kg Trastuzumab Deruxtecan 5.4 mg/kg
(n = 49) (n=41)

3
3

Baseline HER2 IHC status
Hc 2+ (n= 35)
BB Hc 3+ (n = 9)

Baseline HER2 IHC status
[Bic 2+ (n= 17)
Mine 3+ (n= 17)

ORR: 26.5% (15.0-41.1) ORR: 34.1% (20.1-50.6)

Seb Bo BEBE

ie
#3
23
5
85
ik
83
E
a

Best Percentage Change in
Sum of Diameters From Baseline

3

Lancet Oncol 2024251439454. PeerView

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18. PFS and OS With T-DXd in HER2-Overexpressin

1

Metastatic NSC
PFS in cont ay mg/kg)

08
06

04

PFS Probability

PFS in Cohort 1a (5.4 mg/k:
(N= af ako)

mPFS: 6.7 mo
(95% Cl, 4.2-8.4)

PFS Probability

No. at Ris

i =
012345678 ETIENNE TETE) OTI TOO ea as
Time, mo Time, mo
x No, at Risk
so15292620191910877665554222211110 4100 00 2 27 a 18 16 0 8 8 6 4 3 1 0
PeerView

1. Smit EF el al. Lancet Oncol 2024:25:430-154.

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19. The First Tumor-Agnosti C12

HER2-Positive (IHC3+) Solid Tumors

DESTINY-Lung01
(Cohort 1a)
(n= 17)?

Confirmed ORR, % 514 52.9 46.9
(95% Cl) (41.7-61.0) (27.8-77.0) (84.3-59.8)

CR 2.7 5.9 0
PR 48.6 47.1 46.9
mDOR, mo (range) 19.4 (1.3-27.9) 6.9 (4.0-11.7) 5.5 (1.3-9.7)

DESTINY-PanTumor02
(N = 111)

DESTINY-CRCO2
(N=64)

Efficacy Parameter

On April 5, 2024, T-DXd received accelerated approval for patients with unresectable or

metastatic HER2-positive (IHC3+) solid tumors who have received prior systemic
treatment and have no satisfactory alternative treatment options

1 Mo hf govdugtesoucs nfomaton approved. gis grant screed aprovlemteskzumab orten ni resecado amet ner .
2 Smt EF et al Lancot Oncol 2024, 25:490454 PeerView

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20. T-DXd Monotherapy in Pretreated HER2-Overexpressing

Nonsquamous NSCLC: DESTINY-Lung03 Part 11

+ DESTINY-Lung03 (NCT04686305) is an open-label phase 1b study evaluating
T-DXd-based treatments in HER2-overexpressing NSCLC

+ Results from DESTINY-Lung03 part 1 confirmed the clinical benefit of T-DXd
monotherapy (5.4 mg/kg; arm 1D) in pretreated HER2-overexpressing (IHC 3+/2+)

mNSCLC, building on results from DESTINY-Lung01 cohort 1a Hsia,

- Exploratory analyses showed promising activity in HER2-overexpressing expression as an
(IHC 3+/2+) NSCLC, including in patients with and without treatment with prior actionable biomarker
EGFR TKI i

NSCLC and
> HER2 IHC 3+ (ORR: 56.3%; mPFS: 6.9 mo; mOS: 16.4 mo) and HER2 ren the ae for
IHC 2+ (ORR: 35.0%; mPFS: 8.2 mo; mOS: 17.1 mo) subgroups HER2 IHC testing in

> Prior EGFR TKI (ORR: 68.4%; mPFS: 8.2 mo; mOS: 19.6 mo) and no routine NSCLC

prior EGFR TKI (ORR: 17.6%; mPFS: 7.1 mo; mOS: 14.7 mo) subgroups | diagnostic work-up
+ These data suggest that T-DXd is associated with improved outcomes compared
with current 2L SOC for metastatic HER2-overexpressing NSCLC
+ No new safety signals were identified, and the safety profile was consistent with
the known profile of T-DXd
+ DESTINY-Lung03 is ongoing; parts 3 and 4 are assessing T-DXd-based regimens
in treatment-naive HER2-overexpressing mNSCLC
1. Pionchart Det al WOLO 2026, Abstract DASS. PeerView

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21. Discussion and Questions

Copyright © 2000-2024,

22. Targeting HER3: ADC Approach in
Addressing Unmet Needs in
EGFR-Mutated Lung Cancer

23. Phase 1 U3140 102 Study of Patritumab Deruxteca
(HER3-DXd) in EGFR ated NSCLC?

Pooled patients receiving HER3-DXd 5.6 mg/kg who had prior third-generation
EGFR TKI therapy and prior platinum-based chemotherapy (n = 78)

a
ZE o» Confirmed best overall response (BICR) + Ongoing treatment
By = SCREPRESDEPDENE
dez
Pr
EN
8 i 2
sis
38 a
ES
FE ORR: 41%

ropes ade attire mans co cr A (GEN TI) a repairs Rd ar acre mations eos wth ER LER (TION: GR LAO ad
Bese Leas aed NSS eee LD fn base Seen ERS marmo esa
YU HA eta. Ann Oncol 2024253437447 PeerView

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24. Antitumor Activity: Pooled Prior Third-Generation EGFR TKI

Platinum-Based Chemotherapy

10
10
os 08
2 2
3 = os
3 os 3
3 3
2 2
Los a 04
E ©
a o
oz] mPFS: 6.4 mo 02 mOS: 16.2 mo
(95% Cl, 4.4-10.8) (95% Cl, 11.2-21.9)
6: + Censored 5 + Censored
of 6 8 0 is 0 18 20 22 28 02 2 6 8 1012 da 16 18 20 22 24 06 28 30 3204
Time, mo Time, mo
No. at Risk No. at Rsk
78 68 49 2 25 18 11 6 8 6 3 3 1 78 71 62 65 46 39 32 24 2 1842 8 7 4 2 2 2 0
1. YU HA tal Ann Oncol 2024:35437-447, PeerView

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25. HERTHENA-Lung01: HER3-DXd in Advanced EGFR:

NSCLC Following Progression’

A Multicenter, Open-Label, Randomized, Two-Arm, Phase 2 Study (NCT04619004)
HER3-DXd IV Q3W

+ Advanced EGFR-mutated NSCLC Fixed dose: Enrollment continued
‘ . 5.6 mg/kg (N = 225)
+ Progression on most recent systemic :
therapy
+ Prior EGFR TKI and platinum-based
chemotherapy cuerdas protocol required of phase 1 data
prior osimertinib) supported the closure of
+ Inactive or previously treated asymptomatic the uptitration arm
brain metastases allowed Uptitration Enrollment
+ Pretreatment tumor tissue required? C1D1: 3.2 mg/kg discontinued (
C2D1: 4.8 mg/kg
+ Primary endpoint: CORR by BICR C3Dt+: 64 mglkg

+ Key secondary endpoint: DOR by BICR pete u ==>% September 16, 202

+ Par aa to Nom 21, 2022, Dota u o pina anis ocued wen ol role pants ad ether 29 monton rad iconos or the sty

tater Soopaot data ct May 1,2023 (atom 6 mans op) Oat ar presea e Do 8.6 mg usd dose am Modan sy flow 180 range, 149.273) months,

Sly topar a so mantos ro 5S (ang, 07.02) on non brandon THER ea 20 ptr wu vols 2 rece
dora +5! patos wore rod 5 oca > x

TEA taf LG 2008 As 010803 2 YU FA et ol. Futuro Oncol, 2029:19.1919-1329 PeerView

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26. HERTHENA-Lung01: Clinically Meaningful Efficacy Observed in

the Overall Population and Across Subgroups’

Prior EGFR TKI
(Any) and PBC
(N= 225)

Confirmed Responses
and Survival

EGFR TKI
and PBC

CORR, % (95% CI)
CR, n(%)
PR, n (%)
SD, n (%)°
PD, n (%)
NE, n (%)°

29.8 (23.9-36.2) 29.2 (23.1-35.9)

41 (19.6)
16 (7.7)

16 (7.1)

DCR, % (95% Cl) 73.8 (67.5-79.4) 72.7 (66.2-78.6)
oo me 6.4 (4.9-7.8) 6.4 (5.2-7.8)
oxen mo: 5.5(5.1-5.9) 5.5 (5.1-6.4)
teen mo 11.91.2131) 11.9(10.9-13.1)

‘Snapshot data cto May 18, 2023. Median study folowwup: 18.9 (ang
{SD cS ar art ot sy teatment n=)
1. Yu HA etal, WCLC 2023, Abstract OA0S 03,

PeerView.com/CES827

Subset: Prior 3G

CORR by Patient and Disease Characteristics

Overa
sy
Age 2,
Female

= Male
Asian

Raco nie
omer

EGFR-actvaeng Ext9del
‘mutation meer
History of brain YO8
metastass

Yes
No

Prior
Immunotherapy

Prorregmenstor 2
‘advanced disease, n >2

at Study Entry

n comm

EN ++

MM ert

won Te

132 280 md

mus te

ma ren

Per ma

2 429 A.

mm re

a ==

115 287 u

110 309 rte

Per He

“me er

SN ten

wa me

Teh boo om

CORR. %

927.5) mo. Indudes nen-CRInon.PD. «No adequate postbaslin tumor assessment (n= 12) SD oo aary

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27. HERTHENA-Lung01: Tumor Reduction Across

Diverse Mechanisms of EGFR TKI Resistance

HER3-DXd 5.6 mg/kg (N = 225)?
Confirmed best overall response (BICR)
MOR MPR MSD HPO MINE + Ongong vosiment

Best Change in SOD (BICR)
From Baseline, %
meses e.88 888

«pasoo! aa ed May 18,2023, Maan tut lew: 18 (ange, 14.027 5) monde» 210 patents had evaluate rt monsuemont at bah basen and pasase
‘and are included. + T790M was nol included as an EGFR: ‘mechanism of

PNA ta WOLC 2029 Ana OO 0.2 VA at Y Cun Oncol UL DIESE PeerView

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28. HERTHENA-Lung01: Efficacy Observed Across a Broad Range
of Pretreatment Tumor HER3 Expression Levels'?
Association of Baseline Tumor HER3 Membrane H-Score With Confirmed BOR by BICR
Following Treatment With HER3-DXd 5.6 mg/kg (N = 225)>

300
E +
$2 20
33 °
© 200
z —
55 + R
e § 150 a & .
£2 Le oe
Bo 10
El =
50
slo Loe
0 + r
Confirmed BOR (BICR) CRIPR sD PD NE
Biomarker-evaluable patients, nin 54/67 89/99 35/43 1516
H-score, median 205 205 179 195
Range 0-300 0-300 0-300 15-295
“usar dt he pa A May 18,202, Nair a ty ili: man nda 919 pat hos ume an ea or
He Bastne was be sangen or bee ft Son al sn a eater han 20 Der the oes date gran HERS man ns cu ake was weed timate
Focos wore mato A
A VUNA etal WCLC 2029, Abstract OADS 03. PeerView

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29. HERTHENA-Lung01: Safety Profile of HER3-DXd

Was Manageable and Tolerable’

xa Se moka Most Common TEAEs Occurring in 215% of Patients (N = 225)
5)

Any TEAE, n (6) 728 (896) ere 2

‘Associated with treatment discontinuation? 16 (7.1) ratas spero

summary

Associated with treatment dose reduction 48 (21.3) Neutoporia(grauped PT)” 36
Associated with treatment dose interruption 91 (40.4) ‘Constipation 2
Grade 23 TEAE, n (%) 146 (64.9) Anemia (groupe PT) 33
Treatment-related TEAE, n (%) 215 (95.6) fa D st
Associated with death? 4(18) Ft)

Grade 23 102 (45:3) Loutoperia poupe PT)"
Serious TEAE 34 (15.1) Nopecia
Adjudicated interstitial lung disease, n (%) en
(All were adjudicated as treatment-related)
Grade 1 104) Hypokalemia
Grade 2 8(36) Cou
Grade 3 2(09) Abdonina pain grouped PT) “PEE
Grade 4 o oa wm WO
Grades 104) Proportion of Patients, %
Any hematologic toxicities typically occurred early in treatment,
were transient, and not associated with clinical sequelae
Primary data co November 21, 2022, Median veatment Graton 55 (ange, 07-182) montis > TEAES long 1 dconirualn included prownonts (1 = ), 1000 bikin increased
n=2) dyspnea (n = 2), and cholestatic pundce, enema, aun, peral hypertension, duodenal poroaton,wosepsis, oran, and wine Boos count decmases (n= teach) TEAES
‘associate wth death hat wore considered relate o study drag included pneuments respiro alo, Gi potoraton aná pnsumona (ro neutropenia) in na patent each.
ER ct 2029 Apart R08. 08 PeerView

= Grade 23
Gade

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30. HERTHENA-Lu : Intracranial Responses (by CNS BICR)
Observed With HER3-DXd

Intracranial Efficacy of HER3-DXd in Patients With Brain Metastases at Baseline

Patients With Brain Partial CNS Response in a Patient
Intracranial Response by Metastasis at Baseline and With a Measurable CNS BICR Target Lesion
CNS BICR per CNS RECIST No Prior Radiotherapy Screening
(n = 30) J

CORR, % (95% Cl) 33.3 (17.3-52.8)

CR, n (%) 9 (30.0)¢

PR, n (%) 1(83)

SD, n (%)! 13 (43.3)

PD, n (%) 4 (13.3)

NE, n (%) 3 (10.0)
DCR, % (95% Cl) 76.7 (57.7-90.1)
Median DOR, mo (95% Cl) 8.4 (5.8-9.2)

+ Snape data co May 10, 2023. Mecian sty elo: 189 (ange, 149.275) mens 7 pains had measurable tra leon; 23 patents had cy notations: 0 pants
had oly nontarget lesions Incudes non Con PD.
TYUHA tal WEL 2023, Abstract OADSOS. PeerView

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31. Phase 3 HERTHENA: g02: Patritumab Deruxtecan vs
Chemotherapy in Advanced EGFR-Mutated NSCLC After TKI!

Locally advanced/metastatic non-squamous NSCLC
not amenable to curative surgery or radiation

EGFR exon 19 deletion or L858R

1-2 prior lines of EGFR TKI treatment, including third-
generation TKI, in locally advanced/metastatic setting

No other prior systemic therapies in the locally
advanced/metastatic setting

Progression during or after treatment with third-generation
EGFR TKI for locally advanced/metastatic disease

21 measurable lesion
ECOG PS 0-1

Patritumab deruxtecan

Pemetrexed +
cisplatin/carboplatin

(N = -560)

+ Primary endpoint: PFS (BICR RECIST v1.1)
+ Secondary endpoints: OS, PFS (INV), PFS (LSCP), ORR, DOR, CBR, DCR, TTR QOL, and safety
1. seat. govistucyNCTOS338970 PeerView

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32. Phase 1 Study of SHR-A2009, a HER3
in Advanced Solid Tumors!

SHR-A2009, a novel ADC, composed of a fully human anti-HER31gG1 mAb, covalently linked to a DNA
topoisomerase | inhibitor via a cleavable peptide linker (DAR = 4)

All Patients NSCLC Patients
(N=42) (n= 36)
Median age, y (range) 59 (42-68) | 59(42-68)
Female, n (%) 27 (64.3) | 22(61.1)
Asian, n (%) 42 (100) 36 (100)
ECOG PS 1, n (%) 35(83.3) | 35072)
Tumor type, n (%)
NSCLC 36 (85.7) 36 (100)
Others 6 (14.3) 10)
Tumor stage IV, n (%) 42 (100) 36 (100)
Site of metastasis, n (%)
Bone 19 (45.2) 47 (472)
Brain 12 (28.6) 1606)
Liver 11(262) 8022)
EGFR activating mutation, n (%) 34(81.0) | ea)
Ext9Del 17 (40.5) 17 (47.2)
Laser 18 (5.7) 18(41.7)
G719X 2(48) 2668)
Ener ¡demora en ne Median prior lines of systemic therapy (range) - 30-61)
Prior 3rd-generation EGER TK, n (%)

A )
- Treatme in 21 patent a
tment ongoing in 21 patents, PeerView

1. Wu YA etal ESMO 2023. Abstract 6

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33. 9: Antitumor Ac

d Safety!

TRAEs Occurring in 25% of Patients

M5 moig M90 mc Hobo
9 u

e Ses A] Neurop coun decreed

BIER 60 non WC cout doconeed

tng

Deceased appa

‘Alopecia

Fasgue

GGT increased

Hypoalbuminemia

Dizziness

AST increased

ALT increased

‘Abdominal discomfort

Hyponatremia

Diarhea

ORR in NSCLC: 30% (95% CI, 14.7-49.4) Blood ALP increased

Urinary tact infecton

Proteinuria

Best Change in SOD
From Baseline, %

Moun ulceration
moi we BEE 388 Lymphocyte count decrees od
Hypocalamıa
corras Cough
| 1 1 00) il iil ay oes
0 20 40 60
segment. |
u A El Incidence Rat,
1. Wu YA eta ESMO 2023 Abstract SONO, PeerView

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34. Discussion and Questions

Copyright © 2000-2024,

35. Targeting TROP2: Evolving Evidence
on ADCs in Different Treatment
Settings and Patient Populations

Copyright © 2000-2024, PeerView

36. Data in the Second Line

Copyright © 2000-2024,

37. TROPION-PanTumor01: Antitumor Activity

With Datopotamab Deruxtecan (Dato-DXd) in the NSCLC Cohort

Best Change in Sum of Diameters (BICR)

Best Overall Response (BICR)

Dato-DXd Dose

z

Pationts®

©
©
«
4mgkg 6mgikg 8moko RE
(n= 50) COUR 5:
OR? n (4) 12(24) —14(28) 19(24) Es
or o o 10m t of
PR 12(24) 1428) 1809 Bw
SD, n (4) 25(50) 20(40) 42(63) os
Non-CRIPD, n (%) 1@ 20 26 de
Loli) Hit) im) CO Change in Sum of Diameters of Target Lesion (BICR) Over Time
NE, n (4) SM gy van | « so p
er a = ® = US kel
Mactan DOR (BER COS. GENE) GENE) GENE À À ER CCR Ce
+ Anttumor activi was observed at4-,6-,and&mgng doses 8. 4 3
of Dato-DXd cz 2 2
=. Moat responses were durable over time, including ie = =
a median DOR of 10.5 mo in the 6-mgikg cohort 5 oss rana or cesouusunann " 02a eue

+ lnk rponse-vaunble paris wo hd 00 o mero posts tumor assessment r discontinued treatment
YORK and CRIAR nde ono response me 6 agg eoor thats pending cama .
1 Garon EB et al WCLC 2921, Abstract MAS 02 PeerView

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38. Metastatic NSCLC

A Randomized, Phase 3, Open-Label, Global Study (NCT04656652)

Without AGA?

NSCLC (stage IIIB, IIIC, or IV)
ECOG PS 0-1
No prior docetaxel

1-2 prior lines, including platinum chemo

and anti-PD-L1 Pl
With AGA

Positive for EGFR, ALK, NTRK, BRAF,
ROS1, MET exon 14 skipping, or RET
1-2 lines prior approved therapies plus
platinum-based chemo and <1 anti-PD-L1

Stratification

Histology (squamous vs
nonsquamous)

AGA (presence vs
absence)

Anti-PD-L1 mAb included
in most recent prior
therapy (yes vs no)
Geography (United
States/Japan/Western
Europe vs rest of world)

Dato-DXd
6 mg/kg IV Q3W

Doceta:

75 mg/m

Dual primary endpoints: PFS (BICR), OS
Secondary endpoint

RR (BICR), DOR (BICR), safety

Parents with KRAS mutations in the absence of known seionable genome aterations aro eligible; must mest por therapy requirements for patente
without actionable genomic alterations.
1. mis /chn anal gout NCTOSSSEES2 2. Ahn M et a, ESMO 2023, Abstract LBA12.

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39. PeerView.com/CES827

TROPION-Lung01: PFS (ITT)!

Dato-Dxa Docetaxel
Median PFS, mo (35% CI 44 (42-58) 372942)
100: HR (95% Cl) 0.75 (0.62-0.91)
e 04
so Prespecified boundary (2-sided) 008
ORR, % (95% Cl)” 26.4 (21.5-31.8) 12.8 (9.3-17.1)
Re © DOR, mo (95% CI) 7165-109) 5.6 (54-81)
= 408
2
Edo
Dato-DXd
2
o
o 7 7 y y 5 = 1 16 18
Time Since Randomization, mo
No, at Risk
Dato-Dxa 2 26 15 96 74 4 2 10 2 o
Docetaxat 35 186 120 “ 2 19 1 7 o o
+ Median PFS follow-up time was 10.9 months (95% Cl, 9.8-12.5) and 9.6 months (95% Cl, 8.2-11.9) for Dato-DXd and docetaxel, respectively.
*indaodfor CRE ane 73 efor Ono Oke ana 29 PR lor canal A
Y Am Metal ESMO 2023 AbstnctLDAT2 PeerView

Copyright © 2000-2024, PeerView

40. TROPION-Lung01: PFS by Histology’

Nonsquamous Squamous:
With and Without AGA With and Without AGA
= Dato-Dxd Docetaxel tw _Doto-DXd Docetaxel
mTOR BARRO RAR APTO NAO ECS
» Pre oso © un wenn, ¡omo
on at es orm x a2 vr
® OR, mo. 77 ® DOR, mo 59 a
©
¢ E?
E, Es
2 ES
y o
DOI TS 8 0 @ E we i. + 1 0 2 + oe e
Time Since Randomization, mo Time Since Randomization, mo
Dern Den
m 16 6 Où © 7 1 0 Dæoë Om % æ 0 6 6 4 +
decd 2 US D © Œ M 0 4 0 mas HS % 1 0 s 4 3 o
PFS HR for nonsquamous without AGAs: 0.71 (0.56-0.91)
An Metal. ESMO 2029, Abstract LEA 12 PeerView

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41. TROPION-Lung01: Tumor Response and PFS in Patients

With Nonsquamous Histology"?

PFS by BICR-Nonsquamous Population

Dato-DXd Docetaxel
Median (95% Cl), more 55(4369) 3.6 (2.9.4.2)

HR (85% Cl) 0.63 (0.51-0.79)
x 60
‘ORR, n (%) 73 (31) 30 (13) gg
(95% CI) (50-380) — (9.0-18.0) = 40
mDOR 17 56
(95% Cl), mo (5:6-11.1) _(5.4-6.0) 20 H
i Docetaxel
o
o 2 4 6 8 10 12 14 16 18
Time Since Randomization, mo
No. at Risk
DatoDXd 24 181 135 86 67 41 2% 7 1 O0
Docetaxel 24 1389 SO 32 4 10 4 0 0
+ Patents wih CRF derived nonsquamous histology in

fut ana

‘Hagan PS Dion ep esimate by mere Kaplan bear was 109 09% C, 98-124) and 86 (95% Cl, 85-125) mans fr patents tested wih Dat-DX and docetaxel, respecto
Based on Kalan moto, 2-00 ls ao computed using tw Brooker Cray men,

‘Girard N etal ELC 2028 Poster PeerView

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42. TROPION-Lung01: TRAEs Occurring in 210% of Patients!

System Organ Class.
Pi 0

43(15) 14) 59 (20) 14)
12(4) 2(1) 76 (26) 68 (23)
Gastrointestinal
‘Stomatitis 140 (47) 19 (6) 45 (16) 3m)
Nausea 100 (34) 7(2) 48 (17) 3(1)
Vomiting 38 (13) 31 22(8) 103
Constipation 29 (10) 0 30 (10) 0
Diarrhea 28 (9) 10.3) 55 (19) 41m
General
Astheni 55 (19) 8(3) 55,19) 5)
Fatigue 34(11) 20) 40 (14) 6e)
Metabolism and nutrition
Decreased appetite 68 (23) 103) 45 (16) 103)
Skin and subcutaneous
‘Alopecia 95 (32) o 101035) 1103)
Rash 36 (12) o 186) o
Pruritus 30 (10) 0 12(4) 0

category includes the

PeerView.com/CES827

Dato:
(n= 297)

xd

Docetaxel

Stomatitis and nausea were
the most frequent TRAEs seen
with Dato-DXd and were
predominantly grade 1 or 2
Hematologic toxicities,
including neutropenia and
febrile neutropenia,° were more
common with docetaxel

No new safety signals were
observed with Dato-DXd

efor mt neopani nd np ou decanos” Incas a vat cor repara a gro.
TREO lorcccntael and Dar vo
‘atm a ESO 2029 Ab LOMO

PeerView

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43. TROPION-Lung01: AEs of Special Interest!

+ Stomatitis/oral mucositis associated with Dato-
ito-DXd Docetaxel
AES! (n= 297) (n=290) DXd resulted in low discontinuation rate (0.7%)

+ Most common ocular event with Dato-DXd was
dry eye (6.1%, primarily grade <2), followed by

Stomatitis/oral mucositis, n (%)*

All grades 160 (54) 59(20) increased lacrimation (5.4%)

Grade 23 19 (6) am) + Seven adjudicated drug-related grade 5 ILD

Ocular events, n (%)° events

All grades 57 (19) 27 (9) — Primary cause of death in 4 out of 7 patients
was attributed to disease progression by

Grade 23 52 0 (0) investigator

Adjudicated drug-related ILD, n (%)® - Nonsquamous: 4 out of 232 patients (1.7%)

All grades 25 (8) 12(4) and squamous: 3 of 65 patients (4.6%)*

CEA 106) a) * [RRs were observed in 8% of patients in each

arm, all were grade <2 with the exception of
Grade 5 na) 103) one grade 3 event with Dato-DXd
“ens need seca Ps ok casas. Gospel. corestaga sta capa, sts argenta sis ve, ann

Te a neue PeerView

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44. TROPION-Lung05: Phase 2 Study of Dato-DXd in Previously

Treated NSCLC With Actionable Genomic Alterations?

- Stage IB, MG, orIV NSCLC

+ Presence of 21 actionable genomk alteration (EGFR, ALK,
'ROS1, NTRK, BRAF, MET exon 14 skipping, or RET)

+ ECOGPS00r1

+ 21 line of targeted therapy

= 1012 or oooni agont-contaring therapies inthe
rotastate eating

+ Radiographic disease progression after targeted therapy

Primary endpoint: ORR
by BICR

‘Secondary endpoints:
DOR. DCR, CBR. PFS,
and TTR by BICR and

Safety Summary

ERES Occuring in 215% of Patents
‘All Grades (un 57)

‘Best Change From Baseline in Sum of Diameters of Target Lesions

Pew genet raros
“ss

ine in Sum of Diameters of Target Lesions
atients With Confined CRIPR Cons 208

Efficacy Summary

Wah EGFR Whale

ORR Emmen Mu HUE Ems)
nme) aaa (2489 Corsa

Median DOR mo 2 7 7
Cri ein aaa e
OCR confimed, me Ma 2035)
NERO) mo) mins (6870

Cri «

70 (6489 889)

+ BOR: In the overall population (n = 137), four patients
(8%) achieved a CR and 45 (33%) achieved a PR

+ EGFR subset: Among patients with sensitizing or
‘T790M mutations (n = 68), the ORR was 49.1% in
those previously treated with osimeninio

+ The primary completion date wil occur when al patients have had ether a minimum of 9 months of follow-up aller the star of study treatment

or have discontinued rom the study
1.Paz-Ares Letal. ESNO 2023. Abstract 1341M0,

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45. Dato-DXd vs Docetaxel in Patients With NSCLC:

Final OS From TROPION-Lung01!
OS by Histology

Nonsquamous ‘Squamous
o DueDxe Docal
) D

A ¿ooo
REE TEE TERR ARE
Be Time, mo vn Ti

+ In patients with nonsquamous histology, there was a 16% risk reduction for death and
2.3-mo improvement in median OS with Dato-DXd

+ OS improvements in the nonsquamous subset were seen regardless of actionable genomic
alteration status

- Present: 15.6 mo vs 9.8 mo (HR = 0.65 [95% CI, 0.40-1.08])
— Absent: 13.6 mo vs 12.3 mo (HR = 0.89 [95% Cl, 0.70-1.13])

1. Sands Jet WCLC 2024. Abstract 0808.08, PeerView

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46. Normalized Membrane Ratio of TROP2 by QCS

Predictive of Outcomes in TROPION-Lung 011

+ TROP2 NMR as measured by quantitative continuous
‘scoring (QCS) reflected the expression of TROP2 in the Overall BEP: Efficacy by TROP2 QCS-NMR Status
o fit TROPZ eno and TROP2 QCS-NMR positivity is predictive for longer PFS

Nine pase mer opbreien, with Dato-DXd in the biomarker-evaluable population

- TROP2 QCS-NMR+ was more prevalent in
patients with nonsquamous vs squamous histology

3

Ex

One
(66% vs 44%) = m Median PFS.mo. 69
~ Patients receiving Dato-DXd who were TROP2 = Treatment by biomarker status
QCS-NMR+ had a higher ORR and longer PFS 3 interaction:
compared with those who were TROP2 QCS-NMR- ©? = Dato xa, QC NMR
pa ‚mit a 1
- Overalligrade 3+ AE rates with Dato-DXd were similar $ — Docetaxel, ACS AR
regardless of TROP2 QCS-NMR status Ez “a ESA Oe
+ Further investigation of this promising biomarker is a
‘ongoing in the first-line advanced/metastatic NSCLC o »
trials AVANZAR (NCT05687266) and TROPION-Lung 10 o 4 y 12 16
(NCT06357533) Time From Randomization, mo

marker and the
Xd in NSCLC.

TROP2 QCS-NMR has the poter to be the first TROP2
first computational pathology biomarker for predicting clinical response to Date

1. Garassing MO et al WGLG 2024, Abstract PLOZ 1 PeerView

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47. Sacituzumab Govitecan: Safety and Efficacy Outcomes

From the Phase 1/2 IMMU-132-

1 Basket Trial!

NSCLC Cohort (n = 54)
ORR, % (95% Cl) 167 (7.9-29.3)
PR, n (%) 9 (16.7)
SD, n (%) 22 (40.7)
Median DOR, mo (95% Cl) 6.0(2.5-21.0)
‘Median OS, mo (95% Cl) 73(56-14.6)
Median PFS, mo (95% CI) 44(2554)

Best Change From Baseline in the Sum
of the Diameters of Target Lesions

u

1. Barcia À ta. Ann Oncol. 2021:32746-156.

38

Change From Baseline, %.

drets

PeerView.com/CES827

ni (%) NSCLC Cohort (n = 54)
‘AEs leading to dose reduction 23 (43)
‘AEs leading to discontinuation 2(4)

All-Cause AEs

Nausea
Diarrhea
Fatigue
Alopecia
Neutropenia
Vomiting
Anemia
‘Constipation
Anorexia
Hypophosphatemia
Dehydration
Weight decrease
Leukopenia
Hypomagnesemia
Dyspnea
Pneumonia

Sacituzumab govitecan 10 mg/kg
BB Sacituzumab govitecan 8 mg/kg

20 40

60
Patients, %

30 100

PeerView

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48. Phase 3 EVOKE-01: Sacituzumab Govitecan in Previously

Treated Metastatic NSCLC’

+ Stage IV NSCLC Sacituzumab
+ Progression after platinum-based and ee"
PD-1/PD-L1 inhibitor therapies mg/kg IV 0
+ 21 previous targeted treatment for a pcs A 1 and day 9
actionable genomic alterations (AGAs) ee a Continue treatment
5 . until progression
EGFR, ALK, PD-V/PD-L1 results are Ll, Racnanes to lost prior : uni progression
required; resulting for other AGAS is pee oe pre
> fet wee + Received prior targeted
a therapy for AGAs (yes vs no)
+ Measurable disease
+ Adequate organ function

+ Primary endpoint: OS
+ Secondary endpoints: PFS, ORR, DOR, DCR, safety and tolerability, and QOL using NSCLC-SAQ

1. tos cals govstudyINCTOSOESTSA 2. PazAres LG el. ASCO 2024. Abstract LEABSOO PeerView

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49. EVOKE-01: Primary Results!

Sachant
os: ITT Ey OS: Subgroup Analysis
100 = Fr
ES » are RIT
so menea 034 (088-108
= tated an
moon MW or
a er Was) coton
ë 1-sided Ps .0223 1002800)
do ora
aciuzumab goviecan omnis)
=o il E
8» don
»

sem)

o EVOKE-01 study did not meet its primary
UT E À À € à endpoint of OS in patients with previously
Time, mo treated metastatic NSCLC
seen Numerical improvement in OS favoring SG

23910) 275122) 234 (63) 212 (63) 175 (112)140 (137) 76(150) 40 (162) 17 (166) 10,167) 0,168) was observed, including in patients with both
Docs 30410) 277 (23) 234 (65) 201 (08) 188 (131128 151) 64178) 41184) 15.187) 74187) 2187) ‘squamous and nonsquamous histology

1. PazAves LG et al ASCO 2024, Abstract LBABSOD. PeerView

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50. Overall Survival: Best Response to

Last Anti-PD-(L)1-Containing Regimen!

Sacituzumab govitecan had a 3.5-mo mOS improvement over docetaxel
among subgroups with nonresponse (SD/PD) disease

jonresponsive (SD/PD) i Responsive (SD/PD)

100
E rete pu pe ee
ma o Sone
E =a E = a
570 A canny 570 Sha” an eee
Eo mosca “eramos 2 oo mono ena
2 so 477 — Sacituzumad À 50
© 40 govitecan © 40 Docetaxel
= 4 ¿ss
8 20 8 20 Saciuzumab
10 10 govitecan
o o
0 2 4 6 8 10 12 14 16 18 20 0 2 4 6 8 10 12 14 16 18 20
No. at Risk, n (events) Time, mo No. at Risk, n (events) Time; ro,
A mn 0 (OU Om a 4 m M 6 2 0
govitecan (0) (16) (41) (54) (72) (84) (95) (105) (107) wen: m ‘goviecan on (22 a “0 2 (65) oy (59) (60) (60)
ior ira Sar Sve se e we oo ae

Doral QG) a) Um 00) BH) 40D) 00) (1) (D (125) C26) HEHE TY HH) 2) GO) aM GH) GD CD GH) OH

1.PazAres LG etal, ASCO 2024, Abstact LBABSOD. PeerView

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51. Data in the First Line

Copyright © 2000-2024, PeerView

52. ge From Baseline

All Patients Patients in the First:
(n= 124) (n = 84}

Best Change in SOD

mDoublet mTriplet + Treatment ongoing = Dato-DXd 6.0 mg/kg?

+ Part win no basse target son rn posts tumor assessments wore cad um ne val Ds.» Planes doe lve R
1.0 et at ASCO 202%, Ansac 006. PeerView

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53. TROPION-Lung02: Safety!

TEAEs Occurring in 220% of Patients

Doublet therapy __Triplet therapy
Stomaits A
pipa] —— +
DT > rea]
Decreased appetite a
‘Constipation =
Vomiting =
Cough 7
> ES :
‘Amylase increased os
Alopecia er
[Diarmea] 2 EEE
©
a 0 =
La —
—
mn: Monet
o
sa E » © @
Patients, %

1. Goto Y etal ASCO 2023. Abstract 9004.

PeerView.com/CES827

+ The most frequent TEAEs of any
grade were stomatitis, nausea,
anemia, and fatigue

In general, hematologic TEAEs,

particularly those of grade 23,
were more frequently observed
with triplet therapy than with
doublet therapy

PeerView

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54. 100 Total

80 Best overall response
8 A Partial response (n = 30)
a“ D Stable disease (n = 20)
3 an © Progressive disease (n = 4)
a
a
3
E
Fl
El
5
E Cohort A (PD-L1 TPS 250%)
2 M Cohort B (PD-L1 TPS <50%)
En Participant
1.000 80 eat WCL 2023. Abstract OADS 04 PeerView

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55. EVOKE-02: Safety’?

Any-Grade TEAEs Reported Immune-Mediated TEAEs
a in 215% of Patients © mode 23 Grade 1-2
names 2Omer2
o
zo
8 x
ie ie
En Es

‘ (dc
"2272 Se a ff Fu

Al palets who recetas 21 dose of study reatmert were need inte sally analy * Grade 3 preumenit was ie highest grade observed ato (7 2) .
1,000 90 et a WCLC 2023 Abstract 0A0S04, PeerView

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56. OptiTROP-Lung01: Phase 2 Study of 1L

Sacituzumab Tirumotecan (Sac-TMT) + KL-A167 (Anti-PD-L1)*

Study Design

Continue treatment

until progression | Primary endpoint

or unacceptable | + ORR by investigator
toxicity assessment

Cohort 1A
Sac-TMT 5 mgikg
+ KL-A167 1200 mg Q3W

+ Locally recurrent or
‘metastatic NSCLC.
+ NoAGAS

+ No prior systemic
theray Cohort 18 Secondary endpoints
+ ECOGPS 0-4 Sac-TMT 5 mgikg = + DCR, DOR, PFS, OS

+KL-A167 900 mg Q2W + Safety

Cohort 1A Sac-TMT 5 mg/kg Q3W + Cohort 18 Sac-TMT 5 mg/kg
KL-A167 1,200 mg Q3W (n= 40) KL-A167 900 mg Q2W (1
Median follow-up, mo 14.0 69
OR. n/N (%) [95% CI] 18/37 (48.6) (31.9-65.6] 45158 (77.6) [64.7-87.5}
PR, n(%) 18 (48.6) 45 (77.6)
Confirmed PR, n (%) 16 (43.2) 40 (69.0)
SD, n (%) 17 (45.9) 13 (224)
PD, n (%) 2(54) o
DER» niN (%) 35/37 (94.6) 58/58 (100.0)
mDOR (95% CI), mo NR (8.3-NE) NR (6.6-NE)
mPFS (95% CI), mo 15.4 (6.7-NE) NR (8.4-NE)
6-mo PFS rate (95% Cl), % 69.2 (61.2816) 846 (714-921

Including confrmed PRICR os responsa pending confimation. ORR was calculated based on response evaluable population defined as 21 on-sudy scan
DOR was defined as BOR of CR + PR 26 weeks,

1. Fang WE etal, ASCO 2028, Abstract 8502.

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57. Other ADCs on the Horizon
for Lung Cancer

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58. LUMINOSITY: ORR by EGFR Status and c-MET Expressio

With Telisotuzumab Vedotin in ET-Positive NSCLC !

ORR Per Central Review by Cohort/Group

52.2
(30.6-73.2)

36.5
(236-510)

244
(10.3-43.5)

167
(66-347)

ORR, % (95% CI)

111
(2.4-29.2)

116
(39-25.1)

nsa Nsa NSQ NSQ NSQ NSQ a
EGFRut EGFRwt EGFRwt EGFRmut EGFRmut EGFRmut oon
Cohort C-METHigh C-METInt Cohort C-MET High C-MET Int

1. Camidge Reta. ASCO 2022. Abstract 8016.

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+ Nonsquamous EGFR WT
(interim analysis 3)

Met criteria for stage 2 |

Met criteria for futility
+ Nonsquamous EGFRmut
+ Squamous (interim analysis 3)

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59. EGFRwt c-Met Expressing NSCLC!

Best Reductions in Target Lesions* per ICR

squam

gs | een io (N=14)
28 80 ar
= 0 (217352) g eo E
E] ms
dal Pen gg *
gs
S 20 5%
* ¿0
gs ge
e as
SÓ 10 la
5
o Patient (N= 147)
c-Met High c-Met c-Met OE + DCR was 60.3% (c-Met high), 57.8% (c-Met
Intermediate Total intermediate), and 59% (c-Met OE total)
Moderately higher a th increased c-Met expression
1. Camidge Rata ASCO 2022 Ant 9018. PeerView

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60. LUMINOSITY: Adverse Events'

= Total (N = 136) =
EAN) Any Grade | Grade 23 en!

Any TEAE 131(08) 65(48) R
Most common any-grade TEAES (210%) BOY TEAE related to thee Wt soe)
Nausea 30 (22) 1) Any serious TEAE 41 (80)
Hypoalbuminomia 28 (21) 1
Peripheral edema 25.18) o Any TEAE leading to Teliso-V discontinuation 45 (83)
Crea vision 25 (18) 107)
cala 24 (18) 0 Any TEAE leading to Telso-V discontinuation possibly ¡919
Fatiga 2 (16) sa related to Teliso-V»
Anemia 19 (14) 2)
19/14) 40) Any TEAE leading to death possibly related to Teliso-Ve 2(1)
Asthenia 18 (13) 30)
; CR res JE 7 Pneumonitis reported in 9 (6.6%) patients,
en ae + 3 of whom had grade 23 (2.2%) pneumonitis
Cough 14 (10) o
Diarrhea 14 (10) o
Dizziness 14 (10) o
Malignant neoplasm progression 14(10) 118)
Vomi 14 (10 14
HH ee PeerView

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61. Ifinatamab Deruxtecan (I-DXd), a B7-H3-Targeting ADC:
Efficacy in SCLC (24.8-mg/kg Cohort)122
Phase 1/2, two-part, multicenter first-in-human study of I-DXd, a B7-H3-directed ADC composed of a fully

human anti-B7-H3 IgG1 mAb, a topoisomerase | inhibitor payload (an exatecan derivative, DXd), and a
tetrapeptide-based cleavable linker, in patients with advanced solid malignant tumors
© scLc
Starting dose level
80 D 6.4 mg/kg D 8.0 mg/kg Ml 12.0 mg/kg fill 16.0 mg/kg

Confirmed ORR, n (%, 95% CI) 11 (524, 298-743)
Confirmed CR, n (%) 1448)
Confirmed PR, n (%) 10 (47.6)

Median TTR, mo (95% Cl) 12(12:14)
Median DOR, mo (95% Cl) 59(2875)
Median PFS, mo (95% Cl) 5.6 (3.9-8.1)
Median OS, mo (95% Cl) 122 (64-NE)

11.7 (46-129)

Population (All Doses) 2
Number of prior systemic regimens, median (range) — 2(1-7)

Best Change From Baseline, %

Platinum-based chemotherapy. n (%) 22 (100)
Immunotherapy, n (%) 18 (81.8)
Irinotecan or topotecan, n (%) 8 (227)
Jopotecan, n (%) 31135)

+ Change om baton in target sons was assessed por RECIST v1.1. 21 patins wae avaiable a babe, ut on ic ot have ay postbaselne mar assessments aná sowas
na need nthe watral pl.» One patera rece both
‘ThitosencatilsgovitudyINCTOS145622 2 Patel Met a ESMO 2023. Abstract 90°. PeerView

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62. Ifinatamab Deruxtecan (I-DXd) in Extensive-Stage Small Cell

Lung Cancer (ES-SCLC): Interim Analysis of IDeate-Lung01' |

Phase 2 IDeate-Lung01 Study (NCT05280470)

Primary Endpoint
Patient Eligibility + ORRbyBICR®

+ Histologically or cytologically documented end) ERROR
ES-SCLC

+ Age 218 years® Arm 1: DXd 8 mg/kg + DOR BIER andi”

+ 21 prior line of PBC and 53 prior ines of one + PEBby BICR andi
systemic therapy E DCR:

+ Radiologically documented PD à RB BiéR mai
on or after most recent prior systemic be by BICR and inv?

+ ECOG PS0-1 E Seay inve

+ 21 measurable lesion per RECIST 1.12 pi ld

+ Patients with asymptomatic brain + Pharmacokinetics:
metastases (untreated or previously ‘Stratification * _Immunogenicity
Seated ae ae) + 2L CTFI <90 days, 2L CTFI 290 days, 3L, or AL Exploratory Analysis

+ Prior anti-PD-(L)1 treatment (yes or no) + Intracranial ORR by BICRS

1. Rudin CM eta. WOLC 2024, Abstract 040409. PeerView

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63. 1-DXd in ES-SCLC: Promising Antitumor Activity Seen in

Interim Analysis of IDeate-Lung01!

Patients Treated With 12 mg/kg

Had a Higher ORR Than Those Treated With 8 mg/kg

1-DXd 8 mg/kg (n = 46)*

LDXd 12 mg/kg (n = 42)°

Confirmed Response by BICR®
ORR, % (95% Cl)

Patients

CR, n (%)
PR, n (%)

DCR, % (95% Cl)

exe en
8% © ORR: 26.1% (95% CI, MSN) ESO CORR: 64.8% (95% CI, 37-702)
gee @| aro mso men mor gef ©] aro mso mer ne
323 ojos HE
33 o 33 =

„sg. BBS 2
888 dad“

ge co ee

és és

+ E

Xd 8 mg/kg |-DXd 12 mg/kg
46) (n= 42)
26.1 (14.3-41.1) 54.8 (38.7-70.2)
1(2.2) 0
11 (23.9) 23 (54.8)

80.4 (66.1-90.6) 90.5 (77.4-97.3)

1. Rudin CM eta. WGLG 2024, Abstract OA04.03,

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64. I-DXd in ES-SCLC: PFS And OS Were Similar Between say

Arms, Numerically Favoring I-DXd 12-mg/kg Dose!

3

Median (95% CI) PFS, mo
LOXd 8 mg/kg: 4.2 (2.8-5.6)
1DXg 12 mghg: 55 (4.2-6.7)

Median (95% Cl) PFS, mo
LDXd 8 mg/kg: 9.4 (7.8:16.9)
LOXd 12 mgikg: 11.8 (89-153)

12 maka (n = 42) 12 mg/kg (n = 42)

8

PFS Probability, %
8 8

OS Probability, %

85838

TEO Bmghg (n= 46)

o
0113455770 do 12 a das
Time, mo

H
B
E
D

PEA 1m 0 8 7 7 7 ss 1 0 E muuss trios
Wee SUR Robes sr ii u te i ao oy oy eesraies
1. Rudin CM eta WCLC 2028, Abstract OA 03. PeerView

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65. IDeate-Lung02 (NCT06203210): Phase 3 Trial in Relapsed SCLC

After One Prior Line of Platinum-Based Therapy!

Key Inclusion Criteria

Histologically or cytologically confirmed SCLC
Received only one prior line of platinum-based
therapy

21 measurable lesions per RECIST 1.1
Radiologically documented PD on or after
platinum-based therapy

ECOG PS 0-1

Patients with asymptomatic brain metastases are
eligible

Stratification:

CTFI after 1L therapy (<90 vs 200 days)

TPC (topotecan vs amrubicin vs lurbinectedin)
Prior treatment with PO-(L)1 (yes vs no)
Presence/history of asymptomatic brain
‘metastases (yes vs no)

Dual primary efficacy endpoints:
‘ORR per RECIST v1.1 by BICR
and OS

‘Secondary efficacy endpoints:
‘ORR per investigator, PFS; DOR,
DCR and time to response by
BICR and investigator; and PROS

Safety endpoints:
TEAES, deaths, serious TEAES,

TPC (topotecan
lurbinectedin)

and TEAES leading to dose
‘modification or discontinuation

Study treatment continues until disease progression,
unacceptable toxicity, withdrawal of consent, death,
loss to follow-up, or other reasons per protocol,

A phase 2 study (NCT05280470) of patients with 2L or 3L ES-SCLC is also currently ongoing

1. OwonokoT et al, ASCO 2024. Abstract TPS8126

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66. ABBV-706: SEZ6-Targeting ADC!

SEZ6-targeting antibody, conjugated to a topoisomerase 1 inhibitor payload with sub-nM cytotoxic activity

Monotherapy Study Design Change in Target Lesion Size by Dose

ABBV-706 Monotherapy

Part 1: ABBV-706 monotherapy dose escalation
(n= 60 overall)

ABBV-706 dose

( Part 2a: Dose optimization; Part 2b: Dose expansion ]
22 rai dose levels at RP2D

Part 4a: Dose expansion Part 4b: Dose expansion
in CNS tumors (n = 40) high-grade NENs (n = 40))

CO current anaiysis (2 onsoing parts

Best Change in Target Lesions, %

Patients

1. Ghandans SR at al ASCO 2024 Absac 3001 PeerView

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67. Case Discussion and
Final Audience Q&A

68. Let’s Consider a Case

68-year-old man is incidentally found to
have a lung nodule on x-ray
— No history of smoking % Di:
CT scan showed a 2.8-cm spiculated LLL lung LAS DER
nodule v What treatment would you
— PET and MRI with no other areas recommend?
of uptake
Underwent lobectomy Y What dose? o
— T2N1 lung adenocarcinoma v What if HER2 overexpression is
— PD-L1: 5% \ detected instead?
— HER2 exon 20 G776delinsVC
Completed 4 cycles of adjuvant cisplatin +
pemetrexed
Radiographic surveillance
— Three new sclerotic bone lesions;
biopsy = adenocarcinoma

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69. Let’s Consider a Case

68-year-old man is incidentally found to
have a lung nodule on x-ray
— No history of smoking % Di:
CT scan showed a 2.8-cm spiculated LLL lung LES bates
nodule v What if the patient develops
— PET and MRI with no other areas pneumonitis/ILD?

of uptake
Underwent lobectomy

— T2N1 lung adenocarcinoma

— PD-L1:5%

— HER2 exon 20 G776delinsVC
Completed 4 cycles of adjuvant cisplatin +
pemetrexed
Radiographic surveillance

— Three new sclerotic bone lesions;

biopsy = adenocarcinoma

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70. Detecting and Managing T-DXd-Related ILD:

The Five “S” Rules!

! | un
Ne ©

Screen Scan Synergy

Steroids

+ Carefulpatientselachon | | + The fundamental
is warranted before diagnostic tools for ILD
initiating T-DX¢ to remain radiological
‘optimize the monitoring ‘scans, with preference
strategies based on for high-resolution CT
the baseline risk ‘scans of the chest

+ Minimizing the risk + T-DXd should always
Of ILD involves. be interrupted if ILD is.
teamwork, which ‘suspected; it can only
includes educating be restarted in the
patients and all the case of asymptomatic.
care team, as well ILD that fuly resolves

mulidisciplnary

management once

ILD is suspected

+ The mainstay
for treating T-DXd-
induced ILD remains
corticosteroid, with
the dose to be adapted
tothe toxicty grade

Screening continues ‘Abasaline scan is
during treatment, recommended, with
with regular cinical repeat scans lo be
assessments to exclude performed every 6-12
Signs/symptoms of ILD weeks

1. Tarantino P, Tlaneÿ SM. JCO Oncol Prt. 2023:0P2300097. PeerView

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71. Let’s Consider a Variation on Our Case: What If?

68-year-old man is newly diagnosed with

mNSCLC Let’s Discuss

Y What treatment would you

+ NGS biomarker testing: no actionable recommend?
genomic alterations detected; PD-L1 Y” What if the patient receives

TPS 70% treatment with Dato-DXd and
Begins 1L carboplatin, pemetrexed, and develops periocular inflammation?
pembrolizumab with a partial response >

maintenance pemetrexed +

pembrolizumab

After 6 months, CT scans show

progressive disease in the liver

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72. Management of Ocular Surface Events!

Step 1: Prophylaxis Step 3: Manage

Advise patients so Er atient is adhering to prophylactic guideli
+ Use artificial tears (four times daily for prevention and up to RS nes
eight times daiy if elinically needed)
+ Avoid use of contact lenses ‘Gree’
+ Consider obtaining ophthalmologic assessment
+ No change in Dato-Dxd dose
Step 2: Confirm
Grade 2
Ophthalmologic assessment to ensure an accurate * Obtain an ophthalmologic assessment
diagnosis, event grading, appropriate treatment, + Delay dose until event has been resolved to grade <1,
and event resolution should be considered and then maintain dose
nel ne a lec ana ophthalmologic assessment
lear comes, no. n
+ Grade 1: nonconfluent superficial keratitis + Delay dose until event has been resolved to grade 51,
+ Grade 2: nonconfluent superficial keatiis, a comea defect, and then reduce dose by one level
or Sine or more loss in best corrected distance visual acuity
+ Grade 3: corneal ulcer or stromal opacity, or best corrected Grado 4
distance visual acuity <20/200 + Obtain ophthalmologic assessment
\ Grade 4 comeal perforation ) + Discontinue Dato-DXd
1. Hot RS et al. Conor rat Rew 2024125502720. PeerView

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73. Let’s Consider a Variation on Our Case: What If?

68-year-old man is newly diagnosed Let’s Discuss
with mNSCLC v What if the patient receives
+ NGS biomarker testing: no actionable treatment with Dato-DXd and
genomic alterations detected; PD-L1 develops stomatitis?
TPS 70%
Begins 1L carboplatin, pemetrexed, and
pembrolizumab with a partial response
> maintenance pemetrexed +
pembrolizumab
After 3 months, CT scans show
progressive disease in the liver

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74. Management of Oral Mucositis/Stomatitis’?

Step 1: Prophylaxis Step 2: Confirm

in Gp ami
a
eras
ss rare
cn
m
ee
EEE EEE oy
ten
man,
em

Step 3: Manage

‘Supportive Care ‘Optimize prophylactic and supportive medications for any oral
Increase te frequency of bland moutwashes to ‘mucesitisistomatitis event, regardless of grade

upto every hour, necessary

+ Provide pain management Dato-DXd dose recommendations.

As soon as oa pa infarnmation andlor « Grade 1: Maintain dose

Uiceraton develops, stongly consider using à: Grade 2: Consider a dase delay or rection Mf clinical indicated
fterod-conaning mouture ifnctakeady. + Grades

= Woropmytacticsupporive medications have nat yet been optimized, delay dose
+ Cryotherapy (ced chips or iced water eld in the neve has been resolv to rado =1 or baseline, optimize mecicaons,

mouth treughout the inuson) should be ‘pd ton manta dose

considered — propnylacicsupporiva mocieatons have already baen optimized, delay

+ Conse eral 0 dentist eal surgeon, ‘cose unl res to grade 1 or baseline, and then reduce dose by one evel
‘or cermatlogist for cover ce persisten events + Grade 4: Disconinue Dato Xd

1. Heist RS et al. Concer Treat Rev. 2024:125:102720. 2. Image courtesy of Messe L. Johnson, MD.

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75. Let’s Consider a Variation on Our Case: What If?

68-year-old man is newly diagnosed

with mNSCLC

+ NGS biomarker testing: EGFR exon 21 What treatment would you
L858R mutation recommend?

+ Receives 1L osimertinib followed by Y” What factors should we consider
platinum chemotherapy but develops in determining 2L therapy for a
further disease progression patient EGFR-mutated NSCLC

. . who has progressed on 1L

+ Repeat biomarker testing detects no osimertinib?

new targetable genomic alterations

Let's Discuss

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