Charting a New Path to Better Outcomes With TROP2-Targeting ADCs in Lung Cancer: Unveiling Potential, Shaping Tomorrow

Co-Chairs Prof. Nicolas Girard, MD, PhD, and Aaron Lisberg, MD, discuss NSCLC in this CME/MOC/NCPD/AAPA/IPCE activity titled “Charting a New Path to Better Outcomes With TROP2-Targeting ADCs in Lung Cancer: Unveiling Potential, Shaping Tomorrow.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at https://bit.ly/3RmX3dU. CME/MOC/NCPD/AAPA/IPCE credit will be available until April 24, 2025.

1. Charting a New Path to Better Outcomes

With TROP2-Targeting ADCs in Lung Cancer
Unveiling Potential, Shaping Tomorrow

Nicolas Girard, MD, PhD

Professor of Respiratory Medicine

Versailles Saint Quentin University =
Paris Saclay University

Chair, Department of Medical Oncology
Thoracic Oncologist
Institut Curie

Paris, France

Aaron Lisberg, MD
Assistant Professor of Medicine >
Department of Medicine, Hematology/Oncology

UCLA Medical Center à
Santa Monica, California dl

Go online to access full CME/MOC/NCPD/AAPA/IPCE information, including faculty disclosures.

2. Our Goals for Today

Augment your knowledge of the rationale for TROP2-targeting
therapy in lung cancer, characteristics of TROP2-targeting
ADCs, and the evidence supporting their use in lung cancer

Enhance your skills in identifying patients with lung cancer who
are most likely to benefit from novel TROP2-targeting ADCs

Equip you with skills for optimally using the TROP2-targeting
ADCs in the treatment of lung cancer, including managing AEs

Copyright © 2000-2024, PeerView

3. MODULE 1

Understanding

the Basics of TROP2 and
TROP2-Targeting ADCs

Copyright © 2000-2024, PeerView

4. TROP2 in NSCLC"

Adenocarcinoma
+ TROP2, a transmembrane glycoprotein, is highly ‘a
expressed in NSCLC and other solid tumors
+ High TROP2 expression is associated with a poor go
prognosis, making it a promising therapeutic target Bos
304
3
E gp |—Notow TROP expression 99)
À 02d Non TROP expression (12172)
topic Po 02
ooo wo 20 a0
Time, mo

+ There is no current testing recommendation for TROP2
+ Identified by IHC

to ea es

Mere
ha
TROP2 Intensity 0

NRG-1 is released

+
sw

TROPZ ntenany 2
PeerView.com

1.Lenart Seta. Cancers (Base). 2020:12:3328,

PeerView.com/JVH827 Copyright © 2000-2024, PeerView

5. Antibody-Drug Conjugates: The New Kids on the Block!

Important Prope!

s of the Antibody-Drug Conjugate (ADC) Components and Target Antigen

Antigen
= High homogeneous expression on tumor
+ Low or no expression on healthy tissues .
= High affinity and avidity for antibody recognition Linker
= Stable in circulation

Antibody + Efficient release of payload at target site
= High affinity and avidity for tumor antigen = Prevents premature release of payload
= Chimeric or humanized to decrease at nontarget tissue

immunogenicity

= Efficient linker technology (cleavable vs
o noncleavable)
Long half-life and high molecular weight nr

= DAR affects drug distribution and

Cytotoxic Payload
* Highly potent agents:
= Calicheamicin
= Maytansine derivative (DM or DM4)
= Auristatin (MMAE or MMAF)
= SN-38
= DXd topoisomerase | inhibitor
+ Optimal DAR (range: 2 to 8)

+ Cleavable Linkers: depend on physiological
conditions, including pH, proteolysis, or high
intracellular glutathione

+ Noncleavable Linkers: depend on lysosomal
degradation

1. Chau CH et al. Lancet 2019:304793-804. PeerView.com

PeerView.com/JVH827 Copyright © 2000-2024, PeerView

6. Selection of ADCs in Clinical Development for Lung Cancer!

Target
HERZ
HERS
TROP2
omer
ers
co
a
par
PvRLA

EGFR
ROR2

Napo

Drug

Trastuzumab-OM1
Trastuzumab.Dxd

Pattumab-DX4

Datopotamab-Dxd
‘Sacituzumab gowtecan

Telisotuzumab vedotin

Hnatamab-DXd (DS-7300)
MGCO18

Lorvotuzumab mertansine

Enapotamab vedotin
Mecbotamab vedotn

Cofetuzuma peidotin
Enfortumab vedotn
Tisotumab vedotn

MRGO03
Ozuramab vedotn

Upittamab risodotin
Lifastuzumab vedotin

Payload

DM
Deruxtecan

Deruxtecan

Deruxtecan
SN38

MMAE

Deruxtecan
DUBA

om
MMAE

Auistai-0101
MMAE
MMAE
MMAE
MMAE

AF-HPA
MMAE

Linker

Noncleavable (hioether)
CCleavable (tetrapeptide)

CCleavable (tetrapeptide)

CCleavable (tetrapeptide)
‘Cleavabe (carbonate)

CCleavable (vaine-citine)

Cleavable (tetrapeptide)
CCleavable (valine-ciruline)

CCleavable (disulfde)

Cleavable (protease)
CCleavable (valne-ciruline)

Cieavable (vaine-ctrutine)
Cieavable (vaine-citutine)
Cieavable (vaine-ctruiine)
Cieavable (valine-ctrutine)
Cieavable (vaine-tuiine)

Cleavabie (protease)
Cleavable (yaline-cituline)

RP2D and Schedule DAI
3.6 mg/Kg, once every 3 weeks 31

6.4 mg/kg. once every 3 weeks" 8

56 mgkg, once every 3 weeks 8

6.0 mgikg, once every 3 weeks 4

10 mk on day 1 and 8, once every 3weeks 7.8
2.7 mgikg, once every 3 weeks 31
180 4

TED 27

80 E

22 mghg. once every 3 weeks. E
Ted

180
180,
TED

2.0 mg/Kg, once every 3 weeks

80

180
TED

4
4
4
4
4

1245
34

2 The FDA-approved dose of T-OXG iss 54 mg/kg. once every 3 weeks for adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 mutations,

as detected by an FDA-approved test and who have received a rior systemic therapy.

1 Passar At al. J Cin Oncol 2023,1002300013

PeerView.com/JVH827

PeerView.com

Copyright © 2000-2024, PeerView

7. ADC Mechanism of Action!

‘Antibody engagement
to payload-independent antitumor activity
via several mechanisms:

1. Fe-mediated stimulation of immune cell

2. Disruption of receptor dimerization

+ = Femedated
stimulation
ol mmune

Most ADCs are internalized in tumor

The payload is released from endosom

and/or lysosomes, and takes its effect
on cells, leading to cell death

INININIT

gw! ta

Membrane-

neighboring cells, re

xpression and can also kil these cells
(bystander effect)

Fc region of the mAb component of ADCs can orc!

1. Drago JZ et al Nat Rev Cin Oncol. 2021:18:327-344

PeerView.com/JVH827

PeerView.com

Copyright © 2000-2024, PeerView

8. ADCs: Drug-to-Antibody Ratio!

Average number of payload 5 k Y pee 5
moieties attached to each Wye e Sse
monoclonal antibody (mAb) AIN » ¡UN LA 7) 4 $8.
Range from 2 to 8 Tom :
: 3 Cancer N
Crucial in determining ADC cell disruption
poteney and toxiciy #-
Higher drug-to-antibody ratio Growth

arrest cell

(DAR) may increase activity

death »
but also may broaden off- £
target effects Ÿ
: A GS a
Higher DARs might also
enhance drug clearance by T-DXd
the liver
damage
1. Betat WCLC 2022. Oral presentation PeerView.com

PeerView.com/JVH827 Copyright © 2000-2024, PeerView

9. Comparing ADCs Targeting TROP21

Sacituzumab Govitecan Datopotamab Deruxtecan

DARE BH
— rates
Pen y Soeur
+
sus payons / y f
Sins posi
Lo =
ete a ma me
Eee
pei
pen
A nin am reer PeerView.com

PeerView.com/JVH827 Copyright © 2000-2024, Peerview

10. MODULE 2

The Evolving Evidence Supporting

the Use of TROP2-Targeting
ADCs in NSCLC

Copyright © 2000-2024, PeerView

11. Second-Line Data

and Beyond

12. TROPION-PanTumor01: Study Design!

Dose Escalation

Relapsed/refractory
advanced/metastatic NSCLC

Unselected for TROP2 NSCLC Conort

expression® ans A Primary endpoints
. e 218 (US) or 220 (Japan) to 10 mg/kg Q3We | sala Wave aged
es MTD established — A ob lective
El Me nenes per 8 mg/kg aaw 80 patients at 8 mg/kg Efficacy,¢ PK

» Stable, treated brain
metastases allowed

NSCLC
Cohort
tumor types
+ NSCLC enrollment completed
+ TNBC cohort 6 mg/kg Q3W is enrolling; cohorts in other tumor types may be added
+ Here we report updated results for the NSCLC dose expansion cohort (175 patients treated at 4, 6, or 8 mg/kg of Dato-DXd)
* Pretreatment tumor tissue was required for ettospectveanayis of TROP? expresion.” The 4 6- and E-mghg dose eves ae being further evaluated for satty and eticacy
“Incas paient teated in e dose sscaaton and dose espansion porte, Anal exploratory endpats include analyses bomakerssesocied wt respon,

© Response assessments ae based on RECIST v1. N
1.Garon EB etal WCLC 2021. Abstract MADS.02 PeerView.com

PeerView.com/JVH827 Copyright © 2000-2024, Peerview

13. TROPION-PanTumor01: Antitumor Activity
of Dato-DXd in the NSCLC Cohort!

Best Overall Response (BICR) Best Change in Sum of Diameters (BICR)

so
Dato-DXd Dose ie
Patients" Ed
amoo smono mora :-
(n=50) (=) — (n=80) à
‘ORR? n (%) 229 1428) 190%) À
or o o 10 8
PR 20) um we ¿o
$0, 0%) 2560 2000) 42463 0
Non-CRIPD, n (%) 10 24) 2@) ae
PO, n (%) 74 1020) 8(10) Change in Sum of Diameters of Target Lesion (BICR) Over Time
NE, m (%) Sao 5) sm) m w im m
NE 105 94 2 E 2
M DOR BER Sh ee: ene GG) ene E E E
+ Antitumor activity was observed at 4, 6-, and 8-mg/kg doses En 2 2
of Dato-Dxd [e * 2
+ Most responses were durable over time, including HE = 2
‘a median DOR of 10.5 mo in the 6-mg/kg cohort 2° 024 mau 824 6eme

IR and CRUPR include one response in the 8 mg/kg cohort that's pending confirmation. —
1. Garon EB et a, WCLC 2021. Abstract MADS.02, PeerView.com

PeerView.com/JVH827 Copyright © 2000-2024, Peerview

14. TROPION-PanTumor01 (AGAs Subset): Antitumor Activity!

Best Overall Response (BICR) Best Change in SOD (BICR) and Tumor Genotype?

Patenst Date DK
ORR, n (%) 12 (35)
ch 5
PR 12 (35)
SD, n (%) 14 (41)
Non-CR/PD, n (%) 26)
PD, n (%) 2(6)
NE, n (%) 4(12)

DOR, median (95% Cl), mo 9.5 (3.3-NE)

Clinical activity was observed
in EGFR (ex19del, L858R), AE
including after osimertinib and mee EE
across other AGAs 1

“Includes response-evaluabe patients who had 21 post-baseline or discontinued treatment.» Four patients were not included in the waterfall pot two who did not havea target lesion per ICR.
and two who dd nt have on-tudy treatment images, “Patent NE. “Patents with unconfirmed PR. sag
Garon ES etal ESMO 2021. Abstract LEAAG, PeerView.com

PeerView.com/JVH827 Copyright © 2000-2024, PeerView

15. TROPION-PanTumor01: Safety!

Overall Sa Stanimary TEAES in 215% of Patients?

Patients, (%) Nausea

TEAE 80 (100)
Grade 23 40 (52) Fatigue
Drug-related TEAE 78 (98) semé
Grade 23 28 05) Decreased appetite
Serious TEAE 2448) 40,80) Constipation
Grade 23 HUE EST SI saisies reaction
Dose adjustments Anemia
TEAES associated with discontinuation sus 70 1089 Ory eve
TEAES associated with dose interupton 4@) 15(0) 2606) | Mucosalintammascn
TEAES associated with dose reduction 1@) 500 2% Rash
ILD adjudicated as drug related» 500 3@ 140 ‘Cough
Grade <2 4@ 20 70 Diarmea
Grade u 1D 1@ 16 Dyapnen
Grades o o 30)
+ Overall, manageable safety profile and no new safety signals observed Patients, %

+ Some AEs (eg, GI toxicity, anemia) may be reversible; clinical course of AEs will be further analyzed
+ Cases LD agi a doa re compras ve patents ihe 4m otr on grade 1. ee ga 2, negado 2). ve patents in ne mo
Si gra a gado ad 1 ia Umag cor we ase ve pra Zone rate 3. Dr Date 9. OL pts (MO OL 6
SO 128 © mona 80) Osa cat apa. 2021 .
Tan EB etal WLC 2021 Abus MALA 62 PeerView.com

PeerView.com/JVH827 Copyright © 2000-2024, PeerView

16. TROPION-Lung01: Study Design!

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

+ NSCLC (stage IIIB, IIIC, or IV)

+ ECOG PSO0or1

+ No prior docetaxel

Without AGA*

+ 1-2 prior lines, including platinum chemo and anti-PD-(L)1

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-(L)1

Stratification

+ Histology (squamous vs NSQ) zT

Docetaxel

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)

+ Dual primary endpoints: PFS (BICR) and OS
+ Secondary endpoints: ORR (BICR), DOR (BICR), safety
2 Patents wth KRAS mutations inthe absence of known actonable genomic alterations are eigle: must meet rio therapy requirements for patents

thout actonabie genomic ateratons N
Tana meta ESMO 2029, Abstract LBAY2 PeerView.com

PeerView.com/JVH827 Copyright © 2000-2024, Peerview

17. TROPION-Lung01: PFS (ITT)!

Dato-Dxd Docetaxel
Median PFS, mo (95% Cl" 44 (42-58) 37/2942)
100 HR (95% CI) 0.75 (0.62-0.91)
P 004
so Prespecified boundary (2-sided) 008
CORR, % (95% CIP 26.4 (215-318) 12303171)
æ 60 DOR, mo (95% Cl) 7166-109) 5.6 (5.4-8.1)
2 408
y
ra
@ 4
Dato-Dxd
2
o
o 2 4 6 y 10 12 14 16 18
Time Since Randomization, mo
No. at Risk
Dato-Dxd 299 216 156 96 74 46 24 10 2 o
Docetaxel 305 186 120 8 “2 19 4 7 o o

Median PF fou tne was 109 mo (05% Cl, 98125) and 9.5 mo (35% Cl, 82:19) fr Dat-DXA and dois, respecte
*Iniaes our GR ad 75 PR ar Dale OXE and 29 Ps or cetro ñ
1. An Metal, ESMO 2023, Abstract LBA12. PeerView.com

PeerView.com/JVH827 Copyright © 2000-2024, Peerview

18. TROPION-Lung01: PFS by Histology’

No, at Rsk
eos 29
Docta 232

m
136

NSQ
With and Without AGA
DaoDKS Docena
FE mo ERO) 566470 376047
HR SX C0 083,051.078)
ORR m2 128

‘BOR. mo. 77

4 6 8 © u
Time Since Randomization, mo

ur u 41 20 7
o © 2 ww 4

‘Squamous
With and Without AGA

= Dix Docta
Mm PFS, mo SRG) 2801040 2045)
a Rasch 120004202
ORR % 92 127
OR mo se a1

2 4 6 E à % 1
Time Since Randomization, mo

1. Ann Metal, ESMO 2023, Abstract LBA12.

PeerView.com/JVH827

PeerView.com

Copyright © 2000-2024, PeerView

19. TROPION-Lung01: Interim OS (ITT)!

100 Dato-DXd Docetaxel
Pr Median, mo* (95% Cl) 124(108-148) 1198-125)
HR (95% CI) 0.90 (0.72-1.13)

So
o
© 4
Dato-Dxd
20 Information fraction
at interim analysis
(events/total events
o required): 74%
OO
Time Since Randomization, mo
No, at Risk
DatoOxd 289 278 243 201 16 121 85 56 33 14 6 1
Docetaxel 305 278 239 193 156 115 76 42 2% 13 4 4

NSQ HR (95% Cl) = 0.77 (0.59-1.01); Squamous HR (95% Cl) = 1.32 (0.87-2.00)

Trial is continuing to final OS analysis

*Megian OS folow-up was 11.8 mo (95% Cl, 113-127) and 1.7 mo (95% Cl 109-1219) for Dato-DXS and docetaxel respectively. en
1.Ahn Metal, ESMO 2029. Abstract LBATZ PeerView.com

PeerView.com/JVH827

Copyright © 2000-2024, PeerView

20. TROPION-Lung01: Overall Safety Summary’

Docetaxel
297) (n=290)

TRAES, n (%) ES

+ Median treatment durations for
Dato-DXd and docetaxel were

Aloe Zaren AAN) 4.2 and 2.8 mo, respectively
Grade 23 73 (25) 120(41)

A E a + Fewer grade 23 TRAEs were
Associated with dose reduction 58 (20) 85 (29) obearved with Dato-ÓXd
Associated with dose delay 49 (17) 31 (11) compared with docetaxel
Associated with discontinuation 23 (8) 34 (12)

+ Fewer TRAEs leading to dose
Associated with death? 3(1) 2(1) reductions or discontinuations
- were seen with Dato-DXd
Serious TRAEs 30 (10) 36 (12) compared with docetaxel
Grade 23 25 (8) 33 (11)
‘Investigator assessed. Dato0DXG; to cases o ILO/pneuments and one case of sepsis: docetaxel: one case of ILD/pneumenits and one case o sep shock
e ma ARA PeerViewcom

PeerView.com/JVH827 Copyright © 2000-2024, Peerview

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

‘System Organ

Preferred Term, n (

+ Stomatitis and nausea were the
Blood and lymphatic system
Anemia 4315) most frequent TRAEs seen with

Neutropenia® 12(4) 2(1) 76 (26) 68 (23) Dato-DXd and were
Gastrointestinal predominantly grade 1 or 2

Stomatitis 140 (47) 196) 45 (16) 3(1)

Nausea 100 (34) 70) 48 (17) 3(1)

Vomiting 38 (13) 3(1) 22 (8) 10.3) i ic i i
ia = i a = Hematologic toxicities, including

Dares E 46) neutropenia and febrile
General neutropenia,° were more
Asthenia 55 (19) 8(3) 55 (19) 5(2) common with docetaxel
Fatigue 34(11) 2(1) 40 (14) 6(2)
Metabolism and nutrition

Decreased appetite 68 (23) 1003) 45 (16) 1(0.3)
Skin and subcutaneous No new safety signals were

Alopecia 95 (32) o 101 (35) 103% observed with Dato-DXd
Rash 36 (12) 0 18 (6) o
Pruritus 30 (10) o 124) o

{This category includes th preferred terms "neutropenia" and "heurophl count deteased Includes an event nearecy reported as grade 3

7% vs 0.3% or docetaxel and Dato-DXa, respectively 7
1.Ahn M et al ESMO 2029. Abstract LBATZ PeerView.com

PeerView.com/JVH827 Copyright © 2000-2024, PeerView

22. TROPION-Lung01: AEs of Special Interest!

AESI

Stomatitis/oral mucositis, n (%)*

All grades 160 (54) 59 (20)
Grade 23 19 (6) 4m)
Ocular events, n (%)°

All grades 57 (19) 27 (9)
Grade 23 5 (2)° 0(0)
Adjudicated drug-related ILD, n (%)*

All grades 25(8) 12(4)
Grades 23 10(3) 4(1)
Grade 5 7(2) 1(0.3)

Stomatitis/oral mucositis associated with Dato-DXd
resulted in a low rate of discontinuation (0.7%)

Dry eye was the most common ocular event with
Dato-DXd (6.1%, primarily grade <2), followed by
increased lacrimation (5.4%)

Seven adjudicated drug-related grade 5 ILD events

- Primary cause of death in 4 out of 7 patients
was attributed to disease progression by
investigator

- NSQ: 4 out of 232 patients (1.7%)
and squamous: 3 of 65 patients (4.6%)°

IRRs were observed in 8% of patients in each arm,
all were grade <2 with the exception of one grade 3
event with Dato-DXd

Events included te selected PTE oral mucosiiistomaüts, oropharyngeal pain, mout ulceration, odynophagi, dysphagia, ra pain, goes, pharmgeal inflammation, aphthous wer, and oral
mucosa erosion ° Ocular events included selected PTs rom the comeal disorder SMO and selected relevant PTs kam the eye daorder SOC. Included four cases of heratis and one case of
erative Keats. LD includes events that were adjudicated as LD and related o se of Dato-OXG or docetaxel (ncudes cases of potential LDipneumonits based on MedORA v26 0 fer the
‘arrow ILD SMO, selected terms fom the bread ILD SMO, and PTS of respiratory Tale and acute respiratory ale) Among treated patients, histology information

per the case report form.
{abn Met a, ESMO 2023, Abstract LBA12,

PeerView.com/JVH827

PeerView.com

Copyright © 2000-2024, PeerView

23. Conclusions

+ Dato-DXd is the first ADC to demonstrate a statistically significant improvement in PFS over docetaxel in patients with
previously treated, locally advanced or metastatic NSCLC

+ PFS benefit was primarily driven by patients with non-squamous histology

+ Fewer grade 23 TRAEs and no new safety signals were observed with Dato-DXd

+ Grade 23 ILD was seen, highlighting the need for careful monitoring and adherence to ILD management guidelines
+ The interim OS findings favor Dato-DXd, and the trial is continuing to final analysis

ws

Dato-DXd is a potential new meaningful therapy for patients with previously treated non-squamous NSCLC

Based on the Results From the TROPION-Lung01 Trial

February 19, 2024: BLA accepted by FDA in US for Dato-DXd for treatment of adult patients with
locally advanced or metastatic NSCLC who have received prior systemic therapy

March 4, 2024: EMA has validated an application in EU for Dato-DX for treatment of adult patients
with locally advanced or metastatic NSCLC who require systemic therapy following prior treatment

PeerView.com

PeerView.com/JVH827 Copyright © 2000-2024, PeerView

24. Updated Data From ELCC 2024: Focus on Nonsquamous
(NSQ) Histology in TROPION-Lung01 Trial!

TROPION-LUNGO1 STUDY DESIGN: randomized, phase 3, open-label, global study (NCT04656652)

= Pr
(Key eligibility criteria Dato-DXd
A EE ER
+ ECOG PS 041 he .
wenn =
eee rep
rest eee pene arte ee ual rian oe
RE Es
+ Positive for EGFR, ALK, NTRK, BRAF, ROS1, MET exon 14 skipping, and/or RET Secondary endpoints
+ 1-2 lines prior approved targeted therapies plus platinum-based CT and <1 anti— + ORR by BICR*
ees rn
‘Stratification Safety.
+ Histology.? actionable genomic alteration, anti-PD-(L)1 mAb included in most recent prior therapy, geography*
PE ve na or
SE
Sr 2e m
Discontinued from study treatment 184 (79) 206 (93) ‚dian Study Duration
ne | Medan sue u
AE 3314) 35(16) E E
Progressive disease 131 (57) 138 (62)
Clinical progression 76) 7
‘Withdrawal/physician decision 6(3) 19(8)

* Patients with KRAS mutations inthe absence of known actionable genomic alterations are eligible: must meet prior therapy requirements fr patents without
‘actonable genomic alleratons, "Squamous vs NSQ. «Presence vs absence. * Unted Siaes/JapanvWestem Europe vs rest of he word. * Evaluated per RECIST 1.1
"BFS and OS by histology were prespeciñed subgroup analyses. ? Safety analyses by histology and were posthoc, "CRF-derved. Patent wth CRF derived NSQ

istoogy in the

1. Girard Net PeerView.com

PeerView.com/JVH827 Copyright © 2000-2024, Peerview

25. Updated Data From ELCC 2024: Focus on NSQ Histology
in TROPION-Lung01 Trial!

Tumor Response by BICR—NSQ Population
Dato-DXd (n = 234) Docetaxel (n = 234)

ORR,*n (%) 73 (31) 30 (13)
(95% Cl) (25.0-38.0) (9.0-18.0)
BOR, n (%)

CR 4(2) 0

PR 69 (30) 30 (13)

sD 113 (48) 110 (47)

Non-CR/non-PD 2(1) 3(1)

PD 31 (13) 53 (23)

NE 15 (6) 38 (16)
DOR,” median (95% Cl), mo 7.7 (6.6-11.1) 5.6 (5.46.0)
DCR*e n (%) 188 (80) 143 (61)
(95% Cl) (75.0-85.0) (55.0-67.0)

Patents wth CRF-derved NSQ histology inthe N analysis set.
*Tuo-sided Cis are based on Ihe Ciopper-Pearson exact binomial method, > Based on the Kaplan-Meier method; 2-sided Cis are computing the Brockmeyer-Crowiey

method. “CR + PR + SD [nonCRinon-PO) fiéw.
{Girard Net a ELCC 2024, Poster PeerView.com

PeerView.com/JVH827 Copyright © 2000-2024, PeerView

26. Updated Data From ELCC 2024: Focus on NSQ Histology
in TROPION-Lung01 Trial!

PFS by BICR—NSQ Population

Dato-DXd Docetaxel
. Median (95% Cl), mos» 55(4369) 36(2942)
HR (95% Cl) 0.63 (0.51-0.79)
æ 60
g
& 40
20
Docetaxel
ot
0 2 4 8 0 2 4 6 18
Time Since Randomization, mo
No, at Risk
Dato-DXd 234 181 135 86 67 41 20 7 1 0
Docetaxel 24 136 91 50 32 14 10 4 0 0

Patents with CRF-derived NS histology inthe ul analysis set

Median PFS folow-up (estimated by inverse Kaplan Meer) was 10.9 (95% Cl, 98-12.4) and 96 (95% Cl, 85-125) months for patients treated wth Dato-DX and
docetarel respectively.” Based on Kaplan-Meier method, 2-sided CIS are computed using the Brookmeyer-Crowley method.

Y Girard N et at ELCO 2024, Poster.

PeerView.com

PeerView.com/JVH827 Copyright © 2000-2024, PeerView

27. Updated Data From ELCC 2024: Focus on NSQ Histology

in TROPION-Lung01 Trial!

PFS by BICR in Key Subgroups—NSQ Population

Hazard
Ratio
0.56
on

087
0.59

0.66
061
0.44
061

0.67
0.57

0.59
0.64

071
0.35

Eventsin
Dato-DXd Docetaxel
Age at <65 891126 95129 res
randomization, y 265 7008 751105 ee
on Male 98134 1141150 —
Female 61100 56/84 ——
White 69196 60/90 —
aes Asian 5592 66/96 eo
Black En] 313
Other 2836 36/39
Former/current 12777 — 1371184 ren
Seeking sus Never 3257 32148 me
Brain metastases with 2843 27141
at baseline Without 131191 143/193 es
Actionable genomic ‘Absent 134/186 135/184 ——
alterations Present 2548 3550 e—
5 os 10
Hazard Ratio

* Patients with CRF-derved NSQ histology in the ful analysis set.
4. Girard Net a. ELEC 2024, Poster.

PeerView.com/JVH827

15

20

25 30

PeerView.com

Copyright © 2000-2024, PeerView

28. Updated Data From ELCC 2024: Focus on NSQ Histology
in TROPION-Lung01 Trial!

OS (Interim) —NSQ Population*>

Dat
Median (95% Cl), mo 13.4 (12.1-16.4) 114 (10:
HR (95% Ci) 0.79 (0.60-1.02)

æ 60
Go
© 40
en Lys Dato-DXd
Docetaxel
0 2 4 6 8 0 12 14 6 18 2 22
Nick RK Time Since Randomization, mo

Dato-DXd 234 220 20 18 7 © 2 6 30 11 5 0
Docetaxel 234 206 186 10 120 89 58 35 2 8 2 0

Patients with CRF-derved NSG histology inthe ul analysis set
* Median OS folow-up (estimate by inverse Kaplan-Meier) was 124 (95% Cl, 11-313.) and 123 (85% Cl. 112-129) months for patients with NSO histology treated

with Dalo-OX and docetaxel. respectively. * Based on the Kaplan-Meier method; 2-sded Cis ae computed using the Brookmeye-Crowey method a

Y Girard et al ELCO 2026. Poser PeerView.com

PeerView.com/JVH827 Copyright © 2000-2024, Peerview

29. Updated Data From ELCC 2024: Focus on NSQ Histology
in TROPION-Lung01 Trial!

Safety Summary—NSQ Population

Treatment duration

‘Median (range), mo 49 28
03 mo,n (%) TG 125067)
23036 mo, n(%) so) 0)
3610.59 mo, (%) sa) 26(12)
290512 mo, n(%) am 16
212 mo, n (%) 210) ENT

TRAES, n (%)

Any grade 205 (88) 195,68)
Grade 23 5122) a)
Associated with dose reduction 49(21) 86(0)
‘Associated with dose delay 30) 24(11)
‘Associated with discontinuation 20 2712)
‘Associated with death 160 20)
Serious TRAES 196) 25(10
Grade 23 sm) 7300)

Patients with CRF-derived NSQ histology in the safety analysis
set. AEs were considered related to treatment by the investigator.

TRAES Occurring in 210%—NSQ Population

Blood and lymphatic system
‘Anemia 37 (18) 104) 4621) 8(4)
Neutropenia 94) 1) 56 (25) 49 (22)
Gastrointestinal
‘Stomatitis 114 (49) 16(7) 35 (16) am
Nausea 83 (36) sa 45 (20) 3
Vomiting 28 (12) 26) 21 (10) 10)
Diarrhea 24 (10) 1) 45 (20) 3
Constipation 23(10) o 26 (12) o
General
‘Asthenia 45(19) 710) 42119) sa
Fatigue a) o 30 (14) 4
Malaise 146) 11) 22 (10) 24)
Edema peripheral 4 (<1) o 26.12) 10

Metabolism and nutrition
Decreased appetite 5423) 161) 34 (15) 10

‘Skin and subcutaneous
‘Alopecia 83 (36) o 82 (7) 10
Bash 2702 o 14 6 2

+ Stomatitis, nausea, and alopecia were the most frequent TRAES seen with Dato-DXd
+ Hematologic toxicities, including neutropenia and anemia, were more common with docetaxel; no
febrile neutropenia was seen with Dato-DXA (docetaxel, 7%)

Patents with CRF-derved histology in the safety analysis set AEs were considere related 1 treatment by the investigator.
* includes the prefered terms (PTS), "neutropenia" and “neurophi count decreased” Feb neutropenia occurred in 15 (7%) patents treated wih docetaxel;

0 cases were observed in patents treated with Dato-OXd,
1. Girard Net a ELCC 2024, Poster.

PeerView.com/JVH827

PeerView.com

Copyright © 2000-2024, PeerView

30. Updated Data From ELCC 2024: Focus on NSQ Histology
in TROPION-Lung01 Trial!

Adverse Events of Special Interest (AESI)—NSQ Population

232) Docetaxel (n

AESI,n (%) Dato-DXd (
Stomatitis/oral mucositis*

All grades 131 (67) 49 (22)

Grade 23 16(7) 40)
‘Ocular events?

Al grades 46 (20) 25 (11)

Grade 23 5(2) o
Adjudicated drug-related ILD=

All grades? 19@) 76)

5) 40)

Grade 23
Grade 5 40) 14
‘Stomatitis/oral mucositis events with Dato-DXd were predominantly grade 1 (28%) or 2 (22%) and associated with a low rate of discontinuation

(0.9%)
Lacrimation increased was the most common ocular event seen with Dato-DXd (7.8%), followed by dry eye (6.5%); all cases were grade <2
Four adjudicated drug-related grade 5 ILD events (1.7%) were seen; primary cause of death in two of four patients was attributed to disease

progression by investigator
IRRs were observed in 7.8% and 8.6% of patients treated Dato-DXd and docetaxel, respectively; no grade 23 events in either arm were reported

Patents with CRF-derived NSO histology in he safety analysis set

* Events included in he selected PTs oral mucosits/stomatiis, oropharyngeal pain, mouth ulceration, odynophagia, dysphagia, oral pain, goss, pharyngeal

intammaton, aphinous ulcer and oral mucosa erosion > Ocular event included PTs from the comeal disorder SMO and selected relevant PTS from the eye disorder

SOC. “ILD includes events that were audeated as ILD and relate to use of Dato-DX or docetaxel (ncludes cases of potent ILD/pneumonits based on MedDRA

1260 forthe nartow ILO SMO, selected terms rom the broad ILO SMO, and PTs of respiratory alure and acute respiratory ale). One adsitonl patient inthe

‘Dato-DX¢ arm had grade 2 aducicated dug-eate LD (pneumonitis), but this event was na an AE i he cinical database as determined bythe investigator. —
PeerView.com

4. Girard Net al ELEC 2024, Poster.

PeerView.com/JVH827 Copyright © 2000-2024, PeerView

31. TROPION-Lung05: Initial Results’?

Se, WV RSELE Efficacy Summary
5 |: France conti name tasten EGFR.
El ice ven eros 3
3|.® m
Eooapsasıı Response Teen
3 1 line of targeted therapy i per BICR Patients
À |: Paz open men commen ne ®
a metastatic setting =
ape deat progresse aru roy ES
AS
neto EM GED (0722
Safety Summary =
TEAES Occuringin 215% ofPatienis Ÿ 2 es 7 2 7
Er FE Be un uen am
23 ocr
z mu aer 5738)
2 Some à
3: wen m SD (SN
{Change From Baseline in Sum of Diameters of Target Lesions ue, 54 se 43
Pate Win Contimes CAR cemmeguon Za cy CORRE

‘+ BOR: In the overall population (n = 137), four patients
(@%) 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

STITT ITT eee eT throne peevouny beaded vith Caine

2 The primary completion date wil occur when al patients have had either a minimum of 9 months of follow-up after the sar of study treatment

or have discontinued tom the st 2
Par Ar etal ESMO 2029. Akne 13410. PeerView.com

PeerView.com/JVH827 Copyright © 2000-2024, PeerView

32. IMMU-132-01: Study Design and Population’?

IMMU-132-01 (NCT01631552) is a single-arm, open-label, multicenter phase 1/2 dose-escalation
and cohort-expansion study of sacituzumab govitecan in non-TROP2-selected patients with advanced
epithelial cancers who received 21 prior systemic treatments, including NSCLC and SCLC

Sacituzumab gi
Relapsed/refractory advanced/metastatic Di and
NSCLC

Unselected for TROP2 expression*
Age 218 years

ECOG PS 0 ort

Sacituzumab govitecan 10 mg/kg I\

Dose expansion D1 and D8 of 21 le

Measurable disease per RECIST v1.1
Progression after >1 line of therapy for
stage IV disease

TNC, mUC, HR+ mBC,

‘SCLC, CRC, esophageal carcinoma,
‘endometrial, pancreatic ductal adenocarcinoma,
si points ‘RPC, EOC, gastric adenocarcinoma,
imary endpoint GBM, SCCHN, hepatocellular,

+ Confirmed objective response,” safety, PK cervical, clear cell RCC

* Availabe archival tumor specimens were evaluated retrospectively for TROP2 expression by IHC.
* Assessed every 8 weeks unt disease progression by each insttuto’s radiology group o a local contacted radiology service per RECIST v1.1 o
1-Heist RS eta J Cin Oncol, 2017.35 2700-2707. 2 Bardia À et al Ann Oncol 2021:32746-756, PeerView.com

PeerView.com/JVH827 Copyright © 2000-2024, Peerview