Decoding Biomarker Testing and Targeted Therapy in NSCLC: The Complete Guide for 2024

Decoding Biomarker Testing and

Targeted Therapy in NSCLC
The Complete Guide for 2024

Stephen V. Liu, MD Benjamin Levy, MD

Associate Professor of Medicine Associate Professor, Johns Hopkins School of Medicine
Director, Thoracic Oncology Clinical Director, Johns Hopkins Sidney Kimmel Cancer Center
Head, Developmental Therapeutics (SKC) at Sibley Memorial Hospital

Lombardi Comprehensive Cancer Center Medical Director, Thoracic Oncology Program, SKCC at Sibley
Georgetown University Washington, District of Columbia

Washington, District of Columbia

Jessica J. Lin, MD Prof. Solange Peters, MD, PhD
Attending Physician Chair and Professor, Medical Oncology
Massachusetts General Hospital Cancer Center Full Professor

Associate Professor of Medicine University Hospital of Lausanne
Harvard Medical School Lausanne, Switzerland

Boston, Massachusetts FAN

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

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Our Goals for Today

Augment your knowledge of the expanding spectrum of genomic alterations
and targeted therapies in NSCLC

Equip you with essential skills to conduct biomarker testing and integrate

targeted therapies into treatment plans for patients with NSCLC.

Enhance your strategies for multidisciplinary and patient-centered care to
improve outcomes in NSCLC

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LUNGevity as Our Partner: Access Survivorship and
Support Services for Your Patients and Their Care Partners

For Patients &
Caregivers

JA LUNGEVITY
0000

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Modern Practice Principles in NSCLC, Part 1

How to Optimize Biomarker Testing
and Interpretation of Results

NSCLC and Genomic Alterations

Lung Cancer! Genomic Alterations in NSCLC?

FPR o FOFRO

mas em

scLc aeons
15% ERBEEMERZampitenten 07%

NSCLC 85%
Adenocarcinoma
Squamous cel carcinoma
Large cet carcinoma
over
om SK AUPACT rn tan Fontan Frente 4 + 522)

1. tps Mw lungevi orforpatents-caregiversung-cancer-10ypesot-ung-cancer. 2 Skoubd Fetal. Nat Rev Cancer 2019;19:495-509 PeerView.com

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Actionable Targets Guide Decisions’

IMMUNOTARGET: IO in Driver+ NSCLC

Driver | | RR | PFs
Total - 19% 28
KRAS 271 26% 32
EGFR 125 12% 21

BRAF 43 24% 34

MET 36 16% 34
HER2 29 7% 25
ALK 23 0 25
RET 16 6% 24

ROS1 7 17% -

1. Mazieres Jet al. Ann Oncol. 2019,30:1321-1328. PeerView.com

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FDA-Approved Therapies and Their Targets in NSCLC’

Geneltarget FDA-Approved Drug Geneltarget FDA-Approved Drug

EGFR exon 19
deletion or exon 21
L858R

EGFR exon 20
insertion

ALK fusion

ROS1 fusion

Repotrectinib

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Erlotinib
Afatinib
Gefitinib

Osimertinib
Dacomi
Erlotinib + ramucirumab

Amivantamab
Amivantamab + carboplatin + pemetrexed

Crizotinib
Ceritinib
Alectinib

Brigatinib
Loriatinib

Crizotinib
Entrectinib

ib

NTRK1/2/3 fusions

RET fusion

KRAS G12C

BRAF V600E

MET ex14 skipping

ERBB2 (HER2)

Larotrectinib
Entrectinib

Pralsetinib
Selpercatinib

Sotorasib
Adagrasib

Dabrafenib + trametinib
Encorafenib + binimetinib

Capmatinib
Tepotinib

Trastuzumab deruxtecan

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Proper Biomarker Testing Matters:
Single Gene vs Multiplex/NGS"2

Guidelines (NCCN) recommend broad molecular profiling (NGS panels)

Immunohistochemistry (IHC) Next-generation sequencing (NGS) panel
Fluorescence and chromogenic + Small panel (<50 genes)
in situ hybridization (FISH/CISH) * Large panel (>50 genes)
Microsatellite instability (MSI) RNA sequencing (RNASeq)

+ Targeted RNASeq
Polymerase chain reaction (PCR) . Full

Whole-exome sequencing (WES)

Whole-genome sequencing (WGS)
1. Malone ER tal, Genome Med 2020:128. 2. Peters S.ELCC 202.

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Genomic assays
Tumor mutational burden (TMB)

Liquid biopsies

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Proper Biomarker Testing Matters: DNA vs RNA

False Negatives With DNA-Based NGS: RNA-Based Approaches May Overcome Limitations*

Large introns

Repetitive introns

N

Low tumor sample

|

Complex genomic events

1.Davies KO, Alsne DL. Cin Cancer Res. 2019:254586-4588,

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—

(Excessive sequencing)

—,

(Cannot align reads)

—

(Below assay sensitivity)

—,—

(Cannot capture)

v RNA

v RNA

~RNA

Y RNA

(it highly expressed)

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Proper Biomarker Testing Matters: Tissue vs Liquid Biopsy

Liquid Biopsy in Advanced NSCLC (2021 IASLC Consensus)!

os RER aaa ry

Sequential ‘Complementary Plasma First
(when tissue fails) (initiate tissue and liquid) (when biopsy not possible, delayed) ones

1. Rolfo Cet al. J Thorac Oncol. 2021:16:1647-1662. PeerView.com

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ESMO Recommendations on the Use of Liquid Biopsy’

NSCLC

+ ctDNA genotyping is recommended in treatment-naive cancer patients and resistance upon
prior TKIs. In treatment-naive NSCLC, ctDNA can be considered complementary or
alternative to tissue NGS for biomarker evaluation

+ ctDNA assays are especially recommended when a significant delay is expected in
obtaining tumor tissue for genotyping, when invasive procedures may be risky or
contraindicated, or bone is the only site that could be biopsied

+ Caution should be kept as ctDNA assays will miss histological trans-differentiation

+ ctDNA testing may not have adequate sensitivity to detect MET true high copy number gain
as resistance mechanism to osimertinib or lorlatinib

+ Amplification and fusion detection is suboptimal with ctDNA assays, and should be repeated
in tissue where possible

1. Pascual J etal. Ann Oncol 2022:33:780-768, PeerView.com

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Proper Biomarker Testing at Diagnosis
and Prior to Initiation of Therapy Is Essential

+ Biomarker testing prior to therapy is needed to optimize care
+ Provides insight into biology
+» Allows for prognostic information
+ Guides initial therapy
— Proper selection of targeted therapy
— Proper deselection of immunotherapy

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Sequence of Therapy Matters!

Retrospective Analysis of Patients With EGFRmut Interstitial Lung Disease (ILD)
NSCLC Who Received Immunotherapy and TKI" in the TATTON Trial?
@ © @ patients received immunotherapy first E IL
+ 15% experienced severe irAE
+ If TKI given within 3 months of immunotherapy, Osimertinib 2.9% (35/1207:
risk = 24% monotherapy grade 3/4: 14; grade 5: 4)
+ Among 6 patients developed severe irAE:
4 cases of grade 3 pneumonitis, 1 grade 3 colitis,
1 grade 4 hepatitis Durvalumab 2.0% (23/1149;
monotherapy grade 3/4: 6; grade 5: 1)
...
Patients received TKI before
Enmuno therapy, Osimertinib 38% (13/34;
+ Risk of experiencing severe irAE: 0% + durvalumab grade 3/4: 5; grade 5: 0)
1. Schoenfeld AJ et. Ann Oncol 2019:30:830-244. 2. Ahn MJ et al, ELCC 2016. Abstract 1360. PeerView.com

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LUNGevity Biomarker Testing Initiatives
to Drive Optimal Care in NSCLC

Understanding Your Cancer Con Lead to Better Treatment Options

Increasing Access to
Biomarker-Driven Treatment
for Lung Cancer in Alabama

UNGevity is deeply engaged in and leading discussions
ithin the patient advocacy community regarding best
sin biomarker testing patient education. We aim
to ensure that any content created, including language
with the consensus of the broader
patient advocacy community on what is best for patients.
- Nikki Martin
Sr. Director of Precision Medicine

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MYLUNG Pragmatic Study (2020-2022):
Gaps in Biomarker Testing in NSCLC13

bility of Biomarker Testing Results Before 1L Treatment Reasons Biomarker Testing Results Were Not Available Prior to Treatment

Early
18-11A)

nced Cohort
82)

ALKiest 0" 385 (770) Number of patents wh did not rece any = =
ge on Diomarker testing resus poro Westnet
Clinical deterioration, n (%)°4 551) 10 (10.6)
EOFR test (4) mos
Baies to teat ordering (és aaa) 24255)
bata NSPE EE) 'Sample/issue retrieval! - 6 (25.0)
MET test, n (%)* 328 (71.1) Patientiprovider attitudes and perceptions! 28 (66.7) 13 (54.2)
NR 000 253,649) Patentproner notecge about
es 209) 3025)
PD-L1 test, n (1%) 388 (84.2)
Payor overage, rancia bares! 120 203)
RET MAN OP. 305 (08-2) Other barriers’ 9 (21.4) 3(125)
ROS1 test, n (%)" 344 (746) Other reasons, n (%)°* 53 (53.4) 60 (63.8)

+ Advanced-stage NSCLC cohort: Large proportion did not receive comprehensive biomarker testing; 54.6% of patients received biomarker
testing by NGS order prior to first-line treatment

+ Early-stage NSCLC cohort: Biomarker testing rate low (targeted therapies only recently approved); -50% received EGFR and/or PD-L testing

+ À common barrier to biomarker testing ordering was patientprovider attitudes and perceptions

* Denominator: patents wit biomarker testing resus prof frstine treatment.» KRAS testing is approved or laterine treatment. «Denominator: patents without biomarker testing resus

‘orto Weatment * More than one reason could be selected. "Mor than one Baie could be selected, Denominator patients who did not have biomarker testing results

ue to “baer fo es ordering” DTS
1. Evangelist M et al ASCO 2023, Abstract 9109, PeerView.com

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Biomarker Testing in European Countries?

Biomarkers Actionability Scale ESCAT 1

AAA
Ava

+ Most of the validated biomarkers that can be tested using relatively
Simple techniques, not requiring extensive panels, are relatively
widely tested across countries

+ More advanced biomarkers (even some ESCAT 1) are rarely tested
outside clinical trials or research, even across EU countries and
despite available medicines (eg, anti-NTRK, anti-RET,
immunotherapy for TMB high)

1. Bayle At al. Ann Oncol 2023:34:934-045,2. Peters 5. ELCC 2023.

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The Availability of Biomarker Testing Technologies
Across Countries’

Single Gene Multigene

Basic, single-gene techniques are
widely available, whereas access
to advanced biomolecular
technologies, including large NGS
panels and complete genomic
profiles, is heterogeneous

+ In most countries, advanced
biomolecular technologies are
limited to clinical trials or basic
research

1.Bayle At al. Ann Oncol, 2023:34:934-045, 2. Peters 5, ELCC 2023. PeerVie

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Disparities in Biomarker Testing in NSCLC’

Vai All NSC!

Frequency of EGFR and ALK (n
alterations did not differ between
White and Black patients EGFR alteration, n positive (%) 803 (8.2) 107 (8.3) 64
ALK alteration, n positive (%) 151 (1.5) 13 (1.0) 16

Real-world practice: Patients who are Black are less likely to undergo NGS
testing compared with those who are White (39.8% vs 50.1%; P < .0001)

Racial disparities in biomarker
testing rates and clinical trial Black patients in this cohort were significantly less likely to be treated in
enrollment despite no notable clinical trials
differences in prevalence of
biomarker alterations between Participation in clinical trials was higher in patients undergoing NGS testing
White and Black patients + Inadjusted analyses, factors associated with clinical trial participation among
Black and White patients included NGS testing, biomarker testing, age,
histology, race, stage Ill vs IV, and practice volume

( What are the barriers and contributing factors, and how to overcome them?

1. Bruno DS et al, ASCO 2021. Abstract 9005. PeerView.com

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Necessary Biomarker Testing in 2024 for Lung Cancer

+ Biomarker testing prior to therapy is needed to optimize care

+ PD-L1 tumor expression, genomic alterations (EGFR, ALK, ROS1, BRAF,
NTRK, MET, RET, KRAS, HER2)

+ Guides initial therapy in advanced nonsquamous NSCLC and now in earlier
stages of disease (PD-L1, EGFR, ALK)

+ Type of testing matters (NGS, DNA vs RNA)
+ Interpretation of results is just as important
— Know what you're looking for (mutation vs amplification/overexpression)

— Biomarker “positive” is not enough—eg, complexity of testing for EGFR
mutations > more granularity needed

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Modern Practice Principles in NSCLC, Part 2

How to Select, Sequence, and
Maximize the Benefits of Targeted

Therapies in Metastatic, Locally
Advanced, and Early-Stage Settings

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©

EGFR-Targeted Therapy

Different Subtypes of EGFR Mutations!

Exon 19/L858R (~85%)

Erlotinib
Gefitinib
Afatinib
Dacomitinib
Osimertinib

Erlotinib/ramucirumab

+ G719X, L861Q, S768l (-8%-10%)

Afatinib

+ Exon 20 (~5%-7%)

Amivantamab

1. Paez JG et al, Sconce, 2008; 304:1497-1500,

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Exon 19
deletion

“Uncommon”
G719X, L861Q

Exon 20
insertion

L858R

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FLAURA: Osimertinib in First-Line
EGFRmut Advanced NSCLC?

Best Change From Baseline in Target Lesions
Osimertinib

23

88038

mos.me
I a
pa E02 ETC]
8 07 Comparto EGFR TI 31.8 (286:960)
3 06
és + 2 os.
Gefitinib or Erlotinib u
" Eos een

HR = 0.20 5.05% CI, 064-1.00)
Er

o
0 3 6 8 1215 1021 da dr 30 33 36 39 2 45 de OT SS
ne Time Since Randomization, mo

SRoRsas

Best Change From Baseline, % Best Change From Baseline, %
E 3

100) NE

1. Soria JC eta N Engl J Med, 2018;378:113-125. 2. Ramalıngam SS etal. N Engl J Med, 2020;382:41-50, PeerView.com

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FLAURA2: First-Line EGFRmut Advanced NSCLC
Phase 3 Study’?

First-line osimertinib + platinum-pemetrexed in EGFRmut advanced NSCLC

Osimertinib 80 mg QD +
pemetrexed 500 mg/m? +
carboplatin AUCS or cisplatin 75

Follow-Up

+ RECIST 1.1 assessment at weeks
6 and 12, then every 12 weeks.
until rDP or other withdrawal
criteria met

+ Brain imaging mandatory at
‘baseline and progression forall
pis and at scheduled assessments
‘until progression for pts with
baseline CNS mets

+ AILCNS scans assessed by
‘neuroradiologist CNS BICR using
‘modified RECIST guidance

Patients with untreated, EGFRmut advanced NSCLC
+ Aged 218 years (Japan 220 years)

+ Pathologically confirmed non-squamous NSCLC
+ Ex19del or L856R (local/central test)

+ WHOPS0-1

No prior systemic therapy for advanced NSCLC*

+ Primary endpoint: PFS by investigator assessment per RECIST 1.1°¢

+ Key secondary endpoints: OS, ORR, DoR, DCR, HRQOL, safety (AEs by CTCAE v5), PFS2°

wth asymptomatic CNS mets (not requiring steroids) or with a stable neurological status for 22 weeks after completion of defniive treatment and steroids, received, were alowed,
* Pemetrexed maintenance continued und a discontinuation eiterion was met. Effcacy analyses were in the ful analysis set defined as al pts randomized to study, comparison between

aiment arms was regardless ofthe treatment actualy received. The safely analysis sel was defined as al randomized is who received 21 dose of study treatment. one patent who was.
randomized to oamertni plus platnum-pemelrexed received only osimertib and was therefore Included in he osimertnid monotherapy safety analysis set * The study provided 90% power
19 demonstrate a sttstcaly significant difference in PFS assuming HR = 0.68 at 5% two-sided significance level. Pact},
1. Planchard D et al ESMO 2023. Abstract LBASS, 2 IS. lnicavils govistudyINCTO4O35488, PeerView.com

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FLAURA2: PFS of First-Line Osimertinib + Chemotherapy
in EGFRmut Advanced NSCLC12

+ Osimertinib with the addition of platinum/pemetrexed has demonstrated a statistically significant and clinically meaningful
improvement in PFS over osimertinib monotherapy in patients with EGFRmut advanced NSCLC
— Per investigator assessment, median PFS was improved by ~8.8 mo with osimertinib + chemotherapy
vs osimertinib monotherapy
— Per BICR, median PFS was improved by ~9.5 mo with osimertinib + chemotherapy vs osimertinib monotherapy

PFS per Investigator Assessment PFS per BICR Assessment
gos gos
CA
Eo. ot E% comet scemo Bas emt minero chamo
sa | E sama]
EN mens | So sna | Si at
Ea Ea fet, | |
o A H H
o> tt ne HE EEE BE EHE NE ee à ae >
Time Since Randomization, mo Time Since Randomization, mo
Data ett Ap, 2025, —s
1.Janne P et al, WCLC 2023, Abstract PLO3.13. 2, Planchard D et al. ESMO 2023, Abstract LBASB. PeerView.com

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FLAURA2: Interim OS of First-Line
Osimertinib + Chemotherapy’

(OS: HR = 0.75 (95% Cl, 0.57-0.97) Median OS, mo (95% Cl)
Fee ‘Osimertinib + chemotherapy NR (38.000)

Osimertinio 36.7 (3320)

Median follow-up for OS, mo (range)
Osimertiib + platinum-pemetrexed, 31.7 (0.1-43.3)
úOsimertinib monotherapy, 30.5 (0.1-43.0)

Osimertinib + chemo

OS, Proportion
|

00 À 7 0 Sn % % 2 4%

as Time, mo

+ Osimertinib + chemotherapy demonstrated a favorable trend toward OS improvement at two years of follow up

+ The combination also showed a consistent benefit across prespecified post-progression endpoints of time to first
subsequent treatment (TFST; HR 0.73), time to progression on second-line therapy (PFS2; HR 0.70), and time to second
subsequent treatment (TSST; HR 0.69)

1. Natalia V. et al ELCC 2024. Abstract 40, PeerView.com

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MARIPOSA: First-Line EGFRmut Advanced NSCLC
Phase 3 Study!

Amivantamab + lazertinib vs osimertinib as first-line treatment in EGFRmut advanced NSCLC

Amivantamab 1,050 m
first 4 weeks, then

eekly for

very 2 weeks

240 mg QD
open label)

Patients with untreated,
EGFRmut advanced NSCLC

+ Treatment-nalve for Ext9del vs L858R. Se
advanced disease simertinib 80 mg QD
+ Documented EGFR een ups Us 0 no) 429; blinded)

+ History of brain mets®
(yes or no)

Ex19del or LESER.

ECOG PS 0-1
Lazert

Endpoints assessed in amivantamab + lazertinib vs osimertinib arms
+ Primary endpoint: PFS® by BICR per RECIST 1.1
+ Secondary endpoints: OS", ORR, DoR, PFS2, symptomatic PFS*, intracranial PFS*, safety

‘Baseline bran MR was required for al patients and performed 528 days prior to randomization; patients who could not have MAIS were alowed to have CT scans. Brain scan frequency was
‘every 8 weeks forthe frst 30 months and then every 12 weeks thereafter for patents with a history of rain metastasis and every 24 weeks for patients with no istry of ran metastasis,
Exvacrnial tumor assessments were conducted every 8 weeks forthe st 30 months and then every 12 weeks untl disease progression confirmed by BICR. > Key statistical assumptions

800 patents wih 450 PFS events would provide approximately 90% power for amivantamab + laerin vs osímerini to detect an HR of 073 using a log rank test, with an overal orsied
alpha of 0.05 (assuming an incremental median PFS of 7 months). Slatstal hypothesis testing included PFS and then OS, “These secondary endpoints (symptomatic and intracranial PFS)

il be presented ata tur congress. sas

1. Cho BC et al. ESMO 2023, Abstract LEA. PeerView.com

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MARIPOSA: PFS of First-Line Amivantamab + Lazertinib
in EGFRmut Advanced NSCLC‘

Primary Endpoint: PFS by BICR*

Amivantamab + lazertinib reduced the risk of progression or death by 30%

+ Amivantamab + lazertinib significantly
and Improved median PES by 71100 improved PFS over osimertinib in first-line
Maio onu: 220 m0 EGFRmut advanced NSCLC (HR = 0.70;
Media PFS, mo (85% CH 95% Cl, 0.58-0.85; P < .001)
100 ge arm
m Kahn + Amivantamab + lazertinib compared with

osimertinib showed
HR = 0.70 (85% 1,058.85, P<.001)

Ze — Consistent benefit in patients with and
a Amivantamab + azertini without brain metastases
simaninio
2 — _ More durable responses, with
a 9-mo improvement in median DOR
ow à 15 1 À À 27 © 3 (25.8v2:16:8:100)
wu Time, mo

“atthe time of prespecified final PFS analysis, here were a total of 444 PFS events in the amivantama + lazetnio and osímerini arms combined.
1. Cho BC etal ESMO 2029. Abstract LEA

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MARIPOSA: Interim OS of First-Line Amivantamab
+ Lazertinib in EGFRmut Advanced NSCLC!

Early survival data show a trend favoring amivantamab + lazertinib vs osimertinib

Amivantamab + lazertinib

oo 'Osimertinib
8
40
2
o
o 3 6 8 2 5 8 À A 7 2% 33
Time, mo
No at Risk
Amivaniamab +azerinb 429 403 389 382 374 360 208 201 12 58 14 0
Osimerints 4948409305372 HMS ee 0

There were a total of 214 deaths inthe amivantamab + lazertnb and osmerini arms a ime of he prespecied interim OS analysis, which represents 25% of a randomized patents and
55% ofthe =390 projected deaths forthe final OS analysis. Medans a tis me are not estimable, A
1.Cho BC et al. ESMO 2023, Abstract LEA. PeerView.com

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MARIPOSA: Amivantamab + Lazertinib vs Osimertinib in 1L
EGFRmut mNSCLC With Biomarkers of High-Risk Disease’

+ High-tisk features occur commonly in first-line EGFRm (ex19deV/L858R) NSCLC, which carry a
poor prognosis
+ Among patients with pathogenic alterations detected in ctDNA by NGS, 54% of patients had TP53
co-mutations (46% of patients from the ctDN NGS analysis population)
+ Overall, 70% of patients had detectable EGFR mutation by ddPCR
+ Amivantamab + lazertinib significantly improved median PFS vs osimertinib in high-risk subgroups with:
— History of brain metastases (HR = 0.69; P = .010)
— Baseline liver metastases (HR = 0.58; P= .017)
- TP53co-mutations* (HR = 0.65; P= .003)
— Detectable baseline EGFRm ctDNAP (HR = 0.68; P= .002)
> Without EGFRm ctDNA? clearance at week 9 (HR = 0.49; P= .015)
Among the corresponding subgroups without high-risk features, amivantamab + lazertinib showed a
numerical PFS benefit over osimertinib
Trials to optimize treatment administration are ongoing (COCOON, SKIPPirr, PALOMA-2, PALOMA-3)

were detected with the Guardant Health 63609 panel. ® Exon 8del and LESER by Biodesix déPCR.

athogenie mutatons
1. Felip et al ASCO 2024, Abstract 8504.

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RAMOSE (HCRN-LUN18-335): TKI-Naive EGFRmut
Advanced NSCLC Phase 2 Study’

Osimertinib + ramucirumab vs osimertinib alone in TKI-naive EGFRmut advanced NSCLC

Patients with EGFRmut 80 mg QD
advanced NSCLC w (psa
+ Documented EGFR

extOdel or L858R ‘Stratification
+ EGFR TKlnalve
+ VEGF therapy-naive
+ PS04 NS mets (yes or no) Pts receiving osimerni alone
sai NS meta Osimertinib 8 un,

present = a Treatment beyond progression

alowed

+ No recent PE or stroke i

+ RECIST 1.1 at6 weeks and
then every 12 weeks

+ Ps receiving osimertinib +

+ Ext9del vs LESER ramucirumab vist Q3W

+ Primary endpoint: PFS by investigator assessment per RECIST 1.1
+ Secondary endpoints: ORR, DCR, OS, safety

41. Le Xetal. ESMO 2029. Abstract LEAT! PeerView.com

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RAMOSE (HCRN-LUN18-335): PFS by Investigator’

Osimertinib + Ramucirumab _Osimertinib.

1.00 Median PFS (95% Cl) 24.8 (17.9-NR)
HR (95% CH 055 (032.093)
g os Log-rank P 026
4
2
Ê os
é
Ed AAA
¢
Se 02
H Osimertnis
o 4
2 è
Time, mo
No. at Risk
Oaimerind + ramuciuma 93 6 44 2 # 6 2
Oamenind 4 7 19 " 7 4 o

+ Median follow-up: 16.6 months
+ Median duration of ramucirumab treatment (Arm A): 14.2 months
+ Dose intensity ramucirumab 86.6%

1. Le X et. ESMO 2023. Abstract LEAT!

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156 (117228)

Osimertinio
+ ramucirumab

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PALOMA-3: Sub-Q vs IV Amivantamab (Both in Combination
With Lazertinib) in Refractory EGFRmut Advanced NSCLC12

Study Design
Key Eligibility Criteria Amivantamab + Lazertnib
Locally-advanced or metastatic
NSCLC
Co-primary endpoints®:
sara (moninferionity)®; C2 AUC (noninferiority}
y osimertini inum-
ee er Secondary endpoints: ORR (noninferiority);
ri IV mans: 1050 mg weet (400 ma 12209) PFS (supeririy); patent satisfaction, safety
Documented EGFR Ex19del or Pte ee o ro Lot
end zr: 260 mg PO dy Exploratory endpoints: OS
ECOGPS 0-4
N=418
o a Prophylactic anticoagulation
2 EGP matan ype (Edda vs Laer) recommended for the first 4 mo
ee Cr of treatment

+ Type of ast therapy (osimeri vs CT)

PALOMA-S (NCTOS388666) enoiment period: August 2022 to October 2023; data cf: January 3, 2024
*SC amivantamab was coormulated with HUPHZO at a concentration of 160 mm. ® CA for IV: Days 1 o 2 (day 2 applies to IV spl dose only [350 ma on day 1 and the remainder on day 20 8,
15, and 22, C1 for SC: Days 1,8, 15, and 22, after Ct for al: Days 1 and 15 (26-day eyes) “For calculating primary and key secondary outcomes, a sample sie of 400 patents was estimated to
provide 205% power ora -ided alpha of 05 allocate to each ofthe co-primary endpoints and 80% power wth a -ided alpha of 0.025 allocated to ORR. A Nerarchcal esting approach at 2-
Sided alpha of 0.05 was used for the co-pimary endpoints (ninety), flowed by ORR (noninteriarty) and PFS (supero), with a combined 2-ided alpha 010.05. Two detnitons ofthe
same endpoint were used as per regional heath authority guidance Measured between C201 and C2016, "Assessed by modified TASQ. Has

1. Leigh NB et al. ASCO 2024. LBABSOS. 2. Leigh NB et al. J Cin Oncol, 2024:JCO2401001. do: 10.1200C0.24.01001 [Epub ahead of prin PeerView.com

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PALOMA-3: Sub-Q vs IV Amivantamab (Both in Combination
With Lazertinib) in Refractory EGFRmut Advanced NSCLC12

‘ORR, % (95% Cl) * =
nes CES) See £

Rave 002 010120: P= 001 H

Confmedrepondeen ze 272133) E

lave rok 090 072198).7< 001 3

Best response, n (%) 3

E 105 105 5

er 0100 m 3

so sus) arm é

vo 70 200 =
ne “0 26)

DCR» 85% cn 150991 nem Fe wg
Median tine reports, 454208) 150200 News BG

+ ORR was noninferior between the SC and IV amivantamab arms

DOR was 11.2 months in the SC arm vs 8.3 months in the IV arm, with twice as many patients, 29% in the SC arm vs 14%
in the IV arm, having a response 26 months

The objective response (CR or PR) was assessed using RECIST v1.1 and analyzed using logistic regression. The lower bound of the 95% Cl indicated 270% retention of ORR exceeding
the predefined 60% retention assumed or determining noninferriy. ® Not protocol specie,

4 Leight NB eta, ASCO 2024, LBABSOS. 2, Leigh NB et al J Cin Oncol, 2024:JCO2401001. dl: 10.1200UCO.24.01001. Online ahead of print PeerView.com

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PALOMA-3: Sub-Q vs IV Amivantamab (Both in Combination
With Lazertinib) in Refractory EGFRmut Advanced NSCLC12

IV Amivanta

PFS SC Amivanta

WE mE Biase) 434187
a HR (05% C1) 084 05% C1, 064-110) P= 20
e | Mean flow 7 monts
PJ e 50, SC amivantamab =>
Lo F
o H + PFS was numerically longer with SC
H vs IV amivantamab, with an HR of 0.84
A o 2 4 6 8 10 2 “ 1
mn Time, mo
Sema 26 9 MO M M à 9e ©
Vanne 32 M i 8 B 7 3 8 à
w
= SC amiantamab * There was an OS benefit associated with
ze SC amivantamab, with an HR of 0.62
go Sir TE compared to the IV amivantamab arm?
=
0
No. at Risk ° Timd,mo * E
Pe CE 4% 0 0

Namen. 22 Mi M OS 5 2 0 ©
There were 43 deaths ho SC amivantamab arm and 62 deaths inthe IV amivantamab arm. Nominal P value was calculated from a log-rank ts static by history ol rain metastases,
Asian race, EGFR mutation type (ext8del or LESER). and last ine of therapy (osimertin or platinum based therapy) he prespeciied endpoint was exploratory and not part of hierarchical
hipotesis testing 5
‘Leigh NB et a ASCO 2024. LBABSOS, 2. Leigh NB etal. J Clin Oncol, 2024:ICO2401001. al 10.12001JCO.24.01001. Onine ahead of print PeerView.com

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PALOMA-2: SC Amivantamab + Lazertinib
as First-Line Treatment in EGFRmut NSCLC‘

+ SC amivantamab + lazertinib
showed meaningful efficacy in 1L
EGFRmut advanced NSCLC: among all
patients, investigator-assessed ORR was
77% and independent central review-
assessed ORR was 79% (results
comparable to that of IV amivantamab +
lazertinib in MARIPOSA)

+ Safety profile of SC amivantamab +
lazertinib was also similar to MARIPOSA,
other than ARRs and VTES being
markedly lower than with IV administration

+ Prophylactic anticoagulation can be safely
implemented and effectively reduces the
rate of VTE

+ Consistent PK profiles further support use
of SC amivantamab + lazertinib

This bridging study provided promising evidence for the efficacy and safety o! mivantamab + lazerti
suggested that it could be a valuable 1L treatment option for patients with EGFRmut advanced NS

1. Lim SM et al ASCO 2024. Abstract LBABS12. PeerView.com

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Amivantamab + Lazertinib in Patients With
EGFRmut Lung Cancer and Active CNS Disease!

NCT04965090
+ Patients with progressive or new brain metastases (BrM) or leptomeningeal disease (LM)

+ All patients with EGFR exon 19 del/L858R/atypical mutations had prior osimertinib, all patients with EGFR exon 20
insertions (ex20ins) had prior chemotherapy

+ Co-primary endpoints were systemic ORR by RECIST v1.1 and CNS ORR by RANO-BM or LM

BrM Cohort M Cohort

‘Systemic ORR by RECIST, % (95% Cl) 30 (13-54) 32 (15-55)
Intracranial ORR by RANO, % (95% Cl) 40 (20-64) 23 (9-46)
Median time on treatment, mo (range) 3.9 (0.3-18.6) 8.1 (0-21.7)

+ Most frequent TRAEs (230% in overall population) were rash (71%), infusion-related reaction (59%), paronychia (43%),
fatigue (40%), edema (40%), mucositis (33%), and nausea (33%)

+ Most frequent (25%) grade 23 TRAEs were infusion related reactions (7%), thromboembolic event (5%),
elevated AST/ALT (5%), and rash (5%)

+ Three patients (7%) discontinued treatment due to TRAES
1. Yu HA etal, ASCO 2024. Abstract 8517 PeerView.com

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Mechanisms of Resistance to First-Line Osimertinib13

Treatment

3%-7% Fourthgen EGFR TKI
On target EGFRamp 11% 7% Firstsecond-gen EGFR TKI
67248, Liv. 0%-5% 5% EGFR antibody.

Osimertinib + MET inhibitor

oft target METamp 17 10%-18% — Osimerinib + ALK inhibitor

(validation, ALK fusion 2% - Osimertinto with MET,

rug avalable) — BRAF, HERZ, RET 0%-10% 24-74 BRAFRETInibior

TOMITOXA | Unknown
ra
RE 1 O%-15%
NO 1amp he ES
ont arg CONETamp Hs Gx Standard chemotherapy, PR
(00 validation, ARAFamp. = clinical tials ano
no drug) Mycamp, (amitazer, HERS-OX¢)
MOM2amp, CDK4A,
PIKSCA, KRAS. Geo GAS
jamousismal cel
retoman ine Lsac
Uneage plastciy pes 9% 15% Taloredchemotherapy a
EMT, AXE upreguaton 750% era
Standard chemotherapy,
Unknown None on NGS. 30% 15% clinical tals
(aminazer, HER3-DX)
1. Schoenfeld AJ et a. Cin Cancer Res, 2020,26:2654-2663. 2. Ramalngam SS etal. J Cin Oncol. 2018:36:841-849. 3. Figure provided courtesy of Helena A Yu, MO. PeerView.com

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Subsequent-Line Treatment Options After Osimertinib

No Actionable Genomic Alteration

Chemotherapy

Amivantamab + chemotherapy

Actionable Genomic Alteration

Osimertinib combinations

Antiangiogenic + chemotherapy

Antibody-drug conjugates

Immune checkpoint inhibitor
+ chemotherapy

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MARIPOSA-2: Amivantamab + Chemo + Lazertinib vs Chemo
in EGFRmut Adv NSCLC After Progression on Osimertinib*

Amivantamab + chemo + lazertinib vs chemo in EGFRmut advanced NSCLC after progression on osimertinib

Patients with EGFRmut
advanced NSCLC

Documented EGFR
Ext9del or L858R

Progressed on or after

úosimertinib monotherapy
(as most recent ine)
ECOG PS 0-1

Stable brain mets allowed;
treatment was not required

Serial brain MRIs required

for all patients" Amivantamab + Lazertinib +

Dosing (21-Day Cycles)
Stratification Amivantamab: 1,400 mg for fist

4 weeks, then 1,180 mg every 3
Osimertini ine of therapy ‘weeks starting at week 7
(first vs second) Laz

nib: 240 mg QD starting
Asian race (yes or no)

after completing carboplatin®
Chemotherapy at beginning

History of brain mets e

(yes or no)

Amivantamab +
Chemotherapy + Pemetrexed: 500 mgim? until
1 disease progression

Endpoints assessed in amivantamab + lazertinib + chemotherapy vs chemotherapy and amivantamab + chemotherapy vs chemotherapy arms.
+ Dual primary endpoint: PFS* by BICR per RECIST 1.1
+ Secondary endpoints: ORR*, DoR, OS“, intracranial PFS, time to subsequent therapy”, PFS2*, symptomatic PFS®, safety

Patents who coud ot have MRI were alowed to have CT scans. Al patents randomized before November 7, 2022 inated lazrtnib onthe fst day of Cyci 1. Key stastcal assumptons:

600 patients with 350 events across all 3 arms would provide approximately 83% and 93% power for amivantamab-chemotherapy and amivantamab-lazerinb-chemotherapy, respectively,
vs chemotherapy to detect an HR of 0.65 using a log-rank test, with an Overall two-sided alpha 10.05 (median PFS of 8.5 months for amivantamab-contaning arms vs 5.8 months for

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congress,
Passaro A ef al ESMO 2023. Abstract LBAIS,

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MARIPOSA-2: PFS of Amivantamab + Chemo + Lazertinib
in EGFRmut Advanced NSCLC After Osimertinib!

+ Ata median follow-up of 8.7 months, amivantamab + chemotherapy and amivantamab + lazertinib + chemotherapy reduced
the risk of progression of death by 52% and 56%, respectively

PFS by BICR
Amivantamab + chemotherapy | Amivantamab + lazerinib +
100 versus chemotherapy chemotherapy? versus chemothorapy
Median PFS: 6.3 versus 42 mo Median PFS: 8.3 versus 42 mo

“o
# 6
rg
go
20
o
mo
o. Consistent PFS benefit by investigator
ever + cheney .2 versus 4.2 mo; P < .001°) and
eet + azar + cheery mm 4 38 (8.3 versus 4.2 mo; P <.001
tantos ms

* Amivantamab + azerí + chemotherapy am includes al patents regarsess of he dosing regimen received.
Nominal P valve endpoint not pat o hierarchical hypothess testing .
1. Passaro A et al ESMO 2023, Abstract LBAIS. PeerView.com

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MARIPOSA-2: Intracranial PFS of Amivantamab + Chemo +
Lazertinib in EGFRmut Advanced NSCLC After Osimertinib!

+ Amivantamab + chemotherapy and amivantamab + lazertinib + chemotherapy reduced the risk of intracranial progression
or death by 45% and 42%, respectively

Intracranial PFS by BICR

Amivantamab + chemotherapy
vs chemotherapy
Median PFS: 12.

Amivantamab + lazortinb + chemotherapy?

ee
2
Es
2
o
Hs 7 y mi 2 © de
Per Time, mo
Cremona x 20 107 o ” » 1 o

1. Passaro À et al ESMO 2023. Abstract LBATS. PeerView.com

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ADAURA: Stage IB-IIIA NSCLC Adjuvant Phase 3 Study!

Adjuvant osimertinib vs placebo in completely resected stage IB-IIIA EGFRmut NSCLC

Patients with stage IBJIVINA (7th edition®) NSCLC?
‘Aged 218 years (Japan/Taiwan 220 years)
Confirmed nonsquamous NSCLC
Ex19del or L858R EGFR mutation*

WHO PS 0-1 Stage (IB vs Il vs IIIA)
Ext9del vs LESER.

Brain imaging, if not completed pre-operatively

Complete resection with negative margins*

Max interval between surgery and randomization
— 10 weeks without adjuvant chemotherapy
— 26 weeks with adjuvant chemotherapy

+ Primary endpoint: DFS per investigator in stage IVIIIA pts

+ Secondary endpoints: DFS in ITT*, DFS at 2-5 years, OS,
safety, HRQOL

+ Exploratory endpoints: Patterns of recurrence, time to CNS
disease recurrence or death (CNS DFS)

Osimertinib 80 mg PO QD

Stratification Ara

(3-year treatment duration)

Asian race (yes or no)

Placebo

‘Treatment continues until:
+ Disease recurrence

+ Treatment completion

+ Discontinuation criterion met

Follow-up:

Until recurrence: week 12 and 24, then every 24 weeks to 5 years,
then yearly

‘After recurrence: every 24 weeks for 5 years, then yearly

‘atthe time of recruitment, staging was determined bythe AJCCIVICC 7th edition staging manual Prior, post, or planned radiotherapy was not alowed,

“Centrally confirmed in issue. * Patents received a CT scan ater resection and win 28 days prior to treatment “Stage IBN.

1. Tauboi Metal ESMO 2022, Abstract LBA47,

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ADAURA: Updated DFS of Osimertinib as Adjuvant Therapy
in Stage II/IIIA Disease and the Overall Population’?

DFS in Stage II/I1IA Disease (Primary Endpoint)" Overall Survival: Patients With Stage IIIA Disease
m S¥OSRate,
Median DFS, mo (95% Ci = F =
Dsirerin (n= 233) 85.8 (68 4NC) rer OS HR (09 CD 040030070)
Placebo (n= 237) 219(188275) ? ‘aoe
er HR (85% CI) 023 (0180.30)

DFS, Proportion
22

Maturity: 51%
Osimertnio: 32%
Placebo: 70%.

9 6 2 1% À © m à a 6 GMT

Time, mo

No. at isk

One 233 222 216 202 190 102 174 198 00 45 20 2 0 Ommemb 223 220 ZU ZU 221 214 208 206 200 170 115 69 m 9 0
ELE EEE)
*Planned matury for DFS analysis: 50%. =

1. Tsuboi Metal, ESMO 2022. Abstract LBAA7. 2. Herbst Ret al. ASCO 2023, Abstract LBA3. PeerView.com

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ADAURA: Molecular Residual Disease (MRD) Analysis!

+ Tumor-informed MRD in ADAURA was feasible and identified recurrence Ss
with a median lead time of 4.7 months in this study

* DFS and MRD event-free status was maintained for most patients during
osimertinib treatment; most MRD or DFS events occurred post-osimertinib with
58% occurring within 12 months post-osimertinib

* At24 months post-osimertinib treatment, the DFS and MRD event-free rate
was 66%

Tumor-informed MRD analysis demonstrated maintenance of DFS and MRD

event-free status for most patients during and after osimertinib treatment

4. John Tet al, ASCO 2024. Abstract 8005, PeerView.com

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LAURA: Maintenance Osimertinib
in Unresectable Stage-Ill EGFRmut NSCLC"

Press Release =
Positive high-level results from the phase 3 LAURA trial
showed maintenance osimertinib demonstrated a statistically
significant and highly clinically meaningful improvement in
PFS for patients with unresectable stage Ill EGFRmut
NSCLC after CRT vs placebo after CRT!

a pe o

+ In LAURA, osimertinib demonstrated a statistically significant and clinically meaningful improvement in PFS vs placebo by
BICR in unresectable stage Ill EGFRmut NSCLC following definitive chemoradiotherapy
- Median PFS was 39.1 months (95% Cl, 31.5-NC) with osimertinib, 5.6 months (95% Cl, 3.7-7.4) with placebo;
HR = 0.16 (95% Cl, 0.10-0.24), P< .001
— PFS benefit was consistent across subgroups
* Interim OS data showed a positive trend in favor of osimertinib, despite a high proportion of patients crossing over to
osimertinib in the placebo arm (81%)
+ Safety profile of osimertinib post-chemotherapy was as expected and manageable
+ EGFR mutation testing is critical in stage III disease to ensure optimal outcomes for patients with EGFRm NSCLC
Osimertinib will become the new standard of care for patients with unresectable stage III EGFRmut
NSCLC who have not progressed after definitive chemoradiotherapy
‘Patents with a local cobas® EGFR mutation test v2 issue positive result rom a CLIA-ceiie or accredited laboratory d not require part screening. ® Post CRT

imaging performed to assess CR. PR, and SD up o 28 days before randomization. "Assessment of PFS2 wil ot be collected atar he primary PFS analysis a
Y Ramaingam Set al. ASCO 2024, Abstract LAG PeerView.com

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NeoADAURA: Neoadjuvant Osimertinib + Chemotherapy
vs Chemotherapy Alone for EGFRmut NSCLC‘

Placebo + chemotherapy

+ Resectable +
+ Stage IB Adjuvant
NSCLC Osimertinib + chemotherapy investigator

+ EGFRmut choice
NSCLC (optimal care)

(ex19delL858R)

Double-blind treatment arms Adjuvant therapy and follow-up

1. Placebo QD + investigator's choice of pemetrexed
stratication eso ot es cis et eres À Pin a De ai or OS eh get
Stage ul a Vera surgery, wth evaluation at 12 and 24 weeks post

orcas Osimertinib 80 mg QD + investigator's choice survery, (ben every 20 weeks, unl dieense
[torretas of pemetrexed 500 mg/m? plus carboplatin nes os wthcrewal of consent
2
Exi9del.858R AUS re maine ot cp eae Osimertinib will be offered to all patients who
'Open-label (sponsor-blind) treatment arm rompas een postal Slot) bd
3. Osimertinib 80 mg QD up to 3 years or until recurrence

The primary endpoint is centrally assessed major pathological response at the time of resection.

1. Tsuboi Metal, Future Oncology. 2021:17:4045-4055, PeerView.com

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ADAURA2: Adjuvant Osimertinib vs Placebo
in Completely Resected Stage IA EGFRmut NSCLC‘

Patients with stage 1A2 or 1A3 (Sth edition) NSCLC
+ Post complete (RO) resection
+ Exon 19 deletion or L858R EGFR mutation
+ Tumor sample submission for central pathology
assessment of
— Invasive tumor size
— Lymphovascular invasion
— Tumor histology
+ PSO4
No pre/postoperative RT or systemic therapy
Not eligible for any local SOC treatment

Osimertinil an

‘Adjuvant
(&-year treatment duration)

Stratification
+ High risk vs low risk
+ Exon 19 del vs L858R

+ Race (Chinese Asian
vs non-Chinese Asian
vs non-Asian)

Placebo PO Qi

High risk is defined as the presence of 21 of the following factors
— Invasive tumor size >2 cm

+ Primary endpoint: DFS per investigator in high-risk stratum = Lymphovascular invasion
+ Secondary endpoints: DFS in ITT, OS in high-risk stratum, — 220% micropapillary, solid, or complex gland adenocarcinoma
OS in ITT, HR-Qol, safety/tolerability, and PK histology

MRD Low risk is defined as the absence of any high-risk factors
Estimated prevalence of high risk is ~60%
Enrich high risk to 67% of ITT population (33% cap on low risk)

+ Exploratory endpoit

1. ps einicatials gov'et2/5how/NCTOS 120340. PeerView.com

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TARGET: 5-Year Adjuvant Osimertinib in Completely Resected
EGFRmut Stage II-IIIB NSCLC Post Complete Resection’

5-year adjuvant osimertinib in completely resected EGFRmut stage II-IIIB NSCLC post-complete surgical resection

Single treatment arm; cohorts defined by EGFR mutatioı

‘Common EGFR mutations (Ex19del or L858R) cohort (n= 150)
Patients with EGFRmut stage II-IB NSCLC

Radiographic scans

(6th edition} Ada Osimertinib Primary endpoint: DFS* | Grrray Cor
|» Aged 218 years (Taiwan 220 years) chemotherapy ets years. ee ean
+ Confirmed non-squamous NSCLC peroo 0 E pe precio recurrence at 12 and 24
|» EGFR mutations (common or uncommont) one pate ‚at 3 and 4 years: OS | weeks and then every 24
cie 0 at 35 years: safety. type | Weck nereter un

+ WHO PS 0-4
|». MRI or contrast CT brain scan required

of recurrence; CNS mets,

study completion,
disease recurrence, or

pre-surgery or pre-enrollment ‘death In accion © pre-

+ Complete resection with negative margins Uncommon EGFR mutations (G719X, L861Q, 57681) cohort (n= 30) surgery or pre-enrolment

ex iriaval Betis ar brain scans, brain scans.
ee ao A CT + secondary endpoints: | wil be required at

E Se
so weeks wihoutaduvantchemoterery|| RER MEAR Orsai years: soley, lemme |
— 26 weeks with adjuvant chemotherapy per investigator a NS mets treatment follow-up.

continuation,
death

AIGG 8th edition staging entra, staging was classed postoperatively. * Future amendment to age 218 years. For patents with tumors harboring bth common and uncommon mutations,
{he patent i be assigned tothe common EGFR mutations cone. * Investgator-assessed ss
1.500 RA et al. Cin Lung Cancer. 2024;25:80-84. PeerView.com

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CHRYSALIS: Amivantamab in Pretreated
EGFR Exon 20 Insertion-Mutated Advanced NSCLC"

Exon20ins location

EGFR Exon 20 sp À aro upon 097272)
Prior Platinum a 1 ron 0732775)
(N=81) 2 m
ORR (IRC) 40% 2
mDOR (INV) 11.1 mo a
mPFS (IRC) 8.3 mo 4
Key toxicities

+ Infusion-related reactions (66% any grade,
3% grade 23); most commonly on C1D1

+ Derm: rash (86% any grade, 4% grade 23),
paronychia (45%)

+ MET related: hypoalbuminemia (27%), edema (18%)
+ Dose reduction: 13%; dose discontinuation: 4%

1. Park K etal J Cin Oncol. 2021:39:3391-3402 PeerView.com

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CHRYSALIS: Long-Term Outcomes Observed With
Amivantamab in Pretreated EGFRex20ins Advanced NSCLC‘

Progression-Free Survival

Overall Survival

m Median PFS: 6.9 mo. = Median OS: 23 mo
EJ (95% CI. 5.6-8.8) e Am (95% Cl, 18.5-29.5)
5 $ na
7 n
x co xo
6
És gs
es 40
0 x0
20 20
0 0
o o
A EE EEE O38 8 TR EDE PEREDA
Time, mo Time, mo

was 7.5 months, with 48 of 114 (42%) patients alive

1. Gamido P et al. ELCC 2023. Abstract 30.

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As of September 12, 2022, the median follow-up was 19.2 months and median duration of treatment

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PAPILLON: First-Line EGFR Exon 20 Insertion—Mutated
Advanced NSCLC (Phase 3 Study)!

First-Line Amivantamab + Chemotherapy vs Chemotherapy
in EGFR Exon 20 Insertion-Mutated Advanced NSCLC

Dosing (21-Day Cycles)

Amivantamab + Amivantamab: 1,400 mg for

chemotherapy first 4 weeks, then 1,750 mg
every 3 weeks starting at wk 7

Patients with EGFR exon 20 insertion-mutated]
advanced NSCLC
+ Treatment-nalve* advanced disease

+ Documented EGFR exon 20 insertion
‘mutations

+ ECOG PS 0-1

Stratification
+ ECOG PS

+ History of brain mets?
+ Prior EGFR TKI uses

‘Chemotherapy at beginning of

every cycle:

+ Carboplatin: AUCS for first 4
cycles:

+ Pemetrexed: 500 mgim? until

+ Primary endpoint: PFS by BICR per RECIST 1.1°
+ Secondary endpoints: ORR®, DoR, OS“, PFS2, symptomatic PFS*, time to subsequent therapy“, safety

‘Key staateal assumption: 300 patients with 200 events needed for 20% power to detect an HR of 0.625 (estimated PFS of vs 5 months) PES, ORR, and then OS were Included in herarchical
testing. * These secondary endpoints (bme to subsequent therapy and symptomatic progression-ree survival) willbe presented at a future congress. “Crossover was only alowed ater BICR
confirmation of disease progression, amivantama monotherapy on Q3W dosing per main stud. A

{Girard Net al. ESMO 2023. Abstract LBAS, PeerView.com

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PAPILLON: Efficacy of First-Line Amivantamab + Chemo
in EGFR Exon 20 Insertion-Mutated Advanced NSCLC!

Primary Endpoint: PFS by BICR Amivantamab + Chemotherapy

g -
Pet nd o ii OE i: à

een a

w A |}.

ei
Crema 876873) oF

xo my spams) Me

¢ ow
Eo i

E

i = 13

o HE

jan CO 2 a de i:
Lee ww nn wk E
mb vy srt mn A ARS i

+ Amivantamab + chemotherapy significantly improved PFS vs chemo in firstine EGFR ex20ins advanced NSCLC (HR = 0.395; P < .0001)

+ In addition, amivantamab + chemo vs chemo alone showed consistent PFS benefit across all predefined subgroups; significantly higher ORR,
longer DOR, and deeper mean reduction in tumor size; longer PFS2, supporting the first-line use of amivantamab + chemo; favorable interim
OS trend (HR = 0.675; P= .106)

+ The safety profile of amivantamab + chemo was consistent with individual agents, with low rates of treatment-related discontinuations with
amivantamab (79%)

Nominal P vale, endpit not par of rachat hypothesis es :
1 Gran Natal E540 2023 Abst LEAS u PeerView.com

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Other Emerging EGFR TKis
for EGFR Exon 20 Insertion Mutations in NSCLC

Second- and Later-Line Setting First-Line Setting
Amivantamab EGFR-MET mAb
Furmonertinib 3G EGFR TKI Phase 1b eae da Phase 3
Sunvozertinib 3G EGFR TKI Phase 1/2 Sunvozertinib 3G EGFR TKI Phase 1/2
Zipalertinib 3G EGFR TKI Phase 1/2 Furmonertinib 3G EGFR TKI Phase 1b/3

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WU-KONG1 & WU-KONG15: Sunvozertinib as First-Line
Treatment in NSCLC With EGFR Exon 20 Insertion Mutations!

WU-KONG1 Primary Analysis
Data Update on Pretreated NSCLC
The best ORR: 54.3%

Confirmed CR: 2.9%

DCR: 90.8%
Tumor response was observed in patients with

Best Tumor Size Change of Target Lesions (N = 28)
wen Elo nf] aaa we

2
Sx
38 baseline brain metastasis, different demographics
23 and EGFR exon20ins subtypes
Es
ES Efficacy 200 mg (n=19) 300 mg (n=9)
ge

78.6 78.6

CESA 200mg (n= 9)

mDOR, mob 9.2 NR
‘Mutation Subtype mPFS, mos 10.2 124
Data cutoft September 15, 2023.
oR confirmed. ® Median folowup of 10.8 mo. “ Median follow-up of 11.5 mo. 7
PeerView.com

esponse had
4. Yang J CH etal ESMO 2029. Abstract 1325P. 2. Yang J C-H. ASCO 2024, Abstract 8513.

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CHRYSALIS-2: Amivantamab + Lazertinib
in Atypical EGFRmut Advanced NSCLC‘

+ The most common mutations were G719X (54%), L861Q (24%), and 57681 (22%)
+ The ORR was 51% (95% Cl, 41-61)

Treatment Treatment With Prior Afatinib Subset
(n = 40)
ORR, % (95% Cl) 55 (40-69) 45 (29-62)
mDOR, mo (95% Cl) NE (9.9 mo-NE) 8.9 (2.8-NE)
DOR 26 mo, % 78 56
mPFS, mo (95% Cl) 19.5 (11.0-NE) 5.7 (4.2-10.7)

+ The most common AEs were primarily EGFR- and MET-related toxicities, primarily grade 1-2
+ Discontinuations of both amivantamab and lazertinib due to treatment-related AEs occurred in 9% of patients
+ The incidence of VTE was 30%, with the majority of events (71%), occurring in the first 4 months of treatment
+ The rate of pneumonitis/interstitial lung disease was 6%

1. Gho BG etal, ASCO 2024. LBABS16. PeerView.com

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Expert Panel Discussion

and Q&A

ALK-Targeted Therapy

ASCEND-4: First-Line Ceritinib
in Advanced ALK-Rearranged NSCLC"

BIRC-Assessed PFS os

Kaplan-Meier Median PFS, mo (95% Cl) i

m Ser 106 (126272)

Chemotherapy 8168410 Py

HR = 055 (95% Cl, 042-073)
P< 00001 by stated log-rank test

x ¿ Chemotherapy
g
¡A « Kaplan Meier Median PES, mo (95% Ci)
Contin NE GSSNE)
ds 2 | chemeterapy 282 (228N€)
Cenes Moenia HR = 0.73 (95% Cl, 0.50-1.08)
r = 056 by sant ig-rank tet
o CIT ore
ERRE ERE REE
Time, mo Time, mo
Mo. at Risk No. at Risk
Centind 180 155 130 125 116 105 98 76 50 43 32 23 16 11 1 1 1 O Cerin 188180 175 171 165 155 150 198 103 77 56 39 28 18 6 3 2 0
Chemotherapy 187 196 114 82 71 60 53 35 24 16 11 5 3 1 1 0 0 O Chemotherapy 187 172 161 150 146 141 134 124 97 69 49 35 19 10 5 1 0 0
1. Soria JC etal. The Lancet, 2017;389:917-828. PeerView.com

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ALEX: Updated 5-Year OS and PFS of Alectinib
in Treatment-Naive ALK-Positive NSCLC’

PFS,%
5 8 8

8

i

08,%
o 353838

a]
o +

%

e.

R= 0.43 65% 01.032088)
Cr]

Acto = 182)

va D % à
Time, mo

Actin (n = 162)

HR = 067 (65% C1. 048-098) cea 151)
Gr

ENE DE à à à ©

1. Mok Teta. Annals of Oncology. 2020:31:1056-1084,

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Las

One Year

One Year

With CNS Metastases:

5

2 =
Two Years Three Years Four

Without CNS Metastases

| Two Years Three Years Four Years

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ALTA-1L: Final Results of Brigatinib in ALK Inhibitor-Naive
Advanced ALK-Positive NSCLC’

Primary Endpoint: BIRC-Assessed PFS

Patents wan Mean PFS, Probab, % (95% CD)

Events, ns) mo (05% CH)
es i y
ERA 11101190) 19420270) 181110280)

Disease progression or death HR = 0.48 (95% Cl, 035-056)
P< 0001 by log-rank test

Overall Survival: ITT Population

Brgatind
(= 137)

on
x oe
PE 2 Death HR = 0.81 (95% CI.053-122) _ Crzoinn
É g Heure re
£ 0.

oe

: u aa rétro 2.9

Te atts ata
; , TH I Hé
STE sae DE a 2 = So à à ES
Time, mo

Eres sop sos 4 3: Bs s rss ss 8:

1. Camidge OR eta. J Thorae Oncol. 2021:16:2001-2108.

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eXalt3: Key Findings of Ensartinib in ALK Inhibitor-Naïve
Advanced ALK-Positive NSCLC’

eXalt3: A phase 3 study comparing ensartinib with crizotinib among patients with
‘ALK-positive NSCLC who had not received prior treatment with an ALK inhibi

PFS by BIRC
Ense (n= 149) rizo m
PSG CUm ARE 276269 * The confirmed ORR was 74% (95% Cl, 66%-81%)

HR sx cn 081 (036072) with ensartinib vs 67% (95% Cl, 58%-74%) with
Pogrank tet) «oo crizotinib

+ Median DOR among responders was not reached (NR;
95% Cl, 22.0 mo-NR) with ensartinib vs 27.3 mo (95%
Cl, 12.9-NR) with crizotinib

Ensarinib + The intracranial response rate was 63.6% with
ensartinib vs 21.1% with crizotinib for patients
with target brain metastases at baseline

PFS, %

+ Frequencies of treatment-related serious adverse
events were 7.7% with ensartinib and 6.1%
03 6 8 2158 em 2 7 90 a 3 with crizotinib
Time, mo

Crizotinib

No. at Risk
Ensarinib 143 125 106 98 88 78 72 54 30 21 10 5 1
Gracin 147 124 94 75 56 43 32 23 10 8 2 1 1

1.Hom Letal. JAMA Oncol. 2021.7:1617-1825, PeerView.com

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CROWN: First-Line Lorlatinib or Crizotinib
in Advanced ALK-Positive Lung Cancer!

At 60.2 months of median follow-up, median PFS by investigator was still not reached with lorlatinib 2

100 Lorlatinib—— Crizotinib
2 (n=19) (n= 147)
En Events, 55 115
al Loriatinib mPFS, mo (95% Cl) NR (64.3:NR) 9.1 (7.4-10.9)
g 50 HR (95% CI) 0.19 (0.13-0.27)
à 40
30
20
10 At the time of this analysis, the
o required number of OS events for a
O 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 | protocolspecified second interim
— Time, mo analysis had not been reached. OS
Lane HO HB 111 tes 00 GD GD OT en en 7m 77 HT 4 2 4 1 0 follow-up is ongoing
cm wane 0 ween wes 9 8 6 420000
Emerging new ALK mutations were not detected in ctDNA collected at the end of lorlatinib treatment.
1. Solomon B et al. ASCO 2024. Abstract LBABSOS. PeerView.com

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CROWN: Intracranial Activity of Lorlatinib
in Advanced ALK-Positive Lung Cancer!

Lorlatinib showed superior PFS benefit irrespective of presence ==
or absence of baseline brain metastases

With Baseline Bi

Metastases Without Baseline Brain Metastases

Lortaind Crizotinib Lord Crono
1239 in 38) (ett) (n=
EN Eien 16 CE ET El El
a PFS, mo (95%) NRGZENR) 000770 19 PFS, mo(95% CI) NR(GA3NR) 10800128)
e HR (95% ch) 0.06 (0.04-0.18) S HR 25% ch) 024 016036)
e E 7 os
e Reo orlatinib
gs Loriatiid 1 so
Eso Eso
30 30
20 2
» ‚Srizotinib E Crizotinib
0 À & 121620 24 2932 36 404448 5250806468 721080 0 4 8 12162020 283236 4044485236 06408727680.
Per Time, mo xen Time, mo
erat 96 9129 28 2826 28 2529 202020 19 18 1510 7 § 2 0 + Im 114 95 996975 7067 64 G4 61 6150505852519 9 2 1 ©
Game 3221143 100000000000000 Gone 1093271611619 9088420000

1. Solomon 8 et

ASCO 2024. Abstract LBABSOS. PeerView.com

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CROWN: Toxicity of Lorlatinib
in Advanced ALK-Positive Lung Cancer!

Safety profile of lorlatinib was consistent Dose reduction did not impact efficacy of
with that observed in prior analyses lorlatinib in patients who had dose reduction

in the first 16 weeks
All-Cause AEs in 230% of Patients in Either Treatment Arm

Lorlatinib Crizotinib

100

Edema

2 With dose reduction
Hypercholesterolemia o
Diarrhea 70
x
Hypertriglyceridemia a 60 pre <
Nausea £0 ithout dose reducto
Fatigue er With Dose Without Dose
x» Reduction "Reduction
Peripheral neuropathy (nz 1 (n = 108)
Vision disorder = Events, n 3 EJ
Weight increase 10] mme) RON — NRORAR)
o
ALT morue: O 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80
Vomiting À ase 2 EIER Time, mo
Constipation À 1 Grace 3-5 nd ig 47 15 15 16 14 12 12 11 11 10 9 9 8 7 5 3 0 0 0 -
100 80 60 40 20 0 20 40 60 80 100 Mie 08101 8 8 a 70.7775 70 7009 RES 59 8 21 11 4 4 0 -

Incidence, %
1. Solomon 8 et al. ASCO 2024. Abstract LBABSOS.

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ALKOVE-1: NVL-655 in Patients
With ALK Fusion-Positive NSCLC1

Activity in Response-Evaluable Patients With ALK-Positive NSCLC

With ALK Prior ALK TKI
Patients With ALK+ AI NSCLC History of CNS Resistance Mutation“ Including 26 and Lorlatiniy_| 2616,
Nscic Response-Evaluable | Metastases No Lortatinio

“any | Single | Compound | G1202R> au + Chemo

ORR across ll dose $2 450 E m 40 2
levels, % (YN) (15729) (15%) (612 m) Kam) (10725) (eno)

PRE » 6 9
es ©0 7 8 5 2 3 3 7 4 2
” Po “ 4 7 3 4 2 6 5 o

nes 3 2 1 1 o o 2 2 o
‘ORR at doses aa EJ CES [2 7 3 aa er
250 mg QD, % (WN) aa) (13726) (4%) m) ity (me 921) qe) a)

This preliminary dataset indicates encouraging clinical activity in a heavily pretreated population with ALK-positive NSCLC,
with responses observed in patients:
+ With and without diverse single and compound ALK resistance mutations
+ Who have exhausted available therapies, including those who have received second generation ALK TKI(s), lorlatinib,
and chemotherapy, and with brain metastases
* Out of 16 patents harboring presumed compound ALK mutaions eight have evidence o alle configuration by central DNA ana. Includes paints with
ing GI202R mutation (n= 5) and G1202R win compound ALK mutations (n= 1, sx wi evidence of salis contguraton) © nude four patent win ongang

ara responses pending confrmaten * Three patents dsconinued treatment due o cinical progression snthout posbaselne radiograph assessment aa
1. Un JJ et al AACRNCLEORTO 2023. Poster 8154. PeerView.com

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ALINA: Adjuvant Alectinib vs Chemotherapy
in Early-Stage Resected ALK-Positive NSCLC’

Adjuvant alectinib vs chemotherapy in early stage, resected ALK-Positive NSCLC

Alectinib

Patients with resected stage

1BUIIIA (7th edition) ALK+ NSCLC.

+ ECOGPS0-1

+ Eligible to receive platinum-

based chemo

+ Adequate end-organ function

+ No prior systemic cancer
therapy

Further treatment
investigator's choice)
and survival follow-up

vs Il vs IIA

non-Asian

chemotherapy

+ Primary endpoint: DFS? per investigator, tested hierarchically—stage II-IIIA — ITT (stage IB-IIIA)

+ Other endpoints: CNS DFS?, OS, safety
* Cisplatn + pemetrexed, cspatin + vinorelbine or csplatin + gemetabine: cisplatin could be switched to carboplatin in case of intlerabity. DFS defined as the time rom randomisation
to the frst documented recurrence of disease or new primary NSCLC as determined by the investgator, or death from any cause, whichever occurs frst. “Disease assessments (cluding

brain MRI or CT scan MR unavailable) were conducted at baseline, every 12 weeks for year 1-2, every 24 weeks for year 35, then annually, Dandi
1. Solomon 8 et al. ESMO 2023. Abstract LBAZ. PeerView.com

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ALINA: DFS of Adjuvant Alectinib vs Chemotherapy
in Early-Stage Resected ALK-Positive NSCLC’

Disease-Free Survival: Stage II-IIA® Disease-Free Survival: ITT (Stage IB-IIIA)*

oon wu © 8 & @ à
Time, mo
sas moon. was" mm nun 2 wm 3

* Median survival follow-up: alectinib, 27.9 mo; chemotherapy, 27.8 mo * Median survival follow-up: alectinib, 27.8 mo; chemotherapy, 28.4 mo
+ Data cutoff: 26 June 2023; ime from last patient in to data cutoff was + Data cutoff: 26 June 2023; time from last patient in to data cutoff was
-18 months. ~18 months
+ Atthe data cutoff date, OS data were immature with only six (2.3%)
OS events reported:
Per UICCIAICC 7th ediion.* Stratified log rank, DFS defined as the time from randomization tothe fist documented recurence of disease or new primary NSCLC as determined by the
Investigator or death from any cause, whichever occurs fr © Two event inthe alecimib arm, 4 events in the chemo arm: one patient in chemo died but was sensored due to incomplete
date of death recorded.
1. Solomon 8 et al. ESMO 2023. Abstract LBAZ.

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NAUTIKA1: Neoadjuvant Alectinib in Patients
With Stage IB-IIl ALK-Positive NSCLC’

Response Outcomes of Patients From the ALK-Positive Cohort

Major pathological response? 6 (66.7)
Pathological complete response® 3 (33.3)
Complete response 0
Partial response 4 (44.4)
Stable disease 5(55.6)
Progressive disease 0

"Assessed locally. One evaluable patent id not undergo resection and was treated as a nonmajor pathological response patent.
« Pathological complete response inthe patient wih squamous MG). a
1.Lee Metal ESMO 2023. Poster 1785. PeerView.com

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Expert Panel Discussion

and Q&A

©

ROS1-Targeted Therapy

Crizotinib and Entrectinib in ROS1 Fusion-Positive NSCLC‘

Probability of PFS

No, at Risk
Gran

1 Shan AT et al N Engl J Med, 2014:371:1963-19.2, Dron A et a. Lancet Oncol. 2020:21:261-270.

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Crizotinib
Median PFS was 19.2 mo (95% Cl, 14.4 to NR)

Entrectinib

Median PFS was 19.0 mo (95% Cl, 12.2 to 36.6)

10
os
os
os
eos
ss En
Crizotinib
02
= Entrectinib
o o
y y y 5 > 2 0 y 3 ” = = E à
LS 53 43 37 32 2 15 8 6 6 6 3 1 1
so a 2 2 8 7 Ge) 2) 23 220) @ 0000000

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TRIDENT-1: Tumor Response per BICR With Repotrectinib
in TKI-Naïve Patients With ROS1-Positive Advanced NSCLC!

Change in Tumor Burden per BICR* DOR

8

Patients in Response, %

À ges o n= 1) 274 23 1.8)
1 wernt er none n=) ne Biene),

8

Maximum Change From
Baseline in Tumor Size, %
88 8

o
0 3 6 © 12 15 18 21 24 27 30 33 36 39 42 45
Time From First Response, mo

No.atRisk 56 54 49 48 30 32 22 17 13 8 3 2 1 1 1 0

3

# Treatment ongoing

* Ofthe patients in the ROS1 TKI-naïve cohort treated at the RP2D (n = 63), the CORR was 78% (95% Cl, 66-87)
and the median DOR was NE (95% Cl, 25.6-NE)s

Median flowup: 24.0 mo (ange, 14288 8)
Three patents did not have postbaselne tumor size measurement. ® By RECIST v1.1. 10% (n= 7) and 69% (n= 49) of patents had CR and PR, respectively. 95% Cl, 73-02 95% Cl, 68-00

‘ Number of events: 15; number of patents censored (%) 41 (73) 212: and 18-month DOR rates (95% Cl) were 85% (7585) and 80% (6982), respecte, "A
1.Cho BC et al. WCLC 2023, Abstract OAD3 0. PeerView.com

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TRIDENT-1: PFS and OS With Repotrectinib
in TKI-Naive Patients With ROS1-Positive Advanced NSCLC!

PFS os
m + Comore patents rn + Censored patents
#0 80
®
# © Es
€ o
É
« “
ers
» ee a pren)
A es a a e
0 3 6 9 1219 18 21 24 27 90 39 36 30 42 45 4851 0 3 6 9 1215182124272033363942454851 545760636669
Time From First Dose, mo Time From First Dose, mo
No. 71 64 50 52474 BD M 0 S111 10

No, atRisk 71686469598540922615107 433221111110

+ Ofthe patients in the ROS1 TKI-naïve cohort treated at the RP2D (n = 63), the median PFS was NE (95% Cl, 27.4-NE)?
and the median OS was NE"
Megan flow-up: 24.0 mo (ange, 14288 8),

85% Cl 6687. "85% Cl 56581, Number of events: 23; number o patents censored (%): 48 68) 295% Cl 8498, 85% CL £098." Number of events: 12; number ol pants censored (6) 59 (83).
2 12-and 18-monin PFS ates (05% Cl) were 78% (4-87 and 70% (5932) respectvely."12-and 18mont OS rates (95% Ci) were 02% (8599) and 88% (8068), respecte,
41. Cho BC etal WCLC 2023, Abstract OAD3.06.

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TRIDENT-1: Tumor Response per BICR With Repotrectinib
in Pretreated ROS1-Positive Advanced NSCLC‘

+ Patients had received a prior ROS1 TKI and no chemotherapy
Change in Tumor Burden per BICR®

MProrcizoënb MI Prorentrectind Prior certinib

commen onsen
Auen,

Perens (46) 20 2585)
Pret cn 10) 22040)

Maximum Change From
Baseline in Tumor Size, %
383858035338

# Treatment ongoing

DOR
10 + Censored patents
Es
H
go
é
Zo
2 Median DOR. mo (96% CN
¿a causo
3 AS

9 3 6 + 2 © 8 À A
Time From First Response, mo

NoatRisk 21 21 18 12 1 7 2 1 O

+ Ofthe patients in the 1 prior ROS1 TKI and no prior chemo cohort treated at the RP2D (n = 53), the CORR was 38%
(95% Cl, 25-52) and the median DOR was 14.8 mo (95% Cl, 7.5-NE)!

Mexianflowup: 215 mo (ange, 14258 8),

195% CL 66-87.» 09% Cl 50581, Number of evens: 23; number o patents censored (%): 48 68) 295% Cl 498, 85% Cl 60-98. Number of events: 12; number of pasents censored (6) 50 (83).

112 nd tmnt PES as C wen TE (LT) and TX 42 respecte "12 and Yeon OSes EK vr 82% (85) and BN COE) ce) D EE
iew.

1. Cho BC etal WCLC 2023, Abstract OAD3.06.

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com

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TRIDENT-1: Intracranial PFS With Repotrectinib in TKI-Naive
and -Pretreated Patients Without Baseline Brain Metastasis‘

ROS1 TKI Naive>< 1 Prior ROS1 TKI and No Prior Chemo**!

+ Censored patients

100 + Censored patents

Intracranial PFS, %
8 8 8

8

o
D 3 6 © 12 15 18 21 26 27 30 39 30 30 42 45 48

Time From First Dose, mo
No.atRisk 30 24 19 17 14 11 10 6 310000000

0 3 6 © 12 15 18 21 24 27 30 33 6 30 42 45 48
Time From First Dose, mo

No.atRisk 54 48 44 42 37 34 24 19 1512 8 5 2 1 1 1 0

+ Inn analysis of time to first intracranial progression only," none occurred within 18 mo of repotrectinib treatment
in both TKl-naive and TKI-pretreated patients

‘Medan flow up: ROS! Tine, 240 mo (ange, 142.668) 1 po ROS! TK and opi chemo, 21 5 mo ange, 142586)

Explora ana} naci PFS based on time of evelopment ol new ban lesions as asessed by BICR * Includes parts om phase 1 (n= 6) and phase 2(n= 48). “Number of events: 5.95% CL
185-10, includes palets from phase 1 (n=3) and phase 2 (n= 27) "Number events: 5. 68% Cl, 598.” nacranal PFS censored by neracanal progression or Seth 4
1.Cho BC etal. WCLC 2023, Abstract OAD3.06. PeerView.com

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TRIDENT-1: Clinical Update in TKI-Naive Patients

As of 15 Oct 2023, median follow-up in the TKI-naive cohort was 33.9 mo (range, 24.0-76.5) =

TKI-Naive TKI-Naive
n=71 n=71

CORR, % (95% Cl) 79% (68-88) Patients treated beyond progression
Pei ce) per BICR,Pn 2
Median DOR, mo (95% Cl) 34.1 (27.4-NE) Median duration of treatment 2.8 (0.1-46.6)
post-progression,* mo (range) PRE
DOR 2 24 mo, % (95% CI)" 70% (57-83) 21 moin (%) 16(67)
a
Median PFS, mo (95% Cl) 38.7 (24.6-NE) 23mo* n (x) 12 (50)
26 mon (%) 6 (25)
PFS at 24 mo, % (95% Cl) 63% (51-75) 212 moin (%) 3(12)

"Among responders. "Per BICR, 28 pis had progression. “Only includes patents who continued treatment beyond fest progression.
“Percentages based on number of patents who continued treatment Beyond frst progression. PaerVj.
1. Orion AE etal ASCO 2024. Abstract 8522, PeerView.com

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TRUST-I: Taletrectinib in ROS1 Fusion-Positive NSCLC‘

2
9
2
2
2
5

BOR of TKI-Naïve Patience (n = 66)

Pretreated Patients (n = 34)

“o moran msomro so ae

x © “o
£0 “0
ja 52
do do
E E-
¿> Bin
“oo “ 40
y E
2 B20
a. ö

10 a

Patents eo + + + os . e % .
in tr mais er
Responses Tieren Easy 1
IRC-assessed CORR, % (95% CI) 925 (834-975) IAN NON EAN
oe PR DCR (65% cn 1.0(657.023)
Median TR. mo range) 14024)

Man TTR, mo (ange) 141242) ges CES
MDOR, mo (min-max) NR (1327.8) PFS, mo (imax) 98 (00235)
PFS, mo (oir) NR 0020) 620228 OR, (u) 20.0)
1.LiWet al. ELCC 2023. Abstract 14MO. PeerView.com

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TRUST: Efficacy and Safety of Taletrectinib
in ROS1 Fusion-Positive NSCLC"

TKI-Pretreated
(n=65)

Median Follow-Up, mo 97
ORR, % (95% Cl) ee EN « ac + The most frequent TEAEs were AST

E y increase (76%), diarrhea (70%), and
IC-ORR in patients with measurable 88% 75% ALT increase (68%)
baseline brain metastasis, % (95% Cl) (47, 100) (48, 93) + Rates of neurologic TEAES were low

. (dizziness: 23%; dysgeusia: 10%)
ORR in patients with G2032R mutation, NA 67% and mostly grade 1
% (95% Cl) (85, 90)
+ Discontinuation (5%) and dose

Median DoR (IRC), mo NR 10.6 (6.3, NE) reductions (19%) due to TEAEs
12-month DoR 84% (75, 91) 48% (23, 69) were low
24-month DoR 79% (67, 87) 40% (17, 63)
Median PFS (IRC), mo NR 7.6 (6, 12)
12-month PFS 76% (66, 83) 34% (20, 49)
24-month PFS 71% (59, 79) 18% (7, 34)
1.LiW'et al ASCO 2024, Abstract 8520. PeerView.com

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TRUST: Taletrectinib in ROS1-Positive NSCLC

Pretreated (n = 60) =

TKI Naive (n = 104)

5 mcr PR eso ae pr SO = PD
23 so
E ag
3 po
5 eg”
ö EA
FR 55 o
35 Es 2
& 88 4
% LE 0
33 da »
3 00
Ga man + él Se lee

Prior chemotherapy me
Prior chemotherapy à

+ IRC-assessed CORR was 90.6% (95% Cl, 83.33 to 95.38) with + IRC-assessed CORR was 51.5% (95% Cl, 38.88 to 64.01) with
four (3.8%) patients achieving CR and 92 (86.8%) achieving PR 34 (51.5%) patients achieving PR
+ The DCR was 95.3% (95% Cl, 89.33 to 98.45) + The DCR was 83.3% (95% Cl, 72.13 to 91.38)

+ Median DOR and median PFS were not reached + Median DOR was 10.6 mo (95% Cl, 6.31 to NR)
+ Median PFS was 7.6 mo (95% Cl, 5.52 to 11.96)

1.LiW'et al. J Gin Oncol. 2024:00:1-11. 2. Li Wet al. ASCO 2024. Abstract 8520. PeerView.com

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TRUST-II (NCT04395677): Taletrectinib
in ROS1 Fusion-Positive NSCLC‘

Efficacy in ROS1 TKI-Naive Patients Efficacy in ROS1 TKI-Pretreated Patients
8
CORR: 92% (95% Cl, 74.0-99.0) É = CORR: 57.1% (95% Cl, 34.0-78.2)
ax
350
=
ago
sö
Fr
HE
8% 40
Zo.
Im
Brain metastasis . oe ee 6 ee Brainmetastasiso. 0 0... oe ee
Prior Prior
chemotherapy . .. . chemotherapy °° . e. 00 000.
ProrTki CCCCCCCCCCECECECCCCEC
1. Perot Metal. ESMO 2023, Abstract 1373P. PeerView.com

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Zidesamtinib (NVL-520)',

ARROS-1: Phase 1/2 Study of NVL-520 in Patients With Advanced ROS1-Positive NSCLC

Zidesamtinib (NVL-520):

A TKI designed to overcome | NSCLC response-evaluebl 2 > $“ 7
the limitations of currently | Patent”
available ROS1 TKis by | ORRIRECST 11.008) 10.40) 109) sas on
maintaining activity against | Bestresponse
ROS1 resistance mutations, PR 10 7 8 0 9
having brain penetrance, and | so . 2 2 6 7
avoiding TRK inhibition’? | po 2 o 1 1 1
Ne 1 o o 1 1
+ NVL-520 induced tumor response across heavily 2533 H ¿
pretreated patient populations Bars PE |
+ Radiographic tumor regression observed across all “ae 1
NVL-520 dose levels PERRET

1. Tangpeerachaikul À et a, AACR 2024, Poster LB182. 2. Dion A et al. ENA 2022. Abstract 8

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Lorlatinib in TKI-Naïve, ROS1-Positive NSCLC‘

A single-arm, phase 2 study evaluating lorlatinib in TKI-naive patients eS

All patients

+ ORR: 69% (95% CI, 52 to 83)

+ The median PFS: 35.8 mo (95% Cl, NR to NR)
+ OS: NR

Treatment-naive vs previously treated patients
+ ORR: 81% vs 46% (p = 0.042)

+ PFS: NR vs 13.9 mo (p = 0.25)

AEs

+ The most common 3-4 grade TRAEs were hypertriglyceridemia (8 [25%] of 32 patients) and
hypercholesterolemia (5 [16%] of 32 patients)

+ No treatment-related deaths were reported

1. Ann BG et al. ASCO 2024. Abstract 8518. PeerView.com

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Expert Panel Discussion

and Q&A

©

NRG1-Targeted Therapy

NRG1 (Neuregulin1) Fusions’?

* NRG1 fusions are rare driver events
— Present across tumor types
— Best detected with RNA-seq HER2 HERS

EGF-like
— Poor outcomes with standard therapy 5 sonen
* Several targeted agents in development
— Kinase inhibitors
y o NRG1 fusion
> Afatinib, tarloxotinib
— Monoclonal antibodies
> Seribantumab
— Bispecific antibodies
> Zenocutuzumab
PISK/AKT
(cell proliferation/survival)
1.Drion A eta. J Clin Oncol, 2021:3002003307. 2. Schram A et a. ASCO 2021. Abstract 3129, PeerView.com

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eNRGy: Zenocutuzumab in NRG1 Fusion-Positive Cancers!

uzumab blocks the binding of NRG1 to HER3 and >.

the dimerization of HER2 and HER3 =

o7
os
os
vs
03
02
0.

Zenocu

Median DOR: 14.9% (95% Cl, 7.4-20.4)
month rate: 81% (05% CI, 600-020).
12 mont rate: 579% (05% Ci, 340-750)

100

37.2% (95% Cl, 26.5-48.9, 29/78)

ORR (RECIST v1.1 per investigator assessment): AA
Clinical Benefit Rate: 61.5% (95% Cl, 49.8-72.3) +

Response Probability

0 24 6 8 10 12 14 16 18 20 22 À
Time, mo

+ Most TEAEs were grade 1 or 2 in severity
+ The most common TEAEs were diarrhea,
infusion-related reactions, and fatigue
+ No treatment-related discontinuations
+ No grade 5 treatment-related TEAES

Best Percentage Change
3

100
1. Schram A et al. ESMO 2023. Abstract 1315MO. PeerView.com

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RET-Targeted Therapy

LIBRETTO-001: Efficacy of Selpercatinib in Pretreated
and Treatment-Naïve RET Fusion-Positive NSCLC‘

Platinum Chemotherapy Treated (PAS or IAS)

With a median follow-up of 15.7 months, ¿e

“ las 58% (39/67) of responses are ongoing

y
©

ORR 61% (95% Cl, 55-67)

Change From

Change From Baseline by IRC, %

Patients With Response by IRC, %.
ostssessss

estes DOR, mo

4. Beste Bet al. ASCO 2021, Abstract 9065, 2, Don A etal J Cin Oncol, 2023: 41.385304.

PeerView.com/TFK827

Treatment Naïve

ORR 84% (95% Cl, 73-92)

ARA

5

With a median follow-up of 9.8 months,
76% (31/41) of responses are ongoing

2
E
en
82%
33:
gOS

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LIBRETTO-001 Update: Evidence on Robust, Durable Efficacy
of Selpercatinib in RET Fusion-Positive NSCLC’

Treatment Naive Previous Platinum
Response ‘Chemotherapy CNS Response

(n= 247)

‘Objective response by IRC, % (95% Cl) 84.1 (73.3-91.8) 61.1 (54.7-67.2) Objective response by IRC, % (95% Cl) 84.6 (65.1-95.6)
DOR

Median, mo (95% Cl) 202(13.0-NE) 286 (20.4NE) Best respon, 1.0%)

Censoring rate, % 552 609 CR 769)

1-y DOR, % (95% CI) 66.1 (516-773) 73.4 (649-79.7) ER SEIT

2y DOR, % (95% Cl) 41.6 (256-568) 55.8 (46.4-64.2) 18007

Median duration of follow-up, mo 203 212 so 4(154)
PFS

Median, mo (95% Cl) 2.0 (138-NE) 249 (19.3.NE) 2 A

Censoring rate, n (%) 37636) 138 (55.9) Could not be evaluated o

1-y PFS, % (95% CI) 70.6 (57.8-802) 705(41760) Ag oR

2 PFS, % (95% CI) 41.6 (268-558) 51.4 (44.3-58.1)

Median duration of follow-up, mo 219 247 Median, mo (95% Cl) 944153)
os

% 7.

Patients with censored data, n (%) 49 (71.0) 169 (68.4) un 7°

ty OS, % (95% CI) 92.7 (833-969) 87.9(830-91.4) 1-y DOR, % (95% CI) 36.1 (10.4-56.4)

2y 08, % (95% CI) 69.3 (552-797) 68.9 (622-747) 2y DOR, % (95% CI) 206 (6.5-402)

3.y OS, % (95% CI) 57.1 (359-736) 58.5 (497.663)

Median duration of folow-up, mo 252 264 Median duration of follow-up, mo 258
1.Drion A et al. ELCC 2022. Abstract 27P. PeerView.com

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LIBRETTO-431: First-Line Selpercatinib vs Chemotherapy
+ Pembrolizumab in RET Fusion-Positive NSCLC’

Key eligibility criteria
+ Stage IIIB-IIIC,* IV nonsquamous NSCLC.
+ No prior systemic therapy for metastatic disease
+ RET fusion identified via NGS or PCR

+ ECOG PS 0-2

+ Symptomatic CNS metastases excluded

Selpercatinib
160 mg BID

Stratification factors

+ Geography (East Asian vs non-East Asian)

+ Brain metastases (present vs absentunknown)®

+ Investigators choice of treatment with
pembrolizumab

pembrolizumab confirmed PD
crossover

+ Gated primary endpoints: PFS by BICR in ITT-pembrolizumab* and ITT population
+ Secondary endpoints:

- Efficacy (OS, ORR, DOR; CNS [ORR, DOR, time to progression])®

- Safety

— PROSs (NSCLC-SAQ [tertiary endpoint EORTC QLQ-C30))

Not suitable fr radical surgery or radiation therapy. Investigator assessed, © The inal randomization rao was 1:1 ut was amended 1 2:1. ©ITT-pembroizumab are patients strated wit
Investigator intent to receive chemotherapy with pembrolzumab and per protocol had to be 280% of the ITT population. * Baseline and longitudinal intracranial scans were required for a patente
{following an amendment. Prior othe amendment, longitudinal niracrania scans were required patents had known CNS metastases at baseine, eri

1. Loong HHF et al. SMO 2023, Abstract LEAS. PeerView.com

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LIBRETTO-431: PFS of First-Line Selpercatinib
vs Chemotherapy + Pembrolizumab'

ITT-Pembrolizumab Population PFS by BICR ITT Population
(Median Follow-Up ~19 mo) (Median Follow-Up ~18 mo)

HR = 0.465 (95% Cl, 0.309-0.699); P< .001 HR = 0.482 (95% Cl, 0.331-0.700); P <.001

so
a Selpercatinib Selpercatinib
mPFS: 248 mo PFS: 248 mo
x © (95% Cl, 169.NE) x © (95% Cl, 17 3.NE)
ña o
¢ ¢
© 0 {conics E 40 [convoi
mPFS: 112 mo
ap [195% CL Se 160) en
o o
D 6 RR nn a a E 0 6 À a À %
Time, mo Time, mo
No, at Risk No, at Risk
Seperetind 49 OS 72 4 4 2 0 Sep 19 10 0 2 4 à o
cool SS 1 6 0 9 Goma 4 8 3 1 7 1 o

The primary endpoints were met, as selpercatinib resulted in a statistically significant

improvement in PFS in both prespecified populations

1.Loong HF et al ESMO 2023, Abstract LBA4 PeerView.com

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LIBRETTO-431: PFS of First-Line Selpercatinib
in All Preplanned Subgroups’

Beeren consol Saber convoi
PES ROBER Mo Events Mo Event T TREC) PREDIC Mo, Events No, Event ee
‘vera CE a TE UITAT “Disease stage t
ao H age 2 à Yo os 00072761)
sy ex. 2 +=! o4r2(02080776) — SugeNA ou Eh 0585 0207-1108)
ar am” a D21 (0266-1028) Sue VB nom # = Hi orar,
sex ? ran messes ï
Female s 2 « 2 ra 0589 (0351-1020) — [Notuntnown 10.3. 0. 0. i 0470260762)
va “on % 2 += 0386(02120702) [ves » u 1 5 IH 0508 (0234.1.108)
Race H ver meisten i
san mos «2 ral da 2607%0 No muss Fa} ossesieoen
Mondrian sou . 2 Es 07501010 Yes eon 7 8 a ose 025110
region E Re tusion partner h
East sin % 2% 4 2 rai cazqurann | ccocs # 1 8 3 HA omas,
onEstasen ss 2 4 2 FE} ossuasuasre | Kise “ 2 4 2 PAL 04a
‘Smoking sus 7 nee DS A An 00022502)
Newer sus ei (0476 (0297-0763) Postiver een" FH 0648 (03201275)
Fommereurent = 44 15 24 13 ea 0526 0254-1.191) — PDA expression H
cos Ps H Poste s 2 » 2 Hi 0480(0282-0805)
owt CRE el 0500103820752) Negatve uo one 4 ones 02002716)
2 320038 m 0600572760 o sun EH mama)
o —
où 19 30 oot 19 se
—_— — —___ —
Favors solpercatinib Favors contol Favors selpercatinib Favors control
* Results rom PCR tess dd not specty RET fusion partner =
1.Loong HHF et al. ESMO 2023, Abstract LEA PeerView.com

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Intracranial Outcomes of First-Line Selpercatinib

ASCO Updates on Selpercatinib in NSCLC12

in Advanced RET Fusion+ NSCLC: LIBRETTO-431'

Cumulative incidence rates at 12 mo

Control
12 mo CIR

Selpercatinib
12 mo CIR

Site of PD

HRQoL and Symptoms in Patients Wi

RET Fusion+ NSCLC: LIBRETTO-4312 —

Results of TTCD of NSCLC-SAQ symptoms

Median Time, mo (95% Cl)

Hazard Ratio
(95% Cl)

Pts without
brain mets
at baseline
(n= 150)

Pts with
brain mets
at baseline
(n= 42)

Ns PO 1% 15%
nonCNSPD 20% 36%

Ns PO 26% 33%
nonCNSPD 22% 34%

Causesspecine MM uscuc-saa
HrforFirst MM Symptom
Event (95% Cl) Li

cough
0.17 (0.04 - 0.69) =

Pain
045 (0.15 1.36)

Dyspnea
061 (019-192)

Fatigue
048(027-084) poor appetite

Selpercainib Contra
NE NE
NE 88 (10,NE)
140(49,NE) — 26(13,70)
140(29,NE) 0804.29)
164(79,NE) — 23(10,58)

041(021,081 0.008

041(021,081) 0011
0.57 (036,091) 0015
054 (035,084) 0.005

045(028,072) «0.001

Selpercatinib delayed IC progression in advanced RET+
NSCLC patients with or without baseline brain mets

Selpercatinib significantly delayed time to confirmed
deterioration of NSCLC symptoms and improved physical
function vs control after 1 year of treatment

Chemotherapy + pembro,
1. Perol Metal ASCO 2024. Abstract 8547, 2, Zhou Cet a. ASCO 2024, Abstract 11068.

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ARROW: Updated Efficacy of Pralsetinib in Pretreated
and Treatment-Naive RET Fusion-Positive NSCLC"

Positive

ORR, %

(05% ch)

Best overall

response, n (%)

CR 16) 40)

PR oo) som

so 1

PO 1306) sm

NE sw 20)

DCR, % El 9
(26-04) (206)

7 2

(70-82) (6036)

DOR,median 223 NR

(95% CD mo (47NR) (GONR)

urable Disease Population.

Pre.

Eligibily
Revision

40
28 (0)
9 (19)
sm
12

El
7495)

74
(60-88)

10
AENA)

1. Gresinge Fetal, Ann Oncol 2022:33:1168-1178,

PeerView.com/TFK827

Eligibility
Revision

o

200

sa)
o

14)
96
(62-100)
80
0298)

NR
RAR)

76)

7364)

4302)
sm
76)

9

(0495)
7

6581)

23
US Nr)

o
1609)
418)
208)
0
El
(71-90)
7
(6592)

NR
CN

Treatment Naive

ORR: 72%

Prior Platinum-Based Chemotherapy

eT

ORR: 59%

PeerView.com

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EP0031 in Patients With Selective RET Inhibitor-Naïve
or Pretreated Advanced RET-Altered NSCLC’

Efficacy in NSCLC

+ In eight response evaluable NSCLC patients,
four cPRs were observed in seven SRI

pretreated patients, of which two patients
had cCR in the brain, and one SRI-naive
patient had a cCR

1. Garralda E et al ASCO 2024. Abstract 8556.

PeerView.com/TFK827

Safety in All Solid Tumors

No DLTs were observed

Most frequent G1/2 TEAEs (215%) were
constipation, headache, ALT/AST, anemia,
blurred vision, and dizziness

G3 TEAEs were rare and included (25%):
hyponatremia, anemia, hypertension, and
diarrhea

Dose interruptions, reductions and
discontinuations were seen in eight, three,
and one patient, respectively

PeerView.com

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LIBRETTO-432: Stage IB-IIIA RET Fusion-Positive NSCLC
Adjuvant Phase 3 Study!

Adjuvant selpercatinib vs placebo in stage IB-IIIA RET fusion-positive NSCLC

Selpercatinib
Patients with stage 1B-IIIA 160 mg BID
RET fusion-positive NSCLC Stratification (120 mg BID for
» Received locoregional
definitive therapy once rh
(surgery or radiotherapy) o
No evidence of disease + Prior definitive

recurrence following therapy (surgery
definitive therapy as well vs radiotherapy)
as adjuvant therapy

+ Secondary endpoints: EFS in overall population, OS, and time to distant disease recurrence in CNS

* Crossover to sepercatin alowed only at disease recurrence or progression (per RECIST 1.1 andlor hisopatholoica confirmation) PaerV/j.
1. Tsuboi Metal Future Oncol 2022.18:3139-3141 PeerView.com

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Trastuzumab Deruxtecan (T-DXd)'4

36
>
1 4
zo po
12 Gene residue
© Drug inter

Conjugation Chemistry
The linker is connected to cysteine
residue of the antibody

ADC composed of three components
— Humanized HER2-targeted mAb

— Topoisomerase | inhibitor “payload”
— Tetrapeptide-based cleavable linker

ys

High drug-to-antibody ratio (~8:1)

High potency payload that is
membrane permeable > nearby cells
in tumor targeted regardless of HER2

Payload (DXd) expression (“bystander antitumor effect”)
Exatecan derivative

“etal, Chem Pharm Bul (Tokyo) 2019:87:173-185. 2. Optan Y et al. Clin Cancer Res. 201822 087.5108, %
A etal. Pharmacol Ther 2018:181:126-142. 4. Optan Y et al. Cancer Se. 2016:107: 1038-1046, PeerView.com

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DESTINY-Lung01 Cohort 2: Updated Efficacy Results
of T-DXd in HER2mut NSCLC"

Updated data: 7 mo additional follow-up

+ Confirmed ORR by ICR in overall population:
54.9% (95% Cl, 44.2%-65.4%) Best Percentage Change From Baseline in Target Lesions by ICR for the
+ Confirmed ORR by ICR similar across Overall NSCLC HER2mut Population (DCO December 3, 2021)

subgroups (54.5% [95% Cl, 36.4%-71.9%]
and 55.2% [95% Cl, 41.5%-68.3%] in pts
with/without CNS metastases; 55.7%
[95% Cl, 42.5%-68.5%] in pts with <2 prior
lines of therapy and 53.3% [95% Cl,
34.3%-71.1%] in pts with >2 prior lines)

+ Median DOR in overall population: 10.6 mo

+ Median DOR in pts with/without CNS
metastases at baseline: 7.2 mo (95% Cl,
5.3-11.1 mo)/14.7 mo (95% Cl, 5.7 mo-NE)

+ Median DOR 14.1 mo (95% Cl, 5.9-NE mo)
with 52 prior lines of therapy vs 5.8 mo (95%
Cl, 4.2-12.0 mo) with >2 prior lines

Best (Minimum) Change, % (n = 85)

Best Change in Sum of Diameters From Baseline, %

HUB et al ESMO 2022. Abstract 976P. PeerView.com

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DESTINY-Lung02: Efficacy of T-DXd in HER2mut NSCLC12

100 PFS:
=
Es «co
a Loxa 64 mons
E roxsanots
5 «
rer
O A le
man 5
a rel
PBETZLTEZTLITITTITETTTN
Tie, mo
os
F 0 + Consored cases:
ge 191454 ne
5 60
ha Be
1° sant SUR
2 TIO Te
Eo eae oe
o

0123486 7 8 0 10111213141516171819202122

Time, mo

1. Janne P et al. WOLC 2023, Abstract MAT3.10.2. Goto K eta. J Cin Oncol. 2023:41:4852-4863

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Confimed ORR, (%6)(95% Cl] 50(49.0)(39.0-59.1] 26(560)413-700]
10) 2(40)
49480) 26 (620)
45.4.1) 18660)
439) 240)
Nonevaluable 309) 240)

DCR, n (%) [95% CI SENT 46 (92.0) (808.978)

Median DOR, mo(95% CI) 16.8 (64-NE) NE (83:08)

Median TTIR, mo (range) 18(1270) 1502112)

Median Folow-up, mo (range) 1151208) 11806210)

Best Percentage Change In Tumor Size by BICR With T-DXd 5.4 mg/kg
(N= 102)

Responses were observed regardless of HER? mutation type, HER2
fication status, and number or type of prior thera

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DESTINY-Lung02: Overall Safety of T-DXd
in HER2mut NSCLC*?

Overall Safety Adjudicated Drug-Related ILD
I FOX 54 m9ñg I T-OX 64 moño

Drug-Related TEAE, %

acc | y aceso 4329) 1429
Grade 23 ioe © __] cante Fr +
en EM rez 109 son

Asco vio contrae ss » |
Associated with dose reduction Les > | fu oe a
‘Associated with drug interruption Ben | cease ® e
soto wih des aa Grae 5 © 10

+ Median treatment duration was 7.7 mo (range, 0.7-20.8) with T-DXd 5.4 mg/kg and 8.3 mo (range, 0.7-20.3) with T-DXd 6.4 mg/kg

+ The most common any-grade TEAES in the T-DXd 5.4 mg/kg and 6.4 mg/kg arms included nausea (67.3% and 82.0%),
neutropenia (42.6% and 56.0%), and fatigue (44.6% and 50.0%)

+ The most common grade 23 TEAES in the T-DXd 5.4 mg/kg and 6.4 mg/kg arms included neutropenia (18.8% and 36.0%) and
anemia (10.9% and 16.0%)

* The safety analysis setincuded a random assigned patents who received 21 dose of study drug. rn
1.Jänne P et al WCLC 2023. Abstract MA13.10. 2. Goto K et al. J Cin Oncol, 2023:41:4852-4863, PeerView.com

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DESTINY-Lung02: Final Analysis Results of T-DXd
in HER2mut NSCLC‘

Efficacy Summary E

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

+ Grade 23 TEAEs were reported in 39.6% and
60.0% of patients in T-DXd 5.4 and 6.4 mg/kg
ams

(n = 102) (n = 50)

+ Lower rates of TEAES associated with drug
CORR," % (95% Cl) 50.0 (39.9-60.1) 56.0 (41.3-70.0) discontinuation (14.9%), dose reduction
(16.8%), and drug interruption (30.7%) were
observed with T-DXd 5.4 mg/kg than 6.4 mg/kg
Median DoR,* mo (95% Cl) 12.6 (6.4-NE) 12.2 (7.0-NE) (26.0%, 34.0%, and 54.0%)

+ Adjudicated drug-related interstitial lung disease
(ILD)/pneumonitis was reported in 14.9% and

Median PFS,* mo (95% Cl) 10.0 (7.7-15.2) 12.9 (7.2-16.7) 32,0% of patients in the T-DXd 5.4 and 6.4
mg/kg arms, respectively; most events were
grade 1 or 2 (1 grade 5 event in each arm)

Median OS, mo (95% Cl) 19.0 (14.7-NE) 17.3 (13.8-NE)

‘Plame PA tal ASCO 2024. Abstract 854, PeerView.com

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DESTINY-Lung01: Efficacy of T-DXd
in HER2-Overexpressing Cohort

T-DXd 5-4 mg/kg (N = 41) HERO (HOS)
#1] Baseline HER? IHC status Efficacy Parameter
= IHC 2 (a= 17)
ol MIKC3+ (n= 17)
7 CORR, % (95% CI) 278,770)
Ir)
dE” a ‚eh
¿bo Partial Response Rate, % 471
ig»
a Duration of Response, mo 69
(ange) (40,11.74)
10
On April 5, 2024, the FDA granted accelerated approval to T-DXd for patients with
unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received
prior systemic treatment and have no satisfactory alternative treatment options
1. Smit EF et al. Lancet Oncol. 2024:25:430-454, PeerView.com

Copyright © 2000-2024, PeerView

BAY
2927088

Other HER2-Targeting Agents in Development

HERZexon20 __

insertion TKI AA

Zongertinib

NVL-330

HERZ tyrosine kinase

‘domain mutation TKI Free

HER2-selective TKI Pre-clinical

1. Girard Net a, ASCO 2024, Abstract LEASE

PeerView.com/TFK827

Safety and anti-tumor activity of BAY 2927088 in
patients with HER2mut NSCLC: Results from an

expansion cohort of the SOHO-01 phase I/II study!
In patients with heavily pretreated HER2mut NSCLC, treatment
with BAY 2927088 resulted in rapid, substantial, and durable
response

The safety profile of BAY 2927088 was manageable and
consistent with previous reports

Changes in ctDNA levels may be an early indicator of clinical
benefit

These data support the further clinical development of BAY
2927088 in patients with HER2mut NSCLC

PeerView.com

Copyright © 2000-2024, PeerView

Beamion LUNG-1: Zongertinib as Monotherapy
in HER2mut NSCLC12

WSCLe Pron WERZ _Prertoxa
Due sn (MESA
10
| om E E E =
£ vor o 7 e e +
go ==
= ==
Ls =
ga ==:
530 H==:
“3 ===
33» ==
380 =
ge : a
3° = Mso
E =] A PO
+ > Ongoing (57.4%)
00 =

© So 100 150 200 250 300 350 400 450 500
Time, d

In 36 evaluable patients with NSCLC,
+ ORR was 58%
+ DCR was 97%
+ Median PFS was NE (95% Cl: 7.6 mo-NE)

Data et 15 September 2023.
* Evaluable patients defined as those wih 21 postbaseline tumor assessment or disconinued before frst assessment or any reason. ° Kaplan-Meier estimate BUE
1. Wu YL etal. ELCC 2024, Abstact 4P. 2. Heymach J etal ASCO 2024. Abstract 8514. PeerView.com

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Expert Panel Discussion

and Q&A

Dabrafenib + Trametinib in Patients With Previously
Untreated BRAF V600E-Mutant Metastatic NSCLC12

100 5-Year Updates
90
so Pretre Treatment Naive
an (Cohort B) (Cohort C)
5 œ (n= 57)
ES Best response, n (%)
pe CR 36) 216)
20 PR 36 (63) 21 (68)
” Stable disease 7012) 4)
u u > Es PD 7012) 5(14)
ona Wea nie NE m 401)
m 40 m tm Tan OC Response rate
100 A y CR + PR, n (%) 39 (68.4) 23 (63.9)
08: 24.6 mo (95% CI, 12.3-NE) exch (648-801) (462-792)
Disease control rate
CR + PR + stable disease, n(%) 46 (80.7) 27 (75)
(95% CN 68.1-90.0) (678879)

+ ORR was 68.4% and 63.9%, median PFS was 10.2 and 10.8
months, and median OS was 18.2 and 17.3 months in pretreated
and treatment.naive patients, respectively

+ The 4- and 5- year survival rates were 26% and 19% in pretreated

08, %
05838588388

0 5 © 5 2% 2 0 % 40 patients and 34% and 22% in treatment-naive patients, respectively
1. Planchard D et al. Lancet Oncol. 2017:18:1307-1318, 2. Panchard D et al. J Thorae Oncol 2022:17:103-115. PeerView.com

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PHAROS: Encorafenib + Binimetinib in Patients
With BRAF V600E-Mutant Metastatic NSCLC‘

Change From Baseline in the Sum of Diameters of Target Lesions by Investigator Assessment

ORR: 75% ORR: 46%
Treatment Naive (n = 57) Previously Treated (n = 35)

100 100

ex we

E 5 120

3 4 ¿e

El Bs
pe 5

bo EZ

A = ©

8 x» Bo

§ 40 52

qa 40

0

+ +

00 00

Complete response | MPartalresponse Stable disease Progressive disease — MNOL evaluable
1.Reiy G et al. ASCO 2023, Abstract 9018 PeerView.com

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PHAROS: PFS of Encorafenib + Binimetinib in Patients
With BRAF V600E-Mutant Metastatic NSCLC’

PFS by IRR
‘Treatment Naive (n = 59) Previously Treated (n = 39)

had PFS events, n (%) 21 (36) suo PFS events, n (%) 17 (44)

» frends MO NETA) Finnois sank)

»
zu x
go 2
Ee É

»

»

a

N o

POEtET TERETE TPE TT EPRELTLITTTTEET ET
Time, mo Time, mo

No. at Risk
Prodi tested 39 27 23 18 15 12 10 7 6 8 4 4 3 5 2 2 0 0

No at Risk
Tresment nave $9 54 45 38 36 33 90 28 25 19 14 14:12 8 7 7 2 0

1.Reiy G et al ASCO 2023, Abstract 9018, PeerView.com

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PHAROS: Safety of Encorafenib + Binimetinib
in Patients With BRAF V600E-Mutant Metastatic NSCLC’

Incidence of TRAEs of Any Grade >10% in All Patients

Overall (n = 98)
Any Grade Grade 3 Grade 4
‘Any TRAES, n (%) 92 (94) 37 (38) 38),
u ras za) 5 TRAE ofany grade, grade 3, grade 4
$ occurred in 94%, 38%, and 3% of 98

Diarthea 42 (43) 4) 2 tients, respectivel
Fatigue 31 (32) 2(2) o p Tepe
Vomiting 28 (29) 1(1) o + TRAEs led to permanent discontinuation
Anemia Ei) 3.0) o of both encorafenib and binimetinib in
Vision blurred 17 (17) 1) 0 15 of 98 patients (15%)
Constipation 13 (13) o 0
ALT increased 12(12) 5(5) 0 + The most frequent TRAES that lead to
AST increased 12 (12) 7(7) o permanent discontinuation were diarrhea,
Pruritus 12(12) o o nausea, and vomiting
Blood creatine
phosphokinase increased non E E
Edema peripheral 111 o o

1.Rely G etal, ASCO 2023. Abstract 9018, PeerView.com

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Expert Panel Discussion

and Q&A

MET-Targeted Therapy

GEOMETRY mono-1: Capmatinib in METex14 NSCLC’

Best Response to Capmatinib—MET Exon 14 Skipping Mutation Progression-Free Survival--MET Exon 14 Skipping Mutation

MM Complete response — IM Partalresponse MI Stable disease

Previous reaiment
gm
EM
55»
382 2
580 E
¿das =
$ Eso.
gen
E 0
Patients treatment
+ The most frequently reported adverse events were peripheral
‘edema (in 51%) and nausea (in 45%); these events were r
mostly of grade 1 or 2 so
1.WollJetal. N Engl J Med, 2020:383:244:957. PeerView.com

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VISION: Tepotinib in Patients With METex14 NSCLC’

Outcomes Following Tepotinib Treatment in Cohorts A and C According to Line of Therapy?

outcome T Postive T Postive T Poative
andlor L Positive andorL peatve andior Postive
near
"OR
(05% cn Wr 73612) (441-802) assers) 484869) (92508) sun
DCR. % 208 no ER 784 ors
5% Ch garsse) (m 756-004 seo) (603774
Megan GER ON Te LE 24 12 124
Pen mo (124464) (08464 MT (IBBNE) (1S2NE) BEE) (95185) WE — (64350)
De TOUS) WW AM) N) ZI) 250408) EM 24663) 2066)
Tezan GR OT Tz 737 a Fe TS 77 a
mo 0538) mom) as) rn (mon 2137) sro
En SD 1011486) Hrn _1 494) 50145) SE ME SIR sm
Tieden GX CT Tee 25 F5 73 27 TE LE En TZ
me (182229) (188285) 20213) (42259) KEN (10423) (158223) (70285 120210)
Events,
nc)
ame ae, % 72 75 68 es 74 so 68 72 60
(65% Ci) (590810) (690860) 620800) WET) (MD) (090880) (590750 (620400 (80720)
24m rte, % se st 47 “ 55 E 38 «2 ES
(osc) 050300 (7000 groso 60520) 440640) wm moto 20820) poso

+ Among 164 treatment-naive patients, ORR was 57% (95% Cl, 49.0-65.0), with 40% of responders having a DOR 212 months;
among 149 previously treated patients, ORR was 45% (95% Cl, 37.0-53.0), with 36% of responders having a DOR 212 months

|} posiviy was determined by detection of METEX 14 skipping in issue biopsy sample: L positiv by detecton of METext4 skipping in quid biopsy sample.
* One treatmentnaive patent had a complete response; al other objective responses were partal responses, DaerVi
1. Mazieres Jet al JAMA Oncol 2023.9.1280-1260. PeerView.com

200(39) 120(77) 1280108) 98 (598) s5 495) 64,674) 102.685) sen aan

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Savolitinib: Targeting METex14 Mutation’

Savolitinib is approved in China for the treatment
of NSCLC patients that have progressed following prior
systemic therapy or are unable to receive chemotherapy
with MET exon 14 mutation

IRC Assessment

Treatment
Naive
(n=87)

Previously
Treated
3)

Treatment

Naive
ee)

Previously

Tr

Time, mo

PR 54621) 31(392) 52 (59.8) 24 (43) ES
so 26(29.9) 41(519) 28(322) 394)
|Non-CRinon-PD, o 103) o o

po sn 461) son 563)

NE 2(23) 2(25) 2(23) 1(13) A
ORR 43 62.1) 21 (39.2) 52 (59.8) 34 (43) 3
Exact 95% CI 510723 284509 487-701 31.9547 Ê
DER 80 (92) 73 (824) 80 (92) 73.924) 3
Exact 95% CI 841967 842972) 641967 842972

mDOR 125 111 125 11

(95% Cl), mo (63-152) (G6NE) (O7-NE) (82-168)

Fu 14(1415) 16(1427) 14(1414) 14(14-16)

(95% Ch, mo

1. Zhang YC. ELC 2024. Abstract 1MO.

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SAVANNAH: Osimertinib + Savolitinib in EGFRmut
and MET-Positive NSCLC Post Osimertinib!

Preliminary Efficacy Data?

All Patients Patients With High Patients With High Patients With
((HCS0+ and/or Levels of MET? Levels of MET? Lower Levels
Endpoint FISHS+) (IHC80+ and/or FISH10+) _(IHC90+ and/or FISH10+) of MET?
N=193 All: n= 108 No Prior Chemo: n = 87 77
ORR, % (95% CI) 32 (26, 39) 49 (89, 59) 52 (41, 63) 9(4, 18)
Median DOR, mo (95% Cl) 83(69,97) 9.3 (76,106) 96 (7.6, 149) 6:9 (4.1, 169)
Median PFS, mo (95% Cl) 53 (42,58) 7163,80) 72 (47,92) 28 (26,43)
DCR, % (95% CI) 61 (53, 68) 74 (65, 82) 75 (64, 83) 43 (82, 55)

* Analysis data cut-off 27 August 2021. Eight patients excluded from subgroup analyses due to invalid or missing test results A
1-Ahn Med et al WLC 2022 Abstract EPOB.02-140 PeerView.com

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LUMINOSITY: Telisotuzumab-Vedotin (Teliso-V) Monotherapy

LUMINOSITY: A phase 2 study evaluating teliso-V in locally advanced/metastatic c-MET
overexpression (OE) NSCLC, <2 prior lines of therapy (chemo + IO or sequential chemo + 10),
and <1 line of chemotherapy

MET Intermediate ET OE Total
n=83 n=161
A 27 (34.6) 19 (22.9) 46 (28.6)
OR 1 (26) [85% Cl] (24.2, 46.2) (14.4, 33.4] (21.7, 36.2]
. 47 (60.3) 48 (57.3) 95 (69.0)
o [96% CH: (48.5, 71.2] (46.5, 68.6] 151.0, 66.7]
E 90 72 83
Median DOR,* mo [95% CI] (42, 13.0) 153,118) 156, 11.3]
DOR® 26 mo, nino. of responders (%) 17/27 (63.0) 9/19 (47.4) 26/46 (56.5)
rar ss 60 87
Median PFS.* mo [95% CI] (44.83) 45,84] 146,69]
146 142 145
Median OS, mo [95% CI] 192,256] 19.6, 16.6] (99, 16.6)
Median follow-up, mo 202 1 19,
per pr :
4 Samiage DeL ASCO 2024 Attac 108, PeerView.com

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Maximum Change in Target
Lesion Size, %

Sssss.ussss

1. Lin J et al, ASCO 2023, Abstract 0058.

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hen 008. mois

Larotrectinib in NTRK Fusion-Positive Cancer:
Long-Term Efficacy’

acy
won

wits CNS metastases

6 12 18 2 30 36 42 4 & 60 66 72 78
‘Overall Treatment Duration, mo

nee o ES MOR OI 5 mcr 230728)
eos Eo aor ceo meiomo A IAE
Am CT) A Biene Memos sere) Dr

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Entrectinib in NTRK Fusion-Positive Cancer:
Long-Term Efficacy’

Best Percent Change From Baseline per BICR

Bost % From Baseline, %
Sesboxeas

Individual Points

"Wit boseine CNS CRVPR(n=20) MSD(n=4) MPD(n= 1) NEND(n=2)
rasa

As assessed by investigatr. ?BICR-assessed, RECIST v1.1
41, ho BC etal ASCO 2023, Abstract 9047.

PeerView.com/TFK827

‘ORR, n (XP
(95% CI)

Complete/partial
response

Stable disease
Progressive disease
Non-CR/PO
Unevaluable
mDOR, mo (range)?
mPFS, mo (range)?

Overall Efficacy

Baseline CNS No Baseline CN:

All Patients

Meta Metastases"
katt) m 6)
20 (64.5) 9 (60) 11688)

(45.4808) (23837) (413-890)

5(16.1)/15(48.4) 1 (6798 (53:3) — 4(25/7(438)

4129) 300) 163)
162) 167) o

sen o 3088)
sen 20133) 163

271(148204) 294(66:294) — 199(104NE)
208(138304) 303(47-304) 208 (14.9-NE)

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TRIDENT-1: Efficacy of Repotrectinib in Patients With
NTRK Fusion-Positive Solid Tumors (EXP5 and 6)!

Efficacy in TRK TKI-Naive and TKI-Pretreated Patients With NTRK+ NSCLC.

On June 13, 2024, the FDA granted
accelerated approval to repotrectinib for
adult and pediatric patients 12 years and
older with solid tumors that have a NTRK

TRK TKI-Naïve Patients TRKTKI-Pretreated Patients
With NTRK+ NSCLC With NTRK+ NSCLC
(n=21) (n=14)

oy = (95% Cl) 62 Fi oi 0) AU TE y gene fusion, are locally advanced or

PR) 11662) EST metastatic or where surgical resection is
‘CBR, % (96% CI) 86 (640.970) 67 (290-820) likely to result in severe morbidity, and that
12-m0 DOR, % (85% CI) 92 (76.0-100.0) 44 (1.0880) have progressed following treatment or
12:m0 PFs, % (95% CI) 64 (43.0-860) 2300490) have no satisfactory alternative therapy.
Median time to re smo (range) 18(1639) 1941820

TRK TKI-Naive Patients NTRK+ Solid Tumors TRK TKI-Pretreated Patients With Solid Tumors

E ie
FH i

of patients, respectively, had SD or PO. CBR was defined as CR + PR +50;
14% (n= 2) and 21% (n= 3) of patents, respectively. had SD or PD, DaerVi
1. Solomon BJ etal. ESMO 2023. Abstract 1372P. PeerView.com

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“KRAS-Positive” No Longer an Adequate Characterization’?

KRAS: 30% of all lung adenocarcinomas

KRAS G12C is the most common variant: 13% of all lung adenocarcinomas

1. Should F, Heymach JV. Nat Rev Cancer. 2019:19:495-509, 2. Amour KC etal. Clin Cancer Ros. 2018:24:334-340, PaerVj.
3. Schefler M eta J Thorae Oncol 2019;14:608-6%6, PeerView.com

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CodeBreaK 200: Sotorasib vs Docetaxel
in Pretreated NSCLC With KRAS G12C Mutation’

2-Year Analysis
+ ORR was 41% (95% Cl, 33.3 to 48.4), and DCR was 84% (95% Cl, 77.3 to 88.9)

+ Of patients with confirmed response, estimated 72.8% (95% Cl, 60.0 to 82.2) and 50.6% (37.4 to 62.4) remained in
response at 6 and 12 months, respectively

+ Median DOR was 12.3 months (95% Cl, 7.1 to 15.0)

10 19
Bos Bos
au Main PS (95% CH me: 30 Macia 05 (95%
20 5688 2% 125m 10070)
Pos 20
Eos gu
g © ge
© ot Soi] Bess, i ren
o
of. 6 8 OR 16 10 20 mM do a 0245 8 10 12 14 10 10 20 22 24 26 20 90 92 4 36
Time, mo Time, mo
o. o.
AAA 174 19 141121101 88 77-71-65 RA
1. Dy GK et al J Gin Oneol 2023:41:3311-3917. PeerView.com

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CodeBreaK 200: Sotorasib vs Docetaxel
in Pretreated NSCLC With KRAS G12C Mutation’

PFS by BICR CNS PFS in Patients With CNS Lesions at Baseline
Satine Ei is
ge She m een nn
¿e = FA ay fe
i. if
E
SE
OT 1e 1 RU Ut EN Là TER CS 5 à
EN
D Came conse e278 9 oo

1. de Langen AJ eta. Lancet. 2023:401:733-748, 2. Dingemans AM et al. ASCO 2023. LBAGOI6,

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CodeBreaK 200: Sotorasib vs Docetaxel
in Pretreated NSCLC With KRAS G12C Mutation’

Sotorasib 960 mg Docetaxel 75 mg/m?

mue one
“es ‘ses es EE
‘Overall response rate (95% Cl) 28.1 (215-954) — 132(86-192) Doa seed mer ot
MR GG) torera)
con ès sooo cosgarern
en i
Metin don legos mo XCD BETEN 6266283) ig js
dant ant men po its
1 sta boina
ae
o
ie qe
$ o 8 ry a
> HA
ES
A €
BESSERE ne oe IRTE 3 um

1. de Langen AJ eta. Lancet. 2023:401:733-748, 2. Dingemans AM et a. ASCO 2023. LBAGOI6,

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CodeBreaK 101: Sotorasib + Carboplatin + Pemetrexed
in NSCLC With KRAS G12C Mutation!

Grade 2 3 TRAEs occurring in > 5% of all patients Efficacy =
AL (n=37) 2L+(n=21)
Neutropeniaineutrophit
Sotorasib + Carboplatin + Pemetrexed
a ty Confirmed Response E
Vombocytopen :
wT by INV Assessment
Anemi
. ORR, n (%) 22 (65) 8(42)
ALT increased BOR, n (%)
CR o 1(5)
AST increased PR 22 (65) 7 (87)
so 12.85) 8.2)
Febrile neutropenia, PO 0 16)
NE 0 2(11)
Nausea
DCR, n (%) 34 (100) 16 (84)

"include a patients who received 21 dose of study drug had 21 measurable lesion at baseline per RECIST v1.1, and could be flowed for 27 weeks
staring tom day 1 Sat
ALU BT etal, ASCO 2024, Abstract 8512 PeerView.com

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KRYSTAL-1: Adagrasib in NSCLC With KRAS G12C Mutation’

Maximum Tumor Change From Baseline

Progression-Free Survival Overall Survival

“ wo Pr
E > EJ Median overall survival
tel progressiontree survival:
> secs 5 AA
» = BD
da 28 «=
a
En fo 8%
po 2 =
i cr eee E >
3 10 10 Î Î
se : ol
inet inci ENFRENTE
Ea) ES
_——— want nas 64e ma so

+ Of 112 patients, 48 (42.9%) had OR, mDOR: 8.5 mo
(95% Cl, 6.2-13.8), mPFS: 6.5 mo (95% Cl, 4.7-8.4),
MOS: 12.6 mo (95% Cl, 9.2-19.2)

Patents Witha Response

TRAËS occurred in 97.4%—grade 1/2 in 52.6%, 2 grade 3
in 44,8% (including two grade 5 events)—and resulted in drug
O12 34667 8 oon as ow 8 8 om discontinuation In 6.9% of patients

1. Janne PA et al. N Engl J Med. 2022; 387:120-131 PeerView.com

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KRYSTAL-1: Intracranial Efficacy of Adagrasib
in NSCLC With KRAS G12C Mutation!

ge
af
af
3
53 o
ER
ES

4100

1120 JProgressive disease
Patients

PFS,%
08388833888

Median PFS (85% CI}: 54 mo (27-NE)

o 2 5 2 ®
Time, mo
No, at Risk
% mos 3 2 i

1. Negrao MV et al JCO 2023; 41, 4472-4477.

PeerView.com/TFK827

.
E
i
7]
a)
34 |
Ho]
:
Time, mo
>

2 6 2 7 3 4

o
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KRYSTAL-12: Adagrasib vs Docetaxel
in Pretreated NSCLC With KRAS G12C Mutation!

Tumor response per BICR

Primary endpoint: PFS per BICR

ADA DOCE Ê
m men er Os ratio= 4.68 (05% CI, 256-856)
A In DE p< 0001
Fens, nO) 16455) 93161) x
” 35 38 Zz”
mPFS, mo €
PFS, mo SX CY asen ran En
z = HR (95% CI) 0.58 (0.45-0.76)
£. P press
ADA Doce
rim 0801 Hansa
ADA Tumor Response ADA
AT à
ES 236 (18) — 89159)
Time From Randomization, mo ae
art
pe we wm om mh tt + MOOR mo (SX CD 4-104) (29:85)
Pe 9 2 0 6 0 6 0
Remaining in Zu:

response at 6 mo, %

Median ftowup: 72 monts.
ORR is defined asthe percent of patents documented to have a confirmed CRUPR by BICR (per RECIST v1.1), "Disease con rate (OCR) is defined as he percent of

patents documented to have a conimed CRIPRISD by BICR (per RECIST v1.1) ar:

Y Mok TSK et al, ASCO 2024. Abstract LBA8S09. PeerView.com

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KRYSTAL-7: Adagrasib + Pembrolizumab in Patients With
Treatment-Naive NSCLC Harboring a KRAS G12C Mutation!

Maximum Change
Evaluable Patients

Patients

+ Confirmed ORR was 63% (32/51; 95% Cl, 48.0-76.0)

and DCR was 84% (43/51; 95% Cl, 71.0-93.0) TA u

+ Median time to response was 1.4 months ALT increase 13 1
+ Median DOR was NR (95% Cl, 12.6-NE) — cin ci ‘
+ Median PFS was not reached (95% Cl, 8.2-NE) Fatigue 10 4 o
Decreased appette 9 : o

Apaseincensed sg 1

+ 24 (16%) patients had grade 23 treatment-related ALT/AST increase
+ Treatment-related hepatic events occurred in <10% patients
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1. Garassino MG etal. ESMO 2023. Abstract LBAGS.

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KRAS G12C Inhibitor Olomorasib*?

LOXO-RAS-20001 study Olomorasib + pembrolizumab
AL Metastatic Previously Treated 7

Olomorasib monotherapy

ORR: 77% ORR: 40%

+ KRAS G12C inhibitor-naive NSCLC
= MPFS: 7.9 mo (95% Cl, 3-NE)

+ NSCLC with prior KRAS G12C inhibitor
treatment

- ORR was 41% (16/39), with 63% having
received a KRAS G12C inhibitor as their
immediate prior therapy

= _mPFS was 8.1 mo (95% Cl, 5.6-15.6)
+ Preliminary CNS activity was seen

Maximum Percent Change
From Baseline, %

‘Ongoing SUNRAY-01

irst-line olomorasib + pembrolizumab in patients with KRAS G12C NSCLC (PD-L1 250%) or olomorasib +
pembrolizumab + pemetrexed, platinum in patients with KRAS G12C NSCLC (regardless of PD-L1 expression)

1. Heist RS et al ASCO 2024. Abstract 3007.2. Bums TF et al, ASCO 2024. Abstract 8510. 3. Negrao MV etal, ASCO 2024. Abstract TPSB649, PeerView.com

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KRAS G12C Inhibitor JDQ443'

KontRASt-01 Part A: JDQ443 monotherapy in NSCLC

so String dose 1 200 mg QD II 400 mg QD Ill 200 mg 810 200mg ID Al Dose Laval
2 O Dome increase to 200 mg 810 =
so
Es Corée OBRA A An
EX 40
os
85” vor.“ wo ns
fie
¿en BOR, n (4)
LÉ
3 PR arn 12444)
a 0
u so 5057) 1348)
390
asen TED" mm mm
matos SP a Po o o
ats per REAP)
nN COLA u
Masten mn ape Data ot meta Unknom 100 204)
1. Cassier PA. ASCO 2023, Abstract 9007. PeerView.com

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KRAS G12C Inhibitor Divarasib*!

A phase 1 study of divarasib as a single agent in advanced or metastatic solid tumors that harbor a KRAS G12C mutation

est response 7 q”

Efficacy in NSCLC ¿e

HO

ga H

> = = - 2°
jo Time, mo

pe O

be 1

ic . PFS

Dose, mg

+ A confirmed response was observed in 53.4% of patients (95% Cl, 39.9 to 66.7)
+ The median DOR was 14.0 mo (95% Cl, 8.3 to NE)

Porcentage of Patients,
a8

+ The median PFS was 13.1 mo (95% Cl, 8.8 to NE). TE TEE
Time, mo
Do ee 48 97 2314 17 4 1 0
1. Sacher etal. N Engl J Med. 2023:389:710-721. PeerView.com

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Other KRAS-Targeting Therapies*-13

RMC-6291
BI 1823911

KRAS G12X, Garsorasib (D-1553)
excluding G12C

LY3537982
RMC-6236

JAB-21822
MK-1084
D3S-001

IB1351 (GFH925)
HS-10370

Avutometinib

MRTX1133

1. Arbour KC et al. ESMO 2023. Abstract 6520. 2. Reuss JE et al ASCO 2023. Abstract 9100. 3. ts classic clnicatils govietZIshowNCTOS737706. 4. Heymach J et al. ESMO 2023.
Abstract 665P. 5. Sacher A et al N Eng! J Med, 2023, 380:710-721. 6. Janne PA et al AACR 2023. Abstract PROT, 7. LIZM etal. J Thorac Oncol. 2023: 18 (7) 90-951.

8. Mts cinicahals govistudyINCTO495664O#partcipation-erteria, 9. its einialias gov'study/NCTO5002270. 10. tpscinicalrals gov/study/NCTOS410145,

11. ps classi cinicaitials goviet/showiNCTOSO05234. 12. htpsicicatials govistudyINCTO63457297intr=MK-10848rank=1 5

13: ts: felnialiials. govistudyNNCTOS367778 PeerView.com

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Decoding Biomarker Testing and Targeted Therapy in NSCLC: The Complete Guide for 2024

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Decoding Biomarker Testing and Targeted Therapy in NSCLC: The Complete Guide for 2024

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