Deploying the Immune GAMBIT Against Melanoma: Guidance on Advances and Medical Breakthroughs With ImmunoTherapy

Co-Chairs, Hussein Tawbi, MD, PhD, and Prof. Christian Blank, MD, PhD, discuss melanoma in this CME activity titled “Deploying the Immune GAMBIT Against Melanoma: Guidance on Advances and Medical Breakthroughs With ImmunoTherapy.” For the full presentation, downloadable Practice Aids, and complete CME information, and to apply for credit, please visit us at https://bit.ly/4edfNpE. CME credit will be available until July 5, 2025.

1. Deploying the Immune
Against Melanoma

uidance on Advances and Medical Breakthroughs
With ImmunoTherapy

Hussein Tawbi, MD, PhD Prof. Christian Blank, MD, PhD
Deputy Chair and Professor Group Leader, Molecular
Department of Melanoma Medical Oncology a Oncology & Immunology
Co-Director, Andrew M. McDougall Department of Medical Oncology
Brain Metastasis Clinic & Program The Netherlands Cancer Institute
Melanoma Medical Oncology | i> L Amsterdam, The Netherlands
Investigational Cancer Therapeutics
The University of Texas MD Anderson Cancer Center
Houston, Texas

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

Copyright © 2000-2024, PeerView

2. Over a Decade of Sustained OS Improvement
During the Immunotherapy Era in Melanomat+2

— CheckMate -067: iplimumab + nivolumab (N = 314)
— CheckMate -067: nivolumab (N = 316)*

— KEYNOTE-006: pembrolizumab (N = 556)?

— CA184-002: ipilimumab (N = 137)*

10

Anti-PD-1 + anti-CTLA4
08 70%-75% 64%

40%
06 42% Anti-PD-1 + anti-CTLA4

Proportion Alive

04 : Anti-PD-1
BRAFUMEKi
02
$ Ant-CTLA-4
0 +
0 6 12 18 24 30 36 42 78
Time Since Randomization, mo

Era UREA Pm. Sido orginal presented by Georgina V Long. MO NY esrorciorguna
1'Hod PS ot a N Engl J Mod 2010.63711.723.2. Robert © et al. N Engl J Mod. 2010:381.626.636 ñ

3, Robert et al. Lancet Oncol, 2019:20:1239-1251.4. Larkin Jet al. N Engl J Mod. 2019:381:1535-1546. PeerView.com

PeerView.com/BYP827 Copyright © 2000-2024, PeerView

3. Since 2021, Clinical Advances
With Immunotherapy Have Included ...

+ New targets: validation of LAG-3 and approval of PD-1/LAG-3
combinations as a SOC in metastatic, unresectable disease

+ Approval of TIL therapy in the post-ICl setting
+ PD-1 inhibitors as adjuvant therapy for stage Il melanoma

+ Emergence of evidence supporting neoadjuvant immunotherapy
(single-agent and combinations) in resectable disease

PeerView.com

PeerView.com/BYP827 Copyright © 2000-2024, Peerview

4. Our Goals for Today

Improve your knowledge of updated guidelines and evidence supporting
the continued integration of immunotherapy into modern management
protocols

Equip you with the skills you need to develop personalized
immunotherapy platforms for patients with unresectable metastatic
melanoma or for patients with resectable disease who are candidates for
neoadjuvant or adjuvant therapy

Provide you with guidance on managing practical aspects of immune-
based therapy for melanoma

PeerView.com/BYP827

5. The Right Move in Advanced Melanoma:
Established and Emerging Immune
Agents and Combinations

Hussein Tawbi, MD, PhD

Deputy Chair and Professor

Department of Melanoma Medical Oncology

Co-Director, Andrew M. McDougall Brain Metastasis Clinic & Program
Melanoma Medical Oncology | Investigational Cancer Therapeutics
The University of Texas MD Anderson Cancer Center

Houston, Texas

Copyright © 2000-2024, PeerView

6. Case Workshop: An Older Patient With Metastatic Melanoma

(Ep
Max is a 78-year-old

patient active in his
retirement community + Chest CT initially showed multiple 1-cm to 2-cm lung lesions

+ Brain MRI negative

+ LDH normal

+ PS1

+ Mutational testing: BRAF wild-type

He presents with metastatic melanoma

PeerView.com

PeerView.com/BYP827 Copyright © 2000-2024, PeerView

7. Case Workshop: An Older Patient With Metastatic Melanoma

ech
Max is a 78-year-old

patient active in his
retirement community

Metastatic melanoma,
lung lesions, brain
MRI negative, LDH
normal, PS 1, and

BRAF wild-type

PeerView.com/BYP827

he aa
aa Discussion

Is this patient too old for combination immunotherapy?
Is there any role for local therapy, surgery, or radiation?
What are the long-term expectations of PD-1/LAG-3?

What tools can be used to assess geriatric patients and
plan for 1L treatment?

PeerView.com

Copyright © 2000-2024, Peerview

8. Workshop Recommendations in Metastatic Melanoma

je) Max is a 78-year-old patient with metastatic BRAF wild-type
Cab melanoma: PS of 1, normal LDH, and no brain lesions

+ Evidence from RELATIVITY-047 shows PD-1/LAG-3 remains an
effective choice in fit older patients

+ Be vigilant and proactive when planning toxicity mitigation and
management
- Example: Ensure social support when addressing irAEs such as
arthralgia (including when steroid treatment is considered)

PeerView.com

PeerView.com/BYP827 Copyright © 2000-2024, Peerview

9. Patient Advocacy Groups Can Be Resources
for Shared Decision-Making in Melanoma

Advocacy groups can provide resources for patients to learn Symptom and Side Effect Management
more about melanoma and for healthcare professio Resource Guides
jooking for tools to help engage with patients In partnership with leading melanoma oncology
experts, AIM has developed comprehensive and up-to-
date information on the side effects of commonly used
EMPOWER YOURSELF ‘melanoma treatments currently approved by the US
Come Food and Drug Administration
RECENT ouenesen STAGES OF MELANOMA TREATMENT INFORMATION
AE A ey .
ee az AIM

Example of an action plan document
for safety management with
immunotherapy combinations

Groups such as AIM at Melanoma Foundation
have robust educational and practical resources for patients
and clinicians alike

Scan QR code to visit: aimatmelanoma.org aca u
age
ei .
PeerView.com

PeerView.com/BYP827 Copyright © 2000-2024, PeerView

10. Supporting Evidence From
Updated Guidelines and
ASCO 2024 Abstracts

Metastatic, Unresectable
Melanoma

11. Combination Immunotherapy Is the Preferred 1L
Option for Metastatic or Unresectable Melanoma’

Therapy Options (Metastatic or Unresectable Disease)

Preferred regimens

Combination checkpoint blockade (preferred) ‘Supported by
— Nivolumab + ipilimumab (category 1) + CheckMate -067

- Nivolumab and relatlimab (category 1) + DreamSeq (improves
: OS as initial therapy
PD-1/LAG-3 + Anti-PD-1 monotherapy in BRAFm setting vs
combination _ x
ae d by Pembrolizumab (category 1) BRAF/MEKi)
+ RELATIVITY-047 — Nivolumab (category 1)

Other recommended regimens

Combination targeted therapy if BRAF V600 mutation positive
- Dabrafenib + trametinib (category 1)

- Vemurafenib + cobimetinib (category 1)

— Encorafenib + binimetinib (category 1)

Pembrolizumab + low-dose ipilimumab (category 2B)

1 NCCN Cinial Practico Guidoinos in Oncology Melanoma: Cutaneous. Version 22024. 7
nips. ncen org/professionalsiphysician_gs/pcutaneous melanoma pe. PeerView.com

PeerView.com/BYP827 Copyright © 2000-2024, PeerView

12. 3-Year Data From RELATIVITY-047 Confirm
PFS Benefits With NIVO + RELA in Metastatic Melanoma‘

400 NIVO + RELA nivo
(= 355) (n= 359)
oo MPFS, mo (95% Cl) 102(65-154) 480565)
x HR (95% Cl) 0.79 (0.86.05)
3 12:m0 rate (95% Cl)
2 6 49 (43.0-53.8)
3 Bo) a) 38m rate (95% CD 48-m
mo
A 40 30 (255354) AN) omas) ==
£ 270221319) (TES NVO+RELA
20 nivo
o
0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60
Time, mo
No, at Risk
MVO+RELA 355188281 n a ss » 2
Nvo Mo 1 NS (0 2 m si a 2 2 1
1. Tawbi H ot al. ASCO 2024. Abstract 9524. PeerView.com

PeerView.com/BYP827 Copyright © 2000-2024, PeerView

13. Efficacy Benefits With NIVO + RELA
Were Consistent Across Subgroups ...

PFS by BICR ‘ORR by BICR

Unstratiied ORR
... regardless of no + Unstratiied HR vo + iteronce
age, BRAF status, REA N NO, (5%) REAR NON esco
no ; = a Treo a7 REO +
and baseline LDH =
2e 20 0806710) «ra 00 wosezin À
7% 07004009 m2 ma Tan |
146 147 0.98 (0.73-1.32) s27 456 7.2(4218.3) +]

2m 22 0806408) Ms 25 180029

0.83 (065-107)

Cutaneous nonacral 250 253 0.80(065-1.00)

4 35 85(02170)
0.85 (053-138)

132(45303)

136 139 07205400)
Wié:ypo 219 220 084(057-108)

434 317 170329
438 35 88(03178)

0780062098) 15261239)
1
VO + RELA o NO VO + RELA ++ NO
1.Tawbi Hot al. ASCO 2024. Abstract 9524. PeerView.com

PeerView.com/BYP827 Copyright © 2000-2024, PeerView

14. Sustained Survival Benefits With
NIVO + RELA Versus NIVO'

NIVO + RELA nıvo
100 (n= 355) (n= 359)
OS, mo (5% CD SIGAONR) 341252447)
12:mo rate (95% CI)
u HR (05% Cl 0.80 (0.68-0.99)
a 72166 716%) 282mo rate (95% Ci)
62666667) 36:mo rate (95% Ci)4g.mo rate (95% CI
= HIS SUGEEST Meg E pme nc
5 60 48 (427-531)
g sore. Dos
NIVO + RELA
40 nvo
2
o i +
0 3 6 9 12 15 18 21 24 27 30 38 36 39 42 45 48 51 54 57 60 63 66
Time, mo
No. at Rak
NWO RELA 955 304 905 287 270 258 241 228 24 200 106 192 172 I 165 122 107 m3 mm 72 2 2 0
E 300. 200 270 204 200 225 219 209 (ON it IM 151 4D 128 100 90 ET 87 or 15 1 0

1. TawbiH ot a. ASCO 2024, Abstract 9524 PeerView.com

PeerView.com/BYP827 Copyright © 2000-2024, PeerView

15. Melanoma-Specific Survival Improved

With NIVO + RELA Compared With NIVO'

12:m0 rate (98% CI)
81167350)
77022811)

24-m0 rate (95% CI)

0 68 (629723) 36-mo rate (95% €)
64 (68.2585) B3(87 2877) —48-mo rate (95% Cl)
54 (094-592) 60 (56-1850) Median MSS, mo (95% Ci) NR(NR-NR) 46,7 (34.1-NR)
* 50.44.0553) NIVO+RELA
y HR (95% CI) 0.75 (0.60-0.94)
2 Melanoma deaths,’ n(%) 133(38) 166 (46)
uno
40 Censored patients, n(%) 222(62) 193(54)
Nonmelanoma death, n(%) 40(11) 36 (10)
Study drug toxicity? 40) 20)
3 Unknown 20 134)
Other 28) 216)
o
0 3 6 9 1215 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66
PR Time, mo
MO = RELA 955 204 205 207 270 258241 229 214 208 190 162 172 150 148122197 19 11 72 22 2 0
NIVO 28D 300 202 279254 200 225 213 209 11 04 175 151 140 126 100 30 87 87 87 15 1 O
+ Reasons for death wore determined bythe investigator * Death duo 1 tic was considered a nonmelanoma death. Most common reason or ‘tha included
opte shock, myocardial infrcton,svoke, pneumonia, and respeatoy insuficóney, Zi
1. Tawbi Het al. ASCO 2024. Abstract. 9524. PeerView.com

PeerView.com/BYP827

Copyright © 2000-2024, PeerView

16. What’s Next With PD-1/LAG-3?

RELATIVITY-048 Results Response to NIVO-RELA-IPI

Triplet therapy: NIVO 480 mg + i, BOR per INV (N = 46) rn BOR per BICR (N = 46)
RELA 160 mg + IPI 1 mg/kg is “PR «CR BER, en
active in untreated advanced
melanoma!
+ 59% ORR
+ No new safety signals;
grade 23 TRAEs: 39%
+ Ipilimumab dose of 1 mg/kg Q8
weeks; NIVO-RELA Q4 weeks

8 2

Patients, %
5

Patients, %

8

ORR sD PD ORR sD PD

RELATIVITY-127 Is Assessing Fixed-Dose SC NIVO + RELA in Melanoma
In the RCC setting, SC nivolumab demonstrated noninferior pharmacokinetics and objective response
rate compared with IV nivolumab, supporting the use of SC nivolumab to improve healthcare efficiency?

May 2024: Under FDA review for all indications?

4. Ascierto P et a, ASCO 2024. Abstract 9504.2. George S etal. J Cin Oncol. 2024:42(supol 4)
vBistoiyers-Squi

A360
3 pe ano Businessaire con/newaihemer202405206592000 jbb-Announces-Updated-Acton Date-by the-U.S -Foodand-Drug Administration m
or-Subcutaneous-Nivolumab-nivolumab-and-hyaluronkase. PeerView.com

PeerView.com/BYP827 Copyright © 2000-2024, PeerView

17. What Are the
New Developments in
Post-PD-1 Therapy?

18. TIL Is a New Option After Progression on Immunotherapy

Disease
progression,
intolerance,
and/or

Projected risk of

NCCN Second-Line and Subsequent Therapy Options!

Systemic therapy Other recommended regimens
Preferred regimens + Ipilimumab
+ Anti-PD-1 monotherapy + High-dose IL-2

- Pembrolizumab

— Nivolumab

Nivolumab/ipilimumab

Nivolumab and relatlimab

Pembrolizumab/low-dose ipilimumab for progression following
anti-PD-1 therapy

progression with + Combination targeted therapy with BRAF V600-activating
BRAF-targeted mutation
therapy - Dabrafenib/trametinib
- Vemurafenib/cobimetinib In patients refractory to
- Encorafenib/binimetinib an and,
7 5 . an of 41% an
+ Tumor-infiltrating lymphocyte therapy (lifileucel). o respec
1. NCCN cincal Practice Guidelines in Oncology Melanoma: Cutaneous. Version 22024 a
its /hwwnnccn org/prfessionals/physiian_ls/pdlcutanecus_melanoma pl. 2. Samak AA etal. J Cin Oncol, 2021;39:2656-2666, PeerView.com
PeerView.com/BYP827

Copyright © 2000-2024, PeerView

19. New Directions With Immunotherapy in Melanoma:
Brenetafusp (IMC-F106C) PRAME x CD3 Bispecific Proteins!

Ww PRAME-expressing tumor cell

PRAME: most broadly
expressed cancer-testis

OR HLA-A°02:01 4
antigen in several tumor
types but with minimal normal PRAME-derived
i i tide
tissue expression pept Sapiiig ori
N T
Brenetafusp is the first ie „NC-Ftosc
ImmTAC
PRAME x CD3 ImmTAC A |
bispecific to be assessed \ )? scFv-anti-CD3
in solid tumors \ (nM)
CD3 receptor
Ary Tcl
1. Hamid O et al, ESMO 2022. Abstract 7280. PeerView.com

PeerView.com/BYP827 Copyright © 2000-2024, PeerView

20. Brenetafusp Shows Promising Single-Agent Activity in
Heavily Pretreated, ICI-Exposed Melanoma Patients!

+ N=47 patients with DER (PRE SD) % | PR ESD cara | OREA
cutaneous melanoma BARRENS = E = =

+ Median of 2 prior ICI PRAME+ 31 u = 2
regimens PRAME- 5 40 o 0
(monotherapy arm)

+ Most frequent TRAE Efficacy Characterized by Disease Control

was reversible/
manageable grade 1/2
CRS

+ Tolerable in
combination with PD-1
therapy (N = 9)

Tumor reduction observed in
PRAME+ patients (32%)

Best Change from Basel

+ Data support Ph3 brenetafsup + nivolumab in first-line mCM (PRISM-MEL301; NCT06112314)

1. Hamid © et a. ASCO 2024. Abstract 9507. PeerView.com

PeerView.com/BYP827 Copyright © 2000-2024, Peerview

21. Working the Gambit: The Present
and Future of Adjuvant and
Neoadjuvant Immunotherapy

Prof. Christian Blank, MD, PhD

Group Leader, Molecular Oncology & Immunology
Department of Medical Oncology

The Netherlands Cancer Institute

Amsterdam, The Netherlands

Copyright © 2000-2024, PeerView

22. Case Workshop: A Patient With Stage IIIC Melanoma

(Cap
Susan is a 56-year-old
woman with stage IIIC

melanoma + 6-mm depth, 5 mitoses/mm?, and no ulceration on thigh
+ 3 PET avid palpable inguinal lymph nodes

+ BRAF-mutated status

+ No significant past medical history

Baseline assessment showed

PeerView.com

PeerView.com/BYP827 Copyright © 2000-2024, PeerView

23. Case Workshop: A Patient With Stage IIIC Melanoma

Ca

Susan is a 56-year-old

di Discussion
woman with stage IIIC

melanoma + Is this patient a candidate for neoadjuvant therapy?
+ If so, immunotherapy or BRAF/MEKi?

Multiple PET avid palpable
inguinal lymph nodes and
BRAF-mutated status

PeerView.com

PeerView.com/BYP827 Copyright © 2000-2024, PeerView

24. Case Workshop: A Patient With Stage IIIC Melanoma

ya,
Exp aa Discussion
Susan is a 56-year-old
woman with stage IIIC
melanoma + Ifimmunotherapy, single-agent or combination—
and what happens next (based on degree of
pathologic response)?
+ If subsequent adjuvant therapy is needed, what do
you do (and what would you do if this was a
BRAF-wild-type case)?

Multiple PET avid palpable
inguinal lymph nodes and
BRAF-mutated status

PeerView.com

PeerView.com/BYP827 Copyright © 2000-2024, PeerView

25. Workshop Recommendations in Stage IIIC Melanoma

O
Cap

PeerView.com/BYP827

Susan is a 56-year-old woman with stage IIIC BRAF-mutated
melanoma (multiple PET avid palpable inguinal lymph nodes)

Based on her presentation, Susan is a candidate for neoadjuvant
immunotherapy, followed by TLND

Based on the degree of response, subsequent adjuvant options would
include BRAF/MEKi

If she had BRAF-wild-type status, adjuvant PD-1 therapy would be
considered

As we shall see, evidence from NADINA supports neoadjuvant combination
immunotherapy in patients with stage Ill melanoma and LN metastases

- Potential for a 6-week course of neoadjuvant therapy

PeerView.com

Copyright © 2000-2024, PeerView

26. Supporting Evidence From
Updated Guidelines and
ASCO 2024 Abstracts

Resectable Melanoma

27. Adjuvant vs Neoadjuvant Immunotherapy’
Proposed Rationale for Adjuvant Immunotherapy

&

‘Surgeon removes Immunotherapy Activation of few Fewer, and less-cverse,
tumor lesion “dierentT cols. T calls search for tumor

cols
Proposed Rationale for Neoadjuvant Immunotherapy

ae
Le
on, aes

1. Versus JM et al Not Med. 2020.26:475-484. PeerView.com

PeerView.com/BYP827 Copyright © 2000-2024, Peerview

28. Neoadjuvant Therapy Is Supported by Practice Guidelines

The NCCN now recommends neoadjuvant options
(when appropriate) for

v Stage Ill clinically positive node(s)

Sone v Stage Ill clinical satellite/in-transit

renee re Y” Nodal recurrence’

Preferred regimens Other recommended regimens
+ Pembrolizumab * Nivolumab

Supported by + Nivolumab/ipilimumab + Nivolumab and relatlimab
+ OpACIN-neo
+ PRADO Useful in certain circumstances

+ Dabrafenib/trametinib if BRAF V600 mutation positive

41. NCCN Cinial Practice Guidelines in Oncology. Melanoma: Cutaneous. Version 22024, +
tos un nccn.orpproessionalsphysiian_glspdlcutaneous_ melanoma pd PeerView.com

PeerView.com/BYP827 Copyright O 2000-2024, PeerView

29. NADINA Tested Neoadjuvant IPI-NIVO With Standard
Adjuvant NIVO in Macroscopic Stage Ill Melanoma’

Phase 3 trial 2 courses
1P180 mg +
NIVO 240 mg
O ibn) aœw 11 courses NIVO 480 mg Q4W (BRAFW
Reselectable stage I o D+ 2 mg QD (BRAFVER)
| 46 weeks DAB 150 mg BID + TRAM 2 ng QD (BRAF
macroscopic,
pathologically proven LN
metastasis

NIVO 480 mg Q4

4 0 3 6 9 @ 36 60
di di di HO di di i LL
cr, per, Me, er.oor eno craoL er.a0t cr, ao cran era:
Dopey QOL. an,
es zando
Time, wk de

Beyond year 3 according to Instiutesfcounty standards.» During ajuvant therapy four. woeky la. +
1. ips fnicalals goVistudyNCTO4949113. PeerView.com

PeerView.com/BYP827 Copyright © 2000-2024, Peerview

30. In NADINA, Neoadjuvant Therapy Substantially
Improved EFS vs Adjuvant Treatment!

10

08

z Neoadjuvant
Primary endpoint m 8 06
improvement in EFS ... 3 Adjuvant
@ 04
a
02 Neoadjuvant Adjuvant
FER AA M
. ¿nr (69.9% cn 022015056): P < 0001
y 3 y Pa E
Time From Randomization, mo
No. at Risk (No Censored
Neoadant 2120 NON 7) HUE SU -

Am 2 NOT) 2) Sr

Neoadjuvant Adjuvant

EFS improvement across all ed —
subgroups, including in a een ZI En
BRAF-mutated disease Yes 15/112 41112
ASS
pecadora Boo Adina Balter
1. Blank Cet al. ASCO 2024. Abstract LBA2, PeerView.com

PeerView.com/BYP827 Copyright © 2000-2024, PeerView

31. NADINA: Robust Pathologic Responses
With Neoadjuvant Therapy!

Pathologic Response Radiologic Versus Pathologic Response

100%
BPR 100 mpCR

sx Nar
Near pCR SE
¿e = PPR a = pPR
gm “MR - = pNR
E ox Prados jo * Progression
So "nanporesnosu E whe ergs
4 40% =
¿o MPR: 59%
20% 2
10%
0% o
Local Assessment Central Review CR PR so PD NE/NR
Similar to prior trials, in NADINA, neoadjuvant IPI-NIVO induced an MPR of -60%
1. Blank C et al. ASCO 2024. Abstract LBA2. PeerView.com
PeerView.com/BYP827

Copyright © 2000-2024, PeerView

32. NADINA: Neoadjuvant Therapy Was Safe,
With No New Safety Signals Noted’

Neoadjuva Adjuvant
nite) n=212 n= 208
Any AE 204 (96.2) 194 (93.3)
Any grade >3 AE 100 (47.2) 71 (34.1)
Surgery-related AE 120 (60.6) 151 (72.6)
Surgery-related grade 23 AE 28 (14.1) 30 (14.4)
Systemic TRAE 181 (85.4) 123 (72.4)
Systemic grade 23 TRAE 63 (29.7) 25 (14.7)
Death due to TRAE 0 1 (0.5)
1.Blank C etal, ASCO 2024. Abstract LBA2. PeerView.com

PeerView.com/BYP827 Copyright © 2000-2024, PeerView

33. Take-Homes From NADINA

NADINA is the first neoadjuvant checkpoint inhibitor phase 3 trial
in melanoma

+ Itis also the first phase 3 trial for any solid tumor testing a
neoadjuvant checkpoint inhibitor combination without
chemotherapy

+ Neoadjuvant combination of ipilimumab + nivolumab resulted in a
highly statistically significant EFS benefit as compared with SOC
adjuvant PD-1 blockade (HR = 0.32; P < .0001)

+ Nearly 60% of patients in the neoadjuvant arm needed only
6 weeks of treatment

+ All subgroups benefit from neoadjuvant ipilimumab + nivolumab

PeerView.com

PeerView.com/BYP827 Copyright © 2000-2024, Peerview

34. Can We Predict Who Recurs? Role of ctDNA Analysis

1. Plasma preparation and 2.CfDNA preampification 3, Droplet generation 4.ctDNA detection and
Retrospective analysis of DNA extraction analysis
plasma samples > eur NN
collected at baseline and 8 ae

six weeks post-surgery

from 30 patients enrolled

in the OpACIN-neo and
PRADO trials?

Lia

+ Positive ctDNA post-surgery (n = 4)
was 100% predictive of recurrence

Patients, n

+ Post-surgery ctDNA positivity can
signal imminent recurrence and offer a
window for personalized adjuvant aca TRUE CURE OUT
therapy modification
IM Norecurrence MRecurrence

1.Chan WY etal. ASCO 2024. Abstract 9577. PeerView.com

PeerView.com/BYP827 Copyright © 2000-2024, Peerview

35. Is There a Role for Neoadjuvant Immunocytokine Therapy?

Daromun (L19IL2/L19TNF) assessed as neoadjuvant therapy in the phase 3 PIVOTAL trial in patients with
locally advanced disease (stage IIIB/C) eligible for complete surgical resection"

Arm4
'Daromun injection QW for 4 weeks
‘Surgery of all lesions within 4 weeks.

Primary Endpoint

+ RFS (time from
randomization to

: progression or death)

Goce Post-adjuvant Secondary Endpoints
2 therapy at on

GONE investigator's

treatment idiacration| + DMFS

allowed ES

Safety (AEs, ADA)

Pathological response
(study amendment)

1. Hauschäd A et al. ASCO 2024. Abstract LBA9S01 PeerView.com

PeerView.com/BYP827 Copyright © 2000-2024, PeerView

36. Neoadjuvant Daromun Improved RFS and DMFS Versus
Surgery Alone in Locally Advanced Melanoma Patients!

RFS (BICR) DMFS

‘Survival Probability

Time, mo

Deramın Heinen) Ho meaningful and statistically Daromun + surgery 32122
Surgery CEE ant longer RFS and DMFS Susy

Mesa REED RC patient: 12 m0 d with surgery alone

HR (95% Cl): 0.59 (0.41-0.86); P = 005 HR (95% Cl): 0.60 (0.37-0.95)

1.Hauschä A et al ASCO 2024, Abstract LBA9501

PeerView.com/BYP827 Copyright © 2000-2024, Peerview

37. Adjuvant Immunotherapy Has Been
Added to Guidelines for Stage Il Melanoma‘

Clinical Stage Primary Treatment Adjuvant Treatment

Clinical trial for stage I
or
Observation
or
For pathological stage 118 or IC:
Pembrolizumab (category 1)
Nivolumab (category 1)
and/or
Primary tumor site radiation

therapy to reduce local
recurrence (category 28)

PD-1 inhibitors are
now category 1
options in stage IIB/C

Stage IB (T2a) or It
(T2b or higher)

Stage Ill workup and
primary treatment

1 NCCN Cinial Practice Guideines in Oncology Melanoma: Cutaneous. Version 22024. ñ
ps ww ncen org/professionalsiphysician_ge/pcutaneous_metanoma pe. PeerView.com

PeerView.com/BYP827 Copyright © 2000-2024, Peerview

38. Guidelines Continue to Support Adjuvant
Immunotherapy as a SOC in Stage Ill Resected Melanoma’

Dabrafenib +
NCCN Guidelines Nivolumab Pembrolizumab Trametinib

for Adjuvant Therapy (Anti-PD-1) (Anti-PD-1) (BRAF/MEKi)
BRAF V600 Mutated

Stage IIIA-D sentinel node

positive Preferred Preferred Preferred
Stage Ill clinical node

positive Category 1 Category 1 Category 1
Stage III in transit Category 1 Preferred Preferred

1.NCCN Cinial Practice Guideines in Oncology Melanoma: Cutaneous. Version 22024 a
ps: ww nocn orgiprofessionalsiphysician_gs/pdtcutaneous._melanoma pa. PeerView.com

PeerView.com/BYP827 Copyright © 2000-2024, PeerView

39. Is There a Role for Adjuvant Individualized Neoantigen
Therapy (INT) in Combination With PD-1 Inhibitors?!

‘940 Is a Novel Investigational mRNA-Based Personalized Can
of a Single Synthetic mRNA Coding for up to 34 Neoantigı

Sequencing to identity Neoantigen |
mutations in protein therapy design
© neoantigen —>— © individualized mRNA +

> encoding forup 1

1. Khattak À et al. AACR 2023, Abstract LBA9S03,

PeerView.com/BYP827 Copyright © 2000-2024, Peerview

40. KEYNOTE-942: After 3 Years, Sustained
Improvement in RFS With Combination Therapy’

Combination of Adjuvant mRNA-4157/V940 and Pembrolizumab vs Pembrolizumab in Stage Ill Melanoma

100

MRN-4157 (V940) +

z pembrolizumab
fa
Eo
Pembrolizumab
2
o + +
° y y y 2 E E @ ry >
Nos at Rise Time From First Pembrolizumab Dose, mo
MRNA157 (1940) +
EN wor e 8 mn se 2 12 6 1 o
Pembrolzumab, so “ E 20 2 10 5 2 o
Median, mo (9: Events, % (n/N)
mRNA-4157/V940 +
pos NE 23.4 (25/107)
Pembrolizumab 42.51 (16.59-NE) 44.0 (22/50)
HR (95% Ci): 0.51 (0.288-0.906) 19
PeerView.com

1. Weber Jetal. ASCO 2024. Abstract LBA9S12

PeerView.com/BYP827 Copyright © 2000-2024, PeerView

41. Adding mRNA-4157 to Pembrolizumab
Does Not Appear to Potentiate irAEs'

mRNA-4157/V940 +

Pembrolizumab Eömbrolizumab

(n= 104) (HEY)
Eo 00
Any AE 104 (100) 36 (34.6) 46 (92) 18 (36)
Any TRAE 104 (100) 26 (25) 41 (82) 10 (20)
Serious AE 15 (14.4) - 5 (10) -
irAE 39 (37.5) 11 (10.6) 18 (36) 7 (14)

1. Weber Jet a. ASCO 2024. Abstract LBA9S12. PeerView.com

PeerView.com/BYP827 Copyright

42. Audience Q&A © |

Copyright © 2000-2024, PeerView