Expanding Frontline Frontiers in MM: Insights on Delivering Modern Care With Innovative CD38 Quadruplet Platforms

Chair and Moderator, Prof. Mohamad Mohty, MD, PhD, and presenters Professor Thierry Facon, MD, and Joshua Richter, MD, discuss multiple myeloma in this CME activity titled “Expanding Frontline Frontiers in MM: Insights on Delivering Modern Care With Innovative CD38 Quadruplet Platforms.” For the full presentation, downloadable Practice Aids, and complete CME information, and to apply for credit, please visit us at https://bit.ly/3PVroz2. CME credit will be available until July 18, 2025.

1. Expanding Frontline Frontiers in MM
Insights on Delivering Modern Care With Innovative
CD38 Quadruplet Platforms

Thierry Facon, MD
Professor of Haematology, Department
of Haematology

Lille University Hospital

Sorbonne University

Paris, France Associate Professor of Medicine

Tisch Cancer Institute
Icahn School of Medicine at Mount Sinai

Director of Myeloma

Blavatnik Family Chelsea Medical Center at Mount Sinai
New York, New York

Prof. Mohamad Mohty, MD, PhD Lille, France
Professor of Hematology
Hematology and Cellular Therapy
Department
Saint-Antoine Hospital

| | Joshua Richter, MD

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

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2. How CD38 Antibodies Work‘?

On-tumor effects

CDC, ADCC, ADCP,
A penis K
Daratumumab
binds to CD38
Dept coses or
inmiresipresve .

regulatory cells,
promotes T-cell .
expansion, activation
. yeloma)
cell
On-tumor effects death / »
CDC, ADCC, ADCP, >
ES ‘apoptosis SS .
Isatuximab Y
Bindsito CDs) Immunomodulation, La
inhibition of
ectoenzyme activity
1. Dimopoulos MD et ASH 2020. Absract 225.2, Moreau P tal ASH 2020, Abstract 2316, PeerView.com

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3. CD38s Have a Role in Multiple MM Treatment Settings

Current regulatory status of CD38 antibodies

Daratumumab'2 Approved in the EU Approved in the US
NDMM +» In combination with Rd or VMP +» In combination with Rd or VMP
(ASCT ineligible) (ASCT ineligible)
+ In combination with VTd +» In combination with VTd
(ASCT eligible) (ASCT eligible)
RRMM + In combination with Rd, Vd, and +» In combination with Rd, Vd, and pom/dex;
pom/dex; + As monotherapy
+ As monotherapy + In combination with carfilzomib and dex
Isatuximab*+ Approved in the EU Approved in the US
RRMM + In combination with pom/dex + In combination with pom/dex
+ In combination with Kd + In combination with Kd

1. Dareaix (dartumumab) Presenting Information. Np: acessdata fa govdrugsatida_docsabel/202176 103680331 pt
2 Darzalx (aratumumab) Preserbing nfornaben Mts wa ema europa uen documenta product omatonidarza-apor productintormaton_ en pat

3 Sara (satuximab te) Presrbing Information, tps win accessdata Ida govérugsatida_docs/abel”2020/761 11350001 pa. sr:

4. Sarcisa((satuximab-ife) Prescribing Information. is: /Amww.ema europa eulen/documents/overview/sarcisa-epar-medicine-overview_en.pd. PeerView.com

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4. Despite Progress, More Work is Needed
To Integrate CD38 Platforms Into 1L Therapy

+ RW data collected from 2,179

patients with MM treated in the Atdata collection,
EU during 20211 25% of 401 patents

with NDMM
+ Data analysed were collected received 1L CD38-
from five European countries based treatment
(EUS: France, Germany, Italy, (14% quads) w
Spain and the UK) Er

What will role will quadruplets play, Nr
now and going forward?
1L(n=401)

1. Martinez Lopez eta. Futuro Oncol. 2023 Oct:19(31)21092121 PeerView.com

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5. Our Goals for Today

Improve your knowledge of the latest safety and efficacy evidence
supporting the use of CD38-based quadruplet platforms in NDMM

Provide you with the skills you need to integrate CD38-based

quadruplets into personalized, upfront treatment plans

Enhance your ability to address care delivery considerations when
using CD38-based quadruplets, including dosing and safety
considerations

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6. Deploying CD38
Quadruplet Strategies in
Transplant-Eligible NDMM

7. Clinical Consult: An Adult Patient
With R-ISS Il, Standard-Risk NDMM

Phillip, a 66-year-old man with R-ISS II
NDMM

+ Fit patient with active lifestyle

Current status

+ PS of 1

+ Standard-risk cytogenetics

+ Comorbid HTN and hyperlipidemia

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8. Clinical Consult: An Adult Patient
With R-ISS Il, Standard-Risk NDMM

Phillip, a 66-year-old man with R-ISS II Discussion

NDMM + Is this patient a candidate for a quad?
+ Fit patient with active lifestyle

+ Or should standard triplets (eg, VRd)
Current status be considered?

+ PS of 1

+ Standard-risk cytogenetics

+ Comorbid HTN and hyperlipidemia

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9. Clinical Consult: An Adult Patient
With R-ISS Il, Standard-Risk NDMM

Phillip, a 66-year-old man with R-ISS II Discussion
NDMM + If a quad is used, how would that
+ Fit patient with active lifestyle change treatment expectations?

Current status + Depending on quality of remission,
+ PS of1 could ASCT be deferred?

+ Standard-risk cytogenetics
+ Comorbid HTN and hyperlipidemia

+ What is the practice in the EU vs US
when a quad is considered?

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10. In the EU, CD38 Quads Are Being
Integrated Into Practice Guidelines

Eligibility for ASCT

EHA-ESMO Clinical Practice
Guidelines for MM!

Induction =
DaraRd
D:

VRd (IB)

Inclusion of DaraVTD DaraVTD (|, A)
based on CASSIOPAEIA

Lenalidomide
maintenance (|, A)

1. Dimopoulos MA et al. Ann Oncol, 2021:32:309-322 PeerView.com

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11. CD38 Quads Are Now Included as Primary Therapy
in NCCN Guidelines for ASCT-Eligible NDMM'

Primary Therapy for ASCT Candidates

+ Bortezomib/lenalidomide/dex (category 1)
+ Carfilzomib/lenalidomide/dex

Quad Options Useful in Certain Circumstances* Dara + VRd supported by trials such as GRIFFIN
and now PERSEUS?

+ Daratumumab/VTd

+ Daratumumab/KRd

+ Daratumumab/cyclophosphamide/Vd
+ Isatuximab/RVd

+ Daratumumab/bortezomib/lenalidomide/dex

ted regimens to show C038 quadruplts; consult NCCN guidelines for complete st
AGEN Gin race Guetns a Orcobgy, Mei Moa, Verso 42021. Mos vw cen orgrfessonallphysican_glpatineloma pl 7
2. Voorhees PM eta. Blood. 2020:196:996-948 3. Sonneveld Petal. N Engl Med. 2024;390:201-913, PeerView.com

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12. GRIFFIN: In this Phase 2 Trial, Adding Dara to a Standard
Triplet Deepened Response, Improved PFS'

D-RVd Group
mStingent CR ÑCR =VGPR ÑPR 2SD,PD, or NE

100% Ez A

90%

ar

1%

or

0%

0%

20%

2x CRor cher Ro 2%
10% Deter: Betr: 10%

19% 83%
[3 o

Patients, %

Patients, %
3
2

RVd Group

mStingent CR =CR =VGPR mPR ÑSD,PD, or NE

ae cor eRe
oe

End of Induction End of Post-
‘Autologous HSCT
Consolidation

1. Voorhees eta Lancet Haematol 202810: 0825-37.

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Final Analysis End of Induction

4-year PFS,% 87.2 70.0

.45 (95% Cl, 0.21-0.95), P = .032

End of Post- Final Analysis
‘Autologous HSCT
‘Consolidation

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13. CASSIOPEIA: Adding Dara Improved PFS vs Observation
In Patients Treated With VTd Induction/Consolidation!

+ Aprespecified analysis showed
significant interaction between
maintenance and
induction/consolidation therapy

+ PFS benefit was observed for
VTd/daratumumab versus
VTd/observation

Patients Progression Free and Alive, %

+ PFS was not different for

D-VTd/daratumumab versus i

D-VTd/observation IM VTADARA.
m ovtaosv
m DVTADARA

* Nominal P value.
4. Moreau Pt al, ASCO 2021. Abstract 8004.

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——p.vraoav
— ONTADARA
—vraosv
n HR (95% CI) pr
VTADARA vs VTA/OBV 7 0.32 (0.23-0.46) —<0001
D-VTAIDARA vs D-VTd/OB\/ 1.02 (0.71-1.47) 9133
201 176 185 131 83 43 15 1
203 189 182 174 138 79 2% 1
229 223 216 207 195 144 75 38 2
229 226 217 204 198 145 76 30 0

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14. PERSEUS: Phase 3 Comparison of Dara + VRd
Versus VRd Induction in ASCT-Eligible MM!

Induction Consolidation Maintenance
4 cycles of 28 days 2 cycles of 28 days 28-day cycles

VRd VRd
V:1.3 mg/m V: 1.3 mg/m? SC

Inclusion 9 9

CRE days 1, 4,8, and 11 days 1, 4, 8, and 11

Transplant- R:25mgPO
eligible days
NOMM d: 40 mg POIV
Aged 18-70 days 1-4, 9-12
years

ECOG PS <2

10 mg PO da until PD

Transplant

DR

Dara: 1,80

N=709

Discontinue
dara therapy

Discontinue dara therapy only ator | [Restart dara therapy
‘ . 224 months of DR maintenance or | | upon confirme loss
Enimarysendpoint: PES . atenta win CR and 12 months of || of CR witout PO or
+ Key secondary endpoint: overall 2CR rate, overall MRD-negativity sustained MRD negaty recurrence of MRO
rate, OS
1. Sonneveld Peta. N Engl J Med. 2024;380:301-913, PeerView.com

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15. PERSEUS: Adding Dara to VRd Induction
Substantially Improved PFS Versus VRd Alone

PFS at 48 months was 84.3% in
the D-VRd group and 67.7% in
the VRd group!

+ HR for disease progression or
death, 0.42; P <.001

HR for disease progression or death = 0.42 (95% Cl, 0.30-.59)
Pa 00

Patients Surviving Without Disease
Progression, %

o
0 3 6 9 1215 18 21 24 27 30 33 36 39 42 45 48 51 54
Time Since Randomization, mo

No. at Risk

Diva 355345 395329327 322918 316313 309305 302 299295286 226 0 11 0

VRG 354 209 21 911 304 207 201 182278 270258247 238 228219 175 67 13 0

(Modi folow-up: 67.5 mont, m
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1. Sonneveld P et al. N Engl Mod. 2024:290:201-313,

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16. 1. Sonneveld Peta. N Engl J Med. 2024:390:301-313,

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PERSEUS: Safety Summary!

Most Common Adverse Events (Safety Population)

D-VRd (n = 351) VRd (n = 347)
Event, n (%)
Any Grade Grade 3 or 4 Any Grade Grade 3 or 4
Any adverse event 349 (99.4) 321 (91.5) 344 (99.1) 297 (85.6)
Hematologic adverse event
Neutropenia 243 (69.2) 218 (62.1) 204(58.8) 177 (51)
Thrombocytopenia 170 (48.4) 102 (29.1) 119 (34.3) 60 (17.3)
Anemia 78 (22.2) 21 (6) 72 (20.7) 22(6.3)
Febrile neutropenia 34 (9.7) 33 (9.4) 38 (11) 35 (10.1)
Second primary cancer 37 (10.5) NA 25(7.2) NA
Any infusion-related reaction 21 (6) 3(0.9) NIA NA

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17. IsKia: Isa-KRd as Upfront Quadruplet Option in NDMM!

Induction Post-ASCT Consolidation Light Consolidation
4 cycles of 28 days 4 cycles 0128 days 12 cycles of 28 days

4x lsa-KRd

AxisskRa
Inclusion Criteria

+ TENDMM
patients aged <70
years

Stratification

+ Centralized FISH

10 malig IV day 1

Mobilization oa
On 230m days 1and 15
folewod by 1 R: 10 mg PO days 121

G-CSF for stem-cell 4 y :20 mg PO days 1 and 15

(standard

risk/missing vs. MEL-200 ASCT.

high risk defined

as del(17p) and/or MEL: 200 mg/m? Ax kRd
14,14) andlor followed by K: 56 mg IV days 1
(14:16)

+ ISS (Ivs Il and iN)

6:20 mg PO days 1 and 15

1

MRD by NGS MRD by NGS: MRD by NGS MRD by NGS
+ Primary endpoint: MRD negativity rate (10°)

1. Gay et al ASH 2023. Abstract 4. PeerView.com

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18. IsKia: Isa-KRd Induced Higher Rates of MRD-Negative
Responses Compared With KRd Alone

+ Primary endpoint: post-consolidation MRD-negativity (ITT)!

NGS, 105 NGS, 10%
166 OR: 1.67; P=.049 19 OR: 2.29; P <.001
90

80 ar

Patients, %
Patients, %

0
Isa-KRd (n= 151) — KRd (n=151) Isa-KRd (n= 151) KRd (n = 151)

1.Gay otal. ASH 2023. Abstract 4. PeerView.com

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19. Isa-KRd Was Tolerable, With a Consistent
And Predicable Safety Profile!

Event, n (%) SRD It
Any Grade Grade 3 or4 Any Grad
Patients with 21 hematologic toxicity 83 (55) 61 (40) 67 (44)
‘Anemia 32 (21) 5(3) 28 (19) 5(3)
Neutropenia 62 (41) 55 (36) 39 (26) 33 (22)
Thrombocytopenia 51 (34) 2215) 38 (25) 25 (17)
Patients with 21 nonhematologic toxicity 136 (90) 61 (41) 129 (85) 56 (37)
Infections (excluding COVID-19) 55 (36) 2305) 49 (32) 17(11)
Asthenia/fatigue 37 (25) 5 (3 40 (26) 3(2)
Dyspnea 20 (13) 2(1) 26) 1m)
Rash 33 (22) 53) 40 (26) 5(3)
Peripheral neuropathy 22 (15) o 25(17) 0
Infusion-related reactions 30 (20) 5(3) 2() o
Cardiac disorders 117) 1(<1) 19 (13) 5(3)
Vascular disorders 29 (19) 76) 33 (22) 15 (10)
Hypertension 5(3) 2(1) 6(4) 3(2)
Thromboembolism 128) 46) 16 (11) 26
Gastrointestinal disorders 79 (52) 10 (7) 73 (48) 8(5)
Nausea 36 (24) 403) 3121) 2(1)
18 (12) 2(1) 12(8) 4(<1)
4127 st 37 (25) 56)
1.Gay F et al ASH 2023. Abstract, PeerView.com

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20. The SKylaRk Trial: Efficacy of Isa/KRd
in All-Risk Transplant-Eligible NDMM'

Once-weekly 100 88
administration of
Isa/KRd demonstrated a PFS, % OS, %
high ORR and favorable
MRD negativity, Eile cee
indicating its MRD Negativity 105
effectiveness in treating 80
all-risk transplant- & 60
eligible NDMM (N = 50;

€ 40
45 evaluable) 2

£2

Cycle 4

Cycle 8
1.0Dennel EK otal ASH 2029, Abstract 4671,

AutoSCT

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21. GMMG-HD7: Adding Isatuximab to RVd
Enhances Response and MRD Negativity in NDMM

GMMG-HD7: MRD Negativity (Primary Endpoint) and Response Rates at End of Induction‘

Patients With MRD Negativity

Response Rates at End of Induction
at End of Induction

607 OR: 4.89 95% Cl. 1.94251) 100 AA Aita
> a 80 P<.001
à 40 ES
g % 60
= 2 40
¿2 &
10 20
0 o
Isa/RVd (n= 331) RVd (n= 329) CR 2nCR 2VGPR 2PR
Not assessable/missing MRD status Significant increase in 2VGPR with Isa-RVd;

low: Isa-RVd: 10.6%; RVd: 15.2% significant increase in ORR

1. Goldschmidt H eta. Lancet Haematol 2022.5:0810-0821. PeerView.com

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22. Clinical Consult: What if Phillip
Had Presented With High-Risk Disease?

Phillip, a 63-year-old man with R-ISS II Discussion

NDMM + What is the role of quadruplets in
higher-risk settings?

Current status

+ PS of1 + If a quad is considered, would adding
+ Standard-risk cytogenetics a CD38 to a K backbone be the

+ Comorbid HTN and hyperlipidemia optimal choice?
+ How does safety management change

when using CD38s in combination with
carfilzomib?

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23. PERSEUS: Adding Dara to VRd
Was Effective in High-Risk Subgroups’

aan 61205 NE NE
vanes aang NE NE

051 (034077)
029 016.089)

30261 eaze7 NE NE
2094 1987 NE NE

0.30 0200.46)
087 (0521.81)

470 9523 NE NE
325 ÉS) NE NE

0.42 (0300.60)
0.40 (0.11-150)

18/196 asıra NE NE 0.46 (026081)
ons aus NE NE 0.37 02206)
1355 25150 NE 419 042(022089)

0.36 (023-057)

1978 3196 NE NE 0.46 (0240.88)

25764 62266 Ne NE 0.35 (0220.56)
2476 3878 NE aa 0.0 (036.09)
115, 310 NE NE 0.16 (002-156)

281221 60230 ne NE
2 224 una NE NE

0.42 (027-066)
0.41 (0250.69)

1. Sonneveld Peta. N Engl Med. 2024;380:301-313, PeerView.com

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24. IsKia: Use of Isa-KRd Led to Higher
MRD-Negativity Rates Across Patients Subgroups’

10° Cut-Off

167 (1,002.80)

1701092312)
230 (0687.70)

160 078341)
186 0.704157)
2.76 (052-1458)

148 038375)
179 (094-343)

— 1.14 036.360)

3.08 (1,

Favors KRd Favors Isa-KRd

1. Gay Fetal. ASH 2023. Abstract 4.

PeerView.com/QTT827

06638

080

0701

10° Cut-Off
OR (05% ch

Overall 220 (143367)
Cytogenetic risk
as per IMG

Standard rk. 210122381)

High Risk 4.95 (148-161)
Not HRCA

HRCA 221(1.14-427)

HRCA 204 (088470)

2HRCA 905 (1572.14)
Russ.

Rziss

"
uv

203 (0894.63)
235 (130428)

176066489)
371 (1548.89)
1.92 (092402)

02 10 2
== —

Favors KRd Favors Isa-KRd

7766

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25. In GMMG-CONCEPT, Isa-KRd Induced Deep and Sustained
MRD-Negative Remissions in Patients With High-Risk MM!

MRD negativity status at
the end of consolidation

(primary end point)
+ N= 125 patients with high-risk 100
NDMM defined by mandatory ISS
stage II/III combined with del17p, “is oe
1(4;14), t(14;16), or three 1921 Ea (any time point ae
copies as high-risk cytogenetic 3
aberrations (HRCAs)! 2 40 present ng 72(727)
+ After median follow-up of 44 x 20
months in TE arm, median PFS en 62 (622)
was not reached o
TE Patients
(Arm A)
Results in transplant-eligible patients
1. Leypolt LB et al. J Cin Oncol, 2024:42:26-37. PeerView.com

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26. Summary Thoughts on CD38 Quads in ASCT-Eligible MM

+ CD38 quadruplet regimens provide extremely deep remissions (higher rates
of MRD negativity) compared with triplets and do so with a tolerable safety
profile

— Certain high-risk features may be offset with the augmentation of a regimen
from a triplet to a quad

Ongoing studies are evaluating whether or not ASCT is still necessary in
some patients given the ability of quads to achieve MRD negativity at such
high rates

Ongoing studies are evaluating the optimal maintenance strategy following
quadruplet induction followed by ASCT

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27. Extending Innovation With
CD38 Quadruplets in
Transplant-Ineligible NDMM

28. Clinical Consult: A Patient Presenting
With NDMM and Comorbidities

Celine is a 75-year-old woman with
NDMM, T8 compression fracture, and
comorbid COPD

Current status

+ Creatinine 1.1

+ PS of 1

+ Standard-risk cytogenetics

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29. Clinical Consult: A Patient Presenting
With NDMM and Comorbidities

Celine is a 75-year-old woman with Discussion
NDMM, T8 compression fracture, and + Assuming ASCT is not an option, is
comorbid COPD this patient a candidate for a quad?

Current status + Or would a triplet be appropriate in all
+ Creatinine 1.1 cases?

+ PSof1

+ Standard-risk cytogenetics

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30. Clinical Consult: A Patient Presenting
With NDMM and Comorbidities

Celine is a 75-year-old woman with Discussion

NDMM, T8 compression fracture, and + If a CD38 quad is used, how is this

comorbid COPD platform delivered differently in ASCT
ineligible patients—would dose

Current status reductions/modification be useful?

+ Creatinine 1.1

+ PS of 1 + What is the EU and US experience

+ Standard-risk cytogenetics with quads in ASCT-ineligible
patients?

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31. In the EU, CD38 Quads Are Being
Integrated Into Practice Guidelines

Eligibility for ASCT

EHA-ESMO Clinical Practice
Guidelines for MM!

Lenalidomide
maintenance (I, A)

1. Dimopoulos MA etal. Ann Oncol. 2021:32:308-322. PeerView.com

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32. CD38 Triplets and Quads Are Included as
Primary Therapy for ASCT-Ineligible NDMM'

Primary Therapy: Non-ASCT Candidates

+ Bortezomib/lenalidomide/dex (category 1)

Based on MAIA, which established the
Dara + Rd triplet as upfront therapy in

Daratumumab/lenalidomide/dex (category 1) ASCT-ineligible MM?
Other R ded Opt
Based on ALCYONE, which showed
+ Daratumumab/bortezomib/melphalan/prednisone efficacy of quadruplet therapy with
(category 1) Dara + VMP in ASCT-ineligible NDMM3

+ Daratumumab/cyclophosphamide/bortezomib/dex
+ Carfilzomib/lenalidomide/dex

1.NCCN Ginial Practice Guideines in Oncology. Multiple Myeloma Version 4.2024, ps im ncen orpprolessionals physcian_gis/plimyeloma pl. 7
2. Kumar SK et al, ASH 2022. Abstract 4859. 3 Mateos MLV etal. ASH 2022. Abstract 4861. PeerView.com

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33. LYRA: DARA + CyBorD Followed by DARA Maintenance
Achieved Deep, Durable Responses in NDMM'

NDMM Transplant NDMM Non-Transplant
(n= 39) (n=47)
ORR: 79 ORR: 92 ORR: 97 ORR: 79 ORR: 83

100

so

so

70

eo

50

0

50

2

10

o

End of Cycle 4 End of Induction End of Study End of Cycle 4 End of Induction End of Study
(All NDMM, N = 86) (n= 39) (n= 3) (All NDMM, N = 86) (n=47) (n=47)

MPR =VGPR "CR msCR =PR mVGPR "CR msCR

Including in ASCT-ineligible patients

1. Yimer Het a. Louk Lymphoma, 2022:63:23892992. PeerView.com

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34. Daratumumab Quadruplets Continue
to Show Efficacy in Nontransplant Settings

ALCYONE first showed a PFS
improvement with the addition
of dara to VMP in ASCT-
ineligible settings!

+ After a median follow-up of 78.8
mo, D-VMP induced long-term ee à (ir, weg
PFS improvement vs VMP2 AAA - LU

1 vw.
1 median, 37.3 mo

‘Surviving Without Progression, %

o
MERTERZZZTELITLETT)
Treatment Duration, mo

1. Matoos M-V et al. N Engl Med, 2018:378:518:28. 2. Mateos M.V et al. ASH 2022. Abstract 4561. PeerView.com

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35. GEM2017FIT: KRd and D-KRd Versus VMP-Rd in Elderly,
Fit Patients With NDMM (Between 65 and 80 Years of Age)!

GAH score Lower GAH
> wie pi Highost probability
calculation (oye pin, GAH=40 to develop toxicity score > better
GAH=2 SAH=78 status

GAH <20 GAH >20

of Patients

‘Alive and PFS

Proporti

Time, mo

Time, mo

+ Significantly higher MRD negativity with KRd and D-KRd

+ Most frequent reason for toxicityrelated deaths in the 3 arms: infections (13 death events/153 pts in D-KRD)

+ Patients who discontinued because of toxicity or toxicity-related death presented GAH 220 and specifically, higher scores concentrated on
gait speed and nutrition

1. Mateos MAY et al. ASH 2023. Abstract 209, PeerView.com

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36. Adding Isatuximab to VRd was an Effective
Approach in Prior Studies in ASCT-Ineligible MM!

Isatuximab combined with VRd in patients with NDMM
ineligible for/with no intent for immediate ASCT

Onn: 98.6%

+ 73 patients received four 6-week induction
cycles of Isa-VRd, then maintenance with
Isa-Rd in 4-week cycle

+ In the efficacy population (n = 71), the ORR
was 98.6%, with 56.3% achieving 2CR

+ 36/71 (50.7%) patients achieved MRD
negativity (1075 sensitivity).

Mparairesponse M VGPR MOR SCA
1, Ocio EM eta Leukemia, 2023:37:1821-1529 PeerView.com

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37. IMROZ Trial De

gn!

Induction Continuous
treatment?

Treatment until

ISA + RVd Primary endpoin

IMROZ': NDMM Ml 4 x 6-week Fe + PES (40 mo vs
patients ineligible [3 cycles unacceptable 62.5 mo)
for HDT-ASCT ji toxicities Secondary
(N = 440} E
3
E
5
[3

Crossover

Primary endpoint: PFS.

Secondary endpoints: Safety, rate of 2VGPR, MRD negativity rate, and CR rate

atents excluded due to age >00 years or comerbities.
‘inthe continuous phase, patents randomized 1 the VR arm who experience PD may ros over to receive Isa Ra ,
1. hitpsicinicatirals goviet2/show NCTO3319667, PeerView.com

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38. Preparing for Quadruplet Dosing Used in the IMROZ Trial!

Day 1 8 15 22 29 36 43
teat orb] 1091 E E
meza [oros
3 vec ram
E prot || asm
aus 20m
Day 1 3 A 2 =

on day

1.Facon Total. EHA 2018. Abstract PB2185. PeerView.com

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39. PFS Improvement with Isa-VRd
A New CD38 Quad Option in NDMM?

IMROZ primary endpoint met, showing
that the addition of Isa to VRd
significantly improves PFS in ASCT-

ineligible patients with NDMM12

x
20] Ror popusson or dean = 060
2 PDT bylogvonk et Isa-VRd
IE DE VUE UE DE DE DO DEV OR eden
PFS, NR 54.3
Tine, mo
amd DOUTE HR = 0.60 (98.5% Cl, 0.41-0.88)
IsatuumabVRd 265 243 234 217 201 190 177 164 153 104 43 2 0 P <.001
Vidalone 0 ASS ial 12d 96 89 81 70 51 20 2 0

40% reduction in risk of progression or death

1. Facon Total ASCO 2024, Abstract 7500.2. Facon T ot al N Engl J Med. 2024:Jun 3. [Epub ahead of pri. PeerView.com

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40. IFM2020-05/Benefit Compares Isa Quads
With Isa Triplets in ASCT Ineligible NDMM

Screening

Les Beyond
D-20001 1 1 Erde re pol e

Primary

pores ‘endpoint

ETES MRO

2002009 fi Key
Loi |

tes À % mens E abt,

MRD negativity at Ca CE neon BI andpoins:
10° at 18 months oo vr er re] crate,
significantly vechtämm À MRD- CR

igher in Isa- (NGS, 10)
higher in Isa-VRd EE

arm compared to Inston Oy 142 A ren cy 1-90 ia aes
IsaRd arm (53% vs rom PFS,
RPO)2509 Dt ob 06 om om

26%, P <.0001)'2

Re PR u contrae
ono II | pesen ro,
or (Ape Kronen TT vraccegaio
Se acer,

i e] eters

coma!

+ >
MRD (sono marow aspate) 1 In case of PR or better 12 mántns. 18 Months. 24 months Yearly

* Assuming that 15% of patients would be MRO negative at
18 months inthe sa-Rd arm (based on approximated nal rss from MAI), inclusion of 242 patents would give an 80% power to detect an improvement from 15%

Lo 30% inthe Isa-VR arm at a 2sidd 0 of 0.05, To account or potential dropouts, 270 patients wore planned to be enroled A

1. Leleu XP et al. ASCO 2024. Abstract 7501. 2 Leleu XP otal. Na Mad. 2024:Jun 3. (Epub ahead of pri. PeerView.com

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41. Ongoing Phase 3 CEPHEUS Trial Will Provide More

tion Maintenance
28-day cycles

Induction/Consoli

SC daralRd cycles 9+
Dara: 1,800 mg SC Q4W
R: 25 mg PO days 1-21
d: 40 mg PO days 1, 8, 15, 22

Inclusion Criteria

NDMM without
intent for
transplant as

initial therapy
ECOG PS 0-2

CrCl 230
mUmin/1.73 m?

Rd cycles 9+
N= 360

Primary endpoint: overall MRD negativity
Secondary endpoints: PFS; durable MRD; ORR, VGPR, and CR; PFS2; and OS

1. Zwoogman $ et al. J Cin Oncol. 87:{suppl 15) Abstract TPS8056.

PeerView.com/QTT827

Information on Dara Quads as Primary Therapy!

Long-term
safety,
subsequent
therapy, PFS2,
and survival
follow-up

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42. Clinical Consult: What if Celine
Had Presented With High-Risk Features?

Celine is a 75-year-old woman with Discussion
NDMM, T8 compression fracture, and + Would you be more or less likely to
comorbid COPD utilize a quad?

Current status + Is there an ideal partner for a CD38 in
+ Creatinine 1.1 HR patients with ASCT ineligible MM?

+ PS of 1
+ Standard-risk cytogenetics

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43. GMMG-CONCEPT Also Showed That Isa-KRd was Active
In ASCT-Ineligible Patients With High-Risk MM!

TE Patients

(n=99) ‘TNE Patients (n = 26)

MRD negative
(Gay tire pol) 81 (81.8) 18 (69.2)
‘Sustained MRD negativity for 26 mo 72 (72.7) 14 (53.8)

62 (62.2) 12 (46.2)

Sustained MRD negativity for 212 mo

After median s in TNE arm, median PFS was not reached

1. Leypoldt LB et al. J Clin Oncol 2024:4226-37. PeerView.com

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44. Principles for Safe Delivery of CD38 Antibody Therapy‘

Oral HSV prophylaxis (regardless of zoster vaccination status)

Appropriate premedication (acetaminophen, diphenhydramine, dexamethasone, and/or
methylprednisolone, and montelukast)

Pretherapy blood screening: Type and cross match, screen for hepatitis B core Ab and surface
Ag prior to treatment initiation and every 6 months; initiate prophylaxis with entecavir if Hep B
core Ab positive

SC vs IV administration; observation period required after first dose
— 3 hours for SC and 6 hours for IV; average infusion time is >4 hours

Treat infections aggressively

- Consider immunoglobulin replacement for IgG levels <400 mg/dL and if there is a history of
infection with hypogammaglobulinemia

1. Darzalx (daraumumab) Preserbing infomation. Nips an accossdata fa. govarogsalle_docvabel2010776109650190 pdt
2 Sarcisa(satuxmab-e) Prosenbing Information. tps war accessdaa da govdrugsallda-SocsNabo/2020/7611 1380008 pal u
3. Leo SK et al. Cin infect Dis. 2021:73(6):.01372-01375. PeerView.com

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45. Isatuximab Emerging SC Formulation

+ Currently being assessed in a phase 3

+ SC isatuximab delivered via an on- noninferiority trial (IRAKLIA)?
body delivery system (OBDS) shows
comparable efficacy to IV and offers a Estimated N = RRMM patients
hands-free option with controlled (study participants) who have received at least
delivery! 1 prior line of therapy including lenalidomide

and a proteasome inhi

pomalidomide and pomalidomide and
dexamethasone dexamethasone

1. Quach H et a 2023 International Myeloma Society Annual Meeting. Abstract P-206 2. ts Cicas govct2/showNCTOS405166. PeerView.com

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46. Audience Q&A © |

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