IsKia Trial

[Slide 1] IsKia EMN24 Study Design 42 active sites; enrollment: Oct 7, 2020 - Nov 15, 2021 Induction Post-ASCT consolidation Light consolidation Four 28-day cycles Four 28-day cycles Twelve 28-day cycles 4x KRd 4x KRd 12x KRd K: 20 mg/m² IV dd 1 CC 1 only; MOBILIZATION Key eligibility K: 56 /m2 IV dd 1,8,15 K: 56 mg/m² IV dd followed by 56 mg/m² IV dd criteria: Cy: 2-3 g/m² CC 5-8 1,15 8,15 CC 1 and dd 1,8,15 CC 2-4 TE NDMM patients followed by R: 25 mg PO daily dd 1-21 R: 10 mg PO dd 1-21 R: 25 mg PO daily dd 1-21 G-CSF aged <70 years d: 40 mg PO dd 1,8,15,22 d: 20 mg PO dd 1,15 d: 40 mg PO dd 1,8,15,22 for stem-cell collection Stratification: R - Centralized FISH 4x Isa-KRd and (standard risk/missing Isa: 10 mg/kg IV dd 1,8,15,22 4x Isa-KRd MEL200-ASCT 12x Isa-KRd vs. high risk defined as CC 1, followed by 10 mg/kg IV Isa: 10 mg/kg IV dd 1,15 CC del(17p) and/or t(4;14) dd 1 and 15 CC 2 to 4. MEL: 200 mg/m² Isa: 10 mg/kg IV d 1 5-8 and/or t(14;16); - ISS (I vs. II and III) K: 20 mg/m² IV dd 1 CC 1 only; followed by K: 56 mg/m² IV dd K: 56 mg/m² IV dd 1,8,15 followed by 56 mg/m² IV dd ASCT 1,15 CC 5-8 8,15 CC 1 and dd 1,8,15 CC 2-4 R: 10 mg PO dd 1-21 R: 25 mg PO daily dd 1-21 R: 25 mg PO daily dd 1-21 d: 20 mg PO dd 1,15 d: 40 mg PO dd 1,8,15,22 d: 40 mg PO dd 1,8,15,22 The EMN24 IsKia trial is registered with ClinicalTrials.gov: NCT04483739; it was sponsored by the European Myeloma Network (EMN). All patients provided informed consent. This presentation includes discussion of the off-label use of a drug or drugs for the treatment of multiple myeloma. TE, transplant-eligible; NDMM, newly diagnosed multiple myeloma; FISH, fluorescence in situ hybridization; del, deletion; t, translocation; ISS American Society of Hematology International Staging System stage; R, randomization; Isa, isatuximab; K, arfilzomib; R, lenalidomide; d, dexamethasone; IV, intravenous; dd days; cc, cycles; PO, orally; Cy, cyclophosphamide; G-CSF, granulocyte colony-stimulating factor; MEL, melphalan; ASCT, autologous stem-cel transplantation; MRD, minimal residual disease; NGS, next-generation sequencing; PFS, progression-free survival --- [Slide 2] Primary Endpoint: Post-consolidation MRD negativity (ITT analysis) NGS, 10⁻⁵ NGS, 10⁻⁶ 100% OR 1.67, p=0.049 100% OR 2.29, p<0.001 90% 90% 77% 80% 80% 67% 67% 70% 70% 60% 60% Patients (%) 50% Patients (%) 48% 50% 40% 40% 30% 30% 20% 20% 10% 10% 0% 0% Isa-KRd KRd Isa-KRd KRd (N=151) (N=151) (N=151) (N=151) >VGPR after consolidation was 94% in both arms; ≥CR 74% VS 72% and sCR 64% vs 67% in the IsaKRd VS KRd arms. High MRD compliance and sample quality (97-100% of sample evaluable at 10⁻⁵ and 10⁻⁶ cut-offs). Consistent MRD results were detected by next-generation flow In the logistic regression analysis, ORs, 95% Cls, and p-values were adjusted for stratification factor. American Society of Hematology MRD, minimal residual disease; ITT, intention to treat; NGS, next-generation sequencing; OR, odds ratio; p. navalue: ka isaturimabe c carlitionih: 0 lenalidamide: de 1 dexamethasonet CL confidence Interval --- [Slide 3] Post-consolidation MRD negativity by NGS Subgroup analysis by cytogenetic risk NGS, 10⁻⁵ NGS, 10⁻⁶ 100% 100% 90% 90% 79% 78% 80% 77% 80% 77% 72% 69% Patients (%) 70% 65% 70% 65% 60% 53% 60% 53% 48% 50% 50% 40% 40% 30% 30% 27% 20% 20% 10% 10% 0% 0% 0 HRCA 1 HRCA 2+ HRCA 0 HRCA 1 HRCA 2+ HRCA Isa-KRd KRd Isa-KRd KRd 1 HRCA was defined as the presence of one of the following high-risk cytogenetic abnormalities: del(17p13.1), t(4;14) (p16.3;q32.3), t(14;16) (q32.3;q23), gain(1q21), or amp(1q21); 2+ HRCA was defined as the presence of at least two high-risk cytogenetic abnormalities. American Society of Hematology MRD, minimal residual disease; NGS, next-generation sequencing: HRCA, high-risk cytogenetic abnormalities; Is isatuximab; K, carfilzomib; R, lenalidomide; d, dexamethasone; del, deletion; t, translocation; amp, amplification --- [Slide 4] Safety analysis: treatment-related adverse events Isa-KRd (n=151) KRd (n=151) Any grade, n (%) Grade 3-4, n (%) Any grade, n(%) Grade 3-4, n (%) Pts with ≥1 hematologic toxicity 83 (55) 61 (40) 67 (44) 46 (30) Anemia 32 (21) 5 (3) 28 (19) 5 (3) Neutropenia 62 (41) 55 (36)* 39 (26) 33 (22)* Thrombocytopenia 51 (34) 22 (15) 38 (25) 25 (17) Pts with ≥1 Non-Hematologic toxicity 136 (90) 61 (41) 129 (85) 56 (37) SARS-CoV-2 infection Infections (excluding COVID19) 55 (36) 23 (15) 49 (32) 17 (11) Isa-KRd (n=151) KRd (n=151) Asthenia/fatigue 37 (25) 5 (3) 40 (26) 3 (2) Any grade, Grade ≥3, Any grade, Grade >3, Dyspnea 20 (13) 2 (1) 9 (6) 1 (<1) n (%) n (%) n (%) n (%) 39 (26) 3 (2) 28 (19) 2 (1) Rash 33 (22) 5 (3) 40 (26) 5 (3) Peripheral neuropathy 22 (15) 0 25 (17) 0 Infusion-related reactions 30 (20) 5 (3) 2 (1) 0 Cardiac disorders 11 (7) 1 (<1) 19 (13) 5 (3) Vascular disorders 29 (19) 7 (5) 33 (22) 15 (10) Hypertension 5 (3) 2 (1) 6 (4) 3 (2) Thromboembolism 12 (8) 4 (3) 16 (11) 9 (6) Gastrointestinal disorders 79 (52) 10 (7) 73 (48) 8 (5) Nausea 36 (24) 4 (3) 31 (21) 2 (1) Vomiting 18 (12) 2 (1) 12 (8) 1 (<1) *p-value =0.008 Diarrhea 41 (27) 6 (4) 37 (25) 5 (3) American Society of Hematology Isa, isatuximab; K, carfilzomib; R, lenalidomide; d, dexamethasone.

[Slide 1] Primary Endpoint: Post-consolidation MRD negativity (ITT analysis) NGS, 10⁻⁵ NGS, 10⁻⁶ 100% OR 1.67, p=0.049 100% OR 2.29, p<0.001 90% 77% 90% 80% 67% 80% 70% 67% 70% 60% Patients (%) 60% 50% 40% Patients (%) 48% 50% 40% 30% 30% 20% 20% 10% 10% 0% 0% Isa-KRd KRd Isa-KRd KRd (N=151) (N=151) (N=151) (N=151) >VGPR after consolidation was 94% in both arms; >CR 74% vs 72% and sCR 64% VS 67% in the IsaKRd VS KRd arms. High MRD compliance and sample quality (97-100% of sample evaluable at 10⁻⁵ and 10⁻⁶ cut-offs). Consistent MRD results were detected by next-generation flow in the logistic regression analysis, ORs, 95% Cls, and p-values were adjusted for stratification factor. American Society of Hematology MRD, minimal residual doease ITT, intention to treat, NGS, New gener altion requending OR, adds who A prove ha natuslimaly K carfizonib L lenalidomide d, desamethasone CL confidence interval --- [Slide 2] IsKia EMN24 Study Design 42 active sites; enrollment: Oct 7, 2020 Nov 15, 2021 Induction Post-ASCT consolidation Four 28-day cycles 4x KRd Primary endpoint: 4x KRd Key eligibility K: 20 mg/m2 IV dd 1 CC 1 only; MOBILIZATION MRD negativity by NGS after followed by 56 mg/m² IV dd K: 56 mg/m² IV dd 1,8,15 criteria: 8,15 CC 1 and dd 1,8,15 cc 2-4 cy. 2-3 4/m² CC 5-8 post-ASCT consolidation TE NDMM patients R: 25 mg PO daily dd 1-21 followed by R: 25 mg PO daily dd 1-21 aged <70 years G-CSF d: 40 me PO dd 1,8,15,22 Key secondary d: 40 mg PO dd 1,8,15,22 for stem-cell collection endpoints: Stratification: R Centralized FISH 4x Isa-KRd and MRD negativity after (standard risk/missing Isa: 10 mg/kg IV dd 1,8,15,22 4x Isa-KRd induction; vs. high risk defined as MEL200-ASCT PFS del(17p) and/or t(4;14) CC 1, followed by 10 mg/kg IV Isa: 10 mg/kg IV dd 1,15 cc and/or t(14;16); dd 1 and 15 CC 2 to 4. MEL: 200 mg/m3 5-8 ISS (1 vs. II and as) K: 20 mg/m2 IV dd 1 cc 1 only; followed by K: 56 mg/m² IV dd 1,8,15 Other Becondary followed by 56 mg/m2 IV dd ASCT CC 5-8 endpoints: 8,15 CC 1 and dd 1,8,15 CC 2-4 R: 25 mg PO daily dd 1-21 Sustained MRD negativity R: 25 mg PO daily dd 1-21 d: 40 mg PO dd 1,8,15,22 d: 40 mg PO dd 1,8,15,22 MRD by NGS IL templet eligible, NOMM - Aproved - - - - - the / - - \ - BL American Society of Hematology International Reging funishem - 4, - M / 4, - a - 4. - X - - days X POL valy a / G-CM, - - factor) MO, / AKT, - - transportation - - - - NOS - - M - - - --- [Slide 3] Measurable Residual Disease as a Surrogate Endpoint for Studies in Patients with Newly Diagnosed Myeloma Meta-analysis of MRD in 8098 patients Impact of Treatment Effect on MRD and PFS PFS HR 0.33 (95% CI 0.28 - 0.40), OS HR 0.50 05 (95% CI 0.42 - 0.59) in transplant eligible Weighted R²Trial (95% CI): 0.70 (0.41 0.98) patients with newly diagnosed myeloma patients PFS hazard ratio (95% CI) Treatment Effect on PFS (Log Hazard Ratio) " CLARON GEM2012 - No. of 01 DETERMINATION P relue* MAA O CANCIOR 0 ATLAS 10 2127 0.38 (0-32-0-45) <0001 GREEN MRD sensitivity threshold [ 10 CASSIOPEA 5361 031 (0-27-036) <0001 ALCYONE 10 10 1469 022 ID 16-0-29) <0001 High-nsk" 495 0.45 (D-36-058) 0001 CASTOR Cytogenetic risk 1 Standard risk 583 0.40 (0 26-0 60) 0.001 MFC 2201 0.37 (D-30-046) 0001 13 [ NGF 661 022 to 14-033) <0001 45 00 15 1.9 15 20 25 Method of MRD assessment NGS 3974 026 (022-031) <0001 Treatment Effect on MRD (Log Odds Ratio) PCR 321 0.27 ID 19-037) 0001 Depth of clinical response { CR or better 815 038 (0-29-050) 0001 at the time of MRD measurement VGPR or better 959 031 (0 23-0 43) 0001 Measurement of MRD status Pre-maintenance" 979 034 (023-051) <0001 pre-maintenance and at 12 months 12 months after after start of maintenance 851 021 (0-15-029) <0001 start of maintenance 0 0.2 0.4 06 08 I 1.2 Cl=Confidence interval; HR=Hazard ratio; MRD=Measurable residual disease; NGF=Next generation flow cytometry; NGS=Next generation sequencing; OS=Overall survival; PFS=Progression-free survival Munshi NC et al. Blood Adv 2020;4:5988-5999 American Society of Hematology Paiva B et al. Blood Adv 2023 Aug:Online ahead of print --- [Slide 4] Quadruplets in Transplant Eligible Patients with Newly Diagnosed Myeloma GRIFFIN: A Randomized, Phase II Study of Lenalidomide, Bortezomib and Dexamethasone (RVd) VS Daratumumab, Lenalidomide, Bortezomib and Dexamethasone (D-RVd) in Transplant Eligible Patients with Newly Diagnosed Myeloma 100 90 89.0% 87.2% Hypothetical Trial Design 80 80-7% Phase III Trial of D-RVd vs RVd-Bispecific 70 0% Progression-free survival (%) 70 Monoclonal Antibody for Transplant Eligible 60 Patients with Newly Diagnosed Myeloma so 40 Detectable PFS Hazard Ratio of 0.70 30 RVd 90% power, 1-sided a of 0.025 D-RVd 20 HR 0.45 (95% (10-21-0-95). Enrollment: 400 patients / year 10 p=0.032 One interim analysis for efficacy / futility 0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 S1 54 57 60 after half the PFS events have occurred Number at risk (number censored) RVd 103 93 77 72 70 68 63 61 59 53 S1 46 42 39 35 33 25 12 3 3 0 (0) (9) (22) (27) (28) (30) (35) (37) (50) (51) (53) (60)(73) (82) (82) (85) D-RVd 104 98 94 90 90 89 86 85 81 81 79 68 59 58 56 54 45 23 12 3 0 Sample size: 1742 patients (0) (5) (8) (10) (10) (10) (12) (13) (15) (15) (17) (27) (35) (36) (81) Years to Accrue: 4.4 Years to final PFS analysis: 9.5 ASH Abstract LBA-1: Phase 3 Randomized Study of Daratumumab+ Bortezomib, Lenalidomide, and Dexamethasone (VRd) Versus VRd Alone In Patients with Newly Diagnosed Multiple Myeloma Who Are Eligible for Statistical analysis courtesy of Dr. Susan Geyer Autologous Stem Cell Transplantation: Primary Results of the PERSEUS Trial D=Daratumumab; d=Dexamethasone; PFS=Progression-free surviv R=Lenalidomide; V=Bortezomib Voorhees PM et al. Blood 2020;136:936-45 American Society of Hematology Voorhees PM et al. Lancet Haematol 2023;10:e825-e

[Slide 1 — IsKia (EMN24) title slide, 65th ASH Annual Meeting, Dec 9-12 2023, Abstract #4] Results of the Phase III Randomized IsKia Trial: Isatuximab-Carfilzomib-Lenalidomide-Dexamethasone (Isa-KRd) vs Carfilzomib-Lenalidomide-Dexamethasone (KRd) as Pre-Transplant Induction and Post-Transplant Consolidation in Newly Diagnosed Multiple Myeloma Patients. Presenter: Francesca Gay, MD, PhD (University of Torino), on behalf of the European Myeloma Network (EMN). [Full author/affiliation list on slide; conference-logo header omitted.]

[Slide 1] A Phase II Study of Isatuximab, Weekly Carfilzomib, Lenalidomide, and Dexamethasone in Newly Diagnosed, Transplant-Eligible Multiple Myeloma (The SKylaRk Trial) Elizabeth O Donnell 2.4, Clifton 1 Mo24, Andrew J. Yee14 Omar Nadeem24, Jacob Laubach24, Jacalyn Rosenblatt Nikhil Munshi2⁴, Shonali Midha2 Diana Cirstea Nora Horick¹, Paul G Richardson24, Noopur Raje1 MASSACHUSETTS Massachusetts General Hospital Cancer Center, 2 Dana-Farber Cancer Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA MGH GENERAL HOSPITAL Dana-Farber CANCER CENTER HARVARD MEDICAL SCHOOL Cancer Institute Background Results Clinical data support the combination of a CD38 monocional antibody, an immunomodulatory drug, a Patient Characteristics Response to Therapy Survival proteasome inhibitor, and a glucocorticoid for the treatment of newly diagnosed multiple myeloma (MM) Characteristic No Patients A. Progression Free Survival N-50 % 004 NP% WR $ Isatuximab (Isa) is a CD38 monocional antibody that Median Age Diagnosis 1.0 59 509 3) binds to a unique epitope of the CD38 receptor that Sex are 2 10% eliminates MM cells by antibody-dependent cellular Female 23 46.0 PR 0.8 cytotoxicity, antibody-dependent cellular phagocytosis, Male 27 54.0 VGPR 45% Race complement-dependent cytotoxicity and direct Black or Afican-American 10.0 Response (%) a 50% CR 60% 0.6 White 44 68.0 CR Median PFS .3% (95% CI 83.4%- apoptosis without the need for crosslinking 5 Our study evaluates the addition of isatuximab to 2.0 Ce 0.4 99.8%) at 24 months Other 10% weekly carfilzomib, lenalidomide, and dexamethasone 65 Stage Diagnosis 27% 28 56.0 0.2 (Isa-KRd) in all-risk, transplant-eligible patients with 02 16 32.0 newly diagnosed MM (NDMM) and stratifies a 6 12.0 0.0 maintenance based on cytogenetic risk Revised ISS Stage Diagnosis 0 0 3 6 9 12 15 18 21 24 27 30 33 36 56 32.0 Cycle Cycle 8 Auto-SCT - Study Design 32 64.0 n=45 n148 n°5 B. Overall Survival . 2 4.0 - ECOG Performance Status MRD Negativity 10-5 1.0 0 26 56.0 AN 22 44.0 0.8 High-Risk Cytogenetics 72% Yes 23 46.0 0.6 del 17 9 18.0 50% Median OS 95.8%% (95% CI 90.2%- dup of 15 00.0 4% 1(4,14) 4 8.0 43% 0.4 100%) at 24 months ION double hit 5 10.0 ON No 23 46.0 0.2 - Unknown 4 10 ON 20% Serum Heavy/Light Chain c Cycle 4 - - 0.0 - - gG 22 44.0 gA 15 00.0 0 3 6 9 12 15 18 21 24 27 30 33 36 Light chain only 8 16.0 Of the 45 patients evaluable for response, MRD results were includes del 17, dup 10. 14 14), 1(14,20) available after C4 for 28 patients achieving a VGPR or Other Outcomes Study Endpoints or the patients with gain of to had amplification, better. Of those, 43% (12/28) were MRD negative at 10-5, and duplication Primary: After C8, 72% (26/36) of evaluable patients and 20% (1/5) patients undergoing auto-SCT were MRD negative. There were no statistically significant changes in body composition Complete Response (CR + stringent (sCR)) rate after 4 Treatment-related Toxicity (n=50) measurements between baseline and the completion of 4 cycles or cycles of Isa-KRd consolidation/induction. Secondary: Total Quality of Life There was a significant improvement in total lean mass (p=0.01) AE Safety and tolerability of once-weekly Isa-KRd 1(2%) ( 2(4%) between baseline and end of induction adjusted for SCT status. Acute alrey easy NNO Minimal residual disease (MRD) 4 cycles, after 6 cycles Alanine amote walerase increased 8(12%) 6(12%) No significant differences in total cells, total templates, total in patients who undergo transplant (auto-SCT). after 8 2(4%) 2(4%) === Arena : productive templates; total and productive rearrangements; or Cerebral - accident 1(2%) 10%) I as **** cycles in transplant-deferred patients, and at 24 months Feligue 3(0%) 3(9%) I clonality, maximum productive frequency and T cell fraction between CR sCR rate after 6 cycles in patients who undergo 2(4%) 2(4%) " Febrie Neutroponia PARK - those patients achieving MRD negativity and those not and no transplant, after 8 cycles in transplant-deferred patients, 1(2%) - ----- - Fever 1(2%) significant differences between clonality at baseline and post- - and at 24 months for all patients symptoms 1(2%) (2%) PLAA - induction/consolidation Herebysis 1.(2%) - 1(2%) Overall response rate (ORR), Progression free survival - - " CAL Hypertension 1(2%) 1(2%) I (PFS), Overall survival (OS) LIDE Insorma 1(2%) 1(2%) Conclusions and Future Directions THEAS - Myocardial - 1(2%) 1(P%) - Key Eligibility Criteria Neutropens (2(22%) - ! Isa-KRd induces deep and durable responses in patients with Phoumonis 1(2%) 1(2%) - Pulmonary - 1(2%) 1(2%) standard- and high-risk NDMM with an ORR of 100%. Newly diagnosed multiple myeloma Hash 1(2%) 1(2%) - The overall safety profile is favorable and consistent with previous Considered candidate for high-dose chemotherapy with Haversble cerebral vasaconsirictive syndrome 10%) 1(2%) - - reports of similar regimen. stem cell transplant 1(6%) - 3(6%) ECOG performance status <2 (Plcare 1(2%) (2%) - - This regimen can be administered safely and effectively in the community-based practice setting Acceptable hematologic, hepatic, and renal function

[Slide 1 — Cross-study toxicity comparison, 4-drug vs 3-drug regimens, transplant-eligible NDMM (Richter, provided by Integrity CE)] Summary of Toxicities in Selected Studies of 4-Drug Versus 3-Drug Regimens for Transplant-Eligible Newly Diagnosed Multiple Myeloma AE (Any Grade / Grade 3-4), %: PERSEUS VRd(354) / Dara-VRd(355) | MASTER Dara-KRd(123) | GMMG-HD7 VRd(329) / Isa-VRd(331) | IsKia KRd(151) / Isa-KRd(151) Neutropenia: 59/51 | 69/62 | -- | 41/35 | 7.0/7.0 | 23.3/23.3 | 26/22 | 41/36 Anemia: 21/6 | 22/6 | -- | 21/11 | 6.1/6.1 | 3.9/3.9 | 19/3 | 21/3 Thrombocytopenia: 34/17 | 48/29 | -- | 20/8 | 4.6/4.6 | 6.6/6.3 | 25/17 | 34/15 Neuropathy: 51/4 | 53/4 | -- | 21/2 | 31.9/7.6 | 27.2/6.6 | 17/0 | 15/0 Infections: 77/27 | 86/35 | -- | NR | 22.8/9.7 | 25.4/12.1 | 32/11 | 36/15 URI: 25/2 | 32/<1 | -- | 36/1 | NR | NR | NR | NR Pneumonia: 11/6 | 18/11 | -- | NR | NR | NR | NR | NR Diarrhea: 54/8 | 61/11 | -- | 31/4 | NR | NR | 25/3 | 27/4 Sources on slide: 1. Sonneveld NEJM 2024;390:301-313 (PERSEUS) · 2. Costa J Clin Oncol 2021;40:2901-2912 (MASTER) · 3. Goldschmidt Lancet Haematol 2022 (GMMG-HD7) · 4. Gay Blood 2023;142(suppl 1):4 (IsKia). [Cross-trial comparison — trials differ in design/population; not head-to-head.]

[Slide 1] IsKia EMN24 Study Design 42 active sites; enrollment: Oct 7, 2020 Nov 15, 2021 Induction Post-ASCT consolidation Light consolidation Four 28-day cycles Four day cycles Twelve 28-day cycles 4x KRd 4x KRd 12x KRd K: 20 mg/m3 IV dd 1 cc 1 only; MOBILIZATION K: 56 mg/m3 IV dd 1,8,15 K: 56 mg/m2 IV dd Key eligibility followed by 56 mg/m2 IV dd cy: 2-3 g/m3 cc 5-8 1,15 criteria: 8,15 cc and dd 1,8,15 cc 2-4 followed by R: 25 mg PO daily dd 1-21 R: 10 mg PO dd 1-21 TE NDMM patients R: 25 mg PO daily dd 1-21 G-CSF d: 40 mg PO dd 1,8,15,22 d: 20 mg PO dd 1,15 aged <70 years d 40 mg PO dd 1,8,15,22 for stem- cell collection Stratification: R Centralized FISH 4x Isa-KRd and (standard risk/missing 4x Isa-KRd iss: 10 mg/kg IV dd 1,8,15,22 12x Isa-KRd vs. high risk defined as MEL200-ASCT CC 1, followed by 10 mg/kg IV Isa: 10 mg/kg IV dd 1,15 cc del(17p) and/or 1(4,14) MEL: 200 mg/m2 Isa: 10 mg/kg IV d 1 dd 1 and 15 cc 2 to 4. 5-8 and/or 1/14;16]; followed by K: 56 mg/m2 IV dd K: 20 mg/m2 IV dd 1 cc 1 only; K: 56 mg/m2 IV dd 1,8,15 ISS vs. and (ii) 1,15 followed by 56 mg/m2 IV dd ASCT cc 5-8 8,15 cc 1 and dd 1,8,15 cc 2-4 R: 10 mg PO dd 1-21 R: 25 mg PO daily dd 1-21 R: 25 mg PO daily dd 1-21 d: 20 mg PO dd 1,15 d: 40 mg PO dd 1,8,15,22 d: 40 mg PO dd 1,8,15,22 The EMN24 tutia that a registered with Clinicalfrials gov: if was sponsored by the (uropean Myeloma Network (EMN) All patients provided informed consent This presentation includes discussion of the off label use of drug or drugs for the treatment of multiple myeloma FK, transplant eligible NOMM, newly deposed multiple ISK, - the hybridication del deletion, as American Society of Hematology International Staging System stage indomization NA, & cartiounts & lenaldomide, 4 N, - AL days - cycles, PO orally Cy tydophosphemide, G-CSF, grandocyte miny stimulating factor MIL melphalen ASCT, - - transplantation MID, minimal ressidual here NGS next generation injurying PFS, - - and I isKia EMN24 Study Design I --- [Slide 2] Primary Endpoint: Post-consolidation MRD negativity (ITT analysis) NGS, 10⁻⁵ NGS, 10⁻⁶ 100% OR 1.67, p=0.049 100% OR 2.29, p<0.001 90% 90% 77% 80% 80% 67% 67% 70% 70% 60% 60% Patients (%) 50% 40% Patients (%) 48% 50% 40% 30% 30% 20% 20% 10% 10% 0% 0% Isa-KRd KRd Isa-KRd KRd (N=151) (N=151) (N=151) (N=151) ≥VGPR after consolidation was 94% in both arms; ≥CR 74% VS 72% and sCR 64% vs 67% in the IsaKRd vs KRd arms. High MRD compliance and sample quality (97-100% of sample evaluable at 10⁻⁵ and 10⁻⁶ cut-offs). Consistent MRD results were detected by next-generation flow In the logistic regression analysis, ORs, 95% Cls, and p-values were adjusted for stratification factor. American Society of Hematology MRD, minimal residual disease; III. intention to treat: NGS, next generation sequending: OR, odds ratio; A p-value; Isa, Isatuximab; K, carfilzomib; R, lenalidomide; d, dexamethasone; CL, confidence Interval. --- [Slide 3] MRD negativity rates improved over time (10⁻⁵) Isa-KRd KRd (N=151) (N=151) 100% OR 2.34, p<0.001 90% 77% 80% 70% 64% 67% Patients (%) 60% 49% 50% 45% 40% 30% 26% 20% 10% 0% Post induction Post ASCT Post Post induction Post ASCT Post consolidation consolidation American Society of Hematology MRD, minimal residual disease; p, p-value; ASCT, autologous stem-cell transplantation. --- [Slide 4] Conclusions Isa-KRd significantly increased post-consolidation 10⁻⁵ and 10⁻⁶ MRD negativity, as compared with KRd Isa-KRd significantly increased 10⁻⁵ and 10⁻⁶ MRD negativity after each treatment phase (Induction, Transplantation, Consolidation). Isa-KRd consistently increased MRD negativity at 10⁻⁵ and 10⁻⁶ in all subgroups of patients, including high-risk and very high-risk disease. Isa-KRd treatment was tolerable, with a toxicity profile similar to that in previous reports. 10⁻⁶ MRD negativity cut-off is more informative. 1-year sustained MRD negativity will be available in 2024 With a longer follow-up, this trial can offer the opportunity to explore the correlation between depth of MRD negativity and PFS/OS. American Society of Hematology Isa, isatuximab; K filzomib; R, lenalidomide; d, dexamethasone; MRD, minimal residual disease; PFS, progression- free survival; 05, overall survival.

[Slide 1] IsKia EMN24 Study Design 42 active sites; enrollment: Oct 7, 2020 - Nov 15, 2021 Induction Post-ASCT consolidation Light consolidation Four 28-day cycles Four 28-day cycles Twelve 28-day cycles 4x KRd 4x KRd 12x KRd K: 20 mg/m2 IV dd 1 CC 1 only; MOBILIZATION Key eligibility K: 56 mg/m² IV dd 1,8,15 K: 56 mg/m² IV dd followed by 56 mg/m2 IV dd criteria: Cy: 2-3 g/m² CC 5-8 1,15 8,15 CC 1 and dd 1,8,15 CC 2-4 TE NDMM patients followed by R: 25 mg PO daily dd 1-21 R: 10 mg PO dd 1-21 R: 25 mg PO daily dd 1-21 G-CSF aged <70 years d: 40 mg PO dd 1,8,15,22 d: 20 mg PO dd 1,15 d: 40 mg PO dd 1,8,15,22 for stem-cell collection Stratification: R Centralized FISH 4x Isa-KRd and (standard risk/missing Isa: 10 mg/kg IV dd 1,8,15,22 4x Isa-KRd vs. high risk defined as MEL200-ASCT 12x Isa-KRd CC 1, followed by 10 mg/kg IV Isa: 10 mg/kg IV dd 1,15 CC del(17p) and/or t(4;14) dd 1 and 15 CC 2 to 4. MEL: 200 mg/m² 5-8 Isa: 10 mg/kg IV d 1 and/or t(14;16); ISS (I vs. II and III) K: 20 mg/m² IV dd 1 CC 1 only; followed by K: 56 mg/m² IV dd 1,8,15 K: 56 mg/m2 IV dd followed by 56 mg/m2 IV dd ASCT 1,15 CC 5-8 8,15 CC 1 and dd 1,8,15 CC 2-4 R: 10 mg PO dd 1-21 R: 25 mg PO daily dd 1-21 R: 25 mg PO daily dd 1-21 d: 20 mg PO dd 1,15 d: 40 mg PO dd 1,8,15,22 d: 40 mg PO dd 1,8,15,22 MRD by NGS MRD by NGS MRD by NGS MRD by NGS TE, transplant eligible; NOMM, newly diagnosed multiple myeloma; FISH, fluorescence in situ hybridization: del, deletion; t, transfocation; 155, American Society of Hematology international Staging System stage; R, randomization Isa, isatualmab; K, tarfilizamily R, lenalidomide; d, dexamethasone W. intravenous; dd, days cc. cycles: PO. orally: Cy, cyclophosphamide: G-CSF, granulocyte colony stimulating factor; MEL melphalan: ASCT. autologous stem-cell transplantation: MRD minimal residual disease; NGS, naxt generation sequencing: PFS, progression- free survival. --- [Slide 2] MRD negativity rates improved over time (10⁻⁵) Isa-KRd KRd (N=151) (N=151) 100% OR 1.93, p=0.006 90% 77% 80% 64% 67% 70% Patients (%) 60% 49% 50% 45% 40% 30% 26% 20% 10% 0% Post induction Post ASCT Post Post induction Post ASCT Post consolidation consolidation American Society of Hematology MRD, minimal residual disease; P. p-value; ASCT, autologous stem-cell transplantation --- [Slide 3] MRD negativity rates improved over time (10⁻⁶) Isa-KRd KRd (N=151) (N=151) 100% 90% 80% 67% 70% Patients (%) 60% 52% 48% 50% 40% 27% 27% 30% 20% 14% 10% 0% Post induction Post ASCT Post Post induction Post ASCT Post consolidation consolidation American Society of Hematology

[Slide 1] Efficacy of Induction Regimens in Transplant-Eligible Patients with NDMM DETERMINATION GRIFFIN2 PERSEUS³ IsKia⁴ GMMG-HD75 RVd + HDT-ASCT D-RVd VS RVd D-VRd VS VRd Isa-KRd VS KRd Isa-RVd vs RVd Treatment VS RVd alone both +HDT-ASCT both +HDT-ASCT both +HDT-ASCT Both +HDT-ASCT Maintenance RvsR D-R VS R D-R VS R None Isa-R vs R N 365 VS 357 104 VS 103 355 VS 354 151 VS 151 331 V. 329 Median 76.0 49.6 47.5 21 ~48 follow-up, mo ≥ VGPR rate, % 83 VS 80 96 VS 77 95 VS 89 94 vs 94 83 VS 69 87.9 vs 70.1 ≥ CR rate, % 46.8 VS 42.0 83 VS 60 (P <.001) 74 VS 72 44 VS 34 MRD-negative 64 VS 30 75.2 VS 47.5 77 VS 67 66 VS 48 54 vs 40 rate (10⁻⁵), % (P <.001) (P <.001) (P = 049) (P <.001) Median: 4-yr rate: 48-mo rate: PFS 67.5 VS 46.2 mo 87.2% VS 70.0% 84.3% VS 67.7% 1-yr rate: 4-yr rate: 95% VS 95% 76% VS 69% (P <.001) (P = .032) (P <.001) DECERA 1. Richardson. NEJM. 2022;387:132 2 Voorhees. Lancet Haematol. 2023;10:e825. CCO IS NOW CLINICAL Education 3. Sonneveld. NEJM. 2024;390:301. 4. Gay. ASH 2023. Abstr 4.5. Mai. JCO. 2024;43:1279. Slide credit: 108 deceraclinical.com/education