GMMG-HD7 Trial

[Slide 1] Secondary end point of Part 1: PFS from first randomization HD7 Kaplan-Meier estimates for PFS from the first randomization 100 75 PFS (%) 50 25 HR, 0.70 (95% CI, 0.52-0.95): stratified log-rank Pvalue=0 0184 Isa-RVd ASCT R or Isa.R RVd ASCT R or Isa-R 0 0 12 24 36 48 60 Number at risk (censored) Months since first randomization Isa-RVd 331 (0) 300 (8) 271 (6) 255 (6) 122 (116) 6 (111) RVd 329 (0) 273 (17) 252 (4) 222 (8) 104 (102) 5 (92) At a median follow-up of 48 months, 18 weeks of Isa-RVd induction without consolidation resulted in a 30% reduction in risk of progression or death compared with RVd regardless of maintenance therapy received UK ASCT. - on transport CO. contidence Insurance a - HR name 75% - HD GMMG and Heidelberg University Hospital I ASH 2024 PFS. = I I I > I I D --- [Slide 2] Weighted risk set estimator of PFS to account for HD7 second randomization with Len maintenance 100 75 PFS (%) 50 "Stratified weighted log-rank test P value=0.016 Isa-RVd ASCT R or Isa-R 25 Isa-RVd ASCT & RVd ASCT R or Isa-R 0 RVd ASCT & 0 12 24 36 48 60 Months since first randomization Number at risk (censored) Isa-RVd 331 (0) 300 (8) 271 (6) 255 (6) 122 (116) 6 (111) RVd 329 (0) 273 (17) 252 (4) 222 (8) 104 (102) 5 (92) The weighted risk set estimator accounting for second randomization confirms a significant benefit for Isa-RVd vs. RVd induction followed by standard of care lenalidomide maintenance only UK GMMG and Heidelberg University Hospital I ASH 2024 ASCT - intoins - transport it. decumethane - natural PRIM progreman this survivel Rt.am - V. HD 10 --- [Slide 3] PFS benefit by multivariable analysis HD7 HR (95% CI); Pvalue Arm RVd versus Isa-RVd 0.61 (0.45-0.83) P=0 002 Sex Male versus Female 0.95 (0 69-1.31) P=0 75 Age Continuous (per year) 1.02 (1.00-1 04) P=0 031 WHO PS Grade 0/1 versus Grade =1 1.18 (0 75-1.85) P=0 479 Stage I versus Stage II 1.97 (1.35-2.89) P<0 001 ISS Stage I versus Stage III 3.44 (2.06-5.74) P<0 001 LDH Normal versus High* 1.93 (1 28-2 91) P=0 002 Cytogenetic risk Standard risk versus High risk® 2.02 (1.41-2.90) P=0 001 Renal insufficiency No versus Yes 0.42 20-0.91) P=0:027 0.1 02 0.5 1 2 5 Hazard ratio (95% CI) The PFS benefit for Isa-RVd versus RVd was also confirmed on multivariable analysis, including ISS stage, cytogenetics, and renal insufficiency UK Cutret as concentations ground that the upper snot of named vign-nik cytopinetics amount as the - of at wast - of the fullswing HD GMMG and Heidelberg University Hospital I ASH 2024 relutions or 114 = actioned creatinew instruct of MIX that = - - - - of mare than 177 unit CI confidence interval E HR tablets iss 160, international triping 12 System LOM. lacture ML nome R. institute V. WHO FIL Health Organization performance itate --- [Slide 4] Summary HD7 Addition of Isa to RVd during an 18-week induction followed by ASCT without consolidation and regardless of second randomization resulted in an impressive 30% reduction in risk of progression or death compared with standard of care RVd Weighted risk set estimator analyses accounting for second randomization with lenalidomide only confirmed the significant benefit for Isa-RVd vs. RVd induction The PFS benefit was observed across clinically relevant subgroups Isa-RVd is the first regimen to demonstrate a deep and rapid response reflected by a statistically significant MRD- benefit at the end of induction and post-transplant in a Phase 3 trial, which translated to a PFS benefit VS RVd ASCT was feasible after induction therapy, as a similar proportion of patients in both treatment arms proceeded to ASCT, and hematologic recovery was comparable between the Isa-RVd and RVd groups GMMG-HD7 is the first Phase 3 study to show that an 18-week initial quadruplet regimen with Isa, without consolidation, allows for significant long-term benefits regardless of subsequent maintenance therapy UK GMMG and Heidelberg University Hospital I ASH 2024 ACT - item as insurant = documethanance - establish MRD- - resident - regatively PF% programson the HD cardies R. I V 13

[Slide 1] GM MG Study design - Part 1 HD7 Part 1 Part 2 Isa-RVd Isa-R NDMM Induction (3 X 6-week cycles) N=662 +-WOH + ASCT Tandem ASCT if <CR or HR disease Treatment for R 1:1 Maintenance (4-week cycles) 3 years or until PD RVd R Stratification for randomization Isa: 10 mg/kg IV Cycle 1 Cycles 2-3 Cycle 1 Cycles 2-3 Cycles 4+ prior to: Days 1, 8, 15, 22, and 29 Days 1, 15, 29 Days 1, 8, 15, and 22 Days 1 and 15 Day 1 1. Induction: R-ISS stage (1/11 versus III versus not classified) R: 10/15/25 mg PO; Days 1-14 and 22-35 R: 10 mg (up to 15 mg, if tolerated) PO: continuously 2. Maintenance: R-ISS stage at study entry (I/II versus III versus V: 1.3 mg/m2 SC; not classified) and MRD- after last Days 1,4, 8, 11, 22, 25, 29, and 32 d: 20 mg PO: Days 1, 8, 15, HDM (no versus yes versus d: 20 mg POb; Days 1-2, 4-5, 8-9, 11-12, 15, and 22 unknown) 22-23, 25-26, 29-30, and 32-33 Primary end pointsᶜ: Post-induction MRD- (NGF, 10⁻⁵); PFS after second randomization Key secondary end points: PFS (whole study); OS (whole study and from second randomization); post-induction CR; CR and MRD- after HDM and during and after maintenance therapy Selected secondary end point: PFS after first randomization Here, we present the PFS from first randomization comparing Isa-RVd and RVd induction therapies UK Melphalan 200 mg/m2 On days of isatuximab infusion, dexamethasone will be administered intravenously as part of the premedication HD GMMG and Heidelberg University Hospital I ASH 2024 ASCT autologous stom cell transplant CR, complete response d, dexamethasone; HDM, high-dose melphalan; HR, high-risk; Isa, isatuximab; IV, intravenous, MRD- minimal residual disease negativity, NDMM newly diagnosed multiple myeloma, PD, progressive disease, PO, oral, 4 R, lenalidomide R-ISS, Revised International Staging System; SC, subcutaneous V, bortezomib --- [Slide 2] GM MG Patient disposition HD7 Randomized: n=662ª Isa-RVd RVd n=331 (ITT population) n=329 (ITT population) Started/continued after induction therapy Started/continued after induction therapy n=330/312 (94%) n=328/293 (89%) HDM + ASCT 1 HDM + ASCT 1 n=304 (92%) n=278 (84%) HDM + ASCT 2 HDM + ASCT 2 n=79 (24%) n=99 (30%) Randomized to Isa-Len/Len maintenance (87%) Randomized to Isa-Len/Len maintenance (82%) n=150/139 n=131/140 312 (94%) and 293 (89%) Isa-RVd and RVd patients, respectively, continued treatment after induction therapy UK ASH 2024 *2 RVd patients were excluded from the ITT population due to violation of exclusion criteria HD GMMG and Heidelberg University Hospital I ASCT autologous stem cell transplant, d, dexamethasone; HDM, high-dose melphalan, Isa, isatuximab ITT, intent-to-treat, R/Len, lenalidomide; V, bortezomib 6 --- [Slide 3] GM MG Secondary end point of Part 1: PFS from first randomization HD7 Kaplan-Meier estimates for PFS from the first randomization 100 75 PFS (%) 50 25 HR, 0.70 (95% CI, 0.52-0.95); stratified log-rank P value=0.0184 Isa-RVd ASCT R or Isa-R RVd ASCT R or Isa-R 0 0 12 24 36 48 60 Number at risk (censored) Months since first randomization Isa-RVd 331 (0) 300 (8) 271 (6) 255 (6) 122 (116) 6 (111) RVd 329 (0) 273 (17) 252 (4) 222 (8) 104 (102) 5 (92) At a median follow-up of 48 months, 18 weeks of Isa-RVd induction without consolidation resulted in a 30% reduction in risk of progression or death compared with RVd regardless of maintenance therapy received UK GMMG and Heidelberg University Hospital I ASCT autologous stem cell transplant; CI, confidence interval: d. dexamethasone; HR, hazard ratio; Isa, isatuximab; HD ASH 2024 PFS, progression-free survival, R, lenalidomide; V. bortezomib 9 --- [Slide 4] GM MG Weighted risk set estimator of PFS to account for HD7 second randomization with Len maintenance 100 75 PFS (%) 50 *Stratified weighted log-rank test P value=0.016 Isa-RVd ASCT R or Isa-R 25 Isa-RVd ASCT R* RVd ASCT R or Isa-R 0 RVd ASCT R* 0 12 24 36 48 60 Months since first randomization Number at risk (censored) Isa-RVd 331 (0) 300 (8) 271 (6) 255 (6) 122 (116) 6 (111) RVd 329 (0) 273 (17) 252 (4) 222 (8) 104 (102) 5 (92) The weighted risk set estimator accounting for second randomization confirms a significant benefit for Isa-RVd vs. RVd induction followed by standard of care lenalidomide maintenance only UK GMMG and Heidelberg University Hospital I ASH 2024 ASCT autologous stem cell transplant; d, dexamethasone; Isa, isatuximab; PFS, progression free survival; R/Len, lenalidomide; V. bortezomib HD 10

[Slide 1] GMMG-HD10/DSMM-XX/MajesTEC-5: MRD Negativity (10-⁵)a Arm A: Tec (QW)-DR Arm A1: Tec (Q4W)-DR Arm B: Tec (Q4W)-DVR (n=10) (n=20) (n=19) 100 100 100 66th ASH Annual Meeting 90 90 90 80 80 Testing 80 Negative Planned 70 Negative Negative Testing Patients (all treated), % 60 Patients (all treated), % 70 Negative Patients (all treated), % 70 Negative Planned 60 60 50 50 50 40 40 40 Negative 30 30 30 20 20 20 10 10 10 0 0 0 Cycle 3 Cycle 6 Cycle 3b Cycle 6° Cycle 3d Cycle 6* (Evolving) (Evolving) 100% of evaluable patients achieved MRD negativity by C3; no patients were MRD positive Date September 30. 2024 negativity - - defined - proportion patients and achived MND negatively (10th) regardless of response MND - determined by NOF testing - patient - not have Done marrow corrected the C3 " - MOD 06 Am patient - not tested a out - 1 patient discontried before ca and at - study MRD leving * - patient - MRD regative 10* she 06 and I - I patient discontinued before 03 end withing c German speaking Myeroma Multicenter Group/Devische Studengh Mutiples Myesom MRD. name residult - NOF generation for (ylometry QW allergy GEW every sects R enandomide, Tec. indistance bonezome 11 Presented by MS Rash of the 60th American Society of Hematology (ASH) Annual Mooting and exposition, December 10. 2024 Nan Diago, CA USA 66th ASH® Annual Meeting and Exposition --- [Slide 2] Secondary end point of Part 1: PFS from first randomization HD7 Kaplan-Meier estimates for PFS from the first randomization 100 75 66th ASH' Annual Meeting PFS (%) 50 25 HR, 0.70 (95% CI, 0.52-0.95): stratified log-rank P value=0 0184 Isa-RVd ASCT R or Isa-R RVd ASCT R or Isa-R 0 0 12 24 36 48 60 Number at risk (censored) Months since first randomization Isa-RVd 331 (0) 300(8) 271(6) 255(6) 122 (116) 6(111) RVd 329 (0) 273 (17) 252 (4) 222 (8) 104 (102) 5 (92) At a median follow-up of 48 months, 18 weeks of Isa-RVd induction without consolidation resulted in a 30% reduction in risk of progression or death compared with RVd regardless of maintenance therapy received UK ASCT autologous transplant DL confidence interval docamethasone HR ASH 2024 M I HD GMMG and Heidelberg University Hospital PFS, progression boo survival H. imalidomide V 9 66th ASH® Annual Meeting and Exposition

[Slide 1] Isatuximab, Lenalidomide, Bortezomib and Dexamethasone Induction Therapy for Transplant-Eligible Patients With Newly UNIVERSITATS Diagnosed Multiple Myeloma: Final Progression-Free Survival KLINIKUM Analysis of Part 1 of an Open-label, Multicenter, Randomized, GM MG HEIDELBERG Phase 3 Trial (GMMG-HD7) Hartmut Goldschmidt¹², Uta Bertsch¹,², Ema Pozek³, Axel Benner³, Roland Fenk4, Britta Besemer³, Christine Hanoun⁶, Roland Schroers⁷, Ivana von Metzler®, Mathias Hänel', Christoph Mann10, Lisa B. Leypoldt¹, Bernhard Heilmeier¹², Stefanie Huhn1, Sabine K. Vogel¹, Michael Hundemer¹, Christof Scheid13, Igor W. Blau¹⁴, Steffen Luntz15, Tobias A. W. Holderried16, Karolin Trautmann-Grill17, Deniz Gezer¹ᵃ, Maika Klaiber-Hakimi¹, Martin Müller²⁰, Evgenii Shumilov21, Wolfgang Knauf22, Christian S. Michel23, Thomas Geer²⁴, Hendrik Riesenberg²⁵, Christoph Lutz²⁵, Marc S. Raab¹², Martin Hoffmann27, Katja C. Weisel¹¹, Hans J. Salwender28, and Elias K. Mai¹ for the German-speaking Myeloma Multicenter Group (GMMG) HD7 investigators Internal Medicine V, Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heldelberg, Germany, National Center for Tumor Diseases Heidelberg, Heidelberg, Germany; 'Division of Biostatistics, German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, Germany; "Department of Hematology, Oncology and Clinical Immunology, University Hospital Düsseldarf, Disseldorf, Germany, Department of Internal Medicine II, University Hospital Tübingen, Tübingen, Germany, "Department for Hematology and Stem Cell Transplantation, University Hospital Exsen, Essem, Cermany; Medical Clinic R, Ruhe-University Bochum, Bochum, Germany; Department of Medicine 8 Hematology and Oncology, Gioathe-University Frankfurt, University Hospital, Frankfurt am Main, Germany; Department of Internal Medicine HI, Klinikum Chamnits, Chemnitz, Germany, "Department for Hematology, Oncology and Immunulagy, University Hospital GieBen and Marbury, Marburg, Germany; "Department of Oncology, Hemanology and BMT, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; "Clinic for Oneology and Hamatology, Hospital Barmherzige Brueder Regensburg, Regensburg, Germany, "Department of Internal Medicine L University Hospital Cologne, Cologne, Germany, "Medical Clinic, Charité University Medicine Barlin, Berlin, Germany, "Coordination Centre for Clinical Trials [KKS] Heidelborg, Heldelberg, Germany, "Department of Hamatology, Oncology, Stem Cell Transplantation, Insurance and Call Therapy, Clinical Immunology and thaumatology, University Hospital Bonn, Bonn, Germany; Department of Internal Medicine I, University Hospital Dresden, Dreuden, Germany, "Department of Hematology, Oncology, Homostassology, and Stem Call Transplantation, Faculty of Mudicine, RWTH Aachen University, Aachen, Germany, "Clinic for Hematology, Oncology and Palliative Care, Marien Hospital Düsselderf, Düsselderf, Germany, "Clinic for Hematology, Oscology and Immunology, Klinikum Sileah Hannower, Hannover, Germany, "Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Münster, Münster, Germany: "Canter for Hematology and Oneology Bethanien, Frankfurt am Main, Germany, "Department of Internal Medicine us, University Hospital Maina, Mains, Germany, Department all Internal Medicine 11, Diakoneo Clinic Schwäbisch-Hall, Schwäbisch-Hall, Germany, "Niematology/Oncology Center, Biolefald, Germany, "Hamasology/Oncology Center, Kabluns, Germany, "Medical Clinic A, Clinic Ludwigshafen, Ludwigshafen, Germany; UK "Asklepias Tumorzentrum Hamburg, AK Altoma and AK St. Georg, Hamburg, Germany HD ASH 2024; Final Abstract Code: 769 --- [Slide 2] Study design - - Part 1 HD7 Part 1 Pan 2 Isa-RVd Isa-R NDMM Induction (3 * 6-wook cycles) N=662 R HDM ASCT Tandem ABCT If <CR of HR disease Treatment TOX R 1.1 111 Maintants - nystes) 3 Pears - R - PICE RVd R Stratification for randomization Isa: 10 mg/kg IV Cycle 1 Cycles 2-3 Cycle 1 Cyclus 14 Cycles 44 prior to: Days 1. 8, 15, 22. and 29 Days 1. 15 29 Days 1 E 15. and 22 Days 1 and 15 Day 1 1. Induction: R-ISS stage (i/ill versus III versus not classified) R: 10/15/25 mg PO: Days 1-14 and 22-35 R: ⑉ mg page To 18 mg, ⑉ Internated) PD: continuintly 2. Maintenance: R-ISS stage at study entry (VIII versus III versus V 1.3 mg/mL SC, not classified) and MRD- after last Days 1.4.8. 11, 22. 25, 29, and 32 1⑆. 20 sný POL HDM (no versus yes versus Dept E U, EA d: 20 mg PO°, Days 1-2, 4-5, 8-9, 11-12, 15. amet 22. unknown) 22-23, 25-26, 29-30, and 32-33 Primary end points Post-induction MRD- (NGF, 10-5); PFS after second randomization Key secondary end points: PFS (whole study): OS (whole study and from second randomization): post-induction CR: CR and MRD- after HDM and during and after maintenance therapy Selected secondary end point: PFS after first randomization Here, we present the PFS from first randomization comparing Isa-RVd and RVd induction therapies UK Magnature 200 engine 'Us ave - - infusive, - will - administratived - #6 BART of the premedication HD GMMG and Heidelberg University Hospital I ASH 2024 NICT Item - Vaniplant DI compote responsible ( HOM high-dise HR. Ngh-res, From: 188. - IV. - MRD- I residual disause regativity NOMM new disgnosed nutsix Pystems, PID. progressive - PO - 4 Family y ! = I I I I I - --- [Slide 3] Patient disposition HD7 Randomized: n=662 Isa-RVd RVd n=331 (ITT population) n=329 (ITT population) Started/continued after induction therapy Started/continued after induction therapy m30/312 (94%) n=328/293 (89%) HDM + ASCT 1 HDM + ASCT 1 n=304 (92%) no278 (84%) HDM + ASCT 2 HDM + ASCT 2 n=79 (24%) n=99 (30%) Randomized to Isa-Len/Len maintenance (87%) Randomized to Isa-Len/Len maintenance (82%) n=150/139 n=131/140 312 (94%) and 293 (89%) Isa-RVd and RVd patients, respectively, continued treatment after induction therapy UK V Rve passents - mouse iron the ITT experiation Due to notation if exclusion citina HD GMMG and Heidelberg University Hospital I ASH 2024 ABCT autologique illess - transplant 8. HDM high dest Ba. - ITS exam to - N/Am V. 6 --- [Slide 4] MRD- rates post transplant in the ITT population¹ HD7 OR, 2.13 (95% CI, 1.56-2.92) OR, 2.22 P<0.0001 (95% CI, 1.63-3.03) P<0.0001 70 66.2% 63.4% Isa-RVd OR, 1.76 60 RVd (95% CI, 1.25-2.50) 50 47.7% P=0.001 43.8% Patients (%) 40 38.1% 30 25.8% 20 10 0 MRD- CR and MRD- 2VGPR and MRD- Compared with RVd alone, Isa-RVd led to deeper MRD- response post transplant UK a confidence ment CII. complete response, 1, - - ITT. intent is that MRD- mm/ resultual HD GMMG and Heidelberg University Hospital I ASH 2024 dissas nagativity OR adds ratio, R V. consume, VOPR, vary good cartier response 1 Ma E. el - 304 Presented in American florietty of - 2824 8

[Slide 1] Isatuximab, Lenalidomide, Bortezomib and Dexamethasone Induction Therapy for Transplant-Eligible Patients With Newly UNIVERSITÄTS Diagnosed Multiple Myeloma: Final Progression-Free Survival KLINIKUM Analysis of Part 1 of an Open-label, Multicenter, Randomized, GM MG ) HEIDELBERG Phase 3 Trial (GMMG-HD7) ) Hartmut Goldschmidt¹², Uta Bertsch1,2, Ema Pozek³, Axel Benner³, Roland Fenk4, Britta Besemer⁵, Christine Hanoun6, Roland Schroers7, Ivana von Metzler8, Mathias Hänel9, Christoph Mann10, Lisa B. Leypoldt¹¹, Bernhard Heilmeier¹², Stefanie Huhn1, Sabine K. Vogel1, Michael Hundemer¹, Christof Scheid13, Igor W. Blau¹⁴, Steffen Luntz15, Tobias A. W. Holderried16, Karolin Trautmann-Grill17, Deniz Gezer18, Maika Klaiber-Hakimi¹⁹, Martin Müller²⁰, Evgenii Shumilov²¹, Wolfgang Knauf²², Christian S. Michel23, Thomas Geer24, Hendrik Riesenberg²⁵, Christoph Lutz26, Marc S. Raab¹,², Martin Hoffmann2⁷, Katja c. Weisel11, Hans J. Salwender28, and Elias K. Mai¹ for the German-speaking Myeloma Multicenter Group (GMMG) HD7 investigators Biostatistics, German Internal Medicine II, University Hospital Tübingen, Tübingen, Germany; ©Department for Hematology and Stem Cell Transplantation, University Frankfurt Hospital am Main, Germany; Department of Internal 11, Internal Cancer Research Center (DKFZ) Heldelberg, Heldelberg, Germany; "Department of Hematology, Oncology and Clinical Immunology, University Hospital Essen, Düsseldorf, Essen, Germany; 'Medical Germany; Clinic Medicine v, Hematology, Oncology and Rheumatology, Heldelberg University Hospital, Heldelberg, Germany; National Center for Tumor Diseases Heidelberg, Heldelberg, Germany; Düsseldorf, Division of Department of Bochum, Germany; "Department of Medicine II - Hematology and Oncology, Goethe-University Frankfurt, University Gießen and Hospital, Marburg, Marburg, Germany; "Department of Oncology, Ruhr-University Bochum, Chemnitz, Germany; Department for Hematology, Oncology and Immunology, University Hospital Germany; Medicine III, Klinikum Chemnitz, Medical Center Hamburg-Eppendorf, Hamburg, Germany; "Clinic for Oncology and Hematology, Hospital Barmherzige Brueder Regensburg, Clinical Regensburg, Trials (KKS) Heidelberg, Department Heldelberg, Hematology of and BMT, University Hospital Cologne, Cologne, Germany; "Medical Clinic, Charité University Medicine Berlin, Berlin, Germany; "Coordination University Centre Hospital for Bonn, Bonn, Germany; 17Department of Germany; 16Department of Hematology, Dresden, Dresden, Germany; 18Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Oncology and Immunology, Klinikum Siloah Hannover, Internal Medicine I, University Oncology, Stem Cell Transplantation, Immune and Cell Therapy, Clinical Immunology and Rheumatology, Faculty of Medicine, RWTH Aachen University, Hannover, Aachen, Germany; Hematology, Oncology and Pneumology, University Hospital Münster, Schwäbisch-Hall, Schwäbisch-Hall, Germany; Main, Internal Medicine I, University Clinic for Hospital Hematology, Oncology and Palliative Care, Marlen Hospital Düsseldorf, Düsseldorf, Germany; Münster, 20Clinic Germany; for Hematology, "Center for Hematology and Oncology Bethanlen, Frankfurt am Germany; Germany; "Department of of Internal Medicine Medicine A, III, University Hospital Mainz, Mainz, Germany; "Department of Internal "Medical Medicine Clinic III, Diakoneo A, Clinic Ludwigshafen, Clinic Ludwigshafen, Germany; UK HD "Department 25Hematology/Oncology Center, Bielefeld, Germany; Hematology/Oncology Center, Koblenz, Germany; Hamburg, Germany 28Asklepios Tumorzentrum Hamburg, AK Altona and AK St. Georg, --- [Slide 2] Study design - Part 1 HD7 Part 1 Part 2 Isa-RVd Isa-R NDMM N=662 R 1:1 Induction (3 X 6-week cycles) HDM*+ ASCT Tandem ASCT If <CR or HR disease R 1:1 R 1:1 Treatment for Maintenance (4-week cycles) 3 years or RVd R until PD Stratification for randomization Isa: 10 mg/kg IV Cycle 1 Cycles 2-3 Cycle 1 Cycles 2-3 Cycles 4+ prior to: Days 1, 8, 15, 22, and 29 Days 1, 15, 29 Days 1, 8, 15, and 22 Days 1 and 15 Day 1 1. Induction: R-ISS stage (I/II versus III versus not classified) R: 10/15/25 mg PO; Days 1-14 and 22-35 R: 10 mg (up to 15 mg, if tolerated) PO; continuously 2. Maintenance: R-ISS stage at study entry (I/II versus III versus V: 1.3 mg/m2 SC; not classified) and MRD- after last Days 1, 4, 8, 11, 22, 25, 29, and 32 d: 20 mg PO: Days 1, 8, 15, HDM (no versus yes versus d: 20 mg POD; Days 1-2, 4-5, 8-9, 11-12, 15, and 22 unknown) 22-23, 25-26, 29-30, and 32-33 Primary end pointsᶜ: Post-induction MRD- (NGF, 10⁻⁵); PFS after second randomization Key secondary end points: PFS (whole study); OS (whole study and from second randomization); post-induction CR; CR and MRD- after HDM and during and after maintenance therapy Selected secondary end point: PFS after first randomization Here, we present the PFS from first randomization comparing Isa-RVd and RVd induction therapies UK Melphalan 200 mg/m2. On days of isatuximab infusion, dexamethasone will be administered intravenously as part of the premedication. HD GMMG and Heidelberg University Hospital I ASH 2024 intravenous, ASCT, autologous MRD-, stem minimal cell transplant; residual disease CR, complete negativity; response; NDMM, d, newly dexamethasone; diagnosed multiple HDM, high-dose myeloma; melphalan; PD, progressive HR, high-risk; disease; PO, Isa, isatuximab; oral; IV, 4 ISS Revised International Staging System; SC, subcutaneous; V, bortezomib. --- [Slide 3] GM MG MRD- rates post transplant in the ITT population¹ HD7 OR, 2.13 (95% CI, 1.56-2.92) OR, 2.22 P<0.0001 (95% CI, 1.63-3.03) P<0.0001 70 66.2% 63.4% Isa-RVd OR, 1.76 60 RVd (95% CI, 1.25-2.50) P=0.001 47.7% 50 43.8% 38.1% Patients (%) 40 30 25.8% 20 10 0 MRD- CR and MRD- ≥VGPR and MRD- Compared with RVd alone, Isa-RVd led to deeper MRD- response post transplant IC interval: CR. complete response; d, dexamethasone; VGPR Isa, isatuximab; very good ITT, partial intent-to-treat; response. MRD-, minimal residual --- [Slide 4] GM MG Summary HD7 Addition of Isa to RVd during an 18-week induction followed by ASCT without consolidation and regardless of second randomization resulted in an impressive 30% reduction in risk of progression or death compared with standard of care RVd Weighted risk set estimator analyses accounting for second randomization with lenalidomide only confirmed the significant benefit for Isa-RVd vs. RVd induction The PFS benefit was observed across clinically relevant subgroups Isa-RVd is the first regimen to demonstrate a deep and rapid response reflected by a statistically significant MRD- benefit at the end of induction and post-transplant in a Phase 3 trial, which translated to a PFS benefit vs RVd ASCT was feasible after induction therapy, as a similar proportion of patients in both treatment arms proceeded to ASCT, and hematologic recovery was comparable between the Isa-RVd and RVd groups GMMG-HD7 is the first Phase 3 study to show that an 18-week initial quadruplet regimen with Isa, without consolidation, allows for significant long-term benefits regardless of subsequent maintenance therapy UK HD GMMG and Heidelberg University Hospital I ASH 2024 ASCT, survival; autologous R, lenalidomide; stem cell V, transplant; bortezomib. d, dexamethasone; Isa, isatuximab; MRD-, minimal residual disease negativity; PFS, progression-free 13