CEPHEUS Trial

[Slide 1] MAYO CLINIC mSMART - Off-Study Transplant Ineligible STANDARD RISK MYELOMA HIGH RISK MYELOMA t(11;14), t(6;14), and trisomies without Del 17p, Gain/Amp 1q, Del 1p, t(4;14), t(14;16), any high risk abnormalities t(14;20) Dara-VRd or Isa-VRd for ~9 cycles followed by Len Dara-VRd or Isa-VRd for ~9 cycles followed by maintenance bortezomib plus lenalidomide maintenance Or For frail patients: DRda For frail patients: DRd or VRd for ~9 cycles followed by doublet DR or VR maintenance "Duration is usually until progression, based on tolerance Dara-VRd, Daratumumab, bortezomib, lenalidomide, dexamethasone; Isa-VRd, Isatuximab, bortezomib, lenalidomide, dexamethasone; VRd, Bortezomib, lenalidomide, dexamethasone; DRd, daratumumab, lenalidomide, dexamethasone Dispenzieri et al. Mayo Clin Proc 2007;82:323-341; Kumar et al. Mayo Clin Proc 2009 84:1095-1110; Mikhael et al. Mayo Clin Proc 2013;88:360- 376. v22 //last reviewed Oct 2024 MAYO CLINIC mSMART - Off-Study Transplant Eligible STANDARD RISK MYELOMA HIGH RISK MYELOMA t(11;14), t(6;14), and trisomies without Del 17p, Gain/Amp 1q, Del Double or Triple Hit any high risk abnormalities 1p, t(4;14), t(14;16), t(14;20) Dara-VRd or Isa-VRd X ~4 cycles Dara-VRd or Isa-VRd X ~4 cycles Dara-VRd or Isa-VRd X ~4 cycles Collect Stem Cells Autologous Stem Cell Transplant Autologous Stem Cell Transplant (ASCT) (ASCT) Autologous stem cell Dar-VRd or Isa- transplant (preferred) VRd X 4 cycles Len maintenance Len until Bortezomib plus lenalidomide Bortezomib plus lenalidomide progression; maintenance till progression maintenance till progression Delayed ASCTᵇ a If age >65 or > 4 cycles of induction therapy, consider mobilization with G-CSF plus cytoxan or plerixafor; Duration usually until progression based on tolerance; In patients with grade 2 or higher neuropathy at baseline, and for patients in whom bortezomib needs to be dose reduced or discontinued due to neuropathy, consider carfilzomib instead. Dara-VRd, Daratumumab, bortezomib, lenalidomide, dexamethasone; Isa-VRd, Isatuximab, bortezomib, lenalidomide, dexamethasone Dispenzieri et al. Mayo Clin Proc 2007;82:323-341; Kumar et al. Mayo Clin Proc 2009 84:1095-1110; Mikhael et al. Mayo Clin Proc 2013;88:360- 376. v22 //last reviewed Oct 2024

[Slide 1] 8:00 5G Mail nature.com Fig. 3: PFS. From: Daratumumab plus bortezomib, lenalidomide and dexamethasone for transplant-ineligible or transplant-deferred newly diagnosed multiple myeloma: the randomized phase 3 CEPHEUS study 100 80 Percentage of patients surviving without disease progression 68.1 +++++++ D-VRd 60 49.5 +++++ # 40 # VRd 20 Hazard ratio for disease progression or death, 0.57 (95% CI, 0.41-0.79) P 0.0005 0 0 6 12 18 24 30 36 42 48 54 60 66 Months since randomization No. at risk D-VRd 197 180 170 160 149 140 136 132 122 115 33 0 VRd 198 174 157 143 131 123 105 98 88 81 21 0 The results of the Kaplan-Meier estimates of PFS among patients in the intention-to- treat population. The final analysis of PFS was performed after 162 events of disease progression or death occurred. Of these, eight were censored as a result of missing + 66

[Slide 1] CEPHEUS: Phase 3 Study of DARA SC-VRd Versus VRd in TIE or Transplant-deferred Patients With NDMM VRd Rd Primary endpoint: Key eligibility Cycle 9+ criteria: V: 1.3 mg/m2 SC Days 1, 4, 8, 11 Overall MRD R: 25 mg PO Days 1-14 R: 25 mg PO Days 1-21 (>CR) negativity NDMM (TIE or d: 20 mg PO Days 1, 2, 4, 5, 8, 9, 11, 12 d: 40 mg PO Days 1, 8, 15, 22 transplant deferred) Key secondary ECOG PS score endpoints: of 0-2 DARA SC-VRd DARA SC-Rd PFS Frailty score of 0-1 Cycle 9+ Sustained MRD (>CR) DARA: 1,800 mg SC QW Cycles 1-2, negativity (>12 months) Q3W Cycles 3-8 DARA: 1,800 mg SC Q4W >CR rate VRd: schedule as above Rd: schedule as above os 21-day cycles 28-day cycles 8 cycles of bortezomib treatment until disease progression or unacceptable toxicity --- [Slide 2] CEPHEUS: PFS (ITT Population) 100 Median follow-up: 58.7 months 54-month PFS 80 68.1% 60 D-VRd Median: not reached 40 49.5% VRd Median: 52.6 months 20 HR, 0.57; 95% CI, 0.41-0.79; P = 0.0005 0 0 6 12 18 24 30 36 42 48 54 60 66 Months No. at risk D-VRd 197 180 170 160 149 140 136 132 122 115 33 0 VRd 198 174 157 143 131 123 105 98 88 81 21 0 Daratumumab significantly improved PFS, with a 43% reduction in the risk of disease progression or death

[Slide 1] International Myeloma Society Overview of mPFS in phase 3 trials in transplant-ineligible NDMM 1987 2024 Estimated med PFS 100 mos 100 100 90 90 ? 80 80 70 61.9 ? - 70 as an APL 54.3 60 60 IN Median PFS 41.7 MPD- First 50 50 BPL 35.1 SSEE and MD 40 36.4 31.9 - 40 297 - 30 253 26 30 MRD- / a 20 183 19.1 20 12 10 IMS 22nd Annual 0 MEETING & EXPOSITION MRD- /// (ALCYONE) ##! September 17-20, 2025 Toronto, Canada RVSLUIB MP Bort-based Rd VRd CD38-Rd Quad International Myeloma Society

[Slide 1] CEPHEUS Trial Usmani et al., Nat Med 2025,31(4):1195-1202. MRD-NEGATIVITY RATE (10⁻⁵) (%) 60.9% DVRd Odds ratio (n=197) 2.37 (95% CI, 1.58-3.55) 39.4% P<0.0001 VRd (n=198) Bor

[Slide 1] Assessed for eligibility (n = 508) Excluded (screen failures) (n = 113) Randomized (n = 395) Allocated to D-VRd group Allocated to VRd group (n = 197) (n = 198) Randomized, not treated Randomized, not treated (n 0) (n 3) Treated Treated (n = 197) (n = 195) Discontinued treatment (n = 95) Discontinued treatment (n = 128) Progressive disease (n = 27) Progressive disease (n = 51) Death (n = 34) Death (n = 24) Death due to COVID-19 (n = 12) Death due to COVID-19 (n = 6) Adverse event (n = 16) Adverse event (n = 32) Patient refused further treatment (n = 15) Patient refused further treatment (n = 8) Physician decision (n = 3) Physician decision (n = 12) Patient received concurrent treatment Patient received concurrent treatment for multiple myeloma before disease for multiple myeloma before disease progression (n = O) progression (n = 1) Discontinued study (n = 62) Discontinued study (n = 69) Death (n = 50) Death (n = 54) Death due to COVID-19 (n = 15) Death due to COVID-19 (n = 9) Withdrawal by patient (n = 11) Withdrawal by patient (n = 13) Lost to follow-up (n = 1) Lost to follow-up (n = 2) Patients remaining on study Patients remaining on study (n = 135) (n = 126) Patients off treatment (n = 33) Patients remaining Patients remaining Patients off treatment (n = 59) Pre-PD follow-up (n = 21) on treatment on treatment Pre-PD follow-up (n = 18) Post-PD follow-up (n = 12) (n = 102) (n 67) Post-PD follow-up (n = 41) Fig. 1| CONSORT patient flow diagram. Patient disposition at the data cutoff date of 7 May 2024. --- [Slide 2] Table 1 Demographic and clinical characteristics in the intention-to-treat population at baseline Characteristic D-VRd (n=197) VRd (n=198) Age Median (range) (years) 70 (42-79) 70 (31-80) Distribution, no. (%) <65 years 36 (18.3) 35 (17.7) 65 to <70 years 52 (26.4) 53 (26.8) >70 years 109 (55.3) 110 (55.6) Age/transplant eligibility, no. (%) <70 years and transplant ineligible 35 (17.8) 35 (17.7) <70years and transplant deferred 53 (26.9) 53 (26.8) >70 years 109 (55.3) 110 (55.6) Male sex, no. (%)b 87 (44.2) 111 (56.1) Race, no. (%)b White 162 (82.2) 156 (78.8) Black or African American 10 (5.1) 9 (4.5) Asian 11 (5.6) 14 (7.1) Native Hawaiian or other Pacific Islander 0 1 (0.5) Other 1 (0.5) 2 (1.0) Not reported 13 (6.6) 16 (8.1) ECOG performance status score, no. (%)c 0 71 (36.0) 84 (42.4) 1 103 (52.3) 100 (50.5) 2 23 (11.7) 14 (7.1) Frailty score, no. (%)d 0 (fit) 124 (62.9) 132 (66.7) 1 (intermediate fitness) 73 (37.1) 66 (33.3) Type of measurable disease, no. (%) Detected in serum only 120 (60.9) 108 (54.5) IgG 89 (45.2) 76 (38.4) IgA 27 (13.7) 31 (15.7) Other 4 (2.0) 1 (0.5) Detected in serum and urine 41 (20.8) 45 (22.7) Detected in urine only 20 (10.2) 24 (12.1) Detected in serum free light chains only 16 (8.1) 21 (10.6) ISS disease stage, no. (%)' I 68 (34.5) 68 (34.3) II 73 (37.1) 75 (37.9) III 56 (28.4) 55 (27.8) Cytogenetic risk profile, no. (%) Standard risk 149 (75.6) 149 (75.3) High risk 25 (12.7) 27 (13.6) Indeterminate 23 (11.7) 22 (11.1) Median time since diagnosis of multiple 1.2 (0.4-5.8) 1.3 (0.3-8.0) myeloma (range) (months) "The intention-to-treat population was defined as all patients who underwent randomization. "Sex and race were reported by the patient. "ECOG performance status is scored on a scale of 0-5, with 0 indicating no symptoms and higher scores indicating increasing disability. Total additive frailty is scored on a scale of 0-5 based on age, comorbidities and cognitive and physical conditions, with 0 indicating fit, intermediate fitness and >2 frail, per the Myeloma Geriatric Assessment score (http://www.myelomafrailtyscorecalculator.net) "Includes IgD, IgM, IgE and biclonal. 'ISS disease stage is based on the combination of serum By-microglobulin and albumin levels. Higher stages indicate more advanced disease. "Cytogenetic risk was assessed by fluorescence in situ hybridization. High risk was defined as the presence of del(17p), t(4;14) and/or t(14;16). "Indeterminate includes patients with missing or unevaluable samples. --- [Slide 3] 100 90 Odds ratio, 2.37 (95% CI, 1.58-3.55); P < 0.0001 MRD-negativity rate (10⁻⁵) (%) 80 70 60.9 60 50 39.4 40 30 20 10 0 D-VRd VRd (n = 197) (n 198) b 100 90 MRD-negativity rate (10⁻⁶) (%) 80 70 Odds ratio, 2.24 (95% CI, 1.48-3.40); P = 0.0001 60 50 46.2 40 27.3 30 20 10 0 D-VRd VRd (n . 197) (n 198) 100 Sustained MRD-negativity rate C 90 80 70 Odds ratio, 2.63 (95% CI, 1.73-4.00); P < 0.0001 (10⁻⁵) (%) 60 48.7 50 40 30 26.3 20 10 0 D-VRd VRd (n = 197) (n 198) Fig. 2| MRD-negativity rates. a, The primary endpoint of overall MRD-negativity rates in the intention-to-treat population. The overall MRD-negativity rate was defined as the proportion of patients who achieved >CR and MRD negativity (at or below a sensitivity threshold of 10⁻⁵) after randomization but before disease progression, subsequent antimyeloma therapy or both. b, An exploratory analysis of the MRD-negativity rate at or below a sensitivity threshold of 10⁻⁶. c, Sustained MRD-negativity rate in the intention-to-treat population. The sustained MRD-negativity rate was defined as the proportion of patients who achieved >CR and MRD-negative status (at or below a sensitivity threshold of 10⁻³) at two examinations a minimum of 1 year apart without MRD-positive status in between. MRD status was assessed using bone marrow samples and evaluated using a next-generation sequencing assay (clonoSEQ assay, v.2.0; Adaptive Biotechnologies) in accordance with International Myeloma Working Group guidelines for assessing MRD25. The Mantel-Haenszel estimate of the common odds ratio for stratified tables was used. The stratification factors were ISS disease stage (I, II or III) and age/transplant eligibility (<70 years and transplant ineligible, <70 years and transplant deferred or >70 years). An odds ratio >1 indicates an advantage for D-VRd. The value (two sided) was calculated using a Fisher's exact test. --- [Slide 4] 100 80 Percentage of patients surviving without disease progression 68.1 D-VRd 60 49.5 40 VRd 20 Hazard ratio for disease progression or death, 0.57 (95% CI, 0.41-0.79) P 0.0005 0 0 6 12 18 24 30 36 42 48 54 60 66 Months since randomization No. at risk D-VRd 197 180 170 160 149 140 136 132 122 115 33 0 VRd 198 174 157 143 131 123 105 98 88 81 21 0 Fig. 3 PFS. The results of the Kaplan-Meier estimates of PFS among patients in the intention-to-treat population. The final analysis of PFS was performed after 162 events of disease progression or death occurred. Of these, eight were censored as a result of missing two or more consecutive disease evaluations preceding the event. The Pvalue was calculated using the stratified log(rank test). >CR: odds ratio, 2.73 (95% CI, 1.71-4.34); P < 0.0001 100 90 80 70 44.4 65.0 >CR: Best response (%) 60 >CR: 61.6% 81.2% 50 40 17.2 30 16.2 20 25.3 10 11.7 4.1 6.1 0 D-VRd VRd (n=197) (n = 198) sCR CR VGPR PR sCR CR VGPR PR Fig. 4 >CR rates. >CR rates in the intention-to-treat population. The tumor was used. The stratification factors were ISS disease stage (I, II or III) and age/ response was assessed using a validated computer algorithm in accordance transplant eligibility (<70 years and transplant ineligible, <70 years and with the International Myeloma Working Group response criteria26 Complete transplant deferred or >70 years). An odds ratio >1 indicates an advantage for response (CR) or stringent CR (sCR) was achieved at any time during the trial. D-VRd. The Pvalue (two sided) was calculated using the Cochran-Mantel- The Mantel-Haenszel estimate of the common odds ratio for stratified tables Haenszel test. PR, partial response; VGPR, very good partial response.

[Slide 1] CEPHEUS TIE Subgroup: Progression-Free Survival 100 Median follow-up: 58.7 months 54-month PFS 80 69.0% % surviving without DVRd progression 60 Median: not reached 40 48.0% +++ VRd 20 Median: 49.6 months HR, 0.51; 95% CI, 0.35-0.74; P=0.0003 0 0 6 12 18 24 30 36 42 48 54 60 66 No. at risk Months DVRd 144 133 124 118 109 103 100 98 90 83 23 0 VRd 145 125 114 104 96 90 76 70 61 56 18 0 DVRd significantly improved PFS, with a 49% reduction in the risk of disease progression or death — greater than the ITT population (43% reduction in risk with DVRd vs VRd)1 DVRd, daratumumab plus bortezomib, lenalidomide, and dexamethasone; HR, hazard ratio; ITT, intent to treat; PFS, progression-free survival; TIE, transplant ineligible; VRd, bortezomib, lenalidomide, and dexamethasone 1. Usmani SZ, et al. Nat Med 2025. doi: 10.1038/s41591-024-03485-7 9 Presented by SZ Usmani at the American Society of Clinical Oncology (ASCO) Annual Meeting; May 30-June 3, 2025; Chicago, IL, USA & Virtual --- [Slide 2] CEPHEUS TIE Subgroup: Overall Survival OS OS (TIE patients) (TIE patients after censored for deaths due to COVID-19) 100 100 80 80 DVRd DVRd % surviving 60 VRd 40 % surviving, censoring for death due to COVID-19 60 VRd 40 20 20 0 HR, 0.66; 95% CI, 0.42-1.03; P=0.0682 0 HR, 0.55; 95% CI, 0.34-0.90; P=0.0159 0 6 12 18 24 30 36 42 48 54 60 66 0 6 12 18 24 30 36 42 48 54 60 66 Months Months No. at risk No. at risk DVRd 144 139 129 125 118 113 111 107 102 98 32 0 DVRd 144 139 129 125 118 113 111 107 102 98 32 0 VRd 145 134 127 119 114 110 105 102 96 90 27 0 VRd 145 134 127 119 114 110 105 102 96 90 27 0 OS trended favorably for the DVRd arm and was significant when censoring for death due to COVID-19; os HR improved in the TIE subgroup compared with the ITT population DVRd, daratumumab, bortezomib, lenalidomide, and dexamethasone; HR, hazard ratio; ITT, intent to treat; OS, overall survival; TIE, transplant ineligible; VRd, bortezomib, lenalidomide, and dexamethasone 10 Presented by SZ Usmani at the American Society of Clinical Oncology (ASCO) Annual Meeting; May 30-June 3, 2025; Chicago, IL, USA & Virtual --- [Slide 3] CEPHEUS TIE Subgroup: Overall MRD Negativity (10-5) With 2CR and PFS in Prespecified Subgroups MRD negativity PFS at 10⁻⁵ Odds ratio and 95% CI DVRd VRd Odds ratio Hazard ratio and 95% CI DVRd VRd Hazard ratio n/N (%) n/N (%) (95% CI) (95% CI) Event/N mPFS mPFS Sex Sex (months) Event/N (months) Male 42/65 (64.6) 28/82 (34.1) 3.52 (1.78-6.97) Male 15/65 NE 42/82 47.9 0.34 (0.19-0.61) Female 45/79 (57.0) 29/63 (46.0) 1.55 (0.80-3.02) Female 29/79 NE 27/63 NE 0.78 (0.46-1.31) Age Age <70 years 26/35 (74.3) 15/35 (42.9) 3.85 (1.40-10.59) <70 years 11/35 NE 16/35 NE 0.59 (0.27-1.28) >70 years 61/109 (56.0) 42/110 (38.2) 2.06 (1.20-3.53) >70 years 33/109 NE 53/110 49.4 0.50 (0.33-0.78) Region Region Europe 54/96 (56.3) 37/90 (41.1) 1.84 (1.03-3.30) Europe 29/96 NE 44/90 49.6 0.51 (0.32-0.82) North America 20/31 (64.5) 12/28 (42.9) 2.42 (0.85-6.92) North America 8/31 NE 12/28 50.2 0.45 (0.18-1.11) Other 8/27 (29.6) 13/17 (76.5) 7.72 (I.92-31.06) Other 7/17 NE 13/27 NE 0.91 (0.36-2.28) Weight Weight <65 kg 31/46 (67.4) 19/47 (40.4) 3.05 (1.30-7.11) <65 kg 13/46 NE 19/47 NE 0.57 (0.28-1.15) >65-85 kg 39/69 (56.5) 20/64 (31.3) 2.86 (1.40-5.82) >65-85 kg 23/69 NE 31/64 49.2 0.58 (0.34-1.00) >85 kg 17/29 (58.6) 18/34 (52.9) 1.26 (0.46-3.42) >85 kg 8/29 NE 19/34 42.2 0.38 (0.17-0.89) ISS ISS I 33/50 (66.0) 20/48 (41.7) 2.72 (1.20-6.17) I 15/50 NE 21/48 60.6 0.58 (0.30-1.12) II 32/54 (59.3) 25/57 (43.9) 1.86 (0.88-3.96) II 14/54 NE 28/57 49.4 0.41 (0.21-0.77) III 22/40 (55.0) 12/40 (30.0) 2.85 (1.14-7.15) III 15/40 NE 20/40 33.6 0.61 (0.31-1.19) Cytogenetic risk Cytogenetic risk High risk 10/20 (50.0) 9/18 (50.0) 1.00 (0.28-3.57) High risk 9/20 NE 11/18 31.7 0.82 (0.33-2.03) Standard risk 66/105 (62.9) 43/111 (38.7) 2.68 (1.54-4.64) Standard risk 28/105 NE 45/111 60.6 0.54 (0.33-0.86) ECOG PS ECOG PS 0 30/52 (57.7) 25/57 (43.9) 1.75 (0.82-3.73) 0 10/52 NE 24/57 60.6 0.33 (0.16-0.69) 21 57/92 (62.0) 32/88 (36.4) 2.85 (1.56-5.22) 21 34/92 NE 45/88 47.2 0.63 (0.40-0.99) 0.1 1 10 100 0.1 1 10 Favor VRd Favor DVRd Favor DVRd Favor VRd Treatment effect was generally consistent across subgroups CR, complete response; DVRd, daratumumab, bortezomib, lenalidomide, and dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; ISS, International Staging System; mPFS, median progression-free survival; MRD, minimal residual disease; NE, not estimable; PFS, progression-free survival; TIE, transplant ineligible; VRd, bortezomib, lenalidomide, and dexamethasone 11 Presented by SZ Usmani at the American Society of Clinical Oncology (ASCO) Annual Meeting: May 30-June 3, 2025; Chicago, IL, USA & Virtual --- [Slide 4] CEPHEUS TIE Subgroup: Safety Safety overview Common (≥5%) grade 3 or 4 TEAEs of interest DVRd VRd DVRd VRd Event, n (%) (n=144) (n=142) Event, n (%) (n=144) (n=142) Any TEAE 144 (100) 142 (100) Neutropenia 63 (43.8) 45 (31.7) Grade 3 and 4 115 (79.9) 113 (79.6) Thrombocytopenia 44 (30.6) 33 (23.2) Grade 5 non-COVID-19 13 (9.0) 12 (8.5) Anemia 18 (12.5) 18 (12.7) Grade 5 COVID-19 6 (4.2) 1 (0.7) Diarrhea 17 (11.8) 14 (9.9) Any serious TEAE 104 (72.2) 99 (69.7) TEAE leading to discontinuation of all Fatigue 13 (9.0) 15 (10.6) study treatment 11 (7.6) 27 (19.0) COVID-19b 14 (9.7) 5 (3.5) Total deaths during study 33 (22.9) 46 (32.4) Pneumonia 20 (13.9) 17 (12.0) Exposure-adjusted grade 5 TEAE rate, 0.27/100 0.31/100 patient-months Peripheral sensory Any Grade: 86 (59.7) Any Grade: 90 (63.4) Second primary malignancies 14 (9.7) 16 (11.3) neuropathy Grade 3/4: 14 (9.7) Grade 3/4: 12 (8.5) DVRd showed no additional safety concerns in this older, frailer TIE subgroup compared with the ITT population of CEPHEUS "Deaths on or within 30 days of treatment Group term. DVRd, daratumumab, bortezomib, lenalidomide, and dexamethasone; ITT, intent to treat; TEAE, treatment-emergent adverse event; TIE, transplant ineligible; VRd, bortezomib, lenalidomide, and dexamethasone 12 Presented by SZ Usmani at the American Society of Clinical Oncology (ASCO) 4 Annual Meeting: 1. May 30-June 3, 2025; Chicago, / IL, USA & Virtual