ANDROMEDA Trial

[Slide 1] 4 ANDROMEDA Study Design ANDROMEDA is a randomized, open-label, active-controlled, phase 3 study of D-VCd vs VCd alone in patients with newly diagnosed AL amyloidosis Treatment Phase Posttreatment Phase Observation until Key eligibility criteria: DARA SC 1800 mg QW DARA SC 1800 mg Q4W major organ AL amyloidosis with >1 organ Cycles 1-2 Q2W Cycles until major organ deterioration-PFS impacted Screening (Day -28) deterioration-PFS or 1:1 randomization 3-6 + VCd QW x 6 cycles No prior therapy for AL maximum of (if DARA SC discontinued (N=388) n=195 prior to major organ amyloidosis or multiple myeloma 24 total cycles deterioration-PFS) Cardiac stage I-IIIA (Mayo 2004) VCd Estimated glomerular filtration Observation until rate ≥20 mL/min QW X 6 cycles major organ n= 193 deterioration-PFS Stratification criteria: Major organ deterioration-PFS: A composite endpoint defined Cardiac stage (I vs II vs IIIA) Transplant typically offered in local country (yes vs no) as end-stage cardiac disease (requiring cardiac transplant, left Creatinine clearance (>60 mL/min vs <60 mL/min) ventricular assist device, or intra-aortic balloon pump), end- Primary endpoint overall hematologic complete response rate stage renal disease (requiring hemodialysis or renal transplant), Secondary endpoints major organ deterioration-PFS. organ response rate, time to hematologic response, overall survival, safety hematologic progression per consensus guidelines,¹ and death AL. light chain; DARA daratumumab; D-VCd. daratumumab/bortezomib/cyclophosphamide/dexamethasone PFS. progression-free survival QW. weekly: Q2W. every 2 weeks; Q4W. every 4 weeks: SC. subcutaneous 1. Comenzo RL, et al. Leukemia 2012:26:2317-25 Presented By: Efstathios Kastritis #ASCO21 | Content of this presentation is the property of the author, licensed by ASCO. 2021 ASCO Permission required for reuse. ANNUAL MEETING = LIVE

[Slide 1] ANDROMEDA: Overall Survival 100 Median follow-up: 61.4 months 60-month OS rate 80 76.1% D-VCd % surviving 60 VCd 64.7% 40 20 HR, 0.62 (95% CI, 0.42-0.90); P = 0.0121ᵃ 0 0 6 12 18 24 30 36 42 48 54 60 66 72 Months No. at risk VCd 193 163 156 145 132 127 121 119 112 108 70 23 0 D-VCd 195 167 162 161 156 155 151 150 146 145 100 33 0 The addition of DARA to VCd significantly improved OS versus VCd despite cross-over in >70% of VCd patients who received DARA as subsequent therapy, highlighting the importance of DARA use in frontline treatment Crossing the prespecified stopping boundary of 0 0163 10 Presented by E Kastrites at the 66th American Society of Hematology (ASH) Annual Meeting & Exposition December 7-10 2024 San Diago, CA, USA --- [Slide 2] ANDROMEDA: Prespecified Subgroup Analysis of Overall Survival Death, Median os, Death, Median os, n/N months n/N months Subgroup D-VCd VCd D-VCd VCd HR (95% CI) Subgroup D-VCd VCd D-VCd VCd HR (95% CI) Sex Baseline creatinine clearance Male 25/108 43/117 NE NE 0.59(0.36-0.96) z60 mL/min 26/126 34/131 NE NE 0.72 (0.43-1.21) Female 21/87 23/76 NE NE 0.71 (0.39-1.28) <60 mL/min 20/69 32/62 NE 49.61 0.50 (0.29-0.88) Age Baseline cardiac involvement <65 years 16/108 18/97 NE NE 0.74 (0.38-1.46) Yes 42/140 54/137 NE NE 0.68 (0.45-1.02) 265 years 30/87 48/96 NE 60.25 0.63 (0.40-0.99) No 4/55 12/56 NE NE 0.31 (0.10-0.96) Baseline weight Baseline renal stage $65 kg 13/62 32/74 NE NE 0.39 (0.21-0.75) I 7/39 10/36 NE NE 0.49 (0.18-1.28) >65-85 kg 26/96 20/74 NE NE 0.96 (0.54-1.72) II 7/56 18/60 NE NE 0.37 (0.16-0.90) >85 kg 7/37 14/45 NE NE 0.57 (0.23-1.41) III 5/19 8/18 NE NE 0.66 (0.22-2.03) Race Baseline alkaline phosphatase White 37/151 48/143 NE NE 0.68 (0.44-1.04) Abnormal 2/11 6/15 NE 49.61 0.34 (0.07-1.68) Asian 4/30 14/34 NE NE 0.25 (0.08-0.77) Normal 44/184 60/178 NE NE 0.66 (0.44-0.97) Other 5/14 4/16 NE NE 1.71 (0.46-6.37) Baseline ECOG PS score Baseline cardiac stage 0 10/90 18/71 NE NE 0.39 (0.18-0.84) 3/47 7/43 NE NE 0.34 (0.09-1.30) 1 or 2 36/105 48/122 NE NE 0.82 (0.53-1.26) II 14/76 23/80 NE NE 0.63(0.32-1.22) Cytogenetic risk at study entry IIA/IIB 29/72 36/70 NE 36.83 0.64 (0.39-1.05) High risk 3/17 9/19 NE 56.87 0.26 (0.07-0.96) Residence in a country that typically Standard risk 31/138 51/147 NE NE 0.59 (0.37-0.92) offers transplantation for patients with FISH 1(11:14) AL amyloidosis Abnormal 8/51 16/55 NE NE 0.47 (0.20-1.11) Yes 36/147 53/146 NE NE 0.61 (0.40-0.93) Normal 7/44 20/52 NE NE 0.34 (0.14-0.81) No 10/48 13/47 NE NE 0.72 (0.31-1.64) 0.01 0.1 1 10 100 0.01 0.1 1 10 100 D-VCd better VCd better D-VCd better VCd better The addition of DARA to VCd provided OS benefit across preplanned relevant subgroups 11 Presented by E Kastritis at the 66th American Society of Hematology (ASH) Annual Meeting & Exposition December 7-10 2024; San Diago, CA, USA --- [Slide 3] ANDROMEDA: Cardiac and Renal Response Rates Cardiac response rates Renal response rates 100 D-VCd (n = 118) VCd (n = 117) 100 D-VCd (n = 117) VCd (n = 113) 90 90 80 80 Cardiac response rate (%) 70 429% 47.5 426% 41.5 39.0 40 28.2 30 27.1 22.2 Renal response rate (%) 70 A26% A30% 429% 60 56.8 429% 53.8 57.3 A32% 60 419% 51.3 48.7 425% 50 50 40.2 A18% 40 30 27.4 27.4 22.1 18.8 20 12.8 20 16.8 15.0 9.4 10 10 0 0 6 months 12 months 24 months 36 months 48 months 6 months 12 months 24 months 36 months 48 months Graded response, % D-VCd VCd Cardiac CR 40.7 13.7 Cardiac >VGPR 64.4 31.6 The addition of DARA to VCd led to 2 to 3 times higher cardiac and renal response rates versus VCd across study time points CarCR cardiac complete response Both cardiac and renal response rates were determined by independent review committee assessment Cardiac and renal response rates at a specific time point were calculated as the number of patients who had cardiac/renal response at the specific time point within a 1-month window the denominator remained unchanged at each time point and represents the response-evaluable population The cardiac/renal response rates displayed here are results without censonng non-cross-resistant anti-plasma therapy 12 Presented I Kastelis the Finh American of ASH) Annual Montine K Exposition December 2024 San Disao CA USA --- [Slide 4] ANDROMEDA: Conclusions With 5 years of follow-up, D-VCd was superior to VCd and had a manageable safety profile: - Substantially deeper HemCR rates (59.5% VS 19.2%) and more rapid responses (67.5 VS 85.0 days) - Cardiac and renal response rates were 2 to 3 times higher, translating into better MOD-PFS (HR, 0.44) and OS (HR, 0.62) - Improvement in MOD-PFS and OS was generally consistent across preplanned relevant subgroups - Achievement of HemCR (MOD-PFS: HR, 0.30; OS: HR, 0.41) or CarCR (MOD-PFS: HR, 0.23; OS: HR, 0.05) correlated with favorable long-term outcomes - DARA treatment effect on MOD-PFS was demonstrated in both Hem/Car CR and non-CR patients The addition of DARA to VCd significantly improved OS versus VCd despite DARA cross-over in >70% of VCd patients who received subsequent therapy, highlighting the importance of frontline D-VCd ANDROMEDA shows that the addition of DARA to VCd improves survival for patients with newly diagnosed AL amyloidosis and reaffirms frontline D-VCd as the SoC in this difficult-to-treat disease MOD-PFS is a composite endpoint defined as end stage cardiac disease (requiring cardiac transplant, left ventricular assist device or intre-aortic balloon pump). end stage renal disease (requiring hemodialysis or renal transplant). hemetologic progression per consensus guidelines, or death 17 Presented by E Kastntis at the 66th American Society of Hematology (ASH) Annual Meeting & Exposition December 7-10 2024; San Diogo, CA, USA

[Slide 1] ANDROMEDA: Study Design ANDROMEDA is a randomized, open-label, phase 3 study of DARA plus VCd (D-VCd) versus VCd alone in patients with newly diagnosed AL amyloidosis Treatment phase Post-treatment phase DARA SC 1800 mg Key eligibility criteria: DARA SC 1,800 mg Q4W Observation until QW Cycles 1-2 and until MOD-PFS or MOD-PFS AL amyloidosis with >1 organ Cardiac stage I-IIIA (Mayo 2004) Screening (Day -28) 1:1 randomization Q2W Cycles 3-6 + maximum of VCd QW x 6 cycles (if DARA SC discontinued involved No prior therapy for AL 388) Z II n 195 24 total cycles prior to MOD-PFS) amyloidosis or multiple myeloma VCd eGFR >20 mL/min/1.73 m2 Observation until QW x 6 cycles MOD-PFS n = 193 Stratification criteria: Primary endpoint: Overall HemCR rate Cardiac stage (I vs II vs IIIA) Transplant typically offered in local country (yes vs no) Secondary endpoints: MOD-PFS (end-stage cardiac or renal disease, hematologic Creatinine clearance (>60 mL/min vs <60 mL/min) progression, or death),ᵇ OS, organ response rate, time to hematologic response, safety D-VCd, disratumumab 1,800 mg co-formulated with recombinant human hyaluronidase PH20 (rHuPH20 2. 1,000 UmL ENHANZE® drug delivery technology Halozyme, Inc., San Diego, CA USA]] plus VCd; eGFR, estimated glomerular filtration rate; SC, subcutaneous QW, weekly Q2W, every 2 weeks; Q4W every 4 works Defined here as normalization of free light chain (FLC) levels and ratio (FLCr) and negative serum and urine immunofixation confirmed at a subsequent visit normalization of uninvolved FLC level and FLCr were not required if involved FLC was lower than the upper limit of normal A composite endpoint defined as end stage cardiac disease (requiring cardiac transplant left ventricular assist device, or intra aortic balloon pump), and stage renal disease (requiring hemodalysis or renal transplant) hematologic progression per consensus guidelines, or death 1. Comenzo RL, et at Leukemia 2012:26(11) 2317-2325 3 Presented by E Kastritis at the 66th American Society of Hematology (ASH) Annual Meeting & Exposition December 10. 2024 San Diego CA USA --- [Slide 2] ANDROMEDA: Cardiac and Renal Response Rates Cardiac response rates Renal response rates 100 D-VCd (n = 118) VCd (n = 117) 100 D-VCd (n = 117) VCd (n = 113) 90 90 80 80 Cardiac response rate (%) 70 A29% 50 47.5 426% 39.0 40 28.2 Renal response rate (%) 70 426% A30% 429% 60 56.8 429% 53.8 57.3 A32% 60 A19% 51.3 48.7 425% 50 41.5 40.2 418% 40 30 27.1 27.4 22.2 30 27.4 22.1 18.8 20 12.8 20 16.8 15.0 9.4 10 10 0 0 6 months 12 months 24 months 36 months 48 months 6 months 12 months 24 months 36 months 48 months Graded response, % D-VCd VCd Cardiac CR 40.7 13.7 Cardiac >VGPR 64.4 31.6 The addition of DARA to VCd led to 2 to 3 times higher cardiac and renal response rates versus VCd across study time points CarCR cardiac complete response Both cardiac and renal response rates were determined by independent review committee assessment Cardiac and renal response rates at a specific time point were calculated as the number of patients who had cardiac/renal response at the specific time point within a 1-month window the denominator remained unchanged at each time point and represents the response-evaluable population. The cardiac/renal response rates displayed here are results without censoring resistant anti- plasma therapy 12 Presented by E Kastritis at the 66th American Society of Hematology (ASH) Annual Meeting & Exposition December 7-10. 2024 San Diego CA USA --- [Slide 3] ANDROMEDA: Overall Survival 100 Median follow-up: 61.4 months 60-month OS rate 80 76.1% D-VCd % surviving 60 VCd 64.7% 40 20 HR, 0.62 (95% CI, 0.42-0.90); P = 0.0121ᵃ 0 0 6 12 18 24 30 36 42 48 54 60 66 72 Months No. at risk VCd 193 163 156 145 132 127 121 119 112 108 70 23 0 D-VCd 195 167 162 161 156 155 151 150 146 145 100 33 0 The addition of DARA to VCd significantly improved OS versus VCd despite cross-over in >70% of VCd patients who received DARA as subsequent therapy, highlighting the importance of DARA use in frontline treatment *Crossing the prospecified stopping boundary of 0.0163 10 Presented by Kastrites at the American Sociaty of Hematology (ASH) Annual Meeting & Exposition December 7-10 2024 San Dago CA_USA --- [Slide 4] ANDROMEDA: Conclusions With 5 years of follow-up, D-VCd was superior to VCd and had a manageable safety profile: - Substantially deeper HemCR rates (59.5% VS 19.2%) and more rapid responses (67.5 VS 85.0 days) - Cardiac and renal response rates were 2 to 3 times higher, translating into better MOD-PFS (HR, 0.44) and OS (HR, 0.62) - Improvement in MOD-PFS and OS was generally consistent across preplanned relevant subgroups - Achievement of HemCR (MOD-PFS: HR, 0.30; OS: HR, 0.41) or CarCR (MOD-PFS: HR, 0.23; OS: HR, 0.05) correlated with favorable long-term outcomes - DARA treatment effect on MOD-PFS was demonstrated in both Hem/Car CR and non-CR patients The addition of DARA to VCd significantly improved OS versus VCd despite DARA cross-over in >70% of VCd patients who received subsequent therapy, highlighting the importance of frontline D-VCd ANDROMEDA shows that the addition of DARA to VCd improves survival for patients with newly diagnosed AL amyloidosis and reaffirms frontline D-VCd as the SoC in this difficult-to-treat disease MOD PF5 is a composite undpoint defined as and stage cardiec disease requiring cardiac transplant wn contributer asset device, or intia aortic beloon punio) end stage named Issue (Nquiring hemodalysis or renal transplant) hematologic progression per consensus guidelines or death 17 Presented by 1 Kindstin of the see American Society of Herrodokey (ASH) Amount Meeting & Expendent December 10. 2004 San Dango CA USA

[Slide 1] ANDROMEDA: Overall Survival 100 Median follow-up: 61.4 months 60-month OS rate 80 76.1% D-VCd % surviving 60 VCd 64.7% 40 20 HR, 0.62 (95% CI, 0.42-0.90); P = 0.0121ᵃ 0 0 6 12 18 24 30 36 42 48 54 60 66 72 Months No. at risk VCd 193 163 155 145 132 127 121 119 112 108 70 23 0 D-VCd 195 167 162 161 156 155 151 150 146 145 100 33 0 The addition of DARA to VCd significantly improved OS versus VCd despite cross-over in >70% of VCd patients who received DARA as subsequent therapy, highlighting the importance of DARA use in frontline treatment "Crossing the prespecified stopping boundary of 0 0163 10 Presented by E Kastritis at the 66th American Society of Hematology (ASH) Annual Meeting & Exposition; December 7-10 2024; San Diego, CA, USA --- [Slide 2] ANDROMEDA: Major Organ Deterioration (MOD)-PFS by Hematologic and Cardiac Complete Response MOD-PFS by HemCRb MOD-PFSᵃ by CarCRc 100 100 D-VCd, HemCR D-VCd, CarCR 80 80 I % surviving without MOD, hematologic progression, or death 60 VCd, HemCR D-VCd, Non-HemCR 40 D-VCd HemCR vs VCd HemCR: % surviving without MOD, hematologic progression, or death 60 VCd, CarCR D-VCd, Non-CarCR 40 D-VCd CarCR vs VCd CarCR: 20 HR, 0.57; P = 0.1799 VCd, Non-HemCR 20 HR, 0.34; P = 0.073 D-VCd Non-HemCR vs VCd Non-HemCR: D-VCd Non-CarCR vs VCd Non-CarCR: VCd, Non-CarCR HR, 0.39; P = 0.0004 HR, 0.50; P = 0.004 0 0 0 6 12 18 24 30 36 42 48 54 60 66 0 6 12 18 24 30 36 42 48 54 60 66 72 78 Months since 6-month landmark Months No. at risk No. at risk VCd, HemCR 29 24 22 20 19 16 16 15 13 5 1 0 VCd, CarCR 11 11 10 10 10 9 7 7 7 5 3 1 0 0 VCd, Non-HemCR 88 48 35 24 20 13 12 11 9 5 3 0 VCd, CarCR 106 61 35 27 19 17 11 10 9 9 4 2 0 0 D-VCd, HemCR 96 88 87 84 78 76 72 69 66 43 15 0 D-VCd, CarCR 45 45 43 43 42 40 37 34 34 32 18 3 0 0 D.VCd, HemCR 61 50 46 41 33 31 27 24 20 10 1 0 D-VCd, CarCR 73 51 44 40 37 32 32 29 28 25 15 5 0 0 Achieving HemCR or CarCR was associated with improved MOD-PFS DARA treatment effect was demonstrated in both Hem/Car CR and non-CR patients MOD-PFS is a composite endpoint defined as end-stage cardiac disease (requiring cardiac transplant, left ventricular assist device, or intra-aortic balloon pump), end-stage renal disease (requiring hemodialysis or renal transplant), hematologic progression per consensus guidelines, or death 6-month landmark analysis When assessing the correlation between MOD-PFS and CarCR MOD-PFS was censored for non-cross-resistant subsequent therapy. There were 8 patients who achieved CarCR after receiving non-cross-resistant subsequent therapy; these 8 patients were treated as non-CarCR for the evaluation of MOD-PFS 15 Presented by E Kastritis at the 66th American Society of Hematology (ASH) Annual Meeting & Exposition; December 7-10, 2024; San Diego, CA, USA --- [Slide 3] ANDROMEDA: Safetya D-VCd VCd (n = 193) (n = 188) Event, n (%) Any grade Grade 3/4 Any grade Grade 3/4 Peripheral edema 71 (36.8) 6 (3.1) 68 (36.2) 11 (5.9) Diarrhea 70 (36.3) 11 (5.7) 57 (30.3) 7 (3.7) Constipation 70 (36.3) 3 (1.6) 54 (28.7) 0 Peripheral sensory neuropathy 65 (33.7) 5 (2.6) 37 (19.7) 4 (2.1) Fatigue 55 (28.5) 10 (5.2) 53 (28.2) 6 (3.2) Nausea 55 (28.5) 3 (1.6) 52 (27.7) 0 Upper respiratory tract infection 50 (25.9) 1 (0.5) 21 (11.2) 1 (0.5) Anemia 49 (25.4) 8 (4.1) 44 (23.4) 9 (4.8) Insomnia 49 (25.4) 0 47 (25.0) 2 (1.1) Dyspnea 49 (25.4) 5 (2.6) 32 (17.0) 6 (3.2) Lymphopenia 37 (19.2) 25 (13.0) 28 (14.9) 19 (10.1) Hypokalemia 26 (13.5) 4 (2.1) 28 (14.9) 10 (5.3) Pneumonia 24 (12.4) 16 (8.3) 12 (6.4) 8 (4.3) Neutropenia 21 (10.9) 10 (5.2) 12 (6.4) 5 (2.7) Cardiac failure 18 (9.3) 12 (6.2) 10 (5.3) 5 (2.7) Syncope 16 (8.3) 12 (6.2) 12 (6.4) 12 (6.4) Safety data were consistent with the known safety profiles for VCd and DARA *The safety population included patients who received >1 dose of study treatment Adverse events of any grade that were reported in >25% of patients in either treatment group and grade 3 or 4 adverse events that were reported in >5% of patients in either treatment group are listed. 16 Presented by E Kastritis at the 66th American Society of Hematology (ASH) Annual Meeting & Exposition; December 7-10, 2024; San Diego, CA, USA --- [Slide 4] ANDROMEDA: Conclusions With 5 years of follow-up, D-VCd was superior to VCd and had a manageable safety profile: - Substantially deeper HemCR rates (59.5% VS 19.2%) and more rapid responses (67.5 VS 85.0 days) - Cardiac and renal response rates were 2 to 3 times higher, translating into better MOD-PFS (HR, 0.44) and OS (HR, 0.62) - Improvement in MOD-PFS and OS was generally consistent across preplanned relevant subgroups - Achievement of HemCR (MOD-PFS: HR, 0.30; OS: HR, 0.41) or CarCR (MOD-PFS: HR, 0.23; OS: HR, 0.05) correlated with favorable long-term outcomes - DARA treatment effect on MOD-PFS was demonstrated in both Hem/Car CR and non-CR patients The addition of DARA to VCd significantly improved OS versus VCd despite DARA cross-over in >70% of VCd patients who received subsequent therapy, highlighting the importance of frontline D-VCd ANDROMEDA shows that the addition of DARA to VCd improves survival for patients with newly diagnosed AL amyloidosis and reaffirms frontline D-VCd as the SoC in this difficult-to-treat disease MOD-PFS is a composite endpoint defined as end-stage cardiac disease (requiring cardiac transplant, left ventricular assist device, or intra-aortic balloon pump), end-stage renal disease (requiring hemodialysis or renal transplant), hematologic progression per consensus guidelines, or death 17 Presented by E Kastritis at the 66th American Society of Hematology (ASH) Annual Meeting & Exposition; December 7-10. 2024; San Diego, CA, USA

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