AURIGA Trial

[Slide 1] CLINICAL TRIALS AND OBSERVATIONS Daratumumab with lenalidomide as maintenance after transplant in newly diagnosed multiple myeloma: the AURIGA study Ashraf Badros, 1 Laahn Foster, 2 Larry D. Anderson Jr,³ Chakra P. Chaulagain, 4 Erin Pettijohn, 5 Andrew J. Cowan, 6 Caitlin Costello, 7 Sarah Larson, 8 Douglas W. Sborov,⁹ Kenneth H. Shain, 10 Rebecca Silbermann, 11 Nina Shah, 12 Alfred Chung, 12 Maria Krevvata, 13 Huiling Pei, 14 Sharmila Patel, 15 Vipin Khare, 15 Annelore Cortoos, 15 Robin Carson, 13 Thomas S. Lin, 15 and Peter Voorhees 16 Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD; 2 Division of Hematology and Oncology, University of Virginia, Charlottesville, VA; 3 Division of Hematology and Oncology, Myeloma, Waldenstrom's and Amyloidosis Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX; Myeloma and Amyloidosis Program, Department of Hematology and Oncology, Cleveland Clinic Florida, Weston, FL; ⁵The Cancer and Hematology Centers of Western Michigan, Grand Rapids, MI; ⁶Division of Medical Oncology, Fred Hutchinson Cancer Center, University of Washington, Seattle, WA; 7 Moores Cancer Center, University of California San Diego, La Jolla, CA; ⁸Division of Hematology and Oncology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA; ⁹Department of Internal Medicine-Division of Hematology and Hematologic Malignancies, Huntsman Cancer Institute, The University of Utah, Salt Lake City, UT; 10 Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, FL; 11 Division of Hematology/Medical Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland, OR; 12 Department of Medicine, University of California San Francisco, San Francisco, CA; 13 Janssen Research and Development, LLC, Spring House, PA; 14 Janssen Research and Development, LLC, Titusville, NJ; 15 Janssen Scientific Affairs, LLC, a Johnson & Johnson company, Horsham, PA; and 1⁶Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Atrium Health Wake Forest University School of Medicine, Charlotte, NC

[Slide 1] Back International Myeloma Society 21ST ANNUAL Meeting CE Exposition September 25-28, 2024 Riocentro Rio de Janeiro, Brazil Methods: Eligible pts with NDMM were aged 18-79 yrs, in >VGPR and MRD pos (10⁻⁵; NGS) following ASCT, anti- CD38 naïve, received ≥4 ind cycles, and enrolled within 12 mos of start of ind therapy and 6 mos of ASCT. Pts were stratified by cytogenetic risk and randomized 1:1 to receive 28-day cycles of R maint (10mg PO D1-28 [after C3, 15mg PO, if tolerated]) ± subcutaneous DARA (DARA SC; 1,800mg QW C1-2, Q2W C3-6, Q4W C7+) for <36 cycles or until disease progression, unacceptable toxicity, or withdrawal. The primary endpoint was MRD-negative (neg) conversion rate (10⁻⁵) by 12 mos from start of maint therapy. Results: 200 pts were randomized (D-R, n=99; R, n=101). Demographic characteristics were well balanced between arms: median age (yrs) was 63 for D-R and 62 for R, and 25.3% and 23.5% of pts had ISS stage III disease. At diagnosis, 23.9% of D-R and 16.9% of R pts had high cytogenetic risk (del17p/t[4;14]/t[14;16]). Pts received a median of 5 (range, 4-8) ind cycles in both groups prior to study entry. The MRD-neg (10⁻⁵) conversion rate by 12 mos (primary endpoint) was 50.5% for D-R and 18.8% for R (odds ratio [OR], 4.51; 95% CI, 2.37-8.57; P< 0.0001) with a consistent benefit favoring D-R across all relevant subgroups. At median follow-up (32.3 mos), overall MRD- neg (10⁻⁵) rate was 60.6% for D-R and 27.7% for R. Complete response or better rate favored D-R (75.8% VS 61.4%; OR, 2.00; 95% CI, 1.08-3.69; P=0. 55). PFS favored D-R (HR, 0.53; 95% CI, 0.29-0.97); estimated 30-mo PFS rate was 82.7% for D-R and 66.4% for R. Home Speaker(s) Export Favorite Take Notes

[Slide 1] AURIGA: Study Design Objective: To determine the impact of adding DARA to R maintenance on MRD-negative conversion Key eligibility criteria Maintenance: up to 36 cycles (28-day cycles) 18-79 years of age Primary endpoint NDMM with 4 cycles of D-R MRD-negative (10-5) induction therapy and conversion rate from underwent ASCT within D: 1,800 mg SCe QW Cycles 1-2, baseline to 12 months after 12 months of the start Q2W Cycles 3-6, Q4W Cycles 7+ maintenance treatment of induction N = 214 planned to >VGPR at screening R: 10 mg PO daily Days 1-28 achieve >85% power to MRDb positive (10-5) post-ASCT (after Cycle 3, 15 mg PO daily if tolerated) detect 20% improvement No prior anti-CD38 Secondary endpoints Randomization within 6 months of ASCT date R PFS, overall MRD-negative conversion rate, sustained R: 10 mg PO daily Days 1-28 MRD-negative rate, Stratification factor (after Cycle 3, 15 mg PO daily if tolerated) response rates, duration of Cytogenetic risk (standard >CR, OS, safety risk/unknown vs high risk) MRDb obtained after 12, 18, 24, and 36 cycles --- [Slide 2] AURIGA: MRD-negative (10-5) Conversion Rate From Baseline to 12 Months of Maintenance Treatment ORb: 4.62 Primary endpoint (95% CI, 2.20-9.70) ORb: 4.40 70 ORb: 4.51 P <0.0001° (95% CI, 2.26-8.58) (95% CI, 2.37-8.57) P <0.0001° 60 P <0.0001° ORb: 4.61 (95% CI, (2.34-9.09) P <0.0001° 50 40 30 61.3 50.5 56.8 20 44.4 25.8 10 18.8 23.2 14.9 0 D-R R D-R R D-R R D-R R (50/99) (19/101) (46/75) (16/62) (50/88) (19/82) (44/99) (15/101) ITT population Patients achieving >CR at any time® MRD-evaluable population ITT population MRD-negative (10-5) MRD-negative (10-5) >CR conversion rate by 12 months conversion rate by 12 months The addition of DARA to R more than doubled the MRD-negative conversion rate by 12 months Similar benefits were seen in supplemental MRD analyses --- [Slide 3] AURIGA: Study Design Objective: To determine the impact of adding DARA to R maintenance on MRD-negative conversion Key eligibility criteria Maintenance: up to 36 cycles (28-day cycles) 18-79 years of age Primary endpoint NDMM with 4 cycles of D-R MRD-negative (10-5) induction therapy and conversion rate from underwent ASCT within D: 1,800 mg SCe QW Cycles 1-2, baseline to 12 months after 12 months of the start Q2W Cycles 3-6, Q4W Cycles 7+ maintenance treatment of induction N = 214 planned to >VGPR at screening R: 10 mg PO daily Days 1-28 achieve >85% power to MRDb positive (10-5) post-ASCT (after Cycle 3, 15 mg PO daily if tolerated) detect 20% improvement No prior anti-CD38 Secondary endpoints Randomization within 6 months of ASCT date R PFS, overall MRD-negative conversion rate, sustained R: 10 mg PO daily Days 1-28 MRD-negative rate, Stratification factor (after Cycle 3, 15 mg PO daily if tolerated) response rates, duration of Cytogenetic risk (standard >CR, OS, safety risk/unknown vs high risk) MRDb obtained after 12, 18, 24, and 36 cycles

[Slide 1] Objective: To determine the impact of adding DARA to R maintenance on MRD-negative conversion Key eligibility criteria Maintenance: up to 36 cyclesd (28-day cycles) 18-79 years of age Primary endpoint NDMM with >4 cycles of D-R MRD-negative (10-5) induction therapy and conversion rate from underwent ASCT within D: 1,800 mg SCe QW Cycles 1-2, baseline to 12 months after 12 months of the start 1:1 RANDOMIZATION (N = 200) Q2W Cycles 3-6, Q4W Cycles 7+ maintenance treatment of induction N = 214 planned to >VGPR at screening R: 10 mg PO daily Days 1-28 achieve >85% power to MRD positive (10-5) post-ASCT (after Cycle 3, 15 mg PO daily if tolerated) detect 20% improvement No prior anti-CD38 Secondary endpoints Randomization within 6 months of ASCT date R PFS, overall MRD-negative conversion rate, sustained R: 10 mg PO daily Days 1-28 MRD-negative rate, Stratification factor (after Cycle 3, 15 mg PO daily if tolerated) response rates, duration of Cytogenetic riskc (standard >CR, OS, safety risk/unknown VS high risk) MRD obtained after 12, 18, 24, and 36 cycles VGPR, very good partial response; D, daratumumab; SC, subcutaneous; QW, weekly Q2W, every 2 weeks Q4W, every 4 weeks PO, orally; CR, complete response - "As assessed by International Myeloma - Working Group --- [Slide 2] congresshub.com D-R R D-R R Characteristic (n 99) (n = 101) Characteristic (n=99) (n=101) Age, years, n (%) Cytogenetic risk at diagnosis,b n (%) Median (range) 63 (35-77) 62 (35-78) n 92 89 <65 61 (61.6) 61 (60.4) Standard risk 63(68.5) 66(74.2) 65-70 23(23.2) 21 (20.8) High risk 22 (23.9) 15(16.9) >70 15 (15.2) 19 (18.8) Sex, n (%) del[17p] 13 (14.1) 3(3.4) Male 61 (61.6) 58 (57.4) t[4;14] 10 (10.9) 12 (13.5) Race, n (%) t[14;16] 6(6.5) 7 (7.9) White 67 (67.7) 68 (67.3) Unknown 7(7.6) 8(9.0) Black 20 (20.2) 24 (23.8) Revised cytogenetic risk at diagnosis,b n (%) Asian 5(5.1) 1 (1.0) n 93 89 American Indian or Alaska Native 0 1 (1.0) Standard risk Other 52 (55.9) 53(59.6) 5(5.1) 5 (5.0) Not reported 2(2.0) 2(2.0) High riskd 32 (34.4) 30 (33.7) ECOG PS score, n (%) Unknown 9 (9.7) 6 (6.7) 0 45(45.5) 55(54.5) Induction cycles 1 52 52(52.5) 44 (43.6) Median (range)* 5.0 (4.0-8.0) 5.0 (4.0-8.0) 2 2(2.0) 2(2.0) >2 induction cycles with V and R included, n (%) 78 (78.8) 84 (83.2) ISS disease stage at diagnosis, n (%) Patient response category at baseline, n (%) n 91 98 sCR 14(14.1) 13(12.9) I 40(44.0) 38 (38.8) II 28 (30.8) 37 (37.8) CR 14 (14.1) 17 (16.8) III 23 (25.3) 23(23.5) VGPR 71 (71.7) 71 (70.3) ITT, intent-to-treat; ECOG PS, E astem Cooperative Oncology Group performance status; ISS, International Staging System; V, bortezomib; sCR, stringent complete response. Patients reporting multiple races are included under other. Assessed bylocal fuorescence in situ hybridization/karyotype test at diagnosis "High-risk cytogenetics are defined as a1 abnormality including del(17p]. t[4:14]. or t[14;16]. Revised high-risk cytogenetics are defined as a1 abnormality including del[17p]. t[4;14]. t[14;16], t[14;20]. or gain/amp(1q21). "Evaluable patients for the median number of induction cycles included those with 21 induction therapy (D-R. n 98; R, n 99). Response was assessed by computerized algorithm, based on International Uniform Response Criteria Consensus Recommendations 5 Presented by A Badros at the 21st International Society of yeloma (IMS) Annual Meeting: September 25-28. 2024; Rio de Janeiro, Brazil --- [Slide 3] a congresshub.com 46 AURIGA: MRD-negative (10-5) Conversion Rate From Baseline to 12 Months of Maintenance Treatmentᵃ OR 4.62 Primary endpoint (95% CI, 2.20-9.70) OR : 4.40 70 OR 4.51 P <0.0001 (95% CI, 2.26-8.58) (95% CI, 2.37-8.57) P <0.0001 60 P <0.0001 OR 4.61 MRD negativity, % (95% CI, (2.34-9.09) P <0.0001 50 40 30 61.3 50.5 56.8 20 44.4 Patie 25.8 10 18.8 23.2 14.9 0 D-R R D-R R D-R R D-R R (50/99) (19/101) (46/75) (16/62) (50/88) (19/82) (44/99) (15/101) ITT population Patients achieving >CR at any time MRD-evaluable population ITT population MRD-negative (10-5) MRD-negative (10-5) ≥CR conversion rate by 12 months conversion rate by 12 months --- [Slide 4] congresshub.com AURIGA: Increased MRD-negative Conversion Over Time and Sustained MRD Negativity at the 10⁻⁵ Threshold OR*:4.12 Primary endpoint (95% CI, 2.26-7.52) 70 P <0.0001 OR* 4.51 (95% CI, 2.37-8.57) 60 P <0.0001b OR*: 3.40 (95% CI, 1.69-6.83) Patients with MRD negativity, % 50 P -0.0005 40 30 60.6 50.5 20 35.4 27.7 10 18.8 13.9 0 D-R R D-R R D-R R (50/99) (19/101) (60/99) (28/101) (35/99) (14/101) MRD-negative (10-5) Overall MRD-negative (10-5) ≥6-months sustained conversion rate by 12 months conversion ratec MRD-negative (10-5) rated DARA more than doubled overall MRD-negative conversion rate and sustained MRD-negative rate

[Slide 1] Daratumumab With Lenalidomide (D-R) As Maintenance in Anti-CD38 Naïve, MRD-Positive Patients After Transplant in Newly Diagnosed Multiple Myeloma (NDMM): The AURIGA Study The phase 3 AURIGA study is the first randomized study to directly compare D-R versus R maintenance in patients with NDMM who were anti-CD38 naive Ш W Ш E and in >VGPR and MRD positive post-transplant D-R maintenance was associated with a At a median follow-up of 32.3 months, significantly higher MRD-negative conversion PFS favored The estimated rate by 12 months after the start of maintenance D-R versus R 30-month PFS rate treatment versus R alone (HR, 0.53; was higher for 95% CI, 0.29-0.97) D-R versus R 47% D-R R risk reduction in D-R R disease progression 50.5% 18.8% or death for D-R 82.7% 66.4% Odds Ratio, 4.51; 95% CI, 2.37-8.57; P<0.0001 No new safety concerns were observed Conclusions: Among transplant-eligible patients with NDMM who were anti-CD38 naïve and in ≥VGPR and MRD positive post-ASCT, D-R maintenance improved rates of MRD-negative conversion versus R alone. These results support the addition of daratumumab not only to induction/consolidation, but also to standard-of- care R maintenance. blood Badros et al. DOI: 10.xxxx/blood.2024xxxxxx Visual Abstract

[Slide 1] OR,* 4.62 Figure 2 OR,* 4.40 80 OR,* 4.51 (95% CI, 2.20-9.70) P <0.0001+ (95% CI, 2.26-8.58) (95% CI, 2.37-8.57) P<0.0001+ P<0.0001+ MRD-negative (10⁻⁵) conversion rate, % 60 40 20 0 D-R R D-R R D-R R 50.5% 18.8% 61.3% 25.8% 56.8% 23.2% (50/99) (19/101) (46/75) (16/62) (50/88) (19/82) ITT population Patients achieving ≥CR$ MRD-evaluable population" --- [Slide 2] D-R R Figure 3 MRD-negative rate, MRD-negative rate, n/N (%) n/N (%) OR (95% CI) ITT (overall) 50/99 (50.5) 19/101 (18.8) 4.51 (2.37-8.57) Sex Male 32/61 (52.5) 11/58 (19.0) 4.71 (2.06-10.78) Female 18/38 (47.4) 8/43 (18.6) 3.94 (1.45-10.68) Age <65 years 30/61 (49.2) 12/61 (19.7) 3.95 (1.76-8.85) ≥65 years 20/38 (52.6) 7/40 (17.5) 5.24 (1.86-14.74) Race White 31/67 (46.3) 14/68 (20.6) 3.32 (1.55-7.10) Black 12/20 (60.0) 4/24 (16.7) 7.50 (1.85-30.34) Other 7/12 (58.3) 1/9 (11.1) 11.20 (1.04-120.36) Weight <70 kg 12/23 (52.2) 4/18 (22.2) 3.82 (0.96-15.18) >70 kg 38/76 (50.0) 15/81 (18.5) 4.40 (2.14-9.03) Baseline ECOG PS score 0 20/45 (44.4) 9/55 (16.4) 4.09 (1.62-10.31) ≥1 30/54 (55.6) 10/46 (21.7) 4.50 (1.86-10.88) ISS at diagnosis I 19/40 (47.5) 8/38 (21.1) 3.39 (1.25-9.19) II 13/28 (46.4) 7/37 (18.9) 3.71 (1.23-11.25) III 15/23 (65.2) 3/23 (13.0) 12.50 (2.83-55.25) Cytogenetic risk at diagnosis High risk* 7/22 (31.8) 1/15 (6.7) 6.53 (0.71-60.05) Standard risk 35/63 (55.6) 14/66 (21.2) 4.64 (2.15-10.04) Revised cytogenetic risk at diagnosis High risk 14/32 (43.8) 4/30 (13.3) 5.06 (1.43-17.88) Standard risk 28/52 (53.8) 12/53 (22.6) 3.99 (1.72-9.26) 0.1 1 10 100 R better D-R better --- [Slide 3] Figure 100 4 82.7% 80 R % surviving without progression 66.4% 60 D-R 40 20 HR, 0.53 (95% CI, 0.29-0.97); P = 0.0361 0 0 3 6 9 12 15 18 21 24 27 30 33 36+ 39 42 Months No. at risk R 101 88 86 78 71 62 56 48 43 34 27 20 2 1 0 D-R 99 93 90 87 81 78 72 65 59 54 46 38 6 1 0 B 100 # 95.2% 000 CO O R MRD negative 94.1% 80 69.0% % surviving without progression 59.3% 60 A R MRD positive D-R MRD negative 40 D-R MRD positive 20 0 0 3 6 9 12 15 18 21 24 27 30 33 36+ 39 42 Months No. at risk R MRD negative 19 19 19 19 17 17 15 13 11 9 8 4 0 0 0 R MRD positive 82 69 67 59 54 45 41 35 32 25 19 16 2 1 0 D-R MRD negative 50 50 50 50 46 45 42 38 34 32 28 23 3 0 0 D-R MRD positive 49 43 40 37 35 33 30 27 25 22 18 15 3 1 0 --- [Slide 4] Daratumumab With Lenalidomide (D-R) As Maintenance in Anti-CD38 Naive, MRD-Positive Patients After Transplant in Newly Diagnosed Multiple Myeloma (NDMM): The AURIGA Study The phase 3 AURIGA study is the first randomized study to directly compare D-R versus R maintenance in patients with NDMM who were anti-CD38 naive E and in >VGPR and MRD positive post-transplant D-R maintenance was associated with a At a median follow-up of 32.3 months, significantly higher MRD-negative conversion PFS favored The estimated rate by 12 months after the start of maintenance D-R versus R 30-month PFS rate treatment versus R alone (HR, 0.53; was higher for 95% CI, 0.29-0.97) D-R versus R 47% D-R R risk reduction in D-R R disease progression 50.5% 18.8% or death for D-R 82.7% 66.4% Odds Ratio, 4.51; 95% CI, 2.37-8.57; P<0.0001 No new safety concerns were observed Conclusions: Among transplant-eligible patients with NDMM who were anti-CD38 naive and in >VGPR and MRD positive post-ASCT, D-R maintenance improved rates of MRD-negative conversion versus R alone. These results support the addition of daratumumab not only to induction/consolidation, but also to standard-of- care R maintenance. blood Badros et al. DOI: 10.xxxx/blood.2024xxxxxx Visual Abstract

[Slide 1] Daratumumab with Lenalidomide (D-R) as Maintenance in Anti-CD38 Naive, MRD-Positive Patients after Transplant in Newly Diagnosed Multiple Myeloma (NDMM): the AURIGA Study The phase 3 AURIGA study is the first randomized study to directly compare D-R vs R maintenance in patients with NDMM who were anti-CD38 naive and in VGPR ш ⑉ and MRD-positive post-ASCT D-R maintenance was associated with a At a median follow-up of 32.3 months, significantly higher MRD-negative conversion PFS favored The estimated rate by 12 months after the start of maintenance D-R vs R 30-month PFS rate treatment vs R alone (HR, 0.53; was higher for 95% CI, 0.29-0.97) D-R vs R 47% D-R risk reduction in R D-R R disease progression 50.5% 82.7% 66.4% 18.8% or death for D-R Odds Ratio, 4.51; 95% CI, 2.37-8.57; P< 0001 No new safety concerns were observed Conclusions: Among transplant-eligible patients with NDMM who were anti-CD38 naïve and in ≥VGPR and MRD-positive post-ASCT, D-R maintenance improved rates of MRD-negative conversion vs R alone. These results support the addition of daratumumab blood not only to induction/consolidation, but also to standard-of-care R maintenance. Visual Badros et al. DOI: 10.1182/blood.2024025746 Abstract