DREAMM-8 Trial

[Slide 1] The NEW ENGLAND JOURNAL of MEDICINE ORIGINAL ARTICLE Belantamab Mafodotin, Bortezomib, and Dexamethasone for Multiple Myeloma V. Hungria, P. Robak, M. Hus, V. Zherebtsova, C. Ward, P.J. Ho, A.C. Ribas de Almeida, R. Hajek, K. Kim, S. Grosicki, H. Sia, A. Bryant, M. Pitombeira de Lacerda, G. Aparecida Martinez, A.M. Sureda Balarí, I. Sandhu, C. Cerchione, P. Ganly, M. Dimopoulos, C. Fu, M. Garg, A.-O. Abdallah, A. Oriol, M.E. Gatt, M. Cavo, R. Rifkin, T. Fujisaki, M. Mielnik, N. Pirooz, A. McKeown, S. McNamara, X. Zhou, M. Nichols, E. Lewis, R. Rogers, H. Baig, L. Eccersley, S. Roy-Ghanta, J. Opalinska, and M.-V. Mateos, for the DREAMM-7 Investigators* --- [Slide 2] The NEW ENGLAND JOURNAL of MEDICINE ORIGINAL ARTICLE Belantamab Mafodotin, Pomalidomide, and Dexamethasone in Multiple Myeloma Meletios Athanasios Dimopoulos, M.D., Meral Beksac, M.D., Ludek Pour, M.D., Sosana Delimpasi, M.D., Vladimir Vorobyev, M.D., Hang Quach, M.D., Ivan Spicka, C.Sc., Jakub Radocha, M.D., Ph.D., Pawel Robak, M.D., Ph.D., Kihyun Kim, M.D., Michele Cavo, M.D., Kazuhito Suzuki, M.D., Ph.D., Kristin Morris, Pharm.D., Farrah Pompilus, Ph.D., Amy Phillips-Jones, M.Sc., Xiaoou L. Zhou, M.D., Ph.D., Giulia Fulci, Ph.D., Neal Sule, M.B., B.S., M.D., Brandon E. Kremer, M.D., Ph.D., Joanna Opalinska, M.D., Ph.D., María-Victoria Mateos, M.D., Ph.D., and Suzanne Trudel, M.D., for the DREAMM-8 Investigators*

[Slide 1] A Kaplan-Meier Analysis of Progression-free Survival Patients with Patients with Censored Censored 25th Percentile of Data, Data, Progression-free Patients with Follow-up Follow-up Survival an Event Ended Ongoing (95% CI) no. (%) no.(%) no.(%) mo BPd 12 mo 62 (40) 25 (16) 68 (44) 10.3 (5.6-14.0) 100 PVd 80 (54) 34 (23) 33 (22) 5.5 (3.7-6.5) 90 Hazard ratio for disease progression or death, 0.52 80 71 (95% CI, 63-78) (95% CI, 0.37-0.73) P<0.001 Percentage of Patients Alive and 70 60 BPd Progression-free 50 40 51 (95% CI, 42-60) 30 20 PVd 10 0 0 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 Months since Randomization No. at Risk (no. of events) BPd 155 143 130 122 113 109 102 93 80 75 67 59 45 36 23 16 8 2 0 0 0 (0) (5) (15) (21) (28) (32) (37) (42) (47) (50) (53) (56) (59) (61) (62) (62) (62) (62) (62) (62) (62) PVd 147 138 111 96 83 68 56 51 43 39 30 22 19 18 13 7 4 2 1 1 0 (0) (4) (23) (33) (45) (52) (62) (64) (68) (68) (73) (77) (77) (77) (78) (80) (80) (80) (80) (80) (80) B Post Hoc Supplementary Analysis of Progression-free Survival BPd PVd Analysis (N=155) (N=147) no. of patients with event (%) Disease progression or death 71 (46) 89 (61) Disease progression 46 (30) 66 (45) Disease progression after extended loss to follow-up 2 (1) 3 (2) Disease progression after the start of new antimyeloma therapy 0 0 Death 16 (10) 14 (10) Death after extended loss to follow-up 4 (3) 4 (3) Death after the start of new antimyeloma therapy 3 (2) 2 (1) Censored, follow-up ended 16 (10) 25 (17) Censored, follow-up ongoing 68 (44) 33 (22) Hazard ratio (95% CI) 0.55 (0.40-0.76) --- [Slide 2] Patients with Patients with Censored Censored Data, Data, 25th Percentile of Patients with Follow-up Follow-up Overall Survival an Event Ended Ongoing (95% CI) no. (%) no. (%) no. (%) mo BPd 49 (32) 12(8) 94 (61) 19.0 (12.2-23.3) PVd 56 (38) 7(5) 84 (57) 12.7 (8.0-18.5) Hazard ratio for death, 0.77 (95% CI, 0.53-1.14) 12 mo 100 83 (95% CI, 76-88) 90 80 70 BPd Percentage of Patients Alive 76 (95% CI, 68-82) 60 50 PVd 40 30 20 10 0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 Months since Randomization No. at Risk (no. of events) BPd 155 147 142 141 139 132 125 115 112 104 93 83 63 57 35 24 13 7 1 0 0 (0) (4) (9) (10) (12) (18) (25) (30) (31) (35) (38) (42) (47) (47) (48) (48) (48) (49) (49) (49) (49) PVd 147 140 134 128 119 113 110 101 93 89 75 65 50 46 31 21 13 11 7 3 0 (0) (7) (12) (18) (26) (32) (35) (40) (44) (45) (49) (50) (54) (56) (56) (56) (56) (56) (56) (56) (56) --- [Slide 3] BPd PVd Response (N=155) (N=147) Best overall response - no. (%) Stringent complete response 14(9) 4 (3) Complete response 48 (31) 20 (14) Very good partial response 37 (24) 32 (22) Partial response 21 (14) 50 (34) Minimal response 4 (3) 8 (5) Stable disease 19 (12) 22 (15) Progressive disease 5 (3) 1 (<1) Not evaluable 7 (5) 10 (7) Complete response or bettert No. of patients 62 24 % (95% CI) 40 (32-48) 16 (11-23) Very good partial response or better No. of patients 99 56 % (95% CI) 64 (56-71) 38 (30-46) Any response: partial response or better No. of patients 120 106 % (95% CI) 77 (70-84) 72 (64-79) Response duration of 12 mo - % (95% CI): 79 (71-86) 61 (50-70) MRD-negative statustS Patients with complete response or better No. of patients 37 7 % (95% CI) 24 (17-31) 5 (2-10) Patients with very good partial response or betterll No. of patients 50 8 % (95% CI) 32 (25-40) 5 (2-10) MRD-negative status sustained for 212 monthst5 Patients with complete response or better No. of patients 13 2 % (95% CI) 8 (4-14) 1 (<1-5) Confidence intervals have not been adjusted for multiplicity and cannot be used in place of hypothesis testing. 1 Percentages are based on the intention to treat population. Patients who did not meet the applicable response criteria were considered not to have had a response and are included in the denominator when calculating percentages. : Duration of response was defined as the time from first documented evidence of partial response of better until the occurrence of progressive disease or death from any cause. $ Minimal residual disease (MRD)-negative status was determined on the basis of next generation sequencing with a sensitivity of 10 $. 1 Of the 62 patients in the BPd group who had a complete response or better, 54 had available MRD data. Of the 24 patients in the PVd group who had 3 complete response or better, 20 had available MRD data. $ Of the 99 patients in the BPd group who had very good partial response or better, 82 had available MRD data. Of the 56 patients in the PVd group who had 3 very good partial response or better, 38 had available MRD data. --- [Slide 4] BPd PVd Event (N=150) (N=145) Any Grade Grade >3 Any Grade Grade >3 number (percent) Any adverse event 149 (99) 141 (94) 139 (96) 110 (76) Blurred vision 119 (79) 26 (17) 22 (15) 0 Dry eye 91 (61) 12 (8) 14 (10) 0 Foreign-body sensation in eyes 91 (61) 9 (6) 9 (6) 0 Eye irritation 75 (50) 6 (4) 13 (9) 0 Neutropenia 72 (48) 63 (42) 50 (34) 41 (28) Photophobia 66 (44) 5 (3) 6 (4) 0 Coronavirus disease 2019 56 (37) 10 (7) 31 (21) 3 (2) Thrombocytopenia 54 (36) 36 (24) 44 (30) 29 (20) Eye pain 49 (33) 3 (2) 7 (5) 0 Cataract 40 (27) 9 (6) 15 (10) (4) Fatigue 40 (27) 9 (6) 32 (22) (5) Upper respiratory tract infection 40 (27) (1) 25 (17) 0 Pneumonia 36 (24) 26 (17) 17 (12) 11 (8) Anemia 35 (23) 15 (10) 38 (26) 19 (13) Diarrhea 35 (23) (1) 33 (23) 10 (7) Corneal epithelial microcysts 34 (23) 12 (8) 0 0 Punctate keratitis 34 (23) 9 (6) (1) 1 (1) Reduced visual acuity 34 (23) 20 (13) (6) (1) Decreased neutrophil count 31 (21) 31 (21) 19 (13) 18 (12) Decreased platelet count 30 (20) 22 (15) 22 (15) 18 (12) Constipation 23 (15) 2 (1) 33 (23) 2 (1) Peripheral neuropathy 11 (7) (1) 34 (23) 4 (3) The safety population included all patients who received a least one dose of BPd or PVd. Adverse events were graded with the use of the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0.

[Slide 1] 2024 ASCO ANNUAL MEETING 2024ASCO Results from the randomized phase 3 DREAMM-8 study ANNUAL MEETING of belantamab mafodotin plus pomalidomide and dexamethasone vs pomalidomide plus bortezomib and dexamethasone in relapsed/refractory multiple myeloma Suzanne Trudel,¹ Meral Beksac,2 Ludek Pour,³ Sosana Delimpasi,⁴ Hang Quach,⁵ Vladimir I. Vorobyev,6 Michele Cavo,⁷ Kazuhito Suzuki,8 Pawel Robak,9 Kristin Morris,¹⁰ Amy Phillips-Jones,¹¹ Xiaoou L. Zhou,¹² Giulia Fulci,12 Neal Sule,¹³ Brandon E. Kremer,¹³ Joanna Opalinska,¹³ Maria-Victoria Mateos Manteca,¹⁴ Meletios A. Dimopoulos15 Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada; Department of Hematology, Ankara Liv Hospital, Istinye University, Ankara, Turkey; Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic; 'General Hospital Evangelismos, Athens, Greece; University of Melbourne, St. Vincent's Hospital, Melbourne, VIC, Australia; Leningrad Regional Clinical Hospital, St Petersburg, Russian Federation: IRCCS Azienda Ospedaliero-Universitaria di Bologna, Seragnoli Institute of Hematology, and Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; Division of Clinical Oncology/Hematology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan; "Medical University of Lodz, Lodz, Poland; "GSK, Durham, NC, USA; "GSK, Stevenage, UK; GSK, Waltham, MA, USA; BSK, Collegeville, PA, USA; "Hematology Department, University Hospital of Salamanca/IBSAL/Cancer Research Center-IBMCC (USAL-CSIC), Salamanca, Spain; "Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. 2024 ASCO #ASCO24 PRE SENTED BY: Suzanne Trudel, MD ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY ANNUAL MEETING Presentation property the author and ASCO Permission required for - contact permissions@asco.org KNOWLEDGE CONQUERS CANCER 2024 ASCO ANNUAL MEETING --- [Slide 2] CREAMM-8 Study Design - Recruitment period Treatment period October 2020 to December 2022 - PD. death, unacceptable toxicity, and of mady, or withhold of - 2024ASCO N=302 Belantamab mafodotin Eligibility criteria ANNILIAL MEETING BPd (Q4W) 2.5 mg/kg IV (cycle 1) then 1.9 mg IV Q4W from cycle 2 Primary endpoint: Adults with MM onward PFS (IRC assessed per IMWG) as prior line of MM Pomalidomide 4 mg orally on days 1-21 (28-day cycles) therapy including LEN Documented PD No prior treatment 1:1 randomization 13 mg/ml SC on days 1, 4, 8, and 11 of cycles 14 then End-ot Visa Key secondary endpoints: Dexamethasone 40 mg* on days 1.8. 15. and 22 during or after their OS, MRD negativity, DOR most recent therapy Bortezomib PVd (Q3W) Additional secondary with anti-BCMA or days 1 and 8 (21 day cycles) endpoints include: pomalidomide; not refractory/intolerant to Pomalidomide 4 mg orally on days 1-14 (21-day cycles) ORR, CRR, 2VGPR, TTBR, bortezomb TTR. TTP. PFS2. AEs, ocular Dexamethasone 20 mg* on the day of and day after findings, HROOL, and PROs bortezumb Stratification*: Prior lines of treatment (1 vs 2 or , is a4) Prior bortazomib (yes vsi not Prior anti-C038 therapy (yes " no) 2024 ASCO #ASCO24 - Suranne Trudel, MD ASCO MEXTING KNOWLEDGE CONSULES 2024 ASCO ANNUAL MEETING --- [Slide 3] DREAMM-8 Treatment Status MASSEW 302 randomly allocated 2024ASCO ANNUAL MEETING BPd PVd ITT (N=155) ITT (N=147) Belamaf discontinued 64% (n=99) Reasons for discontinuation* Bortezomib discontinued 70% (n=116) Reasons for discontinuation* Progressive disease 28% (nm44) Adverse event 18% (nw25) Progressive disease 48% (nw71) Physician decision 12% Adverse event 19% (s=23) Withdrawal by patient 6% (news) Physician decision 10% (nw14) Protocol deviation <1% (AMT) Withdrawal by patient 5% (nw) Ongoing belamaf Ongoing bortezomib treatment 36% (n=56) treatment 21% (n=31) Median follow-up, 21.8 months (range, 0.03-39.23 months) I # - I I - I | - I : PVS | I - examine $ 2024 ASCO #ASCO24 - Suranne Trudel MD ASCO CUSICAS - MEETING I I I I I I I I I KNOWLEDGE CONSUERS CANCER 2024 ASCO ANNUAL MEETING

[Slide 1] On the approval of Blenrep (belantamab mafodotin) combinations by UK MHRA in relapsed/refractory multiple myeloma Joseph Mikhael, MD, MEd, FRCPC, FACP, FASCO Chief Medical Officer International Myeloma Foundation "We are pleased to see this advancement in the treatment landscape extended across both academic and community settings where many patients are treated." INTERNATIONAL MYELOMA L FOUNDATION YEAR ANNIVERSARY

[Slide 1] A PHASE II, OPEN LABEL, RANDOMIZED, TWO-ARM STUDY TO INVESTIGATE THE EFFICACY AND SAFETY OF TWO DOSES OF THE ANTIBODY DRUG CONJUGATE GSK2857916 IN PARTICIPANTS WITH MULTIPLE MYELOMA WHO HAD 3 OR MORE PRIOR LINES OF TREATMENT, ARE REFRACTORY TO A PROTEASOME INHIBITOR AND AN IMMUNOMODULATORY AGENT AND HAVE FAILED AN ANTI-CD38 ANTIBODY (DREAMM 2) Figure 1. Study design¹⁰ Treatment until disease progression or Primary outcome Key secondary outcomes unacceptable toxicity DoR (time from zPR until Belamaf2.5 mg/kg disease progression IV, Q3W or death due to PD) (n=97) ORR: Other efficacy: CBR, PFS, % of patients with EPR OS, TTBR, TTP. TTR Belamaf 3.4 mg/kg (IMWG 2016 criteria) Safety, including Patients: Screening Randomization IV, Q3W 1:1" (n=99) keratopathy (MECs, an >3L RRMM eye examination finding) 12TH SUMMIT ON Eligibility Criteria HEMATOLOGIC Measurable disease ECOG PS of 0-2 >3 prior lines of therapy MALIGNANCIES Refractory to immunomodulatory Prior ASCT allowed; Not exposed to a prior agents and Pls. and refractory and/or intolerant to an anti-CD38 mAb BCMA-targeted therapy allogeneic stem cell transplant excluded *Patients stratified based on number of previous lines of therapy ($4 vs. >4) and presence or absence of HR cytogenetic features; measurable disease AOncology 2025 Whistler HEME defined as serum myeloma protein (M-protein) 20 5 g/dL; urine protein >200 mg/24 h; serum FLC assay involved FLC level >10 mg/dL and an abnormal serum FLC ratio (<0 or >1.65) 3L, third line; ASCT, autologous stem cell transplant; CBR, clinical benefit rate; ECOG PS, Eastern Cooperative Oncology Group Performance Status FLC, serum free light chain assay, PD, progressive disease, Pls, proteasome inhibitors; TTBR, time to best response; TTP, time to progression; TTR, time to response Lonial S, et al. Lancet Oncol 2020;21:207-21 Winship Cancer Institute Emory University 396 --- [Slide 2] Median PFS was longer for belamaf vs Pd, but PFS HR was 1.03 Median follow-up was 11.5 months for belamaf 1.0- Treatment Detantsmab matiodorin and 10.8 months for Pd. Pomaidomide dexamethasone 0.8- Median PFS was longer for belamaf than for Pd, but PFS HR did not reach statistical Belamaf: 11.2 months (95% CI 6.4 - 14.5). Proporto progression I I 0.6 significance. 0.4 0.2 Pd: 7.0 months (95% CI 4.6 - 10.6). 0.0 HR of 1.03 (95% Cl: 0.72, 1.47, p=0.558). 0 2 3 4 5 6 7 . to 11 12 13 14 15 # 17 18 19 20 21 22 23 12ᵀᴴ SUMMIT ON - - Time since randomization (months) KM curves cross over at ~4 months. I I HEMATOLOGIC - - MALIGNANCIES DAVAOncology 2025 Whistler HEME CI. confidence interval HR. hazard ratio KM. Kaplan-Meier, Pd. pomalidomice plus dexamethasone PFS. progression free survival 2023 ASCO #ASCO23 PRESENTED - Dr Katja Weisel ASCO AMERICAN SOCIETY OF CUMICAL PROCEDUR ANNUAL MEETING Presentation - - - MICO Permission - - KNOWLEDGE CONGUERS CANCER Content of this presentation is the property of the author, licensed by ASCO. Permission required/forreis@ancer Institute I Emory University 400 --- [Slide 3] DREAMM-7: PFS AND os IN THE ITT PFS os 1.0 18 months 1.0 18 months 84% 69% 0.8 Median 0.8 36.6 months 0.6 0.6 73% PFS probability, % #++++ 0.4 Median os probability, % 0.4 13.4 0.2 months 0.2 43% 12ᵀᴴ SUMMIT ON 0.0 0.0 HEMATOLOGIC 014569 01 23 4 5 6 7 8 9101112131415161715192021222324232627209303132333435363738394041 No. at risk Time Since randomization, months Time Since randomization, months MALIGNANCIES PFS' BVd (N=243) DVd (N=251) OS' BVd (N=243) DVd (N=251) Events, n(%) 91 (37) 158 (63) Events, n(%) 54 (22) 87 (35) PFS, median (95% CI). mob 36.6 (28.4-NR) 13.4 (11.1-17.5) OS, median (95% CI). mob NR NR DAVAOncology 2025 Whistler HEME HR (95% CI) 0.41 (0.31-0.53) HR (95% CI) 0.57 (0.4-0.8) P value <.00001 P value 00049 WINSHIP CANCER INSTITUTE OF EMORY UNIVERSITY NCI Designated Comprehensive Cancer Center --- [Slide 4] DREAMM-8: EFFICACY BPd PVd PFS Positive os Trend Favoring BPd VS PVd 1.0 1.0 12 months 12 months 83% 0.8 71% 0.8 Proportion alive and progression free 0.6 0.6 76% 0.4 51% Proportion alive 0.4 0.2 0.2 12ᵀᴴ SUMMIT ON 0.0 0.0 0 123456789 1011 12 13 14 15 16 17 18 192021 25 26 77 28 0 123456789 15 18 22 26 27 30 11 HEMATOLOGIC No. at risk Time Since randomization, months No. at risk Time Since randomization, months MALIGNANCIES PFS' BPd (N=155) PVd (N=147) Interim os BPd (N=155) PVd (N=147) Events, n(%) 62 (40) 80 (54) Events, n(%)a 49 (32) 56 (38) Median PFS (95% CI). months NR (20.6-NR) 12.7 (9.1-18.5) Median OS (95% CI), months NR (33.0-NR) NR (25.2-NR) DAVAOncology 2025 Whistler HEME HR (95% CI): P value 0.52 (0.37-0.73): <.001 HR (95% Cl) 0.77 (0.53-1.14) Trudel et al. ASCO 2024 Clin Oncol 42. 2024 (suppl 17. abstr LBA105) WINSHIP CANCER INSTITUTE OF EMORY UNIVERSITY NCI Designated Comprehensive Cancer Center