SUCCESSOR-2 Trial

SUCCESSOR-2 SUCCESSOR-2: Study Design Stage 1 (dose optimization)* Stage 2 (efficacy and safety) Confirmatory analysis group (N - 479) Primary endpoint Key eligibility criteria Mezikd at PFS per IRC Selected Mezi dose 1.0 mg Mezi MeziKd (N 631° Key secondary endpoint Adult participants 1.0 mg Mezi . os who received 21 prior Mezikd at QW 56 mg/m2 K line of antimyeloma therapy with progressive disease Randomization 3:3:3:2 0.6 mg Mezi Randomization 3:2 Selected secondary (N 63) (N = 225) (N = 371) endpoints (SEZ - N) Recommended Mezi Mezikd at dose (stage 1) - Prior treatment 0.3 mg Mezi Kdᶜ,ᵈ ORR, VGPR, CR with LEN and an (N 64) TTR, DoR BW 56 mg/m² or anti-CD38 mAb PFS2 QW 70 mg/m² K Safety Kd (N 451° (N = 146) In the MeziKd arm, patients received: Mezi 1.0 mg orally once daily on D1-21 of each 28-day cycle K* 56 mg/m² IV on D1, 8, and 15 in C1-12 and on D1 and 15 in C 2 13 DEX 40 mg orally/IV on D1, 8, 15, and 22 NCT05552976 Patients enrolled in stage 1 on . dose of Metal not chosen for stage 2 had the option to move to the selected dose if some criteria were ext; Patients from these Mage 1 asses were included in the confirmatory analysis groups; TEX doving Married arm; 40 mg, option of 20 mg If 75 years of age, - . 18.5 kg/m/, poorly controlled diabetes, or prior Intelerance to steroid therapy; Md annc 20 mg, 10 mg option for stated criteria (tw regineen) or 40 and 20 mg option for stated criteria (QW registered; 92W register made available July 2003; % dose on CNDS was 20 mg/ml, BAK, body mana leader; on, twice weekly; C, cycles D, day; DEX, desamethasone; DoR, duration of response; INC. independent review committees K, os, overall survivel; PF52, second progression fire survices); car, weekly, TTR, time to response. Richardson PG, et at. ASCO 2026. Presentation LBA7506 --- SUCCESSOR-2 SUCCESSOR-2: PFS2 Median PFS2 Hazard ratio 1.0 23.6 months HR 0.53 Subsequent antimyeloma MeziKd Kd 0.9 therapy, %* (N = 288) (N # 191) 13.0 months (95% CI, 0.39-0.72) 0.8 Any subsequent therapy 24.0 49.7 0.7 Bispecific antibodies 10.1 21.5 Probability of PFS2 0.6 IMiDs 6.9 20.4 MeziKd 0.5 POM 5.6 18.3 LEN 0.3 1.0 0.4 Pls 6.6 11.0 0.3 Kd Standard chemotherapyb 6.6 12.6 0.2 Other 4.9 8.9 0.1 Median follow-up: 10.6 months Anti-CD38 mAbs 4.2 7.3 0 Investigational drugs 2.8 7.3 0 3 6 9 12 15 18 21 24 27 30 33 Anti-SLAMF7 mAbs 1.4 5.8 Time (months) No. at risk CAR-T cell therapies 1.4 4.7 MeziKd 288 273 238 173 116 72 39 30 19 9 3 0 Antibody-drug conjugates 0.3 3.1 Kd 191 171 143 101 63 31 19 12 5 2 0 0 Superior PFS2 with MeziKd demonstrates sustained clinical benefit beyond first progression Data cutoff: January 15, 2026. In the confirmatory analysis group, defined as all patients from stages 1 and 2 randomized to 1.0 mg Mezi plus Kd or Kd. PFS2 was per investigator assessment "Includes subsequent antimyeloma therapies that were received by 2 1% of patients in either treatment arm in the confirmatory analysis group; Standard chemotherapy includes: nitrogen mustard analogs, anthracyclines and related substances, podophyllotoxin derivatives, platinum compounds, purine analogs, and vinca alkaloids and analogs; Refers to the output of "Cell and Gene therapies". CAR, chimeric antigen receptor. --- SUCCESSOR-2 SUCCESSOR-2: Overall Survival 1.0 0.9 0.8 0.7 MeziKd Probability of os 0.6 Kd 0.5 No. of events Hazard ratio 0.4 62/288 (21.5%) HR 0.79 0.3 51/191 (26.7%) (95% CI, 54-1.15) 0.2 Median follow-up: 10.6 months 0.1 0 0 3 6 9 12 15 18 21 24 27 30 33 Time (months) No. at risk MeziKd 288 273 244 180 122 79 45 35 25 12 5 0 Kd 191 175 157 118 84 44 31 24 12 5 0 0 Planned futility analysis demonstrates a positive OS trend favoring MeziKd with no cross over of the curves Data cutoff: January 15, 2026. In the confirmatory analysis group, defined as all patients from stages 1 and 2 randomized to 1.0 mg Mezi plus Kd or Kd. Deaths occurred in 21.5% (MeziKd) and 26.7% (Kd) of patients. Richardson PG, et al. ASCO 2026, Presentation LBA7506 --- SUCCESSOR-2 SUCCESSOR-2: Most Common TEAEs MeziKd Kd TEAE,ᵃ n (%) (N = 288) (N = 186)b Neutropenia is an on-target reversible AE; Any grade Grade 3/4 Any grade Grade 3/4 only 1 patient discontinued treatment due to neutropenia with MeziKd (none with Kd) Any TEAE 286 (99.3) 241 (83.7) 178 (95.7) 105 (56.5) Hematological A reduction in grade 3/4 hypertension was Neutropenia 199 (69.1) 176 (61.1) 32 (17.2) 17 (9.1) observed with MeziKd, potentially Febrile neutropenia 24 (8.3) 23 (8.0) 0 0 associated with the lower K dose Thrombocytopenia⁴ 174 (60.4) 113 (39.2) 77 (41.4) 42 (22.6) Anemia 149 (51.7) 75 (26.0) 66 (35.5) 28 (15.1) Grade 3/4 VTEe occurred in 2.8% (Mezikd) White blood cell count decrease 67 (23.3) 54 (18.8) 23 (12.4) 7 (3.8) and 0.5% (Kd) of patients Nonhematological Grade 5 TEAEs were observed in 7.3% Diarrhea 112 (38.9) 10 (3.5) 33 (17.7) 1 (0.5) (Mezikd) and 4.3%VKd) of patients URTI 79 (27.4) 13 (4.5) 31 (16.7) 3 (1.6) Fatigue 67 (23.3) 9 (3.1) 39 (21.0) 7 (3.8) — The majority were in the context of Cough 66 (22.9) 1 (0.3) 22 (11.8) 0 myeloma progression Pneumonia 58 (20.1) 45 (15.6) 21 (11.3) 11 (5.9) Dyspnea 58 (20.1) 11 (3.8) 26 (14.0) 5 (2.7) Hypertension 31 (10.8) 11 (3.8) 40 (21.5) 17 (9.1) Neutropenia was the most common grade 3/4 AE and was managed effectively with dose interruptions/modifications and/or G-CSF Data cutoff: January 15, 2026. "includes TEAEs of any grade that occurred in 2 20% of patients and grade 3/4 TEAEs that occurred in 2 10% of patients in either treatment arm in the confirmatory analysis group of the safety population, defined as all patients from stages 1 and 2 randomized to 1.0 mg Mezi plus Kd or Kd who received 2 1 dose of study treatment. TEAEs were graded per the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0; *Excludes 5 patients who were randomized but not treated; Includes preferred terms of neutropenia and neutrophil count decrease; Includes preferred terms of thrombocytopenia and platelet count decrease; "Standardized MedDRA Query for embolism and thrombosis various terms. MedDRA, Medical Dictionary for Regulatory Activities; SAE, serious adverse event; TEAE, treatment emergent adverse event; URTI, upper respiratory tract infection; VTE, venous thromboembolism. Richardson PG, et al. ASCO 2026, Presentation LBA7506

#ASCO26 Oral Abstract Session LBA7506: Mezigdomide, carfilzomib, and dexamethasone (MeziKd) vs carfilzomab and dexamethasone (Kd) in relapsed/refractory multiple myeloma (RRMM): Results from the phase 3 SuCCESSOR-2 trial Dana-Farber PAUL RICHARDSON, MD Cancer Institute

SUCCESSOR-2 SUCCESSOR-2: Most Common TEAEs MeziKd Kd TEAE,ᵃ n (%) (N = 288) (N = 186)b Neutropenia is an on-target reversible AE; Any grade Grade 3/4 Any grade Grade 3/4 only 1 patient discontinued treatment due to neutropenia with MeziKd (none with Kd) Any TEAE 286 (99.3) 241 (83.7) 178 (95.7) 105 (56.5) Hematological A reduction in grade 3/4 hypertension was Neutropenia 199 (69.1) 176 (61.1) 32 (17.2) 17 (9.1) observed with MeziKd, potentially Febrile neutropenia 24 (8.3) 23 (8.0) 0 0 associated with the lower K dose Thrombocytopenia⁴ 174 (60.4) 113 (39.2) 77 (41.4) 42 (22.6) Anemia 149 (51.7) 75 (26.0) 66 (35.5) 28 (15.1) Grade 3/4 VTEe occurred in 2.8% (Mezikd) White blood cell count decrease 67 (23.3) 54 (18.8) 23 (12.4) 7 (3.8) and 0.5% (Kd) of patients Nonhematological Grade 5 TEAEs were observed in 7.3% Diarrhea 112 (38.9) 10 (3.5) 33 (17.7) 1 (0.5) (Mezikd) and 4.3%(Kd) of patients URTI 79 (27.4) 13 (4.5) 31 (16.7) 3 (1.6) Fatigue 67 (23.3) 9 (3.1) 39 (21.0) 7 (3.8) - The majority were in the context of Cough 66 (22.9) 1 (0.3) 22 (11.8) 0 myeloma progression Pneumonia 58 (20.1) 45 (15.6) 21 (11.3) 11 (5.9) Dyspnea 58 (20.1) 11 (3.8) 26 (14.0) 5 (2.7) Hypertension 31 (10.8) 11 (3.8) 40 (21.5) 17 (9.1) Neutropenia was the most common grade 3/4 AE and was managed effectively with dose interruptions/modifications and/or G-CSF Data cutoff: January 15, 2026. "Includes TEAEs of any grade that occurred in 2 20% of patients and grade 3/4 TEAEs that occurred in 2 10% of patients in either treatment arm in the confirmatory analysis group of the safety population, defined as all patients from stages 1 and 2 randomized to 1.0 mg Mezi plus Kd or Kd who received 2 1 dose of study treatment. TEAEs were graded per the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0; Excludes 5 patients who were randomized but not treated; Includes preferred terms of neutropenia and neutrophil count decrease; Includes preferred terms of thrombocytopenia and platelet count decrease; "Standardized MedDRA Query for embolism and thrombosis various terms. MedDRA, Medical Dictionary for Regulatory Activities; SAE, serious adverse event; TEAE, treatment emergent adverse event; URTI, upper respiratory tract infection; VTE, venous thromboembolism. Richardson PG, et al. ASCO 2026, Presentation LBA7506 --- SUCCESSOR-2 SUCCESSOR-2: Summary of Infections MeziKd Kd (N = 288) (N = 186)b TEAE,ᵃ n (%) Any Grade Grade Any Grade Grade grade 3 4 grade 3 4 Any infection 210 (72.9) 82 (28.5) 16 (5.6) 100 (53.8) 28 (15.1) 1 (0.5) Most infections (68.6% MeziKd; 98.0% Kd) were not associated with URTI 79 (27.4) 13 (4.5) 0 31 (16.7) 3 (1.6) 0 grade 3/4 neutropenia Pneumonia 58 (20.1) 39 (13.5) 6 (2.1) 21 (11.3) 10 (5.4) 1 (0.5) Incidence of hypogammaglobulinemia Influenza 30 (10.4) 9 (3.1) 0 18 (9.7) 2 (1.1) 0 was low COVID-19 29 (10.1) 5 (1.7) 0 11 (5.9) 0 0 10.1% (Mezikd) versus 6.5% (Kd) RTI 29 (10.1) 7 (2.4) 0 8 (4.3) 0 0 31.6% (Mezikd) versus 21.0% (Kd) of UTI 26 (9.0) 8 (2.8) 0 9 (4.8) 1 (0.5) 0 patients received ≥1 dose of IGRT Nasopharyngitis 17 (5.9) 0 0 18 (9.7) 0 0 Incidence of fatal infections was low (2.4% MeziKd; 1.1% Kd) Bronchitis 17 (5.9) 6 (2.1) 0 7 (3.8) 0 0 Infections were mostly well managed following standard clinical practice and supportive care, with low incidence of grade 4 events Data cutoff: January 15, 2026. As of December 2024, Pneumocystis jirovecii pneumonia prophylaxis was required in both arms. "TEAEs that occurred in 2 5% of patients in either treatment arm in the confirmatory analysis group of the safety population, defined as all patients from stages 1 and 2 randomized to 1.0 mg Mezi plus Kd or Kd who received 2 1 dose of study treatment; PExcludes 5 patients who were randomized but not treated. RTI, respiratory tract infection; UTI, urinary tract infection. Richardson PG, et al. ASCO 2026, Presentation LBA7506

cancernetwork® home of the journal ONCOLOGY 3 ABSTRACTS TO WATCH ASCO 2026 I Multiple Myeloma Abstract 7507 MajesTEC-9 Phase 3: Teclistamab monotherapy vs PVd/Kd in relapsed/refractory multiple myeloma (1-3 prior lines) Presenter: Roberto Mina, MD Abstract 7510 Optec/Optal Phase 2: Outpatient teclistamab or talquetamab with prophylactic tocilizumab in RRMM Presenter: Peter Forsberg, MD Abstract LBA7506 SUCCESSOR-2 Phase 3: Mezigdomide + carfilzomib + dexamethasone (Mezikd) vs Kd in RRMM Presenter: Paul G. Richardson, MD Read more on CancerNetwork.com

Study marks the first positive Phase 3 study for mezigdomide and the second positive Phase 3 study for the Bristol Myers Squibb CELMoD program PRINCETON, N.J.--(BUSINESS WIRE)--Bristol Myers Squibb (NYSE: BMY) today announced positive interim Phase 3 results from the SUCCESSOR-2 study (NCT05552976). In the trial, oral mezigdomide in combination with carfilzomib and dexamethasone (MeziKd) demonstrated statistically significant and clinically meaningful improvement in progression-free survival (PFS) versus carfilzomib and dexamethasone alone (Kd) in patients with relapsed or refractory multiple myeloma (RRMM). Safety findings were consistent with the known profile of mezigdomide and the combination regimen. Patients will continue to be followed for survival and safety.