Phase I Trial Updated Analysis of BCMA x

Phase I Trial: Updated Analysis of BCMA x CD 3 Bispecific Antibody Teclistamab (JNJ-64007957) in Patients With R/R MM CCO Independent Conference Highlights of the 2020 Virtual ASH Annual Meeting, December 5 -8, 2020 *CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs. Supported by educational grants from Amgen; Astra. Zeneca; Bristol-Myers Squibb; Epizyme, Inc. ; Glaxo. Smith. Kline; Incyte Corporation; Janssen Biotech; Karyopharm Therapeutics Inc. ; Novartis; Pharma. Essentia Corp. ; Seattle Genetics; and Takeda Oncology.

About These Slides § Please feel free to use, update, and share some or all of these slides in your noncommercial presentations to colleagues or patients § When using our slides, please retain the source attribution: Slide credit: clinicaloptions. com § These slides may not be published, posted online, or used in commercial presentations without permission. Please contact permissions@clinicaloptions. com for details

Teclistamab Phase I Trial Update: Background § Patients with MM who progress on available therapies have a poor prognosis (median OS from time of progression on anti-CD 38: 6 -11 mos)[1] § Teclistamab (JNJ-64007957): investigational humanized BCMA bispecific antibody [2] ‒ Anti-BCMA bispecific antibody engineered to enhance cytotoxic T-cell responses against tumor cells by linking Fc portion of antibody against CD 3 to Fc portion against BCMA ‒ Induced CD 3+ T-cell–mediated killing of BCMA-positive myeloma cells in murine xenograft models and bone marrow samples from patients with MM § Initial results of ongoing first-in-human, dose-escalation/dose-expansion phase I trial reported clinical activity and manageable AEs with teclistamab IV in R/R MM [3] § Current analysis presents updated safety and efficacy data from phase I trial of teclistamab IV or SC in patients with R/R MM[4] 1. Ghandi. Leukemia. 2019; 33: 2266. 2. Pillarisetti. Blood Adv. 2020; 4: 4538. 3. Usmani. ASCO 2020. Abstr 100. 4. Garfall. ASH 2020. Abstr 180. Slide credit: clinicaloptions. com

Teclistamab Phase I Trial Update: Study Design § Updated analysis of first-in-human, openlabel, dose-escalation/-expansion phase I trial (data cutoff: October 26, 2020) Step-Up Dosing: IV (n = 84) Step-Up Dosing: SC (n = 65) 720 µg/kg 3000 µg/kg ‒ Dosing switched from IV Q 2 W to IV or SC wkly with or without step-up dosing 180 µg/kg Adults with measurable MM that is R/R or intolerant to established treatments; Hb ≥ 8 g/d. L; PLT ≥ 75 x 9 10 /L*; ANC ≥ 1. 0 x 109/L; no prior BCMA-targeted agent (N = 149) Teclistamab at 1 -3 step-up doses† Teclistamab at full dose wkly for cycle 1 onwards† § Key endpoints: Part 1, determine RP 2 D; Part 2, safety/tolerability at RP 2 D; antitumor activity, PK/PD NCT 03145181. Garfall. ASH 2020. Abstr 180. 1500 µg/kg 270 µg/kg 120 µg/kg 80 µg/kg RP 2 D‡ 720 µg/kg 240 µg/kg 80 µg/kg 57. 6 µg/kg 38. 4 µg/kg 0. 3 -19. 2 µg/kg *In patients with ≥ 50% BM plasma cells, PLT ≥ 50 x 109/L. †Patients premedicated with glucocorticoid, antihistamine, and antipyretic with step-up doses and first full dose. ‡Step-up doses: 60, 300 µg/kg. Slide credit: clinicaloptions. com

Teclistamab Phase I Trial Update: Baseline Characteristics Total (N = 149) RP 2 D: 1500 µg/kg SC (n = 33) Median prior lines of tx, n (range) 6 (2 -14) 5 (2 -11) Triple-class† exposed, n (%) 143 (96) 33 (100) 22 (67) Penta-drug‡ exposed, n (%) 102 (69) 21 (64) 34/138 (25) 3/29 (10) Extramedullary plasmacytomas ≥ 1, n (%) 18 (12) 6 (18) Median yrs since dx, n (range) 7 (1 -26) 6 (1 -12) 36/111 (32) 8/12 (38) Refractory status, n (%) § Carfilzomib § Pomalidomide § Anti-CD 38§ § Triple-class† refractory § Penta-drug‡ refractory 99 (66) 115 (77) 138 (93) 121 (81) 58 (39) 22 (67) 24 (73) 32 (97) 28 (85) 12 (36) 127 (85) 28 (85) Refractory to last line of tx, ║ n (%) 136 (91) 29 (88) Characteristic Total (N = 149) RP 2 D: 1500 µg/kg SC (n = 33) Median age, yrs (range) § Age ≥ 70 yrs, n (%) 63 (24 -84) 33 (22) 61 (39 -84) 8 (24) 81 (54) BM plasma cells ≥ 60%, n/N (%) Male, n (%) High-risk cytogenetics, * n/N (%) Prior transplantation, n (%) Characteristic *Includes del(17 p), t(4; 14), and t(14; 16) per FISH or karyotyping. †PI, IMi. D, and anti-CD 38. ‡ 2 PIs, 2 IMi. Ds, and 1 anti-CD 38. §Includes isatuximab or daratumumab. ║PD on/within 60 days of last regimen. Garfall. ASH 2020. Abstr 180. Slide credit: clinicaloptions. com

Teclistamab Phase I Trial Update: Safety AEs in ≥ 20% of Total Patients, n (%) Total (N = 149) RP 2 D: 1500 µg/kg SC (n = 33) All Gr Gr ≥ 3 § Neutropenia 85 (57) 69 (46) 17 (52) 11 (33) § Anemia 82 (55) 47 (32) 13 (39) 7 (21) § Thrombocytopenia 59 (40) 32 (22) 11 (33) 4 (12) § Leukopenia 41 (28) 21 (14) 11 (33) 6 (18) § CRS 82 (55) 0 21 (64) 0 § Pyrexia 45 (30) 0 6 (18) 0 § Diarrhea 34 (23) 1 (1) 4 (12) 0 § Nausea 33 (22) 1 (1) 6 (18) 0 § Fatigue 33 (22) 2 (1) 8 (24) 1 (3) § Headache 32 (22) 0 4 (12) 0 § Cough 31 (21) 3 (2) 1 (3) 0 Hematologic Nonhematologic Garfall. ASH 2020. Abstr 180. § 1 death due to TRAE (grade 5 pneumonia at 80 µg/kg IV) § MTD not reached ‒ No DLTs at RP 2 D ‒ Across all doses, n = 2 DLTs (grade 4 delirium at 20 µg/kg IV step-up dose, grade 4 thrombocytopenia at 180 µg/kg IV) § All injection-site reactions were grade 1/2 (all patients, 32%; RP 2 D, 36%) § Infections observed in 52% of all patients (grade ≥ 3 across all doses, 15%) and 27% of patients treated with RP 2 D (grade ≥ 3, 6%) Slide credit: clinicaloptions. com

Teclistamab Phase I Trial Update: Neurotoxicity and Cytokine-Release Syndrome Maximum CRS Grade by Dosing* 80 Patients (%) 60 40 20 0 Grade 1 54% (45/84) 16% 38% IV Grade 2 57% (37/65) 64% (21/33) 15% 27% 42% 37% SC *CRS grading per Lee. Blood. 2014; 124: 188. †Most recent dose at Day 1. ‡Could receive > 1 supportive treatment. Garfall. ASH 2020. Abstr 180. Reproduced with permission. RP 2 D Total (N = 149) IV (n = 84) SC (n = 65) Patients with CRS 82 (55) 45 (54) 37 (57) Median time to onset, † days (range) 2 (1 -5) 1 (1 -3) 2 (1 -5) Median duration, days (range) 2 (1 -8) 1 (1 -7) 2 (1 -8) Supportive treatments for CRS‡ § Tocilizumab § Steroids § Low-flow oxygen § Single low-dose vasopressor 76 (51) 35 (23) 19 (13) 9 (6) 1 (1) 43 (51) 22 (26) 15 (18) 6 (7) 1 (1) 33 (51) 13 (20) 4 (6) 3 (5) 0 CRS Outcome, n (%) § Neurotoxicity observed in n = 7 patients (5%), n = 1 (3%) at RP 2 D ‒ No events with SC vs 2 grade ≥ 3 events with IV § CRS mostly occurred at step-up, first full dose § No grade ≥ 3 CRS, no d/c due to CRS Slide credit: clinicaloptions. com

Teclistamab Phase I Trial Update: Response ORR for SC Cohorts‡ § At RP 2 D (1500 µg/kg SC), median time to first confirmed response: 1 mo (range: 0. 3 -3) ‒ 15/19 (94%) responders alive, progression free at median f/u of 3. 9 mos (range: 1. 7 -7. 4) § ORR was 67% and 71% at most active doses (270 -720 µg/kg IV and 720 -3000 µg/kg SC) ‒ 44/47 (94%) responders still on treatment with ongoing responses at median f/u of 6. 5 mos (range: 1. 7 -14) § Responses durable, deepened over time: MRD-negative CR in 8/11 evaluable patients (10 -6) and 1/11 (10 -5) across all doses ‡Among 60% 46% 40 n=4 n=3 20 0 VGPR 73% 60 Patients (%) ‒ Most triple-class refractory (70%) and pentadrug refractory (75%) responded PR 80 n=4 n 27% =1 n=7 ≥ VGPR 55% n=5 n=4 n=3 80 + 240 µg/kg (n = 13) 720 µg/kg (n = 15) RP 2 D: 1500 µg/kg (n = 22) § In SC cohorts, 32/35 responders still on treatment with ongoing responses† evaluable patients with ≥ 1 study treatment and ≥ 1 postbaseline disease evaluation (includes unconfirmed responses). Slide credit: clinicaloptions. com Garfall. ASH 2020. Abstr 180. Reproduced with permission.

Teclistamab Phase I Trial Update: PK/PD, Immunogenicity in SC Cohorts § Proportionate dose: exposure profile observed after first full SC dosing ‒ Soluble BCMA does not appear to affect teclistamab exposure § RP 2 D (1500 µg/kg SC) exhibited low peak: trough ratio and maintained teclistamab concentration above max EC 90 § PK profiling suggests less frequent SC dosing possible Garfall. ASH 2020. Abstr 180. § Immunogenicity: 2/107 (2%) patients exhibited low titers of antidrug antibodies § Highest levels of IL-10, IL 2 Rα, and IL-6 observed at doses ≥ 720 µg/kg SC § Maximum induction of PD-1+ T-cells (including in periphery) occurred at RP 2 D ‒ T-cell activation consistently observed at RP 2 D Slide credit: clinicaloptions. com

Teclistamab Phase I Trial Update: Conclusions § In this updated analysis from a phase I trial of teclistamab IV or SC in patients with R/R MM, teclistamab at the RP 2 D (1500 µg/kg SC) was well tolerated and associated with a high response rate ‒ MTD not reached ‒ All CRS events were low grade; single grade 1 neurotoxicity event was reversible ‒ ORR: 73% (≥ CR rate: 23% and ≥ VGPR rate: 55%) § Responses durable, deepened with time § PK/PD data support selection of 1500 µg/kg SC as RP 2 D § Investigators concluded that teclistamab exhibited promising activity in heavily pretreated R/R MM ‒ Phase II expansion trial now recruiting (NCT 04557098) Garfall. ASH 2020. Abstr 180. Slide credit: clinicaloptions. com

Go Online for More CCO Coverage of ASH 2020! Short slideset summaries and additional CME-certified analyses with expert commentary on key studies in: § § § Acute and chronic leukemias Lymphomas and chronic lymphocytic leukemia Myelodysplastic syndromes and myeloproliferative neoplasms Myeloma Nonmalignant hematology clinicaloptions. com/oncology