Background. Outcomes in refractory large B-cell lymphoma with traditional standard of care are extremely poor 1

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1 2-Year Follow-Up and High-Risk Subset Analysis of ZUMA-1, the Pivotal Study of Axicabtagene Ciloleucel (Axi-Cel) in Patients with Refractory Large B Cell Lymphoma Abstract 2967 Neelapu SS, Ghobadi A, Jacobson CA, Miklos DB, Lekakis LJ, Oluwole OO, Lin Y, Braunschweig I, Hill BT, Timmerman JM, Deol A, Reagan PM, Stiff PJ, Flinn IW, Farooq U, Goy A, McSweeney PA, Munoz J, Siddiqi T, Chavez JC, Herrera AF, Xue A, Jiang Y, Bot A, Rossi JM, Kim JJ, Go WY, and Locke FL

2 Background Outcomes in refractory large B-cell lymphoma with traditional standard of care are extremely poor 1 The SCHOLAR-1 analysis demonstrated an ORR of 26%, a CR rate of 7%, and a median OS of 6.3 months in this patient population Axi-cel, an autologous anti-cd19 CAR T-cell therapy, is approved in the United States and European Union for the treatment of patients with relapsed or refractory large B-cell lymphoma with 2 prior systemic therapies based on the results of the ZUMA-1 study 2,3 ZUMA-1 1-year analysis (N = 108; median follow-up, 15.4 months) demonstrated 4,5 : ORR, 82%; CR rate, 58% Ongoing response in 42% of patients AEs beyond 6 months were primarily manageable infections, and there were no late-onset axi-cel related incidences of CRS or NEs AE, adverse event; CAR, chimeric antigen receptor; CR, complete response; CRS, cytokine release syndrome; NE, neurologic event; ORR, objective response rate; OS, overall survival; scfv, single-chain variable fragment 1. Crump M, et al. Blood. 2017;130(16): Axicabtagene ciloleucel [prescribing information]. Santa Monica, CA: Kite Pharma, Inc; Axicabtagene ciloleucel (SMPC). Amsterdam, The Netherlands: Kite Pharma EU B.V.; Neelapu SS, et al. Blood. 2017;130 (suppl 1): Abstract Neelapu SS, et al. N Engl J Med. 2017;377(26):

3 Objective To assess long-term safety and efficacy of axi-cel in patients with refractory large B-cell lymphoma

4 ZUMA-1 Study Design Key eligibility criteria Phase 1 (N = 7) Refractory DLBCL/PMBCL/TFL (n = 7) No response to last chemotherapy or relapse 12 month post-asct Prior anti-cd20 monoclonal antibody and anthracycline Conditioning regimen Cyclophosphamide 500 mg/m 2 + fludarabine 30 mg/m 2 for 3 days Axi-cel: CAR+ cells/kg 99% Enrolled were successfully manufactured 91% Enrolled were dosed Phase 2 (N = 101) Cohort 1 Refractory DLBCL (n = 77) Cohort 2 Refractory PMBCL/TFL (n = 24) Data cutoff: August 11, 2018 Median follow-up for Phase 2: 27.1 months Patient populations Safety: N = 108 (Phase 1 + 2) Efficacy: n = 101, assessed by investigator and central review ASCT, autologous stem cell transplantation; DLBCL, diffuse large B-cell lymphoma; PMBCL, primary mediastinal B-cell lymphoma; TFL, transformed follicular lymphoma

5 ZUMA-1 Treatment Schema Screening Leukapheresis Conditioning chemotherapy Axi-Cel Infusion First tumor assessment Manufacturing Day 0 Day 7 Day 28 Hospitalization period Follow-up period (Post-treatment assessment and long-term follow-up) Bridging chemotherapy was not allowed per study protocol

6 Methods A subgroup analysis was performed on patients with double-expressor or high-grade B-cell lymphoma (DE/HGBCL), defined as the following: DE B-cell lymphoma MYC [ 40%] and BCL2 [ 50%] protein expression by IHC 1 HGBCL Double- or triple-hit: Morphologic HGBCL, MYC+ and BCL2+ and/or BCL6+ by fluorescence in situ hybridization 1 HGBCL not otherwise specified (HGBCL NOS): Morphologic HGBCL, MYC, and >70% Ki67 by IHC 2 IHC, immunohistochemistry 1. Swerdlow SH, et al. Blood. 2016;127(20): Broyde A, et al. Am J Hematol. 2009;84(6):

7 Baseline Characteristics Characteristic DE/HGBCL (N = 37) Overall (N = 108) Median age (range), y 60 (28 76) 58 (23 76) 65, n (%) 9 (24) 27 (25) Male, n (%) 25 (68) 73 (68) ECOG 1, n (%) 22 (59) 62 (57) Disease stage III/IV, n (%) 29 (78) 90 (83) IPI score 3 4, n (%) 15 (41) 48 (44) 3 Prior therapies, n (%) 28 (76) 76 (70) Refractory Subgroup Before Enrollment (n = 37) (N = 108) Refractory to second- or later-line therapy, n (%) Best response as PD to last prior therapy 29 (78) 22 (59) 80 (74) 70 (65) Relapse post-asct, n (%) 8 (22) 25 (23) ECOG, Eastern Cooperative Oncology Group performance status; IPI, International Prognostic Index; PD, progressive disease

8 Baseline Characteristics (Continued) Overall, most patients had any-grade cytopenias according to baseline laboratory values: 93% had anemia, 34% had thrombocytopenia, and 15% had neutropenia Of the 47 patients with pretreatment tumor samples, 30 (64%) had DE and 7 (15%) had HGBCL, including 1 patient with triple-hit HGBCL, 4 with double-hit HGBCL, and 2 with HGBCL NOS

9 Objective and Ongoing Response Rates Best objective response, % Investigator- Assessed (n = 101) Central Review (n = 101) ORR CR ORR CR Ongoing, % a % of patients with ongoing response at 12 months remained in response at 24 months 81% concordance of ORR between investigator assessment and central review 91% ORR and 70% CR rate for the 33 Phase 2 patients with DE/HGBCL 48% in ongoing response (all ongoing CR) Only 5% (2/39) ongoing responders underwent allogeneic SCT, and none received autologous SCT a Three patients with ongoing response per investigator review were not ongoing responders per central review. Two of these patients underwent SCT prior to documented progression, which was considered a censor event per central review but not per investigator assessment. The third patient was deemed to have PD per central review after 10.9 months but was assessed to be in ongoing response at 23.4 months per investigator.

10 Duration of Response by Investigator Assessment and Central Review Time, Months Median DOR for complete responders has not been reached Median duration of response was NR (95% CI, 10.9 months NR) by central review because of several patients with early progressive disease who were assessed as in response by central review and had to be censored for receiving next anticancer therapy. DOR, duration of response; NR, not reached

11 Progression-Free Survival Time, Months The 6-month plateau was largely maintained, with only 10 patients progressing beyond the 6-month follow-up PFS, progression-free survival

12 Overall Survival Time, Months Median OS was not reached

13 AE, n (%) Summary of Adverse Events 1-Year Analysis (N = 108) 2-Year Analysis (N = 108) Grade 3 AEs 105 (97) 106 (98) Grade 3 SAEs 50 (46) 52 (48) Grade 3 CRS a 13 (12) 12 (11) Grade 3 NEs a 33 (31) 35 (32) Grade 5 AEs 4 (4) b 4 (4) No new axi-cel related CRS, NEs, or Grade 5 AEs since the 1-year follow-up No cases of replication-competent retrovirus or axi-cel related secondary cancers have been reported a Differences in CRS and NE between the 1-year and 2-year analysis are due to revised coding following data audit. b As previously reported, Grade 5 AEs occurred in 4 patients. 1,2 1. Neelapu SS, et al. N Engl J Med. 2017;377(26): Locke FL, et al. Mol Ther. 2017;25(1): NE, neurologic event; SAE, serious AE.

14 Treatment-Emergent Cytopenias Treatment-Emergent Cytopenia, n (%) Any Grade (N = 108) Grade 3 (N = 108) Any treatment-emergent cytopenia 100 (93) 93 (86) Neutropenia 93 (86) 86 (80) Thrombocytopenia 67 (62) 43 (40) Anemia 73 (68) 49 (45) Any cytopenia present on or after day (55) 41 (38) Neutropenia 39 (36) 28 (26) Thrombocytopenia 44 (41) 26 (24) Anemia 31 (29) 11 (10) Any cytopenia present on or after month 3 37 (34) 18 (17) Neutropenia 20 (19) 12 (11) Thrombocytopenia 19 (18) 8 (7) Anemia 19 (18) 3 (3) The most frequent Grade 3 AEs were cytopenias Neutropenia includes preferred terms febrile neutropenia, neutropenia, and neutrophil count decreased. Per the standard Medical Dictionary for Regulatory Activities queries, thrombocytopenia includes hematopoietic thrombocytopenia (narrow), and anemia includes hematopoietic erythropenia (broad).

15 Late-Onset Serious Adverse Events a Patient Number SAE Start Time After Axi-cel Infusion, Months Grade SAE Attribution b Mental status changes MDS Vasovagal episode in the context of hypovolemia unrelated to axi-cel Prior chemotherapy unrelated to axi-cel Lung infection Unrelated to axi-cel Escherichia Unrelated to axi-cel 4 bacteremia Bacteremia Unrelated to axi-cel a Late-onset event occurring since the previous data cutoff of August 11, b Per investigator. MDS, myelodysplastic syndrome

16 Late-Onset Serious Adverse Events a (Continued) All late-onset SAEs were unrelated to axi-cel 1 Patient with mental status change due to dehydration with vasovagal episode 1 Patient with myelodysplastic syndrome due to previous chemotherapy With the exception of myelodysplastic syndrome, all SAEs resolved There were a total of 4 patients with 6 infections since the previous update 3 Axi-cel unrelated Grade 3 SAEs 3 Grade 2 AEs: 1 patient with 2 axi-cel related infections of recurrent upper respiratory tract infection and pneumonia and 1 patient with an axi-cel unrelated case of shingles a Late-onset event occurring since the previous data cutoff of August 11, 2017.

17 Proportion of Patients With Detectable CAR Gene-Marked T Cells in Blood Among Patients With Ongoing Response Over Time The proportion of patients in ongoing response with detectable CAR T cells decreased over time Gene-marked CAR T cells were enumerated by quantitative PCR. The lower limit of quantification of the assay was 2 gene-marked CAR T cells per 100,000 PBMCs (0.002%). Values shown indicate the proportion (top) and number (in parenthesis) of patients with gene-marked CAR T cells in blood at a given time point. Number of patients evaluated at each time point are shown on x-axis. This analysis excludes 2 patients who received subsequent anticancer therapy while in response to axi-cel. PBMC, peripheral blood mononuclear cell; PCR, polymerase chain reaction

18 Proportion of Patients With Detectable B Cells in Blood Among Patients With Ongoing Response Over Time 75% of patients (24/32) with ongoing responses had detectable B cells 2 years after axi-cel infusion Throughout the course of the study, 31% of patients received intravenous immunoglobulins B cells, defined as CD19+ and/or CD20+, were quantified by flow cytometric analysis. The lower limit of quantification of the assay was 17 B cells per 100,000 viable leukocytes (0.017%). Values shown indicate the proportion (top) and number (in parenthesis) of patients with detectable B cells in blood at a given time point. Number of patients evaluated at each time point are shown on x-axis. This analysis excludes 2 patients who received subsequent anticancer therapy while in response to axi-cel.

19 Conclusions At a median follow-up of 27.1 months, patients continue to benefit from axi-cel 39% of patients maintained ongoing response Median DOR for patients with CR has not been reached Median OS has not been reached High rates of durable response (48%) were observed in patients with DE/HGBCL Late onset AEs were largely manageable infections, and there were no late-onset axi-cel related CRS, NEs, or deaths Evidence of B-cell recovery and decreasing detectable gene-marked CAR T cells suggests that functional CAR T-cell persistence may not be required for long-term remissions Axi-cel induces durable responses in patients with large B-cell lymphoma who otherwise lack curative options

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