KITE’S YESCARTA® (AXICABTAGENE CILOLEUCEL) CAR T-CELL THERAPY DEMONSTRATES SIGNIFICANTLY LONGER OVERALL SURVIVAL, VERSUS STANDARD OF CARE AS INITIAL TREATMENT OF RELAPSED/REFRACTORY LARGE B-CELL LYMPHOMA

KITE’S YESCARTA^® (AXICABTAGENE CILOLEUCEL) CAR T-CELL THERAPY DEMONSTRATES SIGNIFICANTLY LONGER OVERALL SURVIVAL, VERSUS STANDARD OF CARE AS INITIAL TREATMENT OF RELAPSED/REFRACTORY LARGE B-CELL LYMPHOMA

 – First Treatment in Nearly 30 Years to Show Statistically Significant OS With a Median Follow Up of 47.2 Months, for Initial Treatment of R/R LBCL Versus Historical SOC in the Curative Setting –

– Axicabtagene Ciloleucel Results in a 27.4% Reduction in Risk of Death, Corresponding to a 38% Relative Improvement in OS Versus SOC, Despite 57% of Patients Subsequently Receiving Cellular Therapy Off Protocol –

– First European Presentation of Primary OS Analysis from the Landmark ZUMA-7 Study of Axicabtagene Ciloleucel in R/R LBCL at ICML 2023 –

Stockley Park, UK – 15 June 2023 – Kite, a Gilead Company, today announces detailed results from the overall survival (OS) analysis of the landmark Phase 3 ZUMA-7 study of Yescarta^® (axicabtagene ciloleucel [axi-cel]) CAR T-cell therapy compared with historical standard of care (SOC) as initial treatment in the curative setting for patients with relapsed or refractory large B-cell lymphoma (R/R LBCL) (Abstract #22).[1] Axicabtagene ciloleucel is the first treatment in nearly 30 years to demonstrate a significant improvement in survival in this patient population. These data are being presented for the first time in Europe orally at the 2023 International Conference on Malignant Lymphoma (ICML) bi-annual meeting, Lugano, Switzerland.

With a median follow-up of 4 years (47.2 months), a one-time treatment with axicabtagene ciloleucel demonstrated significantly longer overall survival (hazard ratio [HR] 0.726; 95% CI: 0.540-0.977, stratified one-sided log rank p-value=0.0168) compared to SOC with a 27.4% reduction in the risk of death, which corresponds to a 38% relative improvement in overall survival, for patients with R/R LBCL within 12 months of completion of first-line therapy.¹

The primary OS analysis, conducted per protocol five years after the first subject was randomised, demonstrated superior OS with axicabtagene ciloleucel over the SOC arm, despite more than half (57%) of patients in the SOC arm subsequently receiving cellular immunotherapy off protocol; of these, 77% of patients received axicabtagene ciloleucel. Median OS was longer with axicabtagene ciloleucel versus SOC (not reached versus 31.1 months, respectively) and 48-month OS estimates were higher with axicabtagene ciloleucel (54.6% versus 46.0%, respectively). Axicabtagene ciloleucel’s OS benefit versus SOC was also similar across key patient subgroups, including patients with high-risk features, such as those with primary refractory disease, high-grade B-cell lymphoma (including double-hit lymphomas) and aged 65 and above. Progression-free survival (PFS) by investigator review confirmed the benefit of axicabtagene ciloleucel over SOC (HR 0.506; 95% CI: 0.383-0.669), with 48-month PFS estimates of 41.8% with axicabtagene ciloleucel versus 24.4% with SOC.

SOC therapy for this patient population has historically been a multi-step process expected to end with  stem-cell transplant. The process starts with chemoimmunotherapy, and if a patient responds and can tolerate further treatment, they move on to high-dose chemotherapy (HDT), followed by stem cell transplant (ASCT).  It is notable that despite this process being the historical SOC, less than 40% of patients were able to make it through to complete their stem cell transplant compared with 94% of patients in the ZUMA-7 study who received axicabtagene ciloleucel.

“As the first treatment in nearly three decades to significantly improve survival for patients with relapsed/refractory large B-cell lymphoma, axi-cel can potentially change the standard of care for these patients who previously had very limited options for potentially curative therapy,” said Jason Westin, MD, MS, FACP, ZUMA-7 Principal Investigator, Director, Lymphoma Clinical Research, and Associate Professor, Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center. “The totality of the ZUMA-7 data provides a compelling case for axi-cel to be used for patients with large B-cell lymphoma who do not respond to or relapse from first-line treatment.”

Axicabtagene ciloleucel’s safety profile remains consistent with prior studies, including no new cases of cytokine-release syndrome (CRS), Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS) and no new treatment-related deaths occurred since the primary EFS analysis. The primary EFS analysis showed that Grade 3 or higher adverse events (AEs) occurred in 91% of patients treated with axi-cel compared with 83% of those treated with SOC. The most common grade 3 or higher AEs were neutropenia (69% vs 41%, respectively), anemia (30% vs 39%), and leukopenia (29% vs 22%).

About ZUMA-7 Study

Based on the results of primary efficacy endpoint of event-free survival (EFS) in the pivotal ZUMA-7 trial, the U.S. Food & Drug Administration approved axicabtagene ciloleucel as initial treatment of R/R LBCL in April 2022. The European Commission granted marketing authorisation in the European Union (EU), valid in all EU member states, in October 2022, followed by approvals in several other countries such as: Australia, Canada, Great Britain, Israel, Japan and Switzerland.

ZUMA-7 is a randomised, open-label, global, multicentre, Phase 3 study evaluating the safety and efficacy of axicabtagene ciloleucel versus SOC for second-line therapy in adult patients with relapsed or refractory LBCL within 12 months of first-line therapy. In the study, 359 patients in 77 centres around the world were randomised (1:1) to receive a single infusion of axicabtagene ciloleucel or SOC second-line treatment. The primary endpoint was EFS as determined by blinded central review and defined as the time from randomisation to the earliest date of disease progression per Lugano Classification, commencement of new lymphoma therapy, or death from any cause. Key secondary endpoints include objective response rate (ORR) per by blinded central review and overall survival (OS). Additional secondary endpoints included patient reported outcomes (PROs) and safety. Per hierarchical testing of primary and key secondary endpoints and group sequential testing of OS, an interim analysis of overall survival (OS) occurred at the time of the primary EFS.[2]

Axicabtagene ciloleucel demonstrated a 2.5-fold increase in patients who were alive at two years and did not experience cancer progression or require additional cancer treatment (40.5% vs. 16.3%) and a four-fold greater median EFS (8.3 mo. vs. 2.0 mo.) compared to SOC (hazard ratio 0.398; 95% CI: 0.308-0.514, P<0.0001).¹ The ZUMA-7 study is the largest and longest study of its kind.

Nearly three times as many patients randomised to axicabtagene ciloleucel ultimately received the definitive CAR T-cell therapy treatment (94%) versus those randomised to SOC (35%) who received on-protocol HDT+ASCT. More patients responded to axicabtagene ciloleucel (ORR: 83% vs. 50%, odds ratio: 5.31 [95% CI: 3.1-8.9; P<0.0001) and achieved a complete response (CR) with axicabtagene ciloleucel (CR rate: 65% vs. 32%) than with SOC.¹

The prespecified primary OS analysis was to be conducted after approximately 210 deaths or no later than five years after the first patient was randomised, whichever came first, and was triggered by the latter criterion.¹

About Large B-Cell Lymphoma (LBCL)

Globally and in Europe, large B-cell lymphoma (LBCL) is the most common type of non-Hodgkin lymphoma (NHL), representing around 30% of all cases.[3] In Europe, it is estimated that up to 37,000 new cases of LBCL were diagnosed in 2020.[4] Although first-line treatment can be effective in around 60% of cases, up to half of these will relapse (return).[5]^,[6] For people who relapse, or who do not respond to first-line treatment, outcomes are often poor. Most patients with refractory (no response) LBCL have no curative treatment options.[7]

About Axicabtagene Ciloleucel

In October 2022, axicabtagene ciloleucel, a chimeric antigen receptor (CAR) T cell therapy, was approved by the European Commission (EC) for the treatment of adult patients with diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL) who relapse within 12 months from completion of, or are refractory to, first-line chemoimmunotherapy.[8] In June 2022, axicabtagene ciloleucel was approved by the EC for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) after three or more lines of systemic therapy. In August 2018, axicabtagene ciloleucel was approved by the EC for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B cell lymphoma (PMBCL), after two or more lines of systemic therapy.⁷

Kite, a Gilead Company, is a global biopharmaceutical company based in Santa Monica, California, focused on cell therapy to treat and potentially cure cancer. As the global cell therapy leader, Kite has treated more patients with CAR T-cell therapy than any other company. Kite has the largest in-house cell therapy manufacturing network in the world, spanning process development, vector manufacturing, clinical trial supply and commercial product manufacturing.

About Gilead Sciences

Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California.

Forward Looking Statements

This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the possibility of unfavorable results from ongoing or additional clinical trials involving axicabtagene ciloleucel; Kite’s ability to initiate, progress or complete clinical trials within currently anticipated timelines or at all, including those involving axicabtagene ciloleucel; Kite’s ability to receive regulatory approvals in a timely manner or at all, including additional regulatory approvals of axicabtagene ciloleucel, and the risk that any such approvals may be subject to significant limitations on use; the risk that physicians may not see the benefits of prescribing axicabtagene ciloleucel; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and other factors are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2023, as filed with the U.S. Securities and Exchange Commission. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The reader is cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties and is cautioned not to place undue reliance on these forward-looking statements. All forward-looking statements are based on information currently available to Kite and Gilead, and Kite and Gilead assume no obligation and disclaim any intent to update any such forward-looking statements.

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Kite, the Kite logo, Yescarta and GILEAD are trademarks of Gilead Sciences, Inc. or its related companies.

[1] Westin J, et al. Primary Overall Survival Analysis of the Phase 3 Randomized ZUMA-7 Study of Axicabtagene Ciloleucel versus Standard-of-Care Therapy in Relapsed/Refractory Large B-Cell Lymphoma. Presented at the 2023 International Conference on Malignant Lymphoma (ICML) bi-annual meeting.

[2] Clinicaltrials.gov. Efficacy of Axicabtagene Ciloleucel Compared to Standard of Care Therapy in Subjects With Relapsed/ Refractory Diffuse Large B Cell Lymphoma (ZUMA-7). NCT03391466. Available at: https://clinicaltrials.gov/ct2/show/NCT03391466. Accessed May 2023.

[3] Leukemia & Lymphoma Society. NHL subtypes. Available at: https://www.lls.org/lymphoma/non-hodgkin-lymphoma/nhl-subtypes Accessed: May 2023

[4] Globocan 2020. Europe fact sheet. Available at https://gco.iarc.fr/today/data/factsheets/populations/908-europe-fact-sheets.pdf Accessed: May 2023.

[5] Sehn LH and Salles G. Diffuse Large B-Cell Lymphoma. N Engl J Med 2021;384:842-58.

[6] Susanibar-Adaniya, S and Barta SK. 2021 Update on Diffuse large B cell lymphoma: A review of current data and
potential applications on risk stratification and management. Am J Hematol. 2021 May 01; 96(5): 617–629.

[7] Crump M, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR1 study. Blood. 2017 Oct 19;130(16):1800-8.

[8] European Medicines Agency. Yescarta^® (axicabtagene ciloleucel) SPC. Available at: https://www.ema.europa.eu/documents/product-information/yescarta-epar-product-information_en.pdf. Accessed May 2023.