Axicabtagene Ciloleucel

SANTA MONICA, Calif.--( BUSINESS WIRE )--Kite, a Gilead Company (Nasdaq: GILD), today announced results from a five-year follow-up analysis of ZUMA-5, a Phase 2 study of Yescarta ® (axicabtagene ciloleucel) in patients with relapsed/refractory non-Hodgkin lymphomas (NHL) including follicular lymphoma (FL) or marginal zone lymphoma (MZL). The analysis demonstrated that after a median follow-up of more than five years, patients treated with Yescarta continued to experience durable response and long-term survival. The data were shared in an oral presentation (Abstract #864) during the 66th American Society of Hematology (ASH) Annual Meeting and Exposition. “ Relapsed or refractory non-Hodgkin lymphomas, including follicular lymphoma and marginal zone lymphoma, are generally considered to be incurable, with most patients ultimately relapsing,” said Dr. Sattva S. Neelapu, lead investigator, The University of Texas MD Anderson Cancer Center. “ These impressive results demonstrate the continued durable clinical benefit and manageable long-term safety profile of axi-cel and give us hope that it may have a curative effect on these difficult-to-treat blood cancers.” In ZUMA-5, 159 patients were enrolled (127 FL, 31 MZL, 1 DLBCL [later excluded]). At a median follow-up of 64.6 months (range, 32.3-81.4; FL: 65.7, MZL: 55.8), the overall response rate (ORR) was 90% and the complete response (CR) was 75%. Among patients who achieved a CR, 58% remained in CR at the time of data cutoff. The median duration of response (DOR) was 60.4 months (95% CI, 39.7-not estimable [NE]; FL: 60.4, MZL: not reached [NR]), with estimated 60-month DOR of 53.4% (95% CI, 43.9-62.0; FL: 52.2%, MZL: 60.0%). Median progression-free survival (PFS) was 62.2 months (95% CI, 34.9-NE; FL: 57.3, MZL: NR). PFS rates at 60 months in patients with FL were consistent regardless of high-risk characteristics. Median time to next therapy was NR in all patients with NHL (95% CI, 38.6-NE; consistent by disease type), with a 60-month estimated rate of 53.3% (95% CI, 45.0-60.9; FL: 54.0%, MZL: 50.9%). At data cutoff, 55% of patients (n=87) were alive with no new anticancer therapy. The median overall survival (OS) was NR (95% CI, NE-NE; consistent by disease type), and the 60-month OS estimate was 69.0% (95% CI, 60.8-75.8; FL: 68.9, MZL: 71.1). “ There is growing evidence that people with follicular lymphoma and marginal zone lymphoma can experience long-term survival after one Yescarta treatment,” said Dominique Tonelli, VP, Global Head of Medical Affairs, Kite. “ With no lymphoma-specific events in the five-year follow-up of ZUMA-5 patients, Yescarta may offer patients the chance to live longer without need for subsequent therapy and a potential cure.” No new Yescarta-related safety signals emerged in the five-year analysis. One patient progressed after the data cutoff of the four-year analysis and no patients died of disease progression after the prior analysis. Among treated patients (n=152, 124 FL, 28 MZL), three new events not related to Yescarta were reported after the four-year analysis, including Grade 3 metastasis, Grade 1 bladder cancer, and Grade 4 myelodysplastic syndrome (a serious adverse event). One patient died of pneumonia, unrelated to Yescarta. At any time on trial, a total of 46 patients died, due to progressive disease (n=14), secondary malignancies (n=6), infections (n=11), or another or unknown cause (n=15). About ZUMA-5 ZUMA-5 is a single-arm, open-label, international, multicenter Phase 2 study evaluating 159 adult patients with R/R NHL (FL and MZL) who received at least two prior lines of systemic therapy, including the combination of an anti-CD20 monoclonal antibody and an alkylating agent. The primary endpoint was ORR, and secondary endpoints included CR rate, ORR and CR in patients who had received three or more lines of prior therapy, DOR, OS, PFS and incidence of adverse events. About NHL FL and MZL are both forms of indolent NHL in which malignant tumors slowly grow but can become more aggressive over time. FL is the most common form of indolent lymphoma and the second most common type of lymphoma globally. It accounts for approximately 22 percent of all lymphomas diagnosed worldwide. MZL is the third most common lymphoma, accounting for 8 to 12 percent of all B-cell NHLs. Despite advances in management and substantial improvements in long-term survival, patients living with FL have varied outcomes. Currently, there are limited options for the treatment of relapsed or refractory FL and MZL after two or more lines of therapy. About Yescarta Please see full Prescribing Information , including BOXED WARNING and Medication Guide. YESCARTA is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of: Adult patients with large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy. Adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. Limitations of Use: YESCARTA is not indicated for the treatment of patients with primary central nervous system lymphoma. Adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). U.S. IMPORTANT SAFETY INFORMATION BOXED WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES and SECONDARY HEMATOLOGICAL MALIGNANCIES Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving YESCARTA. Do not administer YESCARTA to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids. Neurologic toxicities, including fatal or life-threatening reactions, occurred in patients receiving YESCARTA, including concurrently with CRS or after CRS resolution. Monitor for neurologic toxicities after treatment with YESCARTA. Provide supportive care and/or corticosteroids, as needed. T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including YESCARTA. YESCARTA is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the YESCARTA and TECARTUS REMS Program. CYTOKINE RELEASE SYNDROME (CRS) CRS, including fatal or life-threatening reactions, occurred following treatment with YESCARTA. CRS occurred in 90% (379/422) of patients with non-Hodgkin lymphoma (NHL) receiving YESCARTA, including ≥ Grade 3 (Lee grading system1) CRS in 9%. CRS occurred in 93% (256/276) of patients with large B-cell lymphoma (LBCL), including ≥ Grade 3 CRS in 9%. Among patients with LBCL who died after receiving YESCARTA, four had ongoing CRS events at the time of death. For patients with LBCL in ZUMA-1, the median time to onset of CRS was 2 days following infusion (range: 1 to 12 days) and the median duration of CRS was 7 days (range: 2 to 58 days). For patients with LBCL in ZUMA-7, the median time to onset of CRS was 3 days following infusion (range: 1 to 10 days) and the median duration was 7 days (range: 2 to 43 days). CRS occurred in 84% (123/146) of patients with indolent non-Hodgkin lymphoma (iNHL) in ZUMA-5, including ≥ Grade 3 CRS in 8%. Among patients with iNHL who died after receiving YESCARTA, one patient had an ongoing CRS event at the time of death. The median time to onset of CRS was 4 days (range: 1 to 20 days) and the median duration was 6 days (range: 1 to 27 days) for patients with iNHL. Key manifestations of CRS (≥ 10%) in all patients combined included fever (85%), hypotension (40%), tachycardia (32%), chills (22%), hypoxia (20%), headache (15%), and fatigue (12%). Serious events that may be associated with CRS include, cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), renal insufficiency, cardiac failure, respiratory failure, cardiac arrest, capillary leak syndrome, multi-organ failure, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) . The impact of tocilizumab and/or corticosteroids on the incidence and severity of CRS was assessed in two subsequent cohorts of LBCL patients in ZUMA-1. Among patients who received tocilizumab and/or corticosteroids for ongoing Grade 1 events. CRS occurred in 93% (38/41), including 2% (1/41) with Grade 3 CRS; no patients experienced a Grade 4 or 5 event. The median time to onset of CRS was 2 days (range: 1 to 8 days) and the median duration of CRS was 7 days (range: 2 to 16 days). Prophylactic treatment with corticosteroids was administered to a cohort of 39 patients for 3 days beginning on the day of infusion of YESCARTA. Thirty-one of the 39 patients (79%) developed CRS at which point the patients were managed with tocilizumab and/or therapeutic doses of corticosteroids with no patients developing Grade 3 or higher CRS. The median time to onset of CRS was 5 days (range: 1 to 15 days) and the median duration of CRS was 4 days (range: 1 to 10 days). Although there is no known mechanistic explanation, consider the risk and benefits of prophylactic corticosteroids in the context of pre-existing comorbidities for the individual patient and the potential for the risk of Grade 4 and prolonged neurologic toxicities. Ensure that 2 doses of tocilizumab are available prior to infusion of YESCARTA. Monitor patients at least daily for 7 days at the certified healthcare facility following infusion for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for 4 weeks after infusion. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. At the first sign of CRS, institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids as indicated. NEUROLOGIC TOXICITIES Neurologic toxicities (including immune effector cell-associated neurotoxicity syndrome) that were fatal or life- threatening occurred. Neurologic toxicities occurred in 78% (330/422) of all patients with NHL receiving YESCARTA, including ≥ Grade 3 in 25%. Neurologic toxicities occurred in 87% (94/108) of patients with LBCL in ZUMA-1, including ≥ Grade 3 in 31% and in 74% (124/168) of patients in ZUMA-7 including ≥ Grade 3 in 25%. The median time to onset was 4 days (range: 1-43 days) and the median duration was 17 days for patients with LBCL in ZUMA-1. The median time to onset for neurologic toxicity was 5 days (range:1- 133 days) and median duration was 15 days in patients with LBCL in ZUMA-7. Neurologic toxicities occurred in 77% (112/146) of patients with iNHL, including ≥ Grade 3 in 21%. The median time to onset was 6 days (range: 1-79 days) and the median duration was 16 days. Ninety-eight percent of all neurologic toxicities in patients with LBCL and 99% of all neurologic toxicities in patients with iNHL occurred within the first 8 weeks of YESCARTA infusion. Neurologic toxicities occurred within the first 7 days of infusion for 87% of affected patients with LBCL and 74% of affected patients with iNHL. The most common neurologic toxicities (≥ 10%) in all patients combined included encephalopathy (50%), headache (43%), tremor (29%), dizziness (21%), aphasia (17%), delirium (15%), and insomnia (10%). Prolonged encephalopathy lasting up to 173 days was noted. Serious events, including aphasia, leukoencephalopathy, dysarthria, lethargy, and seizures occurred. Fatal and serious cases of cerebral edema and encephalopathy, including late-onset encephalopathy, have occurred. The impact of tocilizumab and/or corticosteroids on the incidence and severity of neurologic toxicities was assessed in 2 subsequent cohorts of LBCL patients in ZUMA-1. Among patients who received corticosteroids at the onset of Grade 1 toxicities, neurologic toxicities occurred in 78% (32/41) and 20% (8/41) had Grade 3 neurologic toxicities; no patients experienced a Grade 4 or 5 event. The median time to onset of neurologic toxicities was 6 days (range: 1-93 days) with a median duration of 8 days (range: 1-144 days). Prophylactic treatment with corticosteroids was administered to a cohort of 39 patients for 3 days beginning on the day of infusion of YESCARTA. Of those patients, 85% (33/39) developed neurologic toxicities, 8% (3/39) developed Grade 3, and 5% (2/39) developed Grade 4 neurologic toxicities. The median time to onset of neurologic toxicities was 6 days (range: 1-274 days) with a median duration of 12 days (range: 1-107 days). Prophylactic corticosteroids for management of CRS and neurologic toxicities may result in higher grade of neurologic toxicities or prolongation of neurologic toxicities, delay the onset and decrease the duration of CRS. Monitor patients for signs and symptoms of neurologic toxicities at least daily for 7 days at the certified healthcare facility, and for 4 weeks thereafter, and treat promptly. REMS Because of the risk of CRS and neurologic toxicities, YESCARTA is available only through a restricted program called the YESCARTA and TECARTUS REMS Program which requires that: Healthcare facilities that dispense and administer YESCARTA must be enrolled and comply with the REMS requirements and must have on-site, immediate access to a minimum of 2 doses of tocilizumab for each patient for infusion within 2 hours after YESCARTA infusion, if needed for treatment of CRS. Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense, or administer YESCARTA are trained about the management of CRS and neurologic toxicities. Further information is available at www.YescartaTecartusREMS.com or 1-844-454-KITE (5483). HYPERSENSITIVITY REACTIONS Allergic reactions, including serious hypersensitivity reactions or anaphylaxis, may occur with the infusion of YESCARTA. SERIOUS INFECTIONS Severe or life-threatening infections occurred. Infections (all grades) occurred in 45% of patients with NHL. Grade 3 or higher infections occurred in 17% of patients, including ≥ Grade 3 or higher infections with an unspecified pathogen in 12%, bacterial infections in 5%, viral infections in 3%, and fungal infections in 1%. YESCARTA should not be administered to patients with clinically significant active systemic infections. Monitor patients for signs and symptoms of infection before and after infusion and treat appropriately. Administer prophylactic antimicrobials according to local guidelines. Febrile neutropenia was observed in 36% of all patients with NHL and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad-spectrum antibiotics, fluids, and other supportive care as medically indicated. In immunosuppressed patients, including those who have received YESCARTA, life-threatening and fatal opportunistic infections including disseminated fungal infections (e.g., candida sepsis and aspergillus infections) and viral reactivation (e.g., human herpes virus-6 [HHV-6] encephalitis and JC virus progressive multifocal leukoencephalopathy [PML]) have been reported. The possibility of HHV-6 encephalitis and PML should be considered in immunosuppressed patients with neurologic events and appropriate diagnostic evaluations should be performed. Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against B cells, including YESCARTA. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing. PROLONGED CYTOPENIAS Patients may exhibit cytopenias for several weeks following lymphodepleting chemotherapy and YESCARTA infusion. ≥ Grade 3 cytopenias not resolved by Day 30 following YESCARTA infusion occurred in 39% of all patients with NHL and included neutropenia (33%), thrombocytopenia (13%), and anemia (8%). Monitor blood counts after infusion. HYPOGAMMAGLOBULINEMIA B-cell aplasia and hypogammaglobulinemia can occur. Hypogammaglobulinemia was reported as an adverse reaction in 14% of all patients with NHL. Monitor immunoglobulin levels after treatment and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement. The safety of immunization with live viral vaccines during or following YESCARTA treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during YESCARTA treatment, and until immune recovery following treatment. SECONDARY MALIGNANCIES Patients treated with YESCARTA may develop secondary malignancies. T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including YESCARTA. Mature T cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusion, and may include fatal outcomes. Monitor life-long for secondary malignancies. In the event that a secondary malignancy occurs, contact Kite at 1-844-454-KITE (5483) to obtain instructions on patient samples to collect for testing. EFFECTS ON ABILITY TO DRIVE AND USE MACHINES Due to the potential for neurologic events, including altered mental status or seizures, patients are at risk for altered or decreased consciousness or coordination in the 8 weeks following YESCARTA infusion. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, during this initial period. ADVERSE REACTIONS The most common non-laboratory adverse reactions (incidence ≥ 20%) in patients with LBCL in ZUMA-7 included fever, CRS, fatigue, hypotension, encephalopathy, tachycardia, diarrhea, headache, musculoskeletal pain, nausea, febrile neutropenia, chills, cough, infection with unspecified pathogen, dizziness, tremor, decreased appetite, edema, hypoxia, abdominal pain, aphasia, constipation, and vomiting. The most common adverse reactions (incidence ≥ 20%) in patients with LBCL in ZUMA-1 included CRS, fever, hypotension, encephalopathy, tachycardia, fatigue, headache, decreased appetite, chills, diarrhea, febrile neutropenia, infections with pathogen unspecified, nausea, hypoxia, tremor, cough, vomiting, dizziness, constipation, and cardiac arrhythmias. The most common non-laboratory adverse reactions (incidence ≥ 20%) in patients with iNHL in ZUMA-5 included fever, CRS, hypotension, encephalopathy, fatigue, headache, infections with pathogen unspecified, tachycardia, febrile neutropenia, musculoskeletal pain, nausea, tremor, chills, diarrhea, constipation, decreased appetite, cough, vomiting, hypoxia, arrhythmia, and dizziness. About Kite Kite, a Gilead Company, is a global biopharmaceutical company based in Santa Monica, California, focused on achieving cures with cell therapy. 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. For more information on Kite, please visit www.kitepharma.com . 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, COVID-19, cancer, and inflammation. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, Calif. Gilead acquired Kite in 2017. 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 ability of Gilead and Kite to initiate, progress or complete clinical trials within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing or additional clinical studies, including those involving Yescarta (such as ZUMA-5); uncertainties relating to regulatory applications and related filing and approval timelines, including pending or potential applications for indications currently under evaluation; 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 September 30, 2024, 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 Gilead and Kite, and Gilead and Kite assume no obligation and disclaim any intent to update any such forward-looking statements. Yescarta, Gilead, the Gilead logo, Kite, the Kite logo are trademarks of Gilead Sciences, Inc., or its related companies. For more information on Kite, please visit the company’s website at www.kitepharma.com . Follow Kite on social media on X (@KitePharma) and LinkedIn .

SANTA MONICA, Calif.--( BUSINESS WIRE )--Kite, a Gilead Company (Nasdaq: GILD), announced results today from four analyses that continue to demonstrate the durability of response of Tecartus ® (brexucabtagene autoleucel) in patients with relapsed/refractory mantle cell lymphoma (R/R MCL) and relapsed/refractory B-cell precursor acute lymphoblastic leukemia (R/R B-ALL) during the 66th American Society of Hematology (ASH) Annual Meeting and Exposition. The data presented include an oral presentation (Abstract # 748) of a primary analysis of ZUMA-2 cohort 3 demonstrating an overall response rate (ORR) of 91% and complete response (CR) rate of 73% in Bruton tyrosine kinase inhibitor (BTKi)-naïve patients with R/R MCL. Long-term follow-up of patients in ZUMA-2 cohorts 1 and 2 (Abstract #4388), showed that 39% of patients with R/R MCL were still alive after five years, underscoring Tecartus as the only CAR T to have five-year follow-up data in this patient population. In addition, real-world evidence outcomes in adults with R/R B-ALL treated with Tecartus (Abstract # 5092 and #4193) demonstrated a high effectiveness and consistent safety profile in a broader patient population than the pivotal ZUMA-3 study. “ We are proud to share long-term data that continue to underscore durable efficacy and survival benefits with one-time treatment of Tecartus in people with relapsed or refractory mantle cell lymphoma and B-cell precursor acute lymphoblastic leukemia,” said Dominique Tonelli, VP, Global Head of Medical Affairs, Kite. “ This compelling efficacy is consistent across patient subgroups and is observed in the latest follow-up analyses. Additionally, Kite’s industry-leading manufacturing shows that Tecartus can be successfully manufactured and elicit robust objective response rates regardless of white blood cell or lymphocyte count.” Detailed Information on Tecartus Abstracts: Abstract #748 Primary Analysis of ZUMA-2 Cohort 3: Brexucabtagene Autoleucel (Brexu-Cel) in Patients (Pts) With Relapsed/Refractory Mantle Cell Lymphoma (R/R MCL) Who Were Naive to Bruton Tyrosine Kinase Inhibitors (BTKi) ZUMA-2 is a single-arm, multicenter, open-label Phase 2 study that investigated leukapheresed adult patients (≥18 years old) with MCL whose disease is refractory to or has relapsed following up to five prior lines of therapy, including anthracycline or bendamustine-containing chemotherapy, anti-CD20 monoclonal antibody therapy and the BKTi ibrutinib or acalabrutinib. Cohort 3 of ZUMA-2 assesses treatment of Tecartus in 86 patients who have not received treatment with a BTKi. With a median follow-up of 15.5 months (range, 1.4-27.1), the primary endpoint was met with an ORR of 91% (95% CI, 82.5-95.9; P<.0001). Seventy three percent (95% CI, 62.6-82.2) of patients had a CR, 17% (95% CI, 10.1-27.1) had a partial response (PR), 3% (95% CI, 0.7-9.9) had stable disease, and 3% (95% CI, 0.7-9.9) had progressive disease (PD) as best response to Tecartus. This efficacy was durable: Preliminary follow-up shows median duration of all time-to-event endpoints has not been met. The 12-month (95% CI) duration of response (DOR), progression-free survival (PFS), and overall survival (OS) rates were 80% (69.1-87.9), 75% (64.5-83.4), and 90% (80.7-94.4), respectively. “ For years, we have seen strong, durable responses with brexu-cel from patients previously exposed to BTKi treatment,” said Dr. Tom van Meerten, lead investigator, University Medical Center Groningen, Netherlands.​ “ Patients with high-risk relapsed/refractory mantle cell lymphoma have poor outcomes, so it is encouraging to see positive results even in people who are BTKi-naïve. The high overall response rate, complete responses, and durable benefit demonstrated in ZUMA-2 cohort 3 indicate that brexu-cel can be used earlier in the treatment of relapsed/refractory mantle cell lymphoma.” No new safety signals were detected, with a low rate of Grade ≥ 3 cytokine release syndrome (CRS) occurring in five patients (6%) and an expected rate of Grade ≥ 3 neurological events (immune effector cell-associated neurotoxicity syndrome [ICANS]), occurring in 18 patients (21%). Abstract #4388 Five-Year Outcomes of Patients (Pts) With Relapsed/Refractory Mantle Cell Lymphoma (R/R MCL) Treated With Brexucabtagene Autoleucel (Brexu-cel) in ZUMA-2 Cohorts 1 and 2 The abstract features five-year follow-up data from cohort 1 of the ZUMA-2 study. Cohort 1 enrolled 68 patients who received the pivotal dose (2×10 6 anti-CD19 CAR T cells/kg) of Tecartus and received at least two prior lines of therapy. In addition, cohort 2 was designed in 2018 to assess a lower dose (0.5 x 10 6 anti-CD19 CAR T cells/kg) in the same line setting; however, the risk/benefit ratio of the cohort 1 dose was deemed optimal before cohort 2 reached full enrollment. In the primary analysis of cohort 2, 14 patients treated with Tecartus with a median follow-up of 16.0 (13.9-18.0) months demonstrated an ORR of 93% (95% CI, 66.1-99.8) per independent radiology review committee (IRRC); 64% had a CR (95% CI, 35.1-87.2), and 29% had a PR (95% CI, 8.4-58.1). In the five-year analysis, median follow-up for cohorts 1 and 2 were 67.8 months (58.2-88.6) and 72.3 months (70.1-74.3), respectively. Median (95% CI) investigator-assessed DOR and PFS were 36.5 months (17.7-48.9; n=60; 17 patients in ongoing response, all CR) and 25.3 months (12.7-46.6; n=68) in cohort 1; and 57.5 months (4.7-not estimable [NE]; n=12; 3 patients in ongoing response, all CR) and 29.5 months (3.3-NE; n=14) in cohort 2. Median OS (95% CI) and 60-month OS rates (95% CI) were 46.5 months (24.9- 60.2) and 39% (26.7-50.1) in cohort 1, respectively; and not reached (9.4-NE) and 54% (23.8-76.2) in cohort 2, respectively. No new safety signals were detected, and no secondary T‑cell malignancies were reported at any time in ZUMA-2 “ More than three years after its approval, brexu-cel continues to deliver in relapsed/refractory mantle cell lymphoma,” said Dr. Michael Wang, lead investigator, The University of Texas MD Anderson Cancer Center. “ It is encouraging to see these results in a heavily pre-treated population and consistency across both cohorts.” Abstract # 5092 Real-World Outcomes for Brexucabtagene Autoleucel (Brexu-Cel) Treatment in Patients (Pts) With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia (R/R B-ALL) by High-Risk Features and Prior Treatments: Updated Evidence From the CIBMTR Registry This real-world analysis of 242 evaluable adult R/R B-ALL patients treated with Tecartus from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry demonstrated the high effectiveness of CAR T-cell therapy in a broad R/R B-ALL patient population. With a median follow-up of 7.2 months, the CR/CRi (CR with incomplete hematologic recovery) after Tecartus treatment was 80% (95% CI, 75-85; 68% [60-76] for 145 patients not in CR/CRi pre-infusion). Estimated six-month rates (95% CI) of DOR were 67% (58-74; n=192; 66% [51-77] in 99 patients not in CR/CRi pre-infusion), six-month rates of relapse-free survival (RFS) were 55% (95% CI, 48-62; n=242), and six-month rates of OS were 80% (95% CI, 74-84; n=242). Among all patients (n=242), rates of any grade CRS and ICANS by 100 days were 81% (95% CI, 76-86; 13% Grade ≥3 [95% CI, 9-18]), and 46% (95% CI, 39-52; 24% Grade ≥3 [95% CI, 19-30]), respectively. Day 30 prolonged thrombocytopenia and neutropenia rates were 30% (95% CI, 24-36) and 34% (95% CI, 28-41), respectively. “ In this real-world analysis of brexu-cel, we see an efficacy and safety profile consistent with the findings of the pivotal ZUMA-3 study in relapsed/refractory B-cell acute lymphoblastic leukemia, but in a broader patient population,” said Dr. Kitsada Wudhikarn​, lead investigator, Associate Professor of Medicine, Division of Hematology, Chulalongkorn University, Bangkok, Thailand. “ Notably, the high level of effectiveness seen in the patient registry was consistent across prior treatments and most high-risk features. These findings provide further evidence of the substantial utility of brexu-cel in the treatment of this challenging blood cancer.” Abstract #4193 Impact of Disease Burden, CAR-T Expansion, and Mononuclear Cell Recovery on Overall Response and Duration of Response in ZUMA-3 Pivotal Study In the analysis, researchers evaluated clinical and pharmacokinetic/pharmacodynamic data in the context of best response and durability of response among 78 R/R B-ALL patients who received Tecartus in the ZUMA-3 study. Tecartus was successfully manufactured from apheresis material and elicited robust rates of objective response regardless of white blood cell or lymphocyte count. Half of the patients who achieved duration of response lasting >12 months had a bone marrow blast percentage of ≥50%, demonstrating the potential of Tecartus to benefit patients regardless of disease burden. Additionally, CAR expansion within the first month post Tecartus infusion is associated with best response as well as durable response, even without persistence of CAR T cells. Recovery of mononuclear cells post infusion also appeared higher in subjects with longer response. These findings have the potential to support treatment decision-making, such as the need for subsequent allogeneic stem cell transplant as consolidation of remission. About ZUMA-2 The ongoing, single-arm, open-label ZUMA-2 pivotal study enrolled 86 adult patients with relapsed or refractory MCL who had previously received anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 antibody therapy and a Bruton tyrosine kinase inhibitor (ibrutinib or acalabrutinib). The primary endpoint was objective response rate per the Lugano Classification (2014), defined as the combined rate of CR and partial responses as assessed by an Independent Radiologic Review Committee (IRRC). Secondary endpoints include DOR, best objective response, PFS, OS, incidence of adverse events, incidence of anti-CD19 CAR antibodies, levels of anti-CD19 CAR T cells in blood, levels of cytokines in serum, and changes over time in the EQ-5D scale score and visual analogue scale score. About ZUMA-3 ZUMA-3 is an ongoing international multicenter (U.S., Canada, Europe), single-arm, open-label, registrational Phase 1/2 study of Tecartus in adult patients (≥18 years old) with B-ALL whose disease is refractory to or has relapsed following standard systemic therapy or hematopoietic stem cell transplantation. The primary endpoint is the rate of overall complete remission or complete remission with incomplete hematological recovery by central assessment. Duration of remission and RFS, OS, minimal residual disease negativity rate, and allogeneic stem cell transplantation rate were assessed as secondary endpoints. About MCL MCL is a rare form of non-Hodgkin lymphoma (NHL) that arises from cells originating in the “mantle zone” of the lymph node and predominantly affects men over the age of 60. Approximately 33,000 people worldwide are diagnosed with MCL each year. MCL is highly aggressive following relapse, with many patients’ disease progressing following therapy. About ALL ALL is an aggressive and rare type of blood cancer that can also involve the lymph nodes, spleen, liver, central nervous system and other organs. While 80% of ALL occurs in children, it represents a devastating disease in adults. In adults, B-cell precursor ALL is the most common form, accounting for 75% of cases. Survival rates in adults with R/R B-ALL are poor, with median OS at less than eight months. About Tecartus Please see full FDA Prescribing Information , including BOXED WARNING and Medication Guide. Tecartus is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of: Adult patients with relapsed or refractory mantle cell lymphoma (MCL). Adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). This indication is approved under accelerated approval based on overall response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. U.S. IMPORTANT SAFETY INFORMATION BOXED WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES and SECONDARY HEMATOLOGICAL MALIGNANCIES Cytokine Release Syndrome (CRS), including life-threatening reactions, occurred in patients receiving Tecartus. Do not administer Tecartus to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids. Neurologic toxicities, including life-threatening reactions, occurred in patients receiving Tecartus, including concurrently with CRS or after CRS resolution. Monitor for neurologic toxicities after treatment with Tecartus. Provide supportive care and/or corticosteroids as needed. T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies Tecartus is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Yescarta and Tecartus REMS Program. Cytokine Release Syndrome (CRS) , including life-threatening reactions, occurred following treatment with Tecartus. CRS occurred in 92% (72/78) of patients with ALL, including ≥ Grade 3 (Lee grading system) CRS in 26% of patients. Three patients with ALL had ongoing CRS events at the time of death. The median time to onset of CRS was five days (range: 1 to 12 days) and the median duration of CRS was eight days (range: 2 to 63 days) for patients with ALL. Ensure that a minimum of two doses of tocilizumab are available for each patient prior to infusion of Tecartus. Following infusion, monitor patients for signs and symptoms of CRS daily for at least seven days at the certified healthcare facility, and for four weeks thereafter. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. At the first sign of CRS, institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids as indicated. Neurologic Events , including those that were fatal or life-threatening, occurred following treatment with Tecartus. Neurologic events occurred in 87% (68/78) of patients with ALL, including ≥ Grade 3 in 35% of patients. The median time to onset for neurologic events was seven days (range: 1 to 51 days) with a median duration of 15 days (range: 1 to 397 days) in patients with ALL. For patients with MCL, 54 (66%) patients experienced CRS before the onset of neurological events. Five (6%) patients did not experience CRS with neurologic events and eight patients (10%) developed neurological events after the resolution of CRS. Neurologic events resolved for 119 out of 134 (89%) patients treated with Tecartus. Nine patients (three patients with MCL and six patients with ALL) had ongoing neurologic events at the time of death. For patients with ALL, neurologic events occurred before, during, and after CRS in 4 (5%), 57 (73%), and 8 (10%) of patients; respectively. Three patients (4%) had neurologic events without CRS. The onset of neurologic events can be concurrent with CRS, following resolution of CRS or in the absence of CRS. The most common neurologic events (>10%) were similar in MCL and ALL and included encephalopathy (57%), headache (37%), tremor (34%), confusional state (26%), aphasia (23%), delirium (17%), dizziness (15%), anxiety (14%), and agitation (12%). Serious events including encephalopathy, aphasia, confusional state, and seizures occurred after treatment with Tecartus. Monitor patients daily for at least seven days for patients with MCL and at least 14 days for patients with ALL at the certified healthcare facility and for four weeks following infusion for signs and symptoms of neurologic toxicities and treat promptly. REMS Program: Because of the risk of CRS and neurologic toxicities, Tecartus is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Yescarta and Tecartus REMS Program which requires that: Healthcare facilities that dispense and administer Tecartus must be enrolled and comply with the REMS requirements. Certified healthcare facilities must have on-site, immediate access to tocilizumab, and ensure that a minimum of two doses of tocilizumab are available for each patient for infusion within two hours after Tecartus infusion, if needed for treatment of CRS. Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense, or administer Tecartus are trained in the management of CRS and neurologic toxicities. Further information is available at www.YescartaTecartusREMS.com or 1-844-454-KITE (5483). Hypersensitivity Reactions: Serious hypersensitivity reactions, including anaphylaxis, may occur due to dimethyl sulfoxide (DMSO) or residual gentamicin in Tecartus. Severe Infections: Severe or life-threatening infections occurred in patients after Tecartus infusion. Infections (all grades) occurred in 56% (46/82) of patients with MCL and 44% (34/78) of patients with ALL. Grade 3 or higher infections, including bacterial, viral, and fungal infections, occurred in 30% of patients with ALL and MCL. Tecartus should not be administered to patients with clinically significant active systemic infections. Monitor patients for signs and symptoms of infection before and after Tecartus infusion and treat appropriately. Administer prophylactic antimicrobials according to local guidelines. Febrile neutropenia was observed in 6% of patients with MCL and 35% of patients with ALL after Tecartus infusion and may be concurrent with CRS. The febrile neutropenia in 27 (35%) of patients with ALL includes events of “febrile neutropenia” (11 (14%)) plus the concurrent events of “fever” and “neutropenia” (16 (21%)). In the event of febrile neutropenia, evaluate for infection and manage with broad spectrum antibiotics, fluids, and other supportive care as medically indicated. In immunosuppressed patients, life-threatening and fatal opportunistic infections have been reported. The possibility of rare infectious etiologies (e.g., fungal and viral infections such as HHV-6 and progressive multifocal leukoencephalopathy) should be considered in patients with neurologic events and appropriate diagnostic evaluations should be performed. Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against B cells. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing. Prolonged Cytopenias: Patients may exhibit cytopenias for several weeks following lymphodepleting chemotherapy and Tecartus infusion. In patients with MCL, Grade 3 or higher cytopenias not resolved by Day 30 following Tecartus infusion occurred in 55% (45/82) of patients and included thrombocytopenia (38%), neutropenia (37%), and anemia (17%). In patients with ALL who were responders to Tecartus treatment, Grade 3 or higher cytopenias not resolved by Day 30 following Tecartus infusion occurred in 20% (7/35) of the patients and included neutropenia (12%) and thrombocytopenia (12%); Grade 3 or higher cytopenias not resolved by Day 60 following Tecartus infusion occurred in 11% (4/35) of the patients and included neutropenia (9%) and thrombocytopenia (6%). Monitor blood counts after Tecartus infusion. Hypogammaglobulinemia: B cell aplasia and hypogammaglobulinemia can occur in patients receiving treatment with Tecartus. Hypogammaglobulinemia was reported in 16% (13/82) of patients with MCL and 9% (7/78) of patients with ALL. Monitor immunoglobulin levels after treatment with Tecartus and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement. The safety of immunization with live viral vaccines during or following Tecartus treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least six weeks prior to the start of lymphodepleting chemotherapy, during Tecartus treatment, and until immune recovery following treatment with Tecartus. Secondary Malignancies may develop. T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies. Mature T cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusion, and may include fatal outcomes. Monitor life-long for secondary malignancies. In the event that one occurs, contact Kite at 1-844-454-KITE (5483) to obtain instructions on patient samples to collect for testing. Effects on Ability to Drive and Use Machines: Due to the potential for neurologic events, including altered mental status or seizures, patients are at risk for altered or decreased consciousness or coordination in the 8 weeks following Tecartus infusion. Advise patients to refrain from driving and engaging in hazardous activities, such as operating heavy or potentially dangerous machinery, during this period. Adverse Reactions: The most common non-laboratory adverse reactions (≥ 20%) were fever, cytokine release syndrome, hypotension, encephalopathy, tachycardia, nausea, chills, headache, fatigue, febrile neutropenia, diarrhea, musculoskeletal pain, hypoxia, rash, edema, tremor, infection with pathogen unspecified, constipation, decreased appetite, and vomiting. The most common serious adverse reactions (≥ 2%) were cytokine release syndrome, febrile neutropenia, hypotension, encephalopathy, fever, infection with pathogen unspecified, hypoxia, tachycardia, bacterial infections, respiratory failure, seizure, diarrhea, dyspnea, fungal infections, viral infections, coagulopathy, delirium, fatigue, hemophagocytic lymphohistiocytosis, musculoskeletal pain, edema, and paraparesis. Please see full Prescribing Information , including BOXED WARNING and Medication Guide. About Kite Kite, a Gilead Company, is a global biopharmaceutical company based in Santa Monica, California, focused on achieving cures with cell therapy. 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. For more information on Kite, please visit www.kitepharma.com . 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, COVID-19, cancer, and inflammation. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, Calif. Gilead acquired Kite in 2017. 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 ability of Gilead and Kite to initiate, progress or complete clinical trials within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing or additional clinical studies, including those involving Tecartus (such as ZUMA-2, ZUMA-3 and real-world analysis); uncertainties relating to regulatory applications and related filing and approval timelines, including pending or potential applications for indications currently under evaluation; Gilead and Kite’s ability to timely and successfully manufacture and deliver Tecartus, or produce an amount of supply sufficient to satisfy demand for Tecartus; 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 September 30, 2024, 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 Gilead and Kite, and Gilead and Kite assume no obligation and disclaim any intent to update any such forward-looking statements. Tecartus, Gilead, the Gilead logo, Kite, the Kite logo are trademarks of Gilead Sciences, Inc., or its related companies. For more information on Kite, please visit the company’s website at www.kitepharma.com . Follow Kite on social media on X (@KitePharma) and LinkedIn .