Latest news with #largeBcellLymphoma
Yahoo
13-08-2025
- Business
- Yahoo
Lyell Immunopharma Reports Business Highlights and Financial Results for the Second Quarter 2025
Presented positive new clinical data demonstrating high rates of durable complete responses from the Phase 1/2 trial of LYL314 for the treatment of aggressive large B-cell lymphoma Initiated the PiNACLE pivotal trial of LYL314 in patients with large B-cell lymphoma receiving treatment in the third‑ or later-line (3L+) setting; remain on track to initiate a pivotal trial in the second-line (2L) setting by early 2026 Entered into a securities purchase agreement for a private placement for gross proceeds of up to approximately $100 million Pro-forma cash of approximately $347 million inclusive of the initial proceeds from the private placement to support advancing pipeline into mid-2027 through key clinical milestones SOUTH SAN FRANCISCO, Calif., Aug. 12, 2025 (GLOBE NEWSWIRE) -- Lyell Immunopharma, Inc. (Nasdaq: LYEL), a late-stage clinical company advancing next-generation CAR T-cell therapies for patients with cancer, today reported financial results and business highlights for the second quarter ended June 30, 2025. Lyell's lead clinical program, LYL314, is a next-generation autologous dual-targeting CD19/CD20 CAR T-cell product candidate under evaluation in PiNACLE, a single-arm pivotal trial enrolling patients with relapsed and/or refractory (R/R) large B-cell lymphoma (LBCL) in the 3L+ setting and in a Phase 1/2 study in the 2L setting. 'Based on the high rate of durable complete responses achieved by LYL314 in patients with aggressive LBCL presented at the International Conference on Malignant Lymphoma in Lugano, Switzerland, in June, we believe that our CD19/CD20 CAR T-cell therapy will disrupt the therapeutic landscape by delivering meaningfully increased complete response rates and improved durability over the currently approved CD19 CAR T-cell therapies,' said Lynn Seely, M.D., President and CEO of Lyell. 'Our recent private placement with well-respected investors significantly derisks our business, extends our cash runway into mid-2027 and enables us to focus on rapidly advancing the clinical development of LYL314. We have initiated the PiNACLE single-arm pivotal trial for patients with LBCL receiving treatment in the third- or later-line setting and are on track to begin a second pivotal trial of LYL314 for patients with LBCL in the second-line setting by early 2026.' Second Quarter Updates and Recent Business Highlights Lyell is advancing a pipeline of next-generation CAR T-cell product candidates targeting cancers with large unmet need and substantial patient populations. Its lead program, LYL314, is in pivotal development for patients with R/R LBCL and its preclinical programs target solid tumor is an autologous CAR T-cell product candidate with a true 'OR' logic gate to target B cells that express either CD19 or CD20 with full potency and that is manufactured with a process that enriches for CD62L-positive cells to generate more naïve and central memory CAR T cells with enhanced stemlike features and antitumor activity. Following a successful End-of-Phase 1 meeting with the U.S. Food and Drug Administration (FDA), LYL314 is currently being evaluated in the pivotal PiNACLE trial, which is a seamless expansion of the 3L+ cohort of the Phase 1/2 trial of patients with R/R LBCL. The Phase 1/2 trial continues to enroll CAR T-cell therapy naïve patients receiving treatment in the 2L setting and a pivotal trial for these 2L patients is expected be initiated by early 2026. The FDA has granted LYL314 Regenerative Medicine Advanced Therapy (RMAT) and Fast Track designations for the treatment of R/R diffuse LBCL in the 3L+ setting. RMAT provides all the benefits of the Fast Track and Breakthrough Therapy designation programs and enables increased frequency of communications with the FDA on the development of LYL314. PiNACLE is a single-arm pivotal trial evaluating LYL314 at a dose of 100 x 106 CAR T cells in patients with LBCL receiving treatment in the 3L+ setting. The trial is expected to enroll approximately 120 patients with R/R diffuse large B-cell lymphoma, high grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, transformed follicular lymphoma or Grade 3B follicular lymphoma who have not previously received CAR T-cell therapy. Patients may be treated with LYL314 in either the inpatient or outpatient setting and there is no upper age limit for eligibility. The primary endpoint of the trial is the overall response rate, including an evaluation of duration of response. New clinical data from the Phase 1/2 multi-center clinical trial of LYL314 in patients with R/R LBCL were presented at the 18th International Conference on Malignant Lymphoma in June and included more mature data from patients treated in the 3L+ setting and initial data from patients treated in the 2L setting. The data were presented in an oral presentation titled 'LYL314, a CD19/CD20 CAR T‑cell candidate enriched for CD62L+ stem-like cells, achieves high rates of durable complete responses in relapsed and/or refractory large B-cell lymphoma'. Highlights include: Fifty-one CAR T-naive patients with R/R LBCL received LYL314 as of April 15, 2025 (the data cutoff date for the presentation). The efficacy evaluable population consisted of 36 patients with Day 84 assessments or prior disease progression or death. Patient demographics and baseline disease characteristics were consistent with high-risk patient populations: median ages of 65 and 69 years in the 3L+ and 2L, respectively, 41% of 3L+ and 65% of 2L patients had Stage IV disease at trial entry, and 47% of 3L+ and 82% of 2L patients had primary refractory disease. In efficacy-evaluable 3L+ patients, with a median follow-up of 9 months (N = 25): The overall response rate was 88% (22/25 patients), with 72% (18/25) of patients achieving a complete response. 71% (10/14) of patients with complete response remained in complete response at ≥ 6 months. In initial data from efficacy-evaluable 2L patients, with a median follow-up of 5 months (N = 11): The overall response rate was 91% (10/11 patients), with 64% (7/11) achieving a complete response. 100% (7/7) of patients with complete response were in complete response at their last assessment, including 3/3 patients at ≥ 6 months. In patients with primary refractory disease, a difficult to treat population, 70% (7/10) achieved a complete response. In 51 patients, including patients from both the 3L+ and the 2L cohorts, a manageable safety profile appropriate for outpatient administration was observed. No Grade ≥ 3 and low rates of Grade 1 (22%) or Grade 2 (35%) cytokine release syndrome (CRS) were reported. Immune effector cell-associated neurotoxicity syndrome (ICANS) was reported in 6% (Grade 1), 2% (Grade 2), and 14% (Grade ≥ 3) of patients. The median time to complete resolution of all reports of ICANS was 5 days, with rapid improvement (median of 2 days) to Grade 2 or lower with standard therapy. No deaths were related to LYL314 administration. LYL314 demonstrated robust expansion with a time to peak of 10 days. The final drug product contained the desired CD62L-positive naïve T-cell phenotype (median, 95%). Rapid and durable depletion of B cells was demonstrated through month 6 and up to the month 12 assessment. An update on the progress of the PiNACLE trial is planned for late 2025. Data from this trial is expected to form the basis of a Biologics License Application submission to the FDA in 2027 for patients with R/R LBCL receiving treatment in the 3L+ setting. More mature data from the ongoing Phase 1/2 trial in the 2L setting are expected to be presented in late 2025. A Phase 3 randomized controlled trial of LYL314 is expected to be initiated by early 2026 in patients receiving treatment in the 2L setting with R/R LBCL. Preclinical Pipeline, Technologies and Manufacturing Protocols Lyell is advancing next-generation fully-armed CAR T-cell product candidates, each including multiple technologies, designed to overcome T-cell exhaustion and lack of durable stemness, as well as immune suppression within the hostile tumor microenvironment. The first IND for a fully-armed CAR T-cell product candidate with an undisclosed target for solid tumors is expected in 2026. Corporate Updates In July, Lyell entered into a securities purchase agreement for a private placement with certain institutional and other accredited investors, for gross proceeds of up to approximately $100 million. The initial closing of approximately $50 million of common stock at a price of $13.32 per share occurred on July 25, 2025. After deducting offering expenses, Lyell expects to use net proceeds from the private placement, together with its existing cash, cash equivalents, and marketable securities, to advance two pivotal-stage clinical trials of LYL314 as well as working capital for other general corporate purposes. Second Quarter 2025 Financial Results Lyell reported a net loss of $42.7 million for the second quarter ended June 30, 2025, compared to a net loss of $45.8 million for the same period in 2024. The $3.1 million decrease in net loss was primarily due to a decrease of $3.3 million in stock-based compensation expense resulting from lower headcount and the reduced value of new equity awards. Non‑GAAP net loss, which excludes stock-based compensation, non-cash expenses related to the change in the estimated fair value of success payment liabilities and certain non-cash investment gains and charges, decreased to $37.8 million for the second quarter ended June 30, 2025, compared to $39.1 million for the same period in 2024, primarily due to lower interest income primarily driven by decreased interest rates in 2025 coupled with lower cash equivalent and marketable securities balances. GAAP and Non-GAAP Operating Expenses Research and development (R&D) expenses were $34.9 million for the second quarter ended June 30, 2025, compared to $40.3 million for the same period in 2024. The decrease in second quarter 2025 R&D expenses of $5.4 million was primarily due to a $2.9 million reduction in research activities, collaborations and outside services due primarily to a reduction in costs associated with research and laboratory supplies and collaboration agreements and a $2.4 million decrease in personnel‑related expenses primarily due to reduced stock-based compensation expense resulting from lower headcount and the reduced value of new equity awards. Non‑GAAP R&D expenses, which exclude non-cash stock-based compensation and non-cash expenses related to the change in the estimated fair value of success payment liabilities for the second quarter ended June 30, 2025 were $32.6 million, compared to $37.2 million for the same period in 2024. General and administrative (G&A) expenses were $9.8 million for the second quarter ended June 30, 2025, compared to $12.3 million for the same period in 2024. The decrease in second quarter 2025 G&A expenses of $2.5 million was primarily due to a $1.7 million decrease in stock-based compensation expense primarily related to a decrease in the value of new awards granted and a $0.8 million decrease in outside services primarily due to a reduction in legal expenses. Non‑GAAP G&A expenses, which exclude non-cash stock‑based compensation, for the second quarter ended June 30, 2025 were $7.1 million, compared to $7.8 million for the same period in 2024. A discussion of non-GAAP financial measures, including reconciliations of the most comparable GAAP measures to non‑GAAP financial measures, is presented below under 'Non-GAAP Financial Measures.' Cash, cash equivalents and marketable securities Cash, cash equivalents and marketable securities as of June 30, 2025 were approximately $297 million, compared to approximately $384 million as of December 31, 2024. Lyell believes that its cash, cash equivalents and marketable securities balances totaling approximately $347 million inclusive of the initial $50 million of proceeds from its recent private placement, will be sufficient to meet working capital and capital expenditure needs into mid-2027. About Lyell Immunopharma, Inc. Lyell is a late-stage clinical company advancing a pipeline of next-generation CAR T-cell therapies for patients with hematologic malignancies and solid tumors. To realize the potential of cell therapy for cancer, Lyell utilizes a suite of technologies to endow CAR T cells with attributes needed to drive durable tumor cytotoxicity and high rates of long‑lasting clinical responses, including the ability to resist exhaustion, maintain qualities of durable stemness and function in the hostile tumor microenvironment. The Lyell LyFE Manufacturing Center™ has commercial launch capability and can manufacture more than 1,200 CAR T-cell doses at full capacity. To learn more, please visit Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements expressed or implied in this press release include, but are not limited to, statements regarding: Lyell's initiation by early 2026 of a pivotal trial for LYL314 for patients with LBCL in the 2L setting; expectations around the potential for CD19/CD20 CAR T-cell therapies to disrupt the therapeutic landscape; the anticipated benefits of RMAT and Fast Track designations for LYL314; Lyell's expectations around the progress of the PiNACLE trial, including expectations around enrollment and timing of progress update in late 2025, and using data from the trial to form the basis of a Biologics License Application submission to the FDA in 2027 for patients with relapsed and/or refractory LBCL receiving treatment in the 3L+ setting; Lyell's expectations around continued enrollment for and timing of more mature clinical data from its ongoing Phase 1/2 trial for LYL314 in the 2L setting in late 2025; the advancement of Lyell's technology platform; Lyell's advancement of its pipeline and its research, development and clinical capabilities; Lyell's submission of an IND in 2026 for a CAR T-cell product candidate with an undisclosed target for solid tumors; Lyell's plans for using the net proceeds from the private placement and its existing cash, cash equivalents and marketable securities, and its expectation that its financial position and cash runway will support advancement of its pipeline into mid-2027 through key clinical milestones; the sufficiency of the capacity of LyFE to manufacture drug supply for Lyell's ongoing and planned pivotal trials and through potential commercial launch; Lyell's anticipated progress, business plans, business strategy and clinical trials; the potential clinical benefits and therapeutic potential of Lyell's product candidates, including meaningful increased complete response rates and prolonged duration of response; and other statements that are not historical fact. These statements are based on Lyell's current plans, objectives, estimates, expectations and intentions, are not guarantees of future performance and inherently involve significant risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, but are not limited to, risks and uncertainties related to: Lyell's ability to submit planned INDs or initiate or progress clinical trials on the anticipated timelines, if at all; Lyell's limited experience as a company in enrolling and conducting clinical trials, and lack of experience in completing clinical trials; the complexity of manufacturing cellular therapies, which subjects us to a multitude of manufacturing risks, any of which could substantially increase our costs, delay our programs or limit supply of our product candidates; the nonclinical profiles of Lyell's product candidates or technology not translating in clinical trials; the potential for results from clinical trials to differ from nonclinical, early clinical, preliminary or expected results; significant adverse events, toxicities or other undesirable side effects associated with Lyell's product candidates; the significant uncertainty associated with Lyell's product candidates ever receiving any regulatory approvals; RMAT and Fast Track designations may not actually lead to faster development, regulatory review or approval process, and does not assure ultimate FDA approval; Lyell's ability to obtain, maintain or protect intellectual property rights related to its product candidates; implementation of Lyell's strategic plans for its business and product candidates; the sufficiency of Lyell's capital resources and need for additional capital to achieve its goals; the effects of macroeconomic conditions, including the effects of disruption between the U.S. and its trading partners due to tariffs or other policies, and any geopolitical instability; potential changes to U.S. drug pricing, including the potential for 'most-favored nations' pricing limitations; and other risks, including those described under the heading 'Risk Factors' in Lyell's Quarterly Report on Form 10-Q for the quarter ended June 30, 2025, being filed with the SEC today. Forward-looking statements contained in this press release are made as of this date, and Lyell undertakes no duty to update such information except as required under applicable law. Lyell Immunopharma, Inc. Unaudited Selected Consolidated Financial Data (in thousands) Statement of Operations Data: Three Months Ended June 30, Six Months Ended June 30, 2025 2024 2025 2024 Revenue $ 8 $ 13 $ 15 $ 16 Operating expenses: Research and development(1) 34,857 40,261 78,304 83,435 General and administrative 9,786 12,256 23,832 25,750 Other operating loss (income), net 1,062 (976 ) 943 (2,066 ) Impairment of long-lived assets 1,443 — 1,443 — Total operating expenses 47,148 51,541 104,522 107,119 Loss from operations (47,140 ) (51,528 ) (104,507 ) (107,103 ) Interest income, net 3,276 6,364 7,138 13,183 Other income (expense), net(1) 1,180 (645 ) 2,490 445 Impairment of other investments — — — (13,001 ) Total other income, net 4,456 5,719 9,628 627 Net loss $ (42,684 ) $ (45,809 ) $ (94,879 ) $ (106,476 ) (1) As of October 1, 2024, the Company's success payment liability was recognized at fair value as Stanford had provided the requisite service obligation to earn the potential success payment consideration. The change in the estimated fair value of Stanford success payment liabilities in the first half of 2025 was recognized within other income (expense), net in the Condensed Consolidated Statements of Operations and Comprehensive Loss. The change in the estimated fair value of Stanford success payment liabilities in the first half of 2024 was recognized within research and development expenses in the Condensed Consolidated Statements of Operations and Comprehensive Loss. Balance Sheet Data: As of June 30, As of December 31, 2025 2024 Cash, cash equivalents and marketable securities $ 296,849 $ 383,541 Property and equipment, net $ 39,115 $ 48,200 Total assets $ 385,453 $ 490,859 Total stockholders' equity $ 298,923 $ 382,824 Non-GAAP Financial Measures To supplement our financial results and guidance presented in accordance with U.S. generally accepted accounting principles (GAAP), we present non-GAAP net loss, non-GAAP R&D expenses and non-GAAP G&A expenses. Non‑GAAP net loss and non-GAAP R&D expenses exclude non-cash stock-based compensation expense and non-cash expenses related to the change in the estimated fair value of success payment liabilities from GAAP net loss and GAAP R&D expenses, respectively. Non-GAAP net loss is further adjusted by non‑cash investment gains and charges, as applicable. Non‑GAAP G&A expenses exclude non-cash stock-based compensation expense from GAAP G&A expenses. We believe that these non‑GAAP financial measures, when considered together with our financial information prepared in accordance with GAAP, can enhance investors' and analysts' ability to meaningfully compare our results from period to period, and to identify operating trends in our business. We have excluded stock-based compensation expense, changes in the estimated fair value of success payment liabilities, and non-cash investment gains and charges from our non‑GAAP financial measures because they are non-cash gains and charges that may vary significantly from period to period as a result of changes not directly or immediately related to the operational performance for the periods presented. We also regularly use these non‑GAAP financial measures internally to understand, manage and evaluate our business and to make operating decisions. These non-GAAP financial measures are in addition to, and not a substitute for or superior to, measures of financial performance prepared in accordance with GAAP. In addition, these non‑GAAP financial measures have no standardized meaning prescribed by GAAP and are not prepared under any comprehensive set of accounting rules or principles and, therefore, have limits in their usefulness to investors. We encourage investors to carefully consider our results under GAAP, as well as our supplemental non-GAAP financial information, to more fully understand our business. Lyell Immunopharma, Inc. Unaudited Reconciliation of GAAP to Non-GAAP Net Loss (in thousands) Three Months Ended June 30, Six Months Ended June 30, 2025 2024 2025 2024 Net loss - GAAP $ (42,684 ) $ (45,809 ) $ (94,879 ) $ (106,476 ) Adjustments: Stock-based compensation expense 5,004 8,284 11,028 17,439 Change in the estimated fair value of success payment liabilities (115 ) (1,534 ) (240 ) (566 ) Impairment of other investments — — — 13,001 Net loss - Non-GAAP(1) $ (37,795 ) $ (39,059 ) $ (84,091 ) $ (76,602 ) (1) There was no income tax effect related to the adjustments made to calculate non-GAAP net loss because of the full valuation allowance on our net deferred tax assets for all periods presented. Lyell Immunopharma, Inc. Unaudited Reconciliation of GAAP to Non-GAAP Research and Development Expenses (in thousands) Three Months Ended June 30, Six Months Ended June 30, 2025 2024 2025 2024 Research and development - GAAP $ 34,857 $ 40,261 $ 78,304 $ 83,435 Adjustments: Stock-based compensation expense (2,295 ) (3,865 ) (4,683 ) (7,657 ) Change in the estimated fair value of success payment liabilities(1) — 793 — 268 Research and development - Non-GAAP $ 32,562 $ 37,189 $ 73,621 $ 76,046 (1) As of October 1, 2024, the Company's success payment liability was recognized at fair value as Stanford had provided the requisite service obligation to earn the potential success payment consideration. The change in the estimated fair value of Stanford success payment liabilities in the first half of 2025 was recognized within other income (expense), net in the Condensed Consolidated Statements of Operations and Comprehensive Loss. The change in the estimated fair value of Stanford success payment liabilities in the first half of 2024 was recognized within research and development expenses in the Condensed Consolidated Statements of Operations and Comprehensive Loss. Lyell Immunopharma, Inc. Unaudited Reconciliation of GAAP to Non-GAAP General and Administrative Expenses (in thousands) Three Months Ended June 30, Six Months Ended June 30, 2025 2024 2025 2024 General and administrative - GAAP $ 9,786 $ 12,256 $ 23,832 $ 25,750 Adjustments: Stock-based compensation expense (2,709 ) (4,419 ) (6,345 ) (9,782 ) General and administrative - Non-GAAP $ 7,077 $ 7,837 $ 17,487 $ 15,968 Contact: Ellen Rose Senior Vice President, Communications and Investor Relations erose@
Associated Press
01-06-2025
- Business
- Associated Press
Kite Presents New Real-World Data Supporting Use of Potentially Curative Yescarta® in Outpatient Care Setting for Patients with Relapsed/Refractory Large B-Cell Lymphoma at ASCO 2025
SANTA MONICA, Calif.--(BUSINESS WIRE)--Jun 1, 2025-- Kite, a Gilead Company (Nasdaq: GILD), today announced real-world data evaluating the safety and effectiveness of Yescarta ® (axicabtagene ciloleucel) for patients with relapsed/refractory large B-cell lymphoma (R/R LBCL) assigned to treatment in an outpatient setting (no planned hospital stay) versus those assigned to an inpatient setting in a hospital. The analysis, based on data collected from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, observed that safety and effectiveness outcomes for people treated as outpatients were comparable to those patients who received treatment in a hospital. The results were shared in a presentation (Abstract #7023) during the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. 'The encouraging results from this study corroborate reports from treatment centers and prior studies in the real world that illustrate the potential feasibility of administering axi-cel in the outpatient setting for people with relapsed or refractory large B-cell lymphoma,' said Dr. Fateeha Furqan, lead investigator, The University of Texas MD Anderson Cancer Center. 'Outpatient administration of axi-cel has cost-effective advantages over inpatient treatment, including less burden on hospitals. These clinical results reflect the fact that the knowledge and experience needed to safely administer the therapy has only grown since axi-cel was first approved in 2017.' Data were collected from the CIBMTR observational database (between July 2021 to Nov 2023). The final analysis assessed data on patients with R/R LBCL from 75 treatment centers, comparing 119 individuals who were assigned to receive Yescarta in the outpatient setting to 119 patients assigned to receive Yescarta in the inpatient setting. With a median follow-up of 12 months, no general differences were found between the 2 groups in the rates of cytokine release syndrome, neurologic events or immune effector cell-associated neurotoxicity syndrome grade ≥ 3. Almost one-fourth of 119 patients who were assigned to receive Yescarta in the outpatient setting did not require hospital admission within 30 days, and half of 119 patients did not require hospital admission within 3 days based on propensity score-matched dataset. These real-world data are not currently in the U.S. Prescribing Information. 'We are seeing a growing body of evidence that suggests outpatient administration of Yescarta could be reliable and safe in suitable settings, with benefits for the patient, their family and healthcare system,' said Dominique Tonelli, M.D., Vice President and Global Head of Medical Affairs, Kite. 'We are confident that these promising results will help inform providers to expand the number of patients who can achieve the curative potential of a one-time treatment with Yescarta.' Patients assigned to the outpatient and inpatient treatment groups were matched by age, sex, comorbidities, lactate dehydrogenase (LDH), bulky disease, prior lines of therapy, chemosensitivity and infusion year. Patients assigned to the outpatient group had a median age of 63 years (25% ≥ 70), 66% were male and 67% had ≥ 1 comorbidity. Half had elevated LDH and 73% had 1 prior line of therapy. Bulky disease was reported in 3% and 60% had chemo-resistant disease. About LBCL Globally, LBCL is the most common type of non-Hodgkin lymphoma. In the United States, more than 18,000 people are diagnosed with LBCL each year. About 30-40% of patients with LBCL will need second-line treatment, as their cancer will either relapse (return) or become refractory (not respond) to initial treatment. About Yescarta Please see full Prescribing Information, including BOXED WARNING below and Medication Guide. YESCARTA is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of: Limitations of Use: YESCARTA is not indicated for the treatment of patients with primary central nervous system lymphoma. U.S. IMPORTANT SAFETY INFORMATION BOXED WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES and SECONDARY HEMATOLOGICAL MALIGNANCIES 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 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 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; 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 March 31, 2025, 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, and the Kite logo are trademarks of Gilead Sciences, Inc., or its related companies. For more information on Kite, please visit the company's website Follow Kite on social media on X (@KitePharma) andLinkedIn. View source version on CONTACT: Blair Baumwell, Media [email protected] Ross, Investors [email protected] KEYWORD: CALIFORNIA UNITED STATES NORTH AMERICA INDUSTRY KEYWORD: RESEARCH HOSPITALS FDA CLINICAL TRIALS OTHER HEALTH BIOTECHNOLOGY PHARMACEUTICAL HEALTH SCIENCE ONCOLOGY SOURCE: Gilead Sciences, Inc. Copyright Business Wire 2025. PUB: 06/01/2025 08:00 AM/DISC: 06/01/2025 08:01 AM
