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-- First CAR T-Cell Therapy to Report First-Line Data in LBCL --

Stockley Park, UK – 14 December, 2021 – Kite, a Gilead Company, today announced primary results from ZUMA-12, a global, multicenter, single-arm, open-label Phase 2 study evaluating Yescarta® (axicabtagene ciloleucel) as part of first-line treatment in patients with high-risk large B cell lymphoma (LBCL). This is the first study to evaluate CAR T cell therapy as part of first-line therapy in high-risk LBCL, and is based on the hypothesis that earlier use of CAR T cell therapy, when T cells are healthier, may produce better outcomes. The data were presented in an oral session during the 63rd American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract #739).

After a single infusion of axicabtagene ciloleucel, 89% of evaluable patients achieved a response (ORR) (n=37 evaluable for efficacy), including 78% of patients with a complete response (CR) at a median follow-up of 15.9 months. CR rate was consistent among key subgroups. Among evaluable patients, median time to response was one month. At time of data cut-off, 73% of evaluable patients had ongoing responses. Medians for duration of response (DOR), event-free survival (EFS), and progression-free survival (PFS) were not yet reached, with 12-month estimates of 81%, 73%, and 75%, respectively, and an estimated 12-month overall survival (OS) rate of 91%.1

Axicabtagene ciloleucel was successfully manufactured for all 42 enrolled patients with a median turnaround time of 18 days between leukapheresis and delivery to the trial site for treated patients. Levels of CCR7+CD45RA+ T cells (a measure of T cell fitness) found in pre-infused product were more than double what was measured in the heavily pre-treated third line ZUMA-1 patient population. Levels of CCR7+CD45RA+ T cells in pre-infused product have been associated with a favourable pharmacokinetic (PK) profile. CAR T-cell expansion also appeared greater in ZUMA-12 compared with ZUMA-1.1

“Less than half of patients with high-risk LBCL actually achieve long-term remission with standard first-line therapy,” said Sattva S. Neelapu, MD, Professor, Department of Lymphoma-Myeloma, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center. “There have been a number of attempts to improve outcomes for high-risk patients, either by intensification of chemotherapy, immunotherapy, or consolidation with autologous stem cell transplantation, but they have not been successful. The impressive


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response rates in ZUMA-12 support the potential of CAR T cell therapy earlier in treatment to improve outcomes in these high-risk patients.”

Among all treated patients (n=40), safety observations were consistent with the known safety profile for axicabtagene ciloleucel. Grade ≥3 cytokine release syndrome (CRS) occurred in 8% of patients and Grade ≥3 neurologic events occurred in 23% of patients. No Grade 5 CRS or neurological events occurred. There was one Grade 5 adverse event due to COVID-19. All CRS cases and most neurologic events (28/29) of any grade resolved by the time of data cut-off.

“The high rate of durable response to a one-time infusion of axicabtagene ciloleucel in newly diagnosed patients with high-risk LBCL is exceptional,” said Frank Neumann, MD, PhD, Kite’s Global Head of Clinical Development. “Many of these patients typically progress very quickly on current standard-of-care therapies. Further study is needed to understand axicabtagene ciloleucel’s potential as first-line therapy, but we are encouraged by these results.”

Axicabtagene ciloleucel has not been approved by any regulatory agency for the treatment of patients in the first-line setting.

About ZUMA-12

ZUMA-12 is a multicenter, open-label, single-arm Phase 2 study that enrolled 42 adult patients (≥18 years old) with high-risk LBCL. Patients who met the following criteria for high-risk LBCL were considered eligible for the study: double- or triple-hit lymphoma by fluorescent in situ hybridization per investigator or LBCL with IPI score ≥3; and positive interim PET per Lugano Classification after two cycles of an anti-CD20 monoclonal antibody- and anthracycline-containing regimen. Patients underwent leukapheresis (≥ two weeks after prior systemic therapy) and optional non-chemotherapy bridging at investigator discretion, followed by conditioning chemotherapy.

The primary endpoint of the trial is complete response rate per the Lugano Classification. Key secondary objectives include objective response rate, duration of response, event-free survival (EFS), progression-free survival, overall survival, frequency of adverse events, and levels of CAR T cells and cytokines in blood and serum. The study is ongoing.

About Yescarta® (Axicabtagene Ciloleucel)

In August 2018, axicabtagene ciloleucel, a chimeric antigen receptor (CAR) T cell therapy, received European Marketing Authorisation 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.2 About Kite Kite, a Gilead Company, is a global biopharmaceutical company based in Santa Monica, California, with manufacturing operations in North America and Europe. Kite’s singular focus is cell therapy to treat and potentially cure cancer. As the cell therapy leader, Kite has more approved CAR T indications to help more patients than any other company. 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 that Kite may discontinue development of Yescarta as part of first-line treatment in patients with high-risk LBCL. There is also the possibility of unfavorable results from ongoing and additional clinical trials involving Yescarta. 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, 2021, 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. Investors are cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties and are 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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Last Updated: 15-Dec-2021