Kite’s Next-Generation Bicistronic CAR T-Cell Therapies Show Encouraging Phase 1 Results in Relapsed/Refractory B-Cell Lymphoma in New Data at ASH 2025

Key Terms

cytokine release syndrome medical

An intense immune overreaction in which the body's defense system releases a large surge of signaling proteins, causing fever, low blood pressure, breathing trouble or organ stress; imagine the immune system's alarm going into overdrive and flooding the body with emergency responders. Investors care because this side effect can slow or block regulatory approval, increase clinical trial costs and liabilities, limit how widely a therapy can be used, and therefore affect a drug's market value and sales potential.

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The objective response rate (ORR) is the percentage of patients in a clinical trial whose tumors measurably shrink or disappear according to preset rules. Investors use it as a quick, objective signal of a drug’s ability to produce a clear treatment effect—like counting how many plants visibly respond after applying a new fertilizer—and higher ORR can improve odds of regulatory approval, commercial success, and company valuation.

– Initial Results from Kite-753, Optimized with Novel Manufacturing Process That Preserves T-Cell Fitness, Show High Complete Response Rate and Favorable Safety Trend –

– Novel Construct for Two Investigational Therapies Could Enable Safer, More Effective and Accessible CAR Ts –

SANTA MONICA, Calif.--(BUSINESS WIRE)-- Kite, a Gilead Company (Nasdaq: GILD), presented Phase 1 data today with encouraging efficacy and safety results for its two investigational bicistronic CAR T-cell therapies, KITE-753 and KITE-363, respectively, in patients with relapsed/refractory large B-cell lymphoma (R/R LBCL). The results of the analysis were shared in an oral presentation (Abstract #265) at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition.

Both KITE-753 and KITE-363 are bicistronic autologous CAR T-cell therapies. They are designed to target two antigens (CD19 and CD20) found on cancer cells and use two co-stimulatory domains (CD28 and 4-1BB) to help the immune system fight cancer more effectively. The KITE DuoCore™ construct – with two independent CARs working synergistically – may prevent relapse by reducing cancer cells escaping treatment and may help improve safety, making it possible to treat more patients outside of a hospital setting. Additionally, KITE-753 leverages a novel manufacturing process that preserves T-cell fitness. Combined, these attributes may contribute to better efficacy, lower toxicity, durable function, and faster delivery to patients.

"While CAR T-cell therapy has revolutionized treatment for many people with blood cancers, we urgently need options that not only improve upon the curative potential of existing cell therapies for evasive cancers but are also safer and available to a broader patient population,” said Dr. Saurabh Dahiya, MD, FACP, the Stanford School of Medicine. “The encouraging response rates, durability and safety profile of KITE-753 and KITE-363 offer strong clinical evidence to support further development."

The open-label, multicenter, umbrella Phase 1 study enrolled 67 patients with R/R BCL. Thirty patients received KITE-753 and 37 received KITE-363.

Results for KITE-753 showed that at a median follow-up of 4.0 months overall and 2.9 months at dose level three (DL3; 0.2×10⁶ CAR T cells/kg), 11 of 14 CAR-naïve patients (79%) receiving DL3 had a complete response, where the cancer completely disappeared. Bridging options in this Phase 1 study were limited to corticosteroid +/- radiation therapy, and all patients had measurable, active disease at the time of their infusion with KITE-753. No patients responded to these bridging therapy measures at DL3. Notably, KITE-753 demonstrated robust expansion despite a tenfold lower dose than DL3 of KITE-363 (2×10⁶ CAR T cells/kg), which highlights the proliferative capacity of KITE-753. Across all dose levels, 14 of 20 CAR-naïve patients achieved a complete response.

Overall, KITE-753 showed an encouraging safety profile with no dose‑limiting toxicities. At DL3, no Grade ≥3 cytokine release syndrome (CRS) or immune effector cell‑associated neurotoxicity syndrome (ICANS) were observed; Grade ≥3 adverse events occurred in 95% of patients (primarily cytopenias), and serious Grade ≥3 adverse events occurred in 26% of patients. Across all dose levels, one Grade 3 CRS event (none Grade ≥4) and no Grade ≥3 ICANS events occurred.

“Kite is dedicated to pushing the boundaries of CAR T-cell therapy to deliver even greater impact and curative potential,” said Dr. Gallia Levy, Senior Vice President, Global Head of Development at Kite. “By combining CD19/CD20 targeting with dual co‑stimulation, along with a manufacturing process resulting in a fit product, we aim to improve outcomes. Our goal is to bring CAR T to more patients, such as those with advanced disease who have exhausted other options, and to those who prefer to be treated in outpatient and in community oncology practice settings.”

Meanwhile, results for KITE-363 revealed that at a median follow-up of 17.5 months, there was a durable benefit at the highest dose level (2×10⁶ CAR T cells/kg) among CAR-naïve patients, with more than 70% of complete responders evaluable at 12 months remaining in remission. KITE-363 was generally well tolerated with no dose-limiting toxicities or severe side effects that required stopping the study. Grade ≥3 CRS occurred in one patient; Grade 3 ICANS occurred in two patients; no Grade ≥4 CRS/ICANS occurred.

About LBCL

Globally, large B-cell lymphoma (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 the Study

Thirty patients received KITE-753 and 37 received KITE-363. The open-label, multicenter umbrella Phase 1 study enrolled eligible adults with R/R LBCL after ≥2 lines of therapy (patients with LBCL could have second-line primary refractory disease) in dose escalation (1A) and expansion (1B; LBCL only) cohorts. Following leukapheresis and lymphodepletion, patients received dose level (DL) 1, 2, or 3 of KITE-753 (3.0×10⁴, 1.0×10⁵, or 2.0×10⁵ CAR T cells/kg, respectively) or KITE-363 (0.5×10⁶, 1×10⁶, or 2×10⁶ CAR T cells/kg, respectively). Primary endpoints were incidence of dose-limiting toxicities (DLTs; Phase 1A) and investigator-assessed objective response rate (ORR; per Lugano; Phase 1B).

About KITE-753 and KITE-363

KITE-753 and KITE-363 are investigational, bicistronic autologous CAR T-cell therapies engineered to overcome tumor antigen heterogeneity and prevent relapse. The KITE DuoCore™ construct uniquely combines anti-CD19 and anti-CD20 targeting with dual co-stimulation (CD28 and 4-1BB). KITE-753 is an enhanced KITE DuoCore™ CAR T utilizing a novel manufacturing process, aiming to preserve T-cell fitness. Additionally, KITE-363 is being investigated for refractory autoimmune conditions.

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 KITE-753 and KITE-363; uncertainties relating to regulatory applications and related filing and approval timelines, including pending or potential applications for indications currently under evaluation; the possibility that Gilead and Kite may make a strategic decision to discontinue development of these programs and, as a result, these programs may never be successfully commercialized for the indications currently under evaluation; and any assumptions underlying any of the foregoing. These and other risks are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended September 30, 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.

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 at www.kitepharma.com. Follow Kite on social media on X (@KitePharma) and LinkedIn.

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Ashleigh Koss, Media

public_affairs@gilead.com

Jacquie Ross, Investors

investor_relations@gilead.com

Source: Gilead Sciences, Inc.