On March 4, 2026 Citius Oncology, Inc. ("Citius Oncology") (Nasdaq: CTOR), an oncology-focused biopharmaceutical company and majority-owned subsidiary of Citius Pharmaceuticals, Inc. ("Citius Pharma") (Nasdaq: CTXR), reported positive topline safety and efficacy results from an investigator-initiated Phase 1 trial evaluating LYMPHIR (E7777, denileukin diftitox-cxdl) administered prior to commercial CD19-directed CAR-T therapy in patients with high-risk relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The trial was conducted by lead investigator, Dr. Veronika Bachanova, at the University of Minnesota and City of Hope. Full results were presented at the 2026 ASTCT & CIBMTR Tandem Meetings1.

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The Phase 1 trial was designed to augment the lymphodepletion regimen prior to CAR-T infusion through the administration of LYMPHIR to potentially improve the anti-tumor activity of CAR-T therapies. LYMPHIR, an engineered fusion toxin that preferentially binds to the IL-2 receptor expressed on regulatory T-cells (Tregs), is currently FDA-approved and commercially available for the treatment of relapsed or refractory cutaneous T-cell lymphoma (CTCL) after one prior systemic therapy.

"Enhancing Treg depletion prior to CAR-T infusion with LYMPHIR represents a promising immunomodulatory strategy in patients with high-risk DLBCL, and these Phase 1 data provide an encouraging signal of the potential to enhance current CAR-T regimens," said Dr. Myron Czuczman, Executive Vice President and Chief Medical Officer of Citius Oncology and Citius Pharma. "These positive data support our broader strategy of exploring LYMPHIR’s modulatory effect on Tregs in combination with other approved therapies to potentially enhance the body’s own immune system to fight cancerous tumors," he added.

Topline Results & Study Design

● All patients (n=14) completed treatment and proceeded to CAR-T infusion;

● LYMPHIR was well tolerated, with no dose-limiting toxicities observed;

● No Grade ≥3 LYMPHIR-related immune adverse events or infusion reactions were reported; and,

● Data demonstrated effective Treg depletion, and promising efficacy signals of enhanced standard lymphodepletion with the use of Treg-targeting LYMPHIR.

The Phase 1, open-label, dose-escalation study (NCT04855253), enrolled 14 patients with relapsed or refractory DLBCL exhibiting poor prognostic features, including double/triple hit genetics, primary refractory disease, and extranodal involvement. Participants received one dose of LYMPHIR (E7777) at 5, 7, or 9 µg/kg followed by low dose chemotherapy prior to standard commercial CD19-directed CAR-T cell therapy. All patients received an infusion of one of the following FDA-approved, commercially manufactured CAR-T products: axicabtagene ciloleucel (Yescarta; Kite Pharma/Gilead Sciences), lisocabtagene maraleucel (Breyanzi; Bristol Myers Squibb), or tisagenlecleucel (Kymriah; Novartis).

The use of LYMPHIR in this study was investigational and outside of its FDA-approved indication. The Phase 1 study was not designed or powered to evaluate clinical efficacy, and no conclusions can be drawn regarding comparative effectiveness or long-term outcomes.

Key Findings from the Phase 1 Trial

● Overall response rate (ORR) was 86% at one month, including 57% complete responses (CR) and 29% partial responses (PR);

● One-year progression-free survival (PFS) was 77% (95% CI: 43–92%);

● One-year overall survival (OS) was 84% (95% CI: 49–96%);

● A single LYMPHIR dose resulted in depletion of circulating Tregs in all but one patient;

○ Median reduction of 24 Tregs/µL (range 8–65);

○ Treg nadir was observed 24 hours post-LYMPHIR;

● LYMPHIR was well tolerated with no dose-limiting toxicities (DLTs) observed up to 9 µg/kg; and,

● Reported adverse events included manageable Grade 1–2 capillary leak syndrome, fever, and transient liver enzyme elevations; Grade 3 cytopenias were consistent with expected lymphodepletion. CAR-T related cytokine release syndrome (CRS) occurred in 43% of patients (all Grade 1/2), and immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 21% (primarily low grade).

"In this high-risk population, LYMPHIR showed a favorable safety profile and promising pharmacodynamic effects when administered prior to CAR-T therapies. This data sets the stage for a larger study to assess its potential to enhance CAR-T efficacy through longer duration of LYMPHIR use," said Dr. Veronika Bachanova, Principal Investigator and Professor of Medicine at the University of Minnesota.

Dr. Bachanova presented the topline data at the 2026 Tandem Meetings | ASTCT CIBMTR.

Title: E7777 to Enhance Regulatory T-Cell Depletion Prior to CAR-T for High-Risk LBCL

Presentation ID: 677608

Abstract ID: 296369

About Diffuse Large B-Cell Lymphoma (DLBCL)

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL), accounting for approximately 30%–40% of newly diagnosed cases in the United States. DLBCL is an aggressive and rapidly growing cancer of B lymphocytes, a type of white blood cell responsible for producing antibodies. While frontline chemoimmunotherapy regimens such as R-CHOP can be curative for many patients, up to 40% experience relapse or refractory disease. High-risk features are associated with poor outcomes and limited responses to standard therapies, including CAR-T cell therapy. Novel strategies that modulate the tumor microenvironment, such as transient regulatory T-cell depletion, are under investigation to improve treatment efficacy and long-term remission rates in this difficult-to-treat population.

About LYMPHIR (denileukin diftitox-cxdl)

LYMPHIR is a targeted immune therapy for relapsed or refractory cutaneous T-cell lymphoma (CTCL) indicated for use in Stage I-III disease after at least one prior systemic therapy. It is a recombinant fusion protein that combines the IL-2 receptor binding domain with diphtheria toxin (DT) fragments. The agent specifically binds to IL-2 receptors on the cell surface, causing diphtheria toxin fragments that have entered cells to inhibit protein synthesis. After uptake into the cell, the DT fragment is cleaved and the free DT fragments inhibit protein synthesis, resulting in cell death. Denileukin diftitox-cxdl demonstrated the ability to deplete immunosuppressive regulatory T lymphocytes (Tregs) and antitumor activity through a direct cytocidal action on IL-2R-expressing tumors.

In 2021, denileukin diftitox received regulatory approval in Japan for the treatment of relapsed or refractory CTCL and peripheral T-cell lymphoma (PTCL). Subsequently, in 2021, Citius acquired an exclusive license with rights to develop and commercialize denileukin diftitox in all markets except for India, Japan and certain parts of Asia. LYMPHIR (denileukin diftitox-cxdl) was approved by the FDA and subsequently launched in the U.S. in December 2025.

(Press release, Citius Pharmaceuticals, MAR 4, 2026, View Source [SID1234663244])