Citius Pharmaceuticals Receives FDA Approval for LYMPHIR (denileukin diftitox-cxdl) Immunotherapy for the Treatment of Adults with Relapsed or Refractory Cutaneous T-Cell Lymphoma Only systemic treatment for relapsed or

Citius Pharmaceuticals

Receives FDA Approval for LYMPHIR (denileukin diftitox-cxdl) Immunotherapy for the Treatment of Adults with Relapsed or Refractory

Cutaneous T-Cell Lymphoma

CRANFORD, N.J., August 8, 2024 -

Citius Pharmaceuticals, Inc. (NASDAQ: CTXR) ("Citius", "Citius Pharma"), announced today that the U.S. Food and

Drug Administration (FDA) has approved LYMPHIR (denileukin diftitox-cxdl), a novel immunotherapy for the treatment of r/r cutaneous

T-cell lymphoma (CTCL) after at least one prior systemic therapy. LYMPHIR is the only CTCL therapy that targets the interleukin-2 (IL-2)

receptor found on malignant T-cells and Tregs. This is the first indication for LYMPHIR and the first FDA-approved product for Citius

"LYMPHIR offers new hope for patients suffering

from cutaneous T-cell lymphoma, a rare and chronic cancer characterized by debilitating skin lesions and severe itching. This approval

is a significant milestone for CTCL patients. The introduction of LYMPHIR, with its potential to rapidly reduce skin disease and control

symptomatic itching without cumulative toxicity, is expected to expand the CTCL treatment landscape and grow the overall market, currently

estimated to be $300-$400 million," stated Leonard Mazur, Chief Executive Officer of Citius Pharmaceuticals.

"LYMPHIR, with an initial indication in

the treatment of CTCL, is the first of our pipeline candidates to receive FDA approval. Citius is dedicated to working closely with healthcare

providers to ensure that all r/r CTCL patients have timely access to this important new therapy. We are preparing to launch LYMPHIR in

the U.S. market within the next five months," added Mazur.

"We are grateful to the clinicians, patients,

and researchers who contributed to the development of LYMPHIR. We believe LYMPHIR's unique IL-2 receptor-targeted treatment, which

kills tumor cells directly, and concurrently depletes host Tregs in order to boost the body's immune response, is an important differentiator

and offers clinically meaningful benefits to a significant percentage of r/r patients. As the only IL-2 receptor-targeted immunotherapy

for CTCL, LYMPHIR provides a novel and non-cross-resistant treatment option without cumulative toxicity for Stage I-III r/r patients for

whom symptomatic skin involvement interferes with their daily quality of life. LYMPHIR's median time-to-response of only 1.4 months

(min, max: 0.7, 5.6) offers many patients rapid skin relief," added Dr. Myron Czuczman, Chief Medical Officer of Citius Pharmaceuticals.

CTCL is a rare and often debilitating chronic

non-Hodgkin lymphoma that primarily affects the skin. Approximately 2,500-3,000 patients are diagnosed each year with an estimated 40,000

living with the disease. Patients with r/r CTCL have limited treatment options. No universally defined single treatment is used to treat

these patients with incurable cancer. Patients typically cycle through several skin-directed therapies before the cancer becomes resistant

and/or progressive at which point systemic agents are needed to achieve effective disease control. Reducing and controlling skin plaques

and itching without cumulative toxicity is a primary goal of CTCL treatment. Systemic medicines are prescribed until the disease progresses

again or when dose-limiting toxicity occurs, after which HCPs prescribe a different systemic medicine. LYMPHIR provides another viable

option in the treatment landscape with unique benefits to patients. It offers a novel mechanism of action designed to target and eradicate

malignant T-cells while preserving healthy tissue. It is the only treatment option that targets the IL-2 receptors found in T-cell lymphomas

"As a treating oncologist, I have seen

the profound negative effect on the quality of life in patients with r/r CTCL. Given the long-term nature of the disease, pruritus,

ulceration of the tumors, and secondary pyogenic skin infection, it is vital to get this skin involvement under control. LYMPHIR is

the first therapeutic option in many years to offer hope of reducing skin disease, bringing us one step closer to filling the need

for CTCL patients, particularly those that are not able to complete or continue prior therapies," stated Dr. Francine Foss,

Professor of Hematology, and Director of the Multidisciplinary T-cell Lymphoma Program at Yale Cancer Center, New

The approval of LYMPHIR is based on results from

the Phase 3 Pivotal Study 302 (NCT01871727) of CTCL patients who had previously received at least one systemic treatment. Actual study

patients received a median of 4 (min, max: 1, 18) prior anticancer therapies. The primary efficacy population includes 69 patients with

stage I-III CTCL who were treated with denileukin diftitox-cxdl (9 g /kg/day). The primary efficacy outcome measure was Objective

Response Rate (ORR), as assessed by an Independent Review Committee (IRC). The ORR was 36.2%, (95% CI: 25.0-48.7), with 8.7% achieving

a Complete Response (CR).

The median time to response was rapid at 1.41

months, with the majority of responders (~70%) seeing results after 1-2 cycles of treatment. Duration of response was at least 6

months for 52.0% of the patients. 84.4% (54/64) of skin evaluable subjects had a decrease in skin tumor burden and 12.5% (8/64) saw complete

clearing of skin disease. Pruritis was evaluated as an exploratory endpoint with 31.7% of patients demonstrating clinically significant

pruritus improvement. Importantly, no cumulative toxicity was observed in patients receiving LYMPHIR.

LYMPHIR's safety profile is consistent with

the known safety profile for denileukin diftitox. Across three studies of 119 CTCL patients receiving 9 g dose of denileukin diftitox,

the most common ( 20%) adverse reactions, including laboratory abnormalities, were increased transaminases, albumin decreased, nausea,

edema, hemoglobin decreased, fatigue, musculoskeletal pain, rash, chills, constipation, pyrexia, and capillary leak syndrome (CLS).

The U.S. Prescribing Information for LYMPHIR

contains a boxed warning that CLS, including life-threatening or fatal reactions, can occur in patients receiving LYMPHIR. Monitor patients

for signs and symptoms of CLS during treatment. Withhold LYMPHIR until CLS resolves, or permanently discontinue based on severity. Additional

"Important Safety Information" is available below and LYMPHIR's full prescribing information may be accessed here in

This approval includes a postmarketing requirement

from the FDA to characterize the risk of visual impairment in CTCL patients treated with LYMPHIR. Citius is committed to the safety

of patients and will continue to monitor all safety data as it emerges.

The efficacy of LYMPHIR was evaluated in Study

302, an open-label, single-arm, multicenter trial in patients with r/r Stage I to IV CTCL. Eligible patients were required to have expression

of CD25 on 20% of biopsied malignant cells by immunohistochemistry. The study excluded patients with significant cardiac disease

or uncontrolled infections. Patients received LYMPHIR at 9 mcg/kg as an intravenous infusion daily from Day 1 through Day 5 of each 21-day

cycle. Patients continued to receive LYMPHIR until disease progression or unacceptable toxicity.

The efficacy population includes 69 patients with

r/r Stage I to III CTCL. Of the 69 patients, the median age was 64 years (range: 28 to 87 years), 65% were male, 73% were White, 19% Black

or African American, 1% Asian, and 14% Hispanic or Latino. The CTCL disease stage was IA in 7%, IB in 23%, IIA in 13%, IIB in 35%, IIIA

in 12%, and IIIB in 10%. The median number of prior therapies was 4 (range: 1 to 18), including both skin-directed and systemic therapies.

Prior therapies included photodynamic therapy (56%), total skin electron beam therapy (42%), systemic retinoids (49%), methotrexate/pralatrexate

(49%), histone deacetylase inhibitor (35%), brentuximab vedotin (26%) and mogamulizumab (12%).

Efficacy was established based on ORR, according

to ISCL/EORTC Global Response Score (GRS) per Independent Review Committee (Olsen 2011). Efficacy results are shown in the table below.

Table: Efficacy Results of Study 302

Median time to response was 1.4 months (range: 0.7 to 5.6 months).

Among responders, the median follow-up for duration of response was

6.5 months (range: 3.5+, 23.5+ months).

About LYMPHIR (denileukin diftitox-cxdl)

LYMPHIR is a targeted immune therapy for r/r (R/R)

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 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

In 2021, denileukin diftitox received regulatory

approval in Japan for the treatment of CTCL and PTCL. Subsequently, in 2021, Citius acquired an exclusive license with rights to develop

and commercialize LYMPHIR in all markets except for Japan and certain parts of Asia.

About Cutaneous T-cell Lymphoma

Cutaneous T-cell lymphoma is a type of cutaneous

non-Hodgkin lymphoma (NHL) that comes in a variety of forms and is the most common type of cutaneous lymphoma. In CTCL, T-cells, a type

of lymphocyte that plays a role in the immune system, become cancerous and develop into skin lesions, leading to a decrease in the quality

of life of patients with this disease due to severe pain and pruritus. Mycosis Fungoides (MF) and S zary Syndrome (SS) comprise

the majority of CTCL cases. Depending on the type of CTCL, the disease may progress slowly and can take anywhere from several years to

upwards of ten to potentially reach tumor stage. However, once the disease reaches this stage, the cancer is highly malignant and can

spread to the lymph nodes and internal organs, resulting in a poor prognosis. Given the duration of the disease, patients typically cycle

through multiple agents to control disease progression. CTCL affects men twice as often as women and is typically first diagnosed in patients

between the ages of 50 and 60 years of age. Other than allogeneic stem cell transplantation, for which only a small fraction of patients