Citius Pharmaceuticals, Inc. and Citius Oncology, Inc. Announce Promising Preliminary Results of an Investigator-Initiated Phase I Clinical Trial of Pembrolizumab (KEYTRUDA ) and LYMPHIR in Cancer Patients with Recurrent

Citius Pharmaceuticals, Inc. and Citius Oncology,

Promising Preliminary Results of an Investigator-Initiated Phase I

Clinical Trial of Pembrolizumab (KEYTRUDA )

in Cancer Patients with Recurrent Solid Tumors

Study, in patients with solid tumors focusing

on gynecological malignant tumors such as ovarian, endometrial, and cervical, nearing completion with three remaining subjects to be enrolled

27% Objective Response Rate (ORR)

33% Clinical Benefit Rate (CBR) with a median

Progression Free Survival (PFS) of 57 weeks

Chemotherapy-free immunomodulatory regimen well-tolerated

with no documented serious immune-related adverse events

CRANFORD, N.J., November 11, 2024 -- Citius

Pharmaceuticals, Inc. ("Citius Pharma" or the "Company") (Nasdaq: CTXR) and Citius Oncology, Inc. ("Citius Oncology")

(Nasdaq: CTOR), today announced promising preliminary results from an ongoing investigator-initiated Phase I clinical trial evaluating

the safety and efficacy of a combined regimen of pembrolizumab and LYMPHIR (denileukin diftitox-cxdl or E7777) in patients with

recurrent solid tumors. The data was summarized in a poster presentation titled "T-regulatory Cell Depletion with E7777 (denileukin

diftitox-xcdl) Combined with Pembrolizumab in patients with recurrent solid tumors: Phase I trial" presented at the Society for

Immunotherapy of Cancer (SITC) 2024 Annual Meeting held November 8-10, 2024 (Abstract 614).

The trial is being conducted by Haider Mahdi,

M.D., Assistant Professor, Department of Obstetrics, Gynecology & Reproductive Sciences, at the University of Pittsburgh. The study

aims to identify an optimal dose for future trials and explore the impact of a treatment regimen combining pembrolizumab and LYMPHIR on

the tumor immune microenvironment.

"We have seen promising results in patients

with heavily pre-treated recurrent or metastatic gynecologic tumors and will enroll three additional patients before completing the Phase

I portion of this study," said Mahdi. "We will further investigate in patients with gynecologic tumors and those with other

solid tumor histologies. We want to explore the impact of this therapy on Tregs, host immune-effector cells and the tumor microenvironment."

"The preliminary results from this Phase

I trial of patients with recurrent gynecological cancers are highly encouraging. This novel chemo-free immunomodulatory combination regimen

has been well tolerated, including at the highest dosage. This efficacy data strongly suggests that LYMPHIR may have the ability to improve

and prolong the anti-tumor activity of immune checkpoint inhibitors. To date, this unique regimen has not been associated with significant

immune-related adverse events. Moreover, of the 15 evaluable patients, one third experienced a clinical benefit with a median of more

than 12 months of progression free survival," stated Dr. Myron Czuczman, Chief Medical Officer of Citius Pharmaceuticals and Citius

"There is reason to be optimistic about the

potential of LYMPHIR to boost a patient's response to pembrolizumab by temporarily depleting Tregs that modulate the tumor microenvironment,

without triggering an autoimmune response from the patient's body. We believe the positive signals from this data support expanding

the research in a Phase II study to further evaluate the combination's benefits across a broader range of solid tumor types,"

PD-1 inhibitors such as pembrolizumab are a type

of immune checkpoint inhibitor that works by blocking the PD-1 protein on T cells, enabling the immune system to recognize and attack

cancer cells. Pembrolizumab, developed by Merck and sold under the brand name KEYTRUDA , is the leading PD-1 inhibitor

and world's most prescribed drug, generating $25 billion in sales in 2023.

The results of this chemotherapy-free regimen

combining two immuno-modulator agents, pembrolizumab (anti-PD-1) and LYMPHIR (transient Treg depletion) demonstrated:

The trial enrolled 21 patients with recurrent

or metastatic solid tumors. Among the evaluable participants, four patients achieved a partial response, and one patient demonstrated

durable stable disease lasting over six months. The combination regimen was generally well tolerated, with most adverse events related

to the patients' underlying disease. Importantly, no significant immune-related adverse events were observed, and only one case of dose-limiting

toxicity (capillary leak syndrome) was reported at the highest dose level (12 mcg/kg).

Table 1: Efficacy Data

Table 2: Safety Data

The Phase I trial is an open-label study designed

to evaluate the safety and preliminary efficacy of pembrolizumab, an anti PD-1 inhibitor, in combination with LYMPHIR in patients with

recurrent or metastatic solid tumors. The trial employs a dose-escalation approach, with LYMPHIR administered in four dose levels (3,

6, 9, and 12 mcg/kg) in combination with pembrolizumab (200 mg) on a 21-day cycle for eight cycles. Following the combination regimen,

patients receive pembrolizumab monotherapy as maintenance therapy. The study utilizes the Time-to-Event Continual Reassessment Method

(TITE-CRM) to assess dose-limiting toxicities (DLTs) and determine the recommended Phase II dose (RP2D).

Key inclusion criteria include measurable disease,

ECOG performance status of 0-1, and adequate organ function. Patients with recurrent or metastatic solid tumors who have received at least

one prior line of therapy were eligible for enrollment.

The trial enrolled patients with a variety of

recurrent or metastatic solid tumors, including ovarian, endometrial, and cervical cancers.

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 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 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. LYMPHIR was approved by the FDA in August 2024.

LYMPHIR is an IL2-receptor-directed cytotoxin

indicated for the treatment of adult patients with r/r Stage I-III cutaneous T-cell lymphoma (CTCL) after at least one prior systemic

IMPORTANT SAFETY INFORMATION

BOXED WARNING: CAPILLARY LEAK SYNDROME

Capillary leak syndrome (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.

WARNINGS AND PRECAUTIONS

Capillary Leak Syndrome

LYMPHIR can cause capillary leak syndrome (CLS),

including life-threatening or fatal reactions. CLS was defined in the clinical trials as the occurrence of at least 2 of the following

symptoms at any time during LYMPHIR therapy: hypotension, edema, and serum albumin <3 g/dL. These symptoms were not required to occur

simultaneously to be characterized as capillary leak syndrome.

As defined, CLS occurred in 27% of patients in

the pooled population across 3 clinical trials, including 8% with Grade 3. There was one (0.8%) fatal occurrence of CLS. Of the patients

with CLS, 22% had recurrence. The majority of CLS events (81%) occurred within the first 2 cycles of treatment. The median time to onset

from Cycle 1, Day 1 was 6.5 days (range: 1 to 77), the median duration of CLS was 14 days (range: 2 to 40), and 75% of patients had resolution.

The most common symptoms included edema, hypoalbuminemia, and hypotension. Pleural effusion, pericardial effusion, and dehydration also

Regularly assess patients for weight gain, new

onset or worsening of edema, dyspnea, and hypotension (including orthostatic changes). Monitor serum albumin levels prior to the initiation

of each cycle of therapy and more often as clinically indicated.

Withhold, reduce dose, or permanently discontinue

based on severity. If LYMPHIR is withheld, resume LYMPHIR following resolution of CLS and when serum albumin is greater than or equal

LYMPHIR can cause serious visual impairment, including

changes in visual acuity and color vision. In the pooled population across 3 clinical trials, visual impairment occurred in 9%, with Grade

1 in 8% and Grade 2 in 1%. The most commonly reported symptom was blurred vision. Of the patients with visual impairment, 67% had resolution

of their visual impairment.