Preclinical study demonstrates that adding
LYMPHIR to anti-PD-1 treatment augments anti-tumor activity and
improves overall survival compared to monotherapy alone by
transiently depleting Tregs in the tumor microenvironment
CRANFORD, N.J., Oct. 31,
2023 /PRNewswire/ -- Citius Pharmaceuticals, Inc.
("Citius" or the "Company") (Nasdaq: CTXR) today announced that
preclinical research on LYMPHIR ("denileukin diftitox" or "E7777")
was published today in Frontiers in Immunology1,
a leading peer-reviewed journal in the immunology field. The
article reported positive results from a preclinical study
that showed that denileukin diftitox in combination with an
anti-PD-1 checkpoint inhibitor was more effective in the treatment
of solid tumors (liver and colon) than either therapy alone. Data
from this study contributed to the design and dosing regimen of two
Phase 1 investigator-initiated studies currently underway at the
University of Pittsburgh and the
University of Minnesota.
"We are excited to share the published results of this important
animal study with the broader scientific community. The compelling
results of this study showed that LYMPHIR administered in
combination with an anti-PD-1 inhibitor, either sequentially or
concurrently, led to significantly increased anti-tumor activity
and prolonged survival compared to either treatment alone. Based on
the strong signal of the study, two ongoing Phase 1 trials were
initiated by investigators at leading cancer research institutions.
We intend to share interim data from these studies when it becomes
available. Importantly, the results of the preclinical study
highlight LYMPHIR's additional potential as a combination therapy
in the treatment of solid tumors, which may allow Citius to explore
substantially larger market opportunities for LYMPHIR in the
future," stated Leonard Mazur,
Chairman and CEO of Citius.
In recent years, one of the most important advances in solid
tumor management has been the use of anti-PD-1/PDL1 antibody
therapy. However, the effectiveness of treatment has varied,
with not all tumors or patients responding with equivalent
sensitivity to the treatment. The primary role of Treg-targeted
cancer immunotherapy is to transiently deplete Treg cells. It is
believed that regulatory T cells (Tregs) in the tumor
microenvironment play an important role in patient resistance to
anti-PD-1 immunotherapy. Targeting Tregs with LYMPHIR during
treatment with anti-PD1/PDL1 checkpoint inhibitors may change the
dynamics of the immune microenvironment, including anti-PD-1
sensitivity, in situations where Tregs are prominent. Consequently,
the innovative preclinical study evaluated whether adding LYMPHIR
improved the efficacy of anti-PD-1 antibody therapy. Syngeneic
murine solid tumor models in colon cancer CT-26 and liver cancer
H22 were used to conduct the study.
"This landmark study demonstrated that an increase in T-reg cell
infiltration induced by anti-PD-1 treatment can be counterbalanced
by their depletion by LYMPHIR, suggesting potential synergistic
activity in a solid tumor model," stated Dr. Myron Czuczman, Chief Medical Officer of Citius.
"We look forward to future results of ongoing human studies
evaluating the potential benefit of Treg depletion by LYMPHIR in
combination with checkpoint inhibitors and other immunomodulatory
agents."
Key Study Findings
- Targeting Tregs using LYMPHIR combined with anti-PD-1 (either
sequentially or concurrently) demonstrated significant anti-tumor
activity, and consistently targeted and transiently depleted Tregs
in the tumor microenvironment
- Combination treatment was more effective than monotherapy with
either drug alone
- Combination therapy was well-tolerated and significantly
enhanced long-term survival in solid tumor-bearing animals
- Mahdi, H. Woodall-Jappe, M., Singh, P., Czuczman, S., Targeting
Regulatory T cells by E7777 enhances CD8 T-cell-mediated anti-tumor
activity and extends survival benefit of anti-PD-1 in solid tumor
models. Frontiers in Immunology. (Published online ahead of
print, 2023 October 27).
About the Investigator Initiated Trials
A Phase 1 Study is underway at the University of Pittsburgh Medical Center (UPMC),
Hillman Cancer Center. This study is an open label, Phase
1/1b study to investigate the safety
and efficacy of a combined regimen of pembrolizumab with
T-regulatory cell depletion via denileukin diftitox in patients
diagnosed with recurrent or metastatic solid tumors. (Title: The
efficacy of T-regulatory cell depletion with E7777 combined with
immune checkpoint inhibitor, pembrolizumab, in recurrent or
metastatic solid tumors: Phase I/II Study. NCT05200559). The study
consists of two parts. Part I is a dose escalation study of four
cohorts (3,6,9,12 mcg of LYMPHIR) and is expected to enroll 18-30
patients. Part II is a dose expansion study of approximately 40
patients to evaluate the safety and tolerability of the recommended
combination dose of LYMPHIR and pembrolizumab (to include ovarian
cancer and MSI-H cancer cohorts). The study will also investigate
the alteration of the immune microenvironment within tumors and
peripheral blood. Secondary endpoints include the objective
response (complete response plus partial response),
progression-free survival, and overall survival.
A Phase 1 trial has also been initiated at the University of Minnesota, Masonic Cancer Center.
This study is a single-arm open-label trial which has an estimated
enrollment of 20 participants who will be administered denileukin
diftitox prior to receiving Chimeric Antigen Receptor (CAR-T)
therapies. The Phase 1 study consists of two components: dose
finding to establish a maximum tolerated dose (MTD) of denileukin
diftitox in combination with CAR-T therapies and an extension
component to provide an estimate of efficacy at that MTD. (Title:
Phase I/II Trial Using E7777 to Enhance Regulatory T-Cell Depletion
Prior to CAR-T Therapy for Relapsed/Refractory B-Cell Lymphoma
(DLBCL) NCT04855253).
About Citius Pharmaceuticals, Inc.
Citius Pharma is a late-stage biopharmaceutical company
dedicated to the development and commercialization of
first-in-class critical care products, with a focus on oncology,
anti-infectives in adjunct cancer care, unique prescription
products, and stem cell therapies. The Company's diversified
pipeline includes two late-stage product candidates. Mino-Lok®, an
antibiotic lock solution for the treatment of patients with
catheter-related bloodstream infections, is enrolling patients in a
Phase 3 Pivotal superiority trial and was granted Fast Track
designation by the FDA. Citius Pharma is preparing to resubmit the
Biologics License Application for LYMPHIR, a novel IL-2R
immunotherapy for an initial indication in CTCL, in early 2024, and
announced plans to form Citius Oncology, a standalone publicly
traded company with LYMPHIR as its primary asset. LYMPHIR received
orphan drug designation by the FDA for the treatment of CTCL and
PTCL. In addition, at the end of March
2023, Citius Pharma completed enrollment in its Phase
2b trial of CITI-002 (Halo-Lido), a
topical formulation for the relief of hemorrhoids. For more
information, please visit www.citiuspharma.com.
Forward-Looking Statements
This press release may contain "forward-looking statements"
within the meaning of Section 27A of the Securities Act of 1933 and
Section 21E of the Securities Exchange Act of 1934. Such statements
are made based on our expectations and beliefs concerning future
events impacting Citius. You can identify these statements by the
fact that they use words such as "will," "anticipate," "estimate,"
"expect," "plan," "should," and "may" and other words and terms of
similar meaning or use of future dates. Forward-looking statements
are based on management's current expectations and are subject to
risks and uncertainties that could negatively affect our business,
operating results, financial condition and stock price.
Factors that could cause actual results to differ materially from
those currently anticipated are: risks relating to the results of
research and development activities, including those from existing
and new pipeline assets; our need for substantial additional funds;
our ability to commercialize our products if approved by the FDA;
our dependence on third-party suppliers; our ability to procure
cGMP commercial-scale supply; the estimated markets for our product
candidates and the acceptance thereof by any market; the ability of
our product candidates to impact the quality of life of our target
patient populations; our ability to obtain, perform under and
maintain financing and strategic agreements and relationships;
uncertainties relating to preclinical and clinical testing; the
early stage of products under development; market and other
conditions; our ability to attract, integrate, and retain key
personnel; risks related to our growth strategy; patent and
intellectual property matters; our ability to identify, acquire,
close and integrate product candidates and companies successfully
and on a timely basis; government regulation; competition; as well
as other risks described in our SEC filings. These risks have been
and may be further impacted by Covid-19 and could be impacted by
any future public health risks. Accordingly, these forward-looking
statements do not constitute guarantees of future performance, and
you are cautioned not to place undue reliance on these
forward-looking statements. Risks regarding our business are
described in detail in our Securities and Exchange Commission
("SEC") filings which are available on the SEC's website at
www.sec.gov, including in our Annual Report on Form 10-K for the
year ended September 30, 2022, filed
with the SEC on December 22, 2022,
and updated by our subsequent filings with the Securities and
Exchange Commission. These forward-looking statements speak only as
of the date hereof, and we expressly disclaim any obligation or
undertaking to release publicly any updates or revisions to any
forward-looking statements contained herein to reflect any change
in our expectations or any changes in events, conditions or
circumstances on which any such statement is based, except as
required by law.
Investor Contact:
Ilanit Allen
ir@citiuspharma.com
908-967-6677 x113
Media Contact:
STiR-communications
Greg Salsburg
Greg@STiR-communications.com
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