UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 10-K
☒ANNUAL REPORT PURSUANT TO SECTION 13
OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the Fiscal Year Ended September 30, 2025
☐TRANSITION REPORT PURSUANT TO SECTION
13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
Commission File Number 001-38174
Citius Pharmaceuticals, Inc.
(Exact name of Registrant as specified in its
Charter)
11 Commerce Drive, First Floor, Cranford,
NJ07016
(Address of principal executive offices) (Zip
Code)
(908)967-6677
(Registrant’s telephone number, including
area code)
Securities registered pursuant to Section 12(b)
of the Exchange Act:
Title of Each Class Trading Symbol(s) Name of Each Exchange on Which Registered
Common Stock, par value $0.001 per share CTXR The NASDAQ Capital Market
Indicate by check mark if the registrant is a
well-known seasoned issuer, as defined in Rule 405 of the Securities Act. ☐ Yes ☒ No
Indicate by check mark if the registrant is not
required to file reports pursuant to Section 13 or Section 15(d) of the Act. ☐ Yes ☒ No
Indicate by check mark whether the registrant
(1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12
months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements
for the past 90 days. ☒ Yes ☐ No
Indicate by check mark whether the registrant
has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T during the preceding
12 months (or for such shorter period that the registrant was required to submit such files). ☒ Yes ☐ No
Indicate by check mark whether the registrant
is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth company.
See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,”
and “emerging growth company” in Rule 12b-2 of the Exchange Act.
Large accelerated filer ☐ Accelerated filer ☐
Non-accelerated filer ☒ Smaller reporting company ☒
Emerging growth company ☐
If an emerging growth company, indicate by check
mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting
standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Indicate by check mark whether the registrant
has filed a report on and attestation to its management’s assessment of the effectiveness of its internal control over financial
reporting under Section 404(b) of the Sarbanes-Oxley Act by the registered public accounting firm that prepared or issued its audit report.
☐
If securities are registered pursuant to Section
12(b) of the Act, indicate by check mark whether the financial statements of the registrant included in the filing reflect the correction
of an error to previously issued financial statements. ☐
Indicate by check mark whether any of those error
corrections are restatements that required a recovery analysis of incentive-based compensation received by any of the registrant’s
executive officers during the relevant recovery period pursuant to §240.10D-1(b). ☐
Indicate by check mark whether the registrant
is a shell company (as defined in Rule 12b-2 of the Exchange Act). ☐ Yes ☒ No
The aggregate market value of the voting and
non-voting common equity held by non-affiliates computed by reference to the price at which the common equity was last sold, or the average
bid and asked price of such common equity, as of the last business day of the registrant’s most recently completed second fiscal
quarter (March 31, 2025) was approximately $11,390,000.
Affiliates for the purpose of this item refers
to the issuer’s executive officers and directors and/or any persons or firms (excluding those brokerage firms and/or clearing houses
and/or depository companies holding issuer’s securities as record holders only for their respective clients’ beneficial interest)
owning 10% or more of the issuer’s common stock, both of record and beneficially.
Indicate the number of shares outstanding of
each of the registrant’s classes of common stock, as of the latest practicable date:
20,762,917 shares as of December 17, 2025, all
of one class of common stock, $0.001 par value.
DOCUMENTS INCORPORATED BY REFERENCE
Portions of the Company’s Proxy Statement
for the Annual Meeting of Stockholders expected to be filed in January 2026 are incorporated by reference in Part III of this Report.
Citius Pharmaceuticals, Inc.
FORM 10-K
September 30, 2025
TABLE OF CONTENTS
Page
PART I 1
Item 1. Business 1
Item 1A. Risk Factors 33
Item 1B. Unresolved Staff Comments 66
Item 1C. Cybersecurity 66
Item 2. Properties 66
Item 3. Legal Proceedings 66
Item 4. Mine Safety Disclosures 66
Item 6. [Reserved] 67
Item 7A. Quantitative and Qualitative Disclosures About Market Risk 76
Item 8. Financial Statements and Supplementary Data 76
Item 9A. Controls and Procedures 77
Item 9B. Other Information 77
Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections 77
PART III 78
Item 10. Directors, Executive Officers and Corporate Governance 78
Item 11. Executive Compensation 78
Item 14. Principal Accountant Fees and Services 78
Item 15. Exhibits and Financial Statement Schedules 79
Signatures 83
NOTES
In this annual report on Form 10-K, and unless
the context otherwise requires, the “Company,” “we,” “us” and “our” refer to Citius Pharmaceuticals,
Inc. and its wholly-owned subsidiaries Citius Pharmaceuticals, LLC and Leonard-Meron Biosciences, Inc., and its majority-owned subsidiaries,
Citius Oncology, Inc. (Nasdaq: CTOR) (“Citius Oncology”) and NoveCite, Inc., taken as a whole.
Mino-Lok® and LYMPHIRTM (denileukin
diftitox) are our registered trademarks. All other trade names, trademarks and service marks appearing in this annual report are the
property of their respective owners. We have assumed that the reader understands that all such terms are source-indicating. Accordingly,
such terms, when first mentioned in this report, appear with the trade name, trademark or service mark notice and then throughout the
remainder of this report without trade name, trademark or service mark notices for convenience only and should not be construed as being
used in a descriptive or generic sense.
FORWARD-LOOKING STATEMENTS
This Annual Report on Form 10-K contains “forward-looking
statements.” Forward-looking statements include, but are not limited to, statements that express our intentions, beliefs, expectations,
plans, strategies, predictions, or any other statements relating to our future activities or other future events or conditions. These
statements are based on current expectations, estimates and projections about our business based, in part, on assumptions made by management.
These statements are not guarantees of future performance and involve risks, uncertainties and assumptions that are difficult to predict.
Therefore, actual outcomes and results may, and are likely to, differ materially from what is expressed or forecasted in the forward-looking
statements due to numerous factors discussed from time to time in this report, including the risks described under Item 1A - “Risk
Factors,” and Item 7 - “Management’s Discussion and Analysis of Financial Condition and Results of Operations”
in this report and in other documents which we file with the Securities and Exchange Commission (“SEC”). In addition, such
statements could be affected by risks and uncertainties related to:
● our ongoing evaluation of strategic alternatives;
Any forward-looking statements speak only as
of the date on which they are made, and, except as may be required under applicable securities laws, we do not undertake any obligation
to update any forward-looking statement to reflect events or circumstances after the filing date of this report.
SUMMARY OF RISK FACTORS
An investment in our securities involves a high
degree of risk. You should carefully consider the risks summarized in Item 1A, “Risk Factors” included in this report. These
risks include, but are not limited to, the following:
PART I
Item 1. Business
Overview
Citius Pharmaceuticals, Inc., headquartered in
Cranford, New Jersey, is a 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 and unique prescription products. Our goal generally is to
achieve leading market positions by providing therapeutic products that address unmet medical needs yet have a lower development risk
than usually is associated with new chemical entities. New formulations of previously approved drugs with substantial existing safety
and efficacy data are a core focus. We seek to reduce development and clinical risks associated with drug development, yet still focus
on innovative applications. Our strategy centers on products that have intellectual property and regulatory exclusivity protection, while
providing competitive advantages over other existing therapeutic approaches.
In December 2025, we became a commercial company
with the launch of LYMPHIR by our majority owned subsidiary Citius Oncology. We also have late-stage product candidates in development.
Since its inception, the Company has devoted
substantially all of its efforts to business planning, acquiring our proprietary technology, research and development, recruiting management
and technical staff, and raising capital. We are developing three proprietary products Mino-Lok, an antibiotic lock solution used to
treat patients with catheter-related bloodstream infections by salvaging the infected catheter; Halo-Lido, a corticosteroid-lidocaine
topical formulation that is intended to provide anti-inflammatory and anesthetic relief to persons suffering from hemorrhoids; and NoveCite,
a mesenchymal stem cell therapy for the treatment of ARDS. Citius Oncology achieved the approval from the FDA for LYMPHIR, in-licensed
by Citius Pharma in September 2021 (now owned by Citius Oncology), an engineered IL-2 diphtheria toxin fusion protein, for the treatment
of patients with persistent or recurrent cutaneous T-cell lymphoma (“CTCL”). We believe these unique markets for our products
are large, growing, and underserved by the current prescription products or procedures.
We are subject to a number of risks common to
companies in the pharmaceutical industry including, but not limited to, risks related to the development by us or our competitors of
research and development stage products, market acceptance of our products that receive regulatory approval, competition from larger
companies, dependence on key personnel, dependence on key suppliers and strategic partners, the Company’s ability to obtain additional
financing and the Company’s compliance with governmental and other regulations.
The Company was founded as Citius Pharmaceuticals,
LLC, a Massachusetts limited liability company, on January 23, 2007. On September 12, 2014, Citius Pharmaceuticals, LLC entered into
a Share Exchange and Reorganization Agreement, with Citius Pharma (formerly Trail One, Inc.), a publicly traded company incorporated
under the laws of the State of Nevada. Citius Pharmaceuticals, LLC became a wholly-owned subsidiary of Citius Pharma. On March 30, 2016,
Citius Pharma acquired Leonard-Meron Biosciences, Inc. (“LMB”) as a wholly-owned subsidiary. LMB was a pharmaceutical company
focused on the development and commercialization of critical care products with a concentration on anti-infectives. On September 11,
2020, we formed NoveCite, Inc. (“NoveCite”), a Delaware corporation, of which we own 75% of the issued and outstanding capital
stock. NoveCite is focused on the development and commercialization of its proprietary mesenchymal stem cells for the treatment of acute
respiratory disease syndrome (“ARDS”).
Citius Oncology and the Merger
On August 23, 2021, we formed Citius Acquisition
Corp. (“SpinCo”) as a wholly-owned subsidiary in conjunction with the acquisition of LYMPHIR. SpinCo began operations in
April 2022, when Citius Pharma transferred the assets related to LYMPHIR to SpinCo, including the related license agreement with Eisai
Co., Ltd. (“Eisai”) and the related asset purchase agreement with Dr. Reddy’s Laboratories SA, a subsidiary of Dr.
Reddy’s Laboratories, Ltd. (collectively, “Dr. Reddy’s”).
1
On October 23, 2023, Citius Pharma and SpinCo
entered into an agreement and plan of merger and reorganization (the “Merger Agreement”) with TenX Keane Acquisition, a Cayman
Islands exempted company (“TenX”), and TenX Merger Sub Inc., a Delaware corporation and a wholly owned subsidiary of TenX
(“Merger Sub”). On August 12, 2024, pursuant to the terms and conditions of the Merger Agreement, Merger Sub merged with and
into SpinCo, with SpinCo surviving as a wholly owned subsidiary of TenX, which was subsequently renamed Citius Oncology Sub. Prior to
the closing of the Merger (the “Closing”), TenX migrated to and domesticated as a Delaware corporation in accordance with
Section 388 of the General Corporation Law of the State of Delaware and the Cayman Islands Companies Act (As Revised) (the “Domestication”).
As part of the Domestication, TenX changed its name to “Citius Oncology, Inc.” (Nasdaq: CTOR). Immediately after the closing
of the Merger, Citius Pharma owned approximately 92% of the outstanding shares of common stock of Citius Oncology. As of December 17,
2025, Citius Pharma owned approximately 77.9% of Citius Oncology (excluding pre-funded warrants to purchase up to 15,229,358 shares of
Citius Oncology common stock in a transaction that closed on December 10, 2025).
Since its inception, Citius Pharma has funded
and continues to fund Citius Oncology, and Citius Pharma and Citius Oncology are party to an amended and restated shared services agreement
(the “A&R Shared Services Agreement”), which governs certain management and scientific services that Citius Pharma provides
Citius Oncology.
LYMPHIRTM (denileukin diftitox-cdxl)
Overview
In September 2021, the Company announced that
it had entered into an asset purchase agreement with Dr. Reddy’s to acquire its exclusive license of E7777 (denileukin diftitox).
E7777, an engineered IL-2-diphtheria toxin fusion protein, is an improved formulation of oncology agent, ONTAK®, which was previously
approved by the FDA for the treatment of patients with persistent or recurrent CTCL. Dr. Reddy’s had previously exclusively licensed
E777 in select markets from Eisai and as part of the transaction, Eisai entered into a license agreement whereby Eisai assigned all of
its rights to E7777 to Citius Pharma. Citius Pharma renamed E7777 as I/ONTAK and also obtained the trade name LYMPHIR for the product.
Denileukin diftitox is referred to in this report as E7777, I/ONTAK or LYMPHIR, depending on the period of time and context that is being
discussed. In April 2022 LYMPHIR was assigned to Citius Oncology.
LYMPHIR is a recombinant DNA-derived fusion protein
designed to direct the cytocidal action of diphtheria toxin (DT) to cells which express the IL-2 receptor. After uptake into the cell,
the DT fragment is cleaved and the free DT fragments inhibit protein synthesis, resulting in cell death. Consequently, LYMPHIR’s
differentiated mechanism of action supports two therapeutic effects: (i) killing tumors by binding to IL-2 receptors to deliver diphtheria
toxin directly to the tumor cells, and (ii) depleting immunosuppressive regulatory T lymphocytes (Tregs) to enhance antitumor activity.
Phase 3 Trial (E7777-G000-302) Design
LYMPHIR is an improved formulation of oncology
agent, ONTAK®, which was previously approved by the FDA for the treatment of patients with persistent or recurrent CTCL. ONTAK was
marketed in the U.S. previously. The manufacturing formulation improvements were substantial enough that the FDA required a new clinical
study to be performed (Study E7777-G000-302). The safety profile of LYMPHIR from study E7777-G000-302 is comparable to Study 93-04-11/L4389-11,
which served as the basis for the full approval of ONTAK. Study E7777-G000-302, a global, multicenter, open-label single-arm pivotal
clinical trial for the treatment of patients with persistent or recurrent CTCL, commenced (first subject consented) in May 2013 and completed
(data cutoff for primary analysis) in December 2021. The study was sponsored by Eisai and was conducted at 17 sites in the United States
and three sites in Australia. Inclusion criteria for the study were to evaluate patients in advanced stage CTCL (Mycosis Fungoides or
Sézary Syndrome), who received at least one prior CTCL therapy. The objectives were met for Study E7777-G000-302, in both the
lead-in phase and the main phase. Overall, the primary and secondary endpoints of Study E7777-G000-302 demonstrate the tolerability and
clinical benefit of 9 μg/kg/day LYMPHIR for the treatment of adult patients with relapsed or refractory Stage I-III CTCL. No new
safety signals were identified compared to ONTAK.
2
The pivotal trial of E7777 was divided into two
phases, a lead-in phase with 21 subjects that evaluated dose finding, pharmacokinetics and immunogenicity, and assessed the Objective
Response Rate (the “ORR”). An ORR is defined as a greater than 50% reduction in tumor burden. Patients received a daily intravenous
infusion of denileukin diftitox from Day 1 through Day 5 of each 21-day cycle. In the lead-in phase, the main objectives were to determine
the maximum tolerated dose (MTD) of LYMPHIR and to select the dose of LYMPHIR to be used in the main phase (subjects were treated at
doses ranging from 6 to 15 μg/kg/day). The MTD was 12 μg/kg/day and, based on data of the lead-in phase, 9 μg/kg/day
was selected for the main phase of the study. The objectives of the main phase were to evaluate the efficacy and safety of LYMPHIR (at
the dose determined in the lead-in phase of 9 μg/kg/day).
The primary efficacy endpoint was tumor response
rate, i.e. ORR per the Independent Review Committee (IRC) assessment based on International Society for Cutaneous Lymphomas/ European
Organization for Research and Treatment of Cancer Global Response Score (GRS; Olsen, et al., 2011).
The secondary efficacy endpoints were:
● Duration of response (DOR) based on GRS;
● Time to response based on GRS;
● ORR assessed by investigator using GRS;
● Objective response assessed by IRC using Prince (Prince, et al., 2010);
● Duration of skin response; and
● Time to skin response.
Overall, there were 25 responders out of 69 subjects
in the Primary Efficacy Analysis Set (i.e., subjects with CTCL disease Stages I to III (9 μg/kg/day)) as assessed by the IRC, with
an ORR of 36.2% (95% CI: 25.0%, 48.7%), with 8.7% (6/69) achieving a Complete Response (CR) and 27.5% (19/69) achieving a Partial Response.
Among responders, the median follow-up for duration
of response was 6.5 months (range: 3.5+, 23.5+ months). Median time to response was 1.4 months (range: 0.7 to 5.6 months).
ORR (95% CI) by investigator was 42.3% (30.6%,
54.6%) (30 of 71 subjects), with 8.5% (6 subjects) achieving a CR. ORR (95% CI) by IRC assessment using the Prince (2010) criteria was
36.2% (25.0%, 48.7%) (25 of 69 subjects). Further, an ORR of 38.1% in the intent to treat population and 44.4% in the efficacy evaluable
populations were observed. The 2-sided, exact 95% CI of ORR was calculated using the Clopper-Pearson method. Per protocol, LYMPHIR demonstrated
clinical benefit if the lower bound of the 2-sided 95% exact CI of the ORR exceeded 25%.
Skin responses were the same as GRS objective
responses, for both IRC and investigator assessments. Responses were deep, reflected by the substantial decrease in skin tumor burden,
including 8 subjects with 100% clearance of skin lesions per IRC.
In the second and main phase of the pivotal trial,
70 patients were administered the 9 μg/kg/day rate for 5 consecutive days in 21-day cycles. The inclusion criteria were identical
to the lead-in phase.
Phase 3 Trial Efficacy & Safety Results
The efficacy population of the main phase included
69 patients with relapsed or refractory 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%).
3
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.
LYMPHIR
ORR (GRS)%a 36%
Complete Response 9%
Partial Response 27%
Duration of Response
Median (range), months 6.5 (3.0 +, 23.5 +)
Duration ≥ 6 months, n (%) 52%
Median Time to Response, months 1.4
(b) CI = confidence interval
Both the endpoints and objectives of Study E7777-G000-302
were met, while the statistical confidence interval (95% CI) resulted in a marginal shortfall (25% actual achievement vs. >25% from
the statistical plan). Throughout the initial BLA review period, the FDA accepted the Study E7777-G000-302 data which demonstrated both
tolerability and clinical benefit.
Overall, LYMPHIR was well-tolerated with the
use of pre-medications, close patient monitoring, and prompt initiation of supportive measures and drug management. There was no evidence
of cumulative toxicity and most patients experienced low grade 1 or 2 treatment emergent adverse events.
Serious adverse reactions occurred in 38% of
patients who received LYMPHIR. Serious adverse reactions in > 2% of patients included capillary leak syndrome (10%), infusion-related
reaction (9%), sepsis (7%), skin infection (2.9%), pyrexia (2.9%), and rash (2.9%). There were no Grade 5 adverse events in the Study
E7777-G000-302, Stage I-III Safety Set (which is the safety set FDA required for inclusion in the package insert/label).
4
Adverse Reactions (≥ 10%) in Patients with
Relapsed or Refractory Stage I-III CTCL Who Received
LYMPHIR in E7777-G000-302
LYMPHIR N = 69
Adverse Reaction All Grades (%) Grade 3 or 4 (%)
Gastrointestinal disorders
Constipation 12 0
General disorders and administration site conditions
Musculoskeletal and connective tissue disorders
Musculoskeletal paind 27 2.9
Arthralgiae 12 0
Nervous system disorders
Mental status changesg 13 0
Injury, poisoning and procedural complications
Infusion-related reaction 25 6
Skin and subcutaneous tissue disorders
Vascular disorders
Capillary leak syndrome 20 6
Metabolism and nutrition disorders
Decreased appetite 13 1.4
Eye disorders
Vision changesj 13 0
Investigations
Weight increased 13 0
Infections and infestations
Skin infection 13 1.4
Renal and urinary disorders
Renal insufficiencyl 12 2.9
Psychiatric disorders
5
(a) Includes fatigue, asthenia, and lethargy.
(c) Includes fever, pyrexia, tumor associated fever.
(f) Includes headache, migraine.
(i) Includes pruritis, itching.
(j) Includes vision blurred, photopsia, visual impairment.
Grade refers to the severity of the adverse reaction.
The Common Terminology Criteria for Adverse Events displays Grades 1 through 5 with unique clinical descriptions of severity for each
adverse reaction based on this general guideline:
6
● Grade 4 - Life-threatening consequences; urgent intervention indicated.
● Grade 5 - Death related to the adverse reaction.
Investigator Initiated Trials
We believe there is an opportunity in the field
of immuno-oncology and have undertaken two investigator-initiated trials to evaluate the potential safety and efficacy of LYMPHIR as
an immuno-oncology combination therapy.
A Phase 1 trial was initiated in June 2021 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 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 CART-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).
Preliminary results are anticipated in the first quarter of 2026.
A second Phase 1 Study was initiated in September
2022 at the University of Pittsburg Medical Center, 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 and denileukin diftitox in patients diagnosed
with recurrent or metastatic solid tumors in the second line setting. (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.
In November 2024, the Company announced promising
preliminary results of the Phase I Clinical Trial of Pembrolizumab (KEYTRUDA®) and LYMPHIRTM in cancer patients with recurrent
solid tumors conducted at the University of Pittsburg Hillman Cancer Center.
Preliminary Results
The results of this chemotherapy-free regimen
combining two immuno-modulator agents, pembrolizumab (anti-PD-1) and LYMPHIR (transient Treg depletion) demonstrated:
7
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
Value
Patients Enrolled 21
Patients Evaluable for Response 15
Partial Responses (PR) 4 (27%)
Stable Disease (≥ 6 months) 1
Clinical Benefit Rate (CBR) 33% (PR + SD ≥ 6 months)
Median Progression-Free Survival (PFS) 57 weeks (range: 30-96 weeks)
Table 2: Safety Data
Value
Dose-Limiting Toxicities (DLTs) 1 (Capillary Leak Syndrome at 12 mcg/kg)
Immune-Related Adverse Events (irAEs) None documented (≥ Grade 3)
Adverse Events (Grade ≥ 3) Most related to underlying disease
Regulatory Development
In the 1990s, denileukin diftitox was developed
at Boston University and the National Cancer Institute (“NCI”) in collaboration with Seragen, Inc.
In 1999, ONTAK® (denileukin diftitox) was
granted accelerated approval by the FDA for the treatment of persistent or recurrent CTCL. Ligand Pharmaceuticals, Inc. (“Ligand”)
acquired the marketing rights in that same year.
In 2006, Eisai acquired the commercial rights
to ONTAK from Ligand.
In 2008, the FDA granted full approval to ONTAK
for CTCL.
In 2011, a new formulation of denileukin diftitox
was developed under the code name E7777 in response to a post-marketing condition established by the FDA upon approval. As the FDA considered
this a new product, an Investigational New Drug Application (“IND”) was filed. As a part of ensuing discussions, the FDA
agreed to a development plan that included a single arm, open label study to confirm the safety and efficacy of E7777 and a chemistry,
manufacturing, and controls (“CMC”) development plan that demonstrates the new process results in a comparable drug product.
In 2011, the FDA Office of Orphan Products Development
granted E7777 orphan drug designation status for the treatment of Peripheral T-Cell Lymphoma (“PTCL”). In 2013, the FDA Office
of Orphan Products Development granted E7777 orphan drug designation status for the treatment of CTCL.
In 2013, the first patient was enrolled into
the lead-in phase of the pivotal study for the E7777 U.S. CTCL clinical trial.
In 2014, commercial sales of ONTAK were discontinued
when the product was voluntarily withdrawn from the market due to manufacturing issues at the contract manufacturer.
In 2015, the last patient enrolled exited the
lead-in phase of the E7777 U.S. CTCL clinical trial.
8
In March 2016, Dr. Reddy’s exclusively
licensed the global rights to E7777 from Eisai, other than the rights in countries retained by Eisai, which consists of Japan, China,
Korea, Taiwan, Hong Kong, Macau, Indonesia, Thailand, Malaysia, Brunei, Singapore, India, Pakistan, Sri Lanka, Philippines, Vietnam,
Myanmar, Cambodia, Laos, Afghanistan, Bangladesh, Bhutan, Nepal, Mongolia and Papua New Guinea. The license included an option on the
right to develop and market the product in India prior to FDA approval.
In June 2016, the first patient was enrolled
in the main phase of the Phase 3 U.S. CTCL clinical trial for E7777.
In March 2020, Eisai filed a New Drug Application
(“NDA”) for E7777 in Japan for both CTCL and PTCL, and in March 2021 received approvals in both indications.
In September 2021, Citius Pharma acquired the
marketing rights to E7777 in selected markets. Citius Pharma subsequently renamed E7777 as LYMPHIR.
In December 2021, patient
enrollment for the Phase 3 Pivotal study of LYMPHIR was completed.
In April 2022, we reported
that topline results from the Phase 3 trial were consistent with the prior formulation. Moreover, no new safety signals were identified.
In December 2022, a
Biologics License Application (“BLA”) for LYMPHIR was accepted for filing with the FDA and a PDUFA goal date was set for
July 28, 2023.
In July 2023, the FDA
issued a complete response letter (“CRL”) requiring us to incorporate enhanced product testing and additional controls agreed
to with the FDA during the market application review. There were no concerns relating to the safety and efficacy clinical data package
submitted with the BLA, or the proposed prescribing information.
In September 2023, we
announced that the FDA agreed with the plans to address the requirements outlined in the CRL, which guidance provided the Company with
a path for completing the necessary activities to support the resubmission of the BLA for LYMPHIR.
In February 2024, based on the feedback from
the FDA, Citius Pharma completed the CRL remediation activities and filed the resubmission.
In March 2024, Citius Pharma announced the acceptance
of the BLA by the FDA. The FDA assigned a PDUFA goal date of August 13, 2024 and approved LYMPHIR on August 8, 2024.
In August 2024, Citius Pharma announced that
the FDA had approved LYMPHIR. Citius Oncology launched LYMPHIR in December 2025.
Market Opportunity
CTCL’s are a heterogeneous subset of extranodal
non-Hodgkin lymphomas (“NHL”) of mature, skin-homing T-cells that are mainly localized to the skin. The most common types
of CTCL are mycosis fungoides (“MF”) and primary cutaneous CD30+ anaplastic large cell lymphoma (pcALCL), jointly representing
an estimated 80 to 85% of all CTCL. Sézary Syndrome (“SS”), a very rare subtype (~2 to 5% of CTCL) characterized by
diffuse inflammatory, often exfoliative, erythroderma and by leukemic and nodal involvement, displays a significant degree of clinical
and biological overlap with MF and has long been considered a clinical variant of MF, although recent evidence suggests that it may be
a separate entity. The rest is represented by extremely rare, generally more aggressive subtypes.
In light of the overlap between MF and SS, and
considering that many of the systemic therapy options for the two neoplasms are the same, some consider the treatment approach to MF
and SS as if they were a single disease entity (MF/SS). However, some of the drugs currently in use, or in development, for MF/SS appear
to be more effective in clearing different anatomical compartments (skin versus blood, for example) and therefore have differential efficacy
in MF and SS.
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Based on Surveillance Epidemiology and End Results
(SEER) data from 2001 to 2007, the estimated incidence rate of MF/SS in the U.S. is 0.5/100,000 or about 2,500 to 3,000 new cases per
year representing about 25% of all T-cell lymphomas. In total, the Company estimates that there are approximately 30,000 to 40,000 patients
living with CTCL in the U.S.
Based on internal estimates, the Company believes
the addressable U.S. market for LYMPHIR exceeds $400 million and may further expand with the introduction of a new therapeutic.
Mino-Lok®
Overview
Mino-Lok is a patented solution containing minocycline,
disodium ethylenediaminetetraacetic acid (edetate), and ethyl alcohol, all of which act synergistically to treat and salvage infected
central venous catheters (“CVCs”) in patients with catheter related bloodstream infections (“CRBSIs”). Mino-Lok
breaks down biofilm barriers formed by bacterial colonies, eradicates the bacteria, and provides anti-clotting properties to maintain
patency in CVCs.
The administration of Mino-Lok consists of filling
the lumen of the catheter with 0.8 ml to 2.0 ml of Mino-Lok solution. The catheter is then “locked”, meaning that the solution
remains in the catheter without flowing into the vein. The lock is maintained for a dwell-time of two hours while the catheter is not
in use. If the catheter has multiple lumens, all lumens may be locked with the Mino-Lok solution either simultaneously or sequentially.
If patients are receiving continuous infusion therapy, the catheters alternate between being locked with the Mino-Lok solution and delivering
therapy. The Mino-Lok therapy is two hours per day for at least five days, usually with two additional locks in the subsequent two weeks.
After locking the catheter for two hours, the Mino-Lok solution is aspirated, and the catheter is flushed with normal saline. At that
time, either the infusion will be continued, or will be locked with the standard-of-care lock solution until further use of the catheter
is required. In a clinical study conducted by MD Anderson Cancer Center (“MDACC”), there were no serum levels of either minocycline
or edetate detected in the sera of several patients who underwent daily catheter lock solution with minocycline and edetate (“M-EDTA”)
at the concentration level proposed in Mino-Lok treatment. Thus, it has been demonstrated that the amount of either minocycline or edetate
that leaks into the serum is very low or none at all.
Phase 2b Results
From April 2013 to July 2014, 30 patients with
CVC-related bloodstream infection were enrolled at MDACC in a prospective Phase 2b study. Patients received Mino-Lok therapy for two
hours once daily for a minimum of five days within the first week, followed by two additional locks within the next two weeks. Patients
were followed for one month post-lock therapy. Demographic information, clinical characteristics, laboratory data, therapy, as well as
adverse events and outcome were collected for each patient. Median age at diagnosis was 56 years (range: 21-73 years). In all patients,
prior to the use of lock therapy, systemic treatment with a culture-directed, first-line intravenous antibiotic was started. Microbiological
eradication was achieved at the end of therapy in all cases. None of the patients experienced any serious adverse event related to the
lock therapy.
The active arm, which is the Mino-Lok treated
group of patients, was then compared to 60 patients in a matched cohort that experienced removal and replacement of their CVCs within
the same contemporaneous timeframe. The patients were matched for cancer type, infecting organism, and level of neutropenia. All patients
were cancer patients and treated at MDACC. The efficacy of Mino-Lok therapy was 100% in salvaging CVCs, demonstrating equal effectiveness
to removing the infected CVC and replacing it with a new catheter.
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The main purpose of the study was to show that
Mino-Lok therapy was at least as effective as the removal and replacement of CVCs when CRBSIs are present, and that the safety was better,
that is, the complications of removing an infected catheter and replacing with a new one could be avoided. In addition to having a 100%
efficacy rate with all CVCs being salvaged, Mino-Lok therapy had no significant adverse events (“SAEs”), compared to an 18%
SAE rate in the matched cohort where patients had the infected CVCs removed and replaced with a fresh catheter. There were no overall
complication rates in the Mino-Lok arm group compared to 11 patients with events (18%) in the control group. These events included bacterial
relapse (5%) at four weeks post-intervention, and a number of complications associated with mechanical manipulation in the removal or
replacement procedure for the catheter (10%) or development of deep-seated infections such as septic thrombophlebitis and osteomyelitis
(8%). As footnoted, six patients had more than one complication in the control arm group.
Mino-Lok® Arm Control Arm
Parameter N (%) N (%)%
Cancer type
ICU Admission 4 (13 ) 4 (7 )
Mech.Ventilator 3 (10 ) 0 (0 )
Bacteremia
- Relapse 0 (0 ) 3 (5 )
Complications 0 (0 ) 8 (13 )
SAEs related R&R 0 (0 ) 6 (10 )
Overall Complication Rate 0 (0 )% 11 ** (18 )%
* 1 Polymicrobial patient had a Gram+ and a Gram- organism cultured
** 6 Patients had > 1 complication
Source: Dr. Issam Raad, Antimicrobial Agents
and Chemotherapy, June 2016, Vol. 60 No. 6, Page 3429
Phase 3 Trial
In November 2016, the Company initiated site
recruitment for Phase 3 clinical trials. From initiation through the first quarter of 2017, the Company received input from several sites
related to the control arm as being less than standard-of-care for some of the respective institutions. The Company worked closely with
the FDA with respect to the design of the Phase 3 trial and received feedback on August 17, 2017. The FDA stated that they recognized
that there is an unmet medical need in salvaging infected catheters and agreed that an open label, superiority design would address the
Company’s concerns and would be acceptable to meet the requirements of a new drug application. The Company amended the Phase 3
study design to remove the saline and heparin placebo control arm and to use an active control arm that conforms with today’s current
standard-of-care. Patient enrollment commenced in February 2018.
The Mino-Lok Phase 3 Trial was originally planned
to enroll 700 patients in 50 participating institutions, all located in the U.S. There were interim analyses at both the 50% and 75%
points of the trial as measured by the number of patients treated. In September 2019, the Company announced that the FDA agreed
to a new primary efficacy endpoint of “time to catheter failure” in comparing Mino-Lok to the antibiotic lock control arm.
This change in the trial design reduced the required patient sample size of the trial from 700 subjects to approximately 144 available
subjects to achieve the pre-specified 92 catheter failure events needed to conclude the trial. Additionally, the Company submitted a
response to the FDA that it would implement this change in the primary endpoint and expected it to result in less than 150 subjects needed
in its Phase 3 trial. The new primary endpoints require that the time to catheter failure be at least 38 days for Mino-Lok versus 21
days for the standard of care antibiotic locks.
In October 2019, the FDA agreed that the patient
sample size of approximately 144 patients was acceptable.
In October 2019, the Company announced that the
Phase 3 trial had reached the 40% completion triggering an interim futility analysis by the data monitoring committee (the “DMC”).
The DMC is an independent panel of experts that review progress regarding the safety and efficacy of drugs in clinical trials, and to
determine if the trial may be futile in achieving its endpoints or if the trial should be modified in any way.
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In December 2019, the DMC convened and recommended
that the trial continue with no changes because the analysis showed a positive outcome, as it met the prespecified interim futility analysis
criteria.
In May 2020, we announced that we are providing
free access to Mino-Lok for healthcare providers under an Expanded Access protocol to ease the burden associated with the COVID-19 pandemic.
Through the Expanded Access protocol, an infected central venous catheter can now be treated with Mino-Lok, potentially avoiding the
need for the removal and replacement procedure.
In June 2020, we announced that we had received
positive feedback from the FDA on our proposed catheter compatibility studies for Mino-Lok. The studies, if and when successfully completed,
should allow Mino-Lok to be labeled for use with all commercially available CVCs and peripherally inserted central catheters (PICCs)
on the U.S. market. We further assume that these studies will meet European and world standards. The ability to be labeled without restrictions
with respect to catheter type would allow Mino-Lok unrestricted access to the full U.S. and world markets for an effective antibiotic
lock therapy for central line associated blood stream infections (“CLABSIs”).
In September 2020, we announced that another
DMC meeting was held to review the data being generated and analyzed in the Mino-Lok Phase 3 trial based on progress to date, and to
make recommendations to us as to any action that may be necessary regarding the study. After reviewing these data, the DMC members stated
that they did not find any safety signals; and they also recommended continuing the trial without any modifications. The DMC further
conducted an ad hoc meeting and agreed with the Company that a 75% interim analysis be conducted as planned in which superior
efficacy is evaluated. The 75% interim analysis was subsequently changed to a 65% interim analysis by the Company.
In September 2020, the Company announced that
the three registration batches for all components of Mino Lok were manufactured and that clinical sites were resupplied with registration
product.
In November 2020, the Company announced that
the three components of Mino-Lok, minocycline, disodium edetate (“EDTA”), and ethanol, were superior to EDTA and ethanol
in their ability to eradicate resistant staphylococcal biofilms.
The 65% interim analysis was completed in June
2021. In July 2021, the Company announced that following an unblinded data review of safety and efficacy, the independent DMC for the
trial recommended proceeding with the trial as planned. The DMC did not identify any safety concerns and no modifications were recommended
to the protocol-defined sample size or power to achieve the primary endpoint.
In May 2022, the Company selected Biorasi, LLC
(“Biorasi”), a global clinical research organization (“CRO”), to help expand the Company’s Phase 3 Mino-Lok
trial by implementing additional sites outside the U.S The Mino-Lok Phase 3 study enrolled 241 patients across 34 sites in the U.S. and
India. Eligible patients were randomized 1:1 to receive either Mino-Lok or site-specific standard-of-care lock solution plus systemic
antibiotics.
In August 2023, the Company announced all 92
events required to complete the trial had been achieved. Several patients remain in active treatment, which may result in additional
events.
In late December 2023, the Company determined
that patient enrollment for the Mino-Lok trial was complete and that it would begin site shutdown activities.
In May 2024, the Company announced positive topline
results of the trial. The study met its primary endpoint with a statistically significant improvement in the time to failure event in
patients receiving Mino-Lok compared to Control arm patients receiving clinician-directed anti-infective lock solution. The data demonstrates
that Mino-Lok is well-tolerated. Key findings include:
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A subset analysis of the Phase 3 trial, focused
on hemodialysis patients, examined the impact of Mino-Lok in this subgroup and found favorable outcomes for catheter salvage and infection
control compared to the overall study population. Key findings in this hemodialysis population include:
o SOC arm: 25% of catheters failed by Day 6, 50% failed by Day 22; and
o Mino-Lok arm: 25% catheter failure delayed until Day 37.
● Lower catheter failure rate with Mino-Lok:
o 57% (16/28) of SOC patients experienced catheter failure; and
o 31% (8/26) of Mino-Lok patients experienced catheter failure.
These outcomes demonstrate that the differentiated
efficacy and safety profile of Mino-Lok extends into an important hemodialysis subgroup of patients who often have limited vascular access
and face increased risk from catheter removal and replacement. Moreover, this subset reinforces Mino-Lok’s potential clinical utility
in one of the most vulnerable patient populations.
In November 2024, the Company held a Type C meeting
with the FDA to discuss the results of the Phase 3 study and to obtain the FDA’s view on development plans for Mino-Lok. The FDA
provided clear, constructive, and actionable guidance during the discussion, underscoring a pathway to support a future New Drug Application
(NDA) submission for Mino-Lok. Citius continues to engage with the FDA to define the regulatory path forward. No FDA-approved alternative
currently exists to salvage infected indwelling central venous catheters.
Fast Track Designation
In October 2017, the Company received official
notice from the FDA that the investigational program for Mino-Lok was granted “Fast Track” status. Fast Track is a designation
that expedites FDA review to facilitate development of drugs which treat a serious or life-threatening condition and fill an unmet medical
need. A drug that receives Fast Track designation is eligible for the following:
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Mino-Lok International Study
In October 2017, data from an international study
on Mino-Lok was presented at the Infectious Disease Conference, (“ID Week”), in San Diego, California. The 44-patient study
was conducted in Brazil, Lebanon and Japan and showed Mino-Lok therapy was an effective intervention to salvage long-term, infected CVCs
in CRBSIs in patients who had cancer with limited vascular access. This study showed 95% effectiveness for Mino-Lok therapy in achieving
microbiological eradication of the CVCs as compared to 83% for the control. The single failure in the Mino-Lok arm was due to a patient
with Burkholderia cepacia that was resistant to all antibiotics tested.