Citius Pharmaceuticals Profile
Citius Pharmaceuticals, Inc. operates as a late-stage biopharmaceutical company.
The company engages in 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 therapy.
The company is developing five proprietary products: LYMPHIR, in-licensed 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); 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; Mino-Wrap, a liquifying gel-based wrap for reduction of tissue expander infections following breast reconstructive surgeries; and NoveCite, a mesenchymal stem cell therapy for the treatment of ARDS.
LYMPHIR (denileukin diftitox-cdxl)
The company has obtained the trade name of LYMPHIR for E7777. LYMPHIR is 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: killing tumors by binding to IL-2 receptors to deliver diphtheria toxin directly to the tumor cells and depleting immunosuppressive regulatory T lymphocytes (Tregs) to enhance antitumor activity.
Phase 3 Trial (E7777-G000-302) Design: A global, multicenter, open label single arm pivotal clinical trial for the treatment of patients with persistent or recurrent CTCL was initiated in 2013. 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.
In the second and main phase of the pivotal trial, 70 patients were administered the 9 mcg/kg/dose rate for 5 consecutive days in 21-day cycles. The inclusion criteria was identical to the lead-in study and the primary objective was to evaluate the objective response rate (ORR).
Investigator Initiated Trials
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.
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.
Regulatory Development
In December 2022, a biologics license application (BLA) for LYMPHIR was accepted for filing with the United States Food and Drug Administration (FDA) and a PDUFA goal date was set for July 28, 2023.
In July 2023, the FDA issued a complete response letter requiring the company to incorporate enhanced product testing and additional controls agreed to with the FDA during the market application review.
In September 2023, the company announced that the FDA has agreed with the plans to address the requirements outlined in the complete response letter, which guidance has provided it with a path for completing the necessary activities to support the resubmission of the BLA for LYMPHIR.
Mino-Lok
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.
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. As of December 15, 2023, there were 12 active sites in the U.S., including such academic centers as Henry Ford Health Center, Georgetown University Medical Center, and others. There are 16 sites active in India, making a total of 28 participating Mino-Lok institutions globally.
In August 2023, the company announced all 92 events required to complete the trial have been achieved. Several patients remain in active treatment, which may result in additional events.
In December 2023, the company determined that patient enrollment for the Mino-Lok trial was complete and that it would begin site shutdown activities. Topline results are anticipated in the first half of 2024.
Completion of enrollment is expected in 2023.
Fast Track Designation
In 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.
Halo-Lido
Halo-Lido is a topical formulation of halobetasol propionate, a corticosteroid, and lidocaine that is intended for the treatment of hemorrhoids.
CITI-002 Phase 2b Trial
Approximately 300 adults with a clinical diagnosis of symptomatic hemorrhoids were enrolled in the Halo-Lido Phase 2b study (NCT05348200), a multi-center, randomized, dose-ranging, double-blind, parallel group comparison clinical trial, which was initiated in April 2022. In June 2023, the company announced positive results from the Phase 2b study of Halo-Lido for the treatment of hemorrhoids. Treatment effect on hemorrhoidal symptoms was analyzed using the meaningful change threshold (MCT).
Mino-Wrap
The company has a patent and technology license agreement with the Board of Regents of the University of Texas System on behalf of MDACC, whereby the company in-licensed exclusive worldwide rights to the patented technology for any and all uses relating to breast implants, specifically the Mino-Wrap technology. This includes rights to U.S. Patent No. 9,849,217, which was issued on December 16, 2017. The company intends to develop Mino-Wrap as a liquefying, gel-based wrap containing minocycline and rifampin for the reduction of infections associated with breast implants following breast reconstructive surgeries. The company is required to use commercially reasonable efforts to commercialize Mino-Wrap under several regulatory scenarios and achieve milestones associated with these regulatory options leading to an approval from the FDA. Mino-Wrap will require pre-clinical development prior to any regulatory pathway. In December 2023, the company terminated the Mino-Wrap license agreement with the Board of Regents of the University of Texas System on behalf of MDACC.
NoveCite, Inc. (NoveCite)
The company, through its subsidiary, NoveCite, has an exclusive agreement with Novellus Therapeutics Limited (Novellus) to license iPSC-derived mesenchymal stem cells (iMSCs). Under this worldwide exclusive license, the company focuses on developing cellular therapies. Specifically, the company is seeking to develop and commercialize the NoveCite mesenchymal stem cells (NC-iMSCs) to treat acute respiratory conditions with a near term focus on acute respiratory disease syndrome (ARDS).
Sales and Marketing
The company primarily focuses on identifying opportunities within the critical care and cancer care market segments. In the company's product acquisition criteria, it concentrates on markets that are influenced by key opinion leaders, and in which products are prescribed by a relatively small number of physicians, yet provide opportunities for growth and market share. The company intends to license its mass audience, non-specialty product candidates to such companies for sales and marketing.
Intellectual Property
LYMPHIR Intellectual Property
The company owns the exclusive license of E7777 (denileukin diftitox), a late-stage oncology immunotherapy for the treatment of CTCL. The company refers to the agent as LYMPHIR. The exclusive license, which was amended as part of the transaction, is with Eisai Co., Ltd. (Eisai) and includes rights to develop and commercialize LYMPHIR in all markets except for Japan and certain parts of Asia. The license includes an option on the right to develop and market the product in India. In April 2022, the company assigned the license agreement to Citius Oncology, at which time Citius Oncology began operations.
Pursuant to the terms of the license agreement, Eisai is responsible for completing the CTCL clinical trial, and chemistry, manufacturing and controls development activities through the production of the biologics license application (BLA), which the company filed with the FDA in September 2022, while it is responsible for the costs of correcting any major deficiencies in the BLA, as well as the costs of any further studies and development costs associated with potential additional indications.
The company is responsible for preparing, filing, prosecuting and maintaining all patent applications and patents included in the licensed patents that it intends to pursue within the territory.
Patents
The company owns method of use patents in which E7777 is administered in combination with the programmed cell death protein 1 (PD-1) pathway inhibitor drug class. PD-1 plays a vital role in inhibiting immune responses and promoting self-tolerance through modulating the activity of T-cells, activating apoptosis of antigen-specific T cells and inhibiting apoptosis of regulatory T cells.
The following patents were acquired:
US Provisional Application No. 63/070,645, which was filed on August 26, 2020, and subsequently published as US 2022/0062390 A1 on March 3, 2022, entitled Methods of Treating Cancer.
International Patent Application Number: PCT/IB2021/0576733, which was filed with the World Intellectual Property Organization on August 23, 2021, and subsequently published as WO 2022/043863 A1 on March 3, 2022, entitled, Combination for Use in Methods of Treating Cancer.
Mino-Lok Intellectual Property
In 2014, the company's subsidiary, Leonard-Meron Biosciences, Inc. (LMB), entered into a patent and technology license agreement with Novel Anti-Infective Therapeutics, Inc. (NAT), who licensed the intellectual property from MDACC, to develop and commercialize Mino-Lok on an exclusive, worldwide (except for South America), sub-licensable basis. In 2017, LMB entered into an amendment to the license agreement that expanded the licensed territory to include South America, providing LMB with worldwide rights.
Mino-Lok is covered in relation to the composition by issued U.S. patent No. 7,601,731, entitled 'Antimicrobial Flush Solutions', which was issued on October 13, 2009. Mino-Lok is further covered in relation to its method of use by issued U.S. Patent No. 9,078,441, which was issued on July 14, 2015. The patents provide intellectual property protection until June 7, 2024. There are corresponding patents granted in Europe and Canada (European Patent No. EP 1644024, and Canadian Patent No. 2528522).
Stability Patent Application for Mino-Lok
In October 2018, the USPTO issued U.S. Patent No. 10,086,114 (the '114 patent'), entitled 'Antimicrobial Solutions with Enhanced Stability'. In October 2019, the European Patent Office (EPO) granted European Patent No. 3370794, which corresponds to the '114 patent. The grant of these patents strengthens the intellectual property protection for Mino-Lok through November 2036. While the original patents for Mino-Lok cover the basic composition, this invention overcomes limitations in mixing antimicrobial solutions in which components have precipitated because of physical and/or chemical factors, thus limiting the stability of the post-mix solutions. As such, the patents claiming the enhanced stability may effectively extend patent protection for Mino-Lok beyond the 2024 expiration of the original patents since it is expected that the compositions providing enhanced stability would be preferred over any non-stabilized versions that a competitor may introduce after June 7, 2024. The company holds the exclusive worldwide license, which provides access to this patented technology for development and commercialization of Mino-Lok.
Mino-Lok has received a Qualified Infectious Disease Product (QIDP) designation. The QIDP designation provides New Drug Applications an additional five years of market exclusivity, which together with the potential three years of exclusivity for the new strength and formulation of Mino-Lok, would result in a combined total of eight years of market exclusivity regardless of patent protection.
Halo-Lido Intellectual Property
The company is developing Halo-Lido to have a combination of excipients, as well as concentrations of the active ingredients. The company seeks to achieve approval for Halo-Lido by utilizing the FDA's 505(b)(2) pathway.
Mino-Wrap Intellectual Property
In January 2019, the company entered into a patent and technology license agreement with MDACC to develop and commercialize Mino-Wrap on an exclusive worldwide basis, with no rights to sub-license.
In December 2017, the USPTO issued U.S. Patent No. 9,849,217, entitled 'Antimicrobial Wraps for Medical Implants'. This invention overcomes limitations in breast reconstruction utilizing tissue expanders and implants following mastectomies by providing, in certain aspects, biodegradable antimicrobial film that may be wrapped around a medical implant, such as a breast implant prior to the insertion into a subject, such as a human patient. The scientists and technologists at MDACC have developed a biodegradable covering for a medical implant comprising a highly plasticized gelatin and at least one drug to reduce infection.
The company holds the exclusive worldwide license, which provides access to this patented technology for development and commercialization of Mino-Wrap.
NoveCite Intellectual Property
In October 2020, the company, through its subsidiary, NoveCite, Inc. (NoveCite), entered into a license agreement with Novellus Therapeutics Limited (Licensor), whereby NoveCite acquired an exclusive, worldwide license, with the right to sublicense, to develop and commercialize a stem cell therapy based on the Licensor's patented technology for the treatment of acute pneumonitis of any etiology in which inflammation is a major agent in humans. The patented technology consists of mesenchymal stem cells (MSCs) derived from an induced pluripotent stem cell line that is made by Licensor using the mRNA cell reprogramming methods in the patents covering the licensed technology.
During the term of the license agreement, NoveCite is required to use commercially reasonable efforts to make commercially available at least one product in at least two markets: the U.S. and either the United Kingdom, France, Germany, China or Japan.
Strategy
The company's strategy centers on products that have intellectual property and regulatory exclusivity protection, while providing competitive advantages over other existing therapeutic approaches.
Research and Development
For the year ended September 30, 2023, the company's research and development expenses were $14,819,729.
