Citius Pharmaceuticals is a late-stage biopharmaceutical company focused on developing critical care products that improve patients’ lives. Our product development strategy is to explore and invest in assets that address unmet medical needs and have expedited or de-risked developmental and regulatory pathways.
Our diversified pipeline spans five active programs in adjunct cancer care, oncology, stem cell therapy, and unique prescription products. Three of these investigational drugs would be the first and only prescription treatments in their indications, if approved by the FDA. We expect 2022 to continue to be a year of important catalysts for the company. We recently completed a Phase 3 study for the treatment of persistent or recurrent cutaneous T-cell lymphoma and are preparing a Biologics License Application (BLA) that we plan to submit later this year. Our Phase 3 trial for a novel antibiotic lock solution to salvage colonized central venous catheters is nearing completion. And, we initiated a Phase 2b study for the prescription treatment of hemorrhoids.
The genesis of our company began in 2013 when Myron Holubiak, Vice Chairman of Citius, and I founded Leonard Meron Biosciences – which ultimately merged with Citius – to in-license a technology from the University of Texas MD Anderson Cancer Center. That technology is our antibiotic lock solution for sterilizing catheters, known as Mino-Lok.
There was no product on the market like it at the time, and to our knowledge, there is nothing like it under investigation in clinical trials today. Mino-Lok’s unrivaled potential to improve patients’ quality of care is the reason we pursued this technology.
In the U.S., approximately 7 million central venous catheters (CVCs) are inserted annually, and 4 million CVCs are in long-term use (for over 1 month). We estimate there are about 500,000 CRBSI/CLABSI infections annually in the U.S. of which 12 to 20 percent are associated with mortality and morbidity. Globally, we believe the market for Mino-Lok approaches nearly $2 billion.
We believe Mino-Lok has the potential to salvage infected CVCs of patients with catheter-related bloodstream infections (CRBSIs) or central line associated bloodstream infections (CLABSIs). Mino-Lok is being developed to address the complications, discomfort and cost of CVC removal and replacement (R&R).
Citius is currently enrolling patients in a multicenter Phase 3 pivotal superiority trial of Mino-Lok. If approved, Mino-Lok would be the first-to-market solution to salvage CVCs causing CLABSIs. Mino-Lok was granted Qualified Infectious Disease Product (QIDP) and Fast Track designation by the FDA, and has formulation patent protection through 2036.
In a Phase 2b trial, Mino-Lok demonstrated 100 percent efficacy in salvaging colonized CVCs. And, the Mino-Lok trial arm showed no significant adverse events compared to an 18 percent serious adverse event rate for R&R.
There is a widespread medical need for an alternative to removing and replacing a CVC once it becomes infected. The long-standing standard of care for CRBSI/CLABSI involves the removal of the infected CVC and replacement with a new catheter at a different vascular site, which can be risky. Studies show that R&R procedures have a 15 to 20 percent complication rate, including pneumothorax, misplacement, and arterial puncture, with as many as 57 to 67 percent of patients experiencing adverse physical and psychological symptoms. The financial costs to the healthcare system are also high. An R&R procedure can run approximately $10,000, and total costs of a CRBSI/CLABSI episode can reach $46,000 to $65,000.
One of the key problems of the R&R procedure is that it does not address the need to maintain infusion therapy for critically ill patients. Mino-Lok’s two-hour infusion cycle overcomes this limitation by enabling the CVC to be used for its intended purposes for the remaining 22 hours each day. Upon treatment cycle completion, Mino-Lok is aspirated out of the CVC rather than being flushed into the venous system, so it never enters the patient’s body.
Another key advantage of Mino-Lok is its ease of administration. Locking a catheter is a well-practiced standard operating procedure and the procedure can be performed by any healthcare provider.
The newest addition to our pipeline is I/ONTAK, a novel IL-2R immunotherapy being developed for an initial indication in cutaneous T-cell lymphoma (CTCL). CTCL is a rare and incurable form of non-Hodgkin lymphoma. The I/ONTAK Phase 3 trial has been completed and we are on track for submission of a Biologics License Application (BLA) in the second half of this year.
This cancer agent is a reformulation of ONTAK® (denileukin diftitox), a recombinant fusion protein that was granted FDA approval in the U.S. in 1999. Improvements to the original formulation resulted in a therapy that maintains the same amino acid sequence, but features greater purity and bioactivity.
Topline results from the Phase 3 trial demonstrated anti-tumor activity in the treatment of persistent or recurrent CTCL and are consistent with trial results of the prior formulation. We expect I/ONTAK to be an important option for CTCL patients as existing targeted therapies are often poorly tolerated and/or have limited efficacy, and there is no agreed upon standard of care for this disease.
Within the limited universe of available targeted therapies for CTCL, there are none with I/ONTAK’s unique dual mechanism of action: targeting both malignant T-cells and immunosuppressive regulatory T-cells (Tregs). I/ONTAK is able to target malignant T-cells by binding to the interleukin-2 receptor on a cell’s surface. This causes diphtheria toxin fragments to penetrate the cell walls and inhibit protein synthesis, leading to the death of the malignant tumor cells – precisely what we want to happen to cancer cells. And, we believe it does even more by suppressing Tregs simultaneously. Tregs emit powerful signals that suppress the body’s immune system and inhibit its ability to launch a robust response against tumor cells. By acting on the suppressive Tregs, I/ONTAK, either on its own or in combination with another targeted therapeutic, may clear the path for the body to unleash a potent immune response against a solid tumor.
We are initially pursuing an orphan indication in CTCL, and believe there may be a direct path to a second indication in peripheral T-cell lymphoma (PTCL). While each of these indications are important on their own, we also see multiple potential opportunities for I/ONTAK to address the needs of much larger patient populations as a combination therapy with CAR-T or PD-1 inhibitors. The CTCL market is estimated to be approximately $300 million, with larger market potential with PTCL and immuno-oncology indications.
We are very excited about this product. It is quite rare in our industry to have the opportunity to acquire an asset so far along in its development, and with so many additional features that could support commercial success.
Recently, we initiated a Phase 2b study for Halo-Lido, a prescription strength topical formulation of halobetasol and lidocaine designed to provide anti-inflammatory and anesthetic symptomatic relief to people with hemorrhoids. If approved, Halo-Lido would be the first prescription strength product indicated for the treatment of hemorrhoids.
We see substantial worldwide market opportunity for this drug candidate. In the U.S. alone, hemorrhoids affect nearly 5 percent of the population, with approximately 10 million patients reporting symptoms annually. According to IMS, over 25 million units of topical combination prescription products for hemorrhoids are sold in the U.S., and the global prescription hemorrhoid market is estimated to be over $2 billion.
In addition to our three clinical programs, we are advancing two pre-clinical assets, NC i-MSCs (stem cells) and Mino-Wrap. Through Citius’s subsidiary NoveCite, we are developing next generation induced mesenchymal stem cells (i-MSCs) to treat acute respiratory distress syndrome (ARDS) caused by bacteria and viruses including COVID. Stem cells are an exciting new area of focus as potential therapies for ARDS, with ongoing research efforts worldwide. Currently, there is no FDA-approved drug therapy for ARDS. Mino-Wrap is a bioabsorbable extended-release antimicrobial wrap designed to aid in preventing infection and biofilm formation around tissue expanders used in breast reconstruction surgery following a mastectomy. Mino-Wrap is being developed by Citius in partnership with The University of Texas MD Anderson Cancer Center.
We expect 2022 to continue to be a year of multiple value-driving catalysts as we advance our diversified pipeline. The I/ONTAK BLA submission is planned for the second half of 2022, and we anticipate completing trial enrollment for both the Phase 3 Mino-Lok trial and the Phase 2b Halo-Lido study by the end of the year. We are hopeful that the challenges of COVID-19 are behind us, and the macro environment will allow us to continue to make progress as planned. Our focus will remain on execution and delivering long-term value to shareholders.
Editor’s Note: Leonard Mazur is the Chairman & Chief Executive Officer of Citius Pharmaceuticals, Inc.
He is an accomplished entrepreneur and pharmaceutical industry executive with notable success in founding and building multiple healthcare companies and creating value and returns for investors throughout his five-decade career. Mr. Mazur was the co-founder and Chairman of Leonard-Meron Biosciences, Inc. prior to its merger with Citius in March 2016. He was previously the co-founder and Vice Chairman of Akrimax Pharmaceuticals, LLC, which specialized in cardiovascular and general pharmaceutical products.
From 2005 to 2012, Mr. Mazur co-founded and served as the Chief Operating Officer of Triax Pharmaceuticals LLC, a specialty pharmaceutical company producing prescription dermatological drugs. As founder and Chief Executive Officer of Genesis Pharmaceuticals, Inc., a dermatological products company that marketed its products through dermatologists’ offices and co-promoted products for major pharmaceutical companies, he successfully negotiated the company’s sale in 2003 to Pierre Fabre, a leading global pharmaceutical company.
He has extensive sales, marketing, and business development experience from previous tenures at Medicis Pharmaceutical Corporation, ICN Pharmaceuticals, Inc., Knoll Pharma (a division of BASF), and Cooper Laboratories, Inc.
Born in Ansbach, Germany, he emigrated with his family to the U.S. at an early age and served in the U.S. Marine Corps Reserve while studying at Temple University for his undergraduate degree. He earned his MBA from Temple University’s Fox School of Business in 1975.
He is a recipient of the Ellis Island Medal of Honor presented annually to those who immigrated to the United States during the Ellis Island era and have shown an outstanding commitment to serving the United States either professionally, culturally, or civically.
 Shah H., Bosch W., Hellinger W. C., Thompson K. M. (2013). Intravascular catheter-related bloodstream infection. Neurohospitalist 3, 144–151. doi: 10.1177/1941874413476043.
 Antoňáková Němčíková A, Bednárovská E. Catheter-related bloodstream infections: do we know all of it? Klin Onkol. 2017;30(6):405–411. doi: 10.14735/amko2017405.
 Chaftari, AM et al,. Unnecessary Removal of CVCs in Cancer Patients with CRBSI: Impact on Symptom Burden. Poster presentation at ID Week 2017, Infectious Diseases Society of America (IDSA)Oct 04 – 08, 2017