Citius Pharmaceuticals is developing novel medical solutions that address specialized needs for which no products are on the market, from a prescription hemorrhoid treatment to a solution for salvaging infected catheters.

Beginnings as a Startup

Citius Pharmaceuticals has always pursued the development of solutions for unmet medical problems, and the circumstances of the company’s founding illustrate this vision. The story of Citius Pharmaceuticals in its current incarnation began in 2013 when Myron Holubiak and Leonard Mazur founded Leonard-Meron Biosciences (LMB RX) to in-license one such medical solution, a technology from the University of Texas MD Anderson Cancer Center that was invented by its Chair of Infectious Diseases, Dr. Issam Raad. The technology in question is an antibiotic lock solution for sterilizing catheters, known as Mino-Lok^®. Mino-Lok does not go into the patient’s body, but rather is injected into a locked catheter and then left in the line for two hours before being aspirated out. With this technology, the patient can continue receiving IV treatment for 22 hours each day. After five to seven days of treatment, the catheter is completely sterilized. As simple as it sounds, such a treatment had never previously been developed.

The potential for this technology to improve patients’ quality of care is staggering. The current standard of care is to remove the infected catheter and replace it, which requires two separate, painful surgical procedures that are accompanied by adverse effects approximately 20% of the time. “Mino-Lok is the first and only solution of its type for salvaging infected catheters. There is nothing on the market like it today, and as far as we know nothing like it is being investigated in clinical trials,” says Mazur, who is Chief Executive Officer and Chairman of the Board of Directors of Citius Pharmaceuticals.

In order to move this innovation closer to market, Mazur and Holubiak personally funded a phase IIb trial for Mino-Lok, but they soon realized that LMB RX could not conduct a phase III trial on its own. The solution was to merge with the public company Citius Pharmaceuticals in 2016. Shortly after that, they uplisted the company to NASDAQ.

Backed by Extensive Experience

Mazur and Holubiak, who is now Executive Vice Chairman of the Board of Directors of Citius, have the right credentials for starting a company like LMB RX and carrying it forward as Citius Pharmaceuticals. Their collaboration is many years in the making. The two initially met at a training session for pharmaceutical research analysts early in their careers and stayed in touch over the years as each pursued a different career track. Holubiak spent most of his time with Roche, eventually becoming the President of Roche Labs. Mazur started with Cooper Laboratories, where he held positions in marketing, strategic planning, and acquisitions and eventually became head of one of the company’s businesses. Most of the remainder of his career was spent as an entrepreneur, starting and successfully exiting multiple companies.

Building a Unique Portfolio

The merger with Citius added another asset to the pipeline. Halo-Lido is a combination therapy comprising a steroid and lidocaine for the treatment of hemorrhoids. This drug was attractive to Mazur and Holubiak because, just as there are no comparable technologies to Mino-Lok, there are no FDA-approved prescription treatments for hemorrhoids in the U.S. market, according to Mazur. “No one has ever gotten a prescription drug through the entire new drug application (NDA) process. Citius recently received approval of our investigational new drug (IND) application to enter phase IIb trials with Halo-Lido, which we will be implementing shortly. We are excited to be taking this candidate forward,” he states.

Citius has a diversity of other drugs and technologies in their pipeline, the majority of which serve small target populations. I/ONTAK (E7777) is a drug in development for the treatment of cutaneous T cell lymphoma (CTCL), a rare cancer for which I/ONTAK has received Orphan Drug Designation (ODD) from the U.S. Food and Drug Administration (FDA). The phase III clinical trial for this candidate has been completed, with topline data readout anticipated in the first half of 2022. Mazur expects Citius to file a biologics license application (BLA) in the second half of the year and hopes to have I/ONTAK approved and on the market in 2023.

Earlier in Citius’s pipeline is Mino-Wrap, another technology that Citius licensed from the University of Texas MD Anderson Cancer Center. The wrap, a malleable, bioabsorbable film, is designed to prevent infection of tissue expanders used post-mastectomy. “With current approaches, approximately 12–14% of patients develop an infection following this surgery. Mino-Wrap is impregnated with antibiotics to prevent those infections from occurring,” explains Mazur. This product is currently in preclinical development.

Another preclinical-stage candidate being investigated by Citius is based on mesenchymal stem cells for the treatment of acute respiratory distress syndrome (ARDS) and was in-licensed from a Boston-based biotech. There currently is no cure for ARDS, which occurs in about 200,000–250,000 patients annually in the United States and is fatal for about half of them.

As for the catheter salvage solution that started it all, Mino-Lok has been granted status as a qualified infectious disease product (QIDP) by the FDA, which considers the treatment to be a breakthrough therapy, according to Mazur. The phase III trial is underway and would have been completed by now if the COVID-19 pandemic had not interrupted this hospital-based study. Mazur expects it will be successfully completed by the end of 2022, with Citius filing an NDA in 2023.

As Citius has built this unique portfolio, the company has also added expertise to support further development of its pipeline candidates. A key hire, according to Mazur, was Dr. Myron S. Czuczman as Chief Medical Officer. Czuczman spent 23 years at Roswell Park Comprehensive Cancer Center in Buffalo as the Chief of Lymphoma and Myeloma and five years at Celgene as Vice President of Global Research in lymphoma. “Although we try to keep overhead down as much as possible, we have made a real effort to bring solid professionals on board and feel we have a great professional team at Citius,” Mazur comments.

Focused on Critical Care for Unmet Needs

The focus at Citius, says Mazur, is primarily on critical-care products and drugs that address unmet medical needs. The company also mainly seeks opportunities where it would have a competitive advantage as the first-and-only participant in the market segment.

While the pipeline is diversified, Citius does see synergies across several pipeline assets that address the needs of cancer patients, including its leading candidate I/ONTAK. Citius believes that it could effectively reach oncologists with a limited targeted salesforce and is therefore preparing to launch that product independently. The need for a treatment for infected catheters is primarily a problem for cancer patients as well, because they are the ones who require long-term catheters. The same is true for Mino-Wrap, as most mastectomies are performed on patients with breast cancer. Marketing and sales efforts for these three drugs, Mazur says, will therefore overlap.

The Halo-Lido hemorrhoid drug is a different case. The intention, according to Mazur, is to monetize that asset by out-licensing it once the phase IIb trial has been completed and efficacy data has been analyzed.

Strong Funding Position Supported by Personal Investments

One thing that remains unique about Citius is the continued personal investments made by Mazur and Holubiak in the company. “Citius is a bit different from other pharmaceutical companies in that we have made personal investments alongside the other funding we have raised,” Mazur notes. To date, the two have invested a total of $26.5 million in the company.

That high level of investment, Mazur adds, is a testimony to the belief and confidence that the two have in the product candidates that Citius is developing. “The fact that we have put so much of our own money into the company has also helped tremendously with external fundraising,” he says. In 2021, for instance, Citius raised $121 million through financings activities, providing the company with a strong cash position with which to advance its programs.

Significant Market Potential

Although Citius is focusing on highly specialized products that target small patient populations, the market potential for its drug candidates is still significant, according to Mazur. He estimates the global market for the Mino-Lok solution for salvaging infected catheters to be nearly $2 billion. The market for the CTLC treatment I/ONTAK is much smaller, but still sizeable at $300 million — which does not include further growth opportunities in the form of additional indications that Citius will be pursuing in the future, such as peripheral T-cell lymphoma, which Mazur indicates is a much larger market. The market for the Mino-Wrap tissue expander is thought to be $400 million worldwide. The prescription hemorrhoid market, meanwhile, would be “huge”, according to Mazur.

Ultimately, Citius plans to commercialize its leading product candidates, I/ONTAK and Mino-Lok, in the United States and partner to develop and market these products in other parts of the world. Assuming positive data is obtained in the phase IIb trial for Halo-Lido hemorrhoid treatment, this drug would likely be out-licensed to a partner that could support a large consumer-focused salesforce.

Rare Company with an Exciting Future

Looking forward a few years, Mazur hopes that Citius will have a good presence in CTCL and potentially other cancers with I/ONTAK, including its use in combination immuno-oncology treatments with checkpoint inhibitors. Mino-Lok presents another exciting opportunity for Citius that should provide significant revenues and contribute to measurable growth for the company. The number of people diagnosed with cancer and receiving IV treatments continues to increase, as well as the number of patients with other chronic illnesses that require ongoing IV infusions that could benefit from the technology. As one example, Mazur points to dialysis patients.

Mazur believes that it is a rarity to find a small, pre-revenue company like Citius that has two phase III products in its portfolio. He and his colleagues aren’t placing all of their hopes in their existing line of candidates, either. “We are actively pursuing opportunities in the marketplace all the time, constantly looking at different opportunities that would be complementary to our portfolio,” he remarks.

In present circumstances, it is also notable that four members of Citius’s leadership, including Mazur, Holubiak, Czuczman, and one of the company’s board members, are of Ukrainian descent and have enduring ties to the Ukrainian community. “The Citius family stands in solidarity with the people of Ukraine and condemns the Russian assault on an independent democracy. As the tragic events in Ukraine unfold, the humanitarian crisis grows exponentially. We are reminded that progress, including scientific discovery, is made possible by the ability of free people, living in peace, to exercise the values and rights inherent in democratic societies.  As such, we support the Ukrainian people in their effort to remain a sovereign and democratic nation,” Mazur emphasizes.

The leaders of Citius therefore encourage all those that can afford to do so to support relief efforts in Ukraine by donating to creditable organizations such as the American Red Cross, UNICEF, and many others. A list of vetted groups is provided on the Citius website (www.citiuspharma.com).