The key component in CorMedix’s flagship investigational drug product, Defencath™, is taurolidine, a synthetic broad-spectrum antimicrobial and antifungal with anti-inflammatory and potential anti-tumor activities. Taurolidine is derived from the natural amino acid taurine and its antimicrobial activity is directed at the bacterial cell surface.
Taurolidine disrupts cell walls and destroys bacterial fimbriae, which are important for colonization and biofilm formation. It also binds to and neutralizes bacterial exotoxins and endotoxins (lipopolysaccharides, LPS). Products containing taurolidine have been marketed in Europe for many years, and to date, have not shown susceptibility to bacterial resistance mechanisms.
Taurolidine also inhibits expression of key inflammatory molecules tumor necrosis factor – alpha (TNF-α) and interleukin 1b. Although the mechanisms underlying its anti-tumor activity are not fully elucidated, taurolidine has been shown to inhibit new blood vessel formation within tumors and enhance cancer cell death through apoptosis, as well as reduce tumor cell adhesion.
CorMedix is conducting research to explore additional uses for taurolidine, including oncology and medical devices. The Company would look to establish strategic partnerships to advance these products once proof-of-concept is achieved.
Drug Opportunities in Oncology
Preclinical studies suggest that taurolidine has a direct and selective antineoplastic effect on glial and neuronal brain tumor cells, and in addition, has been shown to significantly enhance the activity of cytotoxic cancer drugs, including vincristine.
In 2016, CorMedix announced a collaboration with the Pediatric Oncology Therapeutic Investigators Consortium (POETIC) to evaluate a novel formulation of taurolidine (CMDX-001) as a part of an investigational therapy for rare pediatric cancers including neuroblastoma and osteosarcoma. CorMedix and POETIC are advancing this program through preclinical studies and will determine a potential clinical strategy once in vivo proof-of-concept is achieved.
Pediatric neuroblastoma, an Orphan Disease in the United States, is an adrenal cancer that develops in the nerve cells of the medulla and is the most common extracranial tumor in childhood, usually occurring in infants and children under 10. In February 2018, FDA granted Orphan Drug Designation of taurolidine for the treatment of neuroblastoma.
Cost-Efficient Medical Device Opportunities
Taurolidine’s antimicrobial and anti-inflammatory properties may add significant value for the medical device market. CorMedix is focusing its research and development efforts on the following areas, each of which represent large markets where the Company believes taurolidine-based products can achieve significant market share upon FDA clearance.
- Antimicrobial Sutures: Protect exposed skin from infection
- Topical Hydrogels: Prevent infection in common burns and diabetic foot ulcers
- Non-woven Surgical Meshes: Prevent infection in hernia repair and burns
Initial in vitro studies have generated encouraging data and work is ongoing to achieve in vivo proof-of-concept in animal models. CorMedix also received an NIH grant to develop an advanced nanoparticle formulation of taurolidine hydrogels for use as a deeper-penetrating antimicrobial for severe burn injury. The Company anticipates pursuing approval of its medical device products under the accelerated and cost-efficient 510(k) device pathway, and will seek to establish commercial partnerships upon potential FDA clearance.