Niclosamide is an oral anthelminthic drug. It was first approved by the U.S. Food and Drug Administration (FDA) in 1982 and is included in the World Health Organization (WHO)’s list of essential medicines.
Austin, Texas-based TFF Pharmaceuticals inked a worldwide exclusive licensing deal with Hellerup, Denmark’s UNION Therapeutics for the use of TFF’s Thin Film Freezing technology in combination with niclosamide for COVID-19 treatments.
The TFF platform improves the solubility and absorption of poorly water-soluble drugs. Its primary use is to generate dry powder particles for inhalation delivery, especially deep in the lungs. The TFF process results in a “Brittle Matrix Particle” that has low bulk density and high surface area, which allows the particles to supersaturate the target site, such as lung tissue.
Niclosamide is an oral anthelminthic drug. It was first approved by the U.S. Food and Drug Administration (FDA) in 1982 and is included in the World Health Organization (WHO)’s list of essential medicines. It has recently been identified as a possible treatment for viral infections, such as severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), Zika virus (ZIKV) and others.
Niclosamide is generally inexpensive and has a low toxicity profile. It appears to inhibit SARS-COV-2, but because of its limited aqueous solubility and low absorption and oral effectiveness, there are difficulties in using it as an anti-viral therapy. Which is where the TFF technology comes in, because it would likely allow the oral forms of niclosamide to be converted to a dry powder that could be delivered directly to the lungs.
“We are very excited to be entering into this agreement with UNION Therapeutics, a company that has had an extensive history working with niclosamide and the compound class in a number of therapeutic areas,” said Glenn Mattes, president and chief executive officer of TFF. “We believe this agreement will help speed up efforts to investigate the promising use of niclosamide for potential COVID-19 therapies using our breakthrough TFF technology to provide a viable therapeutic option with a new delivery method.”
Under the terms of the deal, UNION is paying TFF Pharmaceuticals potential development, regulatory and sales milestones up to $210 million, as well as tiered single-digit royalties on product sales. UNION gains an option to a worldwide exclusive license to TFF technology for niclosamide, including oral and inhaled versions of the drug, potentially for COVID-19, but also for other niclosamide-based therapies. The two companies will also collaborate on securing government contracts and grants to fund the development of the therapies for COVID-19.
UNION is currently running a Phase IIb trial of niclosamide in atopic dermatitis.
“Like UNION, TFF has been working with niclosamide for an extended period of time and has taken an interesting approach to the formulation of niclosamide for COVID-19,” said Rasmus Toft-Kehler, chief executive officer and co-founder of UNION. “We are excited to formalize our collaboration with the TFF team and consolidate our joint efforts under the wings of UNION. This will allow us to maximize the likelihood of getting the best possible product to as many COVID-19 patient segments in the shortest possible timeframe.”
On July 1, UNION was granted clearance by the Danish Medicines Agency to launch a clinical trial with an optimized salt version of niclosamide for COVID-19. The trial will be at the Zelo Phase I Unit at Bispebjerg and Frederiksberg Hospital and the Center for Physical Activity Research at Rigshospitalet, in collaboration with Trial Nation Denmark and the Technical University of Denmark, as well as with financial support from the Innovation Fund Denmark.
Morten Sommer, co-founder and chief scientific officer of UNION, said, “Niclosamide is a truly differentiated candidate for the treatment of COVID-19, with its method of action, effectively blocking replication of SARS-COV-2 by targeting host cells to disrupt the viral life cycle.”
