Tonix Pharmaceuticals Holding Corp. has synthesised a live form of horsepox virus (HPXV) which has demonstrated protective acitivity against the smallpox virus in mice.
If given the regulatory go ahead, Tonix will develop its live vaccine candidate TNX-801 under US FDA 21 CFR 601 Subpart(h) registration pathway.
Otherwise known as the ‘Animal Rule’, this regulatory path allows for the approval of biological products when human efficacy studies are not ethical or feasible.
Seth Lederman, CEO of Tonix, told us: “We plan to demonstrate safety of TNX-801 in Phase I trials in humans and demonstrate efficacy using animal models.”
Despite the eradication of smallpox from the general population back in 1980, there is still a market demand for new vaccines against the virus.
“For example, TNX-801 may be particularly relevant to first responders responsible for national biodefense procedures,” Lederman explained.
However, he added “presently the safety concern of existing smallpox-preventing vaccines outweigh the potential benefit to provide immunization of first responders or the general public.”
Developed preclinically with David Evans and Ryan Noyce at the University of Alberta, Canada, Lederman added that he had co-written a patent application for the cell line derived vaccine under his name, and Tonix wholly owns the HPXV virus stock and related sequences.
Lederman told us: “At this point the TNX-801 program is still at a research stage and will be optimized for GMP manufacturing as we move into Phase I trials.”
If issued, the patent will give Tonix 20-years exclusivity for TNX-801.
Safety and the live virus
Originally developed by Edward Jenner, smallpox vaccines are based on a live attenuated version of a pox virus, vaccinia.
An example of a vaccinia-based smallpox vaccine is from Sanofi Pasteur, which got US FDA approval for ACAM2000 in 2007.
Although Lederman declined to specify which cell lines Tonix uses, TXN-801 is also a live virus that shares structural characteristics with vaccinia-based vaccines.
However, where other marketed vaccines have risk of adverse effects such as myopericarditis, Tonix believes TNX-801 “has unique properties” that may lower toxicity and potential safety advantages over existing vaccinia-based vaccines.
“By developing TNX-801 as a horsepox vaccine to prevent smallpox infection, we hope to have a safer vaccine to protect against smallpox than is currently available,” said Lederman.
National Security and ‘The Animal Rule’
However, given the historical scale of the smallpox epidemics and popular dramatisation of epidemic storylines, other companies looking to enter the space have previously been met with some resistance.
Nonetheless, there have previously been freak incidences of the smallpox virus re-emerging, prompting authorities such as the US Center for Disease Control (CDC) to fund and stock versions of the virus just in case.
Lederman: “This demand is reflected in the priority review provisions of the 21st Century Cures Act, which recognizes the need for improved forms of biodefense, called “material threat medical countermeasures’.”
You can find out more on these countermeasures in Section 3086.