Nitric Oxide joins the fight against COVID-19
FAST & FURIOUS LAUGHING GASSES PANDEMIC

A Canadian-based company using Nitric Oxide (NO) to treat topical and respiratory infections has found success using their product to combat COVID-19. In an interview with Chris Miller, Chief Scientific Officer and Cofounder at SaNOtize, we learn about the company that is attacking the virus before it can attack you.

Chris Miller published his first review article on Nitric Oxide in 1992, he says, “I was trying to figure out what to research in my Ph.D. and I had read an abstract about the molecule nitric oxide, so while I knew very little about it at the time, I had an epiphany and Nitric Oxide answered the questions about what I would be doing for the rest of my life.” Miller had been working as a respiratory therapist prior to his Ph.D. and says “I was working with gasses and helping people on life support, so I wanted to learn more about a gas that had been previously considered poisonous.” Miller explains that there was no way to easily measure NO in those days and it was contained in high pressure cylinders, so his team focused on making devices to measure and deliver NO. “In those days, the recently retired Bruce Murray was my right hand man, he stuck by me for decades on this journey.” Murray and Miller worked with another large company to use NO as an approved drug to save infants with Blue Baby Syndrome from 1998 on, significantly decreasing the amount of related deaths.

Miller shares that “during that time I became fascinated with finding that the NO produced in our bodies works as our first line of defence in our innate immune system and basically did another Ph.D. trying to see how we could use this outside the body to help reduce microbes and infection.” The high pressure cylinders were cumbersome so the team started to explore how they could create and deliver nitric oxide in a liquid and with the help of major grants and his new business partner, Dr. Gilly Regev. Regev and Miller began working together in 2009 and created a liquid that kills microbes very fast. The liquid treatment was developed as far as phase 2 human trials, proving safe and effective for potential use for chronic sinusitis and diabetic foot ulcers. Originally, the team wanted to use their findings to help combat the common flu and cold but knew those would be expensive undertakings, so, prior to the pandemic, they were focusing on uses much cheaper to develop. Miller himself would use the nasal spray before and after plane rides and found the method effective to keep him free of common respiratory illnesses for the past decade.

The pandemic changed the focus for team SaNOtize, as they decided to jump in right away to see if they could help in the fight against the SARS-CoV-2 virus, or COVID-19 infection. In March 2020 they began independent lab testing at Utah State University and showed that their NO releasing solution could eradicate the SARS-CoV-2 virus in under two minutes. The SaNOtize nasal spray works similarly to a hand sanitizer for the nose. Miller explains “if you think you’ve been exposed to the virus, you can spray the mist into your nose, which is the major entry point for COVID. The NO in the liquid acts as a physical and chemical barrier using multiple mechanisms to combat the virus.” Miller shares, “If you think of the COVID spike proteins like a key, and your cells like a lock, one mechanism of action is that the NO twists the spikes into a knot so the key cannot enter the lock, and another mechanism is that it acts like pouring glue into the lock itself so the key cannot insert.” He adds, “also if NO gets into the lock/cells, it prevents replication of the virus.”

Miller and Regev’s company has finished a phase 2 clinical trial in the United Kingdom (UK), where “we had a breakthrough that proved a rapid and impressive reduction in SARS-CoV-2 in infected people -- the study conducted by the Ashford & St. Peter’s Hospital in London to people who self-administered the nasal spray, basically eradicated high levels of the virus in 24-72 hours. The most impressive point was it worked equally well against the mutant UK variant of the virus.” These findings have been submitted for publication in a medical journal, and the company has filed these with Health Canada to support their drug submission. Even though the NO is very low, administered topically and approved as an over the counter device in other countries, in Canada NO is already approved as a prescription drug and SaNOtize is obligated to go through the lengthy process of prescription drug for use as a nasal spray to prevent and treat COVID-19 infection in people. Miller states “we have met with Health Canada and are working on the process for submission for emergency use during the pandemic. They have been very helpful and we are working together to get rapid approval- it can never go fast enough but we are still going as fast as we can while keeping the public safe so we don’t cut corners and can prove the safety for users.” The group is designing and starting, under Canada Health’s direction, two phase 3 trials, one for prevention, and one for treatment. Interested parties can keep an eye on their website for future advertisements looking for participants. Miller says “we hope the public helps us with the prevention trial, there will be eligibility criteria, but also we need informed consent. Sadly, someone needs to be grouped in the 50% that receive a placebo of only salt water and are at risk of contracting COVID, but from a risk-benefit perceptive, this study is the only way to get SaNOtize approved as a drug.”

Currently only two countries approve the use of SaNOtize nasal spray to combat COVID-19 infection, but the goal is to make the product affordable and accessible to all, especially in places where vaccines are not readily available. It is in mass production in Israel, as “we couldn’t get access to manufacturing sites in Canada or many parts of the world because vaccine production is, understandably, tying up factories’’. Mass production was instead started in Israel and the current singular production line is producing 20 bottles a minute around the clock. Three more production lines have been ordered and will soon begin, quadrupling the rate at which the product is made for countries like Israel and Bahrain where it has been approved for use. Many countries are currently reviewing the studies and considering approving the use of the SaNOtize nasal spray and the company hopes to eventually bring production back to Canada.

The nasal spray could be especially effective in other countries who don’t have the vaccine. Miller hopes SaNOtize “could bridge the gap while these countries wait for the vaccine” and aid in the prevention of COVID -19 infection. He adds “what I love most about our nasal spray is that this was never just designed just for treating/preventing COVID-19 infection, the effectiveness does not seem to differ by variant, and works on all viruses including the flu and common cold viruses”. This new tool in the tool belt that could reduce the necessity of masking, as the small and simple bottle can be carried in a purse or pocket and sprayed once or twice a day when a person has been possibly exposed.”

Those interested in supporting the work of SaNOtize can continue to encourage regulatory and government agencies to “help small companies like ourselves to be able to move innovative ideas like this forward.” Not a large Pharma company, SaNOtize is not as equally equipped to fund large prevention trials costing tens of millions of dollars to conduct. Many government, non-profit agencies and countries are getting on board with sponsoring and helping to fund the trials, but Canada has not offered financing assistance at this time.

In the meantime, the group is “working with the World Health Organization and other foundations who see the potential of the nitric oxide nasal spray, and want to move forward”. Groups in India, Mexico, and Brazil are working with SaNOtize to get emergency approvals so that their unique corner of the globe can have equal access to the new weapon combatting COVID-19.

Elizabeth Thompson, Local Journalism Initiative Reporter, Temple City Star