FAQ

Yes, R-107 has issued and pending composition of matter and method of use patents in approximately 40 countries, including the U.S., Australia, Brazil, China, Europe, India, Japan, Russia and South Korea. The patents covering use of R-107 in treatment of COVID-19 should provide patent protection through at least 2045.

Claritas has exclusive rights under all patents to commercialize R-107 for treatment of COVID-19 infection.  Claritas was granted these rights under an exclusive, world-wide license agreement with Salzman Group, Ltd., the owner of the patents.What is R-107?

R-107 is an injectable drug that releases nitric oxide into tissues throughout the body.

Data from a clinical study recently announced by Massachusetts General Hospital (“Mass General”) demonstrate that nitric oxide can eliminate the virus that causes COVID-19 infection.

• In the Mass General study, six pregnant patients with severe and critical COVID-19 infection received rescue therapy with inhaled nitric oxide. The treatment was well tolerated. By day 22, five of the six patients, who received no other antiviral medication, tested negative twice for SARS-CoV-2 (the human coronavirus that causes COVID-19 infection). All six patients were discharged, and have delivered healthy, COVID-19 free, infants. These data represent a breakthrough in the potential treatment of COVID-19 infection.
• In addition, Know Bio, LLC recently announced data from vitro studies which demonstrate that nitric oxide can inhibit viral reproduction of SARS-CoV-2. The result was a greater than a 99.9% reduction in virus observed after 24 hours, versus virus observed in untreated cells.
• Researchers at Uppsala University in Sweden recently announced in vitro data demonstrating the dose dependent antiviral effect of nitric oxide on SARS-CoV-2 replication.

Yes, following are links to recent articles regarding the potential of nitric oxide for treatment of COVID-19 infection:

1. Remarkable Nitric Oxide Being Tested as Coronavirus Drug: https://www.mercurynews.com/remarkable-nitric-oxide-being-tested-as-coronavirus-drug
2. UAB To Test Nitric Oxide For Severe Coronavirus Patients | Birmingham, AL Patch:https://patch.com/alabama/birmingham-al/uab-test-nitric-oxide-severe-coronavirus-patients
3. Coronavirus: Nitric Oxide Eyed as a Possible COVID-19 Cure and Answer to Ventilator Shortages: Health: Tech Times: https://www.techtimes.com/articles/248674/20200408/coronavirus-nitric-oxide-eyed-as-a-possible-covid-19-cure-and-answer-to-ventilator-shortages.htm
4. EmphyCorp News: Nitric Oxide is Currently Being Tested in Clinical Trials as a Potential Treatment for Patients Infected with the Coronavirus: https://www.prnewswire.com/news-releases/emphycorp-news-nitric-oxide-is-currently-being-tested-in-clinical-trials-as-a-potential-treatment-for-patients-infected-with-the-coronavirus-301025740.html
5. LSU Health Shreveport Testing to See if Inhaled Nitric Oxide | WWL:  https://wwl.radio.com/articles/louisiana-radio-network-news/lsu-health-shreveport-testing-to-see-if-inhaled-nitric-oxide
6. Mallinckrodt, Novoteris’ Nitric Oxide will Start COVID-19 Trial:  https://pharmaphorum.com/news/mallinckrodt-novoteris-nitric-oxide-will-start-covid-19-trial/
7. Inhaled Nitric Oxide Explored for COVID-19 Oxygenation: https://www.medscape.com/viewarticle/930412
8. Bellerophon Therapeutics Announces FDA Clears Initiation of Phase 3 Study for INOpulse® Inhaled Nitric Oxide Therapy to Treat COVID-19: https://www.benzinga.com/pressreleases/20/05/g15999273/bellerophon-therapeutics-announces-fda-clears-initiation-of-phase-3-study-for-inopulse-inhaled-nit
9. Researchers Say Nitric Oxide Therapy is Safe, Helps COVID Patients Breathe; Further Biological Data Needed: https://www.wbrz.com/news/researchers-say-nitric-oxide-treatment-is-safe-helps-covid-patients-breathe-further-biological-data-needed/
10. Ohio State to Test Novel Nitric Oxide Therapy on COVID-19 Patients: https://medicine.osu.edu/recent-highlights/osu-to-test-novel-nitric-oxide-therapy-on-covid19-patients

Nitric oxide is a gas that is administered to intubated patients through use of a specialized breathing device. The drug must be administered by a trained respiratory therapist, and it must be administered twice daily.

Nitric oxide works against COVID-19 infection in each of the first two stages of the disease:

Stage One (nitric oxide prevents viral infection and multiplication):

• Viral Infection: When the SARS-CoV-2 virus enters the body, nitric oxide prevents the virus from entering and infecting human cells by interfering with the attachment of palmitate to the spike protein on the outer surface of the virus. By interfering with palmitate attachment to the spike protein, the virus is unable to attach to the receptor on the membrane of human cells. When the virus is unable to attach to the membrane of the human cells, it cannot enter and infect the cells.
• Viral Multiplication: If the virus has already infected a cell, nitric oxide inhibits viral replication by inactivating certain proteins that prevent the RNA genome of the virus from replicating. Without the ability to replicate its genome, the coronavirus cannot multiply.

Stage Two (nitric oxide reverses respiratory symptoms of low oxygen levels and shortness of breath):

The second stage is the pulmonary stage, when the immune system becomes strongly involved, leading to primary respiratory symptoms such as persistent cough, shortness of breath and low oxygen levels.

• Nitric Oxide is a Pulmonary Vasodilator: Since its discovery more than 30 years ago, nitric oxide has become well recognized as a pulmonary vasodilator and anti-inflammatory agent. When nitric oxide is released into the lungs, it dilates blood vessels, lowering blood pressure and allowing blood to travel more easily through the lung without building up in the lung tissue. Preventing this build up in the lung tissue is important to health. Excess fluid that spills into the lung tissue makes the lungs stiff and hard to expand with each breath. Excess fluid also clogs up the air spaces in the lung so that air cannot enter the lung properly and oxygen cannot be absorbed into the blood. Nitric oxide prevents this unhealthy build-up of fluid in the lung,

In addition, nitric oxide protects the inner lining of the blood vessels (“the endothelium”). This protection ensures that white cells in the blood pass through the lung without sticking to the endothelium. White cells that stick to the endothelium cannot only damage the blood vessel itself can also pass through the blood vessels and enter the lung tissue where they can cause vast damage from toxins they release. Nitric oxide prevents white cells from entering the lung.

These effects translate into a healthier lung that is able to easily expand and allow oxygen to enter the bloodstream, thereby reversing shortness of breath and low oxygen levels.

Lorenzo Berra, the critical-care specialist at Massachusetts General Hospital who is overseeing an international trial of nitric oxide in treatment of COVID-19 stated, “It’s a pretty remarkable drug. It has a risk profile that is minimal.” Dr. Keith Scott, principal investigator of the Louisiana component of the Mass General trial stated that, “We have tremendous confidence this therapy will alter the devastating effects of COVID-19… If results show promise, and since this gas is already FDA-approved, widespread use could begin immediately.”

Åke Lundkvist, a professor at Uppsala University, who led the Uppsala study, stated, “To our knowledge, nitric oxide is the only substance shown so far to have a direct effect on SARS-CoV-2.”

No, nitric oxide gas must be administered as an inhalation therapy requiring special CPAP-like delivery equipment and administration by a trained respiratory therapist twice per day, which substantially limits the number of patients that can be treated at any one time. As such, nitric oxide is not a practical treatment in a pandemic situation.

• R-107 Transforms Nitric Oxide Into a Practical Therapy: Despite the compelling data demonstrating nitric oxide’s activity against COVID-19 infection, nitric oxide gas is not a practical therapy for use in a pandemic situation. R-107 overcomes the issues with nitric oxide gas, and transforms nitric oxide therapy into a potentially best-of-care treatment for COVID-19 infection – even in a pandemic situation. Unlike nitric oxide, which must be administered as an inhalation therapy, R-107 is a liquid that is readily administered by a single intramuscular injection. Due to its ease of administration, R-107 will allow for thousands of patients to be treated simultaneously, without the need for special delivery equipment or trained respiratory therapists.
• R-107 Provides Sustained Delivery of Nitric Oxide Over a 24-Hour Period: Unlike nitric oxide, which has a half-life of only a few seconds after being absorbed in the lung, R-107 slowly releases nitric oxide all tissues of the body over 24-hours
• R-107 Delivers Nitric Oxide Systemically Throughout the Body – Not Just in the Lungs:  After injection, R-107 enters the bloodstream, where it begins to deliver nitric oxide systemically throughout the body, thus allowing the nitric oxide it release to potentially eliminate the SARS-CoV-2 virus in all tissues, not only in the lungs.

There are other nitric oxide releasing compounds, such as nitroglycerin. However, these other compounds rapidly induce tolerance and lose biological activity after more than a single dose.  In contrast, R-107 does not lose its potency, even after prolonged periods of use.

While vaccines are an important step in combatting the virus, they are not the entire solution.

Some viruses, such as the SARS-CoV-2 virus which causes Covid-19 infection, are constantly mutating and evolving. A recent mutation of the SARS-CoV-2 virus has appeared in the U.K and South Africa, and this raises questions regarding the effectiveness of vaccines against future variants of the virus.

A Covid-19 therapy will remain a crucial element of the medical response to Covid-19 infection for several reasons, including the following: (1) viral mutation may cause vaccines to no longer be effective; (2) lack of durability, causing the vaccines to lose effectiveness over time; and (3) lack of effectiveness in the elderly, the population at greatest risk.

Regardless of the success of vaccines, or lack thereof due to viral mutation, Covid-19 infection may continue due to several factors, including the fact that many may not receive the vaccine for a variety of personal reasons. Influenza vaccination, for example, is not received by 40% of the population, even though it is free and widely available. For these reasons, an effective Covid-19 therapy will be essential to treat patients who contract the virus.

Claritas believes that R-107 has potential to become an effective front-line therapy for patients who contract Covid-19 infection. R-107 is anticipated to be effective against all strains because its mechanism of action is not dependent upon the specifics of the viral structure. The Company believes that R-107 may also have potential as a prophylactic to prevent COVID-19 infection, and the Company intends to also develop R-107 as a nasal spray for this purpose.

So far, only two drugs have demonstrated a therapeutic effect against COVID-19 in randomized clinical trials: the antiviral Veklury (remdesivir) and the common steroid dexamethasone. Remdesivir reduced the recovery time for infected patients and dexamethasone reduced mortality for the sickest patients. However, neither remdesivir nor dexamethasone eliminated the SARS-CoV-2 virus, as did nitric oxide in the Mass General study. To date, Veklury (remdesivir) is the only U.S. FDA approved antiviral drug for use in adult and pediatric patients for the treatment of COVID-19 requiring hospitalization. There is currently no medication recommended to prevent COVID-19, and no cure is available.

Claritas will enter into a strategic collaboration with the Salzman Group, under which the Salzman Group will make available to Claritas the full capabilities of Salzman Group, including their deep expertise in working with nitric oxide and nitric oxide releasing compounds. Andrew Salzman, M.D., Chairman of Salzman Group, was the first physician to administer inhaled nitric oxide to a human patient in 1990, and Salzman Group has been working since 1994 to deliver nitric oxide in a non-gaseous form. R-107 is the non-gaseous form of nitric oxide that was invented by Salzman Group. Salzman Group will provide a platform of services to Claritas, including expertise in the manufacture of R-107, the design of clinical studies and interactions with regulatory bodies in the U.S., Australia and the EU.

The immediate next step is to complete a Phase 1 clinical study to demonstrate that R-107 is safe in humans. This will be followed by Phase 2 and Phase 3 clinicals studies. It is anticipated that the FDA will allow an expedited clinical development pathway for R-107 in this indication.

• R-107 is Phase 1 Ready Right Now: To date, the development of R-107 has been largely funded by approximately $15 million of federal funds that were provided to Salzman Group under a grant provided by the U.S. Department of Health and Human Services.  In addition to this $15 million of federal funding, Salzman Group also invested approximately $5 million of its own funds in the preclinical development of R-107. At this point all pre-IND work is complete, including safety studies in two large animal species.
• Phase 1 Clinical Study: Claritas plans to submit an Investigational New Drug Application (IND) to the Australian Therapeutic Goods Administration (TGA) and the U.S Food and Drug Administration (FDA) in support of the first-in-human Phase 1 clinical study. This Phase 1 study of intramuscular R-107 will be conducted at CMAX, a clinical contract research organization located at Royal Adelaide Hospital in Australia.

• Estimated Cost of Phase 1 Clinical Study: The estimated cost of the Phase 1 study is CAD $1,040,000. Claritas will work with Echelon Wealth Partners to complete a private placement financing to fund the R&D cost of the Phase 1 study, as well as funding for 12-months of G&A expense.
• Follow-On Clinical Studies: Following completion of the Phase 1 study, Claritas intends to apply for funding from the U.S. Department of Health and Human Services for the further development of R-107 in COVID-19 infection.