Claritas Acquires Global Rights to R-107 for PAH, Other Lung Diseases
Claritas Pharmaceuticals now has exclusive worldwide rights to develop and market R-107 — a liquid form of nitric oxide — for the treatment of pulmonary diseases such as pulmonary arterial hypertension (PAH), acute respiratory distress syndrome (ARDS), and persistent pulmonary hypertension of the newborn (PPHN).
In its announcement of the deal, Claritas said R-107 has issued and pending patents in some 40 countries, including the U.S., Australia, Brazil, China, India, Japan, Russia, and South Korea. Patents also have been granted in Europe, according to an earlier press release.
The company completed its acquisition of the therapy candidate following the amendment of a license with the Salzman Group, which had originally granted Claritas the rights to market R-107 as a potential treatment against SARS-CoV-2, the virus that causes COVID-19. Claritas also is developing R-107 for COVID-related ARDS, and COVID-related sepsis, a life-threatening condition that arises when the body has an extreme response to an infection.
“With the addition of R-107 for treatment of PAH, Claritas now has two programs addressing large commercial markets,” said Robert Farrell, president and CEO of Claritas.
“In addition to our program developing R-107 for treatment of viral infections, including COVID-related lung disease, we now also have a potential breakthrough product that could provide unrivalled results in treatment of PAH,” Farrell said.
Claritas expects to launch a Phase 2a study testing R-107 for PAH by September 2022, and a Phase 2a study of R-107 for PPHN by the end of next year.
“R-107 is a technology that transforms nitric oxide therapy from an impractical, expensive, and difficult to administer inhalation therapy, into a practical treatment that can be administered by capsule or by injection,” Farrell said. “It has been demonstrated that nitric oxide is clinically effective in the treatment of PAH. For this reason, we have now acquired exclusive, worldwide rights to develop R-107 as a nitric oxide therapy for PAH.”
Nitric oxide, a gas naturally found in the body, has been shown to work as a vasodilator — a compound that relaxes and widens blood vessels — so that blood flows more easily with less pressure. It also works as an antiviral, fighting off viruses.
Most nitric oxide treatments are inhaled, but Claritas is developing R-107 as an injectable or oral therapy, which will allow it to reach all cells in the body.
Previous data from a rat model of PAH showed that R-107 completely stopped the progression of PAH. It also restored blood pressure in the lungs, with the benefits persisting after treatment stopped. This is an important feature, as existing PAH medications have been shown to ease symptoms but cannot stop the disorder’s progressive damage.
R-107 also provided the tested animals with immediate and nearly total relief of severe symptoms, as shown by a drop of blood pressure within minutes of receiving R-107. A single dose was enough to control the pressure for a full 24 hours, supporting its long-lasting relief effects.
This result was in clear contrast with the effects achieved with animals given the approved PAH therapies Revatio (sildenafil), marketed by Pfizer, and Tracleer (bosentan), manufactured by Janssen. Those therapies provided approximately half of R-107’s observed potency, and over shorter lengths of time.
Furthermore, rats with PAH receiving a two-week pulse of R-107 experienced a 75% reduction of their elevated blood pressure. This was sustained for days even after treatment ended.
Both Revatio and Tracleer also are linked with side effects including liver injury, flushing, dizziness, and nasal congestion. No such effects were detected with R-107.
So far, toxicology and safety studies suggest that the therapy is well-tolerated, according to Claritas.
“Based on the exceptionally positive data we saw in the validated animal model of PAH, we believe that R-107 could become a best-in-class, front-line therapy for PAH,” Farrell said. “If we can demonstrate similar data with R-107 in a Phase 2a clinical study in humans, we believe that R-107 will be viewed as a potentially valuable pharmaceutical asset that we might seek to out-license or sell.”
In a Phase 1a study, currently ongoing, middle-aged healthy volunteers were randomly selected to receive one of four ascending doses of R-107, given as an intramuscular injection, or a placebo. The trial, scheduled for completion by March 2022, is seeking to assess the therapy’s safety and pharmacokinetics, or its movement into, through, and out of the body.
“We will complete our Phase 1 clinical study by Q1 next year, and we expect to complete the Phase 2a study of R-107 in the treatment of PAH in 2022,” Farrell said.
The PAH clinical study will be conducted in Australia and involve hospitalized patients. The goal is to establish proof of concept that R-107 is effective in reducing blood pressure in the lungs.
The company shared more details, in a separate press release, of its planned efforts to develop R-107 for PPHN, one of the main causes of neonatal death and severe disease.
Inhaled nitric oxide is the only approved treatment for PPHN. However, nearly 50% of infants are resistant and/or do not respond to the treatment.
This failure in response is believed to be caused by the high levels of oxidants in babies’ lungs that inactivate nitric oxide. Oxidants are reactive molecules that can damage other molecules and tissues in the body.
According to Claritas, R-107 addresses both issues by providing nitric oxide and degrading oxidants. The company believes that R-107 will be more effective than inhaled nitric oxide in the treatment of PPHN, and has plans to conduct a Phase 2 clinical trial in late 2022. If this trial is successful, Claritas said it will seek to out-license or sell the program.