Kalytera to Acquire R-107, Potential Liquid Nitric Oxide Treatment for PAH

Kalytera Therapeutics intends to acquire Salzman Group, a company developing R-107 — a liquid form of nitric oxide — to possibly treat pulmonary arterial hypertension (PAH), lung disease associated with COVID-19, and other lung disorders, the company announced.

Its acquisition of the Massachusetts-based company should be completed by June 15.

R-107 is a liquid prodrug of nitric oxide (NO), a strong vasodilator that opens blood vessels and is used to treat multiple respiratory conditions. In the lung, NO reduces blood flow resistance to improve oxygenation. At high concentrations, NO is involved in the activity of the immune system in fighting infections.

A prodrug is a medication or compound that, after administration, is metabolized (i.e., converted within the body) into a pharmacologically active drug.

Nitric oxide gas is usually administered via high-pressure cylinders in a hospital, and require handling by trained respiratory therapists.  Companies are working to design easier ways of allowing for its use by patients.

R-107 is a liquid formulation of NO administered by a single intramuscular injection. According to Kalytera, the injection is fairly easy and the therapy’s potency is sustained for prolonged periods following administration. This is in contrast with other NO liquid form products, such as nitroglycerin, which rapidly induces tolerance and loses biological activity after more than one administration.

Preclinical data with animal models of PAH showed that treatment with R-107 led to sustained relief, with pulmonary arterial blood pressure dropping by 70% after a single dose of R-107. The decrease was sustained for more than two days (48 hours).

R-107 also outperformed similar therapies tested in the same animal models of PAH in terms of potency and duration of response.

It is also being developed as a potential treatment for chlorine inhalation lung injury and for COVID-19 associated lung disease.

A study showed that NO inhalation has an inhibitory effect on the replication of the severe acute respiratory syndrome coronavirus (SARS CoV), a virus of the same family as SARS-CoV2 virus — the viral strain that causes COVID-19.

A Phase 2 trial (NCT04306393) is evaluating whether inhaled NO improves oxygenation in hospitalized patients with very low oxygen levels due to SARS-CoV2. The trial is underway in the U.S., and sponsored by Massachusetts General Hospital.

The Salzman Group aims to test R-107 in patients with COVID-19-related acute respiratory distress syndrome who require intubation and mechanical ventilation. The company plans to submit an application for a Biomedical Advanced Research and Development Authority (BARDA) contract to speed the therapy’s consideration for approval by the FDA.