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Pulmonary Arterial Hypertension

Pulmonary Arterial Hypertension (PAH) is a progressive disease caused by the loss of small blood vessels in the lungs. Over time, as the same amount of blood travels through fewer blood vessels, there is an increase in blood pressure in the lungs. This increased blood pressure can cause other damage, such as to the lining of the blood vessels (known as the endothelium) [1]. Northern Therapeutics has focused on a natural way to reduce the high blood pressure in the lungs by restoring an enzyme that dilates pulmonary blood vessels. This enzyme, known as endothelial nitric oxide synthase, or eNOS, also improves the health of the endothelium. Northern Therapeutics has also discovered evidence that eNOS can repair and regenerate blood vessels in the lungs of animals that have PAH [2]. While current treatments attempt to address endothelial dysfunction and excess vasoconstriction, PAH symptoms continue to progress and worsen for most patients [3]. Therefore, there is an unmet need for new therapies for PAH that can restore normal pulmonary blood pressure and lung function. Northern Therapeutics has pioneered an investigational cell therapy referred to as mc-eNOS-transfected EPCs or Aurora-GT(1) that increases eNOS, and which works directly to dilate blood vessels in the lung. This eNOS producing cell therapy is being tested in an advanced clinical trial known as SAPPHIRE. Recruitment for the SAPPHIRE trial began in 2017 and closed in December 2022.

The scientific basis for the SAPPHIRE trial, and the use of eNOS expressing cells is based on the PHACeT clinical trial.

The "Pulmonary Hypertension and Angiogenic Cell Therapy trial" (PHACeT) conducted by Northern Therapeutics was a 'first-in-human', early phase dose-escalation study to assess the safety and efficacy of autologous endothelial progenitor cells (EPCs) transfected with human endothelial NO-synthase (eNOS) gene in patients with severe PAH refractory to available treatment. This trial showed that the study product was well tolerated with promising potential signals of improvements in functional class and exercise tolerance [1] (NCT00469027).

The SAPPHIRE Clinical Trial

The "Study of Angiogenic Cell Therapy for Progressive Pulmonary Hypertension: Intervention with Repeat dosing of eNOS-enhanced EPCs" (SAPPHIRE, NCT03001414) is a late phase cell therapy clinical trial to establish the efficacy and safety of repeat dosing of autologous endothelial progenitor cells (EPCs) transfected with human eNOS gene in patients with PAH in addition to conventional treatments. SAPPHIRE is a randomized, double-blind, placebo-controlled trial designed with a 3-arm protocol. Enrolment is now terminated, and final data analysis will take place once all participants complete the treatment phase of the trial. The SAPPHIRE study enrolled 12 patients in multiple centers across Canada, and is expected to unblind in early 2024.

If you want to learn more about the SAPPHIRE trial, contact Northern Therapeutics at +1 343 291 1197 / email: adminhr@northernther.com.

(1) “mc-eNOS-transfected EPCs, or Aurora-GT, is an investigational therapy, and has not been approved by Health Canada or the U.S. Food and Drug Administration.”