Gesynta Pharma Seeks OK to Assess GS-248 in Trials

Gesynta Pharma has submitted an investigational new drug (IND) application to the U.S. Food and Drug Administration (FDA) seeking approval to test its oral therapy, GS-248, in clinical trials with systemic sclerosis (scleroderma) patients.

GS-248 is an experimental therapy being developed for conditions characterized by microvascular disease, including systemic sclerosis. The therapy is currently being tested in a Phase 2 trial (NCT04744207) in Europe — underway in four European countries — and it already has recruited more than half of the estimated 80 participants. More information about trial enrollment is available here.

“I am delighted with the response and hard work from our clinical trial team to reach the halfway point of the study recruitment despite of COVID-19, and this has allowed us to confidently submit an IND for the systemic sclerosis indication,” Patric Stenberg, CEO at Gesynta Pharma, said in a press release.

People with systemic sclerosis often develop Raynaud’s phenomenon, a condition that causes pain, numbness and tingling in the fingers and toes in response to cold temperatures or stress. Raynaud’s phenomenon occurs because excess collagen narrows the small blood vessels supplying blood to the fingers and toes.

GS-248 works by blocking a protein called microsomal prostaglandin E synthase-1 (mPGES-1) that promotes inflammation in several conditions, including systemic sclerosis. mPGES-1 drives inflammation by activating the release of prostaglandin E2 (PGE2), an inflammatory protein.

By blocking mPGES-1, GS-248 has anti-inflammatory activity as well as a vasodilatory action, widening blood vessels and improving blood flow.

Gesynta’s IND application is based on positive results from a Phase 1 trial (NCT04036227) in healthy individuals, showing that treatment with GS-248 once per day for 10 days was safe and tolerable, and it effectively blocked mPGES-1, reduced PGE2 release, and induced vasodilation.

Following positive Phase 1 clinical data, the company advanced the clinical development of GS-248 into Phase 2 trials.

In the ongoing Phase 2 trial in Europe, up to 80 participants (ages 18 to 75) will be assigned randomly to receive either GS-248 (120 milligrams) or a placebo once daily for four weeks. The goal is to determine the safety and effectiveness of GS-248 in treating Raynaud’s phenomenon, normalizing blood flow, and reducing pain in patients with systemic sclerosis. Top-line data from the trial is expected in the first quarter of 2022.

“GS-248 has a promising mode of action which could bring relief to both patients with systemic sclerosis and with other chronic inflammatory diseases,” said Ariane Herrick, MD, coordinating investigator.

According to Gesynta, the company plans to explore GS-248’s therapeutic potential for other indications, such as cardiovascular diseases and rheumatic diseases.

“We are accelerating research into other indications and are looking forward to announcing results from validation studies in pulmonary hypertension,” Stenberg said.