TMB-003 Therapy to Reduce Scarring Wins FDA Orphan Drug Designation

Scleroderma treatment TMB-003, which aims to improve patients’ quality of life by reducing the scarring that characterizes the autoimmune disorder, has been granted orphan drug designation by the U.S. Food and Drug Administration (FDA).

This designation is awarded to investigational therapies intended to improve treatment for rare diseases, defined as conditions that affect fewer than 200,000 people in the U.S. The designation comes with certain incentives, including tax credits for clinical testing and — if the therapy is ultimately approved — seven years of market exclusivity.

“Currently there is no FDA approved treatment for any cutaneous [skin-affecting] symptoms in scleroderma,” John Koconis, CEO of Timber Pharmaceuticals, the developer of TMB-003, said in a press release.

“We are pleased to receive orphan drug designation for our investigational treatment and look forward to advancing into clinical stage research,” Koconis said.

Also called systemic sclerosis, scleroderma is characterized by inflammation and accumulation of scar tissue in the skin and other bodily organs. The main component in scar tissue is a molecule called collagen, which is over-produced in people with scleroderma.

Collagen, the most abundant protein in the human body, is found in the bones, muscles, skin, and tendons. It provides skin its strength and elasticity.

TMB-003 is a formulation of sitaxsentan, which is an endothelin receptor antagonist. By blocking the activity of the endothelin receptor, sitaxsentan is expected to reduce the production of collagen, thereby reducing scarring.

An oral formulation of sitaxsentan was previously marketed as Thelin, by Pfizer, as a treatment for pulmonary arterial hypertension, which occurs when the pressure in the lungs’ blood vessels is abnormally high. Notably, endothelin receptor antagonists can relax blood vessels and lower blood pressure. However, Pfizer voluntarily withdrew Thelin from the market after it was discovered that the medication could cause fatal liver damage.

Unlike Thelin — which, as an oral medication, was designed to deliver sitaxsentan throughout the body — TMB-003 is a formulation of sitaxsentan designed to be administered locally on the skin. Since TMB-003 is not delivered throughout the body, it is expected to avoid the toxic side effects associated with the oral formulation, according to Timber.

Timber currently is in the preclinical stages of testing TMB-003. The company is expecting to submit an investigational new drug application to the FDA in 2022.

This application, if approved, would allow the company to start testing the investigational therapy in people in clinical trials.