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Fexuprazan

Fexuprazan is a potassium-competitive acid blocker (P-CAB) designed to block proton pumps from secreting gastric acid in the stomach. Fexuprazan is being developed for the treatment of erosive esophagitis (EE), a condition that impacts millions of patients in the US. It is estimated that 65 million people in the US have gastroesophageal reflux disease (GERD) and that 20% of GERD sufferers have EE.

 

EE is characterized by breaks (irritation and damage) in the inner lining of the esophagus (tube that runs from the throat to the stomach) caused by a recurring reflux of acidic stomach contents over time. Symptoms of EE and GERD may include heartburn (a rising, burning sensation behind the breastbone) and regurgitation (sensation of backward flow of liquid content up into the chest or throat). Complications (which are not very common) include narrowing (strictures) of the esophagus that can lead to difficulty swallowing or food getting stuck (in the chest).

 

Current standard treatments for EE and GERD include medicines called Proton Pump Inhibitors (PPIs). PPIs became a standard of care in the treatment of acid-related GI disorders after their introduction in the 1980s. PPIs are useful and widely prescribed drugs around the world. However, they do present some shortcomings, the most important of which are a relatively slow onset and lack of 24-hour acid control. These limitations have left a sizable patient population with EE to look for alternatives that can provide sustained efficacy throughout the day and prevent relapse of EE and heartburn symptoms over time.

 

Fexuprazan is part of a class of drugs called P-CABs, which have been shown to act more rapidly and suppress the secretion of acids more effectively and for a longer duration than PPIs. Fexuprazan has the potential to provide significant improvement over the current standard of care in treating EE and other acid-related GI disorders, providing patients with an alternative to PPIs.

NG101

NG101 is a potent, selective and peripherally restricted dopamine D2 receptor antagonist currently in Phase 2 clinical development for the treatment of gastroparesis. Neurogastrx has generated preclinical data indicating that in addition to its potent antiemetic properties, NG101 is also expected to significantly increase gastric motility, conferring NG101 an ideal pharmacological profile for the treatment of gastroparesis.

 

Gastroparesis is a chronic, severe and debilitating disorder that may be associated with dysfunction in the enteric nervous system, causing the movement of food from the stomach to the small intestine to slow or stop, and preventing or disrupting normal digestion. Common symptoms include nausea, vomiting, bloating, early satiety, fullness after eating and abdominal pain. These symptoms are chronic and often constant, significantly impacting the patient’s quality of life. Severe cases result in the inability to digest foods and liquids and lead to malnutrition, weight loss and dehydration, periodically requiring hospitalization.

 

The only approved therapy for gastroparesis in the US, metoclopramide, is a D2 antagonist developed several decades ago and has significant neurological side effects due to its interactions with a variety of receptors throughout the brain. These CNS toxicities have resulted in a black box warning limiting its use to 12 weeks. Other drugs in the class have shown other adverse events, including cardiovascular problems that have prevented them from being approved in the US. Neurogastrx aims to bring forward a D2 antagonist appropriate for first-line therapy without the side effects that have plagued the class for decades.

 

NG101 has dual mechanisms of action: central antagonism of D2 receptors in the area postrema, an area of the brain stem outside of the blood brain barrier resulting in its potent antiemetic and anti-nauseant properties, and blockade of D2 receptors in the guts which results in a positive effect on motility.

 

Also, NG101 and its major metabolite are substrates of P-Glycoprotein, an important protein of the cell membrane that pumps many foreign substances out of cells, including preventing them from crossing the blood-brain barrier. This important characteristic of NG101 makes central nervous system adverse events unexpected.

 

Preclinical data shows that NG101 has the potential to be an improvement over the current standard of care as it does not cross the blood-brain-barrier and does not alter cardiac rhythm, another concern for products in this class. These features may provide safety and tolerability advantages over existing marketed products.

 

NG101-Blodd-Brain-Barrier

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