Our sGC Programs
We are seeking to harness sGC pharmacology to develop and commercialize breakthrough treatments for serious and orphan diseases.
Ironwood is advancing a pipeline of five innovative soluble guanylate cyclase (sGC) stimulators, which we are investigating in serious and orphan diseases. Each of our sGC stimulators is tailored with unique pharmacologic and biodistribution properties intended to address the diseases in which they are being evaluated.
Our sGC stimulators are designed to enhance nitric oxide signaling by acting upon the nitric oxide / cyclic guanosine monophosphate (cGMP) pathway. In healthy individuals, nitric oxide signaling plays a central role in regulating diverse systems throughout the body, including vascular smooth muscle tone and blood flow as well as processes that influence inflammation, fibrosis, metabolism, and neuronal function. Deficient nitric oxide signaling is linked to a wide range of cardiovascular, metabolic, inflammatory, fibrotic, and neurological diseases.
Our preclinical and early stage clinical studies suggest that sGC stimulators may improve vaso-dilation and blood flow. They may also have anti-inflammatory and anti-fibrotic effects, as well as beneficial effects on metabolic parameters such as lipid and glucose levels – all of which are also influenced by the nitric oxide / cGMP pathway.
Our sGC Product Candidates
Our extensive portfolio of five investigational product candidates comprises distinct sGC stimulators that we are studying in a variety of diseases – including sickle cell disease, diabetic nephropathy, heart failure with preserved ejection fraction (HFpEF), and serious neurodegenerative, liver, and lung disorders. All of these diseases are believed to be linked to a deficiency in nitric oxide signaling, and studies in preclinical models suggest the potential utility of sGC stimulation to treat these diseases. Each of our sGC stimulators is designed to preferentially modulate pathway signaling in tissues of greatest relevance to the diseases they are intended to treat.
- • Vascular: Olinciguat is a vascular sGC stimulator under investigation for the potential once-daily, ongoing treatment of sickle cell disease. In preclinical studies, olinciguat was shown to distribute to both the vasculature and organs such as the kidney and lungs, which are often affected in sickle cell disease. Olinciguat was granted Orphan Drug Designation for sickle cell disease by the FDA and is currently in a Phase II study.
- • Systemic: Praliciguat is a systemic sGC stimulator under investigation for the potential once-daily, ongoing treatment of diabetic nephropathy, and of heart failure with preserved ejection fraction (HFpEF). In preclinical studies, praliciguat was shown to distribute extensively into tissues relevant to cardiometabolic disease, particularly adipose, kidney, heart, and liver. Praliciguat is currently in Phase II studies for both diabetic nephropathy and for HFpEF. Praliciguat was granted Fast Track Designation for HFpEF by the FDA.
- • Central nervous system: IW-6463 is a central nervous system (CNS)-penetrant sGC stimulator under investigation for the potential treatment of serious neurodegenerative diseases. In preclinical models, IW-6463 has been shown to increase cerebral blood flow, reduce markers of neuroinflammation, enhance cognition and provide neuroprotection.
- • Liver: We are advancing a discovery program to evaluate the potential of liver-targeted sGC stimulation in the treatment of serious liver diseases.
- • Lung: We are also advancing a discovery program to evaluate the potential of sGC stimulation in the treatment of pulmonary diseases.