Ironwood Pharmaceuticals progresses vascular and fibrotic disease platform with positive top-line Phase Ia data on soluble Guanylate Cyclase stimulator IW-1701

In the study, IW-1701 demonstrated the expected cardiovascular pharmacodynamic effects, proof of mechanism for sGC stimulation, a dose range that was well tolerated in healthy volunteers as a single dose, and a pharmacokinetic profile suitable for once-daily dosing and consistent with distribution into tissues.

The totality of clinical and preclinical data generated to date supports continued development of IW-1701, and Ironwood intends to initiate a Phase Ib multiple ascending dose study in the first half of 2016, with topline data from this study expected by the end of 2016.

"Soluble guanylate cyclase is part of a signaling pathway that regulates blood flow, inflammation and fibrosis, which is why sGC stimulators offer such a breadth of therapeutic potential in vascular and fibrotic diseases such as congestive heart failure and diabetic nephropathy, as well as certain orphan diseases such as pulmonary arterial hypertension, Duchenne muscular dystrophy and achalasia, among others," said Mark Currie, Ph.D., chief scientific officer and president of research and development at Ironwood.

"Today’s positive Phase Ia results with IW-1701 – along with our recent positive Phase Ia data with our other clinical sGC stimulator IW-1973 – demonstrate that Ironwood’s sGC stimulators have attractive pharmacologic and pharmacokinetic profiles, providing multiple opportunities to develop therapies that, if approved, can address important unmet needs."

These IW-1701 Phase Ia data, along with Phase Ib data for IW-1973 and IW-1701 expected later this year, will inform the selection of doses and priority indications for the expected initiation of multiple Phase II studies with Ironwood’s sGC stimulators in 2016. IW-1701 and IW-1973 have distinct pharmacologic profiles and have the potential to produce multiple blockbuster products for the company.

Similar to Ironwood’s recently completed Phase Ia study of IW-1973, the Phase Ia study of IW-1701 was designed as a randomized, double-blind, placebo-controlled, single ascending dose study. The 24 healthy volunteers enrolled were randomized 3:1 to receive a single dose of IW-1701 or placebo administered once-daily via an oral capsule.

Top-line clinical data were consistent with preclinical findings and included cardiovascular pharmacodynamic effects, dose-proportional pharmacokinetics, and biomarker-based confirmation of target engagement. No serious adverse events were reported. Reported adverse events were consistent with the mechanism of action. Study results are expected to be presented at a future medical conference