Ironwood Progresses Vascular And Fibrotic Disease Platform With Positive Top-Line Phase Ia Data On Soluble Guanylate Cyclase Stimulator IW-1701

-Multiple Phase II Studies Expected to Initiate in 2016-

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Ironwood Pharmaceuticals, Inc. (NASDAQ: IRWD) today announced positive top-line data from a Phase Ia study of IW-1701, an investigational soluble guanylate cyclase (sGC) stimulator from Ironwood’s vascular and fibrotic disease platform. 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.

“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.”

“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.

About Ironwood’s sGC Platform

The enzyme soluble guanylate cyclase (sGC) plays a central role in physiological control of blood flow, inflammation, and fibrosis. Modulating the sGC signaling pathway may have beneficial effects in multiple vascular and fibrotic diseases with high unmet need, 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. Ironwood established its expertise in guanylate cyclases through the discovery and development of linaclotide, a guanylate cyclase C (GC-C) agonist. Stimulation of sGC is a clinically validated approach, and Ironwood has discovered a diverse library of sGC stimulators. Ironwood’s investigational sGC stimulators IW-1973 and IW-1701 are in Phase I studies with multiple Phase II studies expected to initiate in 2016.

About Ironwood Pharmaceuticals

Ironwood Pharmaceuticals (NASDAQ: IRWD) is focused on creating medicines that make a difference for patients, building value to earn the continued support of our fellow shareholders, and empowering our team to passionately pursue excellence. We discovered, developed and are commercializing linaclotide, which is approved in the United States and a number of other countries. Our pipeline priorities include exploring further opportunities for linaclotide, as well as leveraging our therapeutic expertise in gastrointestinal disorders and our pharmacologic expertise in guanylate cyclases to address patient needs across the upper and lower gastrointestinal tract. Ironwood was founded in 1998 and is headquartered in Cambridge, Mass. Connect with us at www.ironwoodpharma.com or on Twitter at www.twitter.com/ironwoodpharma; information that may be important to investors will be routinely posted in both these locations.

This press release contains forward-looking statements. Investors are cautioned not to place undue reliance on these forward-looking statements, including, but not limited to, statements about the design and results of our clinical and preclinical studies of IW-1701 and IW-1973 and the impact thereof, including the Phase Ia study of IW-1701 and the effects, tolerability, tissue distribution, suitability for once daily dosing and proof of mechanism observed; the impact of data from the Phase I studies for IW-1701 and IW-1973 on future development plans for our sGC stimulators; the clinical programs for our sGC stimulators, including the expected Phase Ib and II clinical studies, the goals and design of such studies, the data to be generated from such studies and the timing and impact thereof; the anticipated release of more data on IW-1701 at medical conferences; the therapeutic opportunities for sGC stimulators and the unmet need for such diseases; the blockbuster potential of IW-1701 and IW-1973; and the design, breath, scope and potential of our library of sGC stimulators, their pharmacological and pharmacokinetic profiles, and our development plans and activities with respect thereto. Each forward-looking statement is subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statement. Applicable risks and uncertainties include, but are not limited to, the risk that we are unable to conduct the Phase Ib or II clinical studies for IW-1701 or IW-1973 on the same timelines or with the same results as we currently anticipate, or we are otherwise unable to effectively execute on the clinical programs for our sGC stimulators; the risk that the data from such clinical studies are not available when we currently anticipate them or do not demonstrate the results or provide the information we expect, including with respect to doses and priority indications; the risk that we are not able to publish data on our sGC program on the timeline or through the media that we currently anticipate; the risk that future clinical studies need to be discontinued for any reason, including safety, tolerability, enrollment, manufacturing or economic reasons; the risk that the data from previous non-clinical or clinical studies do not support the data from future clinical studies; the risk that the therapeutic opportunities for sGC stimulators and the potential for our library of sGC stimulators is not as we expect; those related to decisions made by regulatory authorities; and those risks related to competition and future business decisions made by us and our competitors or potential competitors. Applicable risks also include those that are listed in Ironwood’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2015, in addition to the risk factors that are listed from time to time in Ironwood’s Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q and any subsequent SEC filings. Ironwood undertakes no obligation to update these forward-looking statements to reflect events or circumstances occurring after this press release. These forward-looking statements speak only as of the date of this press release. All forward-looking statements are qualified in their entirety by this cautionary statement.