Ironwood Presents Praliciguat Phase IIa Study Data Showing Positive Impact on Metabolic and Cardiovascular Clinical Endpoints at the American Diabetes Association's 78th Scientific Sessions | Financial Buzz

Ironwood Presents Praliciguat Phase IIa Study Data Showing Positive Impact on Metabolic and Cardiovascular Clinical Endpoints at the American Diabetes Associations 78th Scientific Sessions

Ironwood
Pharmaceuticals, Inc. (NASDAQ: IRWD), a commercial biotech company,
today presented additional data from an exploratory Phase IIa study of
praliciguat (IW-1973) in patients with type 2 diabetes and hypertension
during an oral session at the American Diabetes Association’s (ADA) 78th
Scientific Sessions in Orlando, Fla. Praliciguat is an oral, once-daily
soluble guanylate cyclase (sGC) stimulator that is currently being
studied in Phase II clinical trials in patients with diabetic
nephropathy and in patients with heart failure with preserved ejection
fraction (HFpEF).

Building on previously
announced top-line data from the Phase IIa randomized,
placebo-controlled, 14-day study, which showed that treatment with
praliciguat led to reductions in blood pressure, fasting plasma glucose,
cholesterol levels and triglycerides in patients on a stable regimen of
medicines to manage their disease, the newly reported findings also
suggested that praliciguat improved insulin sensitivity. Insulin
resistance is a hallmark of diabetes1 and often linked to
hypertension2. In addition, the data suggested that
praliciguat decreased levels of apolipoprotein B (ApoB), a key lipid
parameter that – when elevated – is associated with increased cardiac
events3. The effect of praliciguat on ApoB in this Phase IIa
study was shown within the context of broader lipid effects, including a
reduction in total cholesterol and low-density lipoprotein (LDL)
cholesterol, the component of total cholesterol associated with
long-term cardiovascular risk.

“In this study, praliciguat demonstrated a positive impact across
critical biomarkers of metabolic and cardiovascular disease – including
blood pressure, lipids, and glucose – providing a strong rationale for
praliciguat as a potential treatment for diabetic nephropathy and for
HFpEF,” said Christopher Wright, M.D., Ph.D., senior vice president,
global development and chief development officer at Ironwood. “We’re
advancing our Phase II programs for these diseases, which both impact
millions of patients worldwide, have limited treatment options and are
associated with serious long-term consequences including organ failure
and death.”

The newly disclosed data presented at the ADA Scientific Sessions were
as follows:

The Phase IIa exploratory study was designed to evaluate the safety,
tolerability, pharmacokinetics and pharmacodynamics of praliciguat in
diabetic patients with hypertension, and included a number of
exploratory biomarkers related to diabetes and cardiovascular disease.
The study included two active dosing regimens: (1) 40 mg once-daily for
days 1 to 14, and (2) 20 mg twice daily for days 1 to 7 followed by 40
mg once daily for days 8 to 14. Overall, results were similar for both
dosing regimens, and data were combined for analysis.

The study was not designed or powered to assess efficacy, but the data
yielded clear and consistent trends indicating a positive effect of
praliciguat on blood pressure, metabolic parameters and endothelial
function biomarkers. These improvements were seen in patients who were
taking a stable regimen of therapies to manage their disease; all
participating patients were taking at least one medication to manage
their hypertension and at least one medication to manage their diabetes,
and a majority were also taking additional medications to manage their
cholesterol and serum lipid levels. The study also confirmed a
pharmacokinetic profile of praliciguat supporting once-daily dosing and
suggested broad distribution to relevant tissues, offering the potential
to maximize anti-inflammatory, anti-fibrotic and metabolic effects.

Praliciguat was generally well-tolerated. Nausea was the only adverse
event (AE) present in the praliciguat group at a greater incidence rate
than placebo. There was a single serious AE, an upper gastrointestinal
hemorrhage in a participant with erosive esophagitis receiving
praliciguat. Across all five clinical studies of praliciguat to date,
praliciguat was found not to impair platelet function or blood clotting,
either on its own or when co-administered with aspirin. No other serious
bleeding episodes have been observed. All other AEs in this Phase IIa
study were characterized as mild.

About Praliciguat

Praliciguat (IW-1973), an oral, once-daily soluble guanylate cyclase
(sGC) stimulator, is being studied in patients with diabetic nephropathy
and in patients with heart failure with preserved ejection fraction
(HFpEF). Diabetic nephropathy affects an estimated eight million
Americans and 20 to 40 percent of all diabetic patients worldwide. It is
the leading cause of end-stage renal disease. Currently available
products do not treat the underlying pathophysiology of the disease or
fully address the needs of this patient population. HFpEF affects an
estimated three million Americans and 40 to 70 percent of heart failure
patients worldwide. It is a highly symptomatic condition with high rates
of morbidity and mortality that can cause insufficient delivery of
oxygen to the tissues, fluid in the lungs and edema of the extremities,
causing patients to be short of breath and have compromised exercise
tolerance. There are no approved therapies to treat HFpEF.

Currently in Phase II development for diabetic nephropathy and for
HFpEF, praliciguat has the potential to address the underlying causes of
these devastating diseases by improving nitric oxide (NO) signaling,
which may improve vascular and metabolic function and decrease the
inflammatory and fibrotic consequences associated with these diseases.

About Ironwood’s sGC Program

As a pioneering expert in cyclic GMP (cGMP), Ironwood is building on its
success with linaclotide, which stimulates guanylate cyclase-C in the
intestine, to develop a pipeline of soluble guanylate cyclase (sGC)
stimulators. sGC plays an important role in regulating diverse
physiological processes; dysregulation of sGC may play a role in
multiple serious diseases. Ironwood’s sGC stimulators are believed to
harness the nitric oxide (NO)/sGC/cGMP pathway by working
synergistically with NO to improve blood flow and metabolism and
decrease inflammation and fibrosis.

Ironwood is advancing praliciguat (IW-1973) for the potential treatment
of diabetic nephropathy and of heart failure with preserved ejection
fraction (HFpEF). Olinciguat (IW-1701) is being developed for the
potential treatment of achalasia and of sickle cell disease. In
addition, Ironwood has a pipeline of other sGC stimulators in
pre-clinical development.

About Ironwood Pharmaceuticals

Ironwood Pharmaceuticals (NASDAQ: IRWD) is a commercial biotechnology
company focused on creating medicines that make a difference for
patients, building value for our fellow shareholders, and empowering our
passionate team. We are commercializing two innovative primary care
products: linaclotide, the U.S. branded prescription market leader for
adults with irritable bowel syndrome with constipation (IBS-C) or
chronic idiopathic constipation (CIC), and lesinurad, which is approved
to be taken with a xanthine oxidase inhibitor (XOI), or as a fixed-dose
combination with allopurinol, for the treatment of hyperuricemia
associated with gout. We are also advancing a pipeline of innovative
product candidates in areas of significant unmet need, including
persistent gastroesophageal reflux disease, diabetic nephropathy, heart
failure with preserved ejection fraction, achalasia and sickle cell
disease. Ironwood was founded in 1998 and is headquartered in Cambridge,
Mass. For more information, please visit www.ironwoodpharma.com
or www.twitter.com/ironwoodpharma;
information that may be important to investors will be routinely posted
in both these locations.

Forward-Looking Statements

This press release contains forward-looking statements. Investors are
cautioned not to place undue reliance on these forward-looking
statements, including statements about Ironwood’s sGC program and the
clinical program for praliciguat; the assessment of the data from the
clinical trials of praliciguat; the mechanism of action of praliciguat;
prevalence and unmet need; the development, regulatory and
commercialization plans for praliciguat; and praliciguat as a potential
treatment for diabetic nephropathy and HFpEF. 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 those related to
preclinical and clinical development, manufacturing and formulation
development; the risk that future clinical studies need to be
discontinued for any reason, including safety, tolerability, enrollment,
manufacturing or economic reasons; the risk that findings from our
completed nonclinical and clinical studies may not be replicated in
later studies; efficacy, safety and tolerability of praliciguat; the
risk that the therapeutic opportunities for praliciguat are not as we
expect; decisions by regulatory authorities; the risk that we may never
get sufficient patent protection for praliciguat or that we are not able
to successfully protect such patents; the outcomes in legal proceedings
to protect or enforce the patents relating to praliciguat; developments
in the intellectual property landscape; challenges from and rights of
competitors or potential competitors; the risk that our planned
investments do not have the anticipated effect on our business or the
praliciguat program; and those risks listed under the heading “Risk
Factors” and elsewhere in Ironwood’s Quarterly Report on Form 10-Q for
the quarter ended March 31, 2018, and in our subsequent SEC filings.
These forward-looking statements (except as otherwise noted) speak only
as of the date of this press release, and Ironwood undertakes no
obligation to update these forward-looking statements.

1 “Insulin Sensitivity.” Diabetes.co.uk. https://www.diabetes.co.uk/insulin/insulin-sensitivity.html.
Accessed June 14, 2018.2 Salvetti A, Brogi G, Di Legge
V, Bernini GP. (1993). The inter-relationship between insulin resistance
and hypertension. Drugs. 1993;46 Suppl 2:149-59. https://www.ncbi.nlm.nih.gov/pubmed/75124683
Walldius, G., & Junger, I. (2004). Apolipoprotein B and apolipoprotein
A-I: risk indicators of coronary heart disease and targets for
lipid-modifying therapy. Journal of Internal Medicine, 255(2), 188-205. https://www.ncbi.nlm.nih.gov/pubmed/14746556

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