Ionis Pharmaceuticals, Inc. announced positive data from a Phase 2 study of IONIS-GCGRRx in 79 patients with type 2 diabetes.  In this study, patients with type 2 diabetes uncontrolled on stable, maximal metformin therapy treated with IONIS-GCGRRx achieved robust and sustained, statistically significant improvements in hemoglobin A1c (HbA1c) and other measures of glucose control after 26 weeks of treatment. Patients treated with 50 mg and 75 mg weekly doses achieved mean reductions in HbA1c of 0.7 percentage points (p ? 0.05) and 1.4 percentage points (p ? 0.001) from baseline, respectively, compared to a reduction of 0.1 percentage points for placebo-treated patients, in an intent to treat (ITT) analysis. A per protocol analysis showed additional improvements in HbA1c in both treatment groups compared to placebo. At baseline, mean HbA1c levels were approximately 8.8% for all cohorts. A substantial number of IONIS-GCGRRx-treated patients achieved HbA1c reductions of equal to or greater than 1 percentage point, including 42% of 50 mg-treated patients and 64% of 75 mg-treated patients, compared to 8% of the placebo-treated patients. IONIS-GCGRRx-treated patients experienced a mean increase in total GLP-1 from baseline compared to a decline in placebo-treated patients. IONIS-GCGRRx is a Generation 2+ antisense drug designed to reduce the production of the glucagon receptor, or GCGR.  Glucagon is a hormone that opposes the action of insulin and stimulates the liver to produce glucose, particularly in type 2 diabetes. The primary goal of the Phase 2 study was to identify a dose that produced robust HbA1c reductions without triggering previously observed on-target liver enzyme elevations or other off-target side effects observed with small molecule inhibitors of GCGR, such as increases in LDL-cholesterol and blood pressure.  This goal was achieved with the 50 mg dose cohort, in which there were no clinically meaningful (>3x upper limit of normal [ULN]) increases in liver enzymes observed.  In the 75 mg cohort, three patients experienced alanine aminotransferase (ALT) elevations >3x ULN that resolved with dose reduction.  In the study, IONIS-GCGRRx was generally safe and well tolerated.  In both cohorts, there were no clinically meaningful changes in lipids, blood pressure, bodyweight, gastrointestinal symptoms or cases of hypoglycemia.  There were no flu-like symptoms, abnormalities in renal function, or clinically meaningful platelet events observed.  The majority of adverse events (AEs) reported were mild.  The most common AE reported was a low incidence of injection site reactions (4.4% of injections).