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Chemistry: Generation 2.5 LICA

ION904 is a ligand-conjugated (LICA) investigational antisense medicine designed to reduce the production of angiotensinogen to decrease blood pressure in patients with treatment resistant hypertension (TRH). Despite availability of generic antihypertensive agents, TRH is a major contributor to cardiovascular and renal disease.

Inhibiting the renin-angiotensin-aldosterone system (RAAS) is a well-established method of treating hypertension and complications of hypertension. While angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are widely used, many patients with high blood pressure are not well controlled by these treatment options. Angiotensinogen, the target of ION904, is upstream of ACE inhibitors and ARBs in the RAAS pathway. Therefore, reducing angiotensinogen levels has the potential to decrease blood pressure in patients whose blood pressure is not adequately controlled by currently available treatment options. Furthermore, inhibiting angiotensinogen, which is made in the liver, may maintain renal compensatory mechanisms, which could lead to fewer side effects compared to current standard of care.

About Treatment Resistant Hypertension (TRH)

Approximately 70 million adults in the United States have hypertension, half of which have uncontrolled hypertension. About 12-15 percent of patients with uncontrolled hypertension have resistant hypertension, defined as failure to achieve a blood pressure goal of 140/90 (systolic/diastolic) despite the use of three or more antihypertensive medications. Current estimates approximate that there are up to three million patients with TRH in the U.S. Patients with TRH have been found to have 3-fold increased odds of having fatal and non-fatal cardiovascular events relative to those with controlled hypertension.