Advancing a best-in-class siRNA for hypertension
- 1.4B
- people globally live with hypertension
- 700M+
- remain uncontrolled or untreated
- 70%
- of treated patients do not achieve target blood pressure levels
In hypertension, the challenge is not whether blood pressure can be lowered.
Medication non-adherence is the leading cause of poor blood pressure control, and hypertension is largely asymptomatic, resulting in poor long-term adherence and treatment persistence.
The challenge is whether it can remain controlled over time.
Persistent uncontrolled blood pressure substantially increases the risk of serious complications for stroke, myocardial infarction, heart failure, chronic kidney disease, end-stage renal disease, peripheral arterial disease, and vascular dementia.
CinPressa is advancing a long-acting AGT siRNA designed to provide durable blood pressure reduction with one to two administrations per year.
The goal is to establish a continuous backbone of blood pressure control independent of daily patient adherence. Meaningful baseline BP reduction may be sufficient for many patients to achieve treatment goals as monotherapy, with complementary antihypertensive agents layered onto an already controlled foundation for patients requiring additional control.
365 doses, compressed into two
Mechanism
Targeting AGT upstream
RAAS modulation at the source
AGT is the precursor in the RAAS pathway and is crucial for blood pressure regulation. Standard RAAS inhibitors act downstream and do not completely suppress the RAAS pathway.
By targeting AGT synthesis in the liver via RNA interference, CIN-111 is designed to block the RAAS cascade upstream.
The RAAS cascade
Where therapy acts
Angiotensinogen (AGT)
CIN-111 silences AGT hereThe precursor of the entire RAAS cascade, synthesized in the liver.
Angiotensin I
Cleaved from AGT by renin.
Angiotensin II
ACE inhibitors · ARBs act hereConverted from angiotensin I by ACE; drives vasoconstriction.
Aldosterone
Released in response to angiotensin II; retains sodium and water.
Elevated blood pressure
The downstream clinical consequence of RAAS activity.
Upstream
CIN-111 suppresses AGT production in the liver, shutting the cascade off at its source.
Downstream
ACE inhibitors and ARBs act late in the pathway and do not completely suppress it, leaving residual activity.