Calcific Aortic Stenosis

CAVS is a significant and devastating disease with limited understanding of the biology driving disease progression.

Calcific aortic valve stenosis (CAVS) is a progressive disease characterized by calcification of the aortic valve and reduced blood flow from the heart. CAVS is the third most common cardiovascular condition in the U.S. and is known to lead to heart failure and death without intervention.

With no approved therapy to treat the cause of this progressive disease, people with CAVS are left to “watchful waiting” as the current standard of care until the condition advances to the severe stage which requires surgery. There is a critical unmet need for new therapies to treat the underlying cause of the disease and mitigate the need for valve replacement surgery, a challenge compounded by limited understanding of the biology driving valvular calcification and disease progression.

Watch the video below to learn more about the cells and pathways that drive CAVS disease progression:

NOTE: This video is for educational and scientific purposes only. Intended for U.S. audiences only.

Ataciguat for CAVS

Ataciguat is an investigational soluble guanylate cyclase (sGC) activator that targets the cells and pathways underlying valvular calcification and remodeling in calcific aortic valve stenosis (CAVS).

In AS, oxidative stress impairs sGC function, disrupting protective nitric oxide (NO)–cGMP signaling. This activates valvular interstitial cells (VICs) that drive osteogenic signaling, valvular remodeling, and downstream calcification
Ataciguat is an investigational oral small molecule that may selectively bind to and reactivate the oxidized form of sGC within VICs
Reactivation of oxidized sGC and restoration of the NO-cGMP pathway may reduce osteogenic signaling, slowing calcium deposition and potentially delaying disease progression and preserving cardiopulmonary function

This is an investigational compound under clinical study. Safety and efficacy have not been proven yet.

Kardigan is developing ataciguat, a once-daily, oral soluble guanylate cyclase activator, as a potential first-in-class treatment for people with moderate CAVS. Current standard of care for the treatment of CAVS is ‘watchful waiting’ until the disease progresses to advanced CAVS which requires valve replacement surgery. Ataciguat has the potential to revolutionize the management of CAVS as the first therapy to treat the underlying cause of the disease by targeting calcium as the driver of disease progression.

In a 6-month, Phase 2 clinical trial, treatment with ataciguat demonstrated over a 50% reduction in aortic valve calcium versus placebo, improved ventricular structure and function, and no observed effects on blood pressure, results that were consistent with preclinical evidence.

The ongoing KATALYST-AV clinical trial is currently enrolling patients and will evaluate the effect of ataciguat on slowing the progression of AVC and cardiopulmonary function.

Learn more about the KATALYST-AV clinical trial.

Kardigan acquired rights to ataciguat, an investigational drug developed by, and in-licensed from, Sanofi and Mayo Clinic.