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CaMKII

CaMKII: A Highly Sought-After Target in Cardiovascular Medicine with Broad Potential

A Previously Undruggable Target

CaMKII’s role in the regulation of normal heart function is disturbed in a number of cardiovascular diseases by hyperactivation of CaMKII. Though the role of CaMKII in cardiovascular diseases has been recognized for several decades through extensive preclinical studies in multiple cardiovascular diseases, developing new drugs to inhibit CaMKII to treat such diseases has been a major challenge for pharmaceutical companies. Cardurion is now the first company to successfully bring a highly potent and specific CaMKII inhibitor into human clinical testing.
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The Role of CaMKII

CaMKII is a protein kinase that plays a central role in normal cardiac function, but when CaMKII becomes hyperactivated, as occurs in a number of settings, it can cause several different cardiovascular diseases.

Normal contraction and relaxation of the heart requires increases and decreases of cytoplasmic calcium and depends on the normal function of CaMKII. CaMKII regulates and fine-tunes the cycling of calcium ions into and out of the cytoplasm of heart muscle cells (cardiomyocytes).

However, under certain conditions, CaMKII can become hyperactivated, resulting in disruption of normal calcium homeostasis, leading to arrythmias and heart failure. By inhibiting CaMKII in the setting of these diseases, and dampening the activity of this hyperactivated CaMKII, our goal is to correct the calcium cycling abnormalities that cause these cardiovascular diseases.

The figure below provides further detail on the process described above and the role of CaMKII.

Our Vision for CaMKII

Cardurion is the first company to test a CaMKII inhibitor in a clinical trial, a goal that has long eluded other pharmaceutical companies. We are currently conducting a Phase 1 clinical trial of our lead CaMKII inhibitor, and we are initiating a first Phase 2 clinical trial for the treatment of the rare genetic disease, catecholaminergic polymorphic ventricular tachycardia (CPVT). We plan to test our CaMKII inhibitors in this disease first, and then in more common cardiovascular diseases, such as heart failure and atrial fibrillation, in the future.

CPVT

∼1 in 10,000
Patient incidence in U.S.

Rare genetic disease that causes sudden arrhythmias, generally at times of high adrenaline levels, such as during exercise or strong emotion

Currently treated off-label or with surgical interventions/devices

Post-operative
Atrial Fibrillation

3-6 Million
People in the U.S. have AF

Post-operative complication in ∼40% of cardiovascular surgery cases

Treatments mostly include prophylaxis of repurposed drugs

Heart Failure

6.5 Million
People in the U.S. have HF

Pharmacologic or genetic inhibition of CaMKII has been shown to revers cardiac dysfunction in HF models

Caurdurion CaMKII inhibitors validated in preclinical HF models

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