Product Development

COR-1

Autoimmune antibodies have been recognized to cause heart failure in many patients. The antibodies are directed against the beta-adrenergic receptor and mimic the effect of natural ligands, such as epinephrine (adrenaline). This leads to a chronic over-stimulation of the receptor and consequently, to hypertrophy and reduced function of the heart. COR-1 is a peptide drug which prevents the auto-antibody-mediated propagation of heart failure. Functional auto-antibodies are an increasingly recognized phenomenon in any form of heart failure, corresponding to a large and previously unmet medical need.

COR-1 is a cyclic peptide which inhibits the effects of the stimulatory antibodies by scavenging and neutralising them. In animal models, COR-1 prevented the generation of heart failure and also reversed existing heart failure. This drug for the treatment of chronic congestive heart failure has already been tested in humans in a placebo-controlled trial, and was shown to be well tolerated. COR-1 showed good efficacy to neutralize anti-ß1 receptor autoantibodies ex vivo. The drug is now being investigated in larger patient trials.

Revacept (PR-15, GPVI-Fc)

Platelet adhesion to arterial vascular lesions and plaques plays a key role in the complications of atherosclerosis leading to acute coronary syndromes and myocardial infarctions as well as ischemic cerebral stroke.

Revacept is a human Fc fusion protein, which prevents the local activation of platelets at sites of vascular injury, acting like a “vascular coating”. Efficacy studies showed that revacept resulted in significantly reduced thrombus formation at these sites. However, systemic hemostasis is not affected.

In a first in man study, all doses were well tolerated, no drug-related adverse events occurred, bleeding time was not prolonged. No bleeding complications nor platelet depletion (thrombopenia) were observed. Also this drug is now being investigated in larger patient trials.

COR-2

During atherosclerosis, inflammatory cells (e. g., monocytes) invade the vessel wall and differentiate into foam cells which accumulate lipids and cholesterol. Existing therapies for the treatment of atherosclerosis intend to inhibit the uptake or the synthesis of cholesterol (e. g. by statins) which is, however, accompanied by negative secondary side effects.

COR-2 is a recombinant protein which specifically interferes with the generation of foam cells. It inhibits the cellular uptake of cholesterol by binding to oxidized LDL ("oxLDL"), and thereby prevents oxLDL uptake to foam cells in atherosclerotic plaques, and reduced local inflammation of the vascular wall, with the potential to reverse plaque progression. COR-2 almost completely inhibited the progression of atherosclerosis in mouse models, and significantly reduced the risk of plaque rupture. COR-2 will be developed to treat high risk atherosclerotic patients.

COR-3

Endothelial progenitor cells have been described as important players in recent years, which protect against cardiovascular disease. Accordingly, people which increased amounts of these cells are less prone to complications of these diseases.

COR-3 is a recombinant protein, which specifically binds to atherosclerotic plaques, and then bi-specifically binds to circulating progenitor cells. This approach allows to optimally trap the endogenously occurring progenitor cells for accelerated plaque healing, without having to inject external cells to the respective patient (which would incur a relevant oncogenic risk).

Efficacy of COR-3 has been shown in several models of vascular injury.