Subarachnoid haemorrhage

SAH – serious indication with high willingness to pay
Subarachnoid haemorrhage (SAH) is a lifethreatening form of stroke that is caused by the rupture of a blood vessel on the surface of the brain. The condition often affects younger patients and leads to death or severe disability in almost half of all cases. Survivors are also at a high risk of secondary complications, such as paralysis, speech difficulties, seizures and cognitive impairment. Although SAH only accounts for a small proportion of all stroke cases, the cost of care per patient is considerably higher than for other forms of stroke, and the willingness to pay for effective treatments is therefore very high. Edvince is developing a portfolio of drug candidates that target subsequent schemia (hypoxia caused by restricted blood supply), which is responsible for many of the secondary complications associated with the initial vascular injury, by inhibiting the MEK/ERK1/2 signalling pathway. The aim of the clinically tested candidate EDV2209, as well as the further development of subsequent pipeline projects is to reduce brain damage while still in the acute phase, thereby improving survival, preserving neurological function and quality of life.

Edvince MEK/ERK1/2 inhibitors – a preclinical proven solution
Edvince’s initial drug candidate, EDV2209, is a small molecule that selectively inhibits MEK1/2 – a key enzyme in the intracellular MEK/ERK1/2 signalling pathway in the smooth muscle cells in the walls of the brain’s blood vessels, which is activated in blockage of a cerebral artery in connection with an ischemic stroke or subsequent to a SAH. This signalling leads to the upregulation of 5 different types of contractile receptors in the brain’s blood vessels, causing a series of increased vascular contractions that occur over time, thereby reducing blood flow resulting in oxygen deprivation and ultimately cell death – ischemia. By blocking this cascade at an early transcriptional stage, EDV2209 aims to prevent the delayed brain damage that often occurs days after the initial onset of the illness – an situation where current treatments are not sufficiently effective. In preclinical models of both GI and FI, as well as SAH, EDV2209 has demonstrated:

• Normalisation of cerebral blood flow

• Counteracts the upregulation of contractile receptors in the brain’s blood vessels

• Significant improvement in neurological function

• Reduced cell death in brain tissue

Clinical status
Completed phase 1b/2a study. The study showed no side effects related to the test drug EDV2209, while also demonstrating strong clinical efficacy signal in the phase 2a study, which together provide a strong basis for the upcoming phase 2b study. The aim is that the phase 2b study will form the basis for the application for Compassionate Use and/or registration approval – which thereby means that a traditional phase 3 study is not deemed necessary. The potential for this is based on orphan drug designation, clinical need, and the regulatory dialogue that is planned with the FDA and EMA.