Lead Indications
Acute Ischaemic Stroke
'Best practice' treatment of stroke is a complex paradigm, with an evolving standard of care that is constantly being driven forward with evidence-based research and clinical trials. The societal cost of stroke is large, and the bulk of the economic cost is borne by Federal and State Governments. The annual cost of stroke in Australia was estimated to be $6.2 billion in direct financial costs and a further $26.0 billion in lost wellbeing and premature mortality.
With no new approved pharmacological therapy for stroke in 17 years, the demonstration that our drugs are safe and effective would constitute a landmark achievement in the treatment of stroke.
The majority (>85%) of strokes are caused by Blood clots that block (occlude) blood flow to the brain.

Current standard-of-care therapies
Treatment of stroke requires the rapid removal of occlusive blood clot(s), with the objective to quickly reopen (recanalize) occluded blood vessel(s) and restore blood flow to cerebral tissue (reperfusion), the latter strongly predictive of a favourable outcome. Existing standard-of-care stroke therapies aim to reperfuse ischemic brain tissue with either Intravenous thrombolysis or endovascular thrombectomy (EVT). Intravenous thrombolysis aims to pharmacologically dissolve blood clots while thrombectomy mechanically extracts them through surgical intervention. In some patients, a combination of both can be used in succession.
Current standard-of-care therapies for stroke are limited
Despite its approval several decades ago, intravenous thrombolysis remains the only pharmacological approach approved by regulatory authorities for the acute treatment of stroke. Thrombolysis is primarily undertaken with rtPA, which is associated with numerous limitations including:
1
Time-restricted administration, within 4.5 hours of stroke onset.
2
Relatively high rate of failed thrombolysis (especially in large arteries - Large Vessel Occlusions or LVOs - where recanalisation rates can be 20%).
3
High rates of rethrombosis in patients with atherosclerotic disease (up to 50%).
4
6-8% risk of symptomatic intracerebral haemorrhage (ICH).
These limitations have led to strict eligibility criteria, wherein rtPA is only administered to 10-13% of all stroke patients, and less than half of these achieve a good therapeutic outcome. Of further concern, an even worse prognosis faces stroke patients living in remote and regional areas.
The recent introduction of thrombectomy has had a major positive impact on stroke outcomes in patients, particularly those with Large Vessel Occlusions (LVOs), who have historically had the lowest rates of successful reperfusion with thrombolysis alone. Although highly efficacious, thrombectomy is time-consuming, expensive, and can only be performed in major tertiary stroke centres, limiting its availability to stroke patients in regional and remove communities.
rtPA remains the mainstay of stroke treatment globally

Large Vessel Occlusion
The size of the brain region affected during stroke is largely dependent on the size of the affected blood vessel. Large vessel occlusion strokes (LVOs) occur when there is an interruption of blood flow to one of the main arteries in the brain, with one of the most common large vessels being the Middle Cerebral Artery (MCA).
When compared to strokes occurring in the smaller vessels, LVOs have different clinical outcomes and often require different treatment strategies. Because large arteries in the brain supply a substantial area of cerebral tissue, LVOs can cause serious and potentially permanent neurological impairment, affecting a stroke victim's physical and mental abilities. They also tend to cause swelling in the brain (or oedema), which exacerbates brain injury. As a result, recovery is generally slow, and rehabilitation is almost always a necessity.
LVO stroke in the setting of "tandem" carotid artery disease (CAD, development of atherosclerotic plaque in diseased arteries - see FIG) otherwise referred to as Tandem occlusions (TO), are present in up to 1-in-3 of all patients with stroke undergoing EVT. TOs are considered one of the most challenging stroke patient subpopulations to treat, with high complication rates, and are associated with worse clinical outcomes (high rates of disability and death).
Current standard-of-care for LVO/TO
rtPA is inadequate in situations where there is occlusion of large cerebral arteries and there is increasing use of EVT in these patients. Stenting of diseased atherosclerotic arteries is becoming more common, and represents a unique problem for the patient and a hazardous dilemma for the surgeon. Combinations of antithrombotic drugs are increasingly used to maintain stent patency (aspirin combined with clopidogrel or ticagrelor).
Combinations of these anti-platelet therapies in stroke can promote disabling brain haemorrhage (6-fold increased risk of haemorrhage with GPIIb-IIIa inhibitors) and inadequate platelet inhibition can cause acute stent thrombosis, which can worsen patient outcomes. Safer antithrombotic agents for use with stenting for intracranial cerebral atherosclerosis is desperately needed.