Summit superstar
Argenica Therapeutics' (AGN: $0.685) CEO Liz Dallimore’s presentation followed Neuren’s at this year’s Bioshares Biotech Summit, with the company seeking to follow a similar path. Pitching her neuroprotective peptide drug candidate for stroke, Dallimore delivered one of the standout presentations, clearly outlining why the ongoing Phase II study in post-stroke patients has a strong chance of success.
Introducing the trialist
Argenica’s lead drug candidate, ARG-007, was discovered in Perth at the Perron Institute. Results are due early next month from a blinded, placebo-controlled Phase II study. The trial has been fully recruited, enrolling 92 patients across eight hospitals in Australia. It took just 13 months from the first to last patient to be dosed, with Dallimore citing the ease of intravenous administration in the acute setting as a reason for the rapid recruitment.
The breadth of preclinical data around the compound was also a factor in getting clinicians on board — there are 26 publications to date around the technology, Dallimore said, plus unpublished data specifically on ARG-007. Thirteen of those publications address ARG-007 efficacy in acute ischemic stroke, though Argenica is also testing the drug for hypoxic ischemic encephalopathy and traumatic brain injury.
The most important of these studies was in non-human primates, which showed a 67% reduction in brain tissue death in a study that mimicked the current Phase II trial. Based on three in vivo studies and MRI data, Argenica has demonstrated that ARG-007 “can significantly slow infarct growth and preserve salvageable penumbral tissue.”
Phase I significantly de-risks drug
From a safety perspective, Argenica was obliged to show the drug did not exacerbate bleeding and that it could be delivered alongside a clot-dissolving drug — the standard of care in stroke. A Phase I safety study in healthy volunteers has also been conducted; the compound demonstrated an extended half-life supporting prolonged efficacy, along with rapid brain uptake — a critical requirement for stroke patients. Its pharmacokinetic profile indicated that effective doses observed in preclinical studies could be achieved, an important feature for peptide drugs that are otherwise cleared quickly from the body.
Initially Targeting Thrombectomy Procedures
While Argenica will eventually seek approval for all ischemic strokes, the current trial is limited to patients undergoing a thrombectomy procedure — about 40% of all ischemic stroke patients. In thrombectomy, major blood clots are surgically removed from the carotid artery. Dallimore noted that thrombectomy has revolutionised stroke treatment over the last eight years, but some 70–80% of patients suffer reperfusion injury, where blood returning to the infarct area causes inflammation and oxidative damage.
Although the infarct core cannot be restored, a secondary area called the vulnerable penumbra is at risk of reperfusion injury, converting otherwise salvageable tissue into permanent damage. In the Phase II study, ARG-007 is administered as a 10-minute IV infusion prior to the thrombectomy. All patients will be imaged 48 hours after the procedure, and results will be compared between arms.
Main Endpoint for Phase II Study
Safety is the primary endpoint, but investors will be watching for a reduction in infarct volume between placebo and active arms. A lower infarct volume — or less tissue death — is expected to translate into lower disability post-stroke (measured by the modified Rankin Scale, mRS). Dallimore expects mRS to be the primary endpoint in a future Phase III study.
A meta-analysis of seven thrombectomy studies suggests that a 1.6% improvement in infarct volume is reflective of functional outcome benefits. To confidently progress a commercially attractive product, however, a 5–10% reduction in dead tissue versus placebo would be required, Dallimore believes. A 5% reduction in infarct volume has been shown to shift five patients out of 100 from moderate or severe disability to no or minimal disability. “Even a 5% reduction would be a huge benefit,” Dallimore said.
Post-Phase II Outlook
The cost of a stroke drug in the US is around US$10,000. The market for thrombolytic drugs in 2022 was US$1.1 billion, with forecasts projecting it to reach US$3.8 billion by 2030. These thrombolytic therapies can be used in just 9% of ischemic stroke patients because they must be administered within 4.5 hours of the initial blockage — the “early window.” Dallimore believes ARG-007 could be used in over 30% of ischemic stroke cases.
Partnering
Argenica may seek a partnering deal if the trial reads out well. However, a Phase III stroke study is not especially expensive to conduct, meaning the company could proceed into Phase III independently.
A competitor, Spanish firm aptaTargets, recently signed a licensing deal with Merck for its ischemic stroke drug candidate after Phase II results; deal terms were not released. aptaTargets’ compound is an anti-inflammatory agent. Argenica aims to become the first neuroprotective compound available worldwide.
Context and Financials
In Australia, someone suffered a stroke every 19 minutes in 2019; that frequency has reportedly increased to every 11 minutes today due to lifestyle factors. In China, stroke is the leading cause of death.
Argenica is capitalised at A$88 million, with A$10.5 million in cash at the end of June. The stock will likely be volatile in the coming weeks because of the Phase IIb readout.
Bioshares recommendation: Speculative Buy — Class B
Argenica has been added to the Bioshares Model Portfolio.
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