Biocurious: Inspired by Neuren, Nyrada aims to change the treatment landscape for brain and heart disorders

News.com.au

2 days ago

Nyrada is focused on a particular ion pathway to tackle disorders including stroke and traumatic brain injury
Preclinical work has shown a significant reduction in secondary brain injury and cardiac damage
CEO James Bonnar spent 15 years at Neuren Pharmaceuticals in the company's formative stage
Nyrada (ASX:NYR) CEO James Bonnar is too modest to admit it, but he played a key role in developing and commercialising Neuren Pharmaceuticals' (ASX:NEU) neurological drug Daybue.
Bonnar was one of the then New Zealand-based Neuren's first employees and spent a decade at the company, which now bears a $1.7 billion market cap.
Bonnar seeks to channel Neuren's virtues as Nyrada pursues small molecule treatments for both brain and heart protection.
Before Neuren, Bonnar was with Protemix, which worked on a drug for diabetes-related cardiomyopathy.
'This is not my first rodeo."
Nyrada's indications of interest include traumatic brain injury (TBI), which Neuren pursued before switching development to the childhood disorder Rett syndrome.
'You learn a lot of lessons along the way, competing in both successful and unsuccessful programs,' Bonnar says.
Have a nice TRPC
Nyrada's lead drug was called NYR-BI03, but last week the company bestowed the 'proper' name of Xolatryp to reflect the drug's 'advancing development'.
The science is based on bodily transient receptor potential canonical (TRPC) ion channels (often pronounced 'tripsy').
These conduits regulate calcium influx into cells.
'Following ischemia or injury, these ion channels are activated and let in calcium into the cell,' Bonnar says.
'That calcium builds up to the extent where they're toxic.'
As with Neuren, Nyrada had a spare clinical program in its back pocket.
The Delaware-incorporated Nyrada listed in 2020, having spun off from immunology play Noxopharm (ASX:NOX).
Nyrada initially focused on oral inhibitors which failed preclinical toxicology studies.
'Fortunately, we had a promising secondary program, which is now the lead program," Bonnar says.
Xolatryp blocks TRPC channels to protect key cells in vital organs when under stress.
In the case of brain neurons, that could be after ischaemia (a blood clot) and reperfusion (the sudden flow of blood returning to an organ or tissue).
Ischemic-reperfusion injury is also a key cause of tissue damage following the restoration of blood flow to the heart post-injury.
It's a knock-out!
Using a 'knock out' mice model, pioneering work at the University of NSW (Uni NSW) showed the rodents were protected from stroke.
The 'knock out' doesn't refer to concussing the critters with a mallet, but genetically modifying and cross breeding them so they no longer express the TRPC channels.
'This confirmed that completely knocking out the channel is safe and for all intents and purposes these mice lived a normal life,' Bonnar says.
Over the last 12 months, Nyrada has focused on expanding efficacy data that builds on this 'knock out' mouse work.
'We went through a few iterations of molecules that showed promise, but they weren't target specific,' Bonnar says.
Let's get clinical
Preclinical work suggests Xolatryp is delivering significant reduction in secondary brain injury and cardiac damage
For cardiac reperfusion, rat models showed an 86% reduction in injury (there are no other approved treatments).
With ischemic strokes, a mouse study showed 42% protection.
The company also ran a neuroprotection study with the Walter Reed Army Institute Research and Uni NSW, deploying a TBI model.
Based on follow-up magnetic resonance imaging, this showed a 'statistically significant' neuroprotective benefit.
Now for a human study
As they say, everything works in mice … or rats.
Nyrada's attention now has turned to a phase I healthy volunteer study to appraise dosing safety.
The randomised, double blinded effort involves three-hour infusions, compared with 20 hours for the first preclinical study.
The study consists of three eight-patient cohorts, six on the active drug and two on the placebo in each group.
Bonnar says the trial will guide the company on what indication to pursue in a phase II study.
'In each one, there is first-in-class potential with large markets and unmet need.'
The company is hoping to complete the study in September.
Later, the company also would like to run a TBI study in the US, given the large addressable population.
'You would struggle to do that in Australia,' Bonnar says.
Tackling a barren treatment landscape
Bonnar describes Xolatryp as a 'Swiss Army knife' drug candidate, in that it could have broad uses.
He says the current TBI treatments only alleviate the symptoms, rather than the condition.
'It's a similar situation with ischaemic stroke, but not quite so bad.'
While clot-busting drugs work effectively, they need to be administered in a narrow time window (the 60 minutes after a stroke is called the Golden Hour).
Given that, they only apply to 10-15% of patients.
As for cardio protection, existing drugs can reduce the ticker's workload after a heart attack, but none of them protects the heart tissue.
Can Nyrada 'do a Neuren?'
Despite Xolatryp's snazzy name, Nyrada faces many years and development dollars before it 'does a Neuren'.
Of course, most drug developers tripsy-up before reaching the end game.
Bonnar dubs TRPC as a 'hot' research area reflected in Nyrada's share price: up 68% over the last month and 160% over the last year, ascribing a $38 million market cap.
'Big Pharma is looking at cardio protection in particular and we think our novel molecule … should attract interest,' Bonnar says.
At the end of March Nyrada had $4.7 million of cash, enough to fund the phase I study.
'We are pretty lean; we work as a virtual company with a low head count.'
Bonnar notes Boehringer Ingelheim has developed a TRPC inhibitors for renal fibrosis, while elsewhere work is afoot to develop one for the chronic condition of cardiac hypertrophy.
'But as far as I'm aware, we are the first company to be looking at a TRPC channel blocker in the clinic in our chosen indications.'