Just to continue on the HIE (Hypoxic-Ischemic Encephalopathy)...

Just to continue on the HIE (Hypoxic-Ischemic Encephalopathy) theme. HIE doesn't just occur in newborns, it can occur in adults also, e.g. from:

• cardiac arrest (heart attack)
• near drowning
• carbon monoxide poisoning
• drug overdose
• severe respiratory failure.

I asked ChatGPT to estimate potential adult US patients per year suffering HIE and it estimated 100,000 to 150,000 per annum. If NNZ-2591 can treat HIE in newborns it seems pretty likely it could also treat adults with HIE also.

I should note there is also Stroke (800,000 per annum USA) and Traumatic Brain Injury (2.5 million per annum USA) which are likely similar to HIE. Stroke for example, is about recovering from brain damage caused by a loss of blood flow to areas of the brain - basically HIE for the brain area affected by the stroke.

None of the above have any successful treatments at all currently from what I can see. My grandmother and my father both had strokes and never recovered, despite being in hospital shortly after the event. A good treatment for stroke would be wonderful.

Of course, we're now well into mainstream blockbuster territory. Although HIE in adults might squeeze under this threshold.

I would note that if there is a chronic treatment component to NNZ-2591 for newborn HIE, as Neuren has suggested, then the number of patients may be far higher than the estimated 10,000 per annum USA. If 6,000 of these patients survive and have an average 50 year lifespan (I understand many have a normal lifespan) then we're talking about an existing pool of treatable patients of 50 x 6,000 x 25% (if 25% of the 6,000 have long term disability) = 75,000 existing patients. Possibly the chronic treatment component is only valid if you've been treated for acute, but I'd have thought not. With Retts, PMD, Angelmans, etc we are already treating existing 'brain damage'.

When you're talking about a true 'aspirin for the brain' which has very low side effects (and thus a low threshold for use) the number of potential patients is truly gigantic.