ProMIS Neurosciences Inc PMN

ARIA-E

[goldtech]

If Brain bleeding is to be identified it will happen earl, my guess is 60 days and 2 dosing events. If we have no ARIA-E then we will have to measure the toxic oligomers and the cognition scale. If both those are successful we will have a mad rush of pharma's coming to court us on a JV. The more we do ourselves, the more they will pay. Exciting times ahead.

[Hafness]

I thought aria-e was ruled out in phase 1-a safety data?

[goldtech]

Phase 1A was to identify any side effects in healthy patients, 1B will be infusing patients with Alzheimer's. If we do not remove monomers or placque and show specificity without any Aria , then we are on the right track.

[Hafness]

aria-e would be a side effect in healthy subjects as well I would think. I pretty sure this would show up in 1-a. Aria is the number one issue with these drugs. They surely were looking for it. What am I missing.    here is a good article talking about aria https://pmc.ncbi.nlm.nih.gov/articles/PMC3693547/

[G1945V]

"aria-e would be a side effect in healthy subjects as well I would think." I don't see why not! I know from publications that before the trial begins, a baseline MRI scan is performed to establish a reference point for each healthy participant. During the trial, participants undergo MRI scans to monitor for any changes in the brain. This will detect any abnormalities, by observing

[Gbathat]

I think there was a publication in Science assessing the brain bleed effect of aducanumab or leqembi... something to do with plaques coating arteries in brain and plaque-targeting anti-bodies dislodging those bound plaques, weaking the wall structure, resulting in leaks. I'll try to find the article.

[Gbathat]

Here it is: https://www.science.org/content/article/clinical-trial-participants-autopsy-brain-exam-stoke-alzheimers-drug-fears? Most straight-forward explanation of how current antibody treatments from Biogen and others that also target plaque (unlike PMN310) can cause brain bleeding: ". In Alzheimer’s disease, beta amyloid accumulates between brain cells in hallmark deposits called

[Hafness]

Nice. I will check it out

[Hafness]

Gavin Malenfant responded and said Aria was not studied during first trail 1a

[G1945V]

If true, it would be a big mistake. ARIA is one of the biggest safety issues that PMN has been boasting about for years. G1945V

[Gbathat]

Testing for ARIA in healthy individuals would have been a big foolish mistake and waste of money. 

[G1945V]

WHY? G1945V

[Speyeder999]

On slide 14 of their most recent overview regarding Phase 1a, we find the mention No ARIA to be expected. So I'm confused. https://d1io3yog0oux5.cloudfront.net/_28c9a01cbe79b70ba7b8bd4e8fa5da15/promisneurosciences/db/933/8819/pdf/ProMIS+Corporate+Presentation+20240807.pdf How can you make this claim if you don't test for it? I thought that was the whole point of Phase 1a....  

[BottomBroker]

From another slide further down in the presentation... ProMIS platform enabled generation of PMN310 which does not bind plaque or monomers, only oligomers Attempts by others to selectively target oligomers have failed. Most drugs are not able to distinguish the different forms of Aβ and therefore bind all three or at least two forms of Aβ Drugs that bind several forms of Aβ limit the amount of

[G1945V]

Yes. BB, I fully agree with your explanation. The binding of AB plaque is more commonly associated with causing ARIA-E. Since the trial involves healthy volunteers, the likelihood of developing ARIA-E might be lower compared to patients with the disease.  G1945V

[Normandt]

A Phase 1a, Double-Blind, Placebo-Controlled, Single Ascending Dose Study of the Safety, Tolerability and Pharmacokinetics of PMN310 Infusions in Healthy Volunteers (non alzheimer, then without amyloid plaques accumulation). Aria :Amyloid-related imaging abnormalities.