Diffusion Pharmaceuticals Inc (DFFN)

[Spideyboy]

Hi wgg2,

As requested, I just had a look at DFFN.

While I don't think there should be a problem with safety of the product, there otherwise is very little to go on to observe efficacy. Even at the highest level of 1.5mg/kg every 6 hours (0.25mg per hour on average), when we consider that this product is trying to increase essentially plasma permeability to oxygen molecules by 'organising water molecules' then there is an awful lot of water molecules in the cardiovascular system. I don't see how that amount of drug related to amount of water will have much of an effect. Not only that but the idea is to enhance the oxygen permeability close to hypoxic tissues, so that means that logically a very very small amount of the molecule will be present in the vasculature at the specific hypoxic tissue site, which I assume would further reduce the efficacy for that tissue.

The covid trial was not only small at 24 patients, but then, that itself was divided up into 4 cohorts. So I assume 6 in each. And no control. I don't really see the ability to come to any conclusions there. Essentially while the drug will probably do what it is designed for, it's not particularly complicated, just using a large hydrophobic chain, I would feel the dosage will likely need to be increased considerably to observe a therapeutic effect. I could be wrong though as in the limited pre-clin data in the company presentation, they apparently observed statistically significant effect in rats at 0.02mg/kg every 10 mins for 60 mins (0.12mg per hour average). So far we have seen, the human dosage of 1.5mg/kg, which is on an average bases 2x greater, was apparently starting to see a benefit.

Also thus far I don't see any information on half-life or clearance, so difficult to understand how much stays in the system for how long, which would of course have important impact on efficacy.

Additionally a quick google search found these 2 papers,
1 of them on dogs, found that a dose of 0.1mg/kg had no effect in hypoxia.
No effect of trans sodium crocetinate on maximal O(2) conductance or V(O(2),max) in moderate hypoxia
https://pubmed.ncbi.nlm.nih.gov/12660103/

Then in this human study in PAD, they present it in a positive light, but the sample again is low and sub-divided into even smaller samples. So I don't feel it is reliable. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182020/

That's all I can say for now.

It will be very important to see efficacy from decent sized cohorts before being able to be clear to see any signal. And again dosage I feel will need to be considerably higher. I don't know how high the dosage will be allowed to go.

Best,
Spidey