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My comment was an appropriate reply to the comment talking about pricing.

About the rest Ghia. Yeah you've been on the opposite side all this time but now it turns out you understood all this all along. Lol

You have no idea how much what I'm providing here for free costs

Finally, if these autoantibodies ONLY appear in very late stage disease (so the patients did not have them before infection, even though we know these exist - what we don't know for 100% sure is if these particular patients in the study had them before covid) that could very well be a symptom of that stage of the disease rather than something that actually *drives* the disease, and therefore perhaps irrelevant from a therapeutic point of view.

Lol I meant to say "sometimes even in healthy individuals"

It is clear that there is a confusion here.

Autoantibodies against ifns exist in some people whether they had this virus or not. They exists in some conditions and never in otherwise healthy individuals. It is a type of autoimmune disorder. See examples below.

https://pubmed.ncbi.nlm.nih.gov/16784312/
https://pubmed.ncbi.nlm.nih.gov/27059145/

What they found with covid, is that about 10% of hospitalised patients with severe disease had autoantibodies against ifn alpha and omega while no one asymptomatic had them. Later, they found some against lamda as well but it seems not so much in ifnb (only very few). We see something similar even in people that never had covid, some have autoantibodies against ifns but again ifnb is one of the least common.

Going back to the covid patients, what this suggests is that if ifn a function hadn't been impaired, then they would not be as likely to have severe covid (since none of the asymptomatic had them). Whether these existed from before is still under investigation (it would have to be a study similar to vaccines where they follow them from before they get infected). Assuming that it is definitely the virus that causes this autoimmune condition, one could in fact argue that the virus does not induce against ifn b because it cares less about it. But given that immunity is probably the least straightforward part of human biology and that in other conditions there is also less preference for auto antibodies against ifnb, it is perhaps because it is simply not as easy to induce autoantibodies against ifnb.

But, IN ANY CASE, when in almost all cases when ifn a is inhibited the patient do worse, and they haven't found asymptomatic cases where autoantibodies against ifn a exist, then we can conclude that ifn a is beneficial when it is there. If can't make this argument for ifn a, then you can't make it for ifn b either based on this imformation.

If that is clear, then it should be clear why ifnb should have an advantage specifically in patients with autoantibodies against other ifns as well as why there is a higher chance it would best work there (because they are already missing at least one other and by the way, alpha and beta share the same receptor).

(Not. If you can't keep up, thats your problem)

Sure sure Anthony. Just hang in there im gonna fetch it for you.

So the advantage of ifn b is specific in cases with antibodies against ifn a or lamda, since even if they worked at higher concentrations, they still need a lot more drug to do anything useful.

Nothing is binary. I don't know the details of that trial. But as a general note (especially relevant in inhaled ifna formukations), there is always a comcentration effect. What happens at the molecular level is that there has to be sufficient antibody to inhibit sufficient % of ifn molecules so that in the end there is not enough unbound ifn to induce an adequate response. (It is also a matter of affinity to specific ab vs receptor which is also concentration dependent). That is why everyone is measuring how much antibody that actually neutralises the virus in the vaccine induced response. So it could be possible that enough ifn a could overcome antibodies against it. I don't know the answer to that question, no one does until they do the experiments. It could be that that level would be too high to be practical or not. And keep this also in mind as well, if patients with ifn a antibodies definitely do worse, then ifn a most likely is beneficial if not impaired.

Anthony, so?

Lol

And just to add, in a large study back in october, when they checked the outcomes all cases with autoantibodies had more severe disease, it just that was only a subset of patients with severe disiease so it is not the only determining factor, but it is *definitely* one.

Still don't get it. It doesn't mean that necessarily only these people are nost likely to respond. It doesn't even guarantee all of them with autoantibodies will definitely respond very well. What it does is enriching for a population that *definitely* has a impairment exactly at the ifn ligand in particular. Then there are other susceptibility factors to severe disease due to the virus and there is a timing issue as well. All of them together will determine how many and to what extend will the patients improve. There was a high chance to recover within the timeframes they tested in the sng001 group in the phase 2, but the devil is in the details. The strength of this data is still driven by a subset of patients in the small trial, chance could easily make the difference between reaching statistical significance (which was marginal and only for some outcomes, release from hospital which is critical from a regulatory point of view wasn't). So the end results was a promising but far from conclusive mix.

We could break down all the known factors if you want, but do you really want to? There is a reason phase 3 trials and thatvis because very often, they don't replicate the phase 2 exactly.

At the end of the day, ot is all about maximising chances of success and that has been my point all along.

The implications of the above is that you probably need to give it as early as possible. Before the virus, has taken hold of many cells in the tissue, therefore protecting as many cells as possibe before they get infected by the new virions produced in the lung .

This is on top of other vatiables like autoantibodies or other known or unknown susceptibilities to extreme reactions to the virus.

Yes. Their suggestion is that ifn would work optimally (and I'm being nice here) before the cells are actuslly infected. That's because the virus uses multiple approaches to block ifn pathway. But again, nothing is as straightforward as people (sometimes including scientists) like to suggest. That is why it is all about going for maximum confidence, no.matter what that may be.

Schrow once again you pretend not to understand and see everything as a 0/1. No one said anything about 0. It is all about reaching the endpoints with statistical significance.

Which one is more other account apart from "scinv" which you all reported en masse?

More precisely the argument is (and I've been making that argument for months, before phase 3 started) that going with a subset is much higher confidence than going for. In fact it is not even one way or another, all they had to do is check and then get the approval for whatever population works batter. This is what activ is planning most likely (they clearly check).

But even if they could not have afforded to do a bigger trial (nevessary if you want to have multiple conditions) one goes for the high certainty first to get the approval and then additional indications (subset of patients) are much easier to get approval for if relevant with an already approved drug. This is a go to strategy for small biotechs and I have been saying that for ages only to get attack by the people who fail to see their arrogance

None of it is straightforward as the people here like to pretend

And that is why I am talking about low vs high confidence.

No Doc. You do not get to pretend that you understand sciemce and automatically conclude BUY BUY BUY and when details are given then attack and refer to other forum so that the usual suspects here continue to pretend to understand scince and comvimce naive people to BUY BUY BUY without challenge. I can do whatever I want just like you can.