Synairgen Share Discussion Threads

[nobbygnome] 04/4/2020 16:17

And yes whenever a spamming poster comes on the thread I ban them!

[nobbygnome] 04/4/2020 16:17

>> 141jaffa

Yes a combination trial is perfectly feasible and completely logical. However, such trials are more difficult and would take a while so first mover advantage would be lost. Clearly there are a number of possible scenarios but the best and most rewarding both clinically and financially is a clear statistically significant result in this trial.

[makendon] 04/4/2020 15:52

Block sharethis spamming all sites. Don’t click the link

Thank you :)

[141jaffa] 04/4/2020 15:06

TK,thanks. Obviously, this group are not the only group in the trial of course.But those in the trial are having this measured before treatment since I believe that lower levels make an individual more prone to complications.

[torreskid] 04/4/2020 14:50

Definitely need DrugS. No one drug will be the answer.

We will definitely need one to fight it with a good switched on immune system (SNG001), and one to stop the virus invading the cells (so a virus blocker) and possibly a vaccine for future epidemics

They are not testing in "patients with naturally lower beta interferon" you are mixing that with the COpD trial

[141jaffa] 04/4/2020 14:42

Another view to consider ??
It occurred to me, that there was potentially another trial outcome which I wasnt sure had been mentioned here ?? That being, if the trial yielded a mix of results eg it was efficacious in "kick starting" the immune response in naturally lower beta interferon Pt's ( those more at risk it seems of serious disease)BUT didnt really lower viral load much. Many conditions are treated with a combined therapy plan either for their independant actions or to work symbiotically. For example,if the above was true, the addition of another drug eg Ritonavir (antiviral) might together achieve a beneficial outcome.
Just to mention for discussion, as even if SNG001 wasn't THE cure, in combination with other drugs, it might still be a valuable resource against COVID 19 ( or others future viruses). So while I take the point that in terms of SNG001 efficacy as a singular drug in this trial (v) COVID 19 it is a binary type of outcome, it may not be a binary event for SNG001 or Synairgen ?? The next rapid trial phase could be looking at combining trials for their respective benefits maybe....others ( eg Nobby)will know much more here.
Who knows, but thought worth bringing up as felt we might all be seeing the trials as Pass or Fail ?? This might not be a race for a miracle drug.....it might be drug"S". Just my view here ..

[torreskid] 04/4/2020 14:29

No AUC, probably simpler stats

[torreskid] 04/4/2020 14:29

NobbyG

It should not, as they will provide data points for every day, and compare it with preceding day and subsequent days' scale

So in the study there will be daily scale assessment starting on Day 0 and finishing on Day 14 (15 data points)

So stats will be done for changes between Dy 0 and D1, D1 and D2 and so on... I suspect the changes will be so small from day to day that a clearer pattern will be more obvious when comparing D0 and D5 or D7 etc. Bottom line is we need statistical significance of BENEFIT when comparing D0 and D14.
After that, and with so much data, they can then data 'dredge' to identify whether there is any indication (signal), that treatment may not be needed for the full 2 weeks (but believe me, no pharma co designs studies to actively minimise the duration of treatment, eg statin trials)

I hope that makes sense

[nobbygnome] 04/4/2020 14:18

My point is that how do you compare curves of data when the scale is discontinuous? For example you can't do area under the curve...or can you?

[the patient investor] 04/4/2020 14:13

Thx nobby

"But overall I must stress the immune system is extremely complex "


Oh yes

What is fascinating is its integration (via the sharing of the very same molecules playing a role in all the 3 systems) with the nervous system and endocrinological (hormones) system.

Let us hope interferon beta will be successful!

[nobbygnome] 04/4/2020 14:13

>> torreskid

Thanks. Does the fact that patients could get worse before they get better complicate the stats?

[hazl] 04/4/2020 13:57

Torreskid.......Good luck and well done!

[torreskid] 04/4/2020 13:51

Need your secondary end-points to guide future trials, in the event the primary end-point is not statistically significant.

Thanks for the link about the Ordinal scale (i mistakenly thought it would be subjective, but clearly denotes 'clinical status'. the only concern i have about the scale is points 1 and 2 (which are a subgroup of Ambulatory) - does it take into account pre-morbid status (ie before they became ill)

Again, stats are my weakness, but if I was to use my experience in heart failure studies, the stats would be straight forward, looking at change in ordinal scale prior to and after treatment.....it maybe that no change is perceived until after several days of treatment (or even some deterioration before any perceived benefit is seen)

Now i'm excited

PS rejoining NHS to manage convalescent cases (will be interesting to see if any are on SNG001)

[nobbygnome] 04/4/2020 13:31

I thought I would take the advantage of the weekend to highlight again the protocol (first link) and in particular the primary endpoint (the ordinal scale for clinical improvement on page 6 of the second link).






So a couple of observations. The ordinal scale is really quite objective but is a non linear scale because the different states are unrelated. Also it appears they are assessed throughout the 14 day dosing period not just the end. Now statistics has never been my strong point but it seems to me this will make the data difficult to analyse statistically. My son actually did a statistics degree so I am going to ask him but I was wondering if anyone here had insight into how you would statistically compare this data.

My other observation is there are lots of intriguing secondary endpoints where there is a high chance of showing differencs. Clearly the only important one really from a regulatory point of view is the primary endpoint but the secondary endpoints give a lot of scope to show a difference. It gives me hope that the result may not be quite as binary as we first thought.

[the stigologist] 04/4/2020 13:28

LOL was that aimed at me ?

THE GOVERNMENT.

With OXFORD UNIVERSITY.

Is pursuing these alternatives.

hydroxychloroquine and Lopinavir / Ritonavir



One of the trials already up and running has been billed as the "world's largest clinical trial", and is being led by researchers at the University of Oxford thanks to £2.1m in funding.

Trials will look at the effectiveness of existing drugs and steroids that could be re-purposed to tackle coronavirus, including malaria treatment hydroxychloroquine and anti-HIV medicine Lopinavir/Ritonavir

[hazl] 04/4/2020 12:14

with reference to earlier post promoting various alternatives.

[kop202] 04/4/2020 09:50

Nobby....couldn't have put it better myself

[nobbygnome] 04/4/2020 08:25

>> the patient investor

Ok to try to answer some of your questions about interferons.

All the interferons are related proteins but have distinctly different sequences. For example beta has only 31% identity with the family of alphas. The alphas and beta all bind to the same receptor proteins so clearly that is the part of the molecules where the identity is very similar.

However, the fact that they all bind to the same receptor doesn't mean they all have the same action. That is because they are produced by different cells and so the temporal and spatial appearance of the molecules is not the same. Beta is produced by fibroblasts whereas the alphas are produced by white blood cells. There are lots of fibroblasts in the lung which is why beta interferon is most likely to be the important family member in anti viral responses in the lung.

But overall I must stress the immune system is extremely complex and it is difficult to assign absolute rules. There is an awful lot of redundancy and overlap which is why multiple approaches have a chance of working. However, I stand by my assertion that beta interferon is arguably the best interferon for delivery into the lungs.

[hazl] 04/4/2020 08:02

yes somebody else alerted me to that site....a good link.

[duxy786] 04/4/2020 06:58

https://nextstrain.org/ncov

[hazl] 04/4/2020 06:47

Phew wouldn't want a malaria drug....I've read about worring side-effects.

[the stigologist] 04/4/2020 06:28

Government really pushing Oxford trial of hydroxychloroquine and Lopinavir / Ritonavir



One of the trials already up and running has been billed as the "world's largest clinical trial", and is being led by researchers at the University of Oxford thanks to £2.1m in funding.

Trials will look at the effectiveness of existing drugs and steroids that could be re-purposed to tackle coronavirus, including malaria treatment hydroxychloroquine and anti-HIV medicine Lopinavir/Ritonavir

[crookie3634] 03/4/2020 23:30

Not sure on that article regarding Link, I can see no evidence of a reduced holding unless we have not been notified yet via an RNS. It does not read right as it intimates that Link sold down on the 30th March however the RNS reads exactly same number of shares so none have been sold. Is this just a factually incorrect article? I am interested to know where Griffiths 14% went? No one else has confirmed they have picked them up so between Licht and Griffiths around 15 million shares have been put back out to market? PI picked these up on recent trading activity or are we going to get news of increased holdings or new buyer? Given the trades suspect Griffiths is now out or very close to being out and someone as another poster indicated has found homes for the 15 million sales hence the big buys after hours.