Member Info for spinnaker

Very good effort F. I'll give you an A!
Maybe H can help if he ever answers his bloody emails..
S

Oakleaf

I am sorry sorry but I don't know the answer to that question. My limited understanding was that the interferon release should normally be early stage signalling backed up by further immune responses and if the interferon bit was missed out then the body over-reacted with cytokines and other responses then causing organ inflammation and poor prognosis.

Obviously much simplified for my brain!

Best

Spinnaker

Thanks SDG I haven't seen that weekend chat so I would like see the comments there.

Apologies, my last post written before I read yours.

Spin

Well thanks for the input but I must say I am not much clearer. Hopefully Faye's email will do the trick!

My understanding is the same as yours philandlynne. The concern about giving SNG001 to late stage patients was that the increased presence of Interferon in the mucosa increased the number of ACE-2 cells potentially giving more entry points for the virus. The discovery was of the short form ACE-2 cells which was the only type of ACE-2 cells to be increased when patient treated with INFB1a. Since Covid spike protein did not use the short form ACE-2 to gain entry this obviated the prior concern of a worsening of the illness from administering additional interferons through SNG-001.

It does not appear to me that the ACE-2 cell type is relevant to the Lancet paper quoted but I await further info from the more scientific of our community. At the moment I feel that my limited understanding has been dented quite severely.

Meanwhile, SP has carried on going up today. 6%up, 160p not seen since last Friday.

Good luck all.

Spinnaker

Quite Meelie.
The P2 hospital trials did not indicate against SNG001 treatment even with very ill patients.
Spin

Thank you Sha

It does seem as though the paper was slanted towards ICU patients. However Geovanni's question has not really been answered. The thrust of the paper is that patients with high endogenous INFB1 have worse outcomes. I thought that almost all the research I have read to date took the opposite view and this was the reason several on this board including me have thought that early test of endogenous interferon levels would be useful to indicate those likely to progress to serious disease. I.E. that low levels of interferons present would indicate a worse outcome. This is the opposite of what the Lancet paper concludes.

If it is a matter of timing of when the interferon levels are checked then the paper should make it clear but it does not. Not to me anyway.

Spinnaker

Thanks Ferrari for that post.

I may be losing my mind.

I thought that a low level of INFB1 in the body would give a worse outcome but this Lancet paper Ferrari referenced seems to say the opposite. Can someone please explain? Thanks - Spinnaker

'Moreover, IFNB1 expression also predicted worse clinical outcome measured by maximal WHO ordinal scale (Mann-Whitney, p=0·027) or maximal oxygen support (Mann-Whitney, p=0·0068) and a composite score (ie, discharge to rehabilitation centre, hospital stay >60 days, or death; Mann-Whitney p=0·040). Notably, 45% (5 of 11) of patients who were positive for IFNB1 required extracorporeal membrane oxygenation versus 9% (4 of 46) of patients who were negative for IFNB1. Total days on extracorporeal membrane oxygenation was also higher in patients who were positive for IFNB1 (median 24·0 days vs 10·5 days; Mann-Whitney p=0·016). IFNB1 expression also predicted multiorgan involvement, another hallmark of critical COVID-19 (median Sequential Organ Failure Assessment score 7 for patients who were negative for IFNB1 vs 12 for patients who were positive for IFNB1; Mann-Whitney p=0·0072). Surprisingly, IFNB1 expression was not correlated to viral load (figure D), in contrast to IFNA2 (r=0·45; p=0·0007) and IFNL2 and IFNL3 (r=0·47; p=0·0003).
Figure thumbnail gr1
FigureUpper respiratory tract IFN transcript expression and length of ICU stay for critical patients with COVID-19'

Thanks Prion and Matterhorn

I didn't spot the 6 weeks to have passed from vaccine dose to become eligible for Activ-2 P2. As you say that is slightly odd. I suppose that would be maximum antibody stage.

It is possible that there may be a difference in outcome between vaccinated and non-vaccinated and therefore a bit like co-morbidities where there was some criticism in our June 20 P2 results relating to different levels of each co-morbidity in placebo and drug cohorts. The more different variables such as age, specific co-morbidities, sex and vaccination status then the larger the trial needs to be to get statistically relevant data I would assume. As you say the numbers of each vax and non-vax need to be equalised between cohorts just as every other variable. A bit of a nightmare for selection.

Anyway let's hope its all going well and we get the P2 trial filled as soon as possible. This should be the next bit of news either before or after SNG018 results. Also encouraging news from India today.

I topped up again yesterday so I hope we have seen the bottom but you never know.

Good luck all.

Spinnaker

Great to see blue today for a change.

I don't know if I have missed something on this in which case I beg to be enlightened.

I have had a quick look through the December final protocol for Activ-2 and find no mention of vaccines under the general eligibility criteria. By the time of release of this current final protocol the first patients in UK and US had been vaccinated and yet no mention under eligibility.

Patients who have been taking part in trials for other drugs are excluded.

It seems that as though there will be substantial proportion of potential trialists that would have been given a vaccine, (at least first dose). If these people are accepted onto the trial will this mean that there will be a further variable to be considered. I am not a statistician but there may be two or three different vaccines administered and perhaps some people with two jabs and some one. Does this mean that it will be more difficult for statistically significant results to be forthcoming from the limited numbers programmed for the trial.

Also, the same question arises in respect of the P3 trials. Less of an issue in Europe and India perhaps. Basically does anyone know if only non-vaccinated people will be eligible? Someone involved in the P3 trial at one of the UK hospitals involved could probably answer this question if they are reading this post.

Many thanks

Spinnaker

Thank you and well done Denny for all that work.

That's a lot of Activ-2 trial centres, I wonder how many of the 168 have SNG available. Still with only four? current trials I am hopeful that the numbers could be filled fairly promptly at P2 level.

Best

Spinnaker

Apologies again, I was obviously tired last night.

My post below first para should have read 'I do not think that is a likely scenario' referring to likelihood of no news by June.

Also para 3 should have read 'all time high' not year high.

This wasn't intended as a ramp/de-ramp. I was replying to Aston's question with my actual thoughts. I am trying to manage my expectations having a huge chunk of my savings invested here

Spin

Whoops sorry HarChris you didn't actually give a share price estimate if no results by June. My apologies for misquote.

Spinn

Aston

My expectation is that we will get initial results during April for the P2 at home trial. If these do not appear during April there will most definitely be severe downward pressure on the share price. People will think there is something wrong and as HarChris says, if we have no news by June it would certainly be sub £1. I do think that is a very unlikely scenario.

If we get positive P2 home results in April then I think the SP will probably not go much lower than 130 and probably stay in the range 130 to 175 probably with a bit of FOMO as we reach mid April with no results. The exception would be if another competing treatment such as Camostat or Ivermectin were given EUA. In this case the SP would dive.

I expect a good increase if P2 initial results are positive and maybe up to the record high. Then there will be some selling and others worrying about peer review not happening quickly and holders becoming more jumpy as time goes on until we have more news from Activ-2. So, in between these times there will again be SP drift. The big focus will then be on Activ-2 and the hoped for roll on from P2 to P3 and EUA application. At this point we should surpass the year high and I am anticipating/ hoping for £4 + assuming no other comparable treatment has emerged and Synairgen has confirmed they are up and running with high production levels available immediately.

This is just my 'without prejudice ' musings and should not be relied on by any investors.

Good wishes to all investors

Spinnaker

Great stuff, thanks Matterhorn and all contributors.

One thing I was surprised to see was that oxygen requirement is one of the required inclusion criteria on the Centrewatch site. I hadn't realised. Thought it was just hospitalisation. I suppose they will be very similar groups anyway.

Anyway it's great to see some positivity and that progress is being made on both Active-2 and P3.

With regard to Activ-2 I don't think we have been told in which of the 160 odd centres in the US we are being trialled in or how many. So that info will not be easy to find. Similarly it doesn't look as though numbers of patients recruited to each trial will be released. We need spys in every hospital not just in the bush in Southampton!

I think SNG is one of my best performing stocks today. Pretty solid, not like GDR, ODX etc.

Spinnaker

Thank you Matterhorn and Doc for carefully reading and understanding my post and my apologies to others who mis-understood or mis-construed my point.

Spinnaker

Matterhorn

Just saw your response. Yes, the problem is that a single 14 day course of SNG-001 is considered unlikely to have long lasting effect, ie interferons inhaled will not hang around too long after the final dose. I agree that there won't be many drugs suitable as a prophylactic for just the reasons you state. The half life of drugs that are excreted is presumably the key. The reason that certain groups of doctors are bashing on about Ivermectin is that it could be an effective and cheap prophylactic since I think only one or two doses per annum are effective for anti-parasitic use and presumably also for Covid. I haven't done much research on it since at present its use in EU and USA is being blocked by the FDA , EMA and Mercke so it seems an uphill battle for them but this could become relevant to SNG if one of the national agencies starts formal trials or metanalysis of prior and existing use is progressed.

Best

Spinnaker

Matterhorn

Thanks for the original post and a much better behaved thread than some.

I agree that the use of SNG-001 as a prophylactic is limited due to both cost and faff.

The other point is that the enhancement of the immune system as presently understood is only short term, ie during treatment. Timing would therefore be key since I cannot see daily nebulisation treatment over a prolonged period would be readily accepted.

Spinnaker

I spoke to a friend today who was at med school with Prof Holgate. He is also a long term investor here. I asked him if he thought that good Home trial results could result in EUA in UK. He thought they quite possibly could. He also thought that meta analysis of Ivermectin usage and results in South America, India and Africa could also be used to get approval for that drug which could be fantastic news for the fight against Covid and certainly help in poorer countries. I doubt Ivermectin would reduce the market for SNG-001 which I regard as likely to be very much a first world drug.

Food for thought.

Best to all

Spinnaker

If anyone thinks my post is de-ramping then I can assure you it is not intended that way. Expectation management is what I would say and I would love to be pleasantly surprised.
Spinnaker

Thanks for the link Peel.

Reality is gradually hitting on this board. We are not going to get any P3 results for any of the international elements of the trial for a long time. It would be great if, as Mav suggests, the UK early results could be separately unblinded and I suppose that is possible depending on P2 at home results but not a cert. I suppose that if our case numbers remain at or about 5,000 per day through the spring and summer it would mean hospitalisations will be low, 5% would be 25 per day and the immediate pressure will be off.

I think we are fairly dependent on Activ-2 delivering. If and when an EUA is applied for in the states following great P2 results in that trial or P3 results unblinded there then that is when interest from the MHRA will soar and there may be some movement in the UK towards EUA.

Given that the job vacancies advertised months ago at SNG mentioned early summer it seems clear that we were all a bit optimistic on timelines and RM never expected that there would be serious demand for the product before the summer and possibly not until the autumn of 21.

The good thing is that the share price is stable and the vaccines are rolling out well. Negative impacts on the SP should now be lessened. Possibly some effect from other drugs that may get EUA before us.

There is likely to be positive news in the meantime particularly on the P2 at home trial and hopefully some progress reports on Activ-2 in due course. If Parexel are worth their money, and at £30,000 per patient I should hope so, then the international trials should be setting up with a bit of urgency over the next two months.

Still positive that SNG will be out there by the end of the summer. Best wishes to all.

Spinnaker