Member Info for Doc.Daneeka

Not on the ACTIV2 slide. Listed at the start but nothing beyond this. V. odd.

And why would I apologise to you Tommy - you rewrite history every day. In your world SNG has had a tremendous trialing career and a brilliant Covid. You even turn the disastrous liaison with AZ into a great success - forgetting that AZ dropped the drug like a hot potato after one minor trialing setback. In your world SNG has been waiting for the science to catch up and reveal the patients it will save - but we know the Auto-abs assays will struggle to find more than 10% of patients and those patients may not fare any worse in the real world than non a-abs anyway.

Good day to you - give my regards to the team.

I seem to have lost my capitals somehow. I'll try to find them in time for next week.

Have a great weekend.

you need to make your mind on why sng didn't appear on the activ2 page. you seem to be offering two possibilities.

1. they ran out of space on the page and sng coming last alphabetically was dropped - oops !

2. it hadn't completed

it can't be both tommy.

1. bad luck - no space. every activ arm page has different formatting and the number of agents listed ranges from 3 (a1 a4c and a5 ) to several with 7 or 8. activ 2 had 7. this is clearly a nonsense suggestion

2. it hadn't completed. sng was halfway through and had not started the p3. so it was in a kind of limbo. this is a more likely explanation but several other drugs are also listed as tlr and included.

i think it was a mistake - but it's a huge error considering the fact that almost all of the dozens of drugs trialled had failed - in whatever setting. either failed the trial process or been deleted by a changed virus by the time of the program's closure. stacey discussed the key highlights in each setting,those that had failed as well as the successes but for some reason didn't think sng's good performance in the p2 phase - and the fact that it was one of the last men standing from the entire program, merited a mention.

it was in fact the only activ2 drug that hadn't failed or been deleted by the changing virus - but stacey adam didn't insist it was included on the slidedeck or mention it. **** up and not conspiracy of course - little old synairgenm, easily forgotten, but it's a possible clue as to why our hopes for the drug's progression in the states have so far come to nothing

and that's what we were talking about

activ2 slide from 28.40 - scroll left or right to see other arms

https://rethinkingclinicaltrials.org/news/grand-rounds-july-15-2022-overview-of-accelerating-covid-19-therapeutic-interventions-and-vaccines-activ-public-private-partnership-and-lessons-learned-stacey-j-adam-phd/

Apologies - all that was from memory, but it was SAB-185's A2 -P3 that was halted at the same time as SNG. Brii had already completed - and had submitted an EUA in the US,.It was authorised in China before falling to Omicron.

"had the budget been available our drug would have continued. " is obviously ******ios.

sng's advancement on activ 2 was not stopped because of money but because in the omicron era not enough people were getting sick to justify a p3. brii's p3 trial was already well underway and it was stopped with just a few hundred patients left to recruit.

nobody's fault ( unlike sprinter) the virus had just become less deadly and nih wanted mass population tabs and mabs in any case. synairgen had already experienced the same difficulty with the home arm of sg016 - and rm said so explicitly. something like "we expected more people to get ill" and that was against alpha and delta.

activ2 for sng was probably doomed from the start with vaccines and a weakening virus and without the kind of patient profiling we're hoping will favour our subsequent hospital trials. profiling that already allows at-risk outpatients to receive paxlovid, the only drug to still be authorised for a mass population.

sng doesn't work well enough in a protected out-patient setting - and neither does anything else except paxlo. shionogi may be authorised for this cohort when it concludes its strive trial and will have fewer interactions

when the trial was confirmed as defunct synairgen said this " lead investigators from activ-2 and synairgen are in ongoing discussions to try to identify an appropriate clinical trial to continue the evaluation of sng001. "

we hoped this might mean nih adding the deep dive date from sprinter and considering sng as a hospital drug - but that didn't happen.

if we ever return to ground zero with a new virus that bypasses vaxes and therapeutics and kills in large numbers - sng would still offer the kind of protection it showed in the first hospital trial - but without this it is never going to be an outpatient drug except with the same profiling employed for paxlovid and for the same vulnerable population.

obviously the stacey adam slide deck omission was an error - but it was very well prepared and the only official summary of the entirety of all arms of the activ program. it was both exhaustive and authoritative. sng could have been missed off in the first draft - or fallen through the cracks because a decision hadn't been made about it - but it should have been picked up by the second draft and other drugs in a similar limbo were included and discussed. it was missed completely because nobody said "hey what about that brit drug ! "

Agreed Doc83 - the deep dive seemed good enough to us to merit further investigation - possibly via STRIVE. For me the signal that we weren't going to get on another US trial came when Stacey Adam rounded up the whole ACTIV program and we weren't on any of the slides and weren't mentioned by name. I know people's opinions oin the dsignificance of this diverged but we were literally the only non failing trialist not to feature in word or script.

And we know to our cost - from interpreting as gospel RM's remarks about his "high degree of confidence" that SNG would be in a trial in the winter of 2022 - that until we see it in an RNS, we shouldn't believe it.

Ah apologies - " members of the BoD post AGM chat " My point is that all of this stuff was off the record & not part of any official announcement - or even in the Q&A - and none of that post AGM chat has subsequently been confirmed. None of it was in the interim report which gave the only detailed summary of what they are planning and therefore it's still all unconfirmed. It's been a long time since the AGM and they may have changed tack many times for a number of reasons that were unforeseeable in June '23 or even at the time of the interim report.

Hi Jint can you elaborate on this "US gov conversations are positive. U.K. government more frustrating. "

Presume this came out in the informal pub chat after the presentation rather than q&a -and that it refers to regulatory authorities rather than govts. Obviously we remember NIH favouring SNG with a place on Activ2 and there was prolongued rancour that the MHRA had not done the same with an invite onto one of the Covid platform trials, or even offered an EUA after SG0O16. But we were granted favoured trialing status ( or whatever the correct terminology is) in both jurisdictions as I recall.

Can't see why there would be hold ups in either jursdiction for the P2s though - unless it's to do with ventilated patients which we've never done - or the UK regulatory authorities reluctance to authorise a multi-viral trial for viruses SNG has not previously tested against. But that would surely be odd, given the small size and the unblemished safety record of the drug in hospitals.

The remarks were made a long time ago of course and 3 months before the full focus was presented in September's interim report, so I'm sure some of the issues mentioned then have been resolved.

I'm with those who say that if there is a subsequent delay it will surely be related to the design of Auto-ab assays for patient identification, which has not been done before by Synairgen or anyone else in this way. But as we're just 6 weeks into a 26 week window, we are not looking at a delay yet and I'm not expecting one.

In any case we need not imagine that off-the-record comments made in June, when the trials were just being conceived will bear a direct relation to what will finally be unveiled.

My expectations haven't slipped into H2. When they changed the start window I presume they did it knowing how important it was to not come back again with another delay. And we have zero info to say there has been a hold up.

I don't think there'd necessarily be the breadcrumb trail Joeyd suggested, so the RNSs are still due, first saying "This is what we're doing & buckle up" - and the second "Here we go !! "

Also likely the first RNS will do the same as the Dec 2020 RNS and provide a clinical update on the whole programme - which should include detail on protocols & patient id etc. They told us the trials won't necessarily start together but the first RNS should fire the gun on both

SGO16

18th March 2020 Synairgen to start trial of SNG001 in COVID-19 imminently

31st March 2020 Synairgen confirms commencement of dosing in trial of SNG001 in COVID-19

SGO18

18th December 2020 Clinical Programme Update & Phase III trial to commence dosing in UK imminently

13th January 2021 Commencement of dosing

It is of course possible that they will RNS something about the Auto-ab collaborations in advance, or a partnership, if Spacman is on the right track, but at this stage I think it's unlikely. We're waiting for the gun.

Linking to the Dec 2020 RNS which will be the template for the first RNS we receive. Lots of important information to be shared, and a Clinical Update, hopefully describing everything that's happened in the last 2 years, is the most likely vehicle.

https://synairgen.ams3.digitaloceanspaces.com/201218-synairgen_updates-to-sg018-phase-iii-trial.pdf

Coming from Mr 10-a day-every single-day-seven-days-a-week, this is a complete hoot. What are you doing for Valentine's evening Tommy ? Any plans, or is it a meal for one at the computer with a single sad red rose. I dare you to take the evening off, to show you have a life. Starting ........................................................................................ now.

You're misrepresenting as usual Td - whilst accusing others of doing it.

I said

"What we can say is ..... that there will be precious little operating cash and absolutley zero left for the P3 (s) to follow "

You said

" So we do not know the company will have zero funds after the p2. "

Obviouslyyou refer to me and it's clear I did not say this. Clearly there won't be much left at the end of the P2s. That is self evident. And the "Zero " in my comment relates to the amount they might have to start the P3s, is also exactly right.

By the time the P2s conclude they'll either have demonstrated clearly that SNG represents an investment opportunity or it'll be lights out.

I'm not being judgemental Mani just suggesting that it'll be an unwinnable discussion unless somebody else backs it up.

Should be reasonably easy for one of our more numerate posters to produce a little spreadsheet of ins and outs. They haven't said how much the trials would cost as they didn't know but they will clearly be spending a lot more as the trials approach and get underway.

I would agree with T-F & G on this Mani. We don't really know how much they have left or how much the trials will cost but banging on about it day after day is not helping anyone. Unless someone else of standing agrees with your workings out, I'd say you should leave it for now. If they call for a cash raise or enter into a dilutory JV to run the P2s we will all credit you for seeing it in advance.

Whar we can say is that it'll be a near run thing that the company has sufficient headroom to conclude the P2s - as long as we make H1 ( on which the company's own predictions are based ) and that there will be precious little operating cash and absolutley zero left for the P3 (s) to follow. We can't say that a cash raise or dilutory jv will be necessary before this.

Death

Taxes

&

Tommyd

Agree on SNG v Long Covid Jd - but disagree on UNIVERSAL causing the delays. Can't see how its data ( from >18s with confirmed viral respiratory infection ) would get anywhere near to informing our P2s in a more significant way than the Sprinter and COPD data. I think it will show that once viral pneumonia starts there are more similarities than differences across the various infection types and that will help for reg approval in areas we haven't trialed in.

And if they have enough very sick patients ( which they might not ) it might help with auto-abs work.

Plus I thought they told us they were using the 300 data and not waiting for the whole thing to complete

I'm afraid that's the reality Mani. They blew the moonshot and have spent 2 years deciding how to build a new rocket with limited funds. Hopefully the new designs are perfect and we still get something back but it's almost inevitable that others will benefit from our good faith and patience. We've known this for a long time - since the remote prospect of a funded platform trial evaporated over a year ago.

It is very interesting - thanks Td and Brand. The idea of a Covid reservoir that never flushes and keeps doing damage long after infection is not something I've read before. And using spike protein biomarkers and then cross referencing with NK cell activity/presence. It's a long way down the road from here though - firstly for the further testing required to confirm the hypothesis and then - if Synairgen is still a going concern - or SNG is being developed elsewhere - to make the link to our drug.

Viral clearance is a key area of future research in LC, it's one of the key reasons for Shionogi's inclusion on STRIVE, and Synairgen does have useful data on this. But it's one for long after our current timelines and ambitions

Doc83 " I’m not really bothered about an EGM at all, but I’m pretty annoyed with the lack of comms, especially after my conversations at the AGM."

Yup. It was the one highlight of company/shareholder relations in the last 2 years.

Wigster ( i think, as others also described the AGM) told us how well you represented us all. As you say - it did no good - but the questions were as robust as anyone could wish. And they probably did intend to improve comms when they heard the level of dissatisfaction - but just didn't follow through on that intent.

No need to target Ghia in relation to today's post though. He's been right before and is entitled to his opinion. I think his main argument for them missing H1 has been well countered and doesn't really stand up. He certainly knows more than most of us and in the complete absence of any kind of comms from the company, more and more are losing faith. And obviously it feels almost inevitable that the sp will drop further.

Strangely it stopped the EGM chat just as it was getting interesting with two completely solid LTHs (Doc83 and Dunk) expressing an interest. I don't know if that debate was going anywhere - and obs it's very unlikely to ever happen - but maybe we should let the convo continue a little under that thread...