Member Info for Doc.Daneeka

Lapdogs in particular Woof

Fruits - small point of order. Whatever your feelings abourt Manifesto - if she posts on here as a woman then please do her the courtesy of either using female pronouns or none at all.

Misgendering is childish and insulting - even by the standards of your paranoiac good cop - bad cop multiverse.

Insult her if you must - she'll give it back - but show some class.

( Not that we haven't had men in skirts before of course - remembering Andybe4's comical Mrs Doubtfire impression - when he said things like " Got to sign off now to get my fella's tea ready - he'll be in soon" )

Absolutely right Axe. There is just one scenario where we might be inclined to keep the pension funds going before the P2s deliver, and that's if somehow the RNS announcing the start of the P2s reveals something incredibly encouraging and relevant from the UNIVERSAL trial. Something that reveals how well they will be able to target patients for the P2s.

It would have to be a brillaint revelation - but then it needs to be anyway or the trials won't work.

It therefore follows that we and the market will have a strong sense of the success /failure ratio before the first patient is dosed. And in that scenario I'm sure the SP will jump a little - and we'll be ready to support it

It's only hindsight for us amateurs - they should have known better. How would SG018 have fared with the same primary endpoint as SG016. ?

Please let us know if the company changes its expected news window from March 24

Here's the context - wrong to not partner - wrong endpoints

Td

" Again in Hindsight we chose the wrong end points or rather we accepted what the FDA wanted as endpoints. and given our P2 we had no reason to believe we couldn’t achieve them. Those end points were almost impossible to beat because of vaccines and SOC.

We should (in hindsight) of chosen severity or death and whilst DOC D suggest most P3 use 1000 patients I think that’s a tongue in cheek number that fits his argument rather than statistical fact. We have Activ2 as an example when they moved from time to recovery to severity and death had the trial gone ahead patient numbers would have been 1600. We

Also know from RM (Richard to his friends) own words that he thought to prove severity / death required a couple of thousand.

The only way we could have known the impact of vaccines and SOC would have and be certain would have been to trial an outcome using those combinations.

We should have partnered earlier. I’m guessing the deal was poor and that was our mistake IMHO "

Here's the context - wrong to not partner - wrong endpoints

Td

" Again in Hindsight we chose the wrong end points or rather we accepted what the FDA wanted as endpoints. and given our P2 we had no reason to believe we couldn’t achieve them. Those end points were almost impossible to beat because of vaccines and SOC.

We should (in hindsight) of chosen severity or death and whilst DOC D suggest most P3 use 1000 patients I think that’s a tongue in cheek number that fits his argument rather than statistical fact. We have Activ2 as an example when they moved from time to recovery to severity and death had the trial gone ahead patient numbers would have been 1600. We

Also know from RM (Richard to his friends) own words that he thought to prove severity / death required a couple of thousand.

The only way we could have known the impact of vaccines and SOC would have and be certain would have been to trial an outcome using those combinations.

We should have partnered earlier. I’m guessing the deal was poor and that was our mistake IMHO "

Therapeutics

May 26th 2020 Remdesevevir EUA. ( Hospitalised patients with ,94% O2

June 18th 2020 Dexamethasone EUA

Dec 2nd 2020 Pfizer Biontech vaccine approved in arms a week later. By October 21 all UK citizens offered 2 jabs

Jan 13th 2021 Sprinter begins.

Nothing further to add. You just don't start a trial with so many known knowns against you. As you admit - they should have partnered up and if they had these mistakes would not have been made.

Sorry I lost part of my post when cutting into 3. This explains that the SOC had changed long in advance of Sprinter

" This scenario cannot apply to SNG001 of course. As the SOC changes - which they must have known would impact the trial occurred before the trial was designed - and in the case of both hospital drugs BEFORE SG016 had even delivered its momentous announcement in July 2020.

Therapeutics

May 26th 2020 Remdesevevir EUA. ( Hospitalised patients with

Enjoy your weekend Tommy. You're still the best poster on this board but it's not really you is it.

Say thanks to everyone

#3

To summarise. The key point is that old Donald Runsfeld quote about knowns and unknowns

“there are things we know we know. We also know there are known unknowns; that is to say we know there are some things we do not know. But there are also unknown unknowns—the ones we don't know we don't know.

In this case the KNOWN KNOWN is hospital SOC and the imminent arrival of vaccinations. The KNOWN UNKNOWN is how much impact all of these factors would have on a trial based almost exactly on SG016 - when none of the protections were in place. The UNKNOWN UNKNOWN is an event like Omicron which scuppered the entire Activ-2 programme.

If the known unknown is potentially so cataclysmic to make the trial fail - then you have to ask yourself whether you continue. Continue with your eyes wide open into almost certain failure . I contend that you don't. You find ways around it - you ask for help from bigger brains and more experienced trail teams. You redesign the trial to try to exclude those who are going to survive anyway. You DO NOT just continue.

Enjoy picking this through. I’m sure I’ve made mistakes, but I’m not a pseudoscientist, just a chronicler of events I’ve witnessed personally since August 2020. I didn’t turn up with a bagful of carefully curated sunshine 2 days after Sprinter failed.

January 2021 - Southampton. Champagne corks popping …

RM “ what can hurt us here Phil ?

PM “ well apart from Dexa and Remdes, the vaccines and the possibility of a weaker variant....... we’re golden “

#2

So - in the autumn of 2020 Synairgen’s scientists are hard at work designing a trial - which they already knowdoes not take any notice of the new SOC - or the tens of millions of doses of vaccine that will start going into arms of the most vulnerable long before the first Sprinter patient is dosed. I don’t know what they’re thing.

Tommyd’s contention is that even knowing all this they had no choice but to continue. He says

“our P2 told us what we needed to do and without a new P2 using vaccines and SOC we couldn’t have known with certainty what the impact would be.

We couldn’t even know how many patients in geographical locations would have been vaccinated or what the SOC would be as it varied across regions and according to availability of drug.”

I say that they did have alternatives. And that if this involved a fast added P2 against SOC and Vax - or maybe just SOC it was reckless in the extreme to continue. Deciding to continue and risk almost all of the SG016 treasure - and our added investment at 175p - without knowing what the impact of changes that occurred before the trial started was reckless and frankly ignorant.

If they decided to continue anyway they could have tightened up the inclusion criteria to point the drug at sicker patients. This IS hindsight of course but they already knew that SNG liked a fire to put out - RM’s quote based on the SG016 analysis.

Final point about partnerships.The reason ( to answer Fruits ) that I’m certain Synairgen would have received partnership offers between P2 and Sprinter, is that - as he well knows. It’s hopw Big pharma works. They sit at the top of the tree in the wonderful world of drug discovery and research and they makehuge profits from acquiring or supporting promising candidates.

This study is from 2019 and involves Pfizer and J&J’s pipeline. It shows that 81% of all these companies drugs came from small acquisitions - usually after P2. They pick up the good stuff and swallow the hit - as happened with many of the Mabs trialists in 2021 if they fail.

https://www.statnews.com/2019/12/10/large-pharma-companies-provide-little-new-drug-development-innovation/

Add to this - if it’s just a smoking gun and that's not enough- is the fact that RM told us every time he was in front of a camera that discussions were ongoing with industry “partners” and regulatory bodies.

If you don’t think anyone picked up the phone and asked if they could help in the aftermath of the global headlines generated by Magic Monday - when SNG was the only prospective treatment on the planet that might save 79% of lives - then you’re as delusional as old Fruits. And if you don't think that partnership would have designed a trial robust enough to work against the altererin landscape then you're beyond help.

#1

I had no intention of continuing this today - my initial post was in response to yet another TD rewriting of history and I wanted to counter that, but as I wake up to find you still at it I'll make one or two final remarks.

There are 2 possibilities for the failure of Sprinter.

1. The trial design was flawed - the company expecting a scaled up SG016 to produce the same outcome, but failing to spot the impact the new SOC of mass vaccination, and the newlyt approved drugs Dexamthasone and Remdesivir would have.

2. The design was fine, but subsequent uncontrollable events led to the failure

There's sympathy if the answer is 2 of course -it happened with lots of drug discovery and development companies and trials during Covid 19. This is indeed what happened to the SNG ACTIV-2 trial. But it didn't happen with Sprinter - and it's not an excuse. All those Mabs that were tailor-made for variants that had been replaced by later VOCs by the time they achieved approval. Billions of litres of hamster juice - produced at vast cost by companies on Activ2 and beyond flushed down the drain when Omicron arrived. Omicron which also killed SNG's outpatients hopes.

Most of the hits from these failures were absorbed by large and mid range pharmas who had partnered with the Mabs designers to get their product across the line, often with massive financial support from Barda. More on this later.

This scenario cannot apply to SNG001 of course. As the SOC changes - which they must have known would impact the trial occurred before the trial was designed - and in the case of both hospital drugs BEFORE SG016 had even delivered its momentous announcement in July 2020.

Therapeutics

May 26th 2020 Remdesevevir EUA. ( Hospitalised patients with

Long post incoming - ignore it please if you don't like my stuff.

Woof

Already am Tommy - u too if they can spare u

Insight from the nodding dog mounted on the dashboard of RM's Landy. Woof woof Tommy - pulling a double shift tonight Woof woof

"Tommy is correct. " Gunto.

Sorry just read your last paragraph "We couldn’t even know how many patients in geographical locations would have been vaccinated or what the SOC would be as it varied across regions and according to availability of drug. "

The globol scope of the trial was another huge and costly error. It's probably why they decided to dump swab testing, thinking the good nurses in Kampala miught not be up to the task. You say "they couldn't know .... but of course they should have known or assumed the worst. We were told it was a genius move to assure pre - approval when the moment came but it cost precious time and money and ruined the data.

They were kings of the Universe back then of course and opted for a gold plated Rolls Royce of a trial - that Parexel promised would get them over the line. How did that work out ?

They didn't only have the option of a 900 patient trial in different dosing groups. They could have run Sprinter as it was run with 900 patients. And when they knew SOC would influence results negatively - as they must have know as there are dozens of studies showing the impact of steroids on immune response - then they should have re-dedesigned it.

That's not hindsight - it's what the CMO should have said to Richard ( to his pals) in the late autumn of 2020.

Boss - this isn't going to work .....

I'll leave it there. Goodnight

"The only way we could have known the impact of vaccines and SOC would have and be certain would have been to trial an outcome using those combinations. "

This is nonsense. They knew absolutely what steroids would do to the immune response and interferons.

How Philip Monk survived all this is one of the great mysteries. RM is just the front of house guy - but PM designed the whole bloody thing.