Member Info for Doc.Daneeka

Sure Tommy - you're always posting about competitors with stellar COPD data. Thanks again for the heads up. Really pleased for Verona, Sanofi and Regeneron. Companies with modern tailor-made drugs that offer long term solutions - even using inhalation as a delivery mechanism ( just imagine !!) - for COPD and most likely every other RVI out there.

Fruits - yes I have become disillusioned and even occasionally bitter when you two are posting your fanboy nonsense. My eyes are wide open and I've finally lost faith in this company - even as it stands on the threshold. I know nothing of what they've been doing over the last year and UNIVERSAL's results are utterly predictable and of no use whatsoever. The company will announce protocols for the P2s with almost exactly the inclusion criteria of the failed Home trial. Age and Comorbidities. Imagine that. They will run a trial or trials that they could have started 2 years ago and with protocols that should have informed the Sprinter trial. Nothing new or ground breaking - none of the tailor made space age diagnostics we were promised - and that Tommy said the drug had been waiting 25 years for - and whatever equity we have left will be surrendered in just getting past the P2s. Even if Casanolabs has done something clever it still needs to be turned into a fast test which if they're lucky will help to deliver an extra 10% of patients who may or may not benefit from SNG. They will go with age and comorbidities and run predictable little trials with predictable results. An improvement in LOS is the best hope. They may have success in incubated patients I guess - if the regulators let them in to the HDU. Then - when the money's gone - some other company will finally get it over the line and one day we'll be able to applaud another AZ success story.

I mean it's great that you are shining a light on another company's very good drug and I salute your continued classy focus on the entirety of the marketplace SNG will one day hope to be selling into. And at the same time thinking of the poor sufferers who will soon find relief. It all does you tremendous credit.

Verona's Ensifentrine - for this is the drug - will benefit greatly from the developmental funds released in this deal - as it awaits almost certain NDA on June 26th. They are discussing their 36% P3 efficacy at ATS so maybe PM can share his specialist knowledge with them, show them his poster and buy them all a beer. While he's at it he can look up Sanofi/Regeneron's Dupilumab team and shout them a stubby too. They presented their 34% P3 data today and are also waiting for a likely sBLA which is expected a day later on June 27th. All pals together in the COPDosphere I'm sure - and plenty of the huge COPD pie to go round.

Tremendous really & I agree with you - 2 fantastic new and complimentary drugs almost ready to bring relief to a wheezing spluttering world.

This is a good read for COPD watchers. " COPD Market poised for paradigm shift "

https://www.biospace.com/article/copd-market-poised-for-paradigm-shift-with-potential-approvals-in-2024-globaldata/#:~:text=Potential%20FDA%20approvals%20this%20year,report%20from%20analytics%20firm%20GlobalData.

Not sure why you've posted this Tommy ? You do know why the funding - which was propossed by Oaktree and not sought by the company - has been agreed ?

Tommyd posted the historical "truth" of the Sprinter trial and timeline of dexa and vaxes but it was fake and deliberately misleading. I corrected some of the false narrative inaccuracies. My correctional post was well researched and accurate. He said they had no way of knowing whether Dexa would have an effect even though it was trialed and approved and already in use in the UK and US before SG016 even finished. He said Dexa wasn't approved in the US, but it was already in use and didn't need to be given further authorisation. They knew for absolute certain an extra 20% of patients on oxygen would be saved but took no notice even though Sprinter's trialists were recruited using exactly this criteria. Tommy also said that they there was no way of knowing whether vaccines would affect the trial - and that was just plain stupid. Even if it wasn't until late 2020 that the data came through it was always incredibly likely that AZ's tried and tested adenovirus would be very effective - without even considering the promise of the new mRNA vaxes.

Hopefully one day SNG will find its place, but we know Synairgen wasted the generational opportunity of Covid and the huge sum of money raised to see it through to authorisation in a poorly designed P3 - as they've admitted themselves, and are now scratching around to find ways of getting the project finished with almost no money left.

Trials do fail of course - but rarely with this level of incompetence.

Myths and fantasy - and then outright lies from Tommyd

So much of this is untrue - particularly the idea that Sprinter was already set in stone by July because they had started talks with regulators then. The trial design wasn't finalized until much later in the Autumn as we know and several changes were made along the way - as reported in the Clinical Update on December 18th. There was plenty of time to take account of Dexa. The Dexa results had been known for just a month when SG016 landed - but it was immediately EUA'd in the UK and the data from the 6000 patient RECOVERY was accepted immediately both in the UK and US. There was no doubt that it would save lives in the very population Sprinter was testing. 20% for people on O2 which was exactly the target population for Sprinter.

" The USA didn’t authorise the drug until August " WRONG There was no need for an EUA in the States as it was already approved, and it was in hospital use immediately in both countries before even the preprint was issued.

Reuters June 19th 2020 https://www.reuters.com/article/idUSKBN23Q2W3/

"So we could hardly have known the impact in July" GARBAGE To suggest that they couldn't know what effect it would have is utter nonsense. The entire medical establishment believed that the 6.5k trial of which 2.1k received Dexamethasone would produce exactly the same results in real world settings. That's how medical trials work when they're done properly and that's why the NHS EUA'd it instantly and hospitals in the States started using it. By the end of 2020 - and before the gun fired on Sprinter, Dexa had saved half a million lives.

"In oxygen patients it was only 1/5th and in none oxygen it made no difference. " ONLY 20% !! The Sprinter inclusion criteria was for patients receiving oxygen. 20% is a huge percentage in our exact patient cohort.

Too nice a day to waste further on your ridiculous narrative - but when you go on to suggest that they couldn't have known what effect vaccines would have it becomes surreal. 23 in trials globally by the summer of 2020 , but yeah they might have all failed or offered minor levels of protection.

You pontificate on here and throw around your pseudo science accusations, but your research is one sided and you promote a false revisionist narrative. RM began this untruth himself in the topline announcement issued on Feb 21st 2020, when he said " SNG001 has been administered to hospitalised patients on top of standard of care which changed substantially between our Phase 2 and Phase 3 trials. " and that was disingenuous in the extreme. They just weren't worried about Dexa or Vaxes even though the impact of both was clearly going to be significant.

We all know the mistakes and oversights made in Sprinter's design were colossal. Ask whoever sends you your material to try harder

On my terrace by the river in sunny Hampton Wick actually Tommy. How's the view from the 15th floor ?

You're a company shill Tommy - not sure which company - but nowhere to be seen before Sprinter collapsed, and then here every day telling us it was all an ACT of GOD and the company could not have done anything else.

Finish this conversation before demanding answers to unrelated questions. What is so special about the ATS poster presentation PM will deliver ( stand next to ) tomorrow ? How does Synairgen's revelation that age, comorbities and obesity are significant factors in Covd outcomes not go straight into the No Sh.it Sherlock bin given the huge volume of pre-existing and detailed ( granular even) work in this field ?

And why were Synairgen so unaware of the growing body of evidence concerning these 3 factors - setting aside if you will the presence of new SOC in hospitals - that they ran Sprinter without any consideration of them and are only now discovering it in their own data, 27 months later . The arrogance and ignorance in the design process and the ham fisted post hoc analysis is still staggering to contemplate.

Having had your pitiful attack on my apparent inconsistencies rammed down your throat, you scutttle sideways and produce something utterly unrelated. I'm only commenting on the importance or lack of it of Philip Monk's stint next to the board tomorrow.

I won't add to my previous comments except to say that news will be with us very soon. If they've finally and cleverly discovered for themselves that age, comorbidities, and obesity are risk factors then I'll throw my hat in the air and shout huzzah with the best of them, if it means they can finally start the bloody trials.

You're not paying attention Tommyd. The ATS paper - if what we've seen is the totality of PM's presentation - is of zero interest to the wider scientific community - which has known about age, comorbodoties and obesity as key risk factors in Covid since at least May 2020 and further back even before Covid in other respiratory conditions. ( see my earlier post if you still believe there's important "granularity" in the tiny dataset compared to the huge wealth of studies about this subject from all over the world )

When PM sits down the tumbleweed will blow past the podium unless he pauses and pulls a second piece of paper from his jacket pocket.......... which is what we all hope will happen.

This contention does not negate or contradict the second point that if Synairgen had employed any, or all, of these as inclusion criteria when designing the Sprinter protocols, that it would almost certainly have been a more successful trial. This is self evidently true.

Instead Sprinter allowed almost everyone on oxygen (OS4) to participate - and as we know this meant far too many were accepted who were younger and fitter than we needed, derived no benefit from SNG whatsoever, and were going to get better anyway ( thanks in part to the SOC that Synairgen also disregarded )

So in summary for my feeble minded interlocutors - YES age - obesity and comorbidities are important in Covid ( and many other respiratory infections ) and will play a part in every single trial Synairgen - or the owners of SNG - conduct in the future, and NO Synairgen's contribution in this particular field of study is not significant.

" Vaccine-induced immune thrombocytopenia and thrombosis (VITT) was a new, rare condition that affected approximately one in 50,000 AZ vaccine recipients under 50 years old, and one in 100,000 for those aged 50 and older. Crucially, this was spotted quickly and studied. Established protocols for vaccine monitoring did their job. It should also be emphasised that no long-term effects have been reported from the vaccine (monitoring of side effects is ongoing long after an initial vaccine roll-out) and the rare occurrences of VITT all happened shortly after vaccination.

Many countries then (in mid-2021) restricted the AZ vaccine to older populations, as long as their populations had access to other vaccines, such as the Pfizer mRNA vaccine. The AZ vaccine remained far safer than catching Covid, even if only considering the likelihood of getting blood clots. For instance, a Covid infection was 190 times more likely to result in a blood clot in the vein and about nine times more likely to result in low blood-platelet count. "

All EUA'd medicine is a case of risk versus reward. 6.3m lives saved works for me on this equation - with just 50 families suing the company, and 24 UK deaths officially attributed to the vaccine. It's been withdrawn now because the mRNA vaxes can be adapted quickly to new threats and not for any safety concerns. If you want to align yourself with the knuckle draggers and conspiracy whackjobs on this Fruits - be my guest.

Godly status ! Honestly Fruits that's pitiful. I'd never heard of AZ except in the most general sense before the pandemic and learned of them, as the world did, when they stepped up and delivered the first approved vaccine. Rolled their sleeves up just as the mRNA boys did - with ground breaking science. Most of them stealing huge amounts from Govts along the way - but not AZ whose vaccine was the first line of defence in poor countries across the globe and was delivered at cost. Synairgen tried to step up and missed the mark, and yut you sit there with your bitter lemon face scrating about the unfairness of it all.

Do you really want to get into the AZ debacle Fruits ? I mean they could have taken a beat and considered new ways forward but they didn't. They just handed the drug back. I've no idea why they didn't keep the faith - but they have funded some of Synairgen's involvement with UNIVERSAL which could be a very good thing.

And I do have an AZ crush it's true. Their largely free vaccine saved over 6 million lives to the end of 2021.

If you have a different perspective on the company please feel free to share........tick tock

"Imperial College estimated that all Covid vaccines saved about 20 million lives by the end of 2021. A further study by vaccine type estimated that the AZ vaccine in particular saved more than six million lives by the end of 2021. " New Statesman- 2 days ago.

https://www.newstatesman.com/spotlight/healthcare/public-health/2024/05/astrazeneca-covid-vaccine-jab-withdrawn-scepticism-coronavirus-pandemic

Sure you are right Size. It didn't feature in any of the early studies of risk factors I looked at this morning though and I may have jumped to the wrong conclusion - although China is still only at #149 in terms of global obesity by nation. I guess it's a growing :) problem there as the country becomes more affluent and diets change.

https://data.worldobesity.org/rankings/

The point is the data doesn't show SNG improving outcomes - it's just adding a tiny tiny piece of work to the mountain of research already over done over the entire the course of the pandemic. Is this useful to Synairgen ? Maybe. Is it useful to the world - definitely not.

This is the conclusion to the paper.

" Conclusions: Baseline factors such as age, comorbidity status and BMI have been investigated and shown to affect the risk of progression to severe disease or death in patients hospitalized with COVID-19. Such factors may

be applied to the inclusion criteria for future trials to select patients at greater risk of poor clinical

outcomes who may benefit most from treatment. "

My cut and pastes show that this has been known to everyone since the first deaths. ( interestingly Obesity is not a factor in the early Chinese studies - for the obvious demographic reasons - but jumps up as soon as the virus hits the fat West )

Forget then, the obvious nature of what they're saying in a global sense, as it's a very minor contribution to a crowded and extraordinarily well researched field of study, and focus on the last sentence. PM is saying that these will be - in part at least - the fundamentals for the new set of Synairgen trials. With whatever UNIVERSAL has revealed and a side order of auto-abs thrown in for the 10% of very sick patients who may benefit.

Which is fine of course - makes perfect sense and what I said ages ago when we discussed this, but it gives the lie to Tommy's ridiculous pronouncement that Sprinter failed because the medical science wasn't ready. That SNG had been waiting for the new biometrics and diagnostics to reveal at last - the truth. That the new age of medical wonder would enable oinpoint identification of ours patients. Apart from Auto-abs the new set of protocols, if they ever arrive wil be based on traditional data analysis and a set of scales

A big competent pharma would have seen this straight after Sprinter and set up new trials with much tighter inclusion criteria for a still very large cohort of patients. Instead RM spent 2 years looking for a platfom trial that wasn't available - and then another year pivoting AWAY from covid. He said this in his only interview in the last year. When all along, all they needed to do was to start dosing the right patients, based on the obvious and well known risk factors and using the still significant numbers of C19 patients.

I'll leave it here too, but we've still a very long way to go if the ATS presentation really is where the company's mind is at the moment.

Just a few dozen of the 100s, perhaps 1000s of studies, starting very early in 2020, that state age, (#1) comorbidities (#2) and obesity as being critical risk factors in Covid 19.

If Philip Monk is at ATS because the big announcement is due and they felt the need to put something current out there then it's perhaps understandable, if he's out there because the trials are not ready and he's offering a holding pattern publication to assuage the critics, good luck with that, but if he's expecting a standing ovation for going all that way to say that Synairgen agrees with the overwhelming and long understood medical orthodoxy on risk factors for c19, then he may be disappointed. It's altogether perplexing, releasing a minor piece of data that would have been one of the first things to emerge from a cursory glance at the Sprinter data. ( er how old were they - er did they have anything else wrong with them ... er I wonder if we had any big lads .. ) The sort of high level analysis Td himself could have whipped up in a few short hours.

So, I've no idea what PM is doing out there or what response he and the company expects to this very minor contribution - unless they've lodged this amuse bouche as a place holder and plan to RNS the trials and subsititute this out on Monday morning as the mini P2s are launched. That would be cool.

Fruits is happy of course - he always is. And the parrot appears to have moved on the perch - so the rest of us can be mildly relieved at that, at least.

" Age is the strongest risk factor for severe COVID-19 outcomes. Patients with one or multiple of certain underlying medical conditions are also at higher risk. " https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html#:~:text=Age%20is%20the%20strongest%20risk,are%20also%20at%20higher%20risk.&text=Additionally%2C%20being%20unvaccinated%20or%20not,of%20severe%20COVID%2D19%20outcomes. 2020 onwards

" The 28 records included, eleven of which are preprints, indicate that conditions and comorbidities connected to a poor state of health such as high age, obesity, diabetes and hypertension are risk factors for severe and fatal disease courses."

https://link.springer.com/article/10.1007/s15010-020-01509-1. Aug 2020

"Comorbid illnesses such as AD and lung diseases may be more influential than aging alone." July 2020

https://link.springer.com/article/10.2991/jegh.k.200721.001

" Obesity: A critical risk factor in the COVID-19 pandemic "

https://onlinelibrary.wiley.com/doi/full/10.1111/cob.12403

"In a study in France, the odds of developing severe COVID-19 were seven times higher in patients with obesity. "

https://www.who.int/docs/default-source/ncds/un-interagency-task-force-on-ncds/uniatf-policy-brief-ncds-and-covid-030920-poster.pdf?ua=1. May 2020

" Increasing age (especially >60 years) may be the most important risk factor for severe outcomes. "

https://bmjopen.bmj.com/content/11/5/e044684. June 2020

it took me far longer to find nothing to be impressed about in this little bit of predictable and inconsequential analysis than it did for you to find impressive levels of ' bmi granularity ' you're an embarrassing old fanboy fruits.

maybe i'm wrong though and ats will be cooing over the tremendous new paper - if it's actually been presented and not just filed in the folder marked no **** sherlock.

tick tock fruits

JD exactly right on this. Being old, overweight, and already ill with something else have long pointed to poor outcomes in Covid since the very earliest 2020 studies. And before this in Flu, COPD and prety much everything else. If anything serious happens to put you in hospital -- whether a car crash or heart attack or respiratory virus - you may not make it if you arrive fat, old and dragging 2 or 3 co-morbidities along with you. Maybe it'll help to know exactly how fat you need to be to have a really bad outcome but it won't be the single key factor in trial design.

What IS interesting is the fact that those with 1 co-morbidity did better than 2 ( as you'd expect) but also better than patients with none. Which is weird. Either this is a statistical anomally from a smallish cohort - or there are other factors at play. Perhaps having one serious life changing condition makes people much more careful of their health ( I stopped smoking immediately I was told I had Type 1 diabetes for example ) but when the risk factors start to multiply it becomes more difficult for patients to look after themselves. Maybe.

In any case - we are now waiting for much more targeted diagnostic tools than what's indicated here, although they'll play a part I'm sure. If any of these 3 had been part of the inclusion criteria in Sprinter's protocol, we would undoubtedly have seen a much better result. If all 3 had been used, the trial might have taken another 6-12 months but it would almost certainly have succeeded. As I've said before - they thought they had a mass population drug when they designed Sprinter and we know now that's not the case.

Glad you agree Fruits. Pehaps you'll now ask the mods to take down the nonsense post about non - dilutory routes forward.

They had the free lunch in the autumn of 2020 - when we supported a placement which they've dined well on ever since and spent mostly on the ill conceived and fated Sprinter trial ( who was it that reported that PM said " in hindsight they'd have changed the endpoints to the same as SG016 " ... )

Despite this, I too am still reasonably, and unaccountably optimistic - given the utter shi.tshow of the last almost 9 months of silence, that one day inhaled interferon will be on offer in my local HDU, but it won't have Synairgen's name on it. If they don't have enough money to complete the trials, this once majestic porker will head for the BP slaughterhouse where we'll probably be looking at ( once the BoD has arranged its own safe and well upholstered private jet exit ) a leg, 3lbs of streaky and a couple of chipolatas. Would that be "mutually beneficial " enough for you ?

Beautiful corporate speak Fruits " Hopefully the recent CFO will have been looking at non-dilutive routes to elongating our cash runway. " but unless the company has the cash to complete its P2s and P3s there can be no free elongating of the cash runway and no chance of a non-dilutory deal.

When AZ came calling in 2014 it was effectively prepared to take SNG off Synairgen's hands. Handing over $7.5m and the promise of up to $225 of developmental investment - but taking almost all of the profits from eventual sales. AstraZeneca promised to pay tiered royalties ranging from single-digit up to mid-teens on commercial sales.

So in exchange for the potentially huge costs of getting it onto pharmacy shelves - AZ was taking the lot.

You'll say that Synairgen is in a stronger position now with decent data in certain patient cohorts and some of the future de-risked - but the bottom line is still the same. It needs someone else to pick up the tab to get it to market. Most of us understand that the cost of this will be huge in terms of surrendered equity, however it happens.

We have to hope either J&J or AZ came here for something beyond UNIVERSAL - and that something is SNG. Chances that Synairgen has enough money left to complete the P2s - which should have been well underway it not finished by now - diminishing by the day. Best case scenario from here is a deal similar to one struck with AZ back in 2015. Worst case is that Synairgen are poddling along at their own speed with no significant partners and are not close to starting.