Member Info for Doc.Daneeka

And - again without giving advice - now that you've missed the OO boat, it might be prudent to wait and be certain that the mimimum raise has been achieved. Which we'll know very soon. Once that threshold is met the repayment promise will lapse and everyone else's new investment will be at prey to the normal vicissitudes of the market. If the threshold isn't met and TFG go it alone, we should expect the price to collapse .

Pretty sure that all Ventilated C-19 patients will already be receiving Dexamethasone. Still SOC for C-19 - and given as soon as patients require suplemental oxygen in hospital . 38% lower risk of death for MV so everyone is on it, and they will not be able to exclude it. Surprising they haven't pursued the Flu trial which seems to be in some kind of limbo - waiting for a Flu Pandemic.

Synairgen didn't mention it I guess because it is not an anti-viral.

Bob - look at the Sprinter RNS history from October 2020 to Jan 2021 to see the process. They've probs had talks with regulators already but as I quoted already the Dec 20th RNS says " subject to regulatory approvals "

The trial will start in March or April if we're lucky.

Thanks chaps. Timeline slipping before the offer even closes. - 2024/2025 virus season disappears from this release. Par for the course with every deadline this company ha ever set and hardly surprising as regulatory approval cannot be sought until funding is in place . Almost inevitable now that they'll miss the winter virus season which they said they'd hit just 3 weeks ago when they aked for our support. Sprinter took 3 months to go from result of placing to commencement.

20th December 2024 " Subject to regulatory approvals, Synairgen plans to initiate a Phase 2 clinical trial (SG021) in mechanically ventilated patients with confirmed respiratory viral infections during the coming 2024/2025 virus season.

28th Jan 2025 Synairgen plans to start its global Phase 2 trial, .....as soon as is practically possible in 2025.

Confirmation also that we won't see the trial protocols until long after they've banked the cash.

The trial plan so far is

1. Confirmed respiratory infection

2. >50 years of age.

3. Co-morbitiies ( details yet to be revealed.)

4. High Viral load ( details also yet to be revealed. )

They've mentioned biomarkers and assays many times in the last few years but there's no evidence of any sophisticated testing to be used, in anything they've released so far.

The most obvious thing to say is that over 50 is really young if you're trying to reach a highly specific vulnerable population - part of Sprinter's failure was the misapprehension that the drug was an all-population wonder treatment - which was nonsense of course. Co-morbidities and most significantly High viral load are then to be the metrics that allow them to say the P2 will have an 85% chance of success. Obvs there must be a chance that we'll be back in the same position as we were after Sprinter if they miss the Primary motality endpoint - but do well againt the secondary endpoints relating to time on ventilation and time in hopital. Let' s hope they haven't got these the wrong way round again as they did with Sprinter. Whether TFG will want to listen to the pitch again is another matter.

To answer the question about Dexamethasone - as far as I'm aware it it still SOC for Ventilated Covid 19 patients - heving been EUAd after the RECOVERY trial in 2020. Strangely Synairgen makes no mention of DExa in the background notes - when they say only Remdesevir has been approved for MV. ( perhaps just a US focus ) Perhaps somone else can clarify. Remember that Syn missed Dexa in the Sprinter design even though it was already approved and in use before the trial began.

There is no 75% chance of success with this trial or the P3 that will follow. TFG are chasing their loss, obviously having seen more of the underlying data that supports Syn's wildly optimistic aim for a 25% morality improvement, than we have - but still essentially investing with the same hope rather than any level of cetainty. SNG has never dosed a single MV patient in all it long history and is basing all of this on some interesting but inconclusive viral clearance data from the unfinished COPD trial, and a lot of other rather nebulous science that may point to a positive outcome in a space where mortality is the product of a welter of layered factors.We have no wy of knowing if it will already be too late for SNG to do any good once patients are being ventilated.

You all seem to be taking RM's word for it without really understanding anything of the dificulties that lie ahead. It's not even a topic of debate on here . Instead you're apparently all in - throwing good money after bad and talking about billions again. And repeating that old nonsense phrase "we know it works" is now just lame. SNG worked in sprinter and ACTIV2 and befoe that in SG016 and before that COPD and even Asthma. It has always worked but never well enough and that's sometimes how it goes and why we are where we are. Has all of that marginal success been leading inexorably to MV or is MV the last role of the dice for a drug that is as underpowered as its last trial proved to be.

TFG have been hoodwinked- just as many of you have - is my best guess - but I'll see what else they publish in the next week or so while contining to wonder why the proposal for this billion $ a year therapeutic somehow still attracted no interest from Big Pharma, why RM was prepared to sell his soul and our share in the company so cheaply and why the company's medical point man and chief architect left in such a hurry just as it was all being finalised. It's worth a Billion year but TG have it for £18m

I've been away from the board for the festive season but hope you all had a good one. I did say thta TFG weas th most likely source of funding to take SNG forward and

January. Or February. Or.....

SYNAFU

The COPD adventure was over long ago. There are no cures for this condition - just maintenance regimes - and all of the new treatments are improving outcomes over a long timescale. Mabs mostly & tailored drugs that dampen exacerbations. Unfortunately SNG doesn't have any compelling data in this area. Maybe if the MV trial succeeds and SNG is a success, a BP will spend money trying to find a new dose or formulation to to make it work for some of the other viral conditions they've been aiming at for so long- but for now it's not a candidate.

My personal feeling is that it's just fatally underpowered. Hopefully something changes in the MV trial - but I'm not confident.

It is indeed a shame Xv - and although nothing to do with Synairgen at the moment, it could be quite soon. In fact it should be very soon.

If they ever pull their fingers out, SNG WILL be in place to save a few of the elderly wheezers being admitted to hospital in the next few weeks, and then into ICU and with luck randomised onto the drug in the forthcoming MV trial.

This is something to take solace in - if you still believe in the drug. And if the company really is about to start the trial.

If it works as they hope, by next Christmas, or the one after, it could be about to start a much larger P3 with full BP backing and the promise of fast authorisation and commercialisation to follow.

It's an end of the road drug now - served to patients with no further hope, and without even the ability to breathe unaided. A neat metaphor for the company you may say, as it wheezes through to Christmas - looking for a financial ventilator to keep BoDy and soul functioning. Synairgen which began its journey as a more or less healthy outpatient in SG016 Home and ACTIV2 - progressed terribly through the Covid wards in Sprinter - and will now either breath its last on an ICU ventilator, or emerge restored and full of robust good health. It'll be one or the other. Success or Failure. Binary. Life or Death.

We're really not fussed when the trial starts - but they gave us this timescale. And even said they hoped they would be delivering inside it. We know too that in the past when they've missed deadlines it means trouble. This time last year we were waiting to hear the starting gun on 2 mini P2s. When they finally gave us that update - 6 months later - we discovered that the main multi-viral area of interest had been cancelled. And that the main clinical architect of everything Synairgen has achieved in the last 4 years had been sacked.

If little Tommyd is triggered by the mild rebukes expressed on this bb he needs to tell RM to stop telling porkies.

Broadly agree with this. Despite Fruits insistence ( without providing any actual examples ) that a magic money tree exists which will offer funding worth 5 or 6 times a company's value - the rest of us know that no such funding exists. You could argue that the patents offer the extra level of worth - but until a trial proves conclusively that SNG works and is commercially viable, the ip is of only theoretical value.

I remain attached to 2 ideas. The first is that TFG will have a direct hand in what comes next, still believes in the drug and is behind the funding. The second is that we are about to see a deal such as the one struck between Synairgen and AZ in 2015, in which a major pharma takes the drug on - in exchange for a minor upfront payment to guarante the company's future, and the promise of royalties if trials are successful.

We're in a very similar situation to 2015 as far as I can see, and although shareholders would be left with very little at the end of this, it would allow SSH and the founders to feel they'd discharged their obligations, to the drug at least, with honour.

"Under the terms of the exclusive licence agreement, AstraZeneca will pay Synairgen a $7.25 million up-front fee and potential development, regulatory and commercial milestones of up to $225 million. In addition, AstraZeneca will pay tiered royalties ranging from single-digit up to mid-teens on commercial sales. AstraZeneca will be responsible for future development costs. "

You'll see the risk was all with AZ - but the rewards were tiered to give the sponsor between 85 and 90% of the future rewards. If the Asthma trial had succeeded Synairgen as a one-drug company, would have been done.

However this deal is done - and of course TFG would need something as well to sweeten it, i can't imagine it'll be any more favourable to Synairgen or its long suffering shareholders. Raising £50m on a dwindling mcap of £8m just doesn't work.

Thanks Mani. Synairgen are just doing what they always do. Over promising. If we'd had a show of hands after the AGM to ask who thought the company would meet the 6-8 week deadline, only the few happy pill merchants would have put their hands up. Doesn't matter really - except for the fun it occasions. I'm only concerned that they don't miss the winter season completely, and I don't thinl they will. This won't be a fast trial to complete.

Seems to me - from further reading of dippfs and wigster's notes and particularly reading what SSH said - that one of the most interesting points is the switch from a mini P2 to the substantial trial they are now planning.

This suggests to me that they had some kind of promise of money ahead of the switch.. Prior to this they were slinking along - hoping to eke out funds and raise a smallish amount of cash to keep the lights on for a mini trial to deliver a good signal that might attract proper interest and support.

Then I think 2 things happened. It's possible the new CMO and Chairman made the suggestion to go big and aim for statistical significance in one trial - but it's also possible the financial backer said we'll give you some money - more money than you've already asked for - but it has to be a P2+.

This also pre-supposes that the backer shares and accepts SSH's and the company's confidence of the specificity of target identification - he mentioned 30% - but without saying exactly what that 30% was. RM didn't bite on the £50m amount - but it must have been close enough. Trialing in MV will be at the top end of costing. So someone is potentially committing a sum of money several times that of the partner company's market cap - which obviously suggests a very high degree of confidence in the trial design and eventual repayment potential. A P2+ with very good statistical significance might also leapfrog the requirement for a P3 in a space where there is only one other treatment and mortality / costs are so high.

Interesting to speculate which came first but it seems likely that when RM talks about the important contribution the new hires have made it might be related to this. We know they made the very difficult decision to suspend ( at the very least ) the bigger 3 year ambition of a multi viral hospital drug in favour of the MV trial - which by its nature is also multi-viral.

If the funding package is still intact and the delays are minor, then despite the many failings and failures of the last 3 years, SNG may finally be heading in the right direction. How much we get back of that old dead cash is moot - as the money can't be raised by a share issue and dilution will be huge - but someone investing in the small allocation of extra shares that will be released with the deal, might eventually realise a decent return.

Final point is that RM seemed to be saying the main exclusion will be to weed out the non-viral MV patients. We don't yet know what the other diagnostic tools might be. The Auto-ab assay was not ready while the trial was being designed - but they don't really need it as it narrows the target population too much.

"Self selected as on vent but need to avoid non virus people. 12 months working on diagnostics to exclude patients. "

So Big Pharma tells Simon Shaw - we're interested - we like it - but show us some real data from a decent sized trial ... but big money says no you're ok, no need for any more data - I used to work for AZ - how much do you need.

****** - adjective ................

I said they'd fund it - not buy it out. Pay attention Fruits

Who then if not TFG Fruits ? SS told us pharma is not interested... talk of Chiesi is just Spacman spitballing ( and amazingly suggesting they'd place an undercover Chairman into the company to prep the buyout. )

Who except TFG is invested physically and psychologically in the drug and company to the extent that they'd risk £35-£50m on a punt. Without just buying it for the patents ?

Are you still waiting for one of your magicial Government grants ?

Thanks Wigster and dippfs. Three things that occcur to me.

1. seems it was RM who first said 6-8 weeks, several times - rather than SS. Not sure why he'd then qualify it as SS over enthusuasm in the after AGM chat ?

2. TFG must be the backer for the trial. SS that pharma will only get involved after seeing good data suggests strongly that they are not funding the P2. I said before that unless a pharma wanted it, TFG would be the only candidate to offer the additional £35-£50m to make good on its original holding. Presuming it has seen and likes the MV rationale and wants to get its money back. Not sure what the mechanism would be but there must be a way it can fund the trial without having to buy the company.

3. They really threw PM under the bus. For RM to describe the architect of the 3 most important trials in the company's history as a "workhorse" and saying he prefers pre-clinical, when there has been zero pre-clinical work for years, is staggeringly insulting.