The latest Investing Matters Podcast episode featuring Jeremy Skillington, CEO of Poolbeg Pharma has just been released. Listen here.
Of course we could swap science all night long
Ten Strategies of Interferon Evasion by Viruses
https://www.sciencedirect.com/science/article/pii/S1931312817302950
But then weâd still be left the same question
Why are you here?
Instead of searching science. If you search trolling, you probably get the answer to that question.
2 out of 10 on the science
Viruses counteract the antiviral response by encoding mechanisms to control IFN signalling, block the actions of IFN-stimulated gene products and disrupt the various levels of cross-talk between IFNs and other cellular pathways. Studies of SARS-CoV-2
, influenza virus, hepatitis C virus, herpes simplex virus and vaccinia virus
If you were a real scientist youâd know this
Great points Fruitz.
Itâs worth noting when looking at history that back in 2014 when Astra offered Synairgen a license deal. Synairgen had around 2m in the bank, the upfront payment was in the region of 3.5 times the value of the companyâs cash balance and the milestone payments valued the company at 100 times that value.
The company had data on just 130 patients.
Today we have data on over 800 patients and that comparison would value the company at nearly a billion.
Astra hardly took a large slice then but based their deal on potential future profits.
Data remains the key and the potential market is huge to a BP partner and thatâs where their focus will be, not the current share price when considering a deal.
GLA
9:45pm
An investor with 5-10mn spends their afternoon and evening discussing a 5p share on a public chat forum with people he doesnât know.
He has no interest in the company or its science and spends every day deriding both.
Is this a serious investor or fantasy trader?
âTime to call itâ
Couldnât be a more inappropriate thread just before news is due.
This drug may fail or may succeed but right now is not the time to make that call.
Patience until we get the RNS and then we will know whether this companies epitaph has been written
GLA
Another day of mainly irrelevant nonsense, summarising the history of Synairgen over and over again and then of course we have the absurdity that is M
People just need a little patience, not long to wait now
For the RNS.
GLA
GLA
What can we expect
The RNS is due in the very near future.
Trials will begin which are likely to move the SP in a more positive direction.
The Market will be able to judge the potential for our our drug.
We should have a road map to commercialisation
Many reasons to remain cautiously optimistic
Patience will see a plan appear shortly and who knows maybe a partner will be forthcoming
GLA
Doc D
Firstly the 900 patients we went to the FDA with, as weâve explained before to you, was a 3 arm trial of different doses. We just dropped one of the doses and the new statistical calculation for two arms was 630 patients to prove the end point. Maybe you should write these answers down so you can remember them.
As for your other point that the trial wasnât pointless from the start.
No it wasnât because the statistical power for the 630 patients was against an end point of âtime to dischargeâ
Size was talking about âhospitalisation or deathâ completely different end point and completely different calculation.
Alway happy to help you understand the finer points of
The share youâre invested in
Have a great weekend
There is nothing wrong with Sizesâs view on the trial being underpowered but it has huge cost and timing calculations for running a trial that is correctly powered.
Fortunately statisticians have already done the calculation for how many patients are needed to meets Sizeâs point
Itâs on page 76 of this document and itâs 1600 patients
https://fnih.org/sites/default/files/2021-10/ACTIV-2_v7.0-wLOA%20073021.pdf
Now Doc D would have us believe you can rock up to the regulator and tell them youâre using 900 patients and justify that by quoting some other trial for some other drug. You canât.
The regulator requires to have carried out proper statistical analysis for the end points youâre trying to prove. That calculation is in the document above.
Then as tends to be Doc Dâs way of arguing a point he changes the context by making sweeping statement about wasting money on a global trial.
But of course running a trial in letâs say India is far less expensive than running it in the USA or U.K. So having some of our trial patients from less affluent nations probably saved not cost us more money.
âThe cost of conducting clinical trials in India ranges between 20 and 60 per cent of the cost in western countriesâ
There are also well know reasons for choosing a diverse population in your trial and the regulators expect that.
The information I posted is from the Activ 2 protocol. Itâs specific to our drug and providing sufficient power for end points of hospitalisation or death.. 1600 patients
But as you said you have no idea and that I do agree with
The trial size calculation to prove hospitalisation or death. This is what Sprinter would have had to do and note for non infused drugs their calculation is 1600 patients to provide sufficient power.
So please do tell us why they are wrong Doc D in their calculations?
Sample Size Justification for Non-infused Investigational Agents
For the evaluation of a specific infused investigational agent, the sample size will include approximately 800 participants randomized to receive the non-infused investigational agent and approximately 800 participants (who were eligible to receive the non-infused investigational agent) concurrently randomized to receive the active comparator agent. This sample size has been chosen to provide very high power (approximately 96%) to establish non-inferiority assuming that the true proportion hospitalized/dead for both the non-infused investigational agent and the active comparator agent is 2.3%, while also providing high power (approximately 85%) assuming that the true proportion hospitalized/dead for the non-infused investigational agent is 0.5% worse, i.e., 2.8%, than the active comparator agent. The rationale for the 2.3% rate for the active comparator agent and for having no adjustment for loss to follow-up is the same as described above in justifying the sample size for infused investigational agents.
80 ACTIV-2/A5401 FINAL Version 7.0 6/29/21
The potential power of the study for non-infused agents was evaluated in the same two ways as described above for infused investigational agents using the PASS version 15 sample size calculation software. Use of the binomial enumeration method not taking account of interim analyses gave a power of 96.6% if the non-infused investigational agent and active comparator agent had the same true rates of hospitalization/death (2.3%), and 85.2% power if the non-infused investigational agent had a slightly lower true rate than the active comparator agent (2.8% versus 2.3%). The second (simulation-based) approach did not use a binomial enumeration but taking account of four equally-spaced interim analyses using the OâBrien and Fleming stopping guideline. This used a simulation approach and gave a power of 96.2% (width of 95% confidence interval around this simulation-based value was 0.08%) if the non-infused investigational agent and the active comparator agent has the same true rate of hospitalization/death (2.3%), and 84.2% power (width 0.15%) if the non- infused investigational agent had a slightly lower true rate than the active
As ever Doc D.
leading activ2 scientist in the USA working on Covid calculate the size of a trial to provide sufficient power for the end points and you declare theyâre wrong.
Your level of arrogance knows no bounds
âRunning a trial under powered for secondary endpoint success is not good risk management. It was a massive oversight and I hope lessons have been learnt.â
Itâs a great phrase but in reality what does it mean. If people are going to say these things they have to explain the consequences.
Our secondary end points were progression to severe disease, hospitalisation, death. Our trial size 630
Now we have a really good example of the implications of Sizes comment in Activ2. The next phase of that trial had it continued would have been outcomes of severe disease, hospitalisation, death. The crucial part to note is the patient size would have been 600-800 patients on drug and 600-800 on placebo. 1200-1600 patients
So we are talking of a trial 2 to 2.5 times the size of Sprinter with associated costs and timescales.
Itâs likely we couldnât afford it and if it had failed, bearing in mind what we now know about the way vaccines and SOC impacted our drug. Without the knowledge we now have from the deep dive and being more selective on patients, it might well have failed and bankrupted the company.
Phrases are easy to write but the consequences are rarely discussed or understood on this board.