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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 we’ve 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 wasn’t pointless from the start.
No it wasn’t because the statistical power for the 630 patients was against an end point of “time to discharge”
Size was talking about “hospitalisation or death” completely different end point and completely different calculation.
Alway happy to help you understand the finer points of
The share you’re invested in
Have a great weekend
There is nothing wrong with Sizes’s 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 Size’s point
It’s on page 76 of this document and it’s 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 you’re using 900 patients and justify that by quoting some other trial for some other drug. You can’t.
The regulator requires to have carried out proper statistical analysis for the end points you’re trying to prove. That calculation is in the document above.
Then as tends to be Doc D’s 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 let’s 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.
“The cost of conducting clinical trials in India ranges between 20 and 60 per cent of the cost in western countries”
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. It’s 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 O’Brien 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 they’re wrong.
Your level of arrogance knows no bounds
“Running 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.’
It’s 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.
It’s likely we couldn’t 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.
The rapid worldwide dissemination of SARS-CoV-2 and the appearance of these new variants present a substantial threat to public health. In several studies, the function of NSP6, a non-structural protein of SARS-CoV-2, has been revealed to hinder the induction of IFNβ by interacting with Tank Binding Kinase 1 (TBK1), allowing the virus to evade the human immune system
https://www.frontiersin.org/articles/10.3389/fchem.2023.1346796/full
We identified six gene products; NSP6, ORF6, ORF7b, NSP1, NSP5 and NSP15, which strongly (>10-fold) blocked MAVS-induced IFNβ production. Expression of the first three of these SARS-CoV-2 genes specifically blocked MAVS-induced IFNβ-promoter activity, whereas all six genes induced a collapse in IFNβ mRNA levels, corresponding with suppressed IFNβ protein secretion.
In sharp contrast, SARS-CoV-2 infected cells remained extremely sensitive to anti-viral activity exerted by added IFN-Is.
None of the SARS-CoV-2 genes were able to block IFN-I signaling, as demonstrated by robust activation of Interferon Stimulated Genes (ISGs) “by added interferon”
However, SARS-CoV-2 fails to suppress IFN-I signaling thus providing an opportunity to exploit IFN-Is as potential therapeutic antiviral drugs
https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1009800
It will probably cost upwards of 100m to eventually get this drug commercialised.
There is no way we will end up still owning 100% of this drug. That boat sailed when Sprinter failed.
If you raised 4m at today’s prices you’d reduce everyone’s holding by a third and still have a tiny fraction of what’s needed to commercialise the drug.
This drug will only be commercialised with a corporate event to take us forward, the question is timing. Will it be during p2 or after p2.
Our value will be impacted by timing
Quality of results
Number of interested parties.
Thats why a raise is nonsense now and won’t happen.
New study led by the University of Oxford has found that a high proportion of SARS-CoV-2 infections in the general population lead to persistent infections lasting a month or more.
Of the 381 persistent infections, 65 had three or more PCR tests taken over the course of their infection. Most (82%) of these individuals demonstrated rebounding viral dynamics, experiencing high, then low, then high viral load dynamics. According to the researchers, this demonstrates that the virus can maintain the ability to actively replicate during prolonged infections.
Certain individuals showed an extremely high number of mutations, including mutations that define new coronavirus variants, alter target sites for monoclonal antibodies, and introduce changes to the coronavirus spike protein.
https://www.nature.com/articles/s41586-024-07029-4
Maria Van Kerkhove - WHO’s Department of Epidemic and Pandemic Preparedness and Prevention
How would you describe the overall state of COVID at this point in the pandemic?
“COVID’s not in the news every day, but it’s still a global health risk. If we look at wastewater estimates, the actual circulation [of SARS-CoV-2] is somewhere between two and 20 times higher than what’s actually being reported by countries. The virus is rampant. We’re still in a pandemic. There’s a lot of complacency at the individual level, and more concerning to me is that at the government level”
Do we believe the worlds leading scientists
Or
Tommoclarke who says it’s all over but spends his days on a chat board for Covid drugs he obviously doesn’t think are needed .
If we talking about bizarre that really is a bizarre thing to be doing
Highlighting a key piece of information in a study you posted saying twice as many paxlovid patients were vaccinated isn’t mud slinging
Quoting World Health Organisation figures isn’t mud slinging.
You do like to over exaggerate Doc D.
Apparently medical science doesn’t agree with you tommockarke
Southampton researchers are investigating if promising COVID-19 treatments can help other hospital patients and ease NHS winter pressures.
The ACCORD trial, led by Prof Tom Wilkinson, was set up during the height of the pandemic. The aim was to accelerate the development of new drugs for patients hospitalised with COVID-19.
Now, promising medicines from this trial are being tested as treatments for patients hospitalised with other lung conditions. If successful, these could greatly reduce NHS winter pressures.
Identifying new treatments
Respiratory diseases affect one in five people in the UK and are the third biggest cause of death in England. They are a major contributor to the winter pressures faced by the NHS.
Two of the three drugs tested in the ACCORD trial – tozorakimab and bemcentinib – have shown promise as treatments for patients with COVID-19 and are now progressing to larger trials.
These have the potential to help patients hospitalised with other lung infections. Tozorakimab, for example, targets a protein that is raised in many different respiratory infections.
Helping more patients
Prof Wilkinson leads the respiratory and allergy theme at the NIHR Southampton Biomedical Research Centre. He is Professor of Respiratory Medicine and Associate Dean for Enterprise at the University of Southampton.
He is now leading the UNIVERSAL study. This is harnessing advances in testing to identify and monitor people hospitalised with a viral respiratory infection. It aims to better understand how and when viral infections in the lungs and airways get worse, and develop effective antiviral treatments.
Alongside this, he is jointly leading the TILIA study, which aims to test the efficacy and safety of tozorakimab in hospital patients with viral lung infections who require oxygen.
The ACCORD trials platform runs in close alliance with a national collaboration of Phase 2 drug development platforms: CATALYST, DEFINE, and TACTIC.
I’m glad you got a little amusement by my mistake
Doc D
40% increase in hospital admissions is very concerning given most people are vaccinated and a tremendous burden on the health system. How many countries are actually counting now?
https://www.tbsnews.net/bangladesh/health/who-warns-covid-still-threat-773166?amp
“Besides the near 10,000 deaths reported to the WHO last month, there was a 42 percent increase in hospitalisations and a 62 percent increase in intensive care unit admissions, compared with November.
However, the figures are based on data from less than 50 countries -- mostly in Europe and the Americas, Tedros said.
"It is certain that there are also increases in other countries that are not being reported”