The latest Investing Matters Podcast with Jean Roche, Co-Manager of Schroder UK Mid Cap Investment Trust has just been released. Listen here.
A new study published today referencing the role type 1 interferons can play.
https://www.nature.com/articles/s41577-021-00588-x
'SARS-CoV-2 infection inhibits early interferon signalling, while activating inflammasome signalling. Loss-of-function mutations in type I interferon pathway genes and autoantibodies to type I interferons are associated with severe COVID-19, and age further dampens type I interferon response. The virus-intrinsic and host-intrinsic dampening of the interferon response in SARS-CoV-2 infection should compromise antiviral immunity but may also contribute to unrestrained cytokine release by removing this negative regulator of inflammasome activity. Unbridled inflammasome activation can drive severe disease complications.'
'Early administered recombinant type I interferon might not only restore an innate antiviral immune response to better control SARS-CoV-2 but might also simultaneously restrain subsequent hyperinflammation.'
'However, clinical trials have not yet demonstrated a clear benefit from type I interferons.'
Polar only lists the top 10 holdings of the Biotechnology fund. There’s no evidence yet to suggest they sold out.
The 12.2% in non public hands is not correct as it excludes some holdings including that of Polar.
We had limited supplies of SNG001 which held us back and was therefore unable to participate at a significant number of sites.
I did a post long ago hypothesising about the reasons for limited supply. In short the original SG018 had 900 patients which means Synairgen ensured it had sufficient supplies for the trial and nothing more. The FDA then came along saying they want to include SNG001 in ACTIV-2 and the only way to facility this was to eliminate the lower dose arm of SG018 and to redirect the product & placebo to ACTIV-2. Hence, we’re kind of ‘lucky’ to have been included from Feb. Subsequent manufacturing would supply phase III with sufficient supplies if we proceed.
mact4 - The subsequent changes to the protocol would be beneficial from a phase III perspective as only high risk patients are eligible. From a phase II perspective I don’t think the changes impacted us - difficult to say really. The initial phase II recruitment criteria had a wider scope (low & high risk). Most importantly for phase II we need to show safety and early reduction of viral load/improvement in symptoms.
mact4 - the inclusion criteria for ACTIV-2 phase II which were applicable to SNG001 were more relaxed than SG016HOME. It’s changed in subsequent versions of the protocol. Based on the latest version phase III is more aligned at least from an age perspective.
BigjohnnyWin - politicians don’t approve drugs!
No, it's Rob(ert) Smyth.
Something is brewing and it's not a pot of Yorkshire tea, something way more potent. If they're planning further trials which is what the job ad alludes to they will need funding so the question is how the funding will be obtained. I guess we'll learn at some stage what's brewing.
Are they planning more trials? Makes no sense to advertise for this role when it comes to SG018.
Now this is quite interesting ….
Senior Clinical Research Associate (full-time, remote working)
An opportunity has arisen within the company for a permanent, experienced Senior Clinical Research Associate, supporting the Head of Clinical Operations and Project Managers, in carrying out and completing tasks associated with Synairgen’s clinical trials.
https://www.synairgen.com/contact-us/employment-opportunities/
Saxondale - we should have more sites than these as countries like Germany, Mexico and Argentina are not listed. Not sure if Romania actually materialised.
SeaBoy - here are the definitions as per the NIH clinical trial site.
Primary completion date: The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure.
Study completion date: The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit).
10 sites added. No other updates other than sites, so we have a disconnect between UK & US versions of trial recruitment end dates.
https://clinicaltrials.gov/ct2/history/NCT04732949?A=4&B=5&C=merged#StudyPageTop
Remember the same happened in the results presentation. It’s not his trial so I guess he’s just not going to mention it.
The following should be borne in mind based on some comments/assumptions made .
1) ACTIV-2: To progress to phase III a drug needs to be safe and secondly demonstrate early changes in viral shedding or improvement in symptoms. SNG001 already proved safety while the in vitro tests showed SNG001 to have potent antiviral activity. Based on this you could suggest SNG001 shouldn’t have an issue progressing to phase III. But, the point I wanted to make is to highlight the graduation criteria.
2) Bear in mind SNG001 was one of four agents trialled in ACTIV-2 phase II and was later joined by another three agents. All competing for patients while the virus was in decline coupled with suggestions that they struggled to recruit patients. This could in part explain why it’s taking so long to complete recruitment.
3) My understanding of SeaBoy’s post is that a patient would be admitted to hospital, immediately assessed and sent home the same day with SNG001. (Correct me if I’m wrong SeaBoy.) It’s like going to your GP. That does not count as hospitalisation. That’s outpatient. The lady from Hull spent a few days in hospital before being sent home which does count as hospitalisation. Need to distinguish between these two scenarios.
4) RM made it clear with the release of the SG016HOME results that the company will not, on its own, be pursuing further trials for outpatients.
I did see it. Thx.
bdcarr123 - 01 Oct is also stated to be the primary completion date. So either it’s an error or a misunderstanding of the meaning of the dates. Either way doesn’t really matter anymore. The latest as per the U.K. version of the abridged protocol is a recruitment end date of 01 Oct.
Doc - An unblinded analysis is planned of which the results will be reviewed by the IDMC (independent data monitoring committee) once a certain number of patients had been recruited to confirm ‘proceed with’ or ‘stop’ the trial. You won’t conduct an expensive phase III trial without this checkpoint. With two months of recruitment left I’m sure we’ve reached that point. Well, hopefully.
This does NOT mean they will do additional analysis if required or being asked to by the Health Agencies for possible early approval, but it’s certainly not inconceivable given the circumstances we’re finding ourselves in. That’s my view which is in line with comments made by RM himself earlier this year of which I've posted the Youtube link.
There’re strong public health and commercial reasons influencing the ‘tipping point’ decision.
Again, I’m not saying it’ll happen as I certainly don’t want to set myself up for disappointment if it does not happen. Just saying it’s possible.
*Tipping point
It’s definitely NOT highly unlikely to get an interim readout. Very possible indeed, does not mean it’ll happen, but quite possible. Remember the trials are delayed by quite a bit, there’s potentially going to be a great clinical need this winter and so if the SG018 interim data, which they will have and may already do, looks promising the Authorities would want to proceed instead of waiting for a Dec readout. It’s about that ‘ripping point’. The trial will/can still be completed without interruption. Why would you go into the winter season knowing SNG001 is efficacious based on strong supporting data, but decide against it for the sake of a full readout while you already have strong interim data. That’s why the idea of rolling reviews were brought in to expedite approvals.
A similar scenario might play itself out re ACTIV-2.
Worth listening to this again from 8.10 - 09.10
https://youtu.be/nhFqeW6sIXg
Don’t get me wrong I don’t bank on an interim, however I’m just of the opinion is very likely.
As you mentioned volatil1ty the same was observed for convalescent plasma (CP), but if I remember correctly it was also in immunocompromised individuals. If so isn’t it then rather caused by the immunocompromised condition as opposed to mAbs or CP and/or a combination of that?
The Beta variant was also believed to have originated from an individual who was immunocompromised.
The PM made it very clear people should not think it’s over. That’s the right message.
Part of the strategy is to force a peak prior to winter in the hope that we don’t have or have a much smaller peak during winter when the expectation is that other respiratory viruses will hit off again which on their own could be worse than prior winters excl 2020/21. That’ll be a double whammy. So it makes sense what they’re trying to do.
I understand the hesitancy, however we must learn to live with the virus and in the process figure out what works and what not through real world scenarios. The road will have bumps, but that’s how you learn. We can’t continue to live based on assumptions and use that to enforce restrictions. The British public won’t tolerate that anyway.
We may have some tough days ahead, but we’ll get to the other side. Just enjoy the ‘now’ and be optimistic. Don’t fret about what may or may not.
By the end of Sep almost 90% of adults would’ve had their 2nd jab. That’s great.
It’s not unusual to see higher case numbers reported on Wednesdays and Thursdays, even by a few thousand. It's too early to tell whether the increase is due to a processing overhang or the start of a genuine increase.
With regard to hospitalisations. Hospitalisations follow the same trend as cases albeit on a week lag basis. As of 26 Jul, five days into the current week, the week-on-week growth in hospitalisations for England have shown a decline for the third week in a row. The WoW growth was 13% as of 26 Jul whereas the previous week was 31%, before that 42% and before that at a peak of 55%. This is good, not bad.