Member Info for JoeyDiamond

Opening of new sites in activ-2 has very little or any bearing on SNGs success/failure in the trial.

After 220 patients have been recruited they will review the endpoints and data to decide if it progresses to P3.

Its not SNG its another company about to start phase 1 trials.

Many scientists saying the same thing, IP rights my be waived but in reality not many places will have the ability to create vaccines. This is a political move more than anything.

https://twitter.com/Dereklowe/status/1390029292290117635

(1/x) There are several bottlenecks to vaccine production, all jostling for the #1 position. One is equipment. Mixers for the mRNA lipid nanoparticles, e.g. Some types of filtration material (not patented!) are in very short supply as well, and there are others.
(2/x) Another bottleneck is in key materials like the lipids needed for the mRNA vaccines. Supply of these has been ramping up, but there's still only so much of these things in the world, and their synthesis is labor-intensive
(3/x) A really tough one is expertise. All of these processes (mRNA, adenovirus) need hands-on tech transfer to troubleshoot as they ramp up, otherwise production can be spotty with poor QC pass rates. There simply aren't enough experienced people to go around!
(4/x) Finally, you need scale. Lots of scale. There are a limited number of facilities/companies able to produce, package, and distribute enough of *any* vaccine to make a worldwide difference, and honestly, I think they've all been recruited already.
(5/5) None of these are "We can't because of patents" type problems, but too many people assume that if the patents went away that hundreds, thousands of production lines would blow off the dust and start cranking this week. Sadly not the case.

Yes Matterhorn the placebo group is the same for all drugs so to prove efficacy a drug will need likely 1000+ people dosed.

With the knowledge of other trials having between 3-4% in the outpatient placebo group being hospitalised you can work out the likely events for Activ-2. For SNG activ-2 there will be a mix of normal and at risk people.

In placebo arm I would make a best guess at 3/4 would likely be hospitalised.

Scinv is correct the COPD trial was closed early. This I suspect due to lack of exacerbations/events on the trial (reminisent of HT and asthma trial). However there is good news mixed in here too. See FDA report notes.

Results for Part 1 of the study showed that COPD patients inhaling SNG001 had significantly increased markers of antiviral activity. Sputum samples were taken before, during and after treatment. Gene expression was measured in cells extracted from sputum. Expression of antiviral genes Mx1 and OAS1 were significantly higher at visits during the treatment phase (p<0.0001; gene expression was increased approximately 10-fold and 5-fold, respectively). These genes code for proteins that are known to interfere with viral replication. Other IFNß-stimulated genes which also have antiviral activity (CXCL10 (IP-10), GBP1 and IFT2) were also upregulated.

In Part 2
Originally, up to 120 patients in total were to be randomized during Part 2, however, due to the SARS-CoV-19 pandemic in 2020, the study was paused and an interim analysis was conducted of all currently available data in order to aid decision making with respect to the potential of SNG001 in treating and preventing COVID-19 symptoms. At this time, 109 (placebo, n=52; SNG001, n=57) patients had been randomized and following the interim analysis a decision was made to close the trial.

Results of the interim analysis of Part 2 of the study indicated that the impact of viral infection on COPD patients was most evident on PEFR and patient-reported symptoms assessed using the Breathlessness Cough and Sputum Score (BCSS), and was particularly apparent in patients with a moderate exacerbation of COPD (i.e. requiring treatment with oral corticosteroids and/or antibiotics at the time of randomisation). Exacerbating patients who received SNG001 had significantly better lung function during the treatment period (difference in change from baseline morning PEFR between patients receiving SNG001 and placebo over days 2-15 was 25.5 L/min; p=0.041). Although there was no statistically significant difference in total BCSS in this group over the treatment period, there was a trend towards improvement of the breathlessness component of the score, suggesting that patients may have recovered more rapidly if they received SNG001 rather than placebo. Viral infections had less impact on non-exacerbating patients and there were no significant treatment effects. Biomarker analysis showed that in the overall population COPD patients inhaling SNG001 had significantly increased markers of antiviral activity.

https://colombiareports.com/colombia-surpasses-500-daily-covid-19-deaths-after-pandemics-most-fatal-week/

Colombia’s health ministry reported more than 500 COVID-19 deaths on Thursday, the highest number of daily fatalities since the beginning of the pandemic.

Good timing for approval.

https://science.thewire.in/the-sciences/zydus-virafin-pegylated-interferon-alpha-2b-india-dcgi-approve-covid-trial-methods-flaw/

India have given an EUA for injected pegylated interferon on lesser results than SNG to use in hospitalised patients.

At this point its not the data but rather the issue of manufacturing at scale for SNG which would be the sticking point for an EUA. Merck have agreed with 5 generics drug factories to mass produce on license their drug in India, I wonder if SNG can do something similar.

Probably get the TR1 notification tomorrow of Blessed22s sale

https://www.cell.com/iscience/fulltext/S2589-0042(21)00445-4#%20

Experimental and natural evidence of SARS-CoV-2 infection-induced activation of type I interferon responses.

Paper is mainly by Canadian and Chinese authors.

Just some of the interesting findings

* SARS-CoV-2 infection is unable to inhibit the activation of STAT1 and STAT2 by exogenous type I IFN.
* SARS-CoV-2 is very sensitive to type 1 interferon. In most cases of SARS-CoV-2 even a low level interferon response is normally sufficient to beat the infection. Why so many people have mild/moderate disease.
* Exogenous type I IFN (IFNb1 and IFN-a2) treatment significantly reduced SARS-CoV-2 replication in human airway
epithelial cells.
* Inhaled interferon Beta is now suggested to be SOC for Chinese Covid patients.

From paper
417 Our data demonstrate that SARS-CoV-2 infection induces phosphorylation of STAT1 and STAT2 (Figure 3E), along
418 with upregulation of ISGs, such as IRF7 and IFIT1 (Figures 3B and 3C). In addition, SARS
419 CoV-2 infection is unable to inhibit the activation of STAT1 and STAT2 by exogenous type I
420 IFN (Figure 3E), along with the expression of downstream ISGs, such as IRF7 and IFIT1

98 Data from our study suggest that replication competent SARS-CoV-2 induces type I IFN responses in human airway
99 epithelial cells, and type I IFN (IFN-a2) levels detected in patients with moderate COVID-19 is
100 sufficient to reduce SARS-CoV-2 replication in these cells.

425 IFN responses compared to other zoonotic CoVs extends support to our hypothesis that the
426 pathogenic consequences of a dampened type I IFN response may be largely negated by the
427 sensitivity of SARS-CoV-2 to this response. Indeed, in our studies, exogenous type I IFN
428 (IFNb1 and IFN-a2) treatment significantly reduced SARS-CoV-2 replication in human airway
429 epithelial cells (Figures 4B, 4E and 4F), consistent with a recent study that compared the
430 susceptibility of SARS-CoV and SARS-CoV-2 to type I IFNs (Lokugamage et al., 2020). Recent
431 studies have identified the role of an impaired type I IFN response in COVID-19 disease severity
432 (Bastard et al., 2020; Zhang et al., 2020), which support our conclusion that SARS-CoV-2 is
433 capable of inducing a type I IFN response, and perhaps the inability of the host to mount this
434 response contributes to disease severity. In addition, our data provide promising support for
435 ongoing clinical trials that include type I IFN treatment.

498 Nebulized IFNß is part of the standard of care for COVID-19 patients in China (Xu et al., 2020).

Some thoughts

We do not have a last patient recruited RNS yet for the Activ-2 trial (P2) so likely next Activ-2 news will be this.

Dr Fauci recently in regard to Activ-2 program told us news on progress of the trial was weeks away. Bear in mind there are a number of drugs on the trial so this could or could not include SNG001.

Dr Castro is due to speak on 13th May giving an Activ-2 update. He is the Kansas chap in charge of Activ-2 trials there which includes SNG001.

So for any big news, month of May would be more likely, however an RNS on last patient dosing could be close.

stu485 I think it is imminent as RM would say ;)

Short version is Scinv is saying Interferon Beta is a better bet than Alpha. :)

Bearing in mind the injected form of IFN-A got an EUA today for hospitalised patients in India. An EUA for SNG looks a certainty upon trial completion. Very postive news.

Why - Better method of delivery and the better Interferon :)

Funnily enough after discussing IFN-a and benefits of it reducing viral replication, India have just given an EUA to Pegylated Interferon alpha-2b administered subcutaneously.

https://zyduscadila.com/public/pdf/pressrelease/Press_Release_Zydus_receives_Emergency_Approval_for_the_use_of_Pegylated_Interferon_alpha_2b_23_4_2021.pdf

Funnily enough IFN-a has jusr

For anyone interested you can download the PDF of the paper from here - https://jvi.asm.org/content/early/2021/04/16/JVI.00266-21

Here is viral load information

160 Next, we
161 examined the sensitivity of SARS-CoV-2 to pre- and post-infection treatment with IFN-a, IFN-y
162 and IFN-lambda. Consistent with recent reports (20, 23, 26, 27), replication of SARS-CoV-2 was
163 strongly inhibited by pre-treatment with IFN-a, whereas post-treatment had only a moderate
164 effect (Fig 5B). Interestingly, neither pre- nor post-treatment of cells with IFN-y reduced viral
165 replication whereas IFN-lambda inhibited virus replication but not to the same degree as IFN-a

Check figure 5B later on in the paper gives a good visual represenation of what these words mean.

Conclusions in regard to viral replication/load
* Type 1 interferons were better than Type 3 interferons.
* Pre-infected cells treated with type 1 interferon strongly inhibited SARS-CoV-2 replicating. Essentially non infected cells were protected by the administration of interferon and massively reduced further viral spread. Thats good news
* For cells already infected by SARS-CoV-2 there was only a moderate effect in reducing viral replication. So there was still a beneficial effect of using type 1 interferon however it clear once a cell has been infected by SARS-CoV-2 the effects are lessened.

These results are in line with many other papers showing the earlier inhaled interferon applied the more likely an affect it will have.

Out of interest has anyone actually read the full paper or just the abstract?

Good news - Budesonide is cheap and mass produced and is a no brainer to give at risk populations.

Budesonide is an anti-inflammatory drug which looks to help with some patient symptoms and can speed up self reported recovery by a couple of days (Probably due to masking symptoms).

To note it isn't an anti-viral and looking at the trial results only had a minimal effect on preventing hospitalisation/death.

Yes as alluded to this isn't a pill :)

Tom W did say there were 15 UK sites in the trial. However whether they were all brought online before cases dropped we not sure :)

Here is the statement - https://www.gov.uk/government/news/government-launches-covid-19-antivirals-taskforce-to-roll-out-innovative-home-treatments-this-autumn

I am a bit puzzled at peoples reaction to the UK government finally giving the green light to purchasing/stockpiling early stage Covid drugs for outpatients. I personally see it as a good thing for SNG. Simply if we have great results then the task force can't ignore us as it would go against their mission statement. SNG also fit the bill for Tory British nationalism and world beating science narratives they so like.

Mission statement
'The taskforce will search for the most promising novel antiviral medicines that can be taken at home and support their development through clinical trials to ensure they can be rapidly rolled out to patients as early as the autumn.'

Key word is novel so drugs like ivermectin or camostat won't make the cut. Incidentally both pills.

'The aim is to have at least 2 effective treatments this year, either in a tablet or capsule form, that the public can take at home following a positive COVID-19 test or exposure to someone with the virus.'

The key word is aim. People have homed in on this negative 'Aim to have treatments in pill or capsule' form. This is exactly the same aim as in Activ-2, in a perfect world people just get a pill off their Doctor. Currently there are no proven pills so other easy to use drugs will likely need to be used at home too.

Bear in mind the UK govt have pre ordered 1 million doses of AZN's mAbs at a huge cost and these are delivered by self administered injection. I am pretty certain in near future they will be 'discovered' by the task force in the absence of an available pill. My view is the novel anti-viral pill is unlikely to be achieved any time soon and this will play out in the Tory narrative of fighting variants and a plan B for this winter. Perfect for them in the absence of a pill to announce they ordered those 1 million mAbs being prudent and having great foresight :)

Maybe cynical of me but I feel this is UK govt paving the way for big pharmas like AZN/GSK to cash in with their mAbs treatments. I hope SNG get a small piece of this pie.

So what other novel drugs are possible contendors?
AZN mAbs - already pre-ordered last year.
GSK mAbs - Need to prove injection delivery is efficacious. Probably some kind of pre order.
Merck Molnupiravir - Pill form but is now likely delayed until Sept/Oct
Phizer PF-07304814 (protease inhibitor) - Still at Phase 1