Member Info for JoeyDiamond

The key thing with South Africa and other African countries is they have a much lower average age of population than the West + low vax rates. As we know age is the key risk for Covid.

So it’s a not a good comparison to make. High average age of UK, seasonality plus a variant with likely vaccine escape doesn’t look good.

https://www.biorxiv.org/content/10.1101/2021.11.16.468777v1.full.pdf

Blimey ;)

Stellar results here for Interferon vs Delta.

Interestingly Delta is more suseptible to Interferon than other variants, this is due to mutations in the virus evolution. It is suspected mutations in Nsp3, ORF6 and N which (reported to be crucial for IFN escape) may be the cause.

https://www.sciencedirect.com/science/article/pii/0165614784905091/pdf?md5=77d8d9ebc543166538eb1268279ed0f9&pid=1-s2.0-0165614784905091-main.pdf

Interesting read from a scientist at the Common Cold Unit in 1984 working on Interferon.

Interferon was highly effective at preventing colds and viral infections(estimated 1000 times more effective than the Eli Lilly antiviral at the time) but it had some issues at the time.

1) Ability to manufacture interferon in sufficient quanties, at the time methods of creating interferon were different than today. So technology in the 1980s was an issue.
2) Incredibly high cost to produce interferon. For cold prevention cost just too high to be viable.
3) Prolonged use of Interferon Alpha at the time caused some side effects. However when used in short durations no side effects noted (4 day duration). So long term use of interferon was not advised, it would be good however if you knew you were exposed to an infection.

Just some historical facts to clear up the notion that interferon didn't work in the 80s when clearly it did but other factors had an impact.

At this point for any LTH's any drops in SP should be viewed as an opportunity for final top-ups. We are all waiting for P3 binary event which will make or break the share.

For any gamblers you have like a 75% chance of success but instead of bookies giving you 1/4 you are getting generous odds of 8/1. From a horse racing view this is like betting on the favourite but the bookie giving you the outsiders odds. :)

jaybubya - SNG are currently waiting for P3 trial results, true value depends on the final P3 result.

So most certainly not is success built into the SP already.

I did share a non SNG interferon science paper yesterday that contained within a comparison of how well interferon worked vs the various variants.

That paper showed interferon worked very well vs Delta, in fact the effect on Delta was higher than other variants such as Alpha. As we know from previous lab tests with SNG001 it was highly effective vs Alpha.

This is just a silly scaremonger tactic/thread as other science papers have clearly show interferon works vs Delta.

That is true SARS-cov-2 can infect many animals including dogs and cats so there is a huge animal reservoir. There may come a point where they need to cull animals, this was suggested as part of UK pandemic plan in a worse case scenario.

Yes thats correct it has similar results to exogenous interferon which is expected as SLR14 relies on the interferon pathway for its anti-viral effect. The molecule essentially turns on the bodies interferon switch and generates a blast of interferons which gives it protective effect.

Yes many years away, would need a drug company to pick it up and support through full human trials etc but has great potential.

Cool area of science- https://en.wikipedia.org/wiki/RIG-I

Scientists have discovered a new RNA molecule that stimulates the body’s early antiviral defense and produces interferon which highly effective in SARS-COV-2 mice models.

https://rupress.org/jem/article/219/1/e20211818/212765/A-stem-loop-RNA-RIG-I-agonist-protects-against

'Here, we examined the in vivo efficacy of SLR14 against viral replication throughout the respiratory tract and disease development in a mouse model of severe SARS-CoV-2 infection. We first showed that SLR14 rapidly triggers local production of IFN-I in the respiratory tract. Consistent with the induction of airway IFN-I responses, we found that SLR14 conferred considerable antiviral resistance in the lower respiratory tract and effectively prevented morbidity and mortality following infection with the ancestral virus. '

This new molecule is cheaper and easier to mass produce than exogenous interferon so could well be a great novel new drug in the future. Possibly if a drug company picks up SLR14 we could invest and enjoy another interferon ride :0

https://shorttracker.co.uk/manager/polygon-global-partners-llp/
https://shorttracker.co.uk/company/GB00B0381Z20/

You would need to declare any short over 0.5% of stock. Checking declared short positions and none found for SNG.

Across the UK we are seeing a large increase in excess deaths, crucially many are not Covid related. The excess deaths is amongst less people on average dying of Alazheimer/Dementia but more people are dying of cancer, heart disease, strokes.

So its a very serious question what is the cause of these excess non Covid-19 deaths?

The 4 more common suggestions are -

1) Vaccine side effects, we know people have died of heart issues / clots.
2) Government Covid policies such as lockdowns impacting peoples general health both physical and mental.
3) NHS service cuts. Underfunded with large waiting lists.
4) Population health, people now doing less excercise, worse diets, more alcohol/drugs than a few years ago.

Likely a combination of all 4 is the contributor but there should be more focus on this important issue.

Here are the minimum requirements for activ-2 progression.

Virology:
The virology-based graduation guideline for an investigational agent to be eligible for phase III evaluation will be evidence of any one of the following:
1. Higher absolute proportion of participants with SARS-CoV-2 below the assay LLoQ in NP swabs by at least 20% at one or more of the scheduled in-person measurement times (e.g., 60% for placebo and 80% for investigational agent at day 7) as compared to placebo (i.e., X in the probability statement above is an absolute 20% increase for this outcome); or
2. A decrease in median SARS-CoV-2 RNA levels in NP swabs of at least 0.5 log10 copies/mL at one or more of the scheduled in-person measurement times as compared to placebo (i.e., X in the probability statement above is 0.5 log10 copies/mL) (measurements after day 7 are not considered as a majority of participants are expected to be undetectable after day 7); or
3. A relative reduction in median area under the curve measure (AUC) of SARS-CoV-2 RNA levels in NP swabs through study day 7 of at least 20%, as compared to placebo (i.e., X in the probability statement above is a relative 20% reduction).

The absolute difference of 20% in (1) and the 0.5 log10 copies/mL difference in (2) were surpassed in a comparison of monoclonal antibody treatments in trials for persons with COVID-19 [16, 17, 24]. The threshold used in (3) also seems
achievable based on the same studies, although the AUC outcome was not formally evaluated in those trials.

Clinical:
The clinical/symptom-based graduation guideline for an investigational agent to be eligible for phase III evaluation will be a relative reduction of at least 40% in the proportion of participants with either moderate or severe symptoms reported at day 7 (of the targeted symptoms in the participant diary) or have been hospitalized or died on or before Day 7 (i.e., X in the probability statement is a relative 40% reduction).

Safety:
Graduation to phase III will also depend on an acceptable safety profile, as determined by the DSMB. This decision will largely be based on differences in the frequency of Grade 3 and 4 AEs between participants receiving the investigational agent and those receiving placebo.

Read version 7 of the activ-2 protocol and it tells you what the progression criteria is to reach P3.

https://ir.ateapharma.com/news-releases/news-release-details/atea-pharmaceuticals-provides-update-and-topline-results-phase-2

In the topline analysis, treatment with AT-527 did not meet the primary endpoint as it did not show a clear reduction in SARS-CoV-2 viral load in the overall population of patients with mild or moderate COVID-19 compared to placebo....

Well thats one big competitor anti-viral pill out the race.

To be fair we are both wrong. Being super pedantic the correct terminology for the active comparator is 'Casirivimab plus Imdevimab' in the study document. :)

I don't think its been discussed on here yet but for me the exciting bits are the SNG only protocol additions. In particular the Casanova based work on Interferon Autoantibodies is also planned to be recorded for patients in P3. So there is a great potential for another subset of patients SNG001 can be used on.

Also they are going to have a subset of the more breathless patients as an outcome.

I think we couldn't have wished for more getting these additions on the trial protocol design. The data generated will be fantastic, so lets hope we definately have progressed :)

@pmjh - Yes its a happy confirmation FDA etc are not just focused on mAbs and see the potential of other treatments.

@Matterhorn - Yes not as exciting as we all first hoped haha but a bonus for sure. Regeneron as a comparator had good results so will be hard to match so gives SNG001 a little advantage.

Broader clinical utility in this case refers to adminstration of the drug.

So pills or inhalers for example are preferred to infused treatments as they can be more easily administered and don't require the same health infrastructure/resource support. Especially important in poorer areas/countries.

In SNG's case (if they progressed) they could have slightly lower efficacy than a mAbs treatment but would be looked on favourably due to easier administration of drug.

The University of Arizona is one of Sprinter P3s trial sites in the USA. Will likely be how much they were paid by SNG to conduct the trial. I do wonder how many people they have recruited for that amount of cash :)

These are the activ-2 p3 entry requirements, they are similar to the home trial.

The following participants are considered at “higher” risk of progression to hospitalization or death as long as they have NOT received any doses of a COVID-19 vaccine with World Health Organization (WHO) Emergency Use Listing (EUL) or FDA
Emergency Use Authorization (EUA) or full approval:
• =65 years of age
• =55 years of age and satisfying at least one of the following:
o Cardiovascular disease defined as history of any of the following: myocardial infarction, stroke, transient ischemic attack, heart failure, angina with prescribed nitroglycerin, coronary artery bypass grafts, percutaneous coronary intervention (PCI), carotid endarterectomy, and aortic bypass
o Hypertension, with at least one medication recommended or prescribed
o Chronic obstructive pulmonary disease or other chronic respiratory disease requiring daily prescribed therapy
• =18 years of age and satisfying at least one of the following:
o Body mass index (BMI) =35 kg/m2
NOTE: BMI is rounded to the nearest whole number, for example, 34.5 is rounded to 35
o Chronic kidney disease requiring hemodialysis or peritoneal dialysis
o Type 1 or type 2 diabetes
o Exogenous or endogenous immunosuppression defined as any of the following:
? HIV infection with CD4 count <200 cells/mm3
? receiving corticosteroids equivalent to prednisone =20 mg daily for at least 14 consecutive days within 30 days prior to study entry
• treatment with biologics (e.g., infliximab, abalizumab, ustekinumab, etc.), immunomodulators (e.g., methotrexate, 6MP, azathioprine, etc.), or cancer chemotherapy within 90 days prior to study entry

All other participants, including all participants who have received at least one dose of a COVID-19 vaccine with WHO EUL or FDA EUA or full approval, are considered to be at “lower” risk for progression to hospitalization or death.

Yes it’s from June. We have known the V7 protocol was written up for a long time but was blocked from release for regulatory/ approval reasons