Member Info for Monkshood

Does anyone know exactly what the mutation is (It is called VUI – 202012/01)?
It is this the same as -England/204961201/2020?
https://nextstrain.org/ncov/europe?f_division=England&f_recency=3-7%20days%20ago
This mutation is in one of the non structural proteins, so no impact either way on any likely LFT's but not sure if it is the one they are talking about.

That is exactly what I was thinking this morning- rather odd, if anything you would expect it to be inversely related due to fx impact.

TL-replied (to the best of my ability..) below
'The optimer figures are 10% saliva. Given that saliva is complex with all sorts of stuff in it, does”diluting” it in buffer allow binding and attraction to increase? Does diluting increase the ability of optimers to meet target and so given 15 minutes or so, diluting makes the test more sensitive not less?'

Yes - you can see it with Avacta's results, saliva reduces LoD ( affects binding/increases background), the more you dilute the better the results.

'Does the Elisa test from Avacta use a buffered solution to add saliva to ? '

A good observation and an interesting point - they say 100% saliva but there are not enough details of any of the assays to be really clear what any of them have done. It does seem odd that no buffer/blocking agent is added.
Abcam have an Assay diluent as a component of their protocol. Let’s say they assay consists of adding 30ul of buffer then 30ul of saliva. If the saliva you add is undiluted do you say the assay was done using ‘saliva’? If you first dilute the added saliva 1:9 with extra buffer first, is this doing the assay with 10% saliva (or 5%)?

'I guess LFD has problem that target flows past quickly all be it in a thin layer.'
I have never worked with LFT's but I would think that the volumes are less than with ELISA's, also remember there is (typically) no signal amplification step as with ELISA. From what I have read the speed of binding plays a role so direct read through of ELISA performance to LFT are not always correct.

Oak are you asking if the Affimers can be used at a higher concentration? I just do not know what the cost/technical issues are with using higher concentrations of either 'binders' are.
Stability wise, I would go for Affimers, but just because generally in the lab, proteins are typically more 'resilient' than polynucleotides.
There will potentially be nucleases and proteases in your samples - not sure how these are stopped - but getting good quality RNA out of cells was more difficult than proteins.

Scardey, I thought they could be peptide or nucleotide (it is what is in Wiki)- but Avacta should know (although that does not mean others will necessarily use the term in the same way that they do....)

Thanks for the link, PL75/travel- just got around to reading this.
Some observations -
I have never done binding studies but my understanding is that the smaller the KD value the greater the affinity of the antibody for its target, you can then wash more stringently and so get better specificity/lower backgrounds.
So, the Optimer to the N protein has the higher affinity- but then they go on and use the S1 proteins. Why?
Do they have problems with specificity? They only show a binding study of S1 against other related S proteins. We know Roche and Innova use the N protein so this protein is not so similar between strains that this is not possible.
One of the most interesting things was their highlighting the ability to bind the trimer and the reference to the paper by Xiong (ref 9) that I had not seen. This paper shows that the trimer is not very stable and so unlikely to be maintained under the conditions used in LFT’s. This is important as the ability of the Affimers to bind when S1 is present as a trimer has never been addressed in any of AS’s presentations.
In the original thread, there initially, was an incorrect comparisons of data, PL75 and PotteryEx sorted this. But to reiterate. You need to be comparing the ELISA (LoQ 5pg/ml in buffer-40/pg/ml in saliva) data not the LFT (<300pg/ml) from Avacta.
The saliva data is hard to compare, Avacta is in 100% saliva, Optimers are in 10%, but looking at the data it looks like the Affimers are at least 10x more sensitive. Avacta/Optimer have values of 2.7/0.5ng/ml for the antibody equivalent but there are not enough details to know if they both used the same assay.
As was pointed out by PE the Optimer data use LoD rather than LoQ so even the above comparisons are problematic.
The competitor aptamer used is clearly not Avacta’s, both on grounds of sensitivity and the issue of trimer binding as they referenced a non-stabilised S1 protein for their (all be it limited) results.
I have been told that the nucleic acid based Optimers are more flexible which can be an advantage, however they do not have the range of charges/hydrophobicity that you can get with peptides which is a disadvantage. Where they potentially could have an interesting role would be in BAMS. Affimers have an advantage over antibodies as they smaller, thus fewer peptides to interfere with the analysis, especially if using a tryptic digest (look at the butterfly plot in Avacta’s presentation), as Optimers are nucleic acid based this would eliminate this complexity altogether.
From this application note, in terms of LFT’s you would expect Avacta’s to be the better (at least for S1).

Was this his tweet from May....

Pigster, I agree with the sentiment, however, there is evidence that this is not entirely unreasonable -

'Virus propagation was successful from five of 60 samples with Ct?>?35;'
From-
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427302/

Now launched in markets accepting the CE Mark. Roche has also filed for Emergency Use Authorisation (EUA) from the U.S. Food and Drug Administration.
It is planned to ramp up production to have a double-digit million number of tests per month, in early 2021
When I see this from Avacta then I too will applaud them.

Roche have launched their antigen test today, it is lab based and so would compete in the BAMS space. The assay has an 18 min analysis time(ex prep), 300 samples/hr throughput. The test showed a 94.5% sensitivity across 200 PCR confirmed symptomatic individuals and a 99.9% specificity across 2747 by PCR negative symptomatic and screening individuals.
How it compares, is difficult to gauge as we (still) do not know anything about the BAMS assay. What I find interesting (other than the method it’s - ElectroChemiLuminescence Immunoassay) is that they have targeted the N protein. There does seem to be a common thread with the commercialised tests, that they are targeting the N rather than S protein, probably for reasons already discussed.
In the last presentation AS reiterated that theirs was still the most sensitive ELISA (for the S protein), but did they make a mistake in targeting the S protein? have Avacta had to pivot to the N protein? They could, they could even potentially even make a test that targets both S and N to get greater sensitivity. I wonder if this, is in part, a reason for the delays we have seen? Will we ever find out…..

The last of these I bought was on the 2nd April (20p) after they announced the subscription but just before the placing, it's why I remember it.
I did buy these as a top up but nowt to do with the 'posh ramper'

RD you need a 1.5, the placing to raise 3.785M just after the subscription.

Tricky running a business like this with several threads. A while back, I heard through the 'grapevine' that he was told to focus on what he had been paid to do - the oncology- and not get distracted by the diagnostics. I guess, at least in the short term, shareholders have a different agenda than companies funding the oncology studies.

Impact of no deal, £ lower which will help as majority of earnings overseas. However tariffs could have an impact in the UK, from CBW-
'The letter calls on Mr Gove to ensure that as part of an ongoing review into the no deal tariff schedule completed coaches and buses and chassis can continue to be imported from the EU tariff free. Currently tariffs of between 10% and 16% are proposed in the event of a no deal Brexit on completed vehicles, which would add tens of thousands of pounds to the cost of a new coach or bus. Around 80% of new coaches registered in the UK each year are imported and the vast majority of these are from the EU.'

Surprised to see it under 1200, but it is a nice opportunity to rebuild my holding . It will be interesting to see the impact of the last lockdown - my guesstimate is around 300M revenues for this quarter, which would still put them comfortably ahead of last years H1.

Outlook-
· The new financial year has started positively and is slightly ahead of our expectations
· Following the acquisition of SDL, the Group has no net debt
. Synergy opportunities in excess of the already announced £15m through enhanced operational performance over the coming 12-18 months

It is to do the proteins which are present, egg allergies are flagged if having a flu jab. They probably add protein to the rna jabs to stabilise the product.

As always, worth listening to the webinar for a frank analysis of how things are going.
I was clearly wrong in expecting hand gels to continue strongly! However it was good to hear that even with these revenues falling they are targeting 60M for the year (so >28M in H2).
Pippa should take up a second career as a marketing lecturer - she clearly has a comprehensive grasp of their markets and combines this with excellent presentation skills.

They just went over 70p earlier in the year so should get there again with these results.

It’s a play on many things, these are some of mine-
Northgate – covid with home deliveries lots of white vans needed. Redde – recovery stock, as vehicle numbers increase on the roads, more claims.
Potential for synergies between Northgate and Redde plus the ex-Nationwide repair centres. Possibility of elevation to FTSE250.
Negatives- no deal Brexit, impact on cost of imported vans/spares. Why did Redde’s revenues drop 10% in Oct? I was expecting them to recover a further 10% not fall. Residual van values going forward with a move to EV’s. They still have a lot of debt.

I was talking to a school bursar the other day. He said that they had spent 10K on hand sanitiser, but what surprised me was that they had taken out a three year supply contract. Evidently this was the most cost effective way as they anticipate that they will still be using it at least through next winter.
Originally I had expected revenues for Crl from this stream to reduce quite quickly but now I am not so sure. Many people have got used to sanitising their hands, hospitals and business’s will still be providing it for their workers even after most have been vaccinated. I also cannot see there being a rush to vaccinate school kids when they have such a low risk from covid. A lower incidence of flu seen this year will also strengthen the argument for maintenance of some the habits that have evolved this year.
At last years, Year End Results, Crl mentioned that they had increasing interest from UK business looking for home supply to help de-risk a no deal Brexit, it will be interesting to see how this has developed given the lack of clarity on this issue to date.