Member Info for Monkshood

I feel that Trist is now in a bit of a sweet spot for sales, they must still be selling lots of surface cleaning products but routine work is now also going on in hospitals.
The expansion into India must also offer a huge potential market.
This is one that I am happy to sit on for quite a few more years...

The revised offer for ELM is pushing this higher, thus Redd moves down the list and the price drops.
If ELM does go up and then get taken over, there will be a slot - it does mean that Redd's intrims will come into play more though.

In4, I have to disagree with you about this ‘we don't know the number of spike proteins per virus.’
I was using 100 spikes per viron (as a round number, but probably an overestimate ..)

From- SARS-CoV-2 structure and replication characterized by in situ cryo-electron tomography | bioRxiv
we estimated the average number of S trimers per virion to be 48 with a range of 25 – 127

From- Structures and distributions of SARS-CoV-2 spike proteins on intact virions | Nature
Individual virions contained 24 ± 9 S trimers (Extended Data Fig. 1b)

I appreciate your points about PCR – I have done some in the past, I can even remember pre- TAQ days when I had to add fresh polymerase after each thermal cycle! I was just using the data presented by Porton, who ultimately are the ones deciding on the tests suitability.

In4, you are correct, 'There is no mathematical conversion between pg/ml, copies/ml and pfu/ml. Samples are tested against a standard curve', but this is what they did at Porton (at least for the last two), the data is in Table 2 and Fig 1a.

pg/ml is an absolute term, we know the MW of the S1 protein, that it is a trimer and how many spikes there are on a viron(ish). You can therefore calculate the theoretical pg/ml of S1 for a specific viron concentration. They will be using purified recombinant S1 to develop and define their assay (this is where the <300pg/ml etc comes from). What I cannot, get to add up, is correlating their sensitivity (in pg/ml) with a sensible viron count.

CO, it is a shame I missed your posts on this, it would have saved me a few hours and then repeating what you had already said, my apologies for this.
I guess, that we have both, separately, come to a similar conclusion is good though!
I am fairly sure that when the are talking about amounts of protein that they are referring to the recombinant S1 so I still cannot correlate this with the proposed vion detection levels. However, given what else we have been told/know this seems to be more of an academic point.

CO, I agree, it is frustrating that there is not more clarity with this. I guess the data will become available over time.
I will look at your posts later, sadly useful posts get lost in the noise now.

enteleon, I do not have any experience of LFT's to know. I would guess that there would be pressure from HMG to have a common one across venders if possible. Innova must have one and it sounds like Avacta do to.
The aim would be to solubilise the proteins and disrupt the peptide bonding - so a detergent, a buffer to control the pH and may be a reducing agent (although this can get oxidised in storage so less sure about this). The issue is then not having this affect the binding of the affimers - which is itself just protein/protein interaction.
The interesting thing will be what they use for BAMS as detergents can give problems with MS's.

Oke, it is quite possible that they can get to 150pg/ml if they use swabs as this may result in a lower % of mucins than a saliva sample.

Tom, 'Ophidian advised there is no conversion for copies/ml to PFU/ml.'
But, if I am interrupting it correctly then that is essentially what the Porton data does show and that the value is 1 PFU=1000 virons.

Oke , I saw them and have been working on it since...

I have spent that afternoon trying to get a grasp of the numbers. The problem is the mixing of PFU’s/ml, pg/ml and then virons/ml.
The LFT is going to be at least 10x less sensitive than the ELISA from what has been presented – ELISA LOD 5pg/ml (buffer) 40pg/ml saliva, LFT <300pg/ml (buffer??). This seems reasonable as the linked enzyme in ELISA amplifies the signal.
If you look at the Avacta presentation of 7th Sept (6.5 min) they show the data of Wyllie et al with a detection limit of the ELISA around 3k copies/ml (they use also virus particles/ml synonymously in the legends) , so one assumes that we are looking at 30-50k virus particles LOD for the LFT.
What I then struggle with is the use of PFU by Porton, they are looking for sensitivity of >50% at 102 pfu/mL, (see Table2)
UK evaluation_PHE Porton Down University of Oxford_final.pdf
At first I assumed one PFU was one viron, but I now do not think this is the case.
The text below Table 2 –
‘We also analysed the association between viral antigen detection and viral load as part of Phase 3a evaluations with clinical samples which were placed in viral transport medium allowing direct comparison of viral load and antigen tests (Fig1). This shows that samples with a CT <25.5 (calculated as a viral load> 100,000 RNA copies/ ml) had a 90% or greater chance of being detected’.

Now a CT<25.5 in their table is equivalent to 100 PFU. So does this mean 1 PFU =1000 virons -which I do not understand (other than only 1 in 1000 virons is viable/capable of forming a plaque in their assay) !

If this is the case, then they are looking for 10>5 virons which Avacta should be well within the range of. This seems reasonable and is agreement with what was said in the presentation - ‘in clinical range’.

I also thought that I would look at it form a protein view. The S1 protein is 76 Kd, this is 1.262 10>-7 pg. there are approx. 100 spikes per viron, each is a trimer, so each viron has 0.000037 pg S1 protein. In this case you would need 10>7 virons/ml to get 300pg/ml S1 which is too high (in all senses…).
(apologies for the 10 > X cannot do powers in text only)
Has anyone got any ideas about this?

The prospectus is worth a read. It goes through the nitty gritty of the company. It gives a good overview of the company including the risks in specific segments as well s where they see future expansion.

Tom, where did you get 300pfu/ml from, I have only ever seen 300pg/ml from Avacta for the LFT (and 40pg/ml for the ELISA in saliva).

NEX is quite weighted to $ fx. There has been a pull back in a lot of my holdings with strong $ earnings as the £/$ has strengthened.

I do not understand why people talk about 'saliva test' and 'swab test' as if they are two different LFT's, the are just two different sampling techniques which will be run on the same LFT (or BAMS /ELISA). It was never going to be a case of spitting on a LFT.

I would not expect the CFO to have been buying shares if he thought that the FCA was going to cause any major problem; they have had a year to look at this now .
Given the rise since he purchased his last tranche, it may be worth us having a whip round and sending him some money to purchase some more.....

My take on it that Cytiva came up with a test (that was their part of the deal) , but the one that they came up with required non standard components and novel manufacturing methods, ( the BBI one uses 'readily available components and routine manufacturing processes'). Whether they, originally, were trying a novel test setup because they were set on saliva or for other reasons, they clearly seem to have had underestimated how hard sourcing new components within the required time frame.
The delays have been because they were initially going down this route then have had to pivot to a different test design, now developed by BBI.
It is unfortunate as it has negated the advantage that they had with the rapid production of selective Affimers compared to mAbs that others use.
I wonder how much blame can/should be levelled at Avacta, they handed the selective Affimers over early. Personally I don't think that Cytiva come out of this well.

I think that the complete absence of a mention of Cytiva indicates where the main problem for the delays has been.
They clearly got into bed with the wrong partner at the start. Hopefully now back on track.

I have had this on a watch list for a while. The investor presentation at the end of October made a convincing case for me.
It looks like the selling has stopped and the price bottomed out so have started a position in this now.

At the moment it is tussling with ELM and MSC for a move up, it only needs another 4M on its MCap to gain a slot.
If the big boys want it up, then up it will go.