Member Info for Monkshood

Even with the enlarged bond value it saves them over Eur 8M pa

I have been buying a few more on the drop, so down about 8%. I'm looking for a 50% increase over two years, this needs the price to go back up to the 21/2200 range which seems doable . They will not set the world on fire, but it is a nice conservatively run company whose finances are in a good shape.

You often see a dip after a company moves up a level in an index (as the last of those held for arbitrage are sold). The ending of the buyback and the delay in the generic Advir will have also contributed. I reduced my holding (not 2m!) but will top up again later in the year as this is a good long term hold.

WOSG reported a strong set off results in their latest quarter, ‘UK performance continues to be driven by strong domestic sales’ …’Luxury watches have continued to outperform while luxury jewellery has performed well with growth in both the UK …’ given that retail sales of watches and jewellery play a significant part in HAT’s revenues hopefully this will be reflected in their sales as well. Gold prices are still high which will also help profits.
As you say, recent director buys of 70k shares is also an indication that things are going well.

Nice bounce back from the recent dip. The results out in a couple of weeks should be good, we know sales were up 59% YoY in July and 25% in August, hard to see this has not been maintained through September.
According to my family, they are very well organised re-covid in the shops, certainly a safer environment than many retailers and their online side works well to.
With the strong housing market and lots of people still working from home they should be able to keep the momentum going through the winter.

I like the product and the price point for this, I had expected it to be more expensive.
Started a small holding in this again, if it can generate enough revenues to tide them over the winter then this could be a good entry point.

I hope that this helps explain glycosylation and its relevance to BAMS.
The S1 spike protein has sugar groups attached along it length, these are linked at asparagine’s (the single letter amino acid code for this is N). The sugar groups are variable -they will change the ‘weight’ (m/z) of the piece of protein they are attached to. As analysis by mass spec’s is by looking at the weight of protein fragments glycosylation can cause problems. Peptides that are glycosylated would have variable m/z (size) and so would appear in different positions on the spectrum. The glycosylation sites are shown in yellow in fig 5. on the Bruker application note.
The data shown in the presentation on Monday was a Mass Spectrum (MS), each peak is a string of amino acids, it is also possible (with the appropriate kit) to do MS/MS this is where you take one of the peaks in the spectrum and fragment it to give the amino acid sequence.
Of the two annotated MS/MS spectra (fig6) on the Bruker application note, one (1358.7) would not be glycosylated (no asparagine- N) the other (2838.3) does have an asparagine but it has not been reported to be glycosylated.
Why this matters is that these could be used as markers (after trypsin digestion) without the need to deglycosylate the protein first. One less step in the analysis. I am guessing that is why these were shown.

They use trypsin to cut up the protein (this cuts after R and K), the tryptic peptide covering the D614G mutation (it is at 598 in their numbering!) runs from 563-619 and contains two glycosylation sites, they show no MS coverage of this region so it was not detected (there are less commonly used, alternative digests, which could possibly enable this though).

I think that they will do a further update with more details and a presentation.
It could be that they are waiting for the CEO position to be finalised first.

Maybe- but a 'typical' tryptic digest could be-
Bind S1, wash, reduce the cysteines (breaks crosslinking), treat with iodoacetamide to alkylate the cysteines (thiol blocking), deglycosylation, then digestion with trypsin.
It is why I was interested if they could use the intact spike protein....
An alternative is that it may be possible to get tryptic peptides which could be used as markers just by digestion with trypsin missing out the other steps (this will give a lower protein coverage in the MS, but is a much simpler assay).
The end use will determine the method, what is not clear yet is what the best will be for say, screening in a hospital.

On of the interesting details in the data is that when doing on bead digests, the small size of the Affimers does not complicate the spectra, as say would a much larger antibody (as a polypeptides they will be digested as well). This makes the use of Affimers very beneficial to Adeptrix so I can see the potential for them working together on future assays.

Ophidian- The more detailed data confirms what I said on Monday, that for the data presented in the talk they have used an on bead digest ‘S1 glycoprotein was digested on-bead with trypsin for one hour at 37°C’
They used a recombinant protein for the profile in the presentation, this slightly truncates the start which is why I was having trouble matching the numbers with a tryptic digest (which is the enzyme typically used). I was going to have a go at aligning the data with this assumption today – so the release of the information has saved me the job….
They also show data for undigested spike protein (so, no 1 hr digestion). What is not clear is if it is feasible to use this for screening in patient samples, from the way things are written and presented I think that they will be using on bead digestion. To reduce another step, rather than deglycosylating the samples they may use peptides that cannot be glycosylated as ‘reporter peptides’ (well it is what I would do...).
There is no LOD data, so all in all, still lots of unknowns, but it good to see a product out there.
What surprises me, is this data would have been available months ago, I assume that they are releasing it now as it has taken the time between to organise the manufacture of the quantities need for the kits.

Erris looks to be a small exploration company. My reading is this is a way of doing a capital raise for Zinnwold with minimal direct dilution for BCN. Is this correct?

An article in the FT highlights the plight of small Coach Companies in the UK, so far over 100 have gone into administration and their are fears that the number could increase to 1000.
Whilst this a tragic affair for those concerned, NEX looks to be one of the companies set to gain going forward -
In an article in Bus and Coach-
'National Express Coventry has taken over the operation of the 585, 585A and 585B bus services previously provided by Travel De Courcey '(who have gone into administration)
It looks like there could be many more similar stories over the next year. It seems quite likely that in a couple of years NEX will come out of this with a larger market share than it started with at the beginning of this year.

The migration through the LFT would, I guess, change with the degree of glycosylation as it will affect the polarity of the protein however I (also guess) that they will still all be caught at the test line.
Buffer modification may help counter some of the differences between high/low glycosylation.
I was curious what the impact was -hence the question...
I too would like know what the LOQ of the BAMS is - I think we will find this out fairly soon, they clearly think it is low enough to be viable as an effective test.

Sorry Enteleon, not sure what you mean about 'c surface protein' , however as they have not said exactly where the Affimer(s) bind it is hard to put their use, as a blocking agent for example, into context.
Nixynoo, the results look fine but hard to tell without further details, I was interested if they used digests as it is another step in the sample processing.

Odd how they move together given how different the respective firms are, both in where they operate and their exposure to train service provision.

Looking at the data for the BAMS assay in the talk, the schematic is rather simplified. They have clearly done an on-bead digestion prior to the MS, but having spent all afternoon on it I have still not worked out what with, I cannot get the peptide fragments to map to the usual enzymes. (FYI -the numbers to 3 decimal places are the m/z and the range below will be the amino acid position of the peptide. The peptides will typically be singly charged [+H] but they can for adducts with salts such as Na+ and have other modifications).
I was also curious to know if they also de-gylcosylated the samples first but until I can work out the digestion method used this is hard to determine.
Looking at the peptide sequence and their profile I am not sure that they will be able to see the D614G mutation – it will depend on the digestion method used, but was not obvious in the profile, note -the point that was made in todays talk, was that it did not affect binding, not that it could be specifically detected.
The S1 protein is a highly glycosylated protein so it was nice to have it confirmed that the binding of the S1 Affimer(s) is not affected by the glycosylation state, I had been concerned about this but assumed it was not a problem after the ELISA results were released. The ELISA is a sandwich method so they must also have a second Affimer binding site that they utilise. Often methods are developed using a protein expressed in E.coli which will not have the same ‘decoration’ of sugars as the protein in saliva samples which is why this was important, if the site the Affimer bound could be glycosylated then it may not bind reliably for all samples, as the level of glycosylation can vary. I am not sure that they would have had the information about this at the start, but they have now used the BAMS to work out exactly where the Affimer(s) bind.

Yes, ferrets and the closely related minks can get covid. They are one of the 'test' animals used. They have closed all of the mink farms in the Netherlands down because they had covid outbreaks. Always wondered why these species are never considered as bridging species from bats - perhaps there are none in China.

Most of the Maldi ToF's in the microbiology labs are from Bruker.

I would be for that, I think that it has a lot of potential outside detection of Sars Cov2 and the technique sits well with the Affimers platform. I would have invested in them directly if it was possible.