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Thanks all for finding, translating and sharing!
Really nice to see that Avacta and Daewoong still own 63% of AffyXell at this stage. This is what I was looking for after the series A funding, but could not find at the time.
It’s not clear still what the split is with Daewoong, but assuming Avacta have c.30% of AffyXell, it’s still a decent chunk of a very exciting business that sounds like it’s making good progress already.
Was just thinking about possible reasons why we might not have heard about dose escalation yet, and this rattled out of my brain. Feel free to shoot me down or discuss as appropriate.
Initial dose of AVA6000 in P1a trial used 90% of the standard amount of doxorubicin, but focussed the release of that payload into the tumour. With normal Dox (I assume), a lot of the payload would be adsorbed or otherwise ‘used up’ outside of the tumour, hence the systemic toxicity. If AVA6000 works as planned in targeting the tumour, then that 90% payload could represent a much greater concentration than usual in the tumour.
Is there any chance they are finding it more than effective enough at this dose, and considering even lowering the dose to further reduce systemic toxicity?
I believe this would be outside of the initial clinical trial plan, but I don’t know what the associated protocol would be.
Great post EGTP.
Some key points for me:
- Every time the crest of a wave of covid breaks (as omicron might be doing in parts of the UK), people start clamouring that it’s all over for the pandemic and we’re all going back to normal tomorrow. Experience suggests this is not the case.
- Future variants will come.
- Every winter season will see a fresh wave of these and existing variants, especially as immunity wanes over time.
- There are always other countries still on the exponential rise leg of their covid journey.
- Governments are still buying, but I think in the longer term the private market will be the one that sticks.
- People in many countries have gotten familiar with using lateral flow tests, and take them before going places or seeing people.
- People (and employers) are willing to pay for lateral flow tests in countries that don’t offer them for free, and even in some that do.
Patience required, but I am sure the market and the chance of success on this in the mid to long term for Avacta is better than most currently think.
330m shares traded today, mostly in the afternoon. Something like 13% of the company’s share capital.
If I recall rightly (per MilkMonsta’s calcs), at the end of 2021, there were about 800m 0.5p warrants outstanding (and the 0.25p warrants were pretty much all gone). Puts those into perspective - equivalent volume to a few good days worth of trading.
Great to see the growth story play out and bring new buyers in. Looking forward to another good day tomorrow!
Fantastic news! I think those warrants will be gone well before April.
Personally - I’d like the warrants exercised, if the money would help to accelerate growth, and/or avoid any placing/loan on the path to sustainable profit.
But if the revenue figures were good enough that suddenly they didn’t need that money… I’d rather they avoided/minimised dilution.
It’s no biggie in the grand scheme of things - and share price movement between now and the expiry will dictate the extent to which the warrants are taken up. I’m happy if the company focuses on continuing to deliver.
Glad I can help someone out of a funk! Of course - don’t take my speculation as a given, I’m just a generic scientist from another field.
Here’s another bit of speculation. What if having an antibody on the coloured “conjugate microparticle” means that it can accommodate a larger microparticle without impairing it’s function, and it takes fewer of them to form a test line that is visible to the naked eye?
Indeed I think monthly trading updates are discretionary, and not required by market rules. The logic for them would be keeping the market updated in a fast-changing sales environment, and the 1st Dec RNS set a precedent, which seemed a natural extension of monthly subscription updates before then.
Is there a potential play by MOS here for the LTHs to keep the SP at or below 0.5p for as long as possible, to reduce dilution from the 0.5p warrants, which expire around April if I’m not mistaken?
Either we get the presumably good news up front, or slightly more delayed, but less dilution. I view it as a win-win if you’ve got the patience for it.
Thanks again all for sharing - enjoyed the discussion.
I assume there is some important logic about maximising the chance of all the bonds in the chain to form such that presence of virus leads to a positive read-out. Obviously it works extremely well with non-omicron variants.
Speculating - since the biotin-streptavidin is an incredibly strong bond, perhaps that’s the best option at the test line for capturing the full complex of biotin-Affimer (12-14kDa?) + spike (180-200kDa?) + antibody (c.150kDa??)-label particle (??) as it flows past?
Likewise, perhaps having the Affimer relatively “unencumbered” and mobile in the sample fluid gives it maximum chance to locate and latch onto the spikes.
Interesting that antibodies are of a very roughly similar size (by weight) to the spike protein. I wonder how large the target binding region is relative to the spike, and implications for future variant resilience? Hopefully there are >1 well-conserved regions on it to bind with. Anyway, that’s one for the development team.
Let’s hope for a nice blue day, and a good recovery before positive news soon.
Monkshood, Ophidian, or anyone else with relevant knowledge - given the info in this more detailed description, would it be easy to replace? Sounds like what needs replacing is:
- Binding agent (whether antibody or Affimer) attached to the coloured labelling microparticle, which needs high affinity for the Affimer-antigen complex.
- Conjugate at control line for this binding agent-microparticle complex
Given that the virus is lysed (broken up, for those following along) in the buffer, I’m assuming that the biotinylated Affimers will be attached to spike proteins in a positive test. So the new antibody/Affimer needs to bind either to a bit of the spike protein the Affimer isn’t attached to, or the Affimer-spike complex as a whole. And it needs a new conjugate at the control line. Is that right? Would there likely be suitable commercial antibody pairs available, or is it a development job, whether for Affimers or antibodies?
Thanks PAH00. Indeed it is more complex than the text quoted in that tweet I referenced. From those IFU:
“If SARS-CoV-2 antigen is present in the patient sample this will bind to biotinylated Affimer® binders highly specific to SARS-CoV-2 antigen. This antigen-Affimer® complex is then in turn specifically bound to conjugated microparticles, with the antigen-Affimer®-microparticle complex migrating along the lateral flow strip by capillary action until it reaches the test line. Immobilised poly-streptavidin is present on the test line which binds the complex via the available biotin label on the Affimer® binder. Remaining unbound microparticles continue to migrate along the lateral flow strip until they reach the control line, where they are captured by an immobilised antibody specific to the conjugated microparticles.”
So apologies Neutronic, you were right that that both Affimers and conjugated microparticles (which presumably contain the antibodies under discussion) flow along the strip. The biotinylated Affimers are caught at the test line by the poly-streptavidin, which has an extremely strong affinity to biotin - they are a commonly used pairing in biochemistry.
It seems we’ve had access to this info all along. However, there is no mention specifically of antibodies in the “conjugated microparticles”, which is the surprise this week.
One minor thing to add - if this safety data sheet from Mologic is to be taken as legitimate and believed, it would suggest that the Affimers with coloured particle conjugate are mobile and bind to the virus as it flows through the cassette, and the antibodies are fixed to the test line, rather than the other way round.
https://twitter.com/yorkshirpuddin/status/1480457991912673285?s=21
And wc, PreCision does have some unique chemistry that binds with high specificity to FAP-alpha, but it doesn’t use Affimers to do that. Look on the Avacta website for more info. If you find something to the contrary, please share with us all.
Hi Neutronic. I believe the idea is the Affimers are fixed to the test line, but the antibodies/gold are mobile, and picked up by the fluid as it flows through the “conjugate pad” between the sample hole and the test strip. The more gold particles attached to virus captured at the test line, the brighter the red colour there.
Then the % of virus particles caught at the test line (and successfully labelled) would not relate directly to the sensitivity value as a %, mainly because the number of virus particles varies between positive samples. 80% of 1000 would obviously be less visible than 50% of 1,000,000.
Hope this helps!
PJT, I reckon it could be cheaper polyclonal antibodies on the test strip. A positive result involves a chain with two links:
(Labelling particle bound to Affimer) - virus - (antibody immobilised on test strip)
I think you only need a highly selective, expensive monoclonal antibody (mAb) or Affimer on one end of that chain. The other end only needs to bind everything covid-like that passes by so can probably be a cheaper off-the-shelf component. I also don’t see why not an Affimer though…
Fredluck, I’d say directors are probably unable to purchase shares right now. Since AVA6000 is in the clinic, results are highly market-sensitive, and insiders will know how it’s going, they will almost certainly be in a closed period for trading.
I’m not sure sentiment on the LFT can get any lower than today. In terms of news flow, I don’t think there is anything else negative that can come out on it now that sales are suspended and we’re back in development (however fast that may be, given that the test architecture and all other components and IFU are working and previously approved).
Wherever the SP stabilises, I would be looking to close out a short if I had one open. When people think the bottom is in, I suspect the buying pressure will be immense. It’s a gamble for them waiting too long, in case AVA6000 results land before they close it out.
Thanks for sharing, McGurk. Hope your covid infections were mild and you’ve all fully recovered.
Imagine if Avacta kept selling the test, knowing what they know, how many more angry customers like yourself would be created. Not good for the long term integrity of the AffiDx brand. As frustrating as today’s news is, AS is building a long term business, there will be this and many future AffiDx tests to market, and reputation is critical for that.
Agree communication could be better.
I guess the delay in telling the market about the reduced sensitivity was so they could work out the cause and solution. At least we have that today.
Given the product data sheet extract shown here:
https://twitter.com/yorkshirpuddin/status/1480457991912673285?s=21
Sounds like the antibodies are on the test line, and Affimers studded onto the “coloured particle conjugates”, rather than the other way round as I said earlier. Same principles still apply otherwise.
PAH00, yes the Affimers bind the virus with high selectivity and sensitivity, probably on the test line. However you also need to bind tiny coloured beads to the virus to get the visual read-out. This happens in the conjugate pad between the sample pad and the test strip.
I had thought both binders might be Affimers as well, but this detail was never disclosed. I think in practice, you can have high sensitivity, low selectivity binders on the beads that grab everything covid-like. As long as the test line binder is highly selective you still get a high specificity test.
Anyway, frustrating news today. I thought the SP had found a base, with signs of pushing out of that. I’m sure they can fix the test relatively quickly, and hopefully approvals are quicker the second time but no guarantee of that. Here’s looking to the AVA6k results, hopefully pretty darn soon.
It’s to do with how the lateral flow test works. There are three locations in the test that need different binding reagents.
One set to bind the virus, studded onto the coloured labelling beads that move through the strip with the fluid.
Another set on the test line, also to bind the virus and therefore the coloured beads they should be stuck to.
And a third set on the control line, to conjugate with the binders on the coloured beads and grab them whether or not virus is present.
The third is almost certainly antibodies, as it has next to no impact on test performance. It sounds like one of the first two is also antibodies. If I had to guess I’d say the Affimers are likely on the test strip, and a pair of conjugating antibodies go onto the beads and control strip.