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Hi, I think it’s been addressed a fair bit.
I think they are on course with the timeline given at the most recent AGM. But yes that has shifted vs earlier guidance.
Once started, the timeline is in the hands of the clinical investigators, who are external to Avacta. It may be slowed down due to unforeseen delays in recruitment / first dose, or if a patient sadly dies while receiving the treatment and they need to add another patient to the cohort. There was some speculation this may have happened during the first cohort, based - if I recall rightly - on a slide somewhere showing that 4 people had been dosed (rather than the expected 3).
Probably a good move Okehurst. I think if it drops to £1 again I’ll be digging down the back of the sofa!
My thinking Ophidian was about how the preCISION pipeline is almost entirely pro versions of existing drugs (or analogues). Another option is pro versions of drugs that haven’t made it through trials because, although highly effective, the side effects have been too great. There must be a lot of such assets in the hands of major pharma companies with deep pockets. I hadn’t considered before how the delivery mechanism might favour a different pharmacokinetic profile for the basic drug than you look for when using them in their unmodified form. Such lines of investigation could give even more options to license the platform rather than specific drugs, if/when such deals start to come in.
Although, perhaps doxorubicin is already close to ideal in this regard, with its very short initial distribution half life? The next level of efficacy may come instead from improved recruitment of the immune system, eg via the TMAC concept.
Thanks for clarification.
Any thoughts on the idea of potentially enabling more aggressive chemo warheads?
It’s a helpful post, thanks Ophidian.
I’d not realised the half life of doxorubicin in the body was only c.5 min, vs (likely based on rats) several hours for AVA6000. That is a huge advantage for AVA6000.
It’s also probably a good thing that dox has such a short half life for preCISION, because you want it to all be taken up as near as possible to where it is released after cleavage of the drug by FAPa in the TME.
Which got me to thinking - perhaps the delivery mechanism could open the door for new, even more aggressive chemo warheads with even shorter residence times in the body (if they exist or can be developed). Without preCISION as a delivery mechanism, you could never use these theoretical chemo warheads, because they would be taken up near the site of injection, before they could circulate to the tumour(s). With the preCISION delivery mechanism, immediately attacking where they are cleaved could actually be a good thing, reducing off-target interactions.
Prove the platform and the possibilities are endless…
JimmyT, that second post made me laugh. I think I preferred the way your post turned out to a rant at the twats. A cheeky wee dram and a heartfelt address to total strangers on t’internet are two of life’s best guilty pleasures to enjoy while the wife’s away.
Similarly hoping for the best here, but we’ll see… I’ve sworn to myself if this share comes good I’m moving my gains to less volatile income stocks! It amuses me to see those articles about what companies ISA millionaires are invested in, that seem to suggest it’s a lesson on how to get there. It’s more a lesson in what to do once you are there.
*mind-bending
Coming from the AIM market, to hear about a company’s SP going UP in anticipation of a raise is just kind-bending.
“particularly in combinations with immuno-oncology drug agents”
Sounds like broadening the doxorubicin market to consider using it alongside third party offerings.
Ha! True, always dangerous to assume too much.
But AGMs are held every year around the same time. I’m not sure what this Therapeutics Research Day is (happy to hear ideas from anyone that was there or knows more), but it sounds like a shop window.
The AGM presentation showed a Therapeutics Research Day is planned for November 2022 (date tba). I dare say they plan to have released data well in advance of then, so they have enough time to dress it up for the shop window.
So many typos, sorry.
*part of the body
*selection bias
*novel scan
Having actually read that full paper now, one key thing to stress is that the chart showing FAP levels per cancer gives the beguiling and misleading suggestion of a confident ranking of cancers by FAP expression.
It’s a great start but in truth based on only 80 patients with 54 primary tumours and 229 metastases (where cancer has spread to another pet of the body). The patient selection bis is that these were patients whose cancers were obviously progressed and complex enough that their clinicians decided they wanted to run this Nobel scan for increased precision in tumour delineation.
The error bars show there is a big range on each cancer type, and relatively low sample size. Primary and metastatic tumours are lumped together, although data suggest slightly different FAP activity for each (albeit not statistically significant).
So my key take-homes are:
- It gives a pointer towards cancer types that might on average have more FAP.
- We can’t definitively say “X cancer type is always low/mod/high FAP because it shows it on this chart.”
- This is probably why we need patient-specific PET scans in Phase Ib, to more directly relate therapeutic benefit to actual FAP activity in the tumour(s).
MrA, our posts crossed. I could clearly be more concise!
Jimmy, good point on the cancer types. I noted they split the cancers into low, moderate and high FAP groups with dividers at SUVs 6 and 12. Ovarian is right in the middle of the moderate group.
I’m sure there was also some logic around market size, unmet need, and/or conditions for which Dox is already used as standard of care.
The figure is from this paper:
https://jnm.snmjournals.org/content/60/6/801
The figure on slide 2 shows average FAP SUVmax (max standard uptake value, a proxy for concentration) for each cancer type, with an error bar, presumably 1 standard deviation. n=8 means that there were 8 measurements from that cancer type.
The paper’s a relatively short read and great for more insight on what they might get from PET scans.
The number of each cancer type measured may involve some selection bias and may or may not relate to the size of the market.
Thanks, I think a good summary.
In fairness they don’t mention whether revenue and EBITDA are as per guidance, so with the delays I’d guess not. May have an impact on how quickly they make capital to reinvest in growth of the site Pipeline. But the guidance was >200% YOY revenue growth, so I think you can forgive them if that is merely pushed back a couple months. The stabilisation of cash position between April and May gives me some confidence though that they have a resilient position to work with.
But the market seems to respond to every RNS these days with “oh yeah, they exist, let’s sell them too”, but as others have discussed, most likely situation is a forced seller here.
Thanks Lovebug. Sounds promising.
Today’s cash injection is good for the best part of a month of cash runway. Not sure when LG Chem will get the IND filing in, but you’d imagine the next milestone payment will be good for a few months at least. Would help if that could come before 2023, but there was no indication of LG Chem’s timeline in the RNS today.
Thanks for sharing - from the link you gave this is pretty clear:
“PD-1 is a checkpoint protein on immune cells called T cells. It normally acts as a type of “off switch” that helps keep the T cells from attacking other cells in the body. It does this when it attaches to PD-L1, a protein on some normal (and cancer) cells. When PD-1 binds to PD-L1, it basically tells the T cell to leave the other cell alone. Some cancer cells have large amounts of PD-L1, which helps them hide from an immune attack.
Monoclonal antibodies that target either PD-1 or PD-L1 can block this binding and boost the immune response against cancer cells.”
So PD-1 is a proteinon the immune T cells.
PD-L1 is a protein on cancer (and some normal) cells.
When the two attach, the immune cells know not to attack.
The PD-L1 inhibitor binds to and “turns off” PD-L1s, so the T cells can recognise and attack the tumour.
Downside is, it turns off PD-L1 in some normal cells, and they get attacked as well. Hence bad side effects.
Not sure what the benefit of Affimers is, besides, as you say, exquisite specificity - not to be sniffed at of course. Possibly size as well, helping it get to parts of the tumour other antibodies can’t reach.
However, by themselves, the Affimers have a short residence time in the body - they would clear fast, possibly through the kidneys, or liver. This is why LG Chem have also licensed the XT serum half-life extension. Essentially they make the Affimers ‘bi-specific’, by putting a second binding surface on the PD-L1 Affimer that attaches to the protein ‘albumen’ in serum (blood plasma). In so doing, the therapeutic Affimer attaches to and hitches a ride on a bigger molecule that helps it stick around in the blood for longer. Whether this hampers its ability to penetrate tumour tissue I don’t know.
Other (commercial) benefits are low cost and easy reproducibility, and a clear patent landscape allowing it to take on antibody equivalents that are protected from similar antibody equivalents eating into their market. If LG Chem’s licensed PD-L1 Affimer therapeutic does at least as good a job as antibody equivalents like Keytruda (one of the highest grossing drugs worldwide at the moment) it will be cheaper to manufacture, and there’s a huge market to capture.
Seriously though, no engagement on this, and nearing 20 posts in the panto “did he/didn’t he” thread?
Thought it might be interesting to discuss observations on the AGM update instead of what other people are doing.
All on track within the guidance range on growth, with some delays at a couple sites.
Cash position looked decent at £6.8m at end May compared with £6.9m at end April, stabilising since falling from £8.2m at end 2021 (partly trading under covid conditions). Bearing in mind they are continuing to invest in growth while open sites are cash positive, that stabilisation looks good to me.
So what is this share price responding to? Those few delays don’t seem such a big issue given the number of sites already open and the continued development of the pipeline.
If - as I think is the case - they can keep going and organically growing revenues on existing funds and income with no foreseeable need for a raise, it seems a crazy drop.