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From pg 25

"• Increased intra-tumoural doxorubicin exposure made possible through patients being able to tolerate higher doses and/or increased number of cycles of AVA6000 relative to conventional doxorubicin"

The tumour concentrations reported so far may exceed the tumour concentrations possible with normal dox. I'd thought that this was because whatever dose you gave was converted within the comparatively small volume of the tumour. If 100% of an equivalent normal dox dose (75mg/m2) were converted in tumour concentrations would be massive. That's the fundamental MOA.

Have I missed something?

Avacta cannot build a place in Dx by simple buy and build.

The companies involved are also already developing new products. We have bought some revenue - no evidence of high growth rates inherent.

The thing Avacta bring is affimers. That is where the synergy seemingly exists.

However, Avacta have had the rights to affimers for over 10 years and have struggled to extract value. Even the covid opportunity failed to deliver any revenue despite being "the best in class".

AS has stated Dx strategy will be focused on during next update. Something needs to change to extract value from affimers and these acquisitions- if he gets these comms right then SH a bit more on board and SP responds but at the moment affimers are an interesting research project for Leeds University.

Perhaps our chairman will make an appearance?

Would be happy if Roche stumped up a comparatively small lump of cash to merge with Avacta - new company to be called RAHvacta.

Just have. Think AS actually points out the inconsistency with what he said. So Have bought manufacturing as a consequence of buying the other parts that avacta atualy wants. LD seem to have most of that covered - maybe Avacta are going on mission to consolidate the Euro Dx market in £7M chunks. Talks about expansion and innovation but presumably these companies already doing that - poss economy of scale but efficiencies don't seem to be mentioned. Also missing is what Avacta bring to the party - presumably affimers but at moment they are restricted in use to PhD thesis in Leeds

From company website....

Our M&A strategy is focused on the highest value parts of the diagnostics sector – innovative product development and the commercial routes to market in both the centralised hospital laboratory and decentralised healthcare markets.

Today highlights issue with using company statements to determine the future.

Last presentation AS states that company not interested in buying manufacturing arm. Today they bought one.

AS stated that affimer based LFD are best in class. It has apparently been in continuing development in a beefed up DX for years. Today it was dropped in favour of a generic LFD.

Not sure what is gained by this - might explain why SP is where it is given statements are not what they seem on an ongoing basis. Strategy might be right or wrong but why the porkies?

Apologies just read other posts about keeping on topic

In terms of C5 ending then we can consider base and worse case scenarios. It will happen when it happens and is largely irrelevant- one month here or there will make little difference. I'm not sure of the relevant of guessing the date - seems important but I've missed it?

Orfraudian. Very good. Spat my tea.

Insert big yellow laughing head

Oh hang on... 😆

If its one buyer one seller then they both try to arrive at a price that suits themselves or walk away.

In a market a single buyer playing hard ball waiting for a lower price will find themselves going without as sellers find buyers more willing to pay. I suspect lots of people here have waited and missed the boat on one share or another. Collectively buyers may calculate that the price will move one way or another but there are literally billions of people not buying avacta shares - however the ones that are match the sellers- economics 101. If price moves then it's to match buyers and sellers - note MMs could be on either side.

The avacta story has been going for awhile. I suspect LTH are happy with their position and are therefore not participating. Therefore low volume and no new news makes SP fairly stagnant added to which the offload of shares creates oversupply.

We have months of this. Any chance we can agree to disagree?

They are testing the leaving group in each case in preclinical - presumably looking for AEs. P1 will then document elimination I humans but won't be big enough for demonstrating much else. My guess is the risk benefit will favour licence on basis of post marketing audits - every patients data entered into database where on-going assessment can be made.

Whist one leaving group would simplify this, there must be good reasons for different groups- fap active site binding makes sense but molecule also has to be stable with significant half life. I go with I don't know but content that it is what it is - complicates a simple story but what a story

Thing about finding DLT in a cohort takes that cohort longer to complete since additional patients are added.

My view is that they won't find DLT in the cohorts but will hit a point where the rate of conversion of ava6000 to dox will plateau as evidenced by the serial blood measurements of the leaving group. At SD lead investigator stated they were miles off MTD but AS implied cohort 5 might be last one - hence the interpretation that they are looking for something else.

Concentrations over time in tumour are the key metric - pK of leaving group is a surrogate marker for this. If it plateaus as all enzyme reactions do then the stated rationale of split dosing makes sense since substrate replenished.

Of the 23 posts on this thread, 19 are focused on one individual member of the BB rather than the original topic. I suspect number 24 will also go that way. There is a potential solution....

Apologies RAH but I think TD have put a value of £64M on Ava6000 rather than zero.

It's slightly hidden but it is in there. Are you sure you are reading their report in full?

I don't think anyone would sell it for that and BP would bite Avactas arm off given its in human trials and the expectation of P1b looking more weighted to efficacy

My thx as well icecool. My attempts at AI were focused on creating a picture of Donald Trump in a convict outfit and that took about 2 hours.

My simplistic view is that normal dox creates a systemic concentration of dox. This will be fairly close to the concentration of dox in the tumour - see mouse model graphs. It is also the concentration in the heart. Total exposure is conc x time = area under the curve.

What I cannot work out is

1. Would the max conc of dox in tumour be at 24 hours when the biopsy taken. I suspect it would be earlier than this - balance of conversion in tumour and removal but will be conc dependent. Body gets hit with a dose that then declines o er time. Therefore we may be seeing much higher tumour max concentrations.

2. Once fap enzyme saturated then conversion happens at constant rate. I think they are still trying to find this and C5 is prime suspect. AS has hinted that only C5 is needed which wouldn't be the case if they are looking for MTD since SD stated they are miles from it.

3. Pk data could be very exciting. Split dosing suggested fir P1b could be a huge AUC

Therefore ava

I'm not sure but i think if patient experiences a DLT then the number of patients in that cohort increases. Since they are trying to provoke MTD then timeline might extend

However, I'm also thinking that they are looking for the point at which the FAP enzyme saturates and leaves a quantity of ava6000 unchanged and eliminated. This may be below MTD since the toxicity comes from converted ava6000 and half life is shorter than dox.

From the systemic concentration at 24hours you can estimate that not all the ava6000 is converted. If it were conc in tumour would be much higher and leakage into circulation would be higher. Hence they are looking for max conversion concentration with a view to multiple rather than single dosing and P1b.

These guys look more serious

https://www.affibody.se/

I'm more worried about the lizard people - they can regrow their tales and everything

AS addressed manufacturing at last presentation (value chain). Said they were not pursuing. Have to consider probably cheaper to out source to China

Don't be so hard on yourself.

To be fair I didn't say how quick to publish. They could present it at conference prior to submission and publishers are aware that companies have a statutory obligation to let market know at least top line ASAP before it leaks out. So full paper could have a lot of detail but RNS could have just 1o variables.

On that score why do people keep comparing admin dose of ava6000 to normal dox. Company have been clear that its inert and animal and human data shows that not all of it is converted. Tumour levels do seem dose dependent but is tumour receiving a bigger dose than normal dox ??? That's what BP is waiting to find out. If it follows mice model then human tumours are receiving massively bigger doses than normal dox and the 3x dose is a distraction from that incredibly important comparison.

I'm thinking end of P1a should be published. We might get earlier look at pK. At that point we can see data BP will base early bid on if they have a mind too

Elliot waves didnt help 4D very much or the other classic pump BMV. Wonder how much individual lost himself and others. Before adopting the xspurt tone have a look in mirror or at least listen to Spreadsheets when he says neeeeeeeigh. Unless of course working up another pump - hope original question helps.