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Not sure anyone on this board has said anything other than dox is dox and that achieving therapeutic levels in the tumour is significant - goes along way to establishing the Precision technology.

Is this a trojan horse deramp?

Boom

https://en.wikipedia.org/wiki/The_Scorpion_and_the_Frog

The recent interview stressed the next cohorts were about finding MTD and the tone of the trial P1b will go ahead even if MTD is C5. Makes me believe that the biopsy data which is public and the pK data which isn't together will be a major presentation and publication. Optimising the dosing regimine should be seen as positive development since its the tolerability profile that makes it possible.

From there we hold hands with Elliott and wave all the way to £1.87. Any ups and downs in between are exactly as I predicted in one of my ever changing forecast / timeline. I'll point out my brilliance as and when.

Boom

Think drug including comparator FOC but trials generate extra work / costse.g. ethics, 0biopsies, data collection, informed consent then hospitals pass these on (with element of overhead).

Would need to consider how many cycles each patient receives. You could imagine 3 patients all receiving only one cycle each or indeed starting together. Not sure if they have to be staggered. The fact that it's been repeated albeit with caveats is an indication - Fiona thingy conservative but AS always a bit more bullish

Yep 80 patients in total and 60 receiving ava6000.

I get the avacta cash position and why its raised. However....

1. Other programs have milestones built in. In particular, LG moving from preclinical is likely to trigger significant payment

2. Avacta have two assets progressing well. Not a huge leap of imagination to make that one of these will be licensed very soon. Deal structure likely to be upfront payment, costs of development, milestones and then royalty. Reduces risk for partner and takes pressure off avacta cash. More importantly establishes precision and hopefully let's avacta bring forward other candidates.

If that is announced then SP will rerate very quickly. I believe both sides are just waiting for completion of P1a - any later weakens avacta negotiation position

If avacta go for another raise then data would support higher SP but I think this now less likely - avacta lack the experience and weight to optimise precision on their own and a deal would be win:win for both sides and SHs.

AS talked about future partners for ava6000 in recent interview.

Slide 87 at science day

Lol - another great milestone on the never ending self acclaimed xspurtise. The retroscope focused and in full use.

The phase 1b may be good enough to secure US government funding for a bigger phase 2 given their drive on oncology. Looks well constructed and outcomes suitable for low numbers to give statistical difference.

Bump bump bump

Genuinely brilliant bit of research.

Just one request. This is a great ramp opportunity but can that team just get the basics right and we build a solid platform. Great stuff doesn't need anything else.

Treatment Arms will include 48 patients and be three times as long as normal dox. Outcomes are PFS and that is about 6 months for norm dox - relapse when not treated.

Hence trial duration in which patients are receiving treatment and hopefully not progressing is significantly higher and maybe statistically powerful enough at that stage to show difference - suspect numbers chosen to achieve that against dox but different ava6000 doses possibly.

20 centres recruiting 60 patients. Lots of heads up. May happen very quick especially if investigators enthusiastic.

Tipster. The way he was talking about C5 and C6 and really emphasising the purpose was to find the range. He went onto say expect to find MTD in C5 or C6 they will be on track with trial.

Then later talked about posology was lower and more frequent so MTD would be above that. Hence C5 and C6 doses above what they think will be their dose.

We know there are some AEs at C4 dose and therapeutic levels in tumour. My guess is they still have to decide on whether to dose smaller and more frequently in order to get a flatter curve - pK data will inform that.

My take is MHRA have signed off on this trial adaption and it's objective to find a MTD. The P1b would have been discussed and draft protocol may be available. Then add in USA signed up - must have had something to look at

Thinking interview helped
1. Already know have a dose for P1b
2. Huge signal P1b starting - P1a looks like dotting i's
3. May get approval after P2

Last couple of days looks like Avacta progress picking up momentum.

The Precision asset looking more robust to IIs - SP responds

Anyone else norice AS talking about the dose escalation being important to Avacta and any future partner. Looks like Ava6000 could be licensed out - presumably with a nice juicy upfront payment. Whoever gets it may have a shorter run to market than normal thanks to focus on STS which will act as a beach head for regulatory approval

That's the market for standard dose.

Then we have to consider that the proposal is many more doses can be given. Dox seems to use to keep progression at bay (my take from SD) so even if each cycle delivered same tumour dose (conservative?) then the market expands just because so many more cycles are being given

Then consider the improved tolerability and PFS and you can consider a price premium.

Hence market becomes much bigger. Even with constraints such as health economics (see NICE) then if ava6000 delivers the promise, Avacta have a substantial asset on their hands.

Then add in all the other precision drugs

Then add in affimer Tx

Then add in joint programs

Then don't forget Dx.

But have patience. I'm still googling car choices. Might have to go with all three. Old school Land-rover is in there but the other two.....?

Oooh look at all my chickens :-)

Think tumours were chosen because as BV points out they have FAP but are dox nieve.

Nursesteve. Yep that's the thing. Dose at tumour is hopefully much much higher than an equivilent "adminstered" dose. Normal dox is distributed throughout body whilst ava6000 is concentrates on tumour.

Hence celebrating we have a very bright light bulb misses the point that Avacta are developing a very focused laser.

Jive - Concentrations were higher in mice and we know now in humans we know ava6000 is being converted. Hence my faith being maintained.

With normal dox the amount hitting the tumour is a function of the systemic dose.

For Ava6000 it is different. The dose hitting the tumour is dependent on the rate of conversion and how long the ava6000 stays around. Faster conversion and long half life would give massive doses to the tumour - suspect much higher than has been reported. It may be that some ava6000 never gets converted - look up its half life. The study is there to tell us that. AuC of the leaving group could act as a marker of dose hitting thr tumour.

Not sure if mouse model shows 100% of dose converted. 50% conversion would still give massive concentrations at tumour wouldn't it ?